Are Physician Estimates of Asthma Severity Less Accurate in Black than in White Patients?

PubMed Central

Wu, Albert W.; Merriman, Barry; Krishnan, Jerry A.; Diette, Gregory B.

2007-01-01

Background Racial differences in asthma care are not fully explained by socioeconomic status, care access, and insurance status. Appropriate care requires accurate physician estimates of severity. It is unknown if accuracy of physician estimates differs between black and white patients, and how this relates to asthma care disparities. Objective We hypothesized that: 1) physician underestimation of asthma severity is more frequent among black patients; 2) among black patients, physician underestimation of severity is associated with poorer quality asthma care. Design, Setting and Patients We conducted a cross-sectional survey among adult patients with asthma cared for in 15 managed care organizations in the United States. We collected physicians’ estimates of their patients’ asthma severity. Physicians’ estimates of patients’ asthma as being less severe than patient-reported symptoms were classified as underestimates of severity. Measurements Frequency of underestimation, asthma care, and communication. Results Three thousand four hundred and ninety-four patients participated (13% were black). Blacks were significantly more likely than white patients to have their asthma severity underestimated (OR = 1.39, 95% CI 1.08–1.79). Among black patients, underestimation was associated with less use of daily inhaled corticosteroids (13% vs 20%, p < .05), less physician instruction on management of asthma flare-ups (33% vs 41%, p < .0001), and lower ratings of asthma care (p = .01) and physician communication (p = .04). Conclusions Biased estimates of asthma severity may contribute to racially disparate asthma care. Interventions to improve physicians’ assessments of asthma severity and patient–physician communication may minimize racial disparities in asthma care. PMID:17453263

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

PubMed Central

Porsbjerg, Celeste; Ulrik, Charlotte; Skjold, Tina; Backer, Vibeke; Laerum, Birger; Lehman, Sverre; Janson, Crister; Sandstrøm, Thomas; Bjermer, Leif; Dahlen, Barbro; Lundbäck, Bo; Ludviksdottir, Dora; Björnsdóttir, Unnur; Altraja, Alan; Lehtimäki, Lauri; Kauppi, Paula; Karjalainen, Jussi; Kankaanranta, Hannu

2018-01-01

ABSTRACT Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma (‘difficult asthma’) should undergo systematic assessment, in order to differentiate between true severe asthma, and ‘difficult-to-treat’ patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care. PMID:29535852

Evaluation of quality of life according to asthma control and asthma severity in children and adolescents.

PubMed

Matsunaga, Natasha Yumi; Ribeiro, Maria Angela Gonçalves de Oliveira; Saad, Ivete Alonso Bredda; Morcillo, André Moreno; Ribeiro, José Dirceu; Toro, Adyléia Aparecida Dalbo Contrera

2015-01-01

To evaluate quality of life according to the level of asthma control and degree of asthma severity in children and adolescents. We selected children and adolescents with asthma (7-17 years of age) from the Pediatric Pulmonology Outpatient Clinic of the State University of Campinas Hospital de Clínicas, located in the city of Campinas, Brazil. Asthma control and asthma severity were assessed by the Asthma Control Test and by the questionnaire based on the Global Initiative for Asthma, respectively. The patients also completed the Paediatric Asthma Quality of Life Questionnaire (PAQLQ), validated for use in Brazil, in order to evaluate their quality of life. The mean age of the patients was 11.22 ± 2.91 years, with a median of 11.20 (7.00-17.60) years. We selected 100 patients, of whom 27, 33, and 40 were classified as having controlled asthma (CA), partially controlled asthma (PCA), and uncontrolled asthma (UA), respectively. As for asthma severity, 34, 19, and 47 were classified as having mild asthma (MiA), moderate asthma (MoA), and severe asthma (SA), respectively. The CA and the PCA groups, when compared with the NCA group, showed higher values for the overall PAQLQ score and all PAQLQ domains (activity limitation, symptoms, and emotional function; p < 0.001 for all). The MiA group showed higher scores for all of the PAQLQ components than did the MoA and SA groups. Quality of life appears to be directly related to asthma control and asthma severity in children and adolescents, being better when asthma is well controlled and asthma severity is lower.

Household biomass fuel use, asthma symptoms severity, and asthma underdiagnosis in rural schoolchildren in Nigeria: a cross-sectional observational study.

PubMed

Oluwole, Oluwafemi; Arinola, Ganiyu O; Huo, Dezheng; Olopade, Christopher O

2017-01-05

In 2014, the International Study of Asthma and Allergies in Childhood (ISAAC) reported that the highest prevalence of symptoms of severe asthma was found in the low- and middle-income countries (LMICs), including Nigeria. While exposure to biomass fuel use may be an important risk factor in the development of asthma, its association with asthma symptoms severity has not been well-established. The aim of this study is to extend the spectrum of environmental risk factors that may be contributing towards increasing asthma morbidity, especially asthma symptoms severity in rural schoolchildren in Nigeria and to examine possible asthma underdiagnosis among this population. Authors conducted a cross-sectional survey in three rural communities in Nigeria. Asthma symptoms were defined according to the ISAAC criteria. Information on the types of household fuel used for cooking was used to determine household cooking fuel status. Asthma symptoms severity was defined based on frequencies of wheeze, day- and night-time symptoms, and speech limitations. Logistic regression analyses were used to explore associations. A total of 1,690 Nigerian schoolchildren participated in the study. Overall, 37 (2.2%) had diagnosed asthma and 413 (24.4%) had possible asthma (asthma-related symptoms but not diagnosed asthma). Children from biomass fuel households had higher proportion of possible asthma (27.7 vs. 22.2%; p < 0.05) and symptoms of severe asthma (18.2 vs. 7.6%; p = 0.048). In adjusted analyses, biomass fuel use was associated with increased odds of severe symptoms of asthma [odds ratios (OR) = 2.37; 95% CI: 1.16-4.84], but not with possible asthma (OR = 1.22; 95% CI: 0.95-1.56). In rural Nigerian children with asthma symptoms, the use of biomass fuel for cooking is associated with an increased risk of severe asthma symptoms. There is additional evidence that rural children might be underdiagnosed for asthma.

Asthma and subjective sleep disordered breathing in a large cohort of urban adolescents.

PubMed

Zandieh, Stephanie O; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M; Bruzzese, Jean-Marie

2017-01-02

Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. 12% reported SDB symptoms. Older and bi-racial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p <.001). Compared to those without probable asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p <.001). Among those with probable asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma.

Asthma and Subjective Sleep Disordered Breathing in a Large Cohort of Urban Adolescents

PubMed Central

Zandieh, Stephanie O.; Cespedes, Amarilis; Ciarleglio, Adam; Bourgeois, Wallace; Rapoport, David M.; Bruzzese, Jean-Marie

2017-01-01

Objective Sleep disordered breathing (SDB) has not been well studied in urban adolescents with asthma in community settings. Nor has the association of SDB symptoms and asthma severity been studied. We characterized self-reported symptoms suggesting SDB and investigated the association of SDB symptoms, probable asthma, and asthma severity. Methods 9,565 adolescents from 21 inner-city high schools were screened for an asthma intervention study. Students reported on symptoms suggesting SDB using questions from the 2007 NHANES, if they were ever diagnosed with asthma, and on asthma symptoms. Using generalized linear mixed models with logit link with school as a random intercept and adjusting for age, gender, and race/ethnicity, we examined associations of SDB symptoms, and demographic characteristics, probable asthma, and asthma severity. Results 12% reported SDB symptoms. Older and biracial participants (compared to Caucasian) had higher odds of symptoms suggesting SDB (p<.001). Compared to those without probable asthma, adolescents with probable asthma had 2.63 greater odds of reporting SDB symptoms (p<.001). Among those with probable asthma, the odds of reporting SDB symptoms increased with asthma severity. When exploring daytime severity and severity due to night wakening separately, results were similar. All results remained significant when controlling for age, gender, and ethnicity. Conclusions In a large urban community cohort of predominately ethnic minority adolescents, self-reported SDB symptoms were associated with probable asthma and increased asthma severity. This study highlights the importance of SDB as a modifiable co-morbidity of asthma. PMID:27740900

Interleukin-5 Inhibitors for Severe Asthma: Rationale and Future Outlook.

PubMed

Shrimanker, Rahul; Pavord, Ian D

2017-04-01

In this review, we outline the pathophysiology of severe asthma and discuss the role of anti-interleukin (IL)-5 inhibitors for the treatment of asthma. Anti-IL-5 treatments have shown efficacy in reducing the rate of severe asthma attacks in eosinophilic asthma. We review the history of the development of these agents, lessons learnt about severe asthma along the way and key clinical trials supporting efficacy of the three anti-IL-5 treatments that are clinically available or undergoing clinical trials in asthma.

Nasal polyps and the severity of asthma.

PubMed

Ceylan, Erkan; Gencer, Mehmet; San, Imran

2007-03-01

Upper airway pathologies often accompany asthma. Because this represents a single airway, the diagnosis, follow up and treatment of both upper and lower respiratory diseases is essential. Samter Syndrome (SS) is known to be associated with more severe asthma. The presence of nasal polyps (NPs) is also associated with asthma. However, the incidence of NPs in asthma and the effect of NPs on asthma severity are not well documented. Three hundred and forty-two asthma patients were evaluated by endoscopic nasal examination, pulmonary function test, skin prick tests and paranasal sinus tomography. Three hundred and eleven patients with asthma without NP, 19 asthma patients with NP and 12 patients with SS were included. It was found that 54.3% of patients without NPs, 63.2% with NP and 66.7% with SS were at step 3 on the Global Initiative for Asthma scale of severity, and 1.9%, 15.8% and 33.3% were at step 4, respectively. The presence of NPs in asthma patients is associated with an increase in asthma severity. In patients with asthma, the possibility of NPs should be investigated and treatment planned accordingly.

The epidemiology of asthma and its comorbidities in Poland--Health problems of patients with severe asthma as evidenced in the Province of Lodz.

PubMed

Panek, Michał; Mokros, Łukasz; Pietras, Tadeusz; Kuna, Piotr

2016-03-01

Population studies supply interesting data regarding the epidemiology, comorbidity and risk factors of asthma, which have direct clinical implications for patients. The aim of the work was to evaluate the degree of severity of asthma in the studied group, the levels of anti-asthma treatment, the prevalence of asthma comorbidities and their influence on the clinical course of the illness. The study encompassed 451 participants: 52.11% were asthma patients (study group) and 47.89% were healthy subjects (controls). Respiratory function tests, ACT™ test and skin prick tests were performed. Asthma severity was mild in 14.89%, moderate in 49.36% and severe in 35.74%. Oral GCS were used by 29%, inhalers 44%, LABA 68%, SABA 67%, LAMA 6%, SAMA 14% and MX 16%. Rhinitis and allergy were significantly more common in patients. GERD and neurological diseases were risk factors for asthma, and GERD significantly intensified the risk of severe asthma. GERD, atherosclerosis, hypertension, ischaemic heart disease and other cardiac diseases, lipid disorders, COPD, and the presence of any neoplastic disease significantly worsened the degree of asthma control. Severe asthma was a significant clinical issue in over 35% of cases. The most commonly-used group of drugs were LABAs, while inhaled GCS and LAMA were uncommon, especially among severe cases. A significant problem was the high percentage of systemic GCS used by severe cases. The most important risk factor for asthma, including its severe form, is GERD. Numerous comorbid conditions significantly worsen the degree of asthma control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeted therapy in severe asthma today: focus on immunoglobulin E.

PubMed

Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

2017-01-01

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard "one size fits all" approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma.

Targeted therapy in severe asthma today: focus on immunoglobulin E

PubMed Central

Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

2017-01-01

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard “one size fits all” approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma. PMID:28721017

An algorithmic approach for the treatment of severe uncontrolled asthma

PubMed Central

Zervas, Eleftherios; Samitas, Konstantinos; Papaioannou, Andriana I.; Bakakos, Petros; Loukides, Stelios; Gaga, Mina

2018-01-01

A small subgroup of patients with asthma suffers from severe disease that is either partially controlled or uncontrolled despite intensive, guideline-based treatment. These patients have significantly impaired quality of life and although they constitute <5% of all asthma patients, they are responsible for more than half of asthma-related healthcare costs. Here, we review a definition for severe asthma and present all therapeutic options currently available for these severe asthma patients. Moreover, we suggest a specific algorithmic treatment approach for the management of severe, difficult-to-treat asthma based on specific phenotype characteristics and biomarkers. The diagnosis and management of severe asthma requires specialised experience, time and effort to comprehend the needs and expectations of each individual patient and incorporate those as well as his/her specific phenotype characteristics into the management planning. Although some new treatment options are currently available for these patients, there is still a need for further research into severe asthma and yet more treatment options. PMID:29531957

Asthma in inner city children: recent insights: United States.

PubMed

Dutmer, Cullen M; Kim, Haejin; Searing, Daniel A; Zoratti, Edward M; Liu, Andrew H

2018-04-01

Children living in US inner cities experience disparate burdens of asthma, especially in severity, impairment, exacerbations, and morbidity. Investigations seeking to better understand the factors and mechanisms underlying asthma prevalence, severity, and exacerbation in children living in these communities can lead to interventions that can narrow asthma disparities and potentially benefit all children with asthma. This update will focus on recent (i.e. late 2016-2017) advances in the understanding of asthma in US inner city children. Studies published in the past year expand understanding of asthma prevalence, severity, exacerbation, and the outcomes of guidelines-based management of these at-risk children, including: asthma phenotypes in US inner city children that are severe and difficult-to-control; key environmental determinants and mechanisms underlying asthma severity and exacerbations (e.g. allergy-mediated exacerbation susceptibility to rhinovirus); the importance of schools as a place for provocative exposures (e.g. mouse allergen, nitrogen dioxide) as well as a place where asthma care and outcomes can be improved; and the development and validation of clinically useful indices for gauging asthma severity and predicting exacerbations. These recent studies provide a trove of actionable findings that can improve asthma care and outcomes for these at-risk children.

The Tempest: Difficult to Control Asthma in Adolescence.

PubMed

Burg, Gregory T; Covar, Ronina; Oland, Alyssa A; Guilbert, Theresa W

Severe asthma is associated with significant morbidity and is a highly heterogeneous disorder. Severe asthma in adolescence has some unique elements compared with the features of severe asthma a medical provider would see in younger children or adults. A specific focus on psychological issues and adherence highlights some of the challenges in the management of asthma in adolescents. Treatment of adolescents with severe asthma now includes 3 approved biologic phenotype-directed therapies. Therapies available to adults may be beneficial to adolescents with severe asthma. Research into predictors of specific treatment response by phenotypes is ongoing. Optimal treatment strategies are not yet defined and warrant further investigation. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Obesity increases the prevalence and the incidence of asthma and worsens asthma severity.

PubMed

Barros, R; Moreira, P; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Moreira, A

2017-08-01

We aimed to explore the association between obesity and asthma prevalence, incidence and severity. The study included 32,644 adults, 52.6% female, from a representative sample of the 4th Portuguese National Health Survey. The following asthma definitions were used: ever asthma (ever medical doctor asthma diagnosis), current asthma (asthma within the last 12 months), current persistent asthma (required asthma medication within the last 12 months), current severe asthma (attending an emergency department because of asthma within the last 12 months), and incident asthma (asthma diagnosis within the last 12 months). Body mass index was calculated based on self-reported weight and height and categorised according to WHO classification. Logistic regression models adjusted for confounders were performed. Prevalence of ever asthma was 5.3%, current asthma 3.5%, current persistent asthma 3.0%, current severe asthma 1.4%, and incident asthma 0.2%. Prevalence of obesity was 16%, overweight 37.6%, normal weight 44.6% and underweight 0.2%. Being overweight, obesity class I and II, and obesity class III were associated with an OR (95% CI) with ever asthma 1.22 (1.21-1.24), 1.39 (1.36-1.41), 3.24 (3.08-3.40) respectively; current asthma 1.16 (1.14-1.18), 1.86 (1.82-1.90), 4.73 (4.49-4.98) respectively; current persistent asthma 1.08 (1.06-1.10), 2.06 (2.01-2.10), 5.24 (4.96-5.53), and current severe asthma 1.36 (1.32-1.40), 1.50 (1.45-1.55) and 3.70 (3.46-3.95), respectively. Considering the incidence of asthma, obesity more than quadrupled the odds (OR = 4.46, 95% CI 4.30, 4.62). Obesity is associated in a dose dependent way with an increase of prevalent and incident asthma, and it seems to increase the odds of a more persistent and severe asthma phenotype independently of socio-demographic determinants, physical activity, and dietary patterns. Our results provide rational for future lifestyle intervention studies for weight reduction in the obesity-asthma phenotype. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The natural history of severe asthma and influences of early risk factors: a population-based cohort study.

PubMed

Chen, Wenjia; Marra, Carlo A; Lynd, Larry D; FitzGerald, J Mark; Zafari, Zafar; Sadatsafavi, Mohsen

2016-03-01

Severe asthma is associated with disproportionately high morbidity, but little is known about its natural history and how risk factors at first year of diagnosis modify its subsequent development. Using administrative health data, we retrospectively followed patients 14-55 years of age with newly diagnosed severe asthma in British Columbia, Canada. Based on intensity of resource use (drug therapy) and occurrence of exacerbations, each patient-year was classified into mild, moderate, or severe asthma. We estimated the probability of transition between severity levels or to death over the study period using a four-state Markov model, and used this to assess the 10-year trajectory of severe asthma and the influence of baseline risk factors. We followed 13,467 patients. Ten years after incident severe asthma, 83% had transitioned to a less severe level (mild: 43%, moderate: 40%). Low socioeconomic status, high comorbidity burden, and high adherence (proportion of days covered (PDC) by asthma controller therapy) in the first year were independently associated with, respectively, 10%, 24% and 35% more time in severe asthma over the next 10 years. Sex was not associated with the clinical course. Most patients with incident severe asthma used fewer resources over time, indicating a long-term transition to milder asthma. Potentially modifiable risk factors for poor prognosis of severe asthma include low socioeconomic status and high comorbidity burden. The association between PDC and future asthma severity is likely due to residual confounding by disease severity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Occupational exposures associated with severe exacerbation of asthma.

PubMed

Henneberger, P K; Liang, X; Lillienberg, L; Dahlman-Höglund, A; Torén, K; Andersson, E

2015-02-01

The exacerbation of asthma by workplace conditions is common, but little is known about which agents pose a risk. We used data from an existing survey of adults with asthma to identify occupational exposures associated with severe exacerbation of asthma. Questionnaires were completed by 557 working adults with asthma. Severe exacerbation of asthma in the past 12 months was defined as asthma-related hospitalization, or reports of both unplanned asthma care and treatment with a short course of oral corticosteroids. Occupational exposures for the same time period were assessed using an asthma-specific job exposure matrix. We modeled severe exacerbation to yield prevalence ratios (PRs) for exposures while controlling for potential confounders. A total of 164 participants (29%) were positive for severe exacerbation, and 227 (40.8%) were assessed as being exposed to asthma agents at work. Elevated PRs were observed for several specific agents, notably the irritant subcategories of environmental tobacco smoke (PR 1.84, 95%CI 1.34-2.51) among all participants, inorganic dusts (PR 2.53, 95%CI 1.37-4.67) among men, and the low molecular weight subcategory of other highly reactive agents (PR 1.97, 95%CI 1.08-3.60) among women. Among working adults with asthma, severe exacerbation was associated with several occupational agents.

Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

PubMed

Boita, Monica; Heffler, Enrico; Omedè, Paola; Bellocchia, Michela; Bussolino, Claudia; Solidoro, Paolo; Giorgis, Veronica; Guerrera, Francesco; Riva, Giuseppe; Brussino, Luisa; Bucca, Caterina; Rolla, Giovanni

2018-01-01

Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity. © 2018 S. Karger AG, Basel.

The airway microbiome in patients with severe asthma: Associations with disease features and severity.

PubMed

Huang, Yvonne J; Nariya, Snehal; Harris, Jeffrey M; Lynch, Susan V; Choy, David F; Arron, Joseph R; Boushey, Homer

2015-10-01

Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in patients with mild-to-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. We sought to evaluate relationships between the bronchial microbiome and features of severe asthma. Bronchial brushings from 40 participants in the Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between patients with severe asthma and previously studied healthy control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41). In patients with severe asthma, bronchial bacterial composition was associated with several disease-related features, including body mass index (P < .05, Bray-Curtis distance-based permutational multivariate analysis of variance; PERMANOVA), changes in Asthma Control Questionnaire (ACQ) scores (P < .01), sputum total leukocyte values (P = .06), and bronchial biopsy eosinophil values (per square millimeter, P = .07). Bacterial communities associated with worsening ACQ scores and sputum total leukocyte values (predominantly Proteobacteria) differed markedly from those associated with body mass index (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ scores and bronchial epithelial gene expression of FK506 binding protein (FKBP5), an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophil values and Proteobacteria. No taxa were associated with a TH2-related epithelial gene expression signature, but expression of TH17-related genes was associated with Proteobacteria. Patients with severe asthma compared with healthy control subjects or patients with mild-to-moderate asthma were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8-fold increase in patients with severe asthma, adjusted P < .001). Specific microbiota are associated with and may modulate inflammatory processes in patients with severe asthma and related phenotypes. Airway dysbiosis in patients with severe asthma appears to differ from that observed in those with milder asthma in the setting of inhaled corticosteroid use. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The relationship between the Leicester cough questionnaire, eosinophilic airway inflammation and asthma patient related outcomes in severe adult asthma.

PubMed

Natarajan, Sushiladevi; Free, Robert C; Bradding, Peter; McGarvey, Lorcan; Siddiqui, Salman

2017-03-04

Severe asthma is characterised by a variety of symptoms, which include chronic cough, however the mechanisms responsible for cough reflex hypersensitivity in asthma remain poorly elucidated. Current asthma patient-related outcome instruments such as the six-point Juniper Asthma Control Score (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) were not primarily designed to capture cough and its related morbidity in asthma. The Leicester Cough Questionnaire (LCQ) is a patient-related outcome instrument designed to capture the health-related quality of life associated with cough. To date the LCQ has not been evaluated in a severe asthma population. We evaluated 262 extensively characterised adult patients with severe asthma attending the Leicester Severe Asthma Service. All patients had a clinician diagnosis of asthma and objective physiological evidence and met the ATS/ERS criterion for servere asthma. In all patients we evaluated a) the LCQ distribution and b) the relationships between the LCQ and ACQ-6, AQLQ, airway inflammation in sputum. The LCQ demonstrated the following properties; mean: 15.0, standard deviation: 4.54, median: 15.48, and range: 11.6-19.2. We found a moderate correlation between LCQ and ACQ-6 (r = - 0.605, p < 0.0001) and a LCQ and AQLQ (r = 0.710, p < 0.0001). There was no relationship between LCQ and log 10 sputum percentage eosinophils (%). A proportion of patients with severe asthma have a significant degree of cough-related morbidity that appears independent of eosinophilic airway inflammation and is not captured fully by existing asthma patient-reported outcome instruments. Our preliminary findings suggest that further research is now required to validate the LCQ and its responsiveness in severe asthma populations to capture cough-related morbidity and response to specific interventions.

The Airway Microbiome in Severe Asthma: Associations with Disease Features and Severity

PubMed Central

Huang, Yvonne J.; Nariya, Snehal; Harris, Jeffrey M.; Lynch, Susan V.; Choy, David F.; Arron, Joseph R.; Boushey, Homer

2015-01-01

Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in mild-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. Objective To evaluate relationships between the bronchial microbiome and features of severe asthma. Methods Bronchial brushings from 40 participants in the BOBCAT study (Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma) were evaluated using 16S rRNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between severe asthmatics, and previously studied healthy controls (n=7), and mild-moderate asthma subjects (n=41). Results In severe asthma, bronchial bacterial composition was associated with several disease-related features, including body-mass index (BMI; Bray-Curtis distance PERMANOVA, p < 0.05), changes in Asthma Control Questionnaire (ACQ) scores (p < 0.01), sputum total leukocytes (p = 0.06) and bronchial biopsy eosinophils (per mm2; p = 0.07). Bacterial communities associated with worsening ACQ and sputum total leukocytes (predominantly Proteobacteria) differed markedly from those associated with BMI (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ and bronchial epithelial gene expression of FKBP5, an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophils and Proteobacteria. No taxa were associated with a T-helper type 2-related epithelial gene expression signature, but expression of Th17-related genes was associated with Proteobacteria. Severe asthma subjects, compared to healthy controls or mild-moderate asthmatics, were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8 fold-increase in severe asthma, padj < 0.001) Conclusions Specific microbiota are associated with and may modulate inflammatory processes in severe asthma and related phenotypes. Airway dysbiosis in severe asthma appears to differ from that observed in milder asthma in the setting of inhaled corticosteroid use. PMID:26220531

Co-morbidities in severe asthma: Clinical impact and management.

PubMed

Porsbjerg, Celeste; Menzies-Gow, Andrew

2017-05-01

Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma to identify treatment barriers and triggers of asthma symptoms, including co-morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma. This review provides the clinician with an overview of the prevalence and clinical impact of the most common co-morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD), bronchiectasis, allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatous with polyangiitis (EGPA). Furthermore, the review offers a summary of recommended diagnostic and management approaches for each co-morbidity. Finally, the review links co-morbid conditions to specific phenotypes of severe asthma, in order to guide the clinician on which co-morbidities to look for in specific patients. © 2017 Asian Pacific Society of Respirology.

Perceptions of non-traditional tobacco products between asthmatic and non-asthmatic college students.

PubMed

Martinasek, Mary P; White, Robin M; Wheldon, Christopher W; Gibson-Young, Linda

2018-05-01

Electronic nicotine delivery systems (ENDS) use is common among college students and there are perceptions that ENDS are not as harmful as traditional cigarettes. The aim of this study was to examine differences in ENDS use, risk perceptions and co-occurring smoking behaviors between college students with and without asthma. The study consisted of a cross-sectional online survey with a final sample size of 898 college students. The voluntary participation survey was disseminated to all undergraduate and graduate students at a mid-sized liberal arts university in the Southeast U.S. in the fall of 2014. Approximately 19.7% reported that they had been previously diagnosed with asthma. Forty three percent of participants (n = 384) used ENDS in the past 30 days. Equivalent percentages of college students with asthma (46.9%) and college students without asthma (46.9%) have tried ENDS. Overall participants indicated that they perceived ENDS use as less (44%) or equally (38%) as harmful as cigarettes. College students with asthma had 2.85 (95% CI: 1.18-6.89) greater odds of being in the poly user class, which was characterized by dual use of ENDS, combustible cigarettes, hookah, and marijuana. In this study, college students with asthma were similar to their peers with regard to their use of ENDS and related risk perceptions; however, a small subsample of those with asthma exhibited problematic smoking behaviors characterized by dual use of multiple tobacco products including marijuana.

Assessment of variations in control of asthma over time.

PubMed

Combescure, C; Chanez, P; Saint-Pierre, P; Daurès, J P; Proudhon, H; Godard, P

2003-08-01

Control and severity of asthma are two different but complementary concepts. The severity of asthma could influence the control over time. The aim of this study was to demonstrate this relationship. A total 365 patients with persistent asthma (severity) were enrolled and followed-up prospectively. Data were analysed using a continuous time homogeneous Markov model of the natural history of asthma. Control of asthma was defined according to three health states which were qualified: optimal, suboptimal and unacceptable control (states 1, 2 and 3). Transition forces (denoted lambda(ij) from state i to state j) and transition probabilities between control states were assessed and the results stratified by asthma severity were compared. Models were validated by comparing expected and observed numbers of patients in the different states. Transition probabilities stabilised between 100-250 days and more rapidly in patients with mild-to-moderate asthma. Patients with mild-to-moderate asthma in suboptimal or unacceptable control had a high probability of transition directly to optimal control. Patients with severe asthma had a tendency to remain in unacceptable control. A Markov model is a useful tool to model the control of asthma over time. Severity modified clearly the health states. It could be used to compare the performance of different approaches to asthma management.

Airway lipoxin A4 generation and lipoxin A4 receptor expression are decreased in severe asthma.

PubMed

Planagumà, Anna; Kazani, Shamsah; Marigowda, Gautham; Haworth, Oliver; Mariani, Thomas J; Israel, Elliot; Bleecker, Eugene R; Curran-Everett, Douglas; Erzurum, Serpil C; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Gaston, Benjamin; Jarjour, Nizar N; Busse, William W; Wenzel, Sally E; Levy, Bruce D

2008-09-15

Airway inflammation is common in severe asthma despite antiinflammatory therapy with corticosteroids. Lipoxin A(4) (LXA(4)) is an arachidonic acid-derived mediator that serves as an agonist for resolution of inflammation. Airway levels of LXA(4), as well as the expression of lipoxin biosynthetic genes and receptors, in severe asthma. Samples of bronchoalveolar lavage fluid were obtained from subjects with asthma and levels of LXA(4) and related eicosanoids were measured. Expression of lipoxin biosynthetic genes was determined in whole blood, bronchoalveolar lavage cells, and endobronchial biopsies by quantitative polymerase chain reaction, and leukocyte LXA(4) receptors were monitored by flow cytometry. Individuals with severe asthma had significantly less LXA(4) in bronchoalveolar lavage fluids (11.2 +/- 2.1 pg/ml) than did subjects with nonsevere asthma (150.1 +/- 38.5 pg/ml; P < 0.05). In contrast, levels of cysteinyl leukotrienes were increased in both asthma cohorts compared with healthy individuals. In severe asthma, 15-lipoxygenase-1 mean expression was decreased fivefold in bronchoalveolar lavage cells. In contrast, 15-lipoxgenase-1 was increased threefold in endobronchial biopsies, but expression of both 5-lipoxygenase and 15-lipoxygenase-2 in these samples was decreased. Cyclooxygenase-2 expression was decreased in all anatomic compartments sampled in severe asthma. Moreover, LXA(4) receptor gene and protein expression were significantly decreased in severe asthma peripheral blood granulocytes. Mechanisms underlying pathological airway responses in severe asthma include lipoxin underproduction with decreased expression of lipoxin biosynthetic enzymes and receptors. Together, these results indicate that severe asthma is characterized, in part, by defective lipoxin counterregulatory signaling circuits.

Characteristics of Perimenstrual Asthma and Its Relation to Asthma Severity and Control

PubMed Central

Rao, Chitra K.; Moore, Charity G.; Bleecker, Eugene; Busse, William W.; Calhoun, William; Castro, Mario; Chung, Kian Fan; Erzurum, Serpil C.; Israel, Elliot; Curran-Everett, Douglas

2013-01-01

Background: Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control. Methods: Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control. Results: Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization. Conclusions: PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype. PMID:23632943

[Predictive factors associated with severity of asthma exacerbations].

PubMed

Atiş, Sibel; Kaplan, Eylem Sercan; Ozge, Cengiz; Bayindir, Suzan

2008-01-01

Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

Factors that influence quality of life in rural children with asthma and their parents.

PubMed

Walker, Jennifer; Winkelstein, Marilyn; Land, Cassia; Lewis-Boyer, Lapricia; Quartey, Ruth; Pham, Luu; Butz, Arlene

2008-01-01

Among rural children with asthma and their parents, this study examined the relationship between parental and child reports of quality of life and described the relationship of several factors such as asthma severity, missed days of work, and asthma education on their quality of life. Two hundred one rural families with asthma were enrolled in a school-based educational program. Intervention parents and children participated in interactive asthma workshop(s) and received asthma devices and literature. Parent and child quality of life measurements were obtained before and after the intervention using Juniper's Paediatric Caregivers Quality of Life and Juniper's Paediatric Quality of Life Questionnaires. Asthma severity was measured using criteria from the National Asthma Education and Prevention Program guidelines. There was no association between parent and child total quality of life scores, and mean parental total quality of life scores were higher at baseline and follow-up than those of the children. All the parents' quality of life scores were correlated with parental reports of missed days of work. For all children, emotional quality of life (EQOL) was significantly associated with parental reports of school days missed (P = .03) and marginally associated with parental reports of hospitalizations due to asthma (P = .08). Parent's EQOL and activity quality of life (AQOL) were significantly associated with children's asthma severity (EQOL, P = .009; AQOL, P = .03), but not the asthma educational intervention. None of the child quality of life measurements was associated with asthma severity. Asthma interventions for rural families should help families focus on gaining and maintaining low asthma severity levels to enjoy an optimal quality of life. Health care providers should try to assess the child's quality of life at each asthma care visit independently of the parents.

The association between endotoxin and beta-(1 → 3)-D-glucan in house dust with asthma severity among schoolchildren.

PubMed

Oluwole, Oluwafemi; Rennie, Donna C; Senthilselvan, Ambikaipakan; Dyck, Roland; Afanasieva, Anna; Kirychuk, Shelley; Katselis, George; Lawson, Joshua A

2018-05-01

Asthma severity can be affected by microbial exposures. However, less is known about the specific indoor agents aggravating the disease in children. We examined the associations between indoor endotoxin and beta-(1 → 3)-D-glucan exposures and asthma severity in children with asthma. A clinical cross-sectional study of schoolchildren (aged 7-17 years) was conducted in the province of Saskatchewan, Canada. Children with asthma (n = 116) were identified from 335 participants using a combination of survey responses and objective clinical assessments. We then ascertained asthma severity based on recommended guidelines (continuous daytime asthma symptoms, frequent nighttime asthma symptoms, and ≤ 60% predicted FEV 1 ). Levels of indoor endotoxin and beta-(1 → 3)-D-glucan were measured in dust samples obtained from play area floors and child's mattresses. The study population of 116 children with asthma was comprised of 75.9% mild asthma and 24.1% moderate/severe asthma. Higher mattress endotoxin concentration was associated with increased odds of moderate/severe asthma [adjusted odds ratio (aOR) = 11.40, 95% confidence interval (CI): 1.45-89.43] while higher beta-(1 → 3)-D-glucan concentration (aOR = 0.16, 95% CI: 0.03-0.89) and load (aOR = 0.10, 95% CI: 0.02-0.72) in play areas were inversely associated with moderate/severe asthma. Furthermore, higher mattress endotoxin concentration was associated with lower FVC (p = 0.01) and FEV 1 (p = 0.03). These associations were not seen for beta-(1 → 3)-D-glucan. Our results showed differential effects of microbial exposures on childhood asthma severity and further highlight domestic endotoxin exposure effects on respiratory health outcomes in children with asthma. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alterations of the arginine metabolome in asthma.

PubMed

Lara, Abigail; Khatri, Sumita B; Wang, Zeneng; Comhair, Suzy A A; Xu, Weiling; Dweik, Raed A; Bodine, Melanie; Levison, Bruce S; Hammel, Jeffrey; Bleecker, Eugene; Busse, William; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar; Moore, Wendy; Peters, Stephen P; Teague, W Gerald; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2008-10-01

As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation. We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity. Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated. Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma. Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.

Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis.

PubMed

Moore, Wendy C; Hastie, Annette T; Li, Xingnan; Li, Huashi; Busse, William W; Jarjour, Nizar N; Wenzel, Sally E; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

2014-06-01

Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma. To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation. Published by Mosby, Inc.

Sputum neutrophils are associated with more severe asthma phenotypes using cluster analysis

PubMed Central

Moore, Wendy C.; Hastie, Annette T.; Li, Xingnan; Li, Huashi; Busse, William W.; Jarjour, Nizar N.; Wenzel, Sally E.; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.

2013-01-01

Background Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified five asthma subphenotypes that represent the severity spectrum of early onset allergic asthma, late onset severe asthma and severe asthma with COPD characteristics. Analysis of induced sputum from a subset of SARP subjects showed four sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophils (≥2%) and neutrophils (≥40%) had characteristics of very severe asthma. Objective To better understand interactions between inflammation and clinical subphenotypes we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods Participants in SARP at three clinical sites who underwent sputum induction were included in this analysis (n=423). Fifteen variables including clinical characteristics and blood and sputum inflammatory cell assessments were selected by factor analysis for unsupervised cluster analysis. Results Four phenotypic clusters were identified. Cluster A (n=132) and B (n=127) subjects had mild-moderate early onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of Cluster C (n=117) and D (n=47) subjects who had moderate-severe asthma with frequent health care utilization despite treatment with high doses of inhaled or oral corticosteroids, and in Cluster D, reduced lung function. The majority these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophils were the most important variables determining cluster assignment. Conclusion This multivariate approach identified four asthma subphenotypes representing the severity spectrum from mild-moderate allergic asthma with minimal or eosinophilic predominant sputum inflammation to moderate-severe asthma with neutrophilic predominant or mixed granulocytic inflammation. PMID:24332216

Body Mass Index and Comorbidities in Adult Severe Asthmatics

PubMed Central

Bruno, Andreina; Pace, Elisabetta; Cibella, Fabio; Chanez, Pascal

2014-01-01

Both severe asthma and obesity are growing health problems. Severe asthma leads to a poor quality of life. The relationship among BMI, comorbidities, and severe asthma control in adults is still unclear. The aim of the study is to better understand the effect of the comorbidities as atopy, type II diabetes, OSAS, gastroesophageal reflux, hypertension, cardiovascular diseases, osteoporosis, infections, and psychological factors with BMI on asthma control in a cohort of adult severe asthmatics. One hundred and two patients were enrolled in a cross-sectional study assessing asthma control, treatments, pulmonary function, inflammatory markers, and comorbidities. Patients were divided into 3 classes according to BMI: normal weight, overweight, and obese. We found that the optimal state of asthma control is lower. whereas the score of Asthma Control Questionnaire, the number of asthma exacerbations during last year, the oral corticosteroids requirement during the previous year, and the LABA treatments are higher in obese than in overweight and normal weight severe asthmatics. The number of subjects with type II diabetes and OSAS are higher among obese and overweight patients than in normal weight asthmatics. In conclusion, BMI represents per se a factor for the deterioration in disease control in severe asthma. PMID:24987694

Positive exercise test and obstructive spirometry in young male conscripts associated with persistent asthma 20 years later.

PubMed

Lindström, Irmeli; Suojalehto, Hille; Lindholm, Harri; Pallasaho, Paula; Luukkonen, Ritva; Karjalainen, Jouko; Lauerma, Antti; Karjalainen, Antti

2012-12-01

Asthma often begins in childhood or early adulthood and is a common disease among conscripts. The identification of long-term predictive factors for persistent asthma may lead to improved treatment opportunities and better disease control. Our aim was to study the prognostic factors of the severity of asthma among 40-year-old male conscripts whose asthma began in youth. We studied 119 conscripts who were referred to the Central Military Hospital during 1987-1990 due to asthma and who attended a follow-up visit approximately 20 years later. Asthma severity was evaluated during military service according to the medical records, and 20 years later during a follow-up visit using Global Initiative for Asthma guidelines. We used the results of lung function and allergy tests at baseline as predictors of current persistent asthma. Compared with baseline, asthma was less severe at follow-up: 11.8% of subjects were in remission, 42.0% had intermittent asthma, 10.9% had mild persistent asthma, and 35.3% had moderate/severe persistent asthma (p < .001). In multivariate models, a positive exercise test at baseline yielded an odds ratio (OR) of 3.2 (95% CI 1.0-9.8, p = .046), a decreased FEV1/FVC % predicted an OR of 4.0 (95% CI 1.7-9.3, p = .002), and a decreased FEF50% % predicted an OR of 2.8 (95% CI 1.3-6.4, p = .012) for current persistent asthma. About half of the men had persistent asthma at the 20-year follow-up. Positive exercise tests and obstructive spirometry results were related to the persistence of asthma and may be useful long-term prognostic factors for asthma severity.

Rubbing ointments and asthma morbidity in adolescents.

PubMed

Reznik, Marina; Sharif, Iman; Ozuah, Philip O

2004-12-01

To determine the relationship between the use of rubbing ointments and asthma morbidity in adolescents. Cross-sectional study. Inner-city high school in the Bronx, New York. 165 adolescents with asthma. Asthma morbidity, defined as emergency department (ED) use for asthma in the past year and over the lifetime. While 127 (77%) of subjects used albuterol as the first treatment for their last asthma attack, 18 (11%) used rubbing ointments. The rubs and albuterol groups were similar in asthma severity, mean age, gender, and ethnicity. However, subjects in the the rubs group were less likely than subjects in the albuterol group to have made an ED visit over the past 12 months or over their lifetime. Regression analysis revealed that, after controlling for asthma severity, use of rubs independently predicted less lifetime ED use. After controlling for asthma severity, use of rubs by adolescents with asthma was associated with lower asthma morbidity as measured by ED use.

B-Glucan exacerbates allergic asthma independent of fungal ...

EPA Pesticide Factsheets

BackgroundAllergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity.ObjectiveWe sought to determine the mechanism by which fungi affect asthma development and severity.MethodsWe integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity.ResultsWe report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with β-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc−/− mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity.ConclusionOur data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma. To describe th

Phenotype-Driven Therapeutics in Severe Asthma.

PubMed

Opina, Maria Theresa D; Moore, Wendy C

2017-02-01

Inhaled corticosteroids are the mainstay of asthma treatment using a step-up approach with incremental dosing and additional controller medications in order to achieve symptom control and prevent exacerbations. While most patients respond well to this treatment approach, some patients remain refractory despite high doses of inhaled corticosteroids and a long-acting β-agonist. The problem lies in the heterogeneity of severe asthma, which is further supported by the emergence of severe asthma phenotypes. This heterogeneity contributes to the variability in treatment response. Randomized controlled trials involving add-on therapies in poorly controlled asthma have challenged the idea of a "one size fits all" approach targeting specific phenotypes in their subject selection. This review discusses severe asthma phenotypes from unbiased clustering approaches and the most recent scientific evidence on novel treatments to provide a guide in personalizing severe asthma treatment.

Risk factors for death in patients with severe asthma*

PubMed Central

Fernandes, Andréia Guedes Oliva; Souza-Machado, Carolina; Coelho, Renata Conceição Pereira; Franco, Priscila Abreu; Esquivel, Renata Miranda; Souza-Machado, Adelmir; Cruz, Álvaro Augusto

2014-01-01

OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4). Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality. PMID:25210958

Prevalence of asthma in Galway school children 2004.

PubMed

Shabu, A; Flanagan, O; Dineen, B; Loftus, B G

2007-06-01

We aimed to ascertain the prevalence of asthma amongst Galway schoolchildren aged 9-10, and to compare the results to a similar study carried out in 1992. A questionnaire was distributed to parents of all children attending 4th class in Galway city schools. 652 of 750(87%) questionnaires were returned. Prevalence of "wheeze ever" was 27.6%, and "current wheeze" 16.3%. The prevalence of asthma was 18.5%. Of those with asthma there was a 2 to 1 male preponderance, 80% had mild asthma, 14% moderate, and 6% severe asthma. 80% were taking anti-asthma therapy, with 48% taking regular inhaled steroids. 84% had a diagnosis of asthma made by a doctor. Comparison with the study of 1992 shows little change in the prevalence of current wheeze, or asthma. There has however been a significant decline in the severity of asthma, and an increase in the use of prophylactic anti-asthma medication. Asthma prevalence appears to be stable in the age group studied. There is a much greater willingness to diagnose, and treat asthma in the community. The severity of asthma, as measured by attack frequency, has declined.

Impact of asthma medication and familial factors on the association between childhood asthma and attention-deficit/hyperactivity disorder: a combined twin- and register-based study: Epidemiology of Allergic Disease.

PubMed

Holmberg, K; Lundholm, C; Anckarsäter, H; Larsson, H; Almqvist, C

2015-05-01

Asthma and attention-deficit/hyperactivity disorder (ADHD) are prevalent in childhood and may cause functional impairment and stress in families. Previous research supports an association between asthma and ADHD in children, but several aspects of this relationship are unclear. Our aim was to study whether the association between asthma and ADHD is restricted to either the inattentive or the hyperactive/impulsive symptoms of ADHD, to explore the impact of asthma severity and asthma medication and the contribution of shared genetic and environmental risk factors on the asthma-ADHD relationship. Data on asthma, ADHD, zygosity and possible confounders were collected from parental questionnaires at 9 or 12 years on 20 072 twins through the Swedish Twin Register, linked to the Swedish Medical Birth Register, the National Patient Register and the Prescribed Drug Register. The association between asthma and ADHD, the impact of asthma severity and medication, was assessed by generalized estimating equations. Cross-twin-cross-trait correlations (CTCT) were estimated to explore the relative importance of genes and environment for the association. Asthmatic children had a higher risk of also having ADHD [odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02]. The association was not restricted to either of the two dimensions of ADHD. The magnitude of the association increased with asthma severity (OR 2.84, 95% CI: 1.86-4.35) for ≥ 4 asthma attacks in the last 12 months and was not affected by asthma treatment. The CTCTs possibly indicate that the genetic component in overlap of the disorders is weak. Childhood asthma, especially severe asthma, is associated with ADHD. Asthma medication seems not to increase the risk of ADHD. Clinicians should be aware of the potential of ADHD in asthma. Optimal asthma care needs to be integrated with effective evaluation and treatment of ADHD in children with co-existing disorders. © 2015 John Wiley & Sons Ltd.

p38 Mitogen-Activated Protein Kinase-γ Inhibition by Long-Acting β2 Adrenergic Agonists Reversed Steroid Insensitivity in Severe Asthma

PubMed Central

Mercado, Nicholas; To, Yasuo; Kobayashi, Yoshiki; Adcock, Ian M.; Barnes, Peter J.

2011-01-01

Corticosteroid insensitivity (CI) is a major barrier to treating severe asthma. Despite intensive research, the molecular mechanism of CI remains uncertain. The aim of this study was to determine abnormality in corticosteroid action in severe asthma and to identify the molecular mechanism of the long-acting β2-adrenergic agonists (LABAs) formoterol and salmeterol on restoration of corticosteroid sensitivity in severe asthma in vitro. Peripheral blood mononuclear cells (PBMCs) were obtained from 16 subjects with severe corticosteroid-insensitive asthma, 6 subjects with mild corticosteroid-sensitive asthma, and 11 healthy volunteers. Corticosteroid (dexamethasone) sensitivity was determined on tumor necrosis factor-α (TNF-α)-induced interleukin (IL)-8 production. Glucocorticoid receptor (GR) phosphorylation and kinase phosphorylation were evaluated by immunoprecipitation-Western blotting analysis and kinase phosphorylation array in IL-2/IL-4-treated corticosteroid insensitive model in PBMCs. In vitro corticosteroid sensitivity on TNF-α-induced IL-8 production was significantly lower in patients with severe asthma than in healthy volunteers and patients with mild asthma. This CI seen in severe asthma was associated with reduced GR nuclear translocation and with hyperphosphorylation of GR, which were reversed by LABAs. In IL-2/IL-4-treated PBMCs, LABAs inhibited phosphorylation of Jun-NH2-terminal kinase and p38 mitogen-activated protein kinase-γ (p38MAPK-γ) as well as GR. In addition, cells with p38MAPK-γ knockdown by RNA interference did not develop CI in the presence of IL-2/IL-4. Furthermore, p38MAPK-γ protein expression was up-regulated in PBMCs from some patients with severe asthma. In conclusion, p38 MAPK-γ activation impairs corticosteroid action and p38 MAPK-γ inhibition by LABAs has potential for the treatment of severe asthma. PMID:21917909

The frequency of asthma exacerbations and healthcare utilization in patients with asthma from the UK and USA.

PubMed

Suruki, Robert Y; Daugherty, Jonas B; Boudiaf, Nada; Albers, Frank C

2017-04-27

Asthma exacerbations are frequent in patients with severe disease. This report describes results from two retrospective cohort studies describing exacerbation frequency and risk, emergency department (ED)/hospital re-admissions, and asthma-related costs by asthma severity in the US and UK. Patients with asthma in the US-based Clinformatics™ DataMart Multiplan IMPACT (2010-2011; WEUSKOP7048) and the UK-based Clinical Practice Research Datalink (2009-2011; WEUSKOP7092) databases were categorized by disease severity (Global Initiative for Asthma [GINA]; Step and exacerbation history) during the 12 months pre-asthma medical code (index date). Outcomes included: frequency of exacerbations (asthma-related ED visit, hospitalization, or oral corticosteroid use with an asthma medical code recorded within ±2 weeks) 12 months post-index, asthma-related ED visits/hospitalization, and asthma-related costs 30 days post-index. Risk of a subsequent exacerbation was determined by proportional hazard model. Of the 222,817 and 211,807 patients with asthma included from the US and UK databases, respectively, 12.5 and 8.4% experienced ≥1 exacerbation during the follow-up period. Exacerbation frequency increased with disease severity. Among the 5,167 and 2,904 patients with an asthma-related ED visit/hospitalization in the US and UK databases, respectively, 9.2 and 4.7% had asthma-related re-admissions within 30 days. Asthma-related re-admission rates and costs increased with disease severity, approximately doubling between GINA Step 1 and 5 and in patients with ≥2 versus <2 exacerbations in the previous year. Risk of a subsequent exacerbation increased 32-35% for an exacerbation requiring ED visit/hospitalization versus oral corticosteroids. Increased disease severity was associated with higher exacerbation frequency, ED/hospitalization re-admission, costs and risk of subsequent exacerbation, indicating that these patients require high-intensity post-exacerbation management.

Obese and Allergic Related Asthma Phenotypes Among Children Across the United States.

PubMed

Ross, Mindy K; Romero, Tahmineh; Sim, Myung S; Szilagyi, Peter G

2018-04-19

Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity and allergy related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and parent-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with parent-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. Among 4,427 children with asthma in this NSCH cohort, the association between race and phenotype is statistically significant (p<0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-non-allergic phenotype (p<0.001). ADD/ADHD was more likely to be present in allergic-not-obese children (OR 1.50, CI 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p<0.001). Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the U.S. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

Relationship of self-reported asthma severity and urgent health care utilization to psychological sequelae of the September 11, 2001 terrorist attacks on the World Trade Center among New York City area residents.

PubMed

Fagan, Joanne; Galea, Sandro; Ahern, Jennifer; Bonner, Sebastian; Vlahov, David

2003-01-01

Posttraumatic psychological stress may be associated with increases in somatic illness, including asthma, but the impact of the psychological sequelae of the September 11, 2001 terrorist attacks on physical illness has not been well documented. The authors assessed the relationship between the psychological sequelae of the attacks and asthma symptom severity and the utilization of urgent health care services for asthma since September 11. The authors performed a random digit dial telephone survey of adults in the New York City (NYC) metropolitan area 6 to 9 months after September 11, 2001. Two thousand seven hundred fifty-five demographically representative adults including 364 asthmatics were recruited. The authors assessed self-reported asthma symptom severity, emergency room (ER) visits, and unscheduled physician office visits for asthma since September 11. After adjustment for asthma measures before September 11, demographics, and event exposure in multivariate models posttraumatic stress disorder (PTSD) were a significant predictor of self-reported moderate-to-severe asthma symptoms (OR = 3.4; CI = 1.2-9.4), seeking care for asthma at an ER since September 11 (OR = 6.6; CI = 1.6-28.0), and unscheduled physician visits for asthma since September 11 (OR = 3.6; CI = 1.1-11.5). The number of PTSD symptoms was also significantly related to moderate-to-severe asthma symptoms and unscheduled physician visits since September 11. Neither a panic attack on September 11 nor depression since September 11 was an independent predictor of asthma severity or utilization in multivariate models after September 11. PTSD related to the September 11 terrorist attacks contributed to symptom severity and the utilization of urgent health care services among asthmatics in the NYC metropolitan area.

Air pollution and asthma severity in adults

PubMed Central

Rage, Estelle; Siroux, Valérie; Künzli, Nino; Pin, Isabelle; Kauffmann, Francine

2009-01-01

Objectives There is evidence that exposure to air pollution affects asthma, but the effect of air pollution on asthma severity has not been addressed. The aim was to assess the relation between asthma severity during the past 12 months and home outdoor concentrations of air pollution. Methods Asthma severity over the last 12 months was assessed in two complementary ways among 328 adult asthmatics from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA) examined between 1991 and 1995. The 4-class severity score integrated clinical events and type of treatment. The 5-level asthma score is based only on the occurrence of symptoms. Nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) concentrations were assigned to each residence using two different methods. The first was based on the closest monitor data from 1991–1995. The second consisted in spatial models that used geostatistical interpolations and then assigned air pollutants to the geo-coded residences (1998). Results Higher asthma severity score was significantly related to the 8-hour average of ozone during April-September (O3-8hr) and the number of days (O3-days) with 8-hour ozone averages above 110 μg.m−3 (for a 36-day increase, equivalent to the inter quartile range, in O3-days, odds ratio (95% confidence interval) 2.22 (1.61–3.07) for one class difference in score). Adjustment for age, sex, smoking habits, occupational exposure, and educational level did not alter results. Asthma severity was unrelated to NO2. Both exposure assessment methods and severity scores resulted in very similar findings. SO2 correlated with severity but reached statistical significance only for the model based assignment of exposure. Conclusions The observed associations between asthma severity and air pollution, in particular O3, support the hypothesis that air pollution at levels far below current standards increases asthma severity. PMID:19017701

Point-of-care blood eosinophil count in a severe asthma clinic setting.

PubMed

Heffler, Enrico; Terranova, Giovanni; Chessari, Carlo; Frazzetto, Valentina; Crimi, Claudia; Fichera, Silvia; Picardi, Giuseppe; Nicolosi, Giuliana; Porto, Morena; Intravaia, Rossella; Crimi, Nunzio

2017-07-01

One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers. A significant correlation between blood eosinophils assessed by the 2 devices was found (R 2  = 0.854, P < .001); similar correlations were found also for white blood cells, neutrophils, and lymphocytes. The point-of-care device had the ability to predict blood eosinophil cutoffs used to select patients for biologic treatments for severe eosinophilic asthma and the ELEN index, a composite score useful to predict sputum eosinophilia. The results of our study contribute to the validation of a point-of-care device to assess blood eosinophils and open the possibility of using this device for the management of severe asthma management. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Longitudinal changes in airway remodeling and air trapping in severe asthma

PubMed Central

Witt, Chad A.; Sheshadri, Ajay; Carlstrom, Luke; Tarsi, Jaime; Kozlowski, James; Wilson, Brad; Gierada, David; Hoffman, Eric; Fain, Sean; Cook-Granroth, Janice; Sajol, Geneline; Sierra, Oscar; Giri, Tusar; O'Neil, Michael; Zheng, Jie; Schechtman, Kenneth B.; Bacharier, Leonard B.; Jarjour, Nizar; Busse, William; Castro, Mario

2014-01-01

Rationale and Objectives Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aims to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma. Materials and Methods Phenotypic characterization and quantitative multidetector computed tomography (MDCT) of the chest was performed at baseline and ∼2.6 years later in 38 participants with asthma (severe n=24, mild-moderate n=14) and 9 normal controls from the Severe Asthma Research Program. Results Subjects with severe asthma had a significant decline in post-bronchodilator FEV1% predicted over time (p = <0.001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent (WA%): p <0.05) and normals (p <0.05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness (WT%) in all subjects (p = 0.030 and 0.009 respectively) with no change in emphysema-like lung or air trapping. Baseline pre-bronchodilator FEV1% inversely correlated with WA% and WT% (both p = <0.05). In a multivariable regression model, baseline WA%, race and healthcare utilization were predictors of subsequent airway remodeling. Conclusions Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling. PMID:25018070

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma

PubMed Central

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin

2015-01-01

Background Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. Methods We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Results Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. Conclusions PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma. PMID:26658828

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

PubMed

Shrestha Palikhe, Nami; Nahirney, Drew; Laratta, Cheryl; Gandhi, Vivek Dipak; Vethanayagam, Dilini; Bhutani, Mohit; Mayers, Irvin; Cameron, Lisa; Vliagoftis, Harissios

2015-01-01

Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma.

Systemic Corticosteroid Responses in Children with Severe Asthma: Phenotypic and Endotypic Features.

PubMed

Fitzpatrick, Anne M; Stephenson, Susan T; Brown, Milton R; Nguyen, Khristopher; Douglas, Shaneka; Brown, Lou Ann S

Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking. This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response. Asthma-related quality of life, exhaled nitric oxide, blood eosinophils, lung function, and inflammatory cytokine and chemokine mRNA gene expression in peripheral blood mononuclear cells were assessed in 56 children with severe asthma at baseline and 14 days after intramuscular triamcinolone injection. The Asthma Control Questionnaire was used to classify children with severe asthma into corticosteroid response groups. Three groups of children with severe asthma were identified: controlled severe asthma, children who achieved control after triamcinolone, and children who did not achieve control. At baseline, these groups were phenotypically similar. After triamcinolone, discordance between symptoms, lung function, exhaled nitric oxide, and blood eosinophils was noted. Clinical phenotypic predictors were of limited utility in predicting the triamcinolone response, whereas systemic mRNA expression of inflammatory cytokines and chemokines related to IL-2, IL-10, and TNF signaling pathways, namely, AIMP1, CCR2, IL10RB, and IL5, strongly differentiated children who failed to achieve control with triamcinolone administration. Systemic corticosteroid responsiveness in children with severe asthma is heterogeneous. Alternative prediction models that include molecular endotypic as well as clinical phenotypic features are needed to identify which children derive the most clinical benefit from systemic corticosteroid step-up therapy given the potential side effects. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Current concepts of severe asthma

PubMed Central

Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

2016-01-01

The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

Depressive Symptomatology, Quality of Life and Disease Control among Individuals with Well-Characterized Severe Asthma

PubMed Central

Yonas, Michael A.; Marsland, Anna L.; Emeremni, Chetachi A.; Moore, Charity G.; Holguin, Fernando; Wenzel, Sally

2014-01-01

Objectives A thorough examination of the relationship of asthma severity and control with symptoms of depression is needed to identify groups of asthmatics at high risk for poor disease control outcomes. This study examines the relationship of symptoms of depression with severity and control in a well characterized cohort of asthmatics and healthy controls. Methods Depressive symptoms and quality of life were assessed using the Beck Depression Inventory. Disease control was measured by a composite index incorporating symptoms, activity limitation, and rescue medication use. Results Individuals with asthma (n=91) reported more symptoms of depression than controls (n=36; p<0.001). Those with Severe asthma (n=49) reported more symptoms of depression (p=0.002) and poorer asthma control (p<0.0001) than those with Not Severe asthma. Worse asthma control was associated with more depressive symptoms in Severe (r=0.46, p=0.002) but not in Not Severe (r=0.13, p=0.40) asthmatics. The relationship of symptoms of depression among Severe asthmatics was attenuated by disease control. Exploratory analyses identified specific disease symptom characteristics, as opposed to exacerbations, as associated with symptoms of depression. Conclusions Among individuals with severe asthma, increased symptom burden is positively associated with risk for co-morbid depression. These findings point to a need for regular mood disorder screenings and treatment referrals among this group. Further research is warranted to examine whether treatment of comorbid depression improves treatment adherence and asthma-related quality of life. PMID:23725317

Adolescent girls with asthma have worse asthma control and health-related quality of life than boys-A population based study.

PubMed

Stridsman, Caroline; Backman, Helena; Eklund, Britt-Marie; Rönmark, Eva; Hedman, Linnea

2017-07-01

Population-based studies investigating health-related quality of life (HRQoL) among asthmatic adolescents are rare. Further, among subjects with asthma, HRQoL may be affected by asthma control and severity. To investigate HRQoL in relation to asthma control and asthma severity among adolescents. As a part of the population-based OLIN pediatric study, 266 adolescents with current asthma (14-15 yr) were identified. N = 247 completed the DISABKIDS HRQoL asthma module, including the domains impact and worry. The Asthma Control Test (ACT) was used and a disease severity score was calculated based on symptoms and medicine use. The prevalence of current asthma was 11%. Well-controlled asthma was reported by 15% of the adolescents, and 53% had partly controlled asthma. The prevalence of uncontrolled asthma was significantly higher among girls than boys (38% vs 25%), and girls also reported lower HRQoL scores. There was a fairly strong correlation between the ACT and DISABKIDS scores. Independent risk factors for low HRQoL impact (a score <67) were female sex (OR 4.66, 95%CI 1.82-9.54) and decreased ACT scores (1.38, 1.18-1.62). Risk factors for low HRQoL worry (a score <70) were female sex (3.33, 1.41-7.86), decreased ACT scores (1.35, 1.16-1.57), severe asthma (6.23, 1.46-16.50), and having current eczema (2.68, 1.00-7.24). Only a minority of the asthmatic adolescents reported well-controlled asthma, and poor asthma control and female sex were risk factors for low HRQoL. Our results demonstrate that evaluation of asthma control is of great importance for asthma management. © 2017 Wiley Periodicals, Inc.

The Medical Home Model and Pediatric Asthma Symptom Severity: Evidence from a National Health Survey.

PubMed

Rojanasarot, Sirikan; Carlson, Angeline M

2018-04-01

The objective was to investigate the association between receiving care under the medical home model and parental assessment of the severity of asthma symptoms. It was hypothesized that parents of children who received care under the medical home model reported less severe asthma symptoms compared with their counterparts, whose care did not meet the medical home criteria. Secondary analyses were conducted using cross-sectional data from the 2011-2012 National Survey of Children's Health. Children with asthma aged 0-17 years were included and classified as receiving care from the medical home if their care contained 5 components: a personal doctor, a usual source of sick care, family-centered care, no problems getting referrals, and effective care coordination. Ordinal logistic regression was used to examine the relationship between parent-rated severity of asthma symptoms (mild, moderate, and severe symptoms) and the medical home. Approximately 52% of 8229 children who reported having asthma received care from the medical home. Only 30.8% of children with severe asthma symptoms received care that met the medical home criteria, compared to 55.7% of children with mild symptoms. After accounting for confounding factors, obtaining care under the medical home model decreased the odds of parent-reported severe asthma symptoms by 31% (adjusted odds ratio 0.69; 95% CI, 0.56-0.85). Study results suggest that the medical home model can reduce parent-rated severity of asthma symptoms. The findings highlight the importance of providing medical home care to children with asthma to improve the outcomes that matter most to children and their families.

Asthma prevalence and severity in low-resource communities.

PubMed

Cruz, Álvaro A; Stelmach, Rafael; Ponte, Eduardo V

2017-06-01

The prevalence of asthma was thought to be low in most low-income countries, but several reports have indicated this is not always true. This is a narrative review of recent publications on the burden of asthma in low and middle-income countries (LMIC) and underprivileged communities from developed countries. Several studies have reported a low prevalence of asthma is LMIC, but indicate it is increasing. In the last few years, however, many surveys demonstrated this may not always be true. An analysis of the International Study for Asthma and Allergy in Childhood phase III database indicated although the prevalence of asthma among children and adolescents is higher in the developed countries, symptoms of asthma are often more severe in less affluent nations. The rate of uncontrolled asthma is also higher among underprivileged communities of developed countries. Secondary analysis of data generated by the WHO's world health survey performed among adults of 70 countries indicate symptoms of asthma are less frequent in middle-income countries and more frequent in the extremes, low income and high income. This sort of U shaped distribution suggests the disease (or syndrome) comprise more than one major phenotype related to diverse underlying mechanisms. In fact, recent reports show symptoms of asthma among the poor are associated with unhygienic living conditions, which may reduce the risk of atopy but increase the risk of nonatopic wheezing. Urbanization and exposure to air pollution also seem to contribute to an increasing prevalence severity of asthma in LMIC. Access to proper diagnosis and treatment with controller medications for asthma, specially with inhaled corticosteroids is feasible and cost-effective, reduce symptoms, health resource utilization, improves quality of life, and reduce mortality in low-resource settings. Prevalence of asthma was thought to be low in low-income countries, but several reports have indicated this is not always true. Under diagnosis, under treatment, exposure to air pollution, and unhygienic living conditions may contribute to a higher frequency and severity of symptoms of asthma among the poor. Proper diagnosis and treatment with controller medications for asthma is feasible and cost-effective in low-resource settings.

Asthma prevalence and severity in Arab American communities in the Detroit area, Michigan.

PubMed

Johnson, Mary; Nriagu, Jerome; Hammad, Adnan; Savoie, Kathryn; Jamil, Hikmet

2005-07-01

Immigrant populations provide a unique intersection of cultural and environmental risk factors implicated in asthma etiology. This study focuses on asthma prevalence and severity in 600 Arab American households in metro Detroit, the largest immigrant reception zone for Arab Americans in North America. The survey method introduced a number of novel features: (a) a ranking scheme for the key environmental risk factors for asthma was used to derive an aggregated environmental risk index (ERI) for each household, and (b) an aggregate measure of asthma severity based on symptom frequency and intensity. Environmental risk factors and surrogates for socioeconomic status (SES) were found to be stronger predictors of asthma prevalence than asthma severity, while demographic variables such as English fluency and birth in the United States were better predictors of asthma severity than asthma prevalence. These results suggest that SES variables may be more reflective of environmental exposures in communities involved in this study, while English fluency and birth in the United States may be linked to health care access and utilization behavior that can influence the asthma management. We also found a significant relationship between asthma prevalence and degree of acculturation. Asthma prevalence was highest among moderately acculturated immigrants compared with new immigrants and those who were well acculturated, suggesting that among Arab Americans in the Detroit area, risk factors associated with new immigrant status are replaced by "western" risk factors as the population becomes more acculturated.

Advances in asthma 2015: Across the lifespan.

PubMed

Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2016-08-01

In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Predicting asthma exacerbations in children.

PubMed

Forno, Erick; Celedón, Juan C

2012-01-01

This review critically assesses recently published literature on predicting asthma exacerbations in children, while also providing general recommendations for future research in this field. Current evidence suggests that every effort should be made to provide optimal treatment to achieve adequate asthma control, as this will significantly reduce the risk of severe disease exacerbations. Children who have had at least one asthma exacerbation in the previous year are at highest risk for subsequent exacerbations, regardless of disease severity and/or control. Although several tools and biomarkers to predict asthma exacerbations have been recently developed, these approaches need further validation and/or have only had partial success in identifying children at risk. Although considerable progress has been made, much remains to be done. Future studies should clearly differentiate severe asthma exacerbations due to inadequate asthma control from those occurring in children whose asthma is well controlled, utilize standardized definitions of asthma exacerbations, and use a systematic approach to identify the best predictors after accounting for the multiple dimensions of the problem. Our ability to correctly predict the development of severe asthma exacerbations in an individual child should improve in parallel with increased knowledge and/or understanding of the complex interactions among genetic, environmental (e.g. viral infections) and lifestyle (e.g. adherence to treatment) factors underlying these events.

Severe or life-threatening asthma exacerbation: patient heterogeneity identified by cluster analysis.

PubMed

Sekiya, K; Nakatani, E; Fukutomi, Y; Kaneda, H; Iikura, M; Yoshida, M; Takahashi, K; Tomii, K; Nishikawa, M; Kaneko, N; Sugino, Y; Shinkai, M; Ueda, T; Tanikawa, Y; Shirai, T; Hirabayashi, M; Aoki, T; Kato, T; Iizuka, K; Homma, S; Taniguchi, M; Tanaka, H

2016-08-01

Severe or life-threatening asthma exacerbation is one of the worst outcomes of asthma because of the risk of death. To date, few studies have explored the potential heterogeneity of this condition. To examine the clinical characteristics and heterogeneity of patients with severe or life-threatening asthma exacerbation. This was a multicentre, prospective study of patients with severe or life-threatening asthma exacerbation and pulse oxygen saturation < 90% who were admitted to 17 institutions across Japan. Cluster analysis was performed using variables from patient- and physician-orientated structured questionnaires. Analysis of data from 175 patients with severe or life-threatening asthma exacerbation revealed five distinct clusters. Cluster 1 (n = 27) was younger-onset asthma with severe symptoms at baseline, including limitation of activities, a higher frequency of treatment with oral corticosteroids and short-acting beta-agonists, and a higher frequency of asthma hospitalizations in the past year. Cluster 2 (n = 35) was predominantly composed of elderly females, with the highest frequency of comorbid, chronic hyperplastic rhinosinusitis/nasal polyposis, and a long disease duration. Cluster 3 (n = 40) was allergic asthma without inhaled corticosteroid use at baseline. Patients in this cluster had a higher frequency of atopy, including allergic rhinitis and furred pet hypersensitivity, and a better prognosis during hospitalization compared with the other clusters. Cluster 4 (n = 34) was characterized by elderly males with concomitant chronic obstructive pulmonary disease (COPD). Although cluster 5 (n = 39) had very mild symptoms at baseline according to the patient questionnaires, 41% had previously been hospitalized for asthma. This study demonstrated that significant heterogeneity exists among patients with severe or life-threatening asthma exacerbation. Differences were observed in the severity of asthma symptoms and use of inhaled corticosteroids at baseline, and the presence of comorbid COPD. These findings may contribute to a deeper understanding and better management of this patient population. © 2016 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Acute severe asthma presenting in late pregnancy.

PubMed

Holland, S M; Thomson, K D

2006-01-01

Asthma is the commonest pre-existing medical condition to complicate pregnancy. Acute severe asthma in pregnancy is rare, but poses difficult problems. In particular, the decision about when and where to deliver the fetus is complex, since maternal response to asthma treatment is unpredictable. We report the successful management of a parturient presenting with acute severe asthma at 37 weeks' gestation. The controversies involved and the importance of adopting a multi-disciplinary team approach to optimise maternal and neonatal outcomes are discussed.

Environmental pollution and lung effects in children.

PubMed

Searing, Daniel A; Rabinovitch, Nathan

2011-06-01

Studies over the last 2 years have added important new information on the relationship between air pollution and asthma incidence and severity. Outdoor air pollution has been associated with asthma exacerbations, including emergency department visits and hospitalizations, as well as with the onset of asthma. Possible mechanisms mediating both incidence and severity effects include the induction of oxidative stress, and/or allergic sensitization, as well as increased susceptibility to viral infections. Some of these mechanisms may be occurring in utero including epigenetic changes that may increase risk for development of asthma. Factors related to increased susceptibility for air pollution-related asthma severity include age, season and genetic polymorphisms related to antioxidant enzymes. Ambient pollution levels may be associated with both asthma incidence and severity. Susceptibility to air pollution may be higher in children with genetic polymorphisms related to the 'oxidant stress pathways'. Potential interventions for susceptible children at risk for asthma development and/or severity include decreased exposure on high air pollution days, especially in the summer months, and antioxidant supplementation. On the population level, changes in school and home zoning to increase distance from busy roadways may help reduce both asthma incidence and severity.

Temperature-controlled laminar airflow in severe asthma for exacerbation reduction (The LASER Trial): study protocol for a randomised controlled trial.

PubMed

Storrar, Will; Fogg, Carole; Brown, Tom; Dennison, Paddy; Yu, Ly-Mee; Dewey, Ann; Luengo-Fernandez, Ramon; Dean, Tara; Rahman, Najib; Mansur, Adel; Howarth, Peter H; Bradding, Peter; Chauhan, Anoop J

2016-01-08

Asthma affects more than 5 million patients in the United Kingdom. Nearly 500,000 of these patients have severe asthma with severe symptoms and frequent exacerbations that are inadequately controlled with available treatments. The burden of severe asthma on the NHS is enormous, accounting for 80 % of the total asthma cost (£1 billion), with frequent exacerbations and expensive medications generating much of this cost. Of those patients with severe asthma, 70 % are sensitised to indoor aeroallergens, and the level of exposure to allergens determines the symptoms; patients exposed to high levels are therefore most at risk of exacerbations and hospital admissions. The LASER trial aims to assess whether a new treatment, temperature controlled laminar airflow (TLA) delivered by the Airsonett™ device, can reduce the frequency of exacerbations in patients with severe allergic asthma by reducing exposure to aeroallergens overnight. This multicentre study is a placebo-controlled, blinded, randomised controlled, parallel group trial. A total of 222 patients with a new or current diagnosis of severe allergic asthma will be assigned with a random element in a 1:1 ratio to receive either an active device for one year or a placebo device. The primary outcome is the frequency of severe asthma exacerbations occurring over a 12-month period, defined in accordance with the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. Secondary outcomes include changes in asthma control, lung function, asthma-specific and global quality of life for participants and their carers, adherence to intervention, healthcare resource use and costs, and cost-effectiveness. Qualitative interviews will be conducted to elicit participant's and their partner's perceptions of the treatment. Effective measures of allergen avoidance have, to date, proved elusive. The LASER trial aims to address this. The study will ascertain whether home-based nocturnal TLA usage over a 12-month period can reduce the frequency of exacerbations and improve asthma control and quality of life as compared to placebo, whilst being cost-effective and acceptable to adults with poorly controlled, severe allergic asthma. The results of this study will be widely applicable to the many patients with allergic asthma both in the UK and internationally. Current controlled trials ISRCTN46346208 (Date assigned 22 January 2014).

Pharmacists' interventions on clinical asthma outcomes: a systematic review.

PubMed

Garcia-Cardenas, Victoria; Armour, Carol; Benrimoj, Shalom I; Martinez-Martinez, Fernando; Rotta, Inajara; Fernandez-Llimos, Fernando

2016-04-01

The objective of this systematic review was to evaluate the impact of pharmacists' interventions on clinical asthma outcomes on adult patients and to identify the outcome indicators used.PubMed, Scopus, Web of Science and Scielo were searched. Studies addressing pharmacists' interventions on adult asthma patients reporting clinical asthma outcomes were incorporated.11 clinical outcomes were identified in 21 studies. 10 studies measured the impact of the intervention on asthma control. Randomised controlled trials (RCT) and non-RCTs found positive results in percentages of controlled patients and Asthma Control Questionnaire (ACQ) scores. Discordant results were found for Asthma Control Test results. Asthma severity was assessed in four studies. One RCT found a significant decrease in the percentage of severe patients; two non-RCTs found significant improvements in severity scores. 11 studies reported pulmonary function indicators, showing inconsistent results. Eight studies measured asthma symptoms; three RCTs and four non-RCTs showed significant improvements.RCTs and non-RCTs generated similar results for most outcomes. Based on the evidence generated by RCTs, pharmacists' have a positive impact on the percentage of controlled patients, ACQ scores, severity and symptoms. Future research should report using the core outcome set of indicators established for asthma (PROSPERO CRD42014007019). Copyright ©ERS 2016.

Depressive symptomatology, quality of life and disease control among individuals with well-characterized severe asthma.

PubMed

Yonas, Michael A; Marsland, Anna L; Emeremni, Chetachi A; Moore, Charity G; Holguin, Fernando; Wenzel, Sally

2013-10-01

A thorough examination of the relationship of asthma severity and control with symptoms of depression is needed to identify groups of asthmatics at high risk for poor disease control outcomes. This study examines the relationship of symptoms of depression with severity and control in a well-characterized cohort of asthmatics and healthy controls. Depressive symptoms and quality of life were assessed using the Beck Depression Inventory. Disease control was measured by a composite index incorporating symptoms, activity limitation and rescue medication use. Individuals with asthma (n = 91) reported more symptoms of depression than controls (n = 36; p < 0.001). Those with severe asthma (n = 49) reported more symptoms of depression (p = 0.002) and poorer asthma control (p < 0.0001) than those with not severe asthma. Worse asthma control was associated with more depressive symptoms in severe (r = 0.46, p = 0.002) but not in not severe (r = 0.13, p = 0.40) asthmatics. The relationship of symptoms of depression among severe asthmatics was attenuated by disease control. Exploratory analyses identified specific disease symptom characteristics, as opposed to exacerbations, as associated with symptoms of depression. Among individuals with severe asthma, increased symptom burden is positively associated with risk for co-morbid depression. These findings point to a need for regular mood disorder screenings and treatment referrals among this group. Further research is warranted to examine whether treatment of comorbid depression improves treatment adherence and asthma-related quality of life.

The Global Asthma Network rationale and methods for Phase I global surveillance: prevalence, severity, management and risk factors.

PubMed

Ellwood, Philippa; Asher, M Innes; Billo, Nils E; Bissell, Karen; Chiang, Chen-Yuan; Ellwood, Eamon M; El-Sony, Asma; García-Marcos, Luis; Mallol, Javier; Marks, Guy B; Pearce, Neil E; Strachan, David P

2017-01-01

The Global Asthma Network (GAN), established in 2012, followed the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Phase One involved over 700 000 adolescents and children from 156 centres in 56 countries; it found marked worldwide variation in symptom prevalence of asthma, rhinitis and eczema that was not explained by the current understanding of these diseases; ISAAC Phase Three involved over 1 187 496 adolescents and children (237 centres in 98 countries). It found that asthma symptom prevalence was increasing in many locations especially in low- and middle-income countries where severity was also high, and identified several environmental factors that required further investigation.GAN Phase I, described in this article, builds on the ISAAC findings by collecting further information on asthma, rhinitis and eczema prevalence, severity, diagnoses, asthma emergency room visits, hospital admissions, management and use of asthma essential medicines. The subjects will be the same age groups as ISAAC, and their parents. In this first global monitoring of asthma in children and adults since 2003, further evidence will be obtained to understand asthma, management practices and risk factors, leading to further recognition that asthma is an important non-communicable disease and to reduce its global burden. Copyright ©ERS 2017.

Obstructive sleep apnea and asthma*

PubMed Central

Salles, Cristina; Terse-Ramos, Regina; Souza-Machado, Adelmir; Cruz, Álvaro A

2013-01-01

Symptoms of sleep-disordered breathing, especially obstructive sleep apnea syndrome (OSAS), are common in asthma patients and have been associated with asthma severity. It is known that asthma symptoms tend to be more severe at night and that asthma-related deaths are most likely to occur during the night or early morning. Nocturnal symptoms occur in 60-74% of asthma patients and are markers of inadequate control of the disease. Various pathophysiological mechanisms are related to the worsening of asthma symptoms, OSAS being one of the most important factors. In patients with asthma, OSAS should be investigated whenever there is inadequate control of symptoms of nocturnal asthma despite the treatment recommended by guidelines having been administered. There is evidence in the literature that the use of continuous positive airway pressure contributes to asthma control in asthma patients with obstructive sleep apnea and uncontrolled asthma. PMID:24310634

Is asthma associated with cognitive impairments? A meta-analytic review.

PubMed

Irani, Farzin; Barbone, Jordan Mark; Beausoleil, Janet; Gerald, Lynn

2017-12-01

Asthma is a chronic disease with significant health burden and socioeconomic and racial/ethnic disparities related to diagnosis and treatment. Asthma primarily affects the lungs, but can impact brain function through direct and indirect mechanisms. Some studies have suggested that asthma negatively impacts cognition, while others have failed to identify asthma-related cognitive compromise. We aimed to conduct a meta-analysis of cognition in individuals with asthma compared to that in healthy controls. We also examined the impact of some key potential moderators. Data on cognitive outcome measures and sociodemographic, illness-related, and study-related variables were extracted from studies reporting cognitive test performance in individuals with asthma compared to that in controls. There was no evidence of publication bias. A random-effects model examining differences in task performance between 2017 individuals with asthma and 2131 healthy controls showed significant effects in the small to medium range. Cognitive deficits associated with asthma were global, with strongest effects on broader measures involving academic achievement and executive functioning, but with additional impact on processing speed, global intellect, attention, visuospatial functioning, language, learning, and memory. Severity of asthma was a key moderator, with greatest cognitive deficits associated with severe asthma. Cognitive burden was also greatest in asthma patients who were younger, males, from low socioeconomic backgrounds, and from racial/ethnic minorities. Effects were independent of type of population (child versus adult), type of study (norm-referenced versus control-referenced), or reported use of oral or inhaled corticosteroid medications. There is cognitive burden associated with asthma, particularly among vulnerable groups with severe asthma. This could be due to increased risk of intermittent cerebral hypoxia in severe asthma. The clinical need to assess cognition in individuals with asthma is underscored.

Cohort Study of Severe Bronchiolitis during Infancy and Risk of Asthma by Age 5 Years.

PubMed

Balekian, Diana S; Linnemann, Rachel W; Hasegawa, Kohei; Thadhani, Ravi; Camargo, Carlos A

Severe bronchiolitis (ie, bronchiolitis requiring hospital admission) is thought to markedly increase asthma risk, with 30%-50% developing asthma by age 5 years. To date, studies of this association are small, and most are from outside the United States. The objective of this study was to investigate the association between severe bronchiolitis and risk of asthma in a US birth cohort. We studied a cohort nested within the Massachusetts General Hospital Obstetric Maternal Study (MOMS), a prospective cohort of pregnant women enrolled during 1998-2006. Children of mothers enrolled in MOMS were included in the analysis if they received care within our health system (n = 3653). Diagnoses and medications were extracted from the children's electronic health records; we also examined pregnancy and perinatal risk factors collected for the underlying pregnancy study. The birth cohort was 52% male, 49% white, and 105 infants (2.9%) had severe bronchiolitis. Overall, 421 children (11.5%) developed asthma by age 5 years. Among the children with severe bronchiolitis, 27.6% developed asthma by age 5 years. In multivariable logistic regression adjusting for 12 risk factors, severe bronchiolitis remained a strong risk factor for developing asthma by age 5 years (odds ratio 2.57; 95% confidence interval 1.61-4.09). In a large Boston birth cohort, the frequency of severe bronchiolitis and childhood asthma was similar to published data. Among children with severe bronchiolitis, the risk of developing asthma was lower than prior studies but still high (27.6%). This difference may be due to different study designs, populations, and outcome definitions studied. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A preliminary study to evaluate a patient-centred asthma education programme on parental control of home environment and asthma signs and symptoms in children with moderate-to-severe asthma.

PubMed

Tzeng, Li-Fen; Chiang, Li-Chi; Hsueh, Kai-Chung; Ma, Wei-Fen; Fu, Lin-Shien

2010-05-01

To evaluate the effectiveness of a nurse-led patient-centred asthma education programme on home environmental control behaviours of parents of children with moderate or severe asthma. Reducing allergic triggers is important self-management behaviour for preventing asthma attacks and patient-centred asthma education has been shown to effectively manage chronic disease. A preliminary quasi-experimental, non-equivalent control group design was used. Dyads (n = 75) of parents and their children with moderate or severe asthma (ages 6-14 years) were purposively recruited from the asthma clinics of two hospitals in central Taiwan. The experimental group of 38 children/parents from one hospital received patient-centred asthma education. The comparison group of 37 children/parents from the other hospital received routine individual education. At pretest and at the end of the three-month patient-centred asthma education programme, we measured parents' control of home environmental triggers, children's asthma signs/symptoms and children's pulmonary function. Data were analysed by the general linear model for repeat measures. The level of improvement in dust and cleaning methods was significantly greater among parents in the experimental group than among those in the comparison group (p < 0.05). Children with moderate or severe asthma in the experimental group had fewer signs/symptoms of asthma and better lung function than children in the comparison group. Our patient-centred asthma education programme improved parents' home environmental control and children's asthma sign/symptoms and lung function. Nurses can play primary roles as patient educators in asthma clinics. Well-trained patient educators can continuously monitor self-management behaviours to improve patients' compliance with home environmental control, thus leading to better physical outcomes in children with asthma than routine individual asthma education alone.

Mouse Sensitization and Exposure Are Associated with Asthma Severity in Urban Children.

PubMed

Grant, Torie; Aloe, Charles; Perzanowski, Matthew; Phipatanakul, Wanda; Bollinger, Mary E; Miller, Rachel; Matsui, Elizabeth C

Mouse sensitization and exposure are associated with uncontrolled asthma, but whether they are associated with asthma severity, an intrinsic disease characteristic and long-term outcome predictor, is unclear. To examine relationships between mouse sensitization and/or exposure and asthma severity in urban children. A total of 645 children (5-17 years) with uncontrolled asthma underwent mouse sensitization evaluation. Sensitized children had mouse allergen measured in bedroom dust. Relationships between mouse sensitization, allergen levels, and asthma severity measures (treatment step and Composite Asthma Severity Index [CASI]) were examined using regression models adjusted for age, sex, atopy, study site, race, ethnicity, and insurance. The study population was predominantly minority (69.6% black, 20.8% Hispanic), low income (61.8%), and mouse sensitized (54.4%). Mean ± SD treatment step was 3.2 ± 1.6, equivalent to medium-dose inhaled corticosteroid. Mean ± SD CASI was 6.5 ± 3.4, reflecting moderate persistent asthma. Mouse sensitization was associated with higher treatment step (3.5 vs 2.9, mouse-sensitized vs nonsensitized, P < .001), independent of potential confounders (β [95% CI], 0.36 [0.07-0.64]; P = .01). Mouse sensitization was associated independently with CASI (β [95% CI], 0.82 [0.16-1.47]; P = .02). Among mouse-sensitized participants, higher bedroom floor and bed Mus m 1 were independently associated with treatment step (β [95% CI], 0.26 [0.09-0.43]; P = .002 and β [95% CI], 0.22 [0.01-0.43]; P = .04), respectively. Higher bedroom floor Mus m 1 was independently associated with CASI (β [95% CI], 0.43 [0.05-0.81]; P = .03). Mouse sensitization and exposure are associated with asthma severity, among low-income, minority children. Further studies are needed to determine whether reducing allergen exposure among mouse-sensitized patients with asthma can reduce severity, ultimately altering childhood asthma natural history. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Airway structural alterations selectively associated with severe asthma.

PubMed

Benayoun, Laurent; Druilhe, Anne; Dombret, Marie-Christine; Aubier, Michel; Pretolani, Marina

2003-05-15

To identify airway pathologic abnormalities selectively associated with severe asthma, we examined 10 control subjects, 10 patients with intermittent asthma, 15 patients with mild-to-moderate persistent asthma, 15 patients with severe persistent asthma, and 10 patients with chronic obstructive pulmonary disease. Bronchial biopsies were assessed for epithelial integrity; subepithelial basement membrane (SBM) thickness; collagen type III deposition; eosinophil, neutrophil, and fibroblast numbers; mucous gland and airway smooth muscle (ASM) areas; SBM-ASM distance; ASM hypertrophy (increased cell size); and the expression of the contractile proteins alpha-actin, smooth muscle myosin heavy-chain isoforms, myosin light-chain kinase, and the phosphorylated form of the regulatory light chain of myosin. Neither mucosal eosinophilia nor neutrophilia, epithelial damage, or SBM thickness reflected asthma severity. In contrast, higher numbers of fibroblasts (p < 0.001), an increase in collagen type III deposition (p < 0.020), larger mucous gland (p < 0.040) and ASM (p < 0.001) areas, augmented ASM cell size (p < 0.001), and myosin light-chain kinase expression (p < 0.005) distinguished patients with severe persistent asthma from patients with milder disease or with chronic obstructive pulmonary disease. Stepwise multivariate regression analysis established that fibroblast numbers and ASM cell size were negatively associated with prebronchodilator and postbronchodilator FEV1 values in patients with asthma. We conclude that fibroblast accumulation and ASM hypertrophy in proximal airways are selective determinants of severe persistent asthma.

Management of asthma: the essentials of good clinical practice.

PubMed

Aït-Khaled, N; Enarson, D A

2006-02-01

Asthma is a condition that affects all countries worldwide. It is a chronic, disabling condition that diminishes the quality of life and the economic prosperity of those who live with it. The majority of persons living with asthma are from developing countries. Asthma management necessitates long-term treatment that is expensive, making it less accessible to poor people. The cost of medications is the key factor preventing people living with asthma from having access to care that has the potential to relieve their suffering, improve their quality of life and enhance their economic status. Asthma is a disease caused by environmental exposures. Genetic factors predispose certain people to developing asthma once they are exposed to the causative agents, and certain factors can trigger symptomatic episodes of asthma in those who have already developed the disease. Certain clinical characteristics differentiate asthma from other chronic lung conditions. The most important of these is that the symptoms and functional disability caused by asthma vary from one occasion to another. In those with less severe asthma, they may be present on some occasions and not others; in those with more severe asthma, their degree of severity varies from one time to another.

Management of severe asthma: targeting the airways, comorbidities and risk factors.

PubMed

Gibson, Peter G; McDonald, Vanessa M

2017-06-01

Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and individualised management initiated. We describe a practical approach to assessment and management of patients with SRA. © 2017 Royal Australasian College of Physicians.

Features of asthma which provide meaningful insights for understanding the disease heterogeneity.

PubMed

Deliu, M; Yavuz, T S; Sperrin, M; Belgrave, D; Sahiner, U M; Sackesen, C; Kalayci, O; Custovic, A

2018-01-01

Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Obesity and adiposity indicators, asthma, and atopy in Puerto Rican children

PubMed Central

Forno, Erick; Acosta-Pérez, Edna; Brehm, John M.; Han, Yueh-Ying; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2013-01-01

Background: Whether adiposity indicators other than body mass index should be used in studies of childhood asthma is largely unknown. The role of atopy in “obese asthma” is also unclear. Objective: To examine the relation among adiposity indicators, asthma, and atopy in Puerto Rican children, and to assess whether atopy mediates the obesity-asthma association. Methods: In a study of Puerto Rican children with (n=351) and without (n=327) asthma, we measured body mass index (BMI), percent body fat (PBF), waist circumference (WC), and waist-to-hip ratio (WHR). The outcomes studied included asthma, lung function, measures of atopy, and, among cases, indicators of asthma severity or control. We performed mediation analysis to assess the contribution of atopy to the relationship between adiposity and asthma. Results: BMI, PBF, and WC were associated with increased odds of asthma. Among cases, all three measures were generally associated with lung function, asthma severity/control, and atopy; however, there were differences depending on the adiposity indicator analyzed. Atopy considerably mediated the adiposity-asthma association in this population: allergic rhinitis accounted for 22-53% of the association with asthma, and sensitization to cockroach mediated 13-20% of the association with FVC and 29-42% of the association with emergency room visits for asthma. Conclusions: Adiposity indicators are associated with asthma, asthma severity/control, and atopy in Puerto Rican children. Atopy significantly mediates the effect of adiposity on asthma outcomes. Longitudinal studies are needed to further investigate the causal role, if any, of adiposity distribution and atopy on “obese asthma” in childhood. Clinical Implications: Assessment of adiposity rather than sole reliance on BMI may be important in studies of childhood asthma. Atopy is an important mediator of the relation between obesity and asthma in Puerto Rican children. Capsule Summary: In a cohort of Puerto Rican children, measures of adiposity were associated with asthma, asthma severity/control, and atopy; however, some differences existed depending on the adiposity indicator utilized. Atopy significantly mediated the association between adiposity indicators and asthma. PMID:24290290

Impact of Age and Sex on Outcomes and Hospital Cost of Acute Asthma in the United States, 2011-2012

PubMed Central

Teague, W. Gerald; Koroukian, Siran M.; Schlitz, Nicholas K.; Bleecker, Eugene R.; Busse, William B.; Calhoun, William J.; Castro, Mario; Comhair, Suzy A.; Fitzpatrick, Anne M.; Israel, Elliot; Wenzel, Sally E.; Holguin, Fernando; Gaston, Benjamin M.

2016-01-01

Background Worldwide, asthma is a leading cause of morbidity, mortality and economic burden, with significant gender and racial disparities. However, little attention has been given to the independent role of age on lifetime asthma severity and hospitalization. We aimed to assess the effect of age, gender, race and ethnicity on indicators of asthma severity including asthma related hospitalization, mortality, hospital cost, and the rate of respiratory failure. Methods We analyzed the 2011 and 2012 Healthcare Cost and Utilization Project- National Inpatient Sample (NIS). We validated and extended those results using the National Heart, Lung, and Blood Institute-Severe Asthma Research Program (SARP; 2002–2011) database. Severe asthma was prospectively defined using the stringent American Thoracic Society (ATS) definition. Results Hospitalization for asthma was reported in 372,685 encounters in 2012 and 368,528 in 2011. The yearly aggregate cost exceeded $2 billion. There were distinct bimodal distributions for hospitalization age, with an initial peak at 5 years and a second at 50 years. Likewise, this bimodal age distribution of patients with severe asthma was identified using SARP. Males comprised the majority of individuals in the first peak, but women in the second. Aggregate hospital cost mirrored the bimodal peak distribution. The probability of respiratory failure increased with age until the age of 60, after which it continued to increase in men, but not in women. Conclusions Severe asthma is primarily a disease of young boys and middle age women. Greater understanding of the biology of lung aging and influence of sex hormones will allow us to plan for targeted interventions during these times in order to reduce the personal and societal burdens of asthma. PMID:27294365

Multitissue Transcriptomics Delineates the Diversity of Airway T Cell Functions in Asthma.

PubMed

Singhania, Akul; Wallington, Joshua C; Smith, Caroline G; Horowitz, Daniel; Staples, Karl J; Howarth, Peter H; Gadola, Stephan D; Djukanović, Ratko; Woelk, Christopher H; Hinks, Timothy S C

2018-02-01

Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3 + T cells from sputum and BAL were obtained from healthy subjects (n = 19) and patients with asthma (mild, moderate, and severe asthma; n = 46). Gene expression was assessed using Affymetrix HT HG-U133 + PM GeneChips, and results were validated by real-time quantitative PCR. In the epithelium, IL-13 response genes (POSTN, SERPINB2, and CLCA1), mast cell mediators (CPA3 and TPSAB1), inducible nitric oxide synthase, and cystatins (CST1, CST2, and CST4) were upregulated in mild asthma, but, except for cystatins, were suppressed by corticosteroids in moderate asthma. In severe asthma-with predominantly neutrophilic phenotype-several distinct processes were upregulated, including neutrophilia (TCN1 and MMP9), mucins, and oxidative stress responses. The majority of the disease signature was evident in sputum T cells in severe asthma, where 267 genes were differentially regulated compared with health, highlighting compartmentalization of inflammation. This signature included IL-17-inducible chemokines (CXCL1, CXCL2, CXCL3, IL8, and CSF3) and chemoattractants for neutrophils (IL8, CCL3, and LGALS3), T cells, and monocytes. A protein interaction network in severe asthma highlighted signatures of responses to bacterial infections across tissues (CEACAM5, CD14, and TLR2), including Toll-like receptor signaling. In conclusion, the activation of innate immune pathways in the airways suggests that activated T cells may be driving neutrophilic inflammation and steroid-insensitive IL-17 response in severe asthma.

Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children.

PubMed

Brehm, John M; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Litonjua, Augusto A; Cabana, Michael; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2012-07-15

Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. A cross-sectional study was conducted of 560 children ages 6-14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and a lower FEV(1)/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P = 0.04) cases. Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.

Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children.

PubMed

Blatter, Joshua; Brehm, John M; Sordillo, Joanne; Forno, Erick; Boutaoui, Nadia; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Weiss, Scott T; Litonjua, Augusto A; Canino, Glorisa; Celedón, Juan C

2016-02-01

Little is known about folate and atopy or severe asthma exacerbations. We examined whether folate deficiency is associated with number of positive skin tests to allergens or severe asthma exacerbations in a high-risk population and further assessed whether such association is explained or modified by vitamin D status. Cross-sectional study of 582 children aged 6 to 14 years with (n = 304) and without (n = 278) asthma in San Juan, Puerto Rico. Folate deficiency was defined as plasma folate less than or equal to 20 ng/ml. Our outcomes were the number of positive skin tests to allergens (range, 0-15) in all children and (in children with asthma) one or more severe exacerbations in the previous year. Logistic and negative binomial regression models were used for the multivariate analysis. All multivariate models were adjusted for age, sex, household income, residential proximity to a major road, and (for atopy) case/control status; those for severe exacerbations were also adjusted for use of inhaled corticosteroids and vitamin D insufficiency (a plasma 25[OH]D < 30 ng/ml). In a multivariate analysis, folate deficiency was significantly associated with an increased degree of atopy and 2.2 times increased odds of at least one severe asthma exacerbation (95% confidence interval for odds ratio, 1.1-4.6). Compared with children who had normal levels of both folate and vitamin D, those with both folate deficiency and vitamin D insufficiency had nearly eightfold increased odds of one or more severe asthma exacerbation (95% confidence interval for adjusted odds ratio, 2.7-21.6). Folate deficiency is associated with increased degree of atopy and severe asthma exacerbations in school-aged Puerto Ricans. Vitamin D insufficiency may further increase detrimental effects of folate deficiency on severe asthma exacerbations.

Asthma Action Plan Receipt among Children with Asthma 2-17 Years of Age, United States, 2002-2013.

PubMed

Simon, Alan E; Akinbami, Lara J

2016-04-01

To examine national trends in the receipt of asthma action plans, an intervention recommended by the National Asthma Education and Prevention Program guidelines. We used data from the sample child component of the National Health Interview Survey from 2002, 2003, 2008, and 2013 to examine the percentage of children 2-17 years of age with asthma (n = 3714) that have ever received an asthma action plan. Bivariate and multivariate (with adjustment for sociodemographic characteristics and asthma outcomes consistent with greater disease severity) logistic regressions were conducted to examine trends from 2002 to 2013 and to examine, with 2013 data only, the relationship between having received an asthma action plan and both sociodemographic characteristics and indicators of asthma severity. The percentage of children with asthma that had ever received an asthma action plan increased from 41.7% in 2002 to 50.7% in 2013 (P < .001 for trend). In 2013, a greater percentage of non-Hispanic black (58.4%) than non-Hispanic white (47.4%) children (P = .028), privately insured (56.2%) vs those with public insurance only (46.3%) (P = .016), and users of inhaled preventive asthma medication vs those that did not (P < .001) had ever received an asthma action plan. Adjusted results were similar. The percentage of US children with asthma that had ever received an asthma action plan increased between 2002 and 2013, although one-half had never received an asthma action plan in 2013. Some sociodemographic and asthma severity measures are related to receipt of an asthma action plan. Published by Elsevier Inc.

Effectiveness and response predictors of omalizumab in a severe allergic asthma population with a high prevalence of comorbidities: the Australian Xolair Registry.

PubMed

Gibson, P G; Reddel, H; McDonald, V M; Marks, G; Jenkins, C; Gillman, A; Upham, J; Sutherland, M; Rimmer, J; Thien, F; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Robinson, P; Wright, C; Yozghatlian, V; Burgess, S; Sivakumaran, P; Jaffe, A; Bowden, J; Wark, P A B; Yan, K Y; Kritikos, V; Peters, M; Hew, M; Aminazad, A; Bint, M; Guo, M

2016-09-01

Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway; however, effectiveness data in a population with significant comorbidities are limited. To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting. © 2016 Royal Australasian College of Physicians.

Stepwise management of asthma.

PubMed

Khalid, Ayesha N

2015-09-01

Stepwise management of asthma remains an area of evolving research. Asthma is one of the most expensive chronic diseases in the United States; stepwise management is an important area of focus, with several recent guidelines recommending management. This is a review of published English language literature, focusing on management guidelines for asthma in adult and pediatric patients. Asthma is a chronic disease whose assessment of severity allows for therapeutic goals to match the impairment noted. Good evidence exists to aid risk reduction, leading to decreased emergency room visits, preventing loss of lung function in adults and lung growth in children, and optimizing pharmacotherapy with reduced side effects profile. Recent asthma management guidelines incorporate 4 components of asthma care including: monitoring of severity, patient education, controlling external triggers, and medications, including recent attention to medication adherence. Asthma is an expensive chronic disease with preventive measures leading to reduced healthcare costs. Future targeted cytokine therapy to decrease serum and blood eosinophils may become an integral part of asthma management. © 2015 ARS-AAOA, LLC.

Recent developments in the role of reactive oxygen species in allergic asthma

PubMed Central

Qu, Jingjing; Li, Yuanyuan; Zhong, Wen

2017-01-01

Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma. Among these mediators, endogenous or exogenous ROS are responsible for the airway inflammation of allergic asthma. Furthermore, several inflammatory cells induce ROS and allergic asthma development. Airway inflammation, airway hyper-responsiveness, tissue injury, and remodeling can be induced by excessive ROS production in animal models. Based on investigations of allergic asthma and ROS formation mechanisms, we have identified several novel anti-inflammatory therapeutic treatments. This review describes the recent data linking ROS to the pathogenesis of allergic asthma. PMID:28203435

Fibromyalgia as a cause of uncontrolled asthma: a case-control multicenter study.

PubMed

Martinez-Moragon, Eva; Plaza, Vicente; Torres, Isabel; Rosado, Ana; Urrutia, Isabel; Casas, Xavier; Hinojosa, Belen; Blanco-Aparicio, Marina; Delgado, Julio; Quirce, Santiago; Sabadell, Carles; Cebollero, Pilar; Muñoz-Fernández, Ana

2017-12-01

Fibromyalgia can affect the control of asthma when both diseases are present in a single patient. To characterize asthma in patients with concomitant fibromyalgia to assess whether fibromyalgia is an independent factor of asthma severity that influences poor asthma control. We also evaluated how dyspnea is perceived by patients in order to demonstrate that alterations in the perception of airway obstruction may be responsible for poor asthma control. This was a cross-sectional case-control multicenter study, in which 56 patients in the asthma and fibromyalgia group were matched to 36 asthmatics by sex, approximate age, and asthma severity level. All patients were women. Study variables included the Asthma Control Test (ACT), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), the Nijmegen hyperventilation syndrome questionnaire, the Hospital Anxiety and Depression Scale, and perception of dyspnea after acute bronchoconstriction. Although patients in both study groups showed similar asthma severity and use of anti-asthmatic drugs, patients in the asthma and fibromyalgia group showed lower scores on the ACT and MiniAQLQ questionnaires, and higher scores of anxiety and depression as well as hyperventilation compared to asthma patients without fibromyalgia. All these differences were statistically significant. Fibromyalgia in patients with asthma influences poor control of the respiratory disease and is associated with altered perception of dyspnea, hyperventilation syndrome, high prevalence of depression and anxiety, and impaired quality of life. Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients suffering from asthma and fibromyalgia concomitantly.

Psychometric properties of a Chinese asthma quality of life questionnaire.

PubMed

Wang, Ningqun; Huang, Xiaobo; Chen, Wenqiang; Zhang, Xiaomei; Zhang, Yongsheng; Chen, Yujing

2017-12-01

To assess the acceptability, reliability, validity, and responsiveness of the Chinese Asthma Quality of Life Questionnaire (C-AQLQ) in a sample of Chinese asthma patients. The C-AQLQ and Short Form 36 Health Survey (SF-36) scales were administered to patients at baseline and 3 months later. Asthma severity condition and lung function were evaluated. Necessary data were gathered to assess the psychometric properties such as the feasibility, internal consistency, test-retest reliability, structural validity, discriminant validity, convergent validity, and responsiveness of the C-AQLQ. One hundred and thirty-seven patients completed the investigation. The Cronbach's alpha coefficient for the total scale was 0.96. Factor analysis yielded five factors that generally corresponded to the five proposed subscales. Patients with mild asthma reported higher scores than patients with moderate/severe asthma on all subscales other than environmental stimuli. Lung function measurement and the asthma severity score correlated significantly with domains of the C-AQOL but with fewer domains of the SF-36. The questionnaire detected within-subject changes in patients' asthma status during follow-up. Results indicated preliminary support that the C-AQLQ is a reliable, valid, discriminating, and responsive measure of quality of life in Chinese asthma patients. It is more sensitive than the generic SF-36 in detecting differences in asthma severity.

Lipoxin Generation Is Related to Soluble Epoxide Hydrolase Activity in Severe Asthma

PubMed Central

Ono, Emiko; Dutile, Stefanie; Kazani, Shamsah; Wechsler, Michael E.; Yang, Jun; Hammock, Bruce D.; Douda, David Nobuhiro; Tabet, Yacine; Khaddaj-Mallat, Rayan; Sirois, Marco; Sirois, Chantal; Rizcallah, Edmond; Rousseau, Éric; Martin, Richard; Sutherland, E. Rand; Castro, Mario; N. Jarjour, Nizar; Israel, Elliot

2014-01-01

Rationale: Severe asthma is characterized by airway inflammatory responses associated with aberrant metabolism of arachidonic acid. Lipoxins (LX) are arachidonate-derived pro-resolving mediators that are decreased in severe asthma, yet mechanisms for defective LX biosynthesis and a means to increase LXs in severe asthma remain to be established. Objectives: To determine if oxidative stress and soluble epoxide hydrolase (sEH) activity are linked to decreased LX biosynthesis in severe asthma. Methods: Aliquots of blood, sputum, and bronchoalveolar lavage fluid were obtained from asthma subjects for mediator determination. Select samples were exposed to t-butyl-hydroperoxide or sEH inhibitor (sEHI) before activation. Peripheral blood leukocyte–platelet aggregates were monitored by flow cytometry, and bronchial contraction was determined with cytokine-treated human lung sections. Measurements and Main Results: 8-Isoprostane levels in sputum supernatants were inversely related to LXA4 in severe asthma (r = −0.55; P = 0.03) and t-butyl-hydroperoxide decreased LXA4 and 15-epi-LXA4 biosynthesis by peripheral blood leukocytes. LXA4 and 15-epi-LXA4 levels were inversely related to sEH activity in sputum supernatants and sEHIs significantly increased 14,15-epoxy-eicosatrienoic acid and 15-epi-LXA4 generation by severe asthma whole blood and bronchoalveolar lavage fluid cells. The abundance of peripheral blood leukocyte–platelet aggregates was related to asthma severity. In a concentration-dependent manner, LXs significantly inhibited platelet-activating factor–induced increases in leukocyte–platelet aggregates (70.8% inhibition [LXA4 100 nM], 78.3% inhibition [15-epi-LXA4 100 nM]) and 15-epi-LXA4 markedly inhibited tumor necrosis factor-α–induced increases in bronchial contraction. Conclusions: LX levels were decreased by oxidative stress and sEH activity. Inhibitors of sEH increased LXs that mediated antiphlogistic actions, suggesting a new therapeutic approach for severe asthma. Clinical trial registered with www.clinicaltrials.gov (NCT 00595114). PMID:25162465

Obesity and adiposity indicators, asthma, and atopy in Puerto Rican children.

PubMed

Forno, Erick; Acosta-Pérez, Edna; Brehm, John M; Han, Yueh-Ying; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

2014-05-01

Whether adiposity indicators other than body mass index (BMI) should be used in studies of childhood asthma is largely unknown. The role of atopy in "obese asthma" is also unclear. To examine the relationship among adiposity indicators, asthma, and atopy in Puerto Rican children, and to assess whether atopy mediates the obesity-asthma association. In a study of Puerto Rican children with (n = 351) and without (n = 327) asthma, we measured BMI, percent of body fat, waist circumference, and waist-to-hip ratio. The outcomes studied included asthma, lung function, measures of atopy, and, among cases, indicators of asthma severity or control. We performed mediation analysis to assess the contribution of atopy to the relationship between adiposity and asthma. BMI, percent of body fat, and waist circumference were associated with increased odds of asthma. Among cases, all 3 measures were generally associated with lung function, asthma severity/control, and atopy; however, there were differences depending on the adiposity indicator analyzed. Atopy considerably mediated the adiposity-asthma association in this population: allergic rhinitis accounted for 22% to 53% of the association with asthma, and sensitization to cockroach mediated 13% to 20% of the association with forced vital capacity and 29% to 42% of the association with emergency department visits for asthma. Adiposity indicators are associated with asthma, asthma severity/control, and atopy in Puerto Rican children. Atopy significantly mediates the effect of adiposity on asthma outcomes. Longitudinal studies are needed to further investigate the causal role, if any, of adiposity distribution and atopy on "obese asthma" in childhood. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics.

PubMed

Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

2015-01-01

Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body's response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction.

Mechanisms of Heightened Airway Sensitivity and Responses to Inhaled SO2 in Asthmatics

PubMed Central

Reno, Anita L; Brooks, Edward G; Ameredes, Bill T

2015-01-01

Sulfur dioxide (SO2) is a problematic inhalable air pollutant in areas of widespread industrialization, not only in the United States but also in countries undergoing rapid industrialization, such as China, and it can be a potential trigger factor for asthma exacerbations. It is known that asthmatics are sensitive to the effects of SO2; however, the basis of this enhanced sensitivity remains incompletely understood. A PubMed search was performed over the course of 2014, encompassing the following terms: asthma, airway inflammation, sulfur dioxide, IL-10, mouse studies, and human studies. This search indicated that biomarkers of SO2 exposure, SO2 effects on airway epithelial cell function, and animal model data are useful in our understanding of the body’s response to SO2, as are SO2-associated amplification of allergic inflammation, and potential promotion of neurogenic inflammation due to chemical irritant properties. While definitive answers are still being sought, these areas comprise important foci of consideration regarding asthmatic responses to inhaled SO2. Furthermore, IL-10 deficiency associated with asthma may be another important factor associated with an inability to resolve inflammation and mitigate oxidative stress resulting from SO2 inhalation, supporting the idea that asthmatics are predisposed to SO2 sensitivity, leading to asthma exacerbations and airway dysfunction. PMID:25922579

A Cluster Analysis of Bronchial Asthma Patients with Depressive Symptoms.

PubMed

Seino, Yo; Hasegawa, Takashi; Koya, Toshiyuki; Sakagami, Takuro; Mashima, Ichiro; Shimizu, Natsue; Muramatsu, Yoshiyuki; Muramatsu, Kumiko; Suzuki, Eiichi; Kikuchi, Toshiaki

2018-03-09

Objective Whether or not depression affects the control or severity of asthma is unclear. We performed a cluster analysis of asthma patients with depressive symptoms to clarify their characteristics. Methods and subjects Multiple medical institutions in Niigata Prefecture, Japan, were surveyed in 2014. We recorded the age, disease duration, body mass index (BMI), medications, and surveyed asthma control status and severity, as well as depressive symptoms and adherence to treatment using questionnaires. A hierarchical cluster analysis was performed on the group of patients assessed as having depression. Results Of 2,273 patients, 128 were assessed as being positive for depressive symptoms (DS[+]). Thirty-three were excluded because of missing data, and the remaining 95 DS[+] patients were classified into 3 clusters (A, B, and C). The patients in cluster A (n=19) were elderly, had severe, poorly controlled asthma, and demonstrated possible adherence barriers; those in cluster B (n=26) were elderly with a low BMI and had no significant adherence barriers but had severe, poorly controlled asthma; and those in cluster C (n=50) were younger, with a high BMI, no significant adherence barriers, well-controlled asthma, and few were severely affected. The scores for depressive symptoms were not significantly different between clusters. Conclusion About half of the patients in the DS[+] group had severe, poorly controlled asthma, and these clusters were able to be distinguished by their ASK-12 score, which reflects adherence barriers. The control status and severity of asthma may also be related to the age, disease duration, and BMI in the DS[+] group.

Asthma severity, child security, and child internalizing: using story stem techniques to assess the meaning children give to family and disease-specific events.

PubMed

Winter, Marcia A; Fiese, Barbara H; Spagnola, Mary; Anbar, Ran D

2011-12-01

Children with persistent asthma are at increased risk for mental health problems. Although mechanisms of effect are not yet known, it may be that children are less trusting of the family as a source of support and security when they have more severe asthma. This study tested whether asthma severity is related to children's perceptions of insecurity in the family, and whether insecurity is in turn associated with child adjustment. Children (N = 168; mean age = 8 years) completed story stems pertaining to routine family events (e.g., mealtimes) and ambiguous but potentially threatening asthma events such as tightness in the chest. Responses were evaluated for the extent to which appraisals portrayed the family as responding in cohesive, security-provoking ways. Asthma severity was assessed by both objective lung function testing and primary caregiver report. Caregivers reported child symptomatology. Beyond medication adherence, caregiver education, and child age and gender, greater asthma severity predicted more internalizing and externalizing symptoms. Greater asthma severity, assessed using spirometry (but not parent report), was related to less secure child narratives of the family, which in turn related to more child internalizing symptoms. Results suggest that asthma can take a considerable toll on children's feelings of security and mental health. Furthermore, given the difficulty in assessing young children's perceptions, this study helps demonstrate the potential of story stem techniques in assessing children's appraisals of illness threat and management in the family.

Asthma Severity, Child Security, and Child Internalizing: Using Story Stem Techniques to Assess the Meaning Children Give to Family and Disease-Specific Events

PubMed Central

Winter, Marcia A.; Fiese, Barbara H.; Spagnola, Mary; Anbar, Ran D.

2016-01-01

Children with persistent asthma are at increased risk for mental health problems. Although mechanisms of effect are not yet known, it may be that children are less trusting of the family as a source of support and security when they have more severe asthma. This study tested whether asthma severity is related to children’s perceptions of insecurity in the family, and whether insecurity is in turn associated with child adjustment. Children (N = 168; mean age = 8 years) completed story stems pertaining to routine family events (e.g., mealtimes) and ambiguous but potentially threatening asthma events such as tightness in the chest. Responses were evaluated for the extent to which appraisals portrayed the family as responding in cohesive, security-provoking ways. Asthma severity was assessed by both objective lung function testing and primary caregiver report. Caregivers reported child symptomatology. Beyond medication adherence, caregiver education, and child age and gender, greater asthma severity predicted more internalizing and externalizing symptoms. Greater asthma severity, assessed using spirometry (but not parent report), was related to less secure child narratives of the family, which in turn related to more child internalizing symptoms. Results suggest that asthma can take a considerable toll on children’s feelings of security and mental health. Furthermore, given the difficulty in assessing young children’s perceptions, this study helps demonstrate the potential of story stem techniques in assessing children’s appraisals of illness threat and management in the family. PMID:22059557

Phagocytosis, bacterial killing, and cytokine activation of circulating blood neutrophils in horses with severe equine asthma and control horses.

PubMed

Vanderstock, Johanne M; Lecours, Marie-Pier; Lavoie-Lamoureux, Annouck; Gottschalk, Marcelo; Segura, Mariela; Lavoie, Jean-Pierre; Jean, Daniel

2018-04-01

OBJECTIVE To evaluate in vitro phagocytosis and bactericidal activity of circulating blood neutrophils in horses with severe equine asthma and control horses and to determine whether circulating blood neutrophils in horses with severe equine asthma have an increase in expression of the proinflammatory cytokine tumor necrosis factor (TNF)-α and the chemokine interleukin (IL)-8 and a decrease in expression of the anti-inflammatory cytokine IL-10 in response to bacteria. ANIMALS 6 horses with severe equine asthma and 6 control horses. PROCEDURES Circulating blood neutrophils were isolated from horses with severe equine asthma and control horses. Phagocytosis was evaluated by use of flow cytometry. Bactericidal activity of circulating blood neutrophils was assessed by use of Streptococcus equi and Streptococcus zooepidemicus as targets, whereas the cytokine mRNA response was assessed by use of a quantitative PCR assay. RESULTS Circulating blood neutrophils from horses with severe equine asthma had significantly lower bactericidal activity toward S zooepidemicus but not toward S equi, compared with results for control horses. Phagocytosis and mRNA expression of TNF-α, IL-8, and IL-10 were not different between groups. CONCLUSIONS AND CLINCAL RELEVANCE Impairment of bactericidal activity of circulating blood neutrophils in horses with severe equine asthma could contribute to an increased susceptibility to infections.

Mild, Moderate, Severe Asthma: What Do Grades Mean?

MedlinePlus

... Text Size Email Print Share Mild, Moderate, Severe Asthma: What Do Grades Mean? Page Content Article Body ... is when assessed at follow-up visits. Intermittent Asthma A child who has symptoms of wheezing and ...

Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

PubMed

McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

2018-03-08

Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN15441965 .).

Attendance for general practitioner asthma care by children with moderate to severe asthma in Auckland, New Zealand.

PubMed

Buetow, Stephen; Richards, Deborah; Mitchell, Ed; Gribben, Barry; Adair, Vivienne; Coster, Gregor; Hight, Makere

2004-11-01

Attendance for general practitioner (GP) care of childhood asthma varies widely in New Zealand (NZ). There is little current research to account for the variations, although groups such as Māori and Pacific peoples have traditionally faced barriers to accessing GP care. This paper aims to describe and account for attendance levels for GP asthma care among 6-9 year-olds with moderate to severe asthma in Auckland, NZ. During 2002, randomly selected schools identified all 6-9 year-olds with possible breathing problems. Completion of a questionnaire by each parent/guardian indicated which children had moderate to severe asthma, and what characteristics influenced their access to GP asthma care. A multilevel, negative binomial regression model (NBRM) was fitted to account for the number of reported GP visits for asthma, with adjustment for clustering within schools. Twenty-six schools (89.7 percent) identified 931 children with possible breathing problems. Useable questionnaires were returned to schools by 455 children (48.9 percent). Results indicated 209 children with moderate to severe asthma, almost one in every three reportedly making 5 or more GP visits for asthma in the previous year. Māori, Pacific and Asian children were disproportionately represented among these 'high attendees'. Low attendees (0-2 visits) were mainly NZ Europeans. The NBRM (n=155) showed that expected visits were increased by perceived need, ill-health, asthma severity and, in particular, Māori and Pacific child ethnicity. It may be that Māori and Pacific children no longer face significant barriers to accessing GP asthma care. However, more likely is that barriers apply only to accessing routine, preventative care, leading to poor asthma control, exacerbations requiring acute care, and paradoxically an increase in GP visits. That barriers may increase total numbers of visits challenges the assumption, for all health systems, that access can be defined in terms of barriers that must be overcome to obtain health care.

A current picture of asthma diagnosis, severity, and control in a low-income minority preteen population.

PubMed

Clark, Noreen M; Dodge, Julia A; Shah, Smita; Thomas, Lara J; Andridge, Rebecca R; Awad, Daniel

2010-03-01

Asthma severity, control, type of medical regimen provided, and compliance with it are not well understood in minority patients at the transition stage from childhood to adolescence. Describe the level of asthma severity and control and the clinical regimens provided to a large population of low-income, African American children at this developmentally significant period. Parents of 1292 children with asthma among 6827 preteens in 19 middle schools in predominantly African American (94%), low-income neighborhoods in Detroit, Michigan, were enrolled in the study. Data were collected through self-administered survey and telephone interviews and were useable for 936 participants. Study queries related to demographics, asthma symptoms, and medication use. Mixed effects models with a random intercept for school were used to determine severity and control and the association of medical regimens to these. Sixty-seven percent of children with probable asthma had received a physician's diagnosis. Being female was associated with being undiagnosed (p = .02). Forty-seven with no diagnosis had persistent asthma and 10% of these were classified as severe. Sixty-eight percent with a diagnosis and asthma medicine prescriptions were not controlled. Compliant use of controller medicine was associated with poorer asthma control compared to noncompliant controller users (p = .04) and reliever-only users (p < .001). Thirty-nine percent of children had controller medicine; of those 40% were not compliant with controller use; 9% nebulized their controller medicine. Care provided low-income minority children at an important stage in their development was not consistent with guidelines for asthma control. Therapy choices for treatment did not account for the actual level of their symptoms. Lack of an asthma diagnosis was significant in the population. Adolescent girls were at risk for not receiving a diagnosis. Patient compliance with asthma regimens was limited. Both clinician and patient education regarding effective asthma management appears needed regarding preteens in low-income minority communities.

Genetic polymorphisms and asthma: findings from a case-control study in the Madeira island population.

PubMed

Berenguer, Anabela Gonçalves; Fernandes, Ana Teresa; Oliveira, Susana; Rodrigues, Mariana; Ornelas, Pedro; Romeira, Diogo; Serrão, Tânia; Rosa, Alexandra; Câmara, Rita

2014-09-04

Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold). In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.

Depression, asthma and bronchodilator response in a nationwide study of U.S. adults

PubMed Central

Han, Yueh-Ying; Forno, Erick; Marsland, Anna L.; Miller, Gregory E.; Celedón, Juan C.

2015-01-01

Background Little is known about the relation between two common co-morbidities (depression and anxiety) and asthma or bronchodilator response (BDR). Objective To examine the association between depressive symptoms and asthma or BDR in U.S. adults. Methods Cross-sectional study of 20,272 adults 20–79 years from the 2007–2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9), and classified as: none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a PHQ-9 ≥15. Anxiety was defined as ≥5 days feeling anxious in the prior month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and ≥1 asthma attack in the previous year. BDR (as percentage of baseline FEV1) was measured in 1,356 participants with FEV1/FVC<0.70 and/or FEV1<70% of predicted. Logistic or linear regression was used for the multivariable analysis. Results Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 higher odds of asthma than those with minimal or no depressive symptoms (95% confidence interval 2.6–4.5, P<0.01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI=−7.5% to −0.8%, P=0.02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR. Conclusion Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma. PMID:26563676

Serum progranulin as an indicator of neutrophilic airway inflammation and asthma severity.

PubMed

Park, So Young; Hong, Gyong Hwa; Park, Sunjoo; Shin, Bomi; Yoon, Sun-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

2016-12-01

Progranulin, a protein secreted from the airway epithelium, is known to attenuate the downstream cascade of neutrophilic inflammation in particular. We hypothesized that progranulin may have a role in inflammatory regulation in asthma. To investigate the association between serum progranulin levels and various clinical features in patients with asthma. Serum samples and clinical data of 475 patients with asthma and 35 healthy controls at a tertiary referral hospital and its affiliated health promotion center were collected. Serum progranulin levels were compared between patients with asthma and healthy controls and then were compared within the patients with asthma in terms of pulmonary function and measures of inflammatory status. Univariate and multivariate analyses were performed to identify factors associated with severity of asthma. Serum progranulin levels were significantly lower in the asthma group than in healthy group and were positively correlated with prebronchodilator forced expiratory volume in 1 second predicted within patients with asthma. We found a negative correlation between serum progranulin levels and blood neutrophil counts. Multivariate analysis revealed that higher serum progranulin levels were associated with a lower risk of severe asthma (odds ratio, 0.888; 95% confidence interval, 0.846-0.932; P < .001) after adjustment for other variables, such as age, sex, smoking status, blood neutrophil count, and current use of systemic corticosteroids. Although the exact mechanism of the anti-inflammatory action of progranulin remains unknown, we suggest that serum progranulin may be an indicator of severe asthma with airflow limitation. Future studies with comprehensive airway sampling strategies are warranted to clarify its role, particularly in neutrophilic asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Obstructive Sleep Apnea Risk, Asthma Burden and Lower Airway Inflammation in Adults in the Severe Asthma Research Program (SARP) II

PubMed Central

Teodorescu, Mihaela; Broytman, Oleg; Curran-Everett, Douglas; Sorkness, Ronald L.; Crisafi, Gina; Bleecker, Eugene R.; Erzurum, Serpil; Gaston, Benjamin M.; Wenzel, Sally E.; Jarjour, Nizar N.

2015-01-01

Background Obstructive sleep apnea (OSA) may worsen asthma, but large studies are lacking and the underlying mechanisms are unknown. Objective Determine the prevalence of OSA risk among patients with asthma of different severity compared to normal controls (NC), and among asthmatics, test the relationship of OSA risk with asthma burden and airway inflammation. Methods Subjects with severe (SA, n=94) and non-severe asthma (NSA, n=161), and NC (n=146) were recruited in an add-on sub-study, to the observational Severe Asthma Research Program (SARP) II; subjects completed sleep quality, sleepiness and OSA risk (Sleep Apnea scale of the Sleep Disorders Questionnaire [SA-SDQ]) questionnaires and clinical assessments. Sputum was induced in a subset of asthmatics. Results Relative to NC, despite similar sleep duration, the SA and NSA subjects had worse sleep quality, were sleepier and had higher SA-SDQ scores. Among asthmatics, higher SA-SDQ was associated with increased asthma symptoms, β-agonist use, health care utilization, and worse asthma quality of life. Significant association of SA-SDQ with sputum polymorphonuclear cells% was noted: each increase in SA-SDQ by its standard deviation (6.85 units) was associated with a rise in % sputum neutrophils of 7.78 (95 % CI 2.33-13.22, p = 0.0006), independent of obesity and other confounders. Conclusions OSA symptoms are more prevalent among asthmatics, in whom they are associated with higher disease burden. OSA risk is associated with a neutrophilic airway inflammation in asthma, suggesting that OSA may be an important contributor to the neutrophilic asthma. Further studies are necessary to confirm these findings and better understand the mechanistic underpinnings of this relationship. PMID:26004304

Targeting the interleukin pathway in the treatment of asthma.

PubMed

Chung, Kian Fan

2015-09-12

Asthma is a common heterogeneous disease with a complex pathophysiology. Current therapies based on inhaled corticosteroids and longacting β2 agonists are effective in controlling asthma in most, but not all patients, with a few patients falling into the severe asthma category. Severe asthma is characterised by poor asthma control, recurrent exacerbations, and chronic airflow obstruction despite adequate and, in many cases, high-dose treatments. There is strong evidence supporting the role for interleukins derived from T-helper-2 (Th2) cells and innate lymphoid cells, such as interleukins 4, 5, and 13, as underlying the eosinophilic and allergic inflammatory processes in nearly half of these patients. An anti-IgE antibody, omalizumab, which binds to circulating IgE, a product of B cells from the actions of interleukin 4 and interleukin 13, is used as treatment for severe allergic asthma. Studies examining cytokine blockers such as anti-interleukin-5, anti-interleukin-4Rα, and anti-interleukin-13 monoclonal antibodies in patients with severe asthma with recurrent exacerbations and high blood eosinophil counts despite use of inhaled corticosteroids have reported improved outcomes in terms of exacerbations, asthma control, and forced expiratory volume in 1 s. The US Food and Drug Administration's recommendation to use an anti-interleukin-5 antibody for the treatment of severe eosinophilic asthma suggests that there will be a therapeutic place for these anti-Th2 agents. Biomarkers should be used to identify the right patients for such targeted approaches. More guidance will be needed as to which patients should receive each of these classes of selective antibody-based treatments. Currently, there is no treatment that targets the cytokines driving asthma associated with non-eosinophilic inflammation and low Th2 expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

The molecular mechanisms of glucocorticoids-mediated neutrophil survival.

PubMed

Saffar, Arash S; Ashdown, Heather; Gounni, Abdelilah S

2011-04-01

Neutrophil-dominated inflammation plays an important role in many airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis and cystic fibrosis. In cases of asthma where neutrophil-dominated inflammation is a major contributing factor to the disease, treatment with corticosteroids can be problematic as corticosteroids have been shown to promote neutrophil survival which, in turn, accentuates neutrophilic inflammation. In light of such cases, novel targeted medications must be developed that could control neutrophilic inflammation while still maintaining their antibacterial/anti-fungal properties, thus allowing individuals to maintain effective innate immune responses to invading pathogens. The aim of this review is to describe the molecular mechanisms of neutrophil apoptosis and how these pathways are modulated by glucocorticoids. These new findings are of potential clinical value and provide further insight into treatment of neutrophilic inflammation in lung disease.

Allergen aerosol from pollen-nucleated precipitation: A novel thunderstorm asthma trigger

NASA Astrophysics Data System (ADS)

Beggs, Paul John

2017-03-01

Thunderstorm asthma is the term used to describe epidemics of asthma exacerbation associated with thunderstorms. Most published reports of thunderstorm asthma have come from the United Kingdom, Canada, and Australia, although several studies have been published on the phenomenon in the USA and Europe (particularly Greece and Italy). Such reports usually consider changes in hospital admissions or emergency department attendances for asthma. For example, Celenza et al. (1996) studied an asthma epidemic in London in June 1994 where 40 patients presented to the accident and emergency department of St Mary's Hospital in the 24 hours after a thunderstorm compared to an average of just over 2 asthma presentations per day over the several weeks before and after this event. More recent examples include the 20 patients who presented to an emergency department in Puglia, Italy, for sudden and severe asthmatic symptoms immediately after a thunderstorm in May 2010, where the average daily emergency department presentations for asthma several weeks before and after this event was only 2 to 3 (Losappio et al., 2011); and the 36 emergency department presentations for acute asthma to the Austin Hospital in Melbourne, Australia, on 25 November 2010 immediately after a thunderstorm (with the number of such presentations on days prior to and following the epidemic ranging from 0 to 10) (Howden et al., 2011).

The economic impact of severe asthma to low-income families.

PubMed

Franco, R; Nascimento, H F; Cruz, A A; Santos, A C; Souza-Machado, C; Ponte, E V; Souza-Machado, A; Rodrigues, L C; Barreto, M L

2009-03-01

To estimate the direct and indirect costs of severe asthma and the economic impact of its management to low-income families in Salvador, Brazil. One hundred and ninety-seven patients with severe asthma and referred to a state-funded asthma center providing free treatment were evaluated. At registration, they were asked about family cost-events in the previous year and had a baseline assessment of lung function, symptoms and quality of life. During the subsequent year, they were reassessed prospectively. One hundred-eighty patients concluded a 12-month follow-up. Eighty-four percent were female patients, and the median family income was US$ 2955/year. Forty-seven percent of family members had lost their jobs because of asthma. Total cost of asthma management took 29% of family income. After proper treatment, asthma control scores improved by 50% and quality of life by 74%. The income of the families increased by US$ 711/year, as their members went back to work. The total cost of asthma to the families was reduced by a median US$ 789/family/year. Consequently, an annual surplus of US$ 1500/family became available. Family costs of severe asthma consumed over one-fourth of the family income of the underprivileged population in a middle-income country. Adequate management brings major economic benefit to individuals and families.

The impact of long-term systemic glucocorticoid use in severe asthma: A UK retrospective cohort analysis.

PubMed

Daugherty, Jonas; Lin, Xiwu; Baxter, Richard; Suruki, Robert; Bradford, Eric

2018-06-01

Systemic glucocorticoids (SGCs) are a treatment option for severe asthma but are associated with the development of adverse events (AEs). Evidence on the extent of SGC use and the relationship between SGC dose and AE risk in severe asthma is limited. Patients with severe asthma (Global Initiative for Asthma step 4/5), with no SGC use during the <6-12 months before severe asthma determination (index date) were identified in the UK-based Clinical Practice Research Datalink database (2004-2012). Patients were assessed for SGC exposure and an incident diagnosis of an SGC-related AE (cataracts, diabetes, myocardial infarction [MI], osteoporosis, peptic ulcer or stroke) during the 8-year observation phase. The dose-related risk of an SGC-related AE was determined using AE-specific Cox proportional hazards models. Overall, 75% of 60,418 patients identified with severe asthma received SGC during the 8-year follow-up, with the majority receiving an average of >0-≤2.5 mg/day. The risk of diabetes (hazard ratio [HR]:1.20 [95% confidence interval (CI): 1.11, 1.30]), MI (HR: 1.25 [95% CI: 1.09, 1.43]) and osteoporosis (HR: 1.64 [95% CI: 1.51, 1.78]) was increased at low SGC doses (0-2.5 mg/day), with further risk increases at doses >2.5 mg/day versus no SGC use. Compared with no SGC use, SGC increased the risk of peptic ulcer in a non-dose-dependent manner, but the risk of stroke was unchanged. Most patients with severe asthma are exposed to SGC, which increases SGC-related AE risk. This suggests that SGC exposure should be minimized as recommended by asthma treatment guidelines.

Allergic sinusitis and severe asthma caused by occupational exposure to locust bean gum: Case report

PubMed Central

Hawley, Brie; Cummings, Kristin J.; Mohammed, Mohammed; Dimmock, Anne E.; Bascom, Rebecca

2017-01-01

We present a case that highlights the difficulties with diagnosis and the dangers of occupational allergic sinusitis and asthma left unrecognized. We describe the case history of a man who experienced work-related symptoms 1 year after beginning work as a cheesemaker at a creamery, and whose respiratory symptoms progressively worsened over 16 years before an occupational cause of his asthma was identified. His initial discrete episodes of sinusitis and acute bronchitis evolved into persistent asthma of increasing severity with exacerbations requiring repeated emergency room treatment. The case described in our report emphasizes the importance of clinician diagnosis of OA, and subsequent removal from exposure, such that asthma severity does not progress to near-fatal or fatal asthma in the sensitized worker. As demonstrated by this case report, identification of an occupational cause of asthma relies on a high degree of suspicion and excellent detective work by the clinician. PMID:28497854

Adiposity, fractional exhaled nitric oxide, and asthma in U.S. children.

PubMed

Han, Yueh-Ying; Forno, Erick; Celedón, Juan C

2014-07-01

Whether allergic airway inflammation mediates the association between overweight or obesity and childhood asthma is unknown. To examine adiposity, asthma, and fractional exhaled nitric oxide (FeNO) in U.S. children. Cross-sectional study of indicators of adiposity or obesity, FeNO (a biomarker of eosinophilic airway inflammation), and asthma in 2,681 children aged 6-17 years in the 2007-2010 National Health and Nutrition Examination Survey. Adiposity measures included body mass index (BMI), percent body fat (PBF), and waist circumference (WC). BMI, PBF, and WC were associated with asthma among children with low FeNO (odds ratio, 1.54-1.68; P < 0.01), but not among children with increased FeNO. Among children without asthma, BMI, PBF, and WC were associated with higher FEV1 and FVC, and lower FEV1/FVC. Among children with asthma and a high FeNO, all adiposity indicators were associated with decreased FEV1/FVC (β = -1.5% to -1.7% per z score) but not with FEV1 or FVC. Higher BMI or PBF was associated with worse asthma severity or control in children with asthma and increased FeNO, but not in children with asthma and low FeNO. Similar results were obtained in a secondary multivariate analysis of overweight or obesity (defined as BMI ≥85th percentile) and asthma or indicators of asthma severity or control, stratified by FeNO level. Adiposity indicators are associated with asthma in children with low FeNO. Among children with asthma, adiposity indicators are associated with worse asthma severity or control in those with high FeNO.

Asthma control in Latin America: the Asthma Insights and Reality in Latin America (AIRLA) survey.

PubMed

Neffen, Hugo; Fritscher, Carlos; Schacht, Francisco Cuevas; Levy, Gur; Chiarella, Pascual; Soriano, Joan B; Mechali, Daniel

2005-03-01

The aims of this survey were (1) to assess the quality of asthma treatment and control in Latin America, (2) to determine how closely asthma management guidelines are being followed, and (3) to assess perception, knowledge and attitudes related to asthma in Latin America. We surveyed a household sample of 2,184 adults or parents of children with asthma in 2003 in 11 countries in Latin America. Respondents were asked about healthcare utilization, symptom severity, activity limitations and medication use. Daytime asthma symptoms were reported by 56% of the respondents, and 51% reported being awakened by their asthma at night. More than half of those surveyed had been hospitalized, attended a hospital emergency service or made unscheduled emergency visits to other healthcare facilities for asthma during the previous year. Patient perception of asthma control did not match symptom severity, even in patients with severe persistent asthma, 44.7% of whom regarded their disease as being well or completely controlled. Only 2.4% (2.3% adults and 2.6% children) met all criteria for asthma control. Although 37% reported treatment with prescription medications, only 6% were using inhaled corticosteroids. Most adults (79%) and children (68%) in this survey reported that asthma symptoms limited their activities. Absence from school and work was reported by 58% of the children and 31% of adults, respectively. Asthma control in Latin America falls short of goals in international guidelines, and in many aspects asthma care and control in Latin America suffer from the same shortcomings as in other areas of the world.

Predicting worsening asthma control following the common cold

PubMed Central

Walter, Michael J.; Castro, Mario; Kunselman, Susan J.; Chinchilli, Vernon M; Reno, Melissa; Ramkumar, Thiruvamoor P.; Avila, Pedro C.; Boushey, Homer A.; Ameredes, Bill T.; Bleecker, Eugene R.; Calhoun, William J.; Cherniack, Reuben M.; Craig, Timothy J.; Denlinger, Loren C.; Israel, Elliot; Fahy, John V.; Jarjour, Nizar N.; Kraft, Monica; Lazarus, Stephen C.; Lemanske, Robert F.; Martin, Richard J.; Peters, Stephen P.; Ramsdell, Joe W.; Sorkness, Christine A.; Rand Sutherland, E.; Szefler, Stanley J.; Wasserman, Stephen I.; Wechsler, Michael E.

2008-01-01

The asthmatic response to the common cold is highly variable and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multi-center cohort study of 413 adult subjects with asthma, we used the mini-Asthma Control Questionnaire (mini-ACQ) to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models examined demographic, physiologic, serologic, and cold-related characteristics for their relationship to changes in asthma control following a cold. We observed a clinically significant worsening of asthma control following a cold (increase in mini-ACQ of 0.69 ± 0.93). Univariate analysis demonstrated season, center location, cold length, and cold severity measurements all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed the day 2 and the cumulative sum of the day 1 and 2 WURSS-21 scores were significant predictors for the subsequent changes in asthma control. In asthmatic subjects the cold severity measured within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold. PMID:18768579

Dietary patterns and asthma prevalence, incidence and control.

PubMed

Barros, R; Moreira, A; Padrão, P; Teixeira, V H; Carvalho, P; Delgado, L; Lopes, C; Severo, M; Moreira, P

2015-11-01

The increased asthma prevalence in westernized societies has been suggested to be related to environment exposures and lifestyle changes, particularly diet. We aimed to explore the association between dietary patterns and asthma prevalence, incidence and control in a nationally representative population. Data from 32,644 adults, 53% female, from the 4th Portuguese National Health Survey were analysed. Prevalence of asthma was 5.3%; 'current asthma', defined by asthma symptoms within previous year, 3.5%; 'current medicated asthma' defined by use of asthma medication within previous year, 3.0%; 'current severe asthma' defined by emergency visit because of asthma within previous year, 1.4%; and 'incident asthma', 0.2%. Dietary patterns (DP) were identified by latent trait models based on dietary intake. Unconditional logistic regression models were performed to analyse association between DP and asthma. Age, gender, education, family income, proxy reporting information, smoking, body mass index and physical activity level were analysed as confounders. Two of the five identified DP were associated with asthma: 'high fat, sugar and salt' DP (positively correlated with pastry, chocolate and sweet desserts, candies, salty snacks, chips, fruit juices, soft drinks and alcoholic beverages consumption at snacks) was associated with asthma prevalence (OR = 1.13, 95% CI = 1.03, 1.24) and current severe asthma (OR = 1.23, 95% CI = 1.03, 1.48), while 'fish, fruit and vegetables' DP (positively correlated with fish, vegetables and fruit intake at meals) was negatively associated with current (OR = 0.84, 95% CI = 0.73, 0.98), and current medicated asthma (OR = 0.84, 95% CI = 0.72, 0.98), after adjustment for confounders. Our results suggest a protective association between 'fish, vegetables and fruit' DP and current asthma and current medicated asthma, and a detrimental association between 'high fat, sugar and salt' DP and severe asthma prevalence, further supporting the rational for diet and lifestyle intervention studies in asthma based on whole dietary patterns and physical activity. © 2015 John Wiley & Sons Ltd.

The effect of obesity, weight gain, and weight loss on asthma inception and control.

PubMed

Forno, Erick; Celedón, Juan C

2017-04-01

There is ample and growing evidence that obesity increases the risk of asthma and morbidity from asthma. Here, we review recent clinical evidence supporting a causal link between obesity and asthma, and the mechanisms that may lead to 'obese asthma'. Although in some children obesity and asthma simply co-occur, those with 'obese asthma' have increased asthma severity, lower quality of life, and reduced medication response. Underlying mechanistic pathways may include anatomical changes of the airways such as obstruction and dysanapsis, systemic inflammation, production of adipokines, impaired glucose-insulin metabolism, altered nutrient levels, genetic and epigenetic changes, and alterations in the airway and/or gut microbiome. A few small studies have shown that weight loss interventions may lead to improvements in asthma outcomes, but thus far research on therapeutic interventions for these children has been limited. Obesity increases the risk of asthma - and worsens asthma severity or control - via multiple mechanisms. 'Obese asthma' is a complex, multifactorial phenotype in children. Obesity and its complications must be managed as part of the treatment of asthma in obese children.

Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children

PubMed Central

Blatter, Joshua; Brehm, John M.; Sordillo, Joanne; Forno, Erick; Boutaoui, Nadia; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Weiss, Scott T.; Litonjua, Augusto A.; Canino, Glorisa

2016-01-01

Background: Little is known about folate and atopy or severe asthma exacerbations. We examined whether folate deficiency is associated with number of positive skin tests to allergens or severe asthma exacerbations in a high-risk population and further assessed whether such association is explained or modified by vitamin D status. Methods: Cross-sectional study of 582 children aged 6 to 14 years with (n = 304) and without (n = 278) asthma in San Juan, Puerto Rico. Folate deficiency was defined as plasma folate less than or equal to 20 ng/ml. Our outcomes were the number of positive skin tests to allergens (range, 0–15) in all children and (in children with asthma) one or more severe exacerbations in the previous year. Logistic and negative binomial regression models were used for the multivariate analysis. All multivariate models were adjusted for age, sex, household income, residential proximity to a major road, and (for atopy) case/control status; those for severe exacerbations were also adjusted for use of inhaled corticosteroids and vitamin D insufficiency (a plasma 25[OH]D < 30 ng/ml). Measurements and Main Results: In a multivariate analysis, folate deficiency was significantly associated with an increased degree of atopy and 2.2 times increased odds of at least one severe asthma exacerbation (95% confidence interval for odds ratio, 1.1–4.6). Compared with children who had normal levels of both folate and vitamin D, those with both folate deficiency and vitamin D insufficiency had nearly eightfold increased odds of one or more severe asthma exacerbation (95% confidence interval for adjusted odds ratio, 2.7–21.6). Conclusions: Folate deficiency is associated with increased degree of atopy and severe asthma exacerbations in school-aged Puerto Ricans. Vitamin D insufficiency may further increase detrimental effects of folate deficiency on severe asthma exacerbations. PMID:26561879

Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children

PubMed Central

Brehm, John M.; Acosta-Pérez, Edna; Klei, Lambertus; Roeder, Kathryn; Barmada, Michael; Boutaoui, Nadia; Forno, Erick; Kelly, Roxanne; Paul, Kathryn; Sylvia, Jody; Litonjua, Augusto A.; Cabana, Michael; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa

2012-01-01

Rationale: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. Objectives: To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. Methods: A cross-sectional study was conducted of 560 children ages 6–14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Measurements and Main Results: Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5–4.9; P = 0.001) and atopy, and a lower FEV1/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2–21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1–4.1; P = 0.04) cases. Conclusions: Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control. PMID:22652028

Association between sensitization to Aureobasidium pullulans (Pullularia sp) and severity of asthma.

PubMed

Niedoszytko, Marek; Chełmińska, Marta; Jassem, Ewa; Czestochowska, Eugenia

2007-02-01

Recent data indicate that fungi may contribute to increased severity of asthma. To determine the prevalence of allergy to 15 mold allergens among patients hospitalized because of exacerbation of asthma and to evaluate the relationship between the severity of the disease and allergy to particular molds. Skin prick tests with standard aeroallergens of airborne allergens, including grass, tree, Dermatophagoides pteronyssinus, Dermatophagoides farinae, feather, and cat and dog fur, and a panel of mold allergens, including Alternaria, Cladosporium, Aspergillus, Penicillium, Trichothecium, Chaetomium globosum, Epicoccum, Epidermophyton, Helminthosporium, Aureobasidium pullulans, Rhizopus nigricans, Fusarium, Mucor, Merulius lacrymans, and yeast mix, were performed in 105 asthmatic patients and 30 controls. Positive skin prick test results were found in 98% of asthmatic patients and 66% of controls. Sensitivity to A pullulans was significantly associated with more severe asthma (odds ratio, 1.4; 95% confidence interval, 1.09-1.75; P = .006). Sensitization to Helminthosporium was associated with an increased number of asthma exacerbations that required hospitalization (17% vs 38%; chi2 test P = .03). Sensitization to A pullulans is a risk factor for severe asthma. Sensitization to Helminthosporium may be related to asthma exacerbation that requires hospitalization.

Advances in asthma in 2016: Designing individualized approaches to management.

PubMed

Anderson, William C; Apter, Andrea J; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2017-09-01

In this year's Advances in Asthma review, we discuss viral infections in asthmatic patients and potential therapeutic agents, the microbiome, novel genetic associations with asthma, air quality and climate effects on asthma, exposures during development and long-term sequelae of childhood asthma, patient-centered outcomes research, and precision medicine. In addition, we discuss application of biomarkers to precision medicine and new information on asthma medications. New evidence indicates that rhinovirus-triggered asthma exacerbations become more severe as the degree of sensitization to dust mite and mouse increase. The 2 biggest drivers of asthma severity are an allergy pathway starting with allergic sensitization and an environmental tobacco smoke pathway. In addition, allergic sensitization and blood eosinophils can be used to select medications for management of early asthma in young children. These current findings, among others covered in this review, represent significant steps toward addressing rapidly advancing areas of knowledge that have implications for asthma management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone.

PubMed

Stempel, David A; Raphiou, Ibrahim H; Kral, Kenneth M; Yeakey, Anne M; Emmett, Amanda H; Prazma, Charlene M; Buaron, Kathleen S; Pascoe, Steven J

2016-05-12

The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.).

Cluster Analysis Identifies 3 Phenotypes within Allergic Asthma.

PubMed

Sendín-Hernández, María Paz; Ávila-Zarza, Carmelo; Sanz, Catalina; García-Sánchez, Asunción; Marcos-Vadillo, Elena; Muñoz-Bellido, Francisco J; Laffond, Elena; Domingo, Christian; Isidoro-García, María; Dávila, Ignacio

Asthma is a heterogeneous chronic disease with different clinical expressions and responses to treatment. In recent years, several unbiased approaches based on clinical, physiological, and molecular features have described several phenotypes of asthma. Some phenotypes are allergic, but little is known about whether these phenotypes can be further subdivided. We aimed to phenotype patients with allergic asthma using an unbiased approach based on multivariate classification techniques (unsupervised hierarchical cluster analysis). From a total of 54 variables of 225 patients with well-characterized allergic asthma diagnosed following American Thoracic Society (ATS) recommendation, positive skin prick test to aeroallergens, and concordant symptoms, we finally selected 19 variables by multiple correspondence analyses. Then a cluster analysis was performed. Three groups were identified. Cluster 1 was constituted by patients with intermittent or mild persistent asthma, without family antecedents of atopy, asthma, or rhinitis. This group showed the lowest total IgE levels. Cluster 2 was constituted by patients with mild asthma with a family history of atopy, asthma, or rhinitis. Total IgE levels were intermediate. Cluster 3 included patients with moderate or severe persistent asthma that needed treatment with corticosteroids and long-acting β-agonists. This group showed the highest total IgE levels. We identified 3 phenotypes of allergic asthma in our population. Furthermore, we described 2 phenotypes of mild atopic asthma mainly differentiated by a family history of allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Influence of β(2)-adrenergic receptor polymorphisms on asthma exacerbation in children with severe asthma regularly receiving salmeterol.

PubMed

Giubergia, Verónica; Gravina, Luis; Castaños, Claudio; Chertkoff, Lilien

2013-03-01

New evidence suggests that different β(2)-adrenergic receptor (β2AR) polymorphisms may influence asthma control in patients receiving long-acting β(2)agonists (LABAs) as regular therapy. To determine the influence of β2AR polymorphisms on asthma exacerbations in children with severe asthma from Argentina receiving inhaled corticosteroid (ICS) and LABAs regularly. Ninety-seven children with severe asthma were genotyped for polymorphisms of β2AR at codons 16 and 27. The number of severe exacerbations, the time of first asthma exacerbation, and the number of hospitalizations during 12 months were assessed. Changes on pulmonary function from the beginning to the end of the study were also evaluated. The number of overall asthma exacerbations and the proportion of children with these events were similar among β2AR genotypes at position 16 (Arg/Arg, Arg/Gly, and Gly/Gly) and at position 27 (Gln/Gln, Gln/Glu, and Glu/Glu). The time to first asthma exacerbation was similar among individuals carrying different β2AR polymorphisms. No β2AR genotype association was found in relation to the number of hospitalizations. Longitudinal analysis of forced expiratory volume in 1 second from baseline to the end of the study also showed no differences among β2AR genotypes at position 16 or 27. No association was observed among the 3 most common haplotypes (Arg/Arg-Gln/Gln, Gly/Gly-Gln/Gln, and Gly/Gly-Glu/Glu) and the number of participants with asthmatic crisis or with the overall number of exacerbations. β2AR polymorphisms were not associated with an increased risk of having asthma exacerbations or lung function decline in a population of Argentinian children with severe asthma receiving ICS and LABAs regularly. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Enhancing Asthma Self-Management in Rural School-Aged Children: A Randomized Controlled Trial.

PubMed

Horner, Sharon D; Brown, Adama; Brown, Sharon A; Rew, D Lynn

2016-06-01

To test the effects of 2 modes of delivering an asthma educational intervention on health outcomes and asthma self-management in school-aged children who live in rural areas. Longitudinal design with data collected 4 times over 12 months. The target sample was composed of children in grades 2-5 who had a provider diagnosis of asthma. Elementary schools were stratified into high or low socioeconomic status based on student enrollment in the free or reduced-cost lunch program. Schools were then randomly assigned to 1 of 3 treatment arms: in-school asthma class, asthma day camp, or the attention-control group. Sample retention was good (87.7%) and equally distributed by study arm. Improvements in emergency department visits and office visits were related to attending either the asthma class or asthma day camp. Asthma severity significantly decreased in both asthma treatment groups. Other factors such as hospitalizations, parent asthma management, and child asthma management improved for all groups. Both asthma class and asthma day camp yielded significant reductions in asthma severity. There were reductions in the emergency department and office visits for the 2 asthma arms, and hospitalizations declined significantly for all groups. Asthma self-management also improved in all groups, while it was somewhat higher in the asthma arms. This may be due to the attention being drawn to asthma management by study participation and the action of completing questionnaires about asthma management, asthma symptoms, and health outcomes. © 2015 National Rural Health Association.

A Multiomics Approach to Identify Genes Associated with Childhood Asthma Risk and Morbidity.

PubMed

Forno, Erick; Wang, Ting; Yan, Qi; Brehm, John; Acosta-Perez, Edna; Colon-Semidey, Angel; Alvarez, Maria; Boutaoui, Nadia; Cloutier, Michelle M; Alcorn, John F; Canino, Glorisa; Chen, Wei; Celedón, Juan C

2017-10-01

Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.

Depression, Asthma, and Bronchodilator Response in a Nationwide Study of US Adults.

PubMed

Han, Yueh-Ying; Forno, Erick; Marsland, Anna L; Miller, Gregory E; Celedón, Juan C

2016-01-01

Little is known about the relation between 2 common comorbidities (depression and anxiety) and asthma or bronchodilator response (BDR). To examine the association between depressive symptoms and asthma or BDR in US adults. Cross-sectional study of 20,272 adults aged 20 to 79 years from the 2007-2012 National Health and Nutrition Examination Survey. Depressive symptoms were measured using the 9-item Patient Health Questionnaire, and classified as none to minimal, mild, moderate, moderately severe, and severe. Major depression (comprising moderately severe to severe symptoms) was defined as a 9-item Patient Health Questionnaire score of 15 or more. Anxiety was defined as 5 or more days feeling anxious in the previous month. Current asthma was defined as having been diagnosed with asthma by a doctor or health professional and 1 or more asthma attack in the previous year. BDR (as percentage of baseline FEV1) was measured in 1356 participants with FEV1/forced vital capacity of less than 0.70 and/or FEV1 less than 70% of predicted. Logistic or linear regression was used for the multivariable analysis. Depressive symptoms were significantly and linearly associated with asthma, independently of anxiety symptoms. Subjects with major depression had 3.4 times higher odds of asthma than did those with minimal or no depressive symptoms (95% CI, 2.6-4.5; P < .01). Among adults with asthma, major depression was associated with a 4.2% reduction in BDR (95% CI, -7.5% to -0.8%; P = .02). Major depression was not associated with BDR among adults without asthma. Anxiety was not associated with asthma or BDR. Depressive symptoms are associated with asthma in adults, independently of anxiety symptoms. Major depression is associated with reduced BDR in adults with asthma. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Phenotypes Determined by Cluster Analysis in Moderate to Severe Bronchial Asthma.

PubMed

Youroukova, Vania M; Dimitrova, Denitsa G; Valerieva, Anna D; Lesichkova, Spaska S; Velikova, Tsvetelina V; Ivanova-Todorova, Ekaterina I; Tumangelova-Yuzeir, Kalina D

2017-06-01

Bronchial asthma is a heterogeneous disease that includes various subtypes. They may share similar clinical characteristics, but probably have different pathological mechanisms. To identify phenotypes using cluster analysis in moderate to severe bronchial asthma and to compare differences in clinical, physiological, immunological and inflammatory data between the clusters. Forty adult patients with moderate to severe bronchial asthma out of exacerbation were included. All underwent clinical assessment, anthropometric measurements, skin prick testing, standard spirometry and measurement fraction of exhaled nitric oxide. Blood eosinophilic count, serum total IgE and periostin levels were determined. Two-step cluster approach, hierarchical clustering method and k-mean analysis were used for identification of the clusters. We have identified four clusters. Cluster 1 (n=14) - late-onset, non-atopic asthma with impaired lung function, Cluster 2 (n=13) - late-onset, atopic asthma, Cluster 3 (n=6) - late-onset, aspirin sensitivity, eosinophilic asthma, and Cluster 4 (n=7) - early-onset, atopic asthma. Our study is the first in Bulgaria in which cluster analysis is applied to asthmatic patients. We identified four clusters. The variables with greatest force for differentiation in our study were: age of asthma onset, duration of diseases, atopy, smoking, blood eosinophils, nonsteroidal anti-inflammatory drugs hypersensitivity, baseline FEV1/FVC and symptoms severity. Our results support the concept of heterogeneity of bronchial asthma and demonstrate that cluster analysis can be an useful tool for phenotyping of disease and personalized approach to the treatment of patients.

Asthma and Adolescents: Review of Strategies to Improve Control

ERIC Educational Resources Information Center

Hennessy-Harstad, Ellen

2013-01-01

One of every 10 adolescents in the United States has asthma. Adolescents who lack asthma control are at increased risk for severe asthma episodes and death. The National Heart, Lung, and Blood Institute 2007 asthma guidelines and research studies indicated that school nurses are instrumental in assisting adolescents to monitor their asthma, learn…

Association Between Severe Vitamin D Deficiency, Lung Function and Asthma Control.

PubMed

Beyhan-Sagmen, Seda; Baykan, Ozgur; Balcan, Baran; Ceyhan, Berrin

2017-04-01

To examine the relationship between severe vitamin D deficiency, asthma control, and pulmonary function in Turkish adults with asthma. One hundred six asthmatic patients underwent pulmonary function tests skin prick test, peripheral blood eosinophil counts, IgE, body mass index and vitamin D levels were determined. Patients were divided into 2 subgroups according to vitamin D levels (vitamin D level<10ng/ml and vitamin D level≥10 ng/ml). Asthma control tests were performed. The mean age of subgroup i (vitamin D level<10) was 37±10 and the mean age of subgroup ii (vitamin D level≥10ng/ml) was 34±8. Sixty-six percent of patients had severe vitamin D deficiency (vitamin D level<10 ng/ml). There was a significant trend towards lower absolute FEV 1 (L) values in patients with lower vitamin D levels (P=.001). Asthma control test scores were significantly low in the severe deficiency group than the other group (P=.02). There were a greater number of patients with uncontrolled asthma (asthma control test scores<20) in the severe vitamin D deficiency group (P=.040). Patients with severe vitamin D deficiency had a higher usage of inhaled corticosteroids than the group without severe vitamin D deficiency (P=.015). There was a significant trend towards lower absolute FEV 1 (L) (P=.005, r=.272) values in patients with lower vitamin D levels. Vitamin D levels were inversely related with body mass index (P=.046). The incidence of severe vitamin D deficiency was high in adult Turkish asthmatics. In addition, lower vitamin D levels were associated with poor asthma control and decreased pulmonary function. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

[Consensus-based approach for severe paediatric asthma in routine clinical practice].

PubMed

Plaza, A M; Ibáñez, M D P; Sánchez-Solís, M; Bosque-García, M; Cabero, M J; Corzo, J L; García-Hernández, G; de la Hoz, B; Korta-Murua, J; Sánchez-Salguero, C; Torres-Borrego, J; Tortajada-Girbés, M; Valverde-Molina, J; Zapatero, L; Nieto, A

2016-02-01

Accurate identification of paediatric patients with severe asthma is essential for an adequate management of the disease. However, criteria for defining severe asthma and recommendations for control vary among different guidelines. An online survey was conducted to explore expert opinions about the definition and management of severe paediatric asthma. To reach a consensus agreement, a modified Delphi technique was used, and practice guidelines were prepared after the analysis of the results. Eleven paediatric chest disease physicians and allergy specialists with wide expertise in severe asthma responded to the survey. Consensus was reached in 50 out of 65 questions (76.92%). It was considered that a patient has severe asthma if during the previous year they have required 2 or more cycles of oral steroids, required daily treatment with medium doses of inhaled corticosteroids (with other controller medication) or high doses (with or without other controller medication), did not respond to optimised conventional treatment, or if the disease threatened the life of the patient or seriously impairs their quality of life. The definition of severe asthma may also include patients who justifiably use health resources on a regular basis, or have psychosocial or environmental factors impeding control. For monitoring, the use of questionnaires designed specifically for paediatric population, such as CAN or ACT, is recommended. As regards treatment, the use of omalizumab should be considered prior to the use of oral corticosteroids. This paper provides consensus recommendations that may be useful in the management of severe paediatric asthma. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Adiposity, Fractional Exhaled Nitric Oxide, and Asthma in U.S. Children

PubMed Central

Han, Yueh-Ying; Forno, Erick

2014-01-01

Rationale: Whether allergic airway inflammation mediates the association between overweight or obesity and childhood asthma is unknown. Objectives: To examine adiposity, asthma, and fractional exhaled nitric oxide (FeNO) in U.S. children. Methods: Cross-sectional study of indicators of adiposity or obesity, FeNO (a biomarker of eosinophilic airway inflammation), and asthma in 2,681 children aged 6–17 years in the 2007–2010 National Health and Nutrition Examination Survey. Adiposity measures included body mass index (BMI), percent body fat (PBF), and waist circumference (WC). Measurements and Main Results: BMI, PBF, and WC were associated with asthma among children with low FeNO (odds ratio, 1.54–1.68; P < 0.01), but not among children with increased FeNO. Among children without asthma, BMI, PBF, and WC were associated with higher FEV1 and FVC, and lower FEV1/FVC. Among children with asthma and a high FeNO, all adiposity indicators were associated with decreased FEV1/FVC (β = −1.5% to −1.7% per z score) but not with FEV1 or FVC. Higher BMI or PBF was associated with worse asthma severity or control in children with asthma and increased FeNO, but not in children with asthma and low FeNO. Similar results were obtained in a secondary multivariate analysis of overweight or obesity (defined as BMI ≥85th percentile) and asthma or indicators of asthma severity or control, stratified by FeNO level. Conclusions: Adiposity indicators are associated with asthma in children with low FeNO. Among children with asthma, adiposity indicators are associated with worse asthma severity or control in those with high FeNO. PMID:24922361

Role for NLRP3 Inflammasome-mediated, IL-1β-Dependent Responses in Severe, Steroid-Resistant Asthma.

PubMed

Kim, Richard Y; Pinkerton, James W; Essilfie, Ama T; Robertson, Avril A B; Baines, Katherine J; Brown, Alexandra C; Mayall, Jemma R; Ali, M Khadem; Starkey, Malcolm R; Hansbro, Nicole G; Hirota, Jeremy A; Wood, Lisa G; Simpson, Jodie L; Knight, Darryl A; Wark, Peter A; Gibson, Peter G; O'Neill, Luke A J; Cooper, Matthew A; Horvat, Jay C; Hansbro, Philip M

2017-08-01

Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1β responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma. To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1β in severe, steroid-resistant asthma. We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1β responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1β responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1β antibody. Roles for IL-1β-induced neutrophilic inflammation were examined using IL-1β and anti-Ly6G. Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1β responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1β expression. Treatment with anti-IL-1β, Ac-YVAD-cho, and MCC950 suppressed IL-1β responses and the important steroid-resistant features of disease in mice, whereas IL-1β administration recapitulated these features. Neutrophil depletion suppressed IL-1β-induced steroid-resistant airway hyperresponsiveness. NLRP3 inflammasome responses drive experimental severe, steroid-resistant asthma and are potential therapeutic targets in this disease.

Factors associated with severe disease in a population of asthmatic children of Bogota, Colombia.

PubMed

Rodriguez Martinez, Carlos; Sossa, Monica; Goss, Christopher H

2008-03-01

There is evidence that prevalence and severity of asthma in children has risen. Risk factors for severe asthma have been studied extensively in children living in developed countries, but little is known about factors determining the severity of asthma in Latin American countries. The aim of this study was to investigate the role of suspected, potential risk factors for asthma severity in a population of children living in urban Bogota. We studied 175 children, 2 to 16 years old, with asthma attending an asthma clinic. Severe cases and nonsevere asthmatic subjects were compared regarding suspected, potential pre-, peri-, and postnatal risk factors. After controlling for asthma duration, we found that children never breast fed (OR, 11.53; 95% CI, 2.35-56.50; p = 0.003), mothers 30 years or younger at the child's birth (OR, 3.44; 95% CI, 1.23-9.63; p = 0.019), usual use of acetaminophen for fever in the child in the 12 months previous to the survey application (OR, 3.13; 95% CI, 1.14-8.56; p = 0.026), older siblings at birth (OR, 3.81; 95% CI, 1.28-11.32; p = 0.016), and primary or secondary school as the highest level of education attained by mother (OR, 3.20; 95% CI, 1.01-10.07; p = 0.046) were all independent predictors of severe asthma. No breastfeeding, maternal age at child's birth of less than 30 years, routine use of acetaminophen for fever in the child in the 12 months previous to the survey application, older siblings at birth, and primary or secondary school as the highest level of education attained by mother were independent predictors of severe asthma. Some of these risk factors are clearly modifiable. Further prospective, population-based studies with a bigger sample size and a more representative sample of the general population residing in the city are needed to retest and clarify these associations.

Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma.

PubMed

Naik, Srilata Puru; P A, Mahesh; B S, Jayaraj; Madhunapantula, SubbaRao V; Jahromi, Sarah Raeiszadeh; Yadav, Manish Kumar

2017-08-01

Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p < 0.001), moderate versus severe persistent asthma (p < 0.001). A significant negative correlation was observed between MMP-9 and pre-bronchodilator FEV 1 and FVC, but not with IL-6. There was no association between IL-6 and MMP-9 with asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV 1 improvement after 2 months of ICS+LABA. Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.

Weekly Monitoring of Children with Asthma for Infections and Illness During Common Cold Seasons

PubMed Central

Olenec, Jaime P; Kim, Woo Kyung; Lee, Wai-Ming; Vang, Fue; Pappas, Tressa E; Salazar, Lisa EP; Evans, Michael D; Bork, Jack; Roberg, Kathleen; Lemanske, Robert F; Gern, James E

2010-01-01

Background Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity. Objectives To evaluate rhinovirus infections during peak seasons in children with asthma, and to analyze relationships between viral infection and illness severity. Methods Fifty-eight children with asthma ages 6-8 years provided 5 consecutive weekly nasal lavage samples during September and April; symptoms, medication use, and peak flow were recorded. Rhinoviruses were identified using multiplex PCR and partial sequencing of viral genomes. Results Viruses were detected in 36-50% of the specimens, and, 72-99% of the viruses were rhinoviruses. There were 52 different strains (including 16 HRV-C) among the 169 rhinovirus isolates; no strains found in more than two collection periods, and all but two children had a respiratory infection. Virus-positive weeks were associated with greater cold and asthma severity (p<0.0001 and p=0.0002 respectively). Furthermore, virus-positive illnesses had increased duration and severity of cold and asthma symptoms, and more frequent loss of asthma control (47% vs. 22%, p=0.008). While allergen-sensitized vs. non-sensitized children had the same number of viral infections, the former had 47% more symptomatic viral illnesses (1.19 vs. 0.81 per month, p=0.03). Conclusions Rhinovirus infections are nearly universal in children with asthma during common cold seasons, likely due to a plethora of new strains appearing each season. Illnesses associated with viruses have greater duration and severity. Finally, atopic asthmatic children experienced more frequent and severe viral-induced illnesses. Clinical Implications The combination of viral infection and allergy increases the morbidity of respiratory illness in children with asthma. PMID:20392488

Weekly monitoring of children with asthma for infections and illness during common cold seasons.

PubMed

Olenec, Jaime P; Kim, Woo Kyung; Lee, Wai-Ming; Vang, Fue; Pappas, Tressa E; Salazar, Lisa E P; Evans, Michael D; Bork, Jack; Roberg, Kathleen; Lemanske, Robert F; Gern, James E

2010-05-01

Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity. We sought to evaluate rhinovirus infections during peak seasons in children with asthma and to analyze relationships between viral infection and illness severity. Fifty-eight children aged 6 to 8 years with asthma provided 5 consecutive weekly nasal lavage samples during September and April; symptoms, medication use, and peak flow were recorded. Rhinoviruses were identified by using multiplex PCR and partial sequencing of viral genomes. Viruses were detected in 36% to 50% of the specimens, and 72% to 99% of the viruses were rhinoviruses. There were 52 different strains (including 16 human rhinovirus C) among the 169 rhinovirus isolates; no strains were found in more than 2 collection periods, and all but 2 children had a respiratory tract infection. Virus-positive weeks were associated with greater cold and asthma symptom severity (P < .0001 and P = .0002, respectively). Furthermore, virus-positive illnesses had increased duration and severity of cold and asthma symptoms and more frequent loss of asthma control (47% vs 22%, P = .008). Although allergen-sensitized versus nonsensitized children had the same number of viral infections, the former had 47% more symptomatic viral illnesses (1.19 vs 0.81 per month, P = .03). Rhinovirus infections are nearly universal in children with asthma during common cold seasons, likely because of a plethora of new strains appearing each season. Illnesses associated with viruses have greater duration and severity. Finally, atopic asthmatic children experienced more frequent and severe virus-induced illnesses. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The role of the indoor environment: Residential determinants of allergy, asthma and pulmonary function in children from a US-Mexico border community.

PubMed

Svendsen, Erik R; Gonzales, Melissa; Commodore, Adwoa

2018-03-01

The El Paso Children's Health Study examined environmental risk factors for allergy and asthma among fourth and fifth grade schoolchildren living in a major United States-Mexico border city. Complete questionnaire information was available for 5210 children, while adequate pulmonary function data were available for a subset of 1874. Herein we studied indoor environmental health risk factors for allergy and asthma. Several indoor environmental risk factors were associated with allergy and asthma. In particular, we found that ant and spider pest problems, pet dogs, fireplace heat, central air conditioning, humidifier use, and cooking with gas stoves were positively associated with both allergy and asthma prevalence. With regards to asthma severity, our analysis indicated that exposure to pet dogs increased monotonically with increasing asthma severity while the lack of any heat source and gas stove use for cooking decreased monotonically with increasing asthma severity. Lung function also decreased among children who lived in homes with reported cockroach pest problem in the past year without concurrent use of pesticides. These effects on pulmonary function were present even after excluding children with a current physician's diagnosis of asthma. Clinicians and public health professionals may need to look closely at the contribution of these indoor risk factors on pulmonary health and quality of life among susceptible populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeted anti-IL-13 therapies in asthma: current data and future perspectives.

PubMed

Ntontsi, Polyxeni; Papathanassiou, Evgenia; Loukides, Stelios; Bakakos, Petros; Hillas, Georgios

2018-02-01

The identification of patients with severe asthma who will benefit from a personalized management approach remains an unmet need. Interleukin-13 (IL-13) is a cytokine possessing a significant role in asthma pathogenesis and progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13 and IL-4 receptors are mainly proposed as add-on therapy in patients with T H 2-high inflammation with uncontrolled asthma despite maximum therapy. Areas covered: The role of IL-13 in airway inflammation in severe asthma, the targeted anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment are discussed. Expert opinion: New effective individualized therapies in severe asthma are urgently needed to block specific inflammatory pathways using monoclonal antibodies. Studies on anti-IL-13 therapies showed that asthmatic patients could benefit from this novel targeted therapy as far as lung function and exacerbation rate are concerned. T H 2-high and especially periostin-high groups of asthmatics with moderate-to-severe uncontrolled asthma seem to compose the group that could benefit from anti-IL-13 therapy. Targeting IL-13 alone may not be sufficient to achieve asthma control. Inhibition of IL-13 and IL-4 with mabs may be more encouraging and patients will probably have additional benefits from these therapeutic interventions because of IL-13/IL-4 overlapping actions in asthma pathophysiology.

The relationship between combination inhaled corticosteroid and long-acting beta-agonist use and severe asthma exacerbations in a diverse population

PubMed Central

Wells, Karen E.; Peterson, Edward L.; Ahmedani, Brian K.; Severson, Richard K.; Gleason-Comstock, Julie; Williams, L. Keoki

2012-01-01

Background Safety concerns surround the use of long-acting beta agonists (LABA) for the treatment of asthma, even in combination with inhaled corticosteroids (ICS) and particularly in high-risk subgroups. Objective To estimate the effect ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population. Methods Inhaled corticosteroid and ICS/LABA exposure was estimated from pharmacy data for patients with asthma age 12 to 56 years who were members of a large health maintenance organization. Inhaled corticosteroid and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (i.e., use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization). Results Among the 1,828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio [HR]=0.65 vs. HR=0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy. Conclusion Treatment with ICS/LABA fixed combination therapy appeared to perform as well or better than ICS alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups. PMID:22281166

Passive Smoking Impairs Histone Deacetylase-2 in Children With Severe Asthma

PubMed Central

Kobayashi, Yoshiki; Bossley, Cara; Gupta, Atul; Akashi, Kenichi; Tsartsali, Lemonia; Mercado, Nicolas; Barnes, Peter J.; Bush, Andrew

2014-01-01

Background: Parental smoking is known to worsen asthma symptoms in children and to make them refractory to asthma treatment, but the molecular mechanism is unclear. Oxidative stress from tobacco smoke has been reported to impair histone deacetylase-2 (HDAC2) via phosphoinositide-3-kinase (PI3K)/Akt activation and, thus, to reduce corticosteroid sensitivity. The aim of this study was to investigate passive smoking-dependent molecular abnormalities in alveolar macrophages (AMs) by comparing passive smoke-exposed children and non-passive smoke-exposed children with uncontrolled severe asthma. Methods: BAL fluid (BALF) was obtained from 19 children with uncontrolled severe asthma (10 non-passive smoking-exposed subjects and nine passive smoking-exposed subjects), and HDAC2 expression/activity, Akt/HDAC2 phosphorylation levels, and corticosteroid responsiveness in AMs were evaluated. Results: Parental smoking reduced HDAC2 protein expression by 54% and activity by 47%, with concomitant enhancement of phosphorylation of Akt1 and HDAC2. In addition, phosphorylation levels of Akt1 correlated positively with HDAC2 phosphorylation levels and negatively with HDAC2 activity. Furthermore, passive smoke exposure reduced the inhibitory effects of dexamethasone on tumor necrosis factor-α-induced CXCL8 release in AMs. There were relatively higher neutrophil counts and CXCL8 concentrations in BALF and lower Asthma Control Test scores compared with non-passive smoke-exposed children with uncontrolled severe asthma. Conclusions: Passive smoking impairs HDAC2 function via PI3K signaling activation, which could contribute to corticosteroid-insensitive inflammation in children with severe asthma. This novel mechanism will be a treatment target in children with severe asthma and stresses the need for a smoke-free environment for asthmatic children. PMID:24030221

Relationship between maternal asthma, its severity and control and abortion.

PubMed

Blais, Lucie; Kettani, Fatima-Zohra; Forget, Amélie

2013-04-01

Are women with asthma, and more specifically those with severe or uncontrolled asthma, at higher risk of spontaneous and induced abortions? Pregnant women with asthma, notably when uncontrolled, are at higher risk of spontaneous abortion. Only one study has examined the association between asthma and spontaneous and induced abortions and revealed a modest increase in the risk of spontaneous abortions, particularly in women with more severe asthma and those with previous exacerbations, and a marginal decrease in the risk of induced abortions. A cohort of pregnancies from asthmatic (n = 15,107) and non-asthmatic (n = 34,331) women was reconstructed by linking three administrative databases from Quebec (Canada), between 1992 and 2002. The cohort included 7870 spontaneous abortions, 14,596 induced abortions and 26,972 live births. Pregnant women with and without asthma were analyzed. Asthma was defined by at least one asthma diagnosis and one dispensed prescription for an asthma medication in the 2 years prior to or during pregnancy. Asthma severity and control were assessed using validated indexes in the year before the 20th week of pregnancy or the termination of the pregnancy. Logistic polytomous regression models were used to estimate the relationship between asthma and asthma severity and control on the risk of abortion, while adjusting for potential confounders. The prevalence of spontaneous and induced abortions was 15.9 and 29.5%, respectively. Maternal asthma was associated with an increased risk of a spontaneous abortion [odds ratio (OR) = 1.41; 95% confidence interval (CI): 1.33-1.49] and a decreased risk of induced abortions (OR = 0.92; 0.88-0.97). No association was observed between asthma severity and abortion, while uncontrolled asthma increased the risk of a spontaneous abortion by 26% (95% CI: 14-41%) and the risk of induced abortions by 11% (95% CI: 1-21%). It is possible that the study results were confounded by imbalances between groups in variables that are not recorded in the databases, but that are known to be associated with spontaneous abortions, such as alcohol consumption, obesity or maternal smoking. However, we performed sensitivity analyses which revealed that these factors are unlikely to explain the observed increased risk for a spontaneous abortion. It is also possible that women with asthma are more likely to have abortions recorded in the databases, because subjects with a chronic disease tend to visit a physician more often than those without asthma. Therefore, our odds estimates for these outcomes may be overestimated when asthmatic women were compared with non-asthmatic women. A further limitation of the study is that it would have been more appropriate to measure the severity and control of asthma only during the pregnancy. Our cohort is less representative of women in the upper socio-economic level. This is not a threat to internal validity, but it could limit the external validity if the impact of asthma on the risk of abortion differed according to the socio-economic status of the mother. Despite the absence of supporting data, this possibility cannot be completely excluded. This study was funded by the Canadian Institutes of Health Research and Genentech. L.B. received research grants from Astra-Zeneca, Pfizer, sanofi-aventis, Novartis and Merck for research projects and co-chairs the Astra-Zeneca Endowment Pharmaceutical Chair in Respiratory Health. F.Z.K and A.F. have no competing interests to declare.

Air pollution and respiratory diseases – a problematic risk factor.

PubMed

Mihălţan, Florin; Deleanu, Oana; Nemeș, Roxana; Ulmeanu, Ruxandra

2016-01-01

Pollution was a neglected factor for years in all the research that took in the viewfinder was examined in the risk factors in of respiratory diseases. Considering the concerns of politicians, scientists, doctors, which have intensified upgraded especially after the last climate “summit”, “summit” climatological we found it necessary to have a review of the effects of pollution, pathogenic mechanisms of interaction, and some diseases strongly influenced by pollutants such as COPD, asthma, bronchialand bronchial and lung cancer.

Japanese Guideline for Adult Asthma 2014.

PubMed

Ohta, Ken; Ichinose, Masakazu; Nagase, Hiroyuki; Yamaguchi, Masao; Sugiura, Hisatoshi; Tohda, Yuji; Yamauchi, Kohei; Adachi, Mitsuru; Akiyama, Kazuo

2014-09-01

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting β2-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled β2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and cough-variant asthma are also important issues that need to be considered.

COPD assessment test and severity of airflow limitation in patients with asthma, COPD, and asthma-COPD overlap syndrome.

PubMed

Kurashima, Kazuyoshi; Takaku, Yotaro; Ohta, Chie; Takayanagi, Noboru; Yanagisawa, Tsutomu; Sugita, Yutaka

2016-01-01

The COPD assessment test (CAT) consists of eight nonspecific scores of quality of life. The aim of this study was to compare the health-related quality of life and severity of airflow limitation in patients with asthma, COPD, and asthma-COPD overlap syndrome (ACOS) using the CAT. We examined CAT and lung functions in 138 patients with asthma, 99 patients with COPD, 51 patients with ACOS, and 44 patients with chronic cough as a control. The CAT score was recorded in all subjects, and the asthma control test was also administered to patients with asthma and ACOS. The CAT scores were compared, and the relationships between the scores and lung function parameters were analyzed. The total CAT scores and scores for cough, phlegm, and dyspnea were higher in patients with ACOS than in patients with asthma and COPD. The total CAT scores were correlated with the percent predicted forced expiratory volume in 1 second only in patients with COPD. The total CAT scores and dyspnea scores adjusted by the percent predicted forced expiratory volume in 1 second were higher in patients with ACOS than in patients with COPD and asthma. The CAT scores and asthma control test scores were more closely correlated in patients with ACOS than in patients with asthma. Patients with ACOS have higher disease impacts and dyspnea sensation unproportional to the severity of airflow limitation.

The association between paracetamol use and asthma: causation or coincidence?

PubMed

Weatherall, M; Ioannides, S; Braithwaite, I; Beasley, R

2015-01-01

A better understanding of the causation of asthma and allergic disorders could potentially lead to intervention strategies that reduce their prevalence and severity. One potential causative factor is the use of paracetamol. Most of the evidence for the link with asthma is from non-experimental studies of paracetamol exposure in utero, infancy, childhood and adult life; however, it has been difficult to rule out confounding and bias in the associations observed. The two randomized clinical trials of the effect of paracetamol in patients with asthma have been difficult to interpret, due to methodological issues. There have been no randomized controlled trials of paracetamol use and the development of asthma. Both asthma and paracetamol use are common, and so even if there is a relatively small effect of paracetamol exposure on the development of asthma or its severity, then such an effect would be of major public health significance. It is proposed that randomized controlled trials of the effect of paracetamol on the development of asthma and its severity are a high research priority. © 2014 John Wiley & Sons Ltd.

Family functioning and child asthma severity: A bio-behavioral approach.

PubMed

Al Ghriwati, Nour; Winter, Marcia A; Everhart, Robin S; Fiese, Barbara H

2017-12-01

Family factors are directly associated with the psychosocial adjustment of children with chronic illnesses such as asthma (Kaugars, Klinnert, & Bender, 2004). Research indicates that negative family factors may also contribute to child disease severity via bio-behavioral mechanisms of effect. For instance, children from more conflicted families often experience greater internalizing symptoms that subsequently impact their asthma severity (Wood et al., 2006). These pathways have yet to be examined with a comprehensive focus on strength-based family factors. This study examined whether factors such as family cohesion, problem-solving abilities, and communication influence asthma severity via their effects on child depression and anxiety symptoms. Participants were 215 children (136 males and 79 females), ages 5 to 12 years old, and their families. Primary caregiver, child, and teacher ratings of child and family functioning in addition to objective measures of parent-child interactions and asthma severity were collected. Using structural equation modeling, the authors identified significant indirect associations between family factors and child asthma severity via child depressive symptoms; however, these associations were not present in models with child anxiety symptoms. Results suggest an indirect effect of family functioning on children's lung function, with differential roles of anxiety and depression in these pathways. This article also highlights the importance of incorporating multirater multimethod measures to understand children's experiences in pediatric asthma. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study.

PubMed

Morales, Daniel R; Lipworth, Brian J; Donnan, Peter T; Jackson, Cathy; Guthrie, Bruce

2017-01-27

Cardiovascular disease (CVD) is a common comorbidity in people with asthma. However, safety concerns have caused heterogeneity in clinical guideline recommendations over the use of cardioselective beta-blockers in people with asthma and CVD, partly because risk in the general population has been poorly quantified. The aim of this study was to measure the risk of asthma exacerbations with beta-blockers prescribed to a general population with asthma and CVD. Linked data from the UK Clinical Practice Research Datalink was used to perform nested case-control studies among people with asthma and CVD matched on age, sex and calendar time. Adjusted incidence rate ratios (IRR) were calculated for the association between oral beta-blocker use and moderate asthma exacerbations (rescue oral steroids) or severe asthma exacerbations (hospitalisation or death) using conditional logistic regression. The cohort consisted of 35,502 people identified with active asthma and CVD, of which 14.1% and 1.2% were prescribed cardioselective and non-selective beta-blockers, respectively, during follow-up. Cardioselective beta-blocker use was not associated with a significantly increased risk of moderate or severe asthma exacerbations. Consistent results were obtained following sensitivity analyses and a self-controlled case series approach. In contrast, non-selective beta-blockers were associated with a significantly increased risk of moderate asthma exacerbations when initiated at low to moderate doses (IRR 5.16, 95% CI 1.83-14.54, P = 0.002), and both moderate and severe exacerbations when prescribed chronically at high dose (IRR 2.68, 95% CI 1.08-6.64, P = 0.033 and IRR 12.11, 95% CI 1.02-144.11, P = 0.048, respectively). Cardioselective beta-blockers prescribed to people with asthma and CVD were not associated with a significantly increased risk of moderate or severe asthma exacerbations and potentially could be used more widely when strongly indicated.

Outcomes of childhood asthma to the age of 50 years.

PubMed

Tai, Andrew; Tran, Haily; Roberts, Mary; Clarke, Nadeene; Gibson, Anne-Marie; Vidmar, Suzanna; Wilson, John; Robertson, Colin F

2014-06-01

In 1964, The Melbourne Asthma Study was established to describe the spectrum and natural history of childhood asthma. To describe the clinical and lung function outcome of childhood asthma to the age of 50 years. Subjects were invited to complete an interviewer-administered questionnaire, skin prick testing, and measurement of lung function from the age of 7 years to the age of 50 years at 7-year intervals. Of 458 survivors (from the original 484 subjects at recruitment), 346 subjects (76%) participated, of whom, 197 completed lung function measurement. Asthma remission at the age of 50 years was 64% in those with wheezy bronchitis, 47% for those with persistent asthma, and 15% for those with severe asthma in childhood. Multivariable analysis identified severe asthma in childhood (odds ratio [OR] 11.9 [95% CI, 3.4-41.8]), female sex (OR 2.0 [95% CI, 1.1-3.6]), and childhood hay fever (OR 2.0 [95% CI, 1.0-4.0]) as risk factors for "current asthma" at age 50 years. There was no evidence of a difference in the rate of decline in FEV1 (mL/y, 95% CI) between the severe asthma group (15 mL/y [95% CI, 9-22 mL/y]) and all the other recruitment groups: control (16 mL/y [95% CI, 12-20 mL/y]), mild wheezy bronchitis (14 mL/y [95% CI, 8-19 mL/y]), wheezy bronchitis (16 mL/y [95% CI, 11-20 mL/y]), and persistent asthma (19 mL/y [95% CI, 13-24 mL/y]). The clinical and lung function outcome in adult life is strongly determined by asthma severity in childhood. The reduced lung function seen in adults is established in childhood and does not appear to decline more rapidly in adult years despite continuing symptoms. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Intravenous ketamine in a dissociating dose as a temporizing measure to avoid mechanical ventilation in adult patient with severe asthma exacerbation.

PubMed

Shlamovitz, Gil Z; Hawthorne, Tracy

2011-11-01

Patients experiencing severe asthma exacerbations occasionally deteriorate to respiratory failure requiring endotracheal intubation and mechanical ventilation. Mechanical ventilation in this setting exposes the patients to substantial iatrogenic risk and should be avoided if at all possible. To describe the use of intravenous ketamine in acute asthma exacerbation. We present a case of severe asthma exacerbation in an adult female patient who failed to improve with standard therapies, but promptly improved with the administration of intravenous ketamine (0.75 mg/kg i.v. bolus followed by continuous drip of 0.15 mg/kg/h). This case suggests that intravenous ketamine given in a dissociative dose may be an effective temporizing measure to avoid mechanical ventilation in adult patients with severe asthma exacerbations. Copyright © 2011 Elsevier Inc. All rights reserved.

Rhinoviruses, Allergic Inflammation, and Asthma

PubMed Central

Gavala, Monica; Bertics, Paul J.; Gern, James E.

2011-01-01

Summary Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma. PMID:21682739

Obesity in children with poorly controlled asthma: Sex differences.

PubMed

Lang, Jason E; Holbrook, Janet T; Wise, Robert A; Dixon, Anne E; Teague, W Gerald; Wei, Christine Y; Irvin, Charles G; Shade, David; Lima, John J

2013-09-01

Obesity increases asthma risk, and may alter asthma severity. In adults, sex appears to modify the effect of obesity on asthma. Among children, the effect of sex on the relationship between obesity and asthma severity remains less clear, particularly when considering race. To determine how obesity affects disease characteristics in a diverse cohort of children with poorly controlled asthma, and if obesity effects are altered by sex. We analyzed 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month trial assessing lansoprazole for asthma control. In this secondary analysis, we determined associations between obesity and symptom severity, spirometry, exacerbation risk, airway biomarkers, bronchial reactivity, and airflow perception. We used both a multivariate linear regression and longitudinal mixed-effect model to determine if obesity interacted with sex to affect asthma severity. Regardless of sex, BMI >95th percentile did not affect asthma control, exacerbation risk or airway biomarkers. Sex changed the effect of obesity on lung function (sex × obesity FEV1%, interaction P-value < 0.01, sex × obesity FEV1/FVC, interaction P-value = 0.03). Obese males had significantly worse airflow obstruction compared to non-obese males, while in females there was no obesity effect on airflow obstruction. In females, obesity was associated with significantly greater FEV1 and FVC, and a trend toward reduced airway reactivity. Obesity did not affect asthma control, airway markers or disease stability; however obesity did affect lung function in a sex-dependent manner. In males, obesity associated with reduced FEV1/FVC, and in females, obesity associated with substantially improved lung function. Copyright © 2012 Wiley Periodicals, Inc.

Omalizumab improves asthma-related quality of life in patients with severe allergic asthma.

PubMed

Finn, Albert; Gross, Gary; van Bavel, Julius; Lee, Theodore; Windom, Hugh; Everhard, François; Fowler-Taylor, Angel; Liu, Jeen; Gupta, Niroo

2003-02-01

We have previously shown that omalizumab, a recombinant humanized monoclonal anti-IgE antibody, reduces asthma exacerbations and decreases inhaled corticosteroid (ICS) requirement in patients with severe allergic asthma who were symptomatic despite moderate-to-high doses of ICSs. The aim of the present study was to assess the effects of omalizumab on asthma-related quality of life (QOL). These analyses were part of a multicenter, 52-week, randomized, double-blind, placebo-controlled study assessing the efficacy, safety, and tolerability of subcutaneous omalizumab (> or =0.016 mg/kg of IgE [in international unit per milliliter] per 4 weeks) in 525 adults with severe allergic asthma. A 16-week steroid-stable phase was followed by a 12-week steroid-reduction phase and a 24-week double-blind extension phase. The effect of treatment on asthma-related QOL was evaluated by using the Asthma Quality of Life Questionnaire (AQLQ) administered at baseline and at weeks 16, 28, and 52. The 2 treatment groups were comparable in terms of baseline AQLQ scores. At weeks 16, 28, and 52, omalizumab-treated patients demonstrated statistically significant improvements across all AQLQ domains, as well as in overall score. Moreover, a greater proportion of patients receiving omalizumab achieved a clinically meaningful improvement in asthma-related QOL during each phase of the study. Greater than 50% of both patients and investigators rated treatment similarly with omalizumab as excellent or good compared with less than 40% of placebo recipients. In patients requiring moderate-to-high doses of ICSs for severe allergic asthma, the measurably improved disease control afforded by add-on omalizumab therapy is paralleled by clinically meaningful improvements in asthma-related QOL.

NOD2 expression, DNA damage and oxido-inflammatory status in atopic bronchial asthma: Exploring their nexus to disease severity.

PubMed

Gaballah, Hanaa H; Gaber, Rasha A; Sharshar, Ragia S; Elshweikh, Samah A

2018-06-20

Allergic asthma is a chronically relapsing inflammatory airway disease with a complex pathophysiology. This study was undertaken to investigate the potential contribution of NOD2 signaling, proinflammatory cytokines, chitotriosidase (CHIT1) activity, oxidative stress and DNA damage to atopic asthma pathogenesis, as well as to explore their possible role as surrogate noninvasive biomarkers for monitoring asthma severity. Sixty patients with atopic bronchial asthma who were divided according to asthma severity into 40 mild-moderate, 20 severe atopic asthmatics, in addition to thirty age-matched healthy controls were enrolled in this study. NOD2 expression in PBMCs was assessed by quantitative real-time RT-PCR. DNA damage indices were assessed by alkaline comet assay. Serum IgE, IL-17, IL-8 and 3-Nitrotyrosine levels were estimated by ELISA. Serum CHIT1and GST activities, as well as MDA levels, were measured. NOD2 mRNA relative expression levels were significantly decreased in atopic asthmatic cases relative to controls with lower values among severe atopic asthmatics. On the other hand, IL-17 and IL-8 serum levels, CHIT1 activity, DNA damage indices and oxidative stress markers were significantly increased in atopic asthmatic cases relative to controls with higher values among severe atopic asthmatics. The change in these parameters correlated significantly with the degree of decline in lung function. The interplay between NOD2 signaling, proinflammatory cytokines, CHIT1 activity, heightened oxidative stress and DNA damage orchestrates allergic airway inflammation and thus contributing to the pathogenesis of atopic asthma. These parameters qualified for measurement as part of new noninvasive biomarker panels for monitoring asthma severity. Copyright © 2018 Elsevier B.V. All rights reserved.

DNA methylation levels associated with race and childhood asthma severity.

PubMed

Chan, Marcia A; Ciaccio, Christina E; Gigliotti, Nicole M; Rezaiekhaligh, Mo; Siedlik, Jacob A; Kennedy, Kevin; Barnes, Charles S

2017-10-01

Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression. We examined the association of global DNA methylation levels with socioeconomic status, asthma severity and race/ethnicity. We measured global DNA methylation in peripheral blood of children with asthma enrolled in the Kansas City Safe and Healthy Homes Program. Inclusion criteria included residing in the same home for a minimum of 4 days per week and total family income of less than 80% of the Kansas City median family income. DNA methylation levels were quantified by an immunoassay that assessed the percentage of 5-methylcytosine. Our results indicate that overall, African American children had higher levels of global DNA methylation than children of other races/ethnicities (p = 0.029). This difference was more pronounced when socioeconomic status and asthma severity were coupled with race/ethnicity (p = 0.042) where low-income, African American children with persistent asthma had significantly elevated methylation levels relative to other races/ethnicities in the same context (p = 0.006, Hedges g = 1.14). Our study demonstrates a significant interaction effect among global DNA methylation levels, asthma severity, race/ethnicity, and socioeconomic status.

Accuracy of a computerized clinical decision-support system for asthma assessment and management.

PubMed

Hoeksema, Laura J; Bazzy-Asaad, Alia; Lomotan, Edwin A; Edmonds, Diana E; Ramírez-Garnica, Gabriela; Shiffman, Richard N; Horwitz, Leora I

2011-05-01

To evaluate the accuracy of a computerized clinical decision-support system (CDSS) designed to support assessment and management of pediatric asthma in a subspecialty clinic. Cohort study of all asthma visits to pediatric pulmonology from January to December, 2009. CDSS and physician assessments of asthma severity, control, and treatment step. Both the clinician and the computerized CDSS generated assessments of asthma control in 767/1032 (74.3%) return patients, assessments of asthma severity in 100/167 (59.9%) new patients, and recommendations for treatment step in 66/167 (39.5%) new patients. Clinicians agreed with the CDSS in 543/767 (70.8%) of control assessments, 37/100 (37%) of severity assessments, and 19/66 (29%) of step recommendations. External review classified 72% of control disagreements (21% of all control assessments), 56% of severity disagreements (37% of all severity assessments), and 76% of step disagreements (54% of all step recommendations) as CDSS errors. The remaining disagreements resulted from pulmonologist error or ambiguous guidelines. Many CDSS flaws, such as attributing all 'cough' to asthma, were easily remediable. Pediatric pulmonologists failed to follow guidelines in 8% of return visits and 18% of new visits. The authors relied on chart notes to determine clinical reasoning. Physicians may have changed their assessments after seeing CDSS recommendations. A computerized CDSS performed relatively accurately compared to clinicians for assessment of asthma control but was inaccurate for treatment. Pediatric pulmonologists failed to follow guideline-based care in a small proportion of patients.

Role of Obesity in Asthma: Mechanisms and Management Strategies.

PubMed

Scott, Hayley A; Wood, Lisa G; Gibson, Peter G

2017-08-01

Obesity is a commonly reported comorbidity in asthma, particularly in severe asthma. Obese asthmatics are highly symptomatic with a poor quality of life, despite using high-dose inhaled corticosteroids. While the clinical manifestations have been documented, the aetiologies of obese-asthma remain unclear. Several potential mechanisms have been proposed, including poor diet quality, physical inactivity and consequent accrual of excess adipose tissue. Each of these factors independently activates inflammatory pathways, potentially exerting effects in the airways. Because the origins of obesity are multifactorial, it is now believed there are multiple obese-asthma phenotypes, with varied aetiologies and clinical consequences. In this review, we will describe the clinical implications of obesity in people with asthma, our current understanding of the mechanisms driving this association and describe recently proposed obese-asthma phenotypes. We will then discuss how asthma management is complicated by obesity, and provide graded recommendations for the management of obesity in this population.

Japanese Guideline for Adult Asthma 2014.

PubMed

Ohta, Ken; Ichinose, Masakazu; Nagase, Hiroyuki; Yamaguchi, Masao; Sugiura, Hisatoshi; Tohda, Yuji; Yamauchi, Kohei; Adachi, Mitsuru; Akiyama, Kazuo

2014-01-01

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause intractable asthma. The number of patients with asthma has increased, and that of patients who die from asthma has decreased (1.5 per 100,000 patients in 2012). The aim of asthma treatment is to enable patients with asthma to lead a normal life without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management with antiasthmatic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high. Long-acting 02-agonists, leukotriene receptor antagonists, and sustained-release theophylline are recommended as concomitant drugs, while anti-immunoglobulin E antibody therapy has been recently developed for the most severe and persistent asthma involving allergic reactions. Inhaled 02-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and others are used as needed in acute exacerbations by choosing treatment steps for asthma exacerbations depending on the severity of attacks. Allergic rhinitis, chronic obstructive pulmonary disease, aspirin-induced asthma, pregnancy, asthma in athletes, and coughvariant asthma are also important issues that need to be considered. © 2014 Japanese Society of Allergology.

Targeting patients with asthma for omalizumab therapy: choosing the right patient to get the best value for money

PubMed Central

Al Said, Abir; Cushen, Breda; Costello, Richard W

2017-01-01

The asthma syndrome has many manifestations, termed phenotypes, that arise by specific cellular and molecular mechanisms, termed endotypes. Understanding an individual’s asthma phenotype helps clinicians make rational therapeutic decisions while the understanding of endotypes has led to the development of specific precision medications. Allergic asthma is an example of an asthma phenotype and omalizumab, a monoclonal antibody that neutralizes serum immunoglobulin (Ig)E, is a specific targeted treatment which was developed as a result of an understanding of the endotype of allergic asthma. Omalizumab has been widely used in clinical practice in Europe for over a decade as an add-on therapy to treat patients who have severe refractory allergic asthma. Over this period, many centres have reported their experience with omalizumab as an add-on therapy in patients with severe asthma. These ‘real world’ clinical effectiveness studies have confirmed the benefits, cost-effectiveness and clinical utility of this medication. Combining the outcomes of both sources of research has yielded important insights that may benefit patients with severe asthma, clinicians who treat them, as well as the funding agencies that reimburse the cost of this medication. The purpose of this review is to describe how to identify and evaluate a patient with asthma for whom treatment with omalizumab may be of clinical and cost-effective benefit. The assessment and investigations used to confirm allergic asthma, the objective assessment of adherence to asthma therapy and the expected benefits of add-on omalizumab treatment are described. PMID:28348726

Incentive spirometry combined with expiratory positive airway pressure improves asthma control and quality of life in asthma: a randomised controlled trial.

PubMed

Rondinel, Tatiana Zacarias; Corrêa, Isadora Faraco; Hoscheidt, Luíza Machado; Bueno, Mirelle Hugo; Da Silva, Luciano Muller Corrêa; Reppold, Caroline Tozzi; Dal Lago, Pedro

2015-03-01

The use of the incentive spirometer (IS) and expiratory positive airway pressure (EPAP) provides several benefits in patients with respiratory disorders. However, the effects of the use of these devices coupled (IS + EPAP) are still unknown in asthmatic patients. The aim of this study was to evaluate the effect of IS associated with EPAP on exercise tolerance (six-minute walk test - 6MWT), lung function (by spirometry), asthma control (Asthma Control Questionnaire - ACQ) and quality of life (Asthma Quality of Life Questionnaire - AQLQ) in patients with severe asthma. Patients were randomised into two groups: IS + EPAP (n = 8) and control (n = 6). The IS + EPAP group performed breathing exercises at home, twice daily for 20 min, over a period of 5 weeks. There was no significant difference in spirometric variables and in the distance walked in the 6MWT in both groups. However, the IS + EPAP group showed an improvement in asthma control (p = 0.002) and quality of life (p = 0.02). These findings demonstrate that the IS + EPAP protocol, when performed at home, provides an improvement in asthma control and quality of life for patients with severe asthma when evaluated by ACQ and AQLQ, respectively.

Fevipiprant in the treatment of asthma.

PubMed

White, Christobelle; Wright, Adam; Brightling, Christopher

2018-02-01

Asthma is common and in many, particularly those with more severe disease, there remains a substantial unmet need. Success with biologics targeting eosinophilic inflammation underscore the value of treating inflammation in asthma beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma. It competitively and reversibly antagonises the prostaglandin D2 receptor 2 (DP2) expressed on inflammatory and structural cells. Areas covered: We reviewed fevipiprant's mode of action and efficacy against other current and emerging pharmacological interventions for moderate-to-severe asthma. We undertook a literature review using the PubMed/Medline database, the U.S. National Library of Medicine's Clinical Trials website and from manufacturers' press releases with the search terms: 'QAW039', 'Fevipiprant', 'CRTH2 antagonists', 'DP2', 'DP1', 'monoclonal antibody', 'eosinophil' with 'asthma' plus the names of individual drugs. Three Phase 2 trials have been conducted and three Phase 3 trials (NCT02563067, NCT03052517, NCT02555683) are in progress. To date Fevipiprant's greatest success has been in targeting severe eosinophilic asthma. Expert opinion: Fevipiprant presents the possibility of a new orally active therapy for asthma. If successful in phase 3 trials it will have an enormous impact on the treatment paradigm for asthma and will potentially widen access for pre-biologic treatment to a larger population.

Screening for obstructive sleep apnea syndrome in asthma patients: a prospective study based on Berlin and STOP-Bang questionnaires.

PubMed

Lu, Huan; Fu, Cuiping; Li, Wenjing; Jiang, Hong; Wu, Xiaodan; Li, Shanqun

2017-07-01

The bidirectional relationship of asthma and obstructive sleep apnea (OSA) has been confirmed in recent years. However, in the clinical practice, majority of asthma patients did not pay adequate attention to their sleep apnea condition. Berlin questionnaire (BQ) and STOP-Bang questionnaire (SBQ) are two most common OSA screening questionnaires to screen high-risk patients for OSA. This study aimed at evaluating the predictive performance of BQ and SBQ for OSA in asthma patients. Asthma outpatients of Zhongshan Hospital were enrolled into the study. All patients were asked to fill in the BQ and SBQ and clinical characteristics and asthma characteristics were recorded. Univariate and multivariate logistic regression analyses were applied to identify risk factors of OSA in asthma patients. With the gold standard of laboratory-based overnight polysomnography (PSG), the predictive performance of SBQ and BQ was evaluated and compared. The probability of OSA severity was predicted by various SBQ scores in asthma patients. A total of 123 asthma patients (average age 47.56±12.12 years; 57.72% males) were enrolled and underwent PSG diagnosis overnight at Sleep Center. Logistic regression analyses showed that rhinitis (adjusted OR =4.30; 95% CI: 1.50-12.37, P=0.007) and dyslipidemia (adjusted OR =2.75; 95% CI: 1.16-6.51, P=0.021) were associated with OSA in asthma patients after adjusting for known OSA risk factors. No asthma functional characteristic differences were found to be associated with OSA severity in the study. The prevalence of moderate-to-severe OSA (AHI ≥15) in the asthmatic population sample was 36.59% (45/123). Questionnaires predictive results showed that compared with BQ, SBQ has higher diagnostic sensitivity (84.4% vs. 60%), lower specificity (79.5% vs. 91%) lower positive predictive value (PPV): (70.4% vs. 79.4%) and higher negative predictive value (NPV) (90% vs. 80%) to detect moderate-to-severe OSA at the cut-off as AHI of 15/h. OSA probability results showed that with the increasing of the questionnaire scores, the moderate and severe OSA probability of SBQ rose significantly. SBQ is a preferable sleep questionnaire better than BQ for detecting moderate and severe OSA in asthma patients which should be validated in larger population sample.

Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression.

PubMed

Sandberg, S; Järvenpää, S; Penttinen, A; Paton, J Y; McCann, D C

2004-12-01

A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress. Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events. An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69, 95% confidence interval 2.33 to 9.44 (p<0.001) [corrected] In the period 3-10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 (95% confidence interval 1.24 to 2.65) [corrected] was found 5-7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children. The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5-7 weeks later.

The burden of unscheduled health care for asthma in Latin America.

PubMed

Neffen, H; Gonzalez, S N; Fritscher, C C; Dovali, C; Williams, A E

2010-01-01

To determine the level and cost of unscheduled health care resource use in adults and children across all asthma symptom severities in Latin America. The level and cost of health care resource use were analysed for 2074 patients with asthma included in the Asthma Insights and Reality in Latin America (AIRLA) survey from 10 Latin American countries. Health care resource use was multiplied by country-specific unit costs to estimate average per-patient annual costs. Patients were classified as adults (> or = 16 years) or children (<16 years), with disease severity categorized using a symptom severity index. Persistent asthma symptoms were experienced by 53.1% of patients (50.1% of children and 54.6% of adults). In the year preceding the survey, 57.1% of patients required unscheduled health care resource use and 45.1% reported at least 1 emergency hospital contact. The percentage of patients reporting unscheduled health care resource use was greatest amongst those with severe persistent symptoms (71.9%) but it was also high in those with mild intermittent symptoms (45.7%). An average of 73.2% of annual costs of asthma-related health care for the 10 countries was due to unscheduled health care. Expenditure on unscheduled care was greatest amongst both adults and children with severe persistent asthma symptoms (US $558 and US $769, respectively). Adults and children with mild intermittent symptoms also incurred considerable unscheduled costs (US $204 and US $215, respectively). Poorly controlled asthma imposes a considerable cost burden driven by unscheduled health care resource use in Latin America. Treatments to control asthma and reduce the need for unscheduled health care could reduce this cost in both adults and children.

The C-C motif chemokine ligands CCL5, CCL11, and CCL24 induce the migration of circulating fibrocytes from patients with severe asthma.

PubMed

Isgrò, M; Bianchetti, L; Marini, M A; Bellini, A; Schmidt, M; Mattoli, S

2013-07-01

The C-C motif chemokine ligand 5 (CCL5), CCL11, and CCL24 are involved in the pathogenesis of asthma, and their function is mainly associated with the airway recruitment of eosinophils. This study tested their ability to induce the migration of circulating fibrocytes, which may contribute to the development of irreversible airflow obstruction in severe asthma. The sputum fluid phase (SFP) from patients with severe/treatment-refractory asthma (PwSA) contained elevated concentrations of CCL5, CCL11, and CCL24 in comparison with the SFP from patients with non-severe/treatment-responsive asthma (PwNSA). The circulating fibrocytes from PwSA expressed the receptors for these chemokines at increased levels and migrated in response to recombinant CCL5, CCL11, and CCL24. The SFP from PwSA induced the migration of autologous fibrocytes, and its activity was significantly attenuated by neutralization of endogenous CCL5, CCL11, and CCL24. These findings suggest that CCL5, CCL11, and CCL24 may contribute to the airway recruitment of fibrocytes in severe asthma.

The Association of Health Literacy with Adherence and Outcomes in Moderate-Severe Asthma

PubMed Central

Apter, Andrea J.; Wan, Fei; Reisine, Susan; Bender, Bruce; Rand, Cynthia; Bogen, Daniel K.; Bennett, Ian M.; Bryant-Stephens, Tyra; Roy, Jason; Gonzalez, Rodalyn; Priolo, Chantel; Have, Thomas Ten; Morales, Knashawn H.

2013-01-01

Background Low health literacy is associated with poor outcomes in asthma and other diseases but the mechanisms governing this relationship are not well-defined. Objective To assess whether literacy is related to subsequent asthma self-management, measured as adherence to inhaled steroids, and asthma outcomes. Methods In a prospective longitudinal cohort study, numeric (Asthma Numeracy Questionnaire (ANQ)) and print literacy (Short Test of Functional Health Literacy in Adults (S-TOFHLA)) were assessed at baseline in adults with moderate or severe asthma for their impact on subsequent electronically monitored adherence and asthma outcomes (asthma control, asthma-related quality of life, and FEV1) over 26 weeks, using mixed-effects linear regression models. Results 284 adults participated: 48±14 years, 71% female, 70% African American, 6% Latino, mean FEV1 66% ± 19%, 86 (30%) with hospitalizations and 148 (52%) with ED visits for asthma in the prior year. Mean ANQ score (range 0–4) was 2.3 ± 1.2; mean S-TOFHLA score 31 ± 8 (range 0–36). In unadjusted analyses numeric and print literacy were associated with better adherence (p=0.01, p=0.08), asthma control (p=0.005, p <0.001), and quality of life (p<0.001, p<0.001). After controlling for age, sex, and race/ethnicity, the associations diminished and only quality of life (numeric: p=0.03, print p=0.006) and asthma control (print p=0.005) remained significantly associated with literacy. Race/ethnicity, income, and educational attainment were correlated (p<0.001). Conclusion While the relationship between literacy and health is complex, interventions which account for and address the literacy needs of patients may improve asthma outcomes. Clinical Implications/Key Summary In adults with moderate or severe asthma, higher health literacy scores were associated with better subsequent quality of life and asthma control. PMID:23591273

Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.

PubMed

Green, Benjamin J; Wiriyachaiporn, Surasa; Grainge, Christopher; Rogers, Geraint B; Kehagia, Valia; Lau, Laurie; Carroll, Mary P; Bruce, Kenneth D; Howarth, Peter H

2014-01-01

Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches. We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers. Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis. In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count. Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that responds less well to current asthma therapies.

Temporal Asthma Patterns Using Repeated Questionnaires over 13 Years in a Large French Cohort of Women

PubMed Central

Sanchez, Margaux; Bousquet, Jean; Le Moual, Nicole; Jacquemin, Bénédicte; Clavel-Chapelon, Françoise; Humbert, Marc; Kauffmann, Francine; Tubert-Bitter, Pascale; Varraso, Raphaëlle

2013-01-01

Variable expression is one aspect of the heterogeneity of asthma. We aimed to define a variable pattern, which is relevant in general health epidemiological cohorts. Our objectives were to assess whether: 1) asthma patterns defined using simple asthma questions through repeated measurements could reflect disease variability 2) these patterns may further be classified according to asthma severity/control. Among 70,428 French women, we used seven questionnaires (1992–2005) and a comprehensive reimbursement database (2004–2009) to define three reliable asthma patterns based on repeated positive answers to the ever asthma attack question: “never asthma” (n = 64,061); “inconsistent” (“yes” followed by “no”, n = 3,514); “consistent” (fully consistent positive answers, n = 2,853). The “Inconsistent” pattern was related to both long-term (childhood-onset asthma with remission in adulthood) and short-term (reported asthma attack in the last 12 months, associated with asthma medication) asthma variability, showing that repeated questions are relevant markers of the variable expression of asthma. Furthermore, in this pattern, the number of positive responses (1992–2005) predicted asthma drug consumption in subsequent years, a marker of disease severity. The “Inconsistent” pattern is a phenotype that may capture the variable expression of asthma. Repeated answers, even to a simple question, are too often neglected. PMID:23741466

Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity

PubMed Central

Naveed, Shams-un-nisa; Clements, Debbie; Jackson, David J.; Philp, Christopher; Billington, Charlotte K.; Soomro, Irshad; Reynolds, Catherine; Harrison, Timothy W.; Johnston, Sebastian L.; Shaw, Dominick E.

2017-01-01

Rationale: Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma. Objectives: To investigate whether MMP-1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP-1 protein and activity were assessed. Measurements and Main Results: Airway smooth muscle cells generated pro–MMP-1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5-fold (P < 0.05), which was dependent on MMP-1 activation. In asthma, airway pro–MMP-1 was 5.4-fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP-1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP-1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms. Conclusions: MMP-1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP-1 levels are associated with bronchial hyperresponsiveness, and MMP-1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness. PMID:27967204

More than a decade follow-up in patients with severe or difficult-to-treat asthma: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) II.

PubMed

Chipps, Bradley E; Haselkorn, Tmirah; Paknis, Brandee; Ortiz, Benjamin; Bleecker, Eugene R; Kianifard, Farid; Foreman, Aimee J; Szefler, Stanley J; Zeiger, Robert S

2018-05-01

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR I) study demonstrated high morbidity in patients with severe or difficult-to-treat asthma despite standard-of-care treatment. We sought to determine the long-term natural history of disease and outcomes in patients in TENOR I after more than a decade. TENOR I was a multicenter observational study (2001-2004) of 4756 patients with severe or difficult-to-treat asthma. TENOR II was a follow-up study of TENOR I patients using a single cross-sectional visit in 2013/2014. Overall, the sites participating in TENOR II originally enrolled 1230 patients in TENOR I. Clinical and patient-reported outcomes were assessed, including very poorly controlled asthma based on National Heart, Lung, and Blood Institute guidelines. A total of 341 (27.7%) patients were enrolled in TENOR II and were representative of the TENOR I cohort. The most frequent comorbidities were rhinitis (84.0%), sinusitis (47.8%), and gastroesophageal reflux disease (46.3%). Mean percent predicted prebronchodilator and postbronchodilator FEV 1 were 72.7% (SD, 21.4%) and 78.2% (SD, 20.7%), respectively. A total of 231 (72.9%) of 317 patients had positive test responses to 1 or more allergen-specific IgEs. The mean blood eosinophil count was 200/μL (SD, 144/μL). Eighty-eight (25.8%) patients experienced an asthma exacerbation in the prior 3 months requiring hospital attention, oral corticosteroids, or both. More than half (197/339 [58.1%]) had very poorly controlled asthma. Medication use suggested undertreatment. TENOR II provides longitudinal data to characterize disease progression, heterogeneity, and severity in patients with severe or difficult-to-treat asthma. Findings show continued morbidity, including a high degree of comorbid conditions, allergic sensitization, exacerbations, and very poorly controlled asthma, including reduced lung function. Copyright © 2017. Published by Elsevier Inc.

IL6R Variation Asp358Ala Is a Potential Modifier of Lung Function in Asthma

PubMed Central

Hawkins, Gregory A; Robinson, Mac B; Hastie, Annette T; Li, Xingnan; Li, Huashi; Moore, Wendy C; Howard, Timothy D; Busse, William W.; Erzurum, Serpil C.; Wenzel, Sally E.; Peters, Stephen P; Meyers, Deborah A; Bleecker, Eugene R

2012-01-01

Background The IL6R SNP rs4129267 has recently been identified as an asthma susceptibility locus in subjects of European ancestry but has not been characterized with respect to asthma severity. The SNP rs4129267 is in linkage disequilibrium (r2=1) with the IL6R coding SNP rs2228145 (Asp358Ala). This IL6R coding change increases IL6 receptor shedding and promotes IL6 transsignaling. Objectives To evaluate the IL6R SNP rs2228145 with respect to asthma severity phenotypes. Methods The IL6R SNP rs2228145 was evaluated in subjects of European ancestry with asthma from the Severe Asthma Research Program (SARP). Lung function associations were replicated in the Collaborative Study on the Genetics of Asthma (CSGA) cohort. Serum soluble IL6 receptor (sIL6R) levels were measured in subjects from SARP. Immunohistochemistry was used to qualitatively evaluate IL6R protein expression in BAL cells and endobronchial biopsies. Results The minor C allele of IL6R SNP rs2228145 was associated with lower ppFEV1 in the SARP cohort (p=0.005), the CSGA cohort (0.008), and in combined cohort analysis (p=0.003). Additional associations with ppFVC, FEV1/FVC, and PC20 were observed. The rs2228145 C allele (Ala358) was more frequent in severe asthma phenotypic clusters. Elevated serum sIL6R was associated with lower ppFEV1 (p=0.02) and lower ppFVC (p=0.008) (N=146). IL6R protein expression was observed in BAL macrophages, airway epithelium, vascular endothelium, and airway smooth muscle. Conclusions The IL6R coding SNP rs2228145 (Asp358Ala) is a potential modifier of lung function in asthma and may identify subjects at risk for more severe asthma. IL6 transsignaling may have a pathogenic role in the lung. PMID:22554704

Biologic Therapy and Asthma.

PubMed

Viswanathan, Ravi K; Busse, William W

2018-02-01

Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Correlation of total serum immunoglobulin E level, sputum, and peripheral eosinophil count in assessing the clinical severity in bronchial asthma.

PubMed

Kumar, Roshan M; Pajanivel, R; Koteeswaran, G; Menon, Surendra K; Charles, Pravin Mv

2017-01-01

Asthma is a chronic inflammatory disorder of the airway with involvement of various cellular populations and release of many inflammatory mediators. Eosinophils and serum immunoglobulin E (IgE) are considered a good marker of airway inflammation in asthma. The correlation of clinical assessment with various markers of airway inflammation in asthma is not well established in the Indian population. This study aims to study the correlation of serum IgE, sputum eosinophil count, and peripheral eosinophil count with clinical severity of Asthma. This is a cross-sectional study involving 76 stable asthmatic patients of 18-60 years of age attending the pulmonary medicine OPD. Spirometry measured at baseline. Participants were categorized according to the GINA criteria based on clinical symptoms and pulmonary function test. Blood samples were collected for peripheral eosinophil count, serum IgE levels, and sputum samples for eosinophil count. All three parameters were compared with severity of asthma. The correlation of sputum eosinophil count, peripheral eosinophil count, and serum IgE with severity of asthma was analyzed by Pearson's Chi-square test, Fisher's exact test, and the correlation coefficient was reported together with standard error of the estimate. The mean age of patients in our study was 37.42 years and 56.6% were male. There was a significant inverse correlation between serum IgE levels and predicted forced expiratory volume 1 s (FEV1). Sputum eosinophilia was significantly seen in severe persistent asthma patients (19.7%). There was a significant inverse correlation between sputum eosinophil count and predicted FEV1and forced vital capacity. We also found there was a significant association between peripheral eosinophil count, sputum eosinophil count, and elevated serum IgE (g100 IU/mL) with severe persistent asthma. The assessment of sputum eosinophil count is simple, inexpensive, noninvasive, and direct measurement of airway inflammation. It could be the preferred method in monitoring airway inflammation and guided management in day-to-day practice.

Nonprescription bronchodilator medication use in asthma.

PubMed

Kuschner, W G; Hankinson, T C; Wong, H H; Blanc, P D

1997-10-01

Many persons with asthma self-medicate with widely available and potentially hazardous nonprescription medicines. This study assessed the demographic and clinical covariates of self-treatment with over-the-counter asthma medications (OTCs). We conducted an analytical investigation using questionnaires and measures of lung function, comparing OTC and prescription medication users. We recruited adults with asthma by public advertisement. We studied 22 exclusive prescription asthma medication users, 15 exclusive OTC users, and 13 other subjects who combined prescription medication use with self-treatment with asthma OTCs. All but one OTC user self-medicated with a nonselective, sympathomimetic metered-dose inhaler. Taking income, access to care, and self-assessed disease severity into account, male gender was strongly associated with exclusive OTC use alone (odds ratio [OR]=8.9, 95% confidence interval [CI]= 1.3 to 61) and mixed OTC-prescription medication use (OR=9.7, 95% CI=1.1 to 83). The covariates of income, access to care, and self-assessed disease severity provided significant additional explanatory power to the model of exclusive OTC use (model chi2 difference 11.3, 5 df, p<0.05). Pulmonary function was similar among OTC and prescription medication users. However, prescription medication users' self-assessed asthma severity (mild compared to more severe) was associated with postbronchodilator reversibility of FEV1 obstruction (6% vs 18% reversibility, p<0.05) while exclusive OTC users' self-assessed severity showed the reverse pattern (19% vs 8%, p=0.2). Asthma education programs attempting to discourage unregulated bronchodilator use should give consideration to this profile of the "asthmatic-at-risk."

Effect of obesity and metabolic syndrome on severity, quality of life, sleep quality and inflammatory markers in patients of asthma in India.

PubMed

Singh, Mandeep; Gupta, Nitesh; Kumar, Raj

2016-01-01

The study aimed to compare the effect of obesity with and without metabolic syndrome on asthma severity, quality of life, sleep quality, sleep disordered breathing and inflammatory markers as compared to non-obese asthma patients. 60 asthma patients recruited for the study were divided equally into non-obese (NOA), obese without metabolic syndrome (OANMS) and obese with metabolic syndrome (OAMS) groups. Study cohorts were assessed for severity of asthma, quality of life and quality of sleep using questionnaires and inflammatory markers (FENO, hs-CRP, IL-5, IL-6 and leptin). Institutional ethical committee approved the study. The results suggests OAMS patients may be a subtype of asthmatics having significantly severe asthma (p < 0.05), poor quality of life (p < 0.05), high risk of OSA (p< 0.05), decreased lung volumes (FRC) (p< 0.05), higher levels of inflammatory markers (leptin and IL-6) (p < 0.05), and high incidence of sleep disordered breathing (p < 0.05) in comparison to NOA and OANMS patients. The present study has shown that obese asthmatics especially with metabolic syndrome represent a subtype of asthmatic population. Hence, the treatment of metabolic syndrome may be necessary in addition to asthma to achieve optimal control.

Achieving and maintaining asthma control in an urban pediatric disease management program: the Breathmobile Program.

PubMed

Jones, Craig A; Clement, Loran T; Morphew, Tricia; Kwong, Kenny Yat Choi; Hanley-Lopez, Jean; Lifson, Francene; Opas, Lawrence; Guterman, Jeffrey J

2007-06-01

National guidelines suggest that, with appropriate care, most patients can control their asthma. The probabilities of children achieving and maintaining control with ongoing care are unknown. We sought to evaluate the degree to which children in a lower socioeconomic urban setting achieve and maintain control of asthma with regular participation in a disease management program that provides guideline-based care. Interdisciplinary teams of asthma specialists use mobile clinics to offer ongoing care at schools and county clinics. A guideline-derived construct of asthma control is recorded at each visit. Two thousand one hundred eighty-five enrollees were eligible to evaluate the time to first achieve control, and 1591 patients were eligible to evaluate subsequent control maintenance. Depending on severity, 70% to 87% of patients with persistent asthma achieved control by visit 3, and 89% to 98% achieved control by visit 6. Subsequent control maintenance was highly variable. Thirty-nine percent of patients displayed well-controlled asthma (control at >90% of subsequent visits), whereas 13% displayed difficult-to-control asthma (<50% of subsequent visits). Patients from each baseline severity category were found in each group. Maintenance of control was influenced by physician-estimated compliance with the treatment plan, baseline severity, and the interval between clinic visits. Many children can achieve asthma control with regular visit intervals and guideline-based care; however, long-term control can be highly variable among patients in all severity categories. These findings highlight the need and feasibility for systematically tracking each patient's clinical response to individualize therapy and guide the use of population management strategies.

Determinants of airflow obstruction in severe alpha‐1‐antitrypsin deficiency

PubMed Central

DeMeo, Dawn L; Sandhaus, Robert A; Barker, Alan F; Brantly, Mark L; Eden, Edward; McElvaney, N Gerard; Rennard, Stephen; Burchard, Esteban; Stocks, James M; Stoller, James K; Strange, Charlie; Turino, Gerard M; Campbell, Edward J; Silverman, Edwin K

2007-01-01

Background Severe α1‐antitrypsin (AAT) deficiency is an autosomal recessive genetic condition associated with an increased but variable risk for chronic obstructive pulmonary disease (COPD). A study was undertaken to assess the impact of chronic bronchitis, pneumonia, asthma and sex on the development of COPD in individuals with severe AAT deficiency. Methods The AAT Genetic Modifier Study is a multicentre family‐based cohort study designed to study the genetic and epidemiological determinants of COPD in AAT deficiency. 378 individuals (age range 33–80 years), confirmed to be homozygous for the SERPINA1 Z mutation, were included in the analyses. The primary outcomes of interest were a quantitative outcome, forced expiratory volume in 1 s (FEV1) percentage predicted, and a qualitative outcome, severe airflow obstruction (FEV1 <50% predicted). Results In multivariate analysis of the overall cohort, cigarette smoking, sex, asthma, chronic bronchitis and pneumonia were risk factors for reduced FEV1 percentage predicted and severe airflow obstruction (p<0.01). Index cases had lower FEV1 values, higher smoking histories and more reports of adult asthma, pneumonia and asthma before age 16 than non‐index cases (p<0.01). Men had lower pre‐ and post‐bronchodilator FEV1 percentage predicted than women (p<0.0001); the lowest FEV1 values were observed in men reporting a history of childhood asthma (26.9%). This trend for more severe obstruction in men remained when index and non‐index groups were examined separately, with men representing the majority of non‐index individuals with airflow obstruction (71%). Chronic bronchitis (OR 3.8, CI 1.8 to 12.0) and a physician's report of asthma (OR 4.2, CI 1.4 to 13.1) were predictors of severe airflow obstruction in multivariate analysis of non‐index men but not women. Conclusion In individuals with severe AAT deficiency, sex, asthma, chronic bronchitis and pneumonia are risk factors for severe COPD, in addition to cigarette smoking. These results suggest that, in subjects severely deficient in AAT, men, individuals with symptoms of chronic bronchitis and/or a past diagnosis of asthma or pneumonia may benefit from closer monitoring and potentially earlier treatment. PMID:17389752

Age is associated with asthma phenotypes.

PubMed

Ponte, Eduardo V; Lima, Aline; Almeida, Paula C A; de Jesus, Juliana P V; Lima, Valmar B; Scichilone, Nicola; Souza-Machado, Adelmir; Cruz, Álvaro A

2017-11-01

The relationship between age and asthma phenotypes is important as population is ageing, asthma is becoming common in older ages and recently developed treatments for asthma are guided by phenotypes. The aim of this study is to evaluate whether age is associated with specific asthma phenotypes. This is a cross-sectional study. We included subjects with asthma of varied degrees of severity. Subjects underwent spirometry, skin prick test to aeroallergens, answered the Asthma Control Questionnaire and had blood samples collected. We performed binary logistic regression analysis to evaluate whether age is associated with asthma phenotypes. We enrolled 868 subjects. In comparison with subjects ≤ 40 years, older subjects had high odds of irreversible airway obstruction (from 41 to 64 years, OR: 1.83 (95% CI: 1.32-2.54); ≥65 years, OR: 3.45 (2.12-5.60)) and severe asthma phenotypes (from 41 to 64 years, OR: 3.23 (2.26-4.62); ≥65 years, OR: 4.55 (2.39-8.67)). Older subjects had low odds of atopic (from 41 to 64 years, OR: 0.56 (0.39-0.79); ≥65 years, OR: 0.47 (0.27-0.84)) and eosinophilic phenotypes (from 41 to 64 years, OR: 0.63 (0.46-0.84); ≥65 years, OR: 0.39 (0.24-0.64)). Older subjects with asthma have low odds of atopic and eosinophilic phenotypes, whereas they present high odds of irreversible airway obstruction and severe asthma. © 2017 Asian Pacific Society of Respirology.

An evaluation of a community pharmacy-based rural asthma management service.

PubMed

Saini, Bandana; Filipovska, Julija; Bosnic-Anticevich, Sinthia; Taylor, Susan; Krass, Ines; Armour, Carol

2008-04-01

To compare the effect of a pharmacist-delivered rural asthma management service (RAMS) on health outcomes for people with asthma in a rural/regional area with 'standard care' delivered through community pharmacies. A parallel group controlled repeated measures study. Community pharmacies in Central West New South Wales. Standardised protocols and resources based on national asthma management guidelines, delivered by specially trained community pharmacists. Patients visited the pharmacy at baseline and 1, 3 and 6 months after baseline in the intervention group and at baseline plus 6 months after baseline in the control group. The intervention pharmacists (n = 12) were trained to deliver the RAMS model, while control pharmacists (n = 8) provided standard asthma care to their recruited patients. Fifty-one and 39 patients were recruited by intervention and control pharmacists. Asthma severity score which was a composite score based on recency, frequency and severity of asthma symptoms, and asthma history. Data compared at the final visit between groups indicated that the RAMS patient group demonstrated a significant reduction in the asthma severity scores (7.9 +/- 2.6 versus 10.4 +/- 2.6, P < 0.001); a reduction in the risk of non-adherence to medication scores (1.6 +/- 0.7 versus 2.3 +/- 1.1, P < 0.001); and an increase in the proportion of patients owning a written action plan (50% versus 23%, P = 0.04). These results indicated that the community pharmacy-based RAMS model can improve asthma outcomes for patients in rural settings, and similar models for asthma and other chronic diseases should be tested rigorously and adopted in rural primary care practice.

Pulmonary vasculature and critical asthma syndromes: a comprehensive review.

PubMed

Avdalovic, Mark

2015-02-01

One of the important factors and consequences in persistent asthma is the change in the vasculature of the airways and lung parenchyma. These changes could contribute to worsening asthma control and predispose asthmatics to critical asthma syndromes. For many years, the contribution of vasculature to severe asthma was limited to discussion of small and medium vessel vasculitis commonly referred to as Churg-Strauss syndrome. This comprehensive review will explore the known mechanisms that are associated with remodeling of the vasculature in a variety of critical asthma presentations. Inflammation of pulmonary and bronchial small blood vessels may contribute significantly but silently to asthma pathobiology. Inflammation in the vasculature of the lung parenchyma can decrease lung capacity while inflammation in airway vasculature can decrease airflow. This review will provide a modern perspective on Churg-Strauss syndromes with a focus on phenotyping, mechanism, and ultimately modern therapeutic approaches. Vascular remodeling and airway remodeling are not mutually exclusive concepts in understanding the progression of asthma and frequency of acute exacerbations. Furthermore, the contribution of vascular leak, particularly in the parenchymal vasculature, has become an increasingly recognized component of certain presentations of poorly controlled, severe persistent asthmatic and during exacerbations. We highlight how these mechanisms can contribute to some the severe presentations of influenza infection in patients with a history of asthma. The ultimate aim of this review is to summarize the current literature concerning vasculitis and the contribution of airway and parenchymal vascular remodeling to presentation of persistent asthma and its consequences during acute exacerbations and critical asthma syndromes.

Extracellular cyclophilin levels associate with parameters of asthma in phenotypic clusters.

PubMed

Stemmy, Erik J; Benton, Angela S; Lerner, Jennifer; Alcala, Sarah; Constant, Stephanie L; Freishtat, Robert J

2011-12-01

Leukocyte persistence during chronic (quiescent) phases of asthma is a major hallmark of the disease. The mechanisms regulating these persistent leukocyte populations are not clearly understood. An alternative family of chemoattracting proteins, cyclophilins (Cyps), has recently been shown to contribute to leukocyte recruitment in animal models of allergic asthma. The goals of this study were to determine whether Cyps are present in asthma patients during the chronic phase of the disease and to investigate whether levels of Cyps associate with clinical parameters of disease severity. Nasal wash samples from an urban cohort of 137 patients of age 6-20 years with physician-diagnosed asthma were examined for the presence of cyclophilin A (CypA), cyclophilin B (CypB), as well as several other classical chemokines. Linear, logistic, or ordinal regressions were performed to identify associations between Cyps, chemokines, and clinical parameters of asthma. The asthma cohort was further divided into previously established phenotypic clusters (cluster 1: n = 55; cluster 2: n = 31; and cluster 3: n = 51) and examined for associations. Levels of CypB in the asthma group were highly elevated compared to nonasthmatic controls, while a slight increase in Monocyte Chemotactic Protein-1 (MCP-1) was also observed. CypA and MCP-1 were associated with levels of eosinophil cationic protein (ECP; a marker of eosinophil activation). Cluster-specific associations were found for CypA and CypB and clinical asthma parameters [e.g. forced expiratory volume in 1 second (FEV(1)) and ECP]. Cyps are present in nasal wash samples of asthma patients and may be a novel biomarker for clinical parameters of asthma severity.

A nested case-control study: personal, social and environmental correlates of vigorous physical activity in adolescents with asthma.

PubMed

Westergren, Thomas; Ommundsen, Yngvar; Lødrup Carlsen, Karin C; Carlsen, Kai-Håkon; Mowinckel, Petter; Fegran, Liv; Berntsen, Sveinung

2015-03-01

Physical activity (PA) is associated with health benefits. Children and adolescents with asthma may be limited in their PA, particularly at vigorous intensity due to asthma symptoms or poor psychological adjustment to asthma. We aimed to investigate if self-perceived competence, enjoyment, support from others and social-physical environment were associated with vigorous physical activity (VPA) and secondarily to assess if such associations were modified by asthma and asthma severity. Data from a nested case-control study at 13 years of age within the birth-cohort Environment and Childhood Asthma Study were compiled from 95 participants with and 79 without asthma. The participants completed a questionnaire designed to capture self-perceived competence, enjoyment, support from others and social-physical environment. VPA, defined as ≥ 6 Metabolic Equivalents, was recorded objectively by SenseWear™ Pro2 Armband. Asthma severity was assessed pragmatically by lung function and use of inhaled glucocorticosteroids and β2-agonists and incidence of exacerbations in the last 14 days. Data were analysed using linear regression analysis. No significant differences between adolescents with and without asthma were identified in terms of VPA, competence-enjoyment, support from others and social-physical environment. Peer support (b = 0.29 (0.05-0.52)) and competence-enjoyment (b = 0.23 (0.01-0.44)) were significantly and positively associated with VPA, and teacher support (b = -0.26 (-0.50 to -0.02)) were inversely associated. The model explained 25% of the variance in VPA. Peer support and competence-enjoyment were positively associated with increased VPN in adolescents irrespectively of asthma and asthma severity.

Evaluation of selected immunological parameters and the concentration of vitamin D in children with asthma. Case-control study

PubMed Central

Wawrzyniak, Agata; Lipińska-Opałka, Agnieszka; Zdanowski, Robert; Murawski, Piotr; Kalicki, Bolesław

2017-01-01

Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled. Disease severity was assessed with the Asthma Control Test (ACT) and spirometry. The control group consisted of 15 healthy children. Venous blood from each patient was collected on EDTA or on “clott”. Phenotypes of lymphocytes were evaluated by flow cytometry. Vitamin D concentration was assessed by chemiluminescent immunoassay (CLIA) technology. There was a significant decrease in the percentage of T regulatory cells (p < 0.006) in children with asthma compared to the control group. There were no significant differences in the other investigated immunological parameters. In addition, in asthma group statistically significant decreased of vitamin D concentration (p < 0.04) was observed. There were also no significant correlations between vitamin D3 concentration and the course of asthma or percentage of regulatory cells. The results confirmed the role of regulatory T cells in the pathogenesis of asthma. Effects of vitamin D on the severity of the disease has not been proven. PMID:28680338

Evaluation of selected immunological parameters and the concentration of vitamin D in children with asthma. Case-control study.

PubMed

Wawrzyniak, Agata; Lipińska-Opałka, Agnieszka; Zdanowski, Robert; Lewicki, Sławomir; Murawski, Piotr; Kalicki, Bolesław

2017-01-01

Due to the increased incidence of allergic diseases and emerging effects of unsatisfactory control of asthma, new mechanisms for supervising the immune system should be searched. The aim of the study was to analyze the percentage of CD3, CD4, CD8, CD19, CD16/56, NKT, CD3 anti-HLADR3 and Foxp3 regulatory lymphocytes in patients with asthma. Additionally the correlation between immune parameters, severity of asthma and serum concentration of vitamin D was performed. 25 children diagnosed with asthma were enrolled. Disease severity was assessed with the Asthma Control Test (ACT) and spirometry. The control group consisted of 15 healthy children. Venous blood from each patient was collected on EDTA or on "clott". Phenotypes of lymphocytes were evaluated by flow cytometry. Vitamin D concentration was assessed by chemiluminescent immunoassay (CLIA) technology. There was a significant decrease in the percentage of T regulatory cells (p < 0.006) in children with asthma compared to the control group. There were no significant differences in the other investigated immunological parameters. In addition, in asthma group statistically significant decreased of vitamin D concentration (p < 0.04) was observed. There were also no significant correlations between vitamin D3 concentration and the course of asthma or percentage of regulatory cells. The results confirmed the role of regulatory T cells in the pathogenesis of asthma. Effects of vitamin D on the severity of the disease has not been proven.

Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study.

PubMed

Loza, Matthew J; Djukanovic, Ratko; Chung, Kian Fan; Horowitz, Daniel; Ma, Keying; Branigan, Patrick; Barnathan, Elliot S; Susulic, Vedrana S; Silkoff, Philip E; Sterk, Peter J; Baribaud, Frédéric

2016-12-15

Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. NCT01274507 (ADEPT), registered October 28, 2010 and NCT01982162 (U-BIOPRED), registered October 30, 2013.

Preventive asthma care delivery in the primary care office: missed opportunities for children with persistent asthma symptoms.

PubMed

Yee, Alison B; Fagnano, Maria; Halterman, Jill S

2013-01-01

To describe which National Heart Lung and Blood Institute preventive actions are taken for children with persistent asthma symptoms at the time of a primary care visit and determine how care delivery varies by asthma symptom severity. We approached children (2 to 12 years old) with asthma from Rochester, NY, in the waiting room at their doctor's office. Eligibility required current persistent symptoms. Caregivers were interviewed via telephone within 2 weeks after the visit regarding specific preventive care actions delivered. Bivariate and regression analyses assessed the relationship between asthma symptom severity and actions taken during the visit. We identified 171 children with persistent asthma symptoms (34% black, 64% Medicaid) from October 2009 to January 2011 at 6 pediatric offices. Overall delivery of guideline-based preventive actions during visits was low. Children with mild persistent symptoms were least likely to receive preventive care. Regression analyses controlling for demographics and visit type (acute or follow-up asthma visit vs non-asthma-related visit) confirmed that children with mild persistent asthma symptoms were less likely than those with more severe asthma symptoms to receive preventive medication action (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.14-0.84), trigger reduction discussion (OR 0.39, 95% CI 0.19-0.82), recommendation of follow-up (OR 0.40, 95% CI 0.19-0.87), and receipt of action plan (OR 0.37, 95% CI 0.16-0.86). Many children with persistent asthma symptoms do not receive recommended preventive actions during office visits, and children with mild persistent symptoms are the least likely to receive care. Efforts to improve guideline-based asthma care are needed, and children with mild persistent asthma symptoms warrant further consideration. Copyright © 2013 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Childhood asthma-predictive phenotype.

PubMed

Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

2014-01-01

Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Sleep Disorders in Patients with Bronchial Asthma

PubMed Central

Cukic, Vesna; Lovre, Vladimir; Dragisic, Dejan

2011-01-01

Respiratory disturbances during sleep are recognized as extremely common disorders with important clinical consequences. Breathing disorders during sleep can result in broad range of clinical manifestations, the most prevalent of which are unrefreshing sleep, daytime sleepiness and fatigue, and cognitive impairmant. There is also evidence that respiratory-related sleep disturbances can contribute to several common cardiovascular and metabolic disorders, including systemic hypertension, cardiac dysfunction, and insulin-resistance. Correlations are found between asthma-related symptoms and sleep disturbances. Difficulties inducing sleep, sleep fragmentation on polysomnography, early morning awakenings and daytime sleepiness are more common in asthmatics compared with subjects without asthma. The “morning deep” in asthma is relevant for the characterization of asthma severity, and impact drugs’ choices. Sleep and night control of asthma could be relevant to evaluate disease’s control. Appropriate asthma control recovering is guarantor for better sleep quality in these patients and less clinical consequences of respiratory disturbances during sleep. PMID:23678304

The relationship between migraine headache and asthma features.

PubMed

Dirican, Nigar; Demirci, Seden; Cakir, Munire

2017-06-01

Migraine and asthma are comorbid chronic disorders with episodic attacks thought to involve inflammatory and neurological mechanisms. The objective of the present study is to investigate the relationship of asthma features between the asthma patients with migraine and those without migraine headache. A cross-sectional study was conducted from October 2015 to June 2016. Physician-diagnosed asthma patients aged 18 years and above were included. Demographic data, pulmonary function test and treatment of asthma were recorded. Asthma control was assessed using the asthma control test (ACT) and asthma control questionnaire (ACQ). The diagnosis of migraine was made by the neurologist with face-to face examinations based on the International Classification of Headache Disorders, third edition beta (ICHD-III-beta) criteria. Data about the age at onset, frequency of headache attacks, duration of headache attack, the presence of aura, and severity of headache were recorded. The severity of headache was evaluated using visual analogue scale (VAS). Overall 121 asthma patients were included in this study. Migraine was found to be present in 32 (26.4%) of patients. No statistically significant difference was found between asthma group and asthma with migraine groups in terms of pulmonary function test parameters. The mean ACT score in asthma with migraine patients group was significantly lower than the asthma groups. Morever, in the group asthma with migraine, a negative significant correlations were found between ACT scores with VAS scores. This study demonstrates that migraine headache may be associated with poor asthma control. On the other hand, it should not be forgotten that ACT is a subjective test and can be affected from by many clinical parameters.

IL-13 and its genetic variants: effect on current asthma treatments.

PubMed

Townley, Robert G; Sapkota, Muna; Sapkota, Kiran

2011-12-01

Airway hyperresponsiveness is an essential part of the definition of asthma associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain organic chemicals. Interleukin-13 (IL-13) is implicated as a central regulator in immunoglobulin E (IgE) synthesis, mucus hypersecretion, airway hyperresponsiveness, and fibrosis. The importance of IL-13 in allergic disorders in humans is supported by consistent associations between tissue IL-13 levels and genetic variants in the IL-13 gene and asthma and related traits. Single-nucleotide polymorphisms in IL-13 are associated with allergic phenotypes in several ethnically diverse populations. Glucocorticoids are anti-inflammatory medications often used as maintenance therapy in acute and chronic asthma; however, some patients with severe asthma are steroid resistant. IL-13 remains elevated in glucocorticoid insensitive asthma but not in glucocorticoid sensitive asthma. Thus targeting IL-13 and its associated receptors may be a therapeutic approach to the treatment of asthma and/or allergy. This review focuses on the role of IL-13 on airway hyperresponsiveness and corticosteroids resistant asthma both preclinically and clinically. © Discovery Medicine

Prevalence and Severity of Asthma, Rhinitis, and Atopic Eczema in 13- to 14-Year-Old Schoolchildren from Southern Brazil

PubMed Central

2006-01-01

The objective of this study was to investigate the prevalence and severity of asthma, rhinitis, and atopic eczema in schoolchildren from southern Brazil. A cross-sectional study was carried out with the International Study of Asthma and Allergies in Childhood phase III written questionnaire. The questionnaire was self-applied by 2,948 randomly selected schoolchildren aged 13 to 14 years. The lifetime prevalence rates of symptoms were as follows: wheezing, 40.8%; rhinitis, 40.7%; eczema, 13.6%; self-reported asthma, 14.6%; rhinitis, 31.4%; eczema, 13.4%. Rhinitis was reported by 55% of adolescents with current asthma (60% females vs 46.9% males). Girls 13 to 14 years of age had higher prevalence rates of asthma, rhinitis, and eczema than boys had. Atopic eczema was reported by 42.7% of girls and 31.4% of boys with asthma. The prevalence rates were statistically significant for symptoms of asthma, rhinitis, and atopic eczema in females. However, there were no statistically significant differences between the sexes in regard to reported asthma and bronchospasm induced by exercise. PMID:20529214

KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma

PubMed Central

Cahill, Katherine N.; Katz, Howard R.; Cui, Jing; Lai, Juying; Kazani, Shamsah; Crosby-Thompson, Allison; Garofalo, Denise; Castro, Mario; Jarjour, Nizar; DiMango, Emily; Erzurum, Serpil; Trevor, Jennifer L.; Shenoy, Kartik; Chinchilli, Vernon M.; Wechsler, Michael E.; Laidlaw, Tanya M.; Boyce, Joshua A.; Israel, Elliot

2017-01-01

BACKGROUND Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyper-responsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. METHODS We conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy. RESULTS Among the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P = 0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P = 0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group. CONCLUSIONS In patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01097694.) PMID:28514613

Drug Development and Biologics in Asthma. A New Era.

PubMed

Doyle, Ramona

2016-03-01

Considerable progress has been made toward developing targeted biological therapeutics for asthma, due in large part to a deeper understanding of asthma pathophysiology. This explosion of knowledge has revealed asthma to be a much more complex and heterogeneous entity than previously understood. The identification of particular asthma phenotypes with distinct pathophysiologic mechanisms has opened up a new era for patient populations not well served by current therapies, especially patients with severe asthma.

Psychological treatment of comorbid asthma and panic disorder in Latino adults: Results from a randomized controlled trial

PubMed Central

Feldman, Jonathan M.; Matte, Lynne; Interian, Alejandro; Lehrer, Paul M.; Lu, Shou-En; Scheckner, Bari; Steinberg, Dara M.; Oken, Tanya; Kotay, Anu; Sinha, Sumita; Shim, Chang

2016-01-01

Confusion between panic and asthma symptoms can result in serious self-management errors. A cognitive behavior psychophysiological therapy (CBPT) intervention was culturally adapted for Latinos consisting of CBT for panic disorder (PD), asthma education, differentiation between panic and asthma symptoms, and heart rate variability biofeedback. An RCT compared CBPT to music and relaxation therapy (MRT), which included listening to relaxing music and paced breathing at resting respiration rates. Fifty-three Latino (primarily Puerto Rican) adults with asthma and PD were randomly assigned to CBPT or MRT for 8 weekly sessions. Both groups showed improvements in PD severity, asthma control, and several other anxiety and asthma outcome measures from baseline to post-treatment and 3-month follow-up. CBPT showed an advantage over MRT for improvement in adherence to inhaled corticosteroids. Improvements in PD severity were mediated by anxiety sensitivity in CBPT and by depression in MRT, although earlier levels of these mediators did not predict subsequent improvements. Attrition was high (40%) in both groups, albeit comparable to CBT studies targeting anxiety in Latinos. Additional strategies are needed to improve retention in this high-risk population. Both CBPT and MRT may be efficacious interventions for comorbid asthma-PD, and CBPT may offer additional benefits for improving medication adherence. PMID:27668723

How Do Storms Affect Asthma?

PubMed

D'Amato, Gennaro; Annesi-Maesano, Isabella; Vaghi, Adriano; Cecchi, Lorenzo; D'Amato, Maria

2018-03-24

There are observations in various geographical areas that thunderstorms occurring during pollen seasons can induce severe asthma attacks in pollinosis patients. An accredited hypothesis explaining the association between thunderstorms and asthma suggests that storms can concentrate pollen grains at ground level, which may then release allergenic particles of respirable size in the atmosphere after their imbibition of water and rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients affected by pollen allergy may inhale a high quantity of the allergenic material that is dispersed into the atmosphere as a bioaerosol of allergenic particles, which can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. A key message is that all subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe asthma exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events. Patients with respiratory allergy induced by pollens and molds need to be informed about a correct therapeutic approach of bronchial asthma by inhalation, including the use of bronchodilators and inhaled corticosteroids. The purpose of this review is to focalize epidemiological, etiopathogenetic, and clinical aspects of thunderstorm-related asthma.

Asthma and Fungus: Role in Allergic Bronchopulmonary Aspergillosis (ABPA) and Other Conditions.

PubMed

Singh, Meenu; Paul, Nandini; Singh, Shreya; Nayak, Gyan Ranjan

2018-03-17

Asthma is an allergic, respiratory disorder characterized by hyper responsiveness of the airway to external stimuli. Considerable research is currently being directed towards understanding the role of environmental and genetic factors contributing to the development of asthma and its severity. Recent years have seen a substantial rise in evidence linking fungi to asthma. Few major clinical conditions associated with fungal sensitization and hypersensitive immune response are Allergic bronchopulmonary aspergillosis (ABPA), Allergic fungal rhinosinusitis (AFRS) and Severe asthma with fungal sensitization (SAFS). The most common fungi implicated in these conditions belong to genus Aspergillus, although an association with several other fungi has been described. In this review authors discuss the varying clinical characteristics of fungus induced respiratory complications in individuals with asthma. They also highlight the epidemiology of these conditions including their prevalence in children and their fungal etiological profile. Laboratory diagnostic methods and clinical case definitions have also been discussed. Future studies evaluating the role of fungal exposure and susceptibility to asthma are required. Till date there are no guidelines for the diagnosis and treatment of ABPA in pediatric population, thus it is also imperative to establish validated clinical definitions of fungal allergic manifestations in pediatric patients with asthma to fully understand this complex interaction.

Advances in environmental and occupational disorders in 2013.

PubMed

Peden, David B; Bush, Robert K

2014-05-01

In this review of articles published in the Journal in 2013, we report on the significant advances in environmental and occupational disorders. Research advances have led to the identification and defined the structure and function of several major allergens. A meta-analysis confirmed the importance of mold exposure in patients with allergic rhinitis, and a new immunologic classification of aspergillosis emerged. Insights into the role of diesel exhaust particles in patients with severe asthma were clarified. Improvements in stinging insect allergy diagnostics were reported. Genetic, immunologic, and biomarker studies advanced the understanding of adverse drug reactions. New practice parameters for cockroach allergen control were presented. The pathologic role of viruses and bacterial agents in patients with asthma and chronic obstructive pulmonary disease were further defined. An excellent review of allergen bronchoprovocation testing was reported. The roles of bronchoprovocation and bronchodilator responsiveness in asthma diagnosis were further clarified. A biomarker for neutrophilic asthma was identified. Therapeutic advances in asthma research include the inhibition of IL-13 by lebrikizumab, use of montelukast in asthmatic smokers, and a thorough review of bronchial thermoplasty in patients with severe asthma. Lastly, maternal asthma was linked to a number of adverse neonatal outcomes. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

PubMed

Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

2017-06-01

Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease

PubMed Central

Modena, Brian D.; Bleecker, Eugene R.; Busse, William W.; Erzurum, Serpil C.; Gaston, Benjamin M.; Jarjour, Nizar N.; Meyers, Deborah A.; Milosevic, Jadranka; Tedrow, John R.; Wu, Wei; Kaminski, Naftali

2017-01-01

Rationale: Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Objectives: Identify networks of genes reflective of underlying biological processes that define SA. Methods: Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Measurements and Main Results: Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12–21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. Conclusions: In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes. PMID:27984699

Strategies to alter the natural history of childhood asthma

PubMed Central

Lee-Sarwar, K; Bacharier, L; Litonjua, A

2017-01-01

Purpose of review Asthma exhibits significant heterogeneity in occurrence and severity over the lifespan. Our goal is to discuss recent evidence regarding determinants of the natural history of asthma during childhood, and review the rationale behind and status of major efforts to alter its course. Recent findings Variations in microbial exposures are associated with risk of allergic disease, and the use of bacterial lysates may be a promising preventive strategy. Exposure to air pollution appears to be particularly damaging in prenatal and early life, and interventions to reduce pollution are feasible and result in clinical benefit. E-cigarette use may have a role in harm reduction for conventional cigarette smokers with asthma, but has undefined short- and long-term effects that must be clarified. Vitamin D insufficiency over the first several years of life is associated with risk of asthma, and vitamin D supplementation reduces the risk of severe exacerbations. Summary The identification of risk factors for asthma occurrence, persistence and severity will continue to guide efforts to alter the natural history of the disease. We have reviewed several promising strategies that are currently under investigation. Vitamin D supplementation and air pollution reduction have been shown to be effective strategies and warrant increased investigation and implementation. PMID:28079559

Greater involvement of neurokinins found in Guinea pig models of severe asthma compared with mild asthma.

PubMed

Mukaiyama, Osamu; Morimoto, Kiyoshi; Nosaka, Emi; Takahashi, Sakiko; Yamashita, Makoto

2004-08-01

Involvement of neurokinins in asthma has been previously pointed out by several reports. However, the relationship between neurokinins and the severity of asthma has remained unclear. We developed a model of mild asthma (model I) and severe asthma (model II) in guinea pigs, and investigated the function of neurokinins in both models. In models I and II, systemically sensitized guinea pigs were made to inhale ovalbumin once and three times, respectively. Substance P (SP) and neurokinin A (NKA) concentrations in the bronchoalveolar lavage fluid (BALF) were measured in models I and II. Then, the effects of a capsaicin pretreatment, which depletes neurokinins, in both animal models on airway narrowing induced by the last ovalbumin inhalation, airway hyperresponsiveness to inhaled methacholine, and eosinophil accumulation in BALF, were investigated. SP concentration tended to increase and the NKA concentration increased significantly in model II, but not in model I. Capsaicin pretreatment significantly inhibited the late bronchial response that was observed 2-6 h after the last ovalbumin inhalation, airway hyperresponsiveness and eosinophil accumulation in model II. On the other hand, it had no effects on the responses in model I. It is suggested that the more severe the disease, the greater the involvement of neurokinins. Copyright 2004 S. Karger AG, Basel

Electronic monitoring of adherence to inhaled corticosteroids: an essential tool in identifying severe asthma in children.

PubMed

Jochmann, Anja; Artusio, Luca; Jamalzadeh, Angela; Nagakumar, Prasad; Delgado-Eckert, Edgar; Saglani, Sejal; Bush, Andrew; Frey, Urs; Fleming, Louise J

2017-12-01

International guidelines recommend that severe asthma can only be diagnosed after contributory factors, including adherence, have been addressed. Accurate assessment of adherence is difficult in clinical practice. We hypothesised that electronic monitoring in children would identify nonadherence, thus delineating the small number with true severe asthma.Asthmatic children already prescribed inhaled corticosteroids were prospectively recruited and persistence of adherence assessed using electronic monitoring devices. Spirometry, airway inflammation and asthma control were measured at the start and end of the monitoring period.93 children (62 male; median age 12.4 years) were monitored for a median of 92 days. Median (range) monitored adherence was 74% (21-99%). We identified four groups: 1) good adherence during monitoring with improved control, 24% (likely previous poor adherence); 2) good adherence with poor control, 18% (severe therapy-resistant asthma); 3) poor adherence with good control, 26% (likely overtreated); and 4) poor adherence with poor control, 32%. No clinical parameter prior to monitoring distinguished these groups.Electronic monitoring is a useful tool for identifying children in whom a step up in treatment is indicated. Different approaches are needed in those who are controlled when adherent or who are nonadherent. Electronic monitoring is essential in a paediatric severe asthma clinic. Copyright ©ERS 2017.

Problematic Internet use, well-being, self-esteem and self-control: Data from a high-school survey in China

PubMed Central

Mei, Songli; Yau, Yvonne H. C.; Chai, Jingxin; Guo, Jinhua; Potenza, Marc N.

2016-01-01

Given the prevalence of Internet use among youth, there is concern that a subset of Internet-using youth may exhibit problematic or addictive patterns of Internet use. The present study examines the association between problematic Internet use (PIU), demographic variables, and health-related measures among Chinese adolescents. Survey data from 1552 adolescents (male = 653, mean age = 15.43 years) from Jilin Province, China, were collected. According to the Young Diagnostic Questionnaire for Internet Addiction (YDQ), 77.8% (n=1,207), 16.8% (n=260), and 5.5% (n=85) showed adaptive, maladaptive, and problematic Internet use, respectively. Multinomial logistic regression analysis revealed that gender and family income per month differed between youth showing problematic and adaptive patterns of Internet use. Well-being, self-esteem, and self-control were related to severity of problematic Internet use, with greater severity typically associated with poorer measures in each domain. The findings that severity of problematic Internet use is associated with specific socio-demographic features and temperamental and well-being measures suggest that specific groups of youth may be particularly vulnerable to developing problematic Internet use. Early prevention/intervention programs targeting at-risk groups may help improve public health. PMID:27249805

Detrimental effects of environmental tobacco smoke in relation to asthma severity.

PubMed

Comhair, Suzy A A; Gaston, Benjamin M; Ricci, Kristin S; Hammel, Jeffrey; Dweik, Raed A; Teague, W Gerald; Meyers, Deborah; Ampleford, Elizabeth J; Bleecker, Eugene R; Busse, William W; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Israel, Elliot; Jarjour, W Nizar; Moore, Wendy; Peters, Stephen P; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2011-05-04

Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown. In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity. From 2002-2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage. ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.

ALX receptor ligands define a biochemical endotype for severe asthma

PubMed Central

Ricklefs, Isabell; Barkas, Ioanna; Duvall, Melody G.; Grossman, Nicole L.; Israel, Elliot; Bleecker, Eugene R.; Castro, Mario; Erzurum, Serpil C.; Fahy, John V.; Gaston, Benjamin M.; Denlinger, Loren C.; Mauger, David T.; Wenzel, Sally E.; Comhair, Suzy A.; Coverstone, Andrea M.; Fajt, Merritt L.; Hastie, Annette T.; Johansson, Mats W.; Peters, Michael C.; Phillips, Brenda R.; Levy, Bruce D.

2017-01-01

BACKGROUND. In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). METHODS. ALX expression and levels of proresolving ligands (lipoxin A4 [LXA4], 15-epi-LXA4, and annexin A1 [ANXA1]), and a proinflammatory ligand (serum amyloid A [SAA]) were measured in bronchoscopy samples collected in Severe Asthma Research Program-3 (SA [n = 69], non-SA [NSA, n = 51] or healthy donors [HDs, n = 47]). RESULTS. Bronchoalveolar lavage (BAL) fluid LXA4 and 15-epi-LXA4 were decreased and SAA was increased in SA relative to NSA. BAL macrophage ALX expression was increased in SA. Subjects with LXA4loSAAhi levels had increased BAL neutrophils, more asthma symptoms, lower lung function, increased relative risk for asthma exacerbation, sinusitis, and gastroesophageal reflux disease, and were assigned more frequently to SA clinical clusters. SAA and aliquots of LXA4loSAAhi BAL fluid induced IL-8 production by lung epithelial cells expressing ALX receptors, which was inhibited by coincubation with 15-epi-LXA4. CONCLUSIONS. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. TRIAL REGISTRATION. Severe Asthma Research Program-3 (SARP-3; ClinicalTrials.gov NCT01606826) FUNDING Sources. National Heart, Lung and Blood Institute, the NIH, and the German Society of Pediatric Pneumology. PMID:28724795

Cytokine profile of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during seasonal H1N1 infection.

PubMed

Hasegawa, Shunji; Wakiguchi, Hiroyuki; Okada, Seigo; Gui Kang, Yu; Fujii, Nao; Hasegawa, Masanari; Hasegawa, Hideki; Ainai, Akira; Atsuta, Ryo; Shirabe, Komei; Toda, Shoichi; Wakabayashi-Takahara, Midori; Morishima, Tsuneo; Ichiyama, Takashi

2014-10-01

Several studies support the role of viral infections in the pathogenesis of asthma exacerbation. However, several pediatricians believe that influenza virus infection does not exacerbate bronchial asthma, except for influenza A H1N1 2009 pandemic [A(H1N1)pdm09] virus infection. We previously reported that A(H1N1)pdm09 infection possibly induces severe pulmonary inflammation or severe asthmatic attack in a mouse model of bronchial asthma and in asthmatic children. However, the ability of seasonal H1N1 influenza (H1N1) infection to exacerbate asthmatic attacks in bronchial asthma patients has not been previously reported, and the differences in the pathogenicity profiles, such as cytokine profiles, remains unclear in bronchial asthma patients after A(H1N1)pdm09 and H1N1 infections. The cytokine levels and viral titers in the bronchoalveolar lavage (BAL) fluid from mice with and without asthma after H1N1 infection (A/Yamagata and A/Puerto Rico strains) were compared. The interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, IL-5, interferon (IFN)-α, IFN-β, and IFN-γ levels were significantly higher in the BAL fluids from the control/H1N1 mice than from the asthmatic/H1N1 mice. The viral titers in the BAL fluid were also significantly higher in the control/H1N1mice than in the asthmatic/H1N1 mice infected with either A/Yamagata or A/Puerto Rico. A(H1N1)pdm09 infection, but not H1N1 infection, can induce severe pulmonary inflammation through elevated cytokine levels in a mouse model of asthma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica

PubMed Central

Brehm, John M.; Celedón, Juan C.; Soto-Quiros, Manuel E.; Avila, Lydiana; Hunninghake, Gary M.; Forno, Erick; Laskey, Daniel; Sylvia, Jody S.; Hollis, Bruce W.; Weiss, Scott T.; Litonjua, Augusto A.

2009-01-01

Rationale: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. Objectives: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. Methods: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. Measurements and Main Results: Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log10 unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004–0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% CI, 0.05–0.67; P = 0.01), and increased airway responsiveness (a ≤8.58-μmol provocative dose of methacholine producing a 20% fall in baseline FEV1 [OR, 0.15; 95% CI, 0.024–0.97; P = 0.05]). Conclusions: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity. PMID:19179486

School-Based Asthma Case Finding: The Arkansas Experience

ERIC Educational Resources Information Center

Vargas, Perla A.; Magee, James S.; Bushmiaer, Margo; Simpson, Pippa M.; Jones, Craig A.; Feild, Charles R.; Jones, Stacie M.

2006-01-01

This population-based case-finding study sought to determine asthma prevalence and characterize disease severity and burden among school-aged children in the Little Rock School District. Asthma cases were identified by validated algorithm and parental report of asthma diagnosis. The overall response rate was low. Among schools with greater than…

Asthma history, job type and job changes among US nurses.

PubMed

Dumas, Orianne; Varraso, Raphaëlle; Zock, Jan Paul; Henneberger, Paul K; Speizer, Frank E; Wiley, Aleta S; Le Moual, Nicole; Camargo, Carlos A

2015-07-01

Nurses are at increased risk of occupational asthma, an observation that may be related to disinfectants exposure. Whether asthma history influences job type or job changes among nurses is unknown. We investigated this issue in a large cohort of nurses. The Nurses' Health Study II is a prospective study of US female nurses enrolled in 1989 (ages 24-44 years). Job status and asthma were assessed in biennial (1989-2011) and asthma-specific questionnaires (1998, 2003). Associations between asthma history at baseline (diagnosis before 1989, n=5311) and job type at baseline were evaluated by multinomial logistic regression. The relations of asthma history and severity during follow-up to subsequent job changes were evaluated by Cox models. The analytic cohort included 98 048 nurses. Compared with nurses in education/administration (likely low disinfectant exposure jobs), women with asthma history at baseline were less often employed in jobs with likely high disinfectant exposure, such as operating rooms (odds ratio 0.73 (95% CI 0.63 to 0.86)) and emergency room/inpatient units (0.89 (0.82 to 0.97)). During a 22-year follow-up, nurses with a baseline history of asthma were more likely to move to jobs with lower exposure to disinfectants (HR 1.13 (1.07 to 1.18)), especially among those with more severe asthma (HR for mild persistent: 1.13; moderate persistent 1.26; severe persistent: 1.50, compared with intermittent asthma, p trend: 0.004). Asthma history was associated with baseline job type and subsequent job changes among nurses. This may partly reflect avoidance of tasks involving disinfectant use, and may introduce bias in cross-sectional studies on disinfectant exposure and asthma in nurses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Asthma Diagnosis, Severity, Control and Medication Use In Low Income Minority Preteens

PubMed Central

Clark, Noreen M.; Dodge, Julia A.; Shah, Smita; Thomas, Lara J.; Andridge, Rebecca R.; Awad, Daniel

2010-01-01

Background Asthma severity, control, type of medical regimen provided and compliance with it are not well understood in minority patients at the transition stage from childhood to adolescence. Objective Identify factors in clinical practice and patient behavior associated with negative outcomes for children at this developmentally significant period. Methods Parents of 1292 children with asthma among 6827 pre-teens in 19 middle schools in predominantly African American (94%), low income neighborhoods in Detroit, Michigan were enrolled. Data collected through self administered survey and telephone interviews were useable for 936 parents. Study queries related to demographics, asthma symptoms, and medication use. Mixed effects models with a random intercept for school used to determine severity and control and association of medical regimens to these. Results Sixty-seven percent children with probable asthma had received a physician's diagnosis. Being female was associated with being undiagnosed (p=0.02); 47% with no diagnosis had persistent asthma and 68% with a diagnosis and asthma medicines were not controlled. Over half with a diagnosis and no medicine were not controlled. Thirty nine percent had controller medicine; 40% were not compliant with controller use; 9% nebulized controller medicine. Compliant use of controller medicine was not associated with asthma control (p=0.001). Conclusions Lack of an asthma diagnosis was significant in these low income communities. Adolescent girls were at risk for not receiving a diagnosis. Regimens provided children at an important stage in their development were not consistent with therapies recommended for asthma control. Patient compliance with asthma regimens was low. Both clinical and patient education regarding effective asthma management is needed regarding pre teens in low income minority communities. Clinical Implications Diagnosis and medical therapy choices for low income, African American pre-adolescents may not account for the actual level of their symptoms. Asthma is likely to be uncontrolled at this significant developmental stage in this population. Girls may be at risk for diagnosis failure. PMID:20170321

A randomised controlled feasibility trial of Group Cognitive Behavioural Therapy for people with severe asthma.

PubMed

Yorke, Janelle; Adair, Pauline; Doyle, Anne-Marie; Dubrow-Marshall, Linda; Fleming, Sharon; Holmes, Leanne; Menzies-Gow, Andrew; Niven, Rob; Pilling, Mark; Shuldham, Caroline

2017-06-01

Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group. This study aimed to assess the feasibility and acceptability of Group-CBT in severe asthma. This was a two-centre, randomised controlled parallel group feasibility study. Eligible participants (patients with severe asthma and a clinically significant diagnosis of anxiety and/or depression - Hospital Anxiety and Depression Scale (HAD) score greater than 8 for the anxiety or depression sub-scale) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only. Follow-up was for 16 weeks and end points were: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea-12, EuroQual-5D and EuroQuol-VAS. 51 patients were randomised: 36% (51 out of 140) consent rate and attrition at week 16 was 12. Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly demands of the programme. Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health. Participants who contributed to focus group discussions reported that Group-CBT contributed to a better understanding of their illness and related approaches to anxiety management and acceptance of their asthma condition. Although weekly face-to-face sessions were challenging, this was the preferred method of delivery for these participants. This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma. It has been possible but not easy to recruit and retain the sample. Options for a less demanding intervention schedule, such as less frequent face-to-face visits and the use of web-based interventions, require careful consideration.

The impact of alexithymia on asthma patient management and communication with health care providers: a pilot study.

PubMed

Chugg, Kelly; Barton, Christopher; Antic, Ral; Crockett, Alan

2009-03-01

Alexithymia is a personality trait associated with difficulty identifying and verbalizing feelings. It has been associated with poorly controlled asthma and near-fatal asthma. The primary objectives were to (1) determine the prevalence of alexithymia in a group of moderate to severe asthmatics who attended an Outpatient Clinic; and (2) investigate the relationship between alexithymia and asthma control, management, and communication. Twenty-five moderate to severe asthma patients were recruited from the Royal Adelaide Hospital Outpatient Respiratory Clinic. Participants were either mailed the questionnaire pack or completed it after a clinic appointment. Existing validated questionnaires were used to collect data. The primary outcome measures were alexithymia, asthma control, adherence to medication; patient satisfaction with communication with health care providers and health-related quality of life. Data were analyzed using Pearson correlations, linear regression and analysis of variance (ANOVA) in SPSS. A p value

Audit of acute asthma management at the Paediatric Emergency Department at Wad Madani Children’s Hospital, Sudan

PubMed Central

Haroun, Huda M.; Ali, Hassan M.; Tag Eldeen, Imad Eldeen M.

2012-01-01

This audit of hospital care of acute wheeze and asthma aimed to assess the degree of adherence of the acute care of the asthma patients to the published international guidelines. Information was collected in six key areas: patient demographics; initial asthma severity assessment; in-hospital treatment; asthma prophylaxis; asthma education and emergency planning; and follow-up arrangements. The area of initial asthma severity assessment showed defciencies in the clinical measures currently used to verify case severity. In- hospital treatment on the other hand was consistent with recommendations in the use of the inhaled β-2 agonist salbutamol as bronchodilator, the discrete use of aminophylline and the small number of patients ordered chest X-ray. However, the treatment was incoherent with recommendations in the delivery method used for inhaled bronchodilator in relation to the age group of treated patients, absence of ipratropium bromide as a bronchodilator in the management and the large use of antibiotics. Assessment of the areas of asthma prophylaxis, asthma education and emergency- planning and follow-up arrangements illustrated that little efforts were made to assure safe discharge, although these measures have been shown to reduce morbidity after the exacerbation and reduce relapse rates and signifcantly reduce hospitalizations, unscheduled acute visits, missed work days, as well as improving quality of life. This audit emphasizes the need for the adoption of a management protocol for acute asthma care in the emergency department based on published international guidelines and the assurance of its implementation, monitoring and evaluation using the right tools to improve patient care. PMID:27493337

Do young adults with childhood asthma avoid occupational exposures at first hire?

PubMed

Dumas, O; Smit, L A M; Pin, I; Kromhout, H; Siroux, V; Nadif, R; Vermeulen, R; Heederik, D; Hery, M; Choudat, D; Kauffmann, F; Le Moual, N

2011-05-01

Information on the healthy worker hire effect in relation to asthma is scant. We aimed to assess whether and how childhood asthma-related characteristics (before hire) relate to occupational exposures at first hire. Analyses were conducted in 298 children examined at the first survey of the Epidemiological Study on the Genetics and Environment of Asthma (1991-1995), who reported a training period or a job at follow-up in 2003-2007 (aged 17-29 yrs; 53% males). Exposure likelihood to dust, gases and/or fumes in their first occupation was estimated by the ALOHA job exposure matrix. Asthma before the first occupation and two asthma classifications for severity (Global Initiative for Asthma 2002 guidelines) and symptoms were defined by questionnaire. In their first job, 47% of subjects were exposed. After adjustment (age, sex and education), pre-hire onset asthmatics (59%) were nonsignificantly less likely to be exposed (OR 0.67, 95% CI 0.41-1.11). Associations were stronger when considering those with severe asthma or high symptom score in childhood (OR 0.27 (95% CI 0.11-0.63) and OR 0.49 (95% CI 0.25-0.99), respectively). The association was observed in those who completed a university degree (OR 0.55, 95% CI 0.29-1.04) but not in the others (OR 0.98, 95% CI 0.44-2.22), with consistent results for all asthma characteristics. Results suggest a healthy worker hire effect in subjects with more severe or more symptomatic asthma in childhood. Education may modulate self-selection.

Sleep-disordered breathing in children with asthma: a systematic review on the impact of treatment.

PubMed

Sánchez, Trinidad; Castro-Rodríguez, José A; Brockmann, Pablo E

2016-01-01

The objective was to perform a systematic review in order to describe the relationship between asthma and sleep-disordered breathing (SDB) in children, especially regarding the impact of treatment and management. We performed an electronic search in MEDLINE, EMBASE, and LILACS database. Study inclusion criteria were the following: 1) studies that examined the relationship between asthma/wheezing and SDB/obstructive sleep apnea (OSA); and 2) studies conducted in children <18 years of age. Primary outcomes were the prevalence of asthma and SDB, the tests used for diagnosis, and the influence of their treatment and management. One thousand and twenty studies were identified, among which 32 were selected (n=143,343 children; 51% males; age [mean ± standard deviation] 8.4±2.5 years). Most studies (n=26) diagnosed SDB using questionnaires or clinical history. Nine studies performed a sleep study for diagnosing OSA. The diagnosis of asthma was based on clinical history (n=16), previous medical diagnosis (n=4), questionnaires (n=12), and spirometry (n=5). Children with asthma were more likely to develop habitual snoring and OSA, and children with SDB were more likely to develop asthma. Moreover, asthma was associated with more severe OSA, and the presence of SDB was associated with severe asthma. Treatment of SDB with adenotonsillectomy was associated with significant asthma improvement. The relationship between asthma and SDB appears to be bidirectional, and adenotonsillectomy appears to improve asthma control. Future trials on how asthma treatment could impact on SDB are needed.

[A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

PubMed

Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

2009-08-01

A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications.

Outdoor air pollution and asthma

PubMed Central

Guarnieri, Michael; Balmes, John R.

2015-01-01

Traffic and power generation are the main sources of urban air pollution. The idea that outdoor air pollution can cause exacerbations of pre-existing asthma is supported by an evidence base that has been accumulating for several decades, with several studies suggesting a contribution to new-onset asthma as well. In this Series paper, we discuss the effects of particulate matter (PM), gaseous pollutants (ozone, nitrogen dioxide, and sulphur dioxide), and mixed traffic-related air pollution. We focus on clinical studies, both epidemiological and experimental, published in the previous 5 years. From a mechanistic perspective, air pollutants probably cause oxidative injury to the airways, leading to inflammation, remodelling, and increased risk of sensitisation. Although several pollutants have been linked to new-onset asthma, the strength of the evidence is variable. We also discuss clinical implications, policy issues, and research gaps relevant to air pollution and asthma. PMID:24792855

Cluster analysis in phenotyping a Portuguese population.

PubMed

Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

2015-09-03

Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

Achieving Good Outcomes for Asthma Living (GOAL): mixed methods feasibility and pilot cluster randomised controlled trial of a practical intervention for eliciting, setting and achieving goals for adults with asthma.

PubMed

Hoskins, Gaylor; Williams, Brian; Abhyankar, Purva; Donnan, Peter; Duncan, Edward; Pinnock, Hilary; van der Pol, Marjon; Rauchhaus, Petra; Taylor, Anne; Sheikh, Aziz

2016-12-08

Despite being a core component of self-management, goal setting is rarely used in routine care. We piloted a primary care, nurse-led intervention called Achieving Good Outcomes for Asthma Living (GOAL) for adults with asthma. Patients were invited to identify and prioritise their goals in preparation for discussing and negotiating an action/coping plan with the nurse at a routine asthma review. The 18-month mixed methods feasibility cluster pilot trial stratified and then randomised practices to deliver usual care (UC) or a goal-setting intervention (GOAL). Practice asthma nurses and adult patients with active asthma were invited to participate. The primary outcome was asthma-specific quality of life. Semi-structured interviews with a purposive patient sample (n = 14) and 10 participating nurses explored GOAL perception. The constructs of normalisation process theory (NPT) were used to analyse and interpret data. Ten practices participated (five in each arm), exceeding our target of eight. However, only 48 patients (target 80) were recruited (18 in GOAL practices). At 6 months post-intervention, the difference in mean asthma-related quality of life (mAQLQ) between intervention and control was 0.1 (GOAL 6.20: SD 0.76 (CI 5.76-6.65) versus UC 6.1: SD 0.81 (CI 5.63-6.57)), less than the minimal clinically important difference (MCID) of 0.5. However, change from baseline was stronger in the intervention group: at 6 months the change in the emotions sub-score was 0.8 for intervention versus 0.2 for control. Costs were higher in the intervention group by £22.17. Routine review with goal setting was considered more holistic, enhancing rapport and enabling patients to become active rather than passive participants in healthcare. However, time was a major barrier for nurses, who admitted to screening out patient goals they believed were unrelated to asthma. The difference in AQLQ score from baseline is larger in the intervention arm than the control, indicating the intervention may have impact if appropriately strengthened. The GOAL intervention changed the review dynamic and was well received by patients, but necessitated additional time, which was problematic in the confines of the traditional nurse appointment. Modification to recruitment methods and further development of the intervention are needed before proceeding to a definitive cluster randomised controlled trial. ISRCTN18912042 . Registered on 26 June 2012.

Innate lymphoid cells and asthma.

PubMed

Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

2014-04-01

Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Identifying the heterogeneity of young adult rhinitis through cluster analysis in the Isle of Wight birth cohort.

PubMed

Kurukulaaratchy, Ramesh J; Zhang, Hongmei; Patil, Veeresh; Raza, Abid; Karmaus, Wilfried; Ewart, Susan; Arshad, S Hasan

2015-01-01

Rhinitis affects many young adults and often shows comorbidity with asthma. We hypothesized that young adult rhinitis, like asthma, exhibits clinical heterogeneity identifiable by means of cluster analysis. Participants in the Isle of Wight birth cohort (n = 1456) were assessed at 1, 2, 4, 10, and 18 years of age. Cluster analysis was performed on those with rhinitis at age 18 years (n = 468) by using 13 variables defining clinical characteristics. Four clusters were identified. Patients in cluster 1 (n = 128 [27.4%]; ie, moderate childhood-onset rhinitis) had high atopy and eczema prevalence and high total IgE levels but low asthma prevalence. They showed the best lung function at 18 years of age, with normal fraction of exhaled nitric oxide (Feno), low bronchial hyperresponsiveness (BHR), and low bronchodilator reversibility (BDR) but high rhinitis symptoms and treatment. Patients in cluster 2 (n = 199 [42.5%]; ie, mild-adolescence-onset female rhinitis) had the lowest prevalence of comorbid atopy, asthma, and eczema. They had normal lung function and low BHR, BDR, Feno values, and total IgE levels plus low rhinitis symptoms, severity, and treatment. Patients in cluster 3 (n = 59 [12.6%]; ie, severe earliest-onset rhinitis with asthma) had the youngest rhinitis onset plus the highest comorbid asthma (of simultaneous onset) and atopy. They showed the most obstructed lung function with high BHR, BDR, and Feno values plus high rhinitis symptoms, severity, and treatment. Patient 4 in cluster 4 (n = 82 [17.5%]; ie, moderate childhood-onset male rhinitis with asthma) had high atopy, intermediate asthma, and low eczema. They had impaired lung function with high Feno values and total IgE levels but intermediate BHR and BDR. They had moderate rhinitis symptoms. Clinically distinctive adolescent rhinitis clusters are apparent with varying sex and asthma associations plus differing rhinitis severity and treatment needs. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Asthma, hay fever, and food allergy are associated with caregiver-reported speech disorders in US children

PubMed Central

Strom, Mark A.; Silverberg, Jonathan I.

2016-01-01

Background Children with asthma, hay fever, and food allergy may have several factors that increase their risk of speech disorder, including allergic inflammation, ADD/ADHD, and sleep disturbance. However, few studies have examined a relationship between asthma, allergic disease, and speech disorder. We sought to determine whether asthma, hay fever, and food allergy are associated with speech disorder in children and whether disease severity, sleep disturbance, or ADD/ADHD modified such associations. Methods We analyzed cross-sectional data on 337,285 children aged 2–17 years from 19 US population-based studies, including the 1997–2013 National Health Interview Survey and the 2003/4 and 2007/8 National Survey of Children’s Health. Results In multivariate models, controlling for age, demographic factors, healthcare utilization, and history of eczema, lifetime history of asthma (odds ratio [95% confidence interval]: 1.18 [1.04–1.34], p = 0.01), and one-year history of hay fever (1.44 [1.28–1.62], p < 0.0001) and food allergy (1.35 [1.13–1.62], p = 0.001) were associated with increased odds of speech disorder. Children with current (1.37 [1.15–1.59] p = 0.0003) but not past (p = 0.06) asthma had increased risk of speech disorder. In one study that assessed caregiver-reported asthma severity, mild (1.58 [1.20–2.08], p = 0.001) and moderate (2.99 [1.54–3.41], p < 0.0001) asthma were associated with increased odds of speech disorder; however, severe asthma was associated with the highest odds of speech disorder (5.70 [2.36–13.78], p = 0.0001). Conclusion Childhood asthma, hay fever, and food allergy are associated with increased risk of speech disorder. Future prospective studies are needed to characterize the associations. PMID:27091599

Asthma, hay fever, and food allergy are associated with caregiver-reported speech disorders in US children.

PubMed

Strom, Mark A; Silverberg, Jonathan I

2016-09-01

Children with asthma, hay fever, and food allergy may have several factors that increase their risk of speech disorder, including allergic inflammation, ADD/ADHD, and sleep disturbance. However, few studies have examined a relationship between asthma, allergic disease, and speech disorder. We sought to determine whether asthma, hay fever, and food allergy are associated with speech disorder in children and whether disease severity, sleep disturbance, or ADD/ADHD modified such associations. We analyzed cross-sectional data on 337,285 children aged 2-17 years from 19 US population-based studies, including the 1997-2013 National Health Interview Survey and the 2003/4 and 2007/8 National Survey of Children's Health. In multivariate models, controlling for age, demographic factors, healthcare utilization, and history of eczema, lifetime history of asthma (odds ratio [95% confidence interval]: 1.18 [1.04-1.34], p = 0.01), and one-year history of hay fever (1.44 [1.28-1.62], p < 0.0001) and food allergy (1.35 [1.13-1.62], p = 0.001) were associated with increased odds of speech disorder. Children with current (1.37 [1.15-1.59] p = 0.0003) but not past (p = 0.06) asthma had increased risk of speech disorder. In one study that assessed caregiver-reported asthma severity, mild (1.58 [1.20-2.08], p = 0.001) and moderate (2.99 [1.54-3.41], p < 0.0001) asthma were associated with increased odds of speech disorder; however, severe asthma was associated with the highest odds of speech disorder (5.70 [2.36-13.78], p = 0.0001). Childhood asthma, hay fever, and food allergy are associated with increased risk of speech disorder. Future prospective studies are needed to characterize the associations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Budesonide nebulization added to systemic prednisolone in the treatment of acute asthma in children: a double-blind, randomized, controlled trial.

PubMed

Alangari, Abdullah A; Malhis, Nidal; Mubasher, Mohamed; Al-Ghamedi, Najwa; Al-Tannir, Mohamad; Riaz, Muhammad; Umetsu, Dale T; Al-Tamimi, Saleh

2014-04-01

Inhaled corticosteroids, known to be effective as a maintenance medication in chronic asthma, have also been suggested as a therapy for acute asthma when given at high doses. A double-blind, randomized, placebo-controlled trial was conducted in children aged 2 to 12 years with moderate or severe acute asthma, as determined based on a clinical score of 5 to 15 points, where 15 is the most severe. We compared the addition of budesonide 1,500 μg vs placebo to standard acute asthma treatment, which included salbutamol, ipratropium bromide, and a single dose of prednisolone 2 mg/kg given at the beginning of therapy. The primary outcome was hospital admission rate within 4 h. A total of 906 ED visits by children with moderate or severe acute asthma were evaluated. Seventy-five cases out of 458 (16.4%) in the budesonide group vs 82 of 448 (18.3%) in the placebo group were admitted (OR, 0.84; 95% CI, 0.58-1.23; P=.38). However, among cases with high baseline clinical score (≥13), significantly fewer children were admitted in the budesonide group (27 of 76 [35.5%]) than in the placebo group (39 of 73 [53.4%]; OR, 0.42; 95% CI, 0.19-0.94; P=.03). The addition of budesonide nebulization did not decrease the admission rate of children with acute asthma overall. However, it may decrease the admission rate of children with severe acute asthma. ClinicalTrials.gov; No.: NCT01524198; URL: www.clinicaltrials.gov

Pregnancy-associated plasma protein-A (PAPP-A) levels in patients with severe allergic asthma are reduced by omalizumab.

PubMed

Bulut, Ismet; Ozseker, Zeynep F; Coskun, Abdurrahman; Serteser, Mustafa; Unsal, Ibrahim

2017-12-06

Remodeling is a crucial feature of severe asthma and may be associated with activation of the allergic cascade by immunoglobulin E (IgE). Omalizumab, an anti-IgE monoclonal antibody, effectively targets the severe allergic asthma phenotype. Pregnancy-associated plasma protein-A (PAPP-A) is an insulin-like growth factor binding protein-4 (IGFBP-4) protease, increasing local insulin-like growth factor (IGF)-1 concentrations, which in turn initiating a cascade involved in the regulation of cell growth, differentiation, and proliferation in various tissues. In the present study, we evaluated the effects of omalizumab on serum PAPP-A, IGFBP-4, and IGF-1 levels in subjects with severe allergic asthma. We studied 36 asthmatic subjects and 36 healthy controls. An ultrasensitive enzyme-linked immunosorbent assay (ELISA) kit was used to measure serum PAPP-A levels, and routine commercial ELISA kits were employed to assess serum levels of IGF-1, IGFBP-4 in control subjects and asthmatic subjects before therapy (baseline) and after six months of omalizumab therapy in patients with severe asthma. Compared to control subjects, serum PAPP-A and IGFB-4 levels were significantly higher in asthmatic subjects (both p values < 0.001). However, the serum IGF-I levels of asthmatic subjects were similar to those of control subjects (p > 0.05). In asthma subjects, 6-month omalizumab treatment significantly decreased the serum PAPP-A (p < 0.001), IGF-I (p = 0.031), and IGFB4 (p = 0.025) levels. PAPP-A level may be a useful biomarker for predicting airway remodeling in patients with severe asthma receiving omalizumab, and may also reflect the response to treatment.

Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies.

PubMed

Chupp, Geoffrey; Laviolette, Michel; Cohn, Lauren; McEvoy, Charlene; Bansal, Sandeep; Shifren, Adrian; Khatri, Sumita; Grubb, G Mark; McMullen, Edmund; Strauven, Racho; Kline, Joel N

2017-08-01

Bronchial thermoplasty is an endoscopic therapy for severe asthma. The previously reported, randomised sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits and hospitalisations after bronchial thermoplasty. More "real-world" clinical outcome data is needed.This article compares outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial.279 subjects were treated with bronchial thermoplasty in the PAS2 study. We compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty-treated subjects in the AIR2 trial at 3 years of follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg·m -2 ) and took higher doses of inhaled corticosteroids (mean dose 2301 versus 1961 μg·day -1 ). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalisations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results.The PAS2 study demonstrates similar improvements in asthma control after bronchial thermoplasty compared with the AIR2 trial despite enrolling subjects who may have had poorer asthma control. Copyright ©ERS 2017.

Evaluation of the use of Swedish integrated electronic health records and register health care data as support clinical trials in severe asthma: the PACEHR study.

PubMed

Franzén, Stefan; Janson, Christer; Larsson, Kjell; Petzold, Max; Olsson, Urban; Magnusson, Gunnar; Telg, Gunilla; Colice, Gene; Johansson, Gunnar; Sundgren, Mats

2016-11-15

In the development of new drugs for severe asthma, it is a challenge from an ethical point of view to randomize severe asthma patients to placebo, and to obtain long-term safety data due to discontinuations. The aim of this study was to evaluate the feasibility of using electronic health record (EHR) data to create a real-world reference population of uncontrolled asthmatic patients to supplement the concurrent control/placebo group in long-term studies of asthma. EHR data from 36 primary care centres and a University hospital in Sweden were linked to Swedish mandatory health registers (2005-2013), creating a population covering 33 890 asthma patients, including data on co-morbidities, risk factors and laboratory/respiratory measurements. A severe asthma EHR reference cohort was established. We used logistic regression to estimate the propensity score (probability) of each RCT or EHR patient existing in the EHR cohort given their covariates. We created an EHR-derived reference cohort of 240 patients, matching the placebo group (N = 151) in an RCT of severe asthma. The exacerbation rate during follow-up in the EHR study population was 1.24 (weighted) compared to 0.9 in the RCT placebo group. Patients in the EHR cohort were of similar age as in the RCT placebo group, 50.6 years versus 50.1 years; had slightly higher body mass index 27.0 kg/m 2 versus 27.3 kg/m 2 ; and consisted of 40% versus 34% males. The results indicate that EHRs provide an opportunity to supplement the control group in RCTs of severe diseases.

Different effects of long-term exposures to SO2 and NO2 air pollutants on asthma severity in young adults.

PubMed

Greenberg, Nili; Carel, Rafael S; Derazne, Estela; Bibi, Haim; Shpriz, Manor; Tzur, Dorit; Portnov, Boris A

2016-01-01

Numerous studies demonstrated that exposure to ambient air pollutants contributes to severity and frequency of asthma exacerbations. However, whether common air pollutants, such as nitrogen dioxide (NO2) and sulfur dioxide (SO2), exert differential effects on asthma occurrence and severity is unclear. The aim of this investigation was to determine whether exposure to NO2 and/or SO2 may initiate different long-term effects on prevalence and severity of asthma in young adults. Medical records of 137,040 males, 17 years old, who underwent standard premilitary service health examinations during 1999-2008 were examined. Air-pollution data for NO2 and SO2 were linked to the place of residence of each subject. The influence of specific air pollutants on asthma prevalence and severity was evaluated using bivariate logistic regression, controlling for individuals' sociodemographic attributes. For both ambient air pollutants, there was a significant dose-response effect on severity of asthma at ambient concentrations below the current National Ambient Air Quality Standards. However, in residential areas with high levels of SO2 (13.3-592.7µg/m(3)) and high levels of NO2 (27.2-43.2µg/m(3)) the risk of asthma occurrence was significantly higher than that in residential areas with high levels of NO2 (27.2-43.2 µg/m(3)) and intermediate levels (6.7-13.3 µg/m(3)) of SO2 pollution. The effects of exposure to SO2 and NO2 air pollutants on the respiratory airways system appear to differ, with possible implications regarding medical management, even in cases of exposure to mixtures of these pollutants.

Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies

PubMed Central

Laviolette, Michel; Cohn, Lauren; McEvoy, Charlene; Bansal, Sandeep; Shifren, Adrian; Khatri, Sumita; Grubb, G. Mark; McMullen, Edmund; Strauven, Racho; Kline, Joel N.

2017-01-01

Bronchial thermoplasty is an endoscopic therapy for severe asthma. The previously reported, randomised sham-controlled AIR2 (Asthma Intervention Research 2) trial showed a significant reduction in severe asthma exacerbations, emergency department visits and hospitalisations after bronchial thermoplasty. More “real-world” clinical outcome data is needed. This article compares outcomes in bronchial thermoplasty subjects with 3 years of follow-up from the ongoing, post-market PAS2 (Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma) study with those from the AIR2 trial. 279 subjects were treated with bronchial thermoplasty in the PAS2 study. We compared the first 190 PAS2 subjects with the 190 bronchial thermoplasty-treated subjects in the AIR2 trial at 3 years of follow-up. The PAS2 subjects were older (mean age 45.9 versus 40.7 years) and more obese (mean body mass index 32.5 versus 29.3 kg·m−2) and took higher doses of inhaled corticosteroids (mean dose 2301 versus 1961 μg·day−1). More PAS2 subjects had experienced severe exacerbations (74% versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty. At year 3 after bronchial thermoplasty, the percentage of PAS2 subjects with severe exacerbations, emergency department visits and hospitalisations significantly decreased by 45%, 55% and 40%, respectively, echoing the AIR2 results. The PAS2 study demonstrates similar improvements in asthma control after bronchial thermoplasty compared with the AIR2 trial despite enrolling subjects who may have had poorer asthma control. PMID:28860266

The asthma ePrompt: a novel electronic solution for chronic disease management.

PubMed

Lim, Kaiser G; Rank, Matthew A; Cabanela, Rosa L; Furst, Joseph W; Rohrer, James E; Liesinger, Juliette; Muller, Lisa; Wagie, Amy E; Naessens, James M

2012-03-01

This study tested the ability of an electronic prompt to promote an asthma assessment during primary care visits. We performed a prospective study of all eligible adult patients with previously diagnosed asthma in three geographically distinct ambulatory family medicine clinics within a 4-month period. The usual clinic visit process was performed at two geographically distinct control sites (n = 75 and n = 55 patients, respectively). The intervention group site (n = 64) had an electronic flag embedded in the Patient Check-in Locator field which prompted the distribution of a self-administered Asthma Management Questionnaire (AMQ) in the waiting room. The primary outcome measure was a documented asthma severity assessment. The front desk distributed the AMQ successfully in 100% of possible opportunities and the AMQ was completed by 84% of patients. Providers in the intervention group were significantly more likely than providers in the two non-intervention groups to document asthma severity in the medical record during a non-asthma ambulatory clinic visit (63.3% vs. 18.7% vs. 3.6%; p < .001). The provision of standardized asthma information triggered by an electronic prompt at the time of check-in effectively initiates an asthma assessment during the primary care visits.

A Biobehavioral Approach to Managing Childhood Asthma.

ERIC Educational Resources Information Center

Kohen, Daniel P.

1987-01-01

Describes childhood asthma and a program which teaches relaxation and mental imagery (RMI) exercises to children and adolescents as an adjunct in the management of asthma. Clinical experience indicates children who learn RMI rate their asthma as significantly reduced in severity, miss fewer days of school, and make fewer visits to emergency rooms.…

The Influence of Health Education on Family Management of Childhood Asthma.

ERIC Educational Resources Information Center

Brazil, Kevin; McLean, Leslie; Abbey, David; Musselman, Carol

1997-01-01

Differences in asthma management among families with a child who has moderate to severe asthma were examined when they participated in an in-patient versus a day-camp program. Two broad categories of outcome were examined: illness and self-management skills. Findings and observations regarding children's feelings about asthma are discussed.…

Asthma Status and Severity Affects Missed School Days

ERIC Educational Resources Information Center

Moonie, Sheniz A.; Sterling, David A.; Figgs, Larry; Castro, Mario

2006-01-01

Excessive school absence disrupts learning and is a strong predictor of premature school dropout. School-aged children with asthma are absent more often compared to their healthy peers without asthma; yet, the causes are inadequately documented. We sought to determine the difference in mean absence days between children with and without asthma,…

Short-term ozone exposure and asthma severity: Weight-of-evidence analysis.

PubMed

Goodman, Julie E; Zu, Ke; Loftus, Christine T; Lynch, Heather N; Prueitt, Robyn L; Mohar, Isaac; Shubin, Sara Pacheco; Sax, Sonja N

2018-01-01

To determine whether evidence indicates that short-term exposure to ambient concentrations of ozone in the United States can affect asthma severity, we systematically reviewed published controlled human exposure, epidemiology, and animal toxicity studies. The strongest evidence for a potential causal relationship came from epidemiology studies reporting increased emergency department visits and hospital admissions for asthma following elevated ambient ozone concentrations. However, while controlled exposure studies reported lung function decrements and increased asthma symptoms following high ozone exposures 160-400 parts per billion [ppb]), epidemiology studies evaluating similar outcomes reported less consistent results. Animal studies showed changes in pulmonary function at high ozone concentrations (> 500ppb), although there is substantial uncertainty regarding the relevance of these animal models to human asthma. Taken together, the weight of evidence indicates that there is at least an equal likelihood that either explanation is true, i.e., the strength of the evidence for a causal relationship between short-term exposure to ambient ozone concentrations and asthma severity is "equipoise and above." Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical ventilation for severe asthma.

PubMed

Leatherman, James

2015-06-01

Acute exacerbations of asthma can lead to respiratory failure requiring ventilatory assistance. Noninvasive ventilation may prevent the need for endotracheal intubation in selected patients. For patients who are intubated and undergo mechanical ventilation, a strategy that prioritizes avoidance of ventilator-related complications over correction of hypercapnia was first proposed 30 years ago and has become the preferred approach. Excessive pulmonary hyperinflation is a major cause of hypotension and barotrauma. An appreciation of the key determinants of hyperinflation is essential to rational ventilator management. Standard therapy for patients with asthma undergoing mechanical ventilation consists of inhaled bronchodilators, corticosteroids, and drugs used to facilitate controlled hypoventilation. Nonconventional interventions such as heliox, general anesthesia, bronchoscopy, and extracorporeal life support have also been advocated for patients with fulminant asthma but are rarely necessary. Immediate mortality for patients who are mechanically ventilated for acute severe asthma is very low and is often associated with out-of-hospital cardiorespiratory arrest before intubation. However, patients who have been intubated for severe asthma are at increased risk for death from subsequent exacerbations and must be managed accordingly in the outpatient setting.

Role of periostin, FENO, IL-13, lebrikzumab, other IL-13 antagonist and dual IL-4/IL-13 antagonist in asthma.

PubMed

Agrawal, Swati; Townley, Robert G

2014-02-01

Asthma markedly diminishes quality of life due to limited activity, absences from work or school and hospitalizations. Patients with severe asthma which are not controlled despite taking effective therapy are most in need of new treatment approaches. IL-13 was demonstrated as 'central mediator of allergic asthma'. IL-13 has been implicated in the pathogenesis of asthma, idiopathic pulmonary fibrosis and COPD. IL-13 levels in the sputum and bronchial biopsy samples remain elevated in severe asthma despite the use of inhaled and systemic corticosteroids. Thus, IL-13 is a mediator involved in corticosteroid resistance. Periostin enhances profibrotic TGF-β signaling in subepithelial fibrosis associated with asthma. IL-13 induces bronchial epithelial cells to secrete periostin. Periostin may be a biomarker for Th2 induced airway inflammation. Lebrikizumab is a monoclonal antibody against IL-13. Lebrikizumab improved lung function in asthmatics who were symptomatic despite treatment with long acting beta agonist and inhaled corticosteroids and provided benefit in the treatment of severe uncontrolled asthma. Lebrikizumab block IL-13 signaling through the IL-13Rα1/IL-4Rα receptor. There was a larger reduction in FENO in the high periostin subgroup than in the low periostin subgroup (34.4 vs 4.3%). Serum CCL17, CCL13 and total IgE levels decreased in the lebrikizumab group.

Respiratory reviews in asthma 2013.

PubMed

Kim, Tae-Hyung

2014-03-01

From January 2012 up until March 2013, many articles with huge clinical importance in asthma were published based on large numbered clinical trials or meta-analysis. The main subjects of these studies were the new therapeutic plan based on the asthma phenotype or efficacy along with the safety issues regarding the current treatment guidelines. For efficacy and safety issues, inhaled corticosteroid tapering strategy or continued long-acting beta agonists use was the major concern. As new therapeutic trials, monoclonal antibodies or macrolide antibiotics based on inflammatory phenotypes have been under investigation, with promising preliminary results. There were other issues on the disease susceptibility or genetic background of asthma, particularly for the "severe asthma" phenotype. In the era of genome and pharmacogenetics, there have been extensive studies to identify susceptible candidate genes based on the results of genome wide association studies (GWAS). However, for severe asthma, which is where most of the mortality or medical costs develop, it is very unclear. Moreover, there have been some efforts to find important genetic information in order to predict the possible disease progression, but with few significant results up until now. In conclusion, there are new on-going aspects in the phenotypic classification of asthma and therapeutic strategy according to the phenotypic variations. With more pharmacogenomic information and clear identification of the "severe asthma" group even before disease progression from GWAS data, more adequate and individualized therapeutic strategy could be realized in the future.

Clinical evolution and nutritional status in asthmatic children and adolescents enrolled in Primary Health Care

PubMed Central

Morishita, Rosinha Yoko Matsubayaci; Strufaldi, Maria Wany Louzada; Puccini, Rosana Fiorini

2015-01-01

Objective: To evaluate the clinical evolution and the association between nutritional status and severity of asthma in children and adolescents enrolled in Primary Health Care. Methods: A retrospective cohort study of 219 asthmatic patients (3-17 years old) enrolled in Primary Care Services (PCSs) in Embu das Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma severity, other atopic diseases, family history of atopy, and body mass index. To evaluate the clinical outcome of asthma, data were collected on number of asthma exacerbations, number of emergency room consultations and doses of inhaled corticosteroids at follow-up visits in the 6th and 12th months. The statistical analysis included chi-square and Kappa agreement index, with 5% set as the significance level. Results: 50.5% of patients started wheezing before the age of 2 years, 99.5% had allergic rhinitis and 65.2% had a positive family history of atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in relation to nutritional status, 65.8% of patients had normal weight. There was no association between nutritional status and asthma severity (p=0.409). After 1 year of follow-up, 25.2% of patients showed reduction in exacerbations and emergency room consultations, and 16.2% reduced the amount of inhaled corticosteroids. Conclusions: The monitoring of asthmatic patients in Primary Care Services showed improvement in clinical outcome, with a decreased number of exacerbations, emergency room consultations and doses of inhaled corticosteroids. No association between nutritional status and asthma severity was observed in this study. PMID:26316387

CDC Vital Signs: Asthma in the US

MedlinePlus

... for people with asthma. Promote improvements in indoor air quality for people with asthma through measures such as ... healthy schools and workplaces, and improvements in outdoor air quality. Health care providers can Determine the severity of ...

Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

PubMed Central

Greenwald, Roby; Fitzpatrick, Anne M.; Gaston, Benjamin; Marozkina, Nadzeya V.; Erzurum, Serpil; Teague, W. Gerald

2010-01-01

Background Children with severe asthma have poor symptom control and elevated markers of airway oxidative and nitrosative stress. Paradoxically, they have decreased airway levels of S-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism. Methods and Findings We collected EBC samples from children and adolescents, including 38 with severe asthma, 46 with mild-to-moderate asthma and 16 healthy adolescent controls, and the concentration of ionic constituents was quantified using ion chromatography. The concentrations of EBC components with volatile conjugates were log-normally distributed. Formate was the principal ion that displayed a significant difference between asthma status classifications. The mean EBC formate concentration was 40% higher in samples collected from all asthmatics than from healthy controls (mean = 5.7 µM, mean±standard deviation = 3.1−10.3 µM vs. 4.0, 2.8−5.8 µM, p = 0.05). EBC formate was higher in severe asthmatics than in mild-to-moderate asthmatics (6.8, 3.7−12.3 µM vs. 4.9, 2.8−8.7 µM, p = 0.012). In addition, formate concentration was negatively correlated with methacholine PC20 (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose. Conclusions We conclude that EBC formate concentration is significantly higher in the breath of children with asthma than in those without asthma. In addition, amongst asthmatics, formate is elevated in the breath of those with severe asthma compared to those with mild-to-moderate asthma. We suggest that this difference is related to asthma pathology and may be a product of increased catabolism of endogenous S-nitrosothiols. PMID:20689836

Sensitization to pets is a major determinant of persistent asthma and new asthma onset in Sweden

PubMed Central

Uddenfeldt, Monica; Janson, Christer; Lampa, Erik

2013-01-01

Introduction Our knowledge about atopy as a longitudinal predictor of asthma is limited. The purpose of this study was to investigate the prognosis of asthma and risk factors for asthma onset, especially sensitization of specific allergens in a population sample. Material and methods A cohort responded to a respiratory questionnaire in 1990 and 2003. At baseline, 2,060 subjects who, in the screening questionnaire, reported respiratory symptoms and 482 controls were investigated with interviews, spirometry, and skin-prick test. A total of 721 asthmatics and 976 subjects without respiratory disease were clinically verified. At follow-up in 2003, 340 subjects with persistent asthma and 186 subjects with asthma remission were identified, while 76 subjects reported new asthma onset. Results Sensitization to pets and a high symptom score were significant determinants of persistent asthma (odds ratio (OR) 3.2 (95% CI 1.9–5.6) and 5.7 (2.5–13.3), respectively) and onset of asthma (OR 2.6 (1.1–6.0), and 1.7 (1.2–2.3)). A high self-reported responsiveness to airway irritants (OR 1.6 (1.1–2.2)), and more asthma medications (OR 2.0 (1.3–2.9)) were additional indicators of persistent asthma at the follow-up. Belonging to the older age group decreased the risk both of having persistent asthma and asthma onset. Discussion Asthmatics sensitized to pets have a more severe outcome than asthmatics not sensitized to pets. Sensitization to pets was also a strong predictor for onset of asthma. Special attention should be given to asthmatics who report having severe symptoms and problems with airway irritants as such patients are more likely to have persistent problems. PMID:23339512

Myocardial ischemia induced by nebulized fenoterol for severe childhood asthma.

PubMed

Zanoni, L Z; Palhares, D B; Consolo, L C T

2005-10-01

We examined for myocardial ischemia induced by continuous inhalation of fenoterol in children with severe acute asthma. Thirty children with severe acute asthma were evaluated for signs of myocardial ischemia when treated with 0.5 mg kg dose (maximum 15 mg) of inhaled fenoterol for one hour. The heart rate was measured before and after inhalation. Cardiac enzymes (creatine kinase, creatine kinase MB fraction and troponin levels) were measured at admission and 12 hours later. An EKG was recorded before inhalation was started and immediately after its completion to detect the presence of any evidence of myocardial ischemia. All patients developed significant increase in heart rate. Six patients showed EKG changes compatible with myocardial ischemia, despite normal enzyme levels. Patients with severe acute asthma show tachycardia and may show EKG changes of myocardial ischemia.

Vaccines: could asthma in young children be a preventable disease? ‬‬‬‬‬‬‬.

PubMed

Elenius, Varpu; Jartti, Tuomas

2016-11-01

‬The long battle with asthma is far from over in developed countries. Its incidence, prevalence, and severity have been increasing for decades. By reducing the risk for asthma, significant healthcare costs can be saved. The desire to create a vaccine that might prevent asthma in young children is attractive and widely considered one of the main goals in translational asthma research. Several vaccination strategies have been tested. These include allergen-specific immunotherapy, vaccination against infectious pathogens, and modification of cell and cytokine responses. The lack of success in the prevention of asthma in young children lies on the complexity of the disease, which involves many genetic, epigenetic, and environmental interactions. This review provides a summary of current literature and aims to address key questions how to develop vaccines to prevent asthma in young children. ‬‬‬‬‬‬‬‬‬‬‬‬‬‬. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aryl Hydrocarbon Receptor activation by diesel exhaust particles mediates epithelium-derived cytokines expression in severe allergic asthma.

PubMed

Weng, Chih-Ming; Wang, Chun-Hua; Lee, Meng-Jung; He, Jung-Re; Huang, Hsin-Yu; Chao, Ming-Wei; Chung, Kian Fan; Kuo, Han-Pin

2018-04-19

Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium-derived thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma. Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles (DEP) to determine AhR-mediated IL-33, Il-25 and TSLP synthesis and release. Primary bronchial epithelial cells exposed to DEP showed up-regulation of IL-33, IL-25 and TSLP. These effects were abolished by knock-down of AhR by siRNA. Increased AhR/ARNT binding to promoters of IL-33, IL-25, and TSLP was found using chromatin immunoprecipitation (ChIP) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL-33, IL-25 and TSLP. These patients derived clinical benefit from anti-IgE treatment. AhR activation by DEP mediates up-regulation of IL-33, IL-25 and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Characteristics of atopic children with pandemic H1N1 influenza viral infection: pandemic H1N1 influenza reveals 'occult' asthma of childhood.

PubMed

Hasegawa, Shunji; Hirano, Reiji; Hashimoto, Kunio; Haneda, Yasuhiro; Shirabe, Komei; Ichiyama, Takashi

2011-02-01

The number of human cases of pandemic H1N1 influenza viral infection has increased in Japan since April 2009, as it has worldwide. This virus is widespread in the Yamaguchi prefecture in western Japan, where most infected children exhibited respiratory symptoms. Bronchial asthma is thought to be one of the risk factors that exacerbate respiratory symptoms of pandemic H1N1-infected patients, but the pathogenesis remains unclear. We retrospectively investigated the records of 33 children with pandemic H1N1 influenza viral infection who were admitted to our hospital between October and December 2009 and analyzed their clinical features. The percentage of children with asthma attack, with or without abnormal findings on chest radiographs (pneumonia, atelectasis, etc.), caused by pandemic H1N1 influenza infection was significantly higher than that of children with asthma attack and 2008-2009 seasonal influenza infection. Of the 33 children in our study, 22 (66.7%) experienced an asthma attack. Among these children, 20 (90.9%) did not receive long-term management for bronchial asthma, whereas 7 (31.8%) were not diagnosed with bronchial asthma and had experienced their first asthma attack. However, the severity of the attack did not correlate with the severity of the pulmonary complications of pandemic H1N1 influenza viral infection. The pandemic H1N1 influenza virus greatly increases the risk of lower respiratory tract complications such as asthma attack, pneumonia, and atelectasis, when compared to the seasonal influenza virus. Furthermore, our results suggest that pandemic H1N1 influenza viral infection can easily induce a severe asthma attack, pneumonia, and atelectasis in atopic children without any history of either an asthma attack or asthma treatment. © 2011 John Wiley & Sons A/S.

Association between Electronic Cigarette Use and Asthma among High School Students in South Korea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cho, Jun Ho; Paik, Samuel Y.

Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months. Results showed prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (nmore » = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users. In conclusion, when compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.« less

Association between Electronic Cigarette Use and Asthma among High School Students in South Korea

DOE PAGES

Cho, Jun Ho; Paik, Samuel Y.

2016-03-04

Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months. Results showed prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (nmore » = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users. In conclusion, when compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.« less

Progression to Uncontrolled Severe Asthma: A Novel Risk Equation.

PubMed

Casciano, Julian; Krishnan, Jerry; Small, Mary Buatti; Li, Chenghui; Dotiwala, Zenobia; Martin, Bradley C

2017-01-01

Recently published asthma guidelines by the European Respiratory Society and the American Thoracic Society (ERS-ATS) define severe disease based on medication use and control level. These guidelines also emphasize that asthma severity involves certain biomarker phenotypes, one of them being eosinophilic phenotype. The quantification of the influence of eosinophil level toward predicting disease severity can help decision makers manage therapy better earlier. To develop a risk-scoring algorithm to identify patients at greater risk of developing uncontrolled severe asthma as defined by ERS-ATS guidelines. Data on asthma patients were extracted from the EMRClaims + database from January 2004 to July 2011. Patients with continuous enrollment 12 months before and after the date of the first encounter with a diagnosis of asthma (index date) with at least 1 blood eosinophil test result in the 12 months after the index date, but before the development of uncontrolled severe asthma or the study end date, were included. Uncontrolled severe asthma was defined as the first date on which all criteria of the ERS-ATS definition were first satisfied in the 12 months after the index date. Age (≥ 50 years vs. < 50 years), race, and sex were measured at index, and the Charlson Comorbidity Index (CCI) score (> 0 vs. 0) was measured in the pre-index period. Elevated eosinophil level was defined as a test result with ≥ 400 cells/µL. The study cohort was randomly split 50-50 into derivation and validation samples. Cox proportional hazards regression was used to develop the risk score for uncontrolled severe asthma using the derivation cohort with independent variables of eosinophil level, age, sex, race, and CCI. A bootstrapping procedure was used to generate 1,000 samples from the derivation cohort. Variables significant in ≥ 50% of the samples were retained in the final regression model. A risk score was then calculated based on the coefficient estimates of the final model. C-statistic was used to test the model's discrimination power. The study included 2,405 patients, 147 (6%) of whom developed uncontrolled severe asthma. Higher eosinophil level and CCI score > 0 were significantly and independently associated with an increased risk of uncontrolled severe asthma in the derivation cohort (HR = 1.90, 95% CI = 1.17-3.08 and HR = 2.00, 95% CI = 1.28-3.13, respectively); findings were similar in the validation cohort. Total risk score was categorized as 0, 2, and 4. All models showed good C-statistics (0.79-0.80), indicating favorable model discrimination. There was a significantly greater number of patients with uncontrolled severe asthma in the risk score segments of 2 and 4 compared with 0 (each P < 0.0001). A risk stratification tool using peripheral eosinophil counts and CCI can be used to predict the development of uncontrolled severe asthma. This study was funded by Teva Pharmaceuticals. eMAX Health Systems was a consultant to Teva Pharmaceuticals for this study and received payment from Teva Pharmaceuticals for work on this study. Casciano and Dotiwala are employed by eMAX Health Systems. Krishnan, Li, and Martin received payment from eMAX Health Systems for work on this study. Small was employed by Teva Pharmaceuticals at the time of this study. Study concept and design were contributed primarily by Casciano, Krishnan, Small, and Martin, along with Li and Dotiwala. Dotiwala, Casciano, Small, and Li collected the data, along with Martin and Li and Krishnan. Data interpretation was provided by Martin, Casciano, and Li, with assistance from the other authors. The manuscript was written by Li, Casciano, Dotiwala, and Small, with assistance from the other authors, and revised by Dotiwala, Small, Li, and Martin, with assistance from Krishnan and Casciano.

Problematic Internet use, well-being, self-esteem and self-control: Data from a high-school survey in China.

PubMed

Mei, Songli; Yau, Yvonne H C; Chai, Jingxin; Guo, Jinhua; Potenza, Marc N

2016-10-01

Given the prevalence of Internet use among youth, there is concern that a subset of Internet-using youth may exhibit problematic or addictive patterns of Internet use. The present study examines the association between problematic Internet use (PIU), demographic variables, and health-related measures among Chinese adolescents. Survey data from 1552 adolescents (male=653, mean age=15.43years) from Jilin Province, China, were collected. According to the Young Diagnostic Questionnaire for Internet Addiction (YDQ), 77.8% (n=1207), 16.8% (n=260), and 5.5% (n=85) showed adaptive, maladaptive, and problematic Internet use, respectively. Multinomial logistic regression analysis revealed that gender and family income per month differed between youth showing problematic and adaptive patterns of Internet use. Well-being, self-esteem, and self-control were related to severity of problematic Internet use, with greater severity typically associated with poorer measures in each domain. The findings that severity of problematic Internet use is associated with specific socio-demographic features and temperamental and well-being measures suggest that specific groups of youth may be particularly vulnerable to developing problematic Internet use. Early prevention/intervention programs targeting at-risk groups may help improve public health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

PubMed

Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

2017-11-01

Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

Glutathione Redox Control of Asthma: From Molecular Mechanisms to Therapeutic Opportunities

PubMed Central

Jones, Dean P.; Brown, Lou Ann S.

2012-01-01

Abstract Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. Antioxid. Redox Signal. 17, 375–408. PMID:22304503

Risk factors for childhood asthma deaths from the UK Eastern Region Confidential Enquiry 2001-2006.

PubMed

Anagnostou, Katherine; Harrison, Brian; Iles, Richard; Nasser, Shuaib

2012-03-01

Confidential enquiries into asthma deaths can identify inadequacies in medical management and factors which contribute to patients' death. To identify risk factors for paediatric asthma deaths over a 6-year period. Observational case-series study of paediatric asthma deaths between 2001-2006 in the UK Eastern Region. Hospital, primary care and post-mortem data were obtained for every child (≤17 yrs) with asthma recorded on the death certificate, and a detailed questionnaire was completed. Information was obtained on asthma severity, medications, hospital admissions, GP and hospital follow-up, adherence, psychosocial / behavioural factors, allergies, details of the terminal attack and precipitating factors. 20 children (10 male; 8-17 yrs; median: 11.5 yrs) died of asthma between 2001-2006. 9/20 had mild to moderate asthma (BTS/ SIGN criteria), 10/20 had severe asthma and 1 child was not known to have asthma. 13/20 were clinically atopic. Only 3 had undergone allergy assessment. 10/20 died between June and August. 12/20 children had adverse psychosocial and behavioural factors. 7/20 children were on non-combination long-acting β2-agonist (LABA) treatment without inhaled corticosteroids (ICS). Almost half the deaths occurred in children with mild/moderate asthma. We recommend that allergic factors and seasonal allergy should be identified early, non-combination LABAs avoided, and speculate that overuse of short-acting β2-agonists (SABAs) may indicate non-adherence with ICS. Asthma deaths in children can be avoided if risk factors are identified early.

Accreditation of specialized asthma units for adults in Spain: an applicable experience for the management of difficult-to-control asthma

PubMed Central

Cisneros, Carolina; Díaz-Campos, Rocío Magdalena; Marina, Núria; Melero, Carlos; Padilla, Alicia; Pascual, Silvia; Pinedo, Celia; Trisán, Andrea

2017-01-01

This paper, developed by consensus of staff physicians of accredited asthma units for the management of severe asthma, presents information on the process and requirements for already-existing asthma units to achieve official accreditation by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Three levels of specialized asthma care have been established based on available resources, which include specialized units for highly complex asthma, specialized asthma units, and basic asthma units. Regardless of the level of accreditation obtained, the distinction of “excellence” could be granted when more requirements in the areas of provision of care, technical and human resources, training in asthma, and teaching and research activities were met at each level. The Spanish experience in the process of accreditation of specialized asthma units, particularly for the care of patients with difficult-to-control asthma, may be applicable to other health care settings. PMID:28533690

Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma.

PubMed

Schatz, Michael; Hsu, Jin-Wen Y; Zeiger, Robert S; Chen, Wansu; Dorenbaum, Alejandro; Chipps, Bradley E; Haselkorn, Tmirah

2014-06-01

Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Childhood asthma and indoor woodsmoke from cooking in Guatemala.

PubMed

Schei, Morten A; Hessen, Jens O; Smith, Kirk R; Bruce, Nigel; McCracken, John; Lopez, Victorina

2004-01-01

We estimated the prevalence and severity of asthma, and the association with cooking on open wood fires, as preparation for a large-scale randomized field trial on effects of indoor air pollution and child health. This is one of the first systematic studies of asthma and indoor wood-smoke pollution and to our knowledge the first asthma study in a purely indigeneous population in Latin America. The mothers of 1058 children aged 4-6 years were interviewed, using the standardized ISAAC (International Study of Asthma and Allergies in Childhood) procedures and questionnaire. The study population is a Mam-speaking (Maya), indigenous group living at relatively high altitude (2000 m) in Western Guatemalan Highlands. We found that asthma prevalence is low among indigenous children in Guatemala, compared to other populations in Latin America. Only 3.3% of the children reported wheezing symptoms in the last 12 months, and 72% wheezing symptoms ever. The majority of the current wheezers had at least one of the criteria for severe asthma. The prevalence of all the symptoms of asthma was higher in children from households that used open fires compared to improved stoves with chimneys. In a logistic regression model, use of open fire for cooking was a significant risk factor for a number of asthma symptoms, with odds ratios varying from 2.0 to 3.5. Among the different cooking technologies (1-improved stove with chimney, 2-mixture of gas and open fire, 3-open fire) trends of higher prevalence with more pollution was found for some of the symptoms. Hence use of open fire for cooking, may be an important risk factor for asthma symptoms and severity.

Jackie Joyner-Kersee: Living with Asthma | NIH MedlinePlus the Magazine

MedlinePlus

... top woman athlete in the heptathlon and long-jump competitions, despite severe asthma. While she was a ... asthma there was no way you could run, jump, or do the things I was doing athletically. ...

Validity of two common asthma-specific quality of life questionnaires: Juniper mini asthma quality of life questionnaire and Sydney asthma quality of life questionnaire

PubMed Central

2012-01-01

Background This study explored the psychometric properties (internal consistency, construct validity, discriminative ability) of the Juniper Mini Asthma Quality of Life Questionnaire (Mini AQLQ-J) and the Sydney Asthma Quality of Life Questionnaire (AQLQ-S). Methods One hundred fourty-six adults (18–45 years) with asthma requiring regular inhaled corticosteroids were recruited to a trial of written emotional disclosure. Correlational analyses were performed to understand the relationship of the two measures with each other, with symptoms, lung function, asthma control, asthma bother and generic quality of life. Median quality of life scores were compared according to gender, health care usage and levels of asthma severity. Results AQLQ-J and AQLQ-S total scores correlated strongly with each other (rho = −0.80) and moderately with the EuroQol Current Health Status Scale (AQLQ-J: rho = 0.35; AQLQ-S: rho = −0.40). Domain score correlations between AQLQ-J and AQLQ-S were mostly moderate (0.50 < rho < 0.80). Both QoL measures were significantly correlated with symptom score. Correlations with the symptom score asthma module (AQLQ-J: rho = −0.69; AQLQ-S: rho = 0.50) were stronger compared with the total symptom score and the symptom score rhinitis module (AQLQ-J: rho = −0.41; AQLQ-S: rho =0.31). Neither QoL measure was significantly correlated with FEV1, % predicted at the total or the domain level. Total scores of both measures were significantly correlated with subjective asthma control (AQLQ-J: rho = 0.68; AQLQ-S: rho = −0.61) and asthma bother (AQLQ-J: rho = −0.73; AQLQ-M: rho = 0.73). Total AQLQ-J score and total AQLQ-S score were significantly associated with perceived asthma severity (AQLQ-J: p=0.004, AQLQ-S: p=0.002) and having visited a GP in the past four months (AQLQ-J: p=0.003, AQLQ-S: p=0.002). Conclusions This study provides further evidence for the validity of the AQLQ-J and the AQLQ-S in a British population of adult patients with asthma managed in primary care. Correlations with lung function parameters were weak or absent. Correlations with generic quality of life were moderate, those with asthma symptoms, asthma control and asthma bother were strong. Both measures are able to discriminate between levels of asthma severity and health care usage. PMID:22906054

Validity of two common asthma-specific quality of life questionnaires: Juniper mini asthma quality of life questionnaire and Sydney asthma quality of life questionnaire.

PubMed

Apfelbacher, Christian Joachim; Jones, Christina; Hankins, Matthew; Smith, Helen

2012-08-20

This study explored the psychometric properties (internal consistency, construct validity, discriminative ability) of the Juniper Mini Asthma Quality of Life Questionnaire (Mini AQLQ-J) and the Sydney Asthma Quality of Life Questionnaire (AQLQ-S). One hundred fourty-six adults (18-45 years) with asthma requiring regular inhaled corticosteroids were recruited to a trial of written emotional disclosure. Correlational analyses were performed to understand the relationship of the two measures with each other, with symptoms, lung function, asthma control, asthma bother and generic quality of life. Median quality of life scores were compared according to gender, health care usage and levels of asthma severity. AQLQ-J and AQLQ-S total scores correlated strongly with each other (rho = -0.80) and moderately with the EuroQol Current Health Status Scale (AQLQ-J: rho = 0.35; AQLQ-S: rho = -0.40). Domain score correlations between AQLQ-J and AQLQ-S were mostly moderate (0.50 < rho < 0.80).Both QoL measures were significantly correlated with symptom score. Correlations with the symptom score asthma module (AQLQ-J: rho = -0.69; AQLQ-S: rho = 0.50) were stronger compared with the total symptom score and the symptom score rhinitis module (AQLQ-J: rho = -0.41; AQLQ-S: rho =0.31).Neither QoL measure was significantly correlated with FEV1, % predicted at the total or the domain level.Total scores of both measures were significantly correlated with subjective asthma control (AQLQ-J: rho = 0.68; AQLQ-S: rho = -0.61) and asthma bother (AQLQ-J: rho = -0.73; AQLQ-M: rho = 0.73).Total AQLQ-J score and total AQLQ-S score were significantly associated with perceived asthma severity (AQLQ-J: p=0.004, AQLQ-S: p=0.002) and having visited a GP in the past four months (AQLQ-J: p=0.003, AQLQ-S: p=0.002). This study provides further evidence for the validity of the AQLQ-J and the AQLQ-S in a British population of adult patients with asthma managed in primary care. Correlations with lung function parameters were weak or absent. Correlations with generic quality of life were moderate, those with asthma symptoms, asthma control and asthma bother were strong. Both measures are able to discriminate between levels of asthma severity and health care usage.

Polyclonal and allergen-induced cytokine responses in adults with asthma: resolution of asthma is associated with normalization of IFN-gamma responses.

PubMed

Smart, Joanne M; Horak, Elisabeth; Kemp, Andrew S; Robertson, Colin F; Tang, Mimi L K

2002-09-01

Atopic disease is associated with skewing of immune responses away from a T(H)1 toward a T(H)2 profile. Previous studies have implicated this cytokine imbalance in the development of disease. However, it is not known whether normalization of this imbalance is conversely associated with disease resolution. To further delineate the role of reduced T(H)1 and increased T(H)2 cytokine production in the pathogenesis of atopic disease and to determine whether disease resolution is associated with alteration of cytokine profiles, we investigated cytokine responses in a cohort of adult patients with asthma followed from childhood. A cohort of wheezy children and control subjects aged 7 to 10 years were recruited from 1964 to 1967. Subjects were reevaluated every 7 years to monitor the outcome of childhood asthma. At the 42-year follow-up, 89 subjects from this cohort were evaluated for mitogen and house dust mite (HDM)-induced T(H)1 (IFN-gamma) and T(H)2 (IL-4, IL-5, and IL-13) cytokine responses. Cytokine responses were compared in patients with ongoing asthma, patients with resolved asthma, and control subjects. Patients with severe ongoing asthma had significantly reduced HDM-induced IFN-gamma production compared with that of control subjects and patients with resolved asthma. In contrast, HDM-induced IFN-gamma production in patients with resolved asthma was equivalent to that seen in control subjects. Patients with ongoing and resolved asthma produced significantly higher levels of IL-5 in response to HDM compared with that seen in control subjects, with levels being equivalent in patients with active and resolved asthma. HDM-induced IL-13 production was significantly increased in the patients with resolved asthma when compared with that seen in the control subjects. PHA-induced cytokine responses did not parallel HDM-induced responses. Patients with persistent and severe atopic asthma have a reduced HDM-induced T(H)1 response, whereas those with resolved asthma do not. This suggests that reduced HDM-induced IFN-gamma production might be an important factor contributing to ongoing severe asthma and that normalization of allergen-induced T(H)1 responses might be important for disease resolution. The finding that all subjects with a history of asthma displayed increased HDM-induced T(H)2 (IL-5 and IL-13) cytokine responses, irrespective of the presence or absence of asthma, suggests that increased T(H)2 responses reflect the presence of the atopic state per se rather than being specifically linked to asthma.

Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK).

PubMed

Heaney, Liam G; Djukanovic, Ratko; Woodcock, Ashley; Walker, Samantha; Matthews, John G; Pavord, Ian D; Bradding, Peter; Niven, Robert; Brightling, Chris E; Chaudhuri, Rekha; Arron, Joseph R; Choy, David F; Cowan, Douglas; Mansur, Adel; Menzies-Gow, Andrew; Adcock, Ian; Chung, Kian F; Corrigan, Chris; Coyle, Peter; Harrison, Timothy; Johnston, Sebastian; Howarth, Peter; Lordan, James; Sabroe, Ian; Bigler, Jeannette; Smith, Dirk; Catley, Matthew; May, Richard; Pierre, Lisa; Stevenson, Chris; Crater, Glenn; Keane, Frank; Costello, Richard W; Hudson, Val; Supple, David; Hardman, Tim

2016-02-01

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Pulmonary edema after electroconvulsive therapy in a patient treated for long-standing asthma with a beta2 stimulant.

PubMed

Hatta, Kotaro; Kitajima, Akiyoshi; Ito, Masanobu; Usui, Chie; Arai, Heii

2007-03-01

A 68-year-old man was scheduled to receive 8 treatments of electroconvulsive therapy (ECT) for severe depression. He was being treated for long-standing asthma with a beta2 stimulant, clenbuterol hydrochloride, and had experienced no asthma attack for 9 years. Although he experienced no adverse consequence in his 7 treatments, pulmonary edema ensued from his eighth treatment despite no change in anesthesia and in the technical parameters of ECT. He was treated with oxygen and intravenous hydrocortisone, after which he quickly recovered. Transient eosinophilia was observed, but clinical symptoms of asthma did not appear. Although the association between pulmonary edema and well-controlled asthma was unclear, thiopental as induction of anesthesia or esmolol as poststimulus delivery might have played a role in the event. There may be a possibility of pulmonary edema even after several uneventful ECT treatments in a patient with asthma.

Sleep-disordered breathing in children with asthma: a systematic review on the impact of treatment

PubMed Central

Sánchez, Trinidad; Castro-Rodríguez, José A; Brockmann, Pablo E

2016-01-01

Background The objective was to perform a systematic review in order to describe the relationship between asthma and sleep-disordered breathing (SDB) in children, especially regarding the impact of treatment and management. Methods We performed an electronic search in MEDLINE, EMBASE, and LILACS database. Study inclusion criteria were the following: 1) studies that examined the relationship between asthma/wheezing and SDB/obstructive sleep apnea (OSA); and 2) studies conducted in children <18 years of age. Primary outcomes were the prevalence of asthma and SDB, the tests used for diagnosis, and the influence of their treatment and management. Results One thousand and twenty studies were identified, among which 32 were selected (n=143,343 children; 51% males; age [mean ± standard deviation] 8.4±2.5 years). Most studies (n=26) diagnosed SDB using questionnaires or clinical history. Nine studies performed a sleep study for diagnosing OSA. The diagnosis of asthma was based on clinical history (n=16), previous medical diagnosis (n=4), questionnaires (n=12), and spirometry (n=5). Children with asthma were more likely to develop habitual snoring and OSA, and children with SDB were more likely to develop asthma. Moreover, asthma was associated with more severe OSA, and the presence of SDB was associated with severe asthma. Treatment of SDB with adenotonsillectomy was associated with significant asthma improvement. Conclusion The relationship between asthma and SDB appears to be bidirectional, and adenotonsillectomy appears to improve asthma control. Future trials on how asthma treatment could impact on SDB are needed. PMID:27143940

Path to health asthma study: A survey of pediatric asthma in an urban community.

PubMed

Alicea-Alvarez, Norma; Foppiano Palacios, Carlo; Ortiz, Melanie; Huang, Diana; Reeves, Kathleen

2017-04-01

Minority children with asthma who live in low-income urban communities bear a disproportionate burden of the disease. This study explores the perceived health care needs related to asthma care, identifies asthma triggers, potential barriers to care, and assesses the need for additional community resources. We conducted a cross-sectional survey of Hispanic and African American adults (n = 53) who take care of a child with asthma and live in an urban community of North Philadelphia. Input from community leaders was obtained in the development the survey tool resulting in a unique 'community-centric' questionnaire. The survey was also available in Spanish. All surveys were conducted in the community setting. Variables were used to measure asthma severity and triggers. Children were categorized with intermittent (n = 24, 45.3%), mild persistent (n = 13, 24.5%), or moderate-to-severe persistent asthma (n = 16, 30.2%). Most children with persistent asthma were enrolled under Medicaid or CHIP (n = 24, p = 0.011) and reflected a low-income socioeconomic status. Persistent asthma was found to be associated with most triggers: pets, dust mites, mice, mold, and cockroaches. There was no significant association between environmental tobacco smoke and persistent asthma. Children with persistent asthma and 2 or more triggers were more likely to be hospitalized and go to the Emergency Department. Urban minority children living in low-income communities face neighborhood-specific asthma triggers and challenges to care. Studies conducted in urban neighborhoods, with collaboration from community members, will highlight the need of comprehensive services to account for community-centric social determinants.

The public health implications of asthma.

PubMed Central

Bousquet, Jean; Bousquet, Philippe J.; Godard, Philippe; Daures, Jean-Pierre

2005-01-01

Asthma is a very common chronic disease that occurs in all age groups and is the focus of various clinical and public health interventions. Both morbidity and mortality from asthma are significant. The number of disability-adjusted life years (DALYs) lost due to asthma worldwide is similar to that for diabetes, liver cirrhosis and schizophrenia. Asthma management plans have, however, reduced mortality and severity in countries where they have been applied. Several barriers reduce the availability, affordability, dissemination and efficacy of optimal asthma management plans in both developed and developing countries. The workplace environment contributes significantly to the general burden of asthma. Patients with occupational asthma have higher rates of hospitalization and mortality than healthy workers. The surveillance of asthma as part of a global WHO programme is essential. The economic cost of asthma is considerable both in terms of direct medical costs (such as hospital admissions and the cost of pharmaceuticals) and indirect medical costs (such as time lost from work and premature death). Direct costs are significant in most countries. In order to reduce costs and improve quality of care, employers and health plans are exploring more precisely targeted ways of controlling rapidly rising health costs. Poor control of asthma symptoms is a major issue that can result in adverse clinical and economic outcomes. A model of asthma costs is needed to aid attempts to reduce them while permitting optimal management of the disease. This paper presents a discussion of the burden of asthma and its socioeconomic implications and proposes a model to predict the costs incurred by the disease. PMID:16175830

Underrecognition of the severity of asthma and undertreatment of asthma in a rural area of Japan.

PubMed

Tomita, Katsuyuki; Hanaki, Keiichi; Hasegawa, Yasuyuki; Watanabe, Masanari; Sano, Hiroyuki; Igishi, Tadashi; Burioka, Naoto; Hitsuda, Yutaka; Horimukai, Kenta; Fukutani, Kouji; Sugimoto, Yuji; Yamamoto, Mitsunobu; Kato, Kazuhiro; Ikeda, Toshikazu; Konishi, Tatsuya; Tokuyasu, Hirokazu; Kawasaki, Yuji; Yajima, Hiroki; Sejima, Hitoshi; Isobe, Takeshi; Takabatake, Toshikazu; Shimizu, Eiji

2005-10-01

Revised guidelines were released in Japan in 2003 for the assessment, treatment, and management of adult asthmatics, and similar guidelines for child asthmatics were released in 2002. We reassessed the severity and possible undertreatment of asthma according to these guidelines in stable asthmatics. We reviewed medical records of 861 well-controlled asthmatic patients who, in April through June 2004 were cared for by 47 pulmonologists at 29 medical centers and 13 asthma clinics in a rural community in the San-in area of Japan. The physician obtained completed medical records about their symptoms and current treatment of the subjects, 726 adult and 135 children (aged 6 years or older) who were in stable condition and had had no exacerbations in the previous 3 months. The severity of asthma and current treatment for each patient were assessed according to the newly revised Japanese guidelines for the assessment, treatment, and management of adult and child asthmatics. In adult and child asthmatics, the percentage of predicted forced expiratory volume at 1 second (FEV1.0) was smaller and has a narrower distribution range than the percentage of predicted peak expiratory flow (PEF). When the severity of asthma was classified according to symptoms alone, 50% and 35% of those classified as mildly asthmatics patients with adults and children, respectively, had moderate to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of adult and 14.9% of child patients. When we compared the treatments that patients were actually receiving against the optimal treatments indexed according to a combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics were overtreated, 21% were properly treated, and 30% were undertreated. Among children, the respective percentages were 35%, 25%, and 40%. In well-controlled adult and child asthmatics, the severity of asthma is poorly judged when symptoms alone are considered. We suggest that the severity of asthma should be assessed through a combination of symptoms and the measurement of FEV1.0 during office visits. We also suggest that the proper dose of inhaled steroid needed to maintain stable conditions should be judged according to this combined symptoms-FEV1.0 classification.

Assessment of long-term omalizumab treatment in patients with severe allergic asthma long-term omalizumab treatment in severe asthma.

PubMed

Özgür, Eylem Sercan; Özge, Cengiz; Ïlvan, Ahmet; Naycı, Sibel Atış

2013-08-01

Several clinical studies have demonstrated the effectiveness of omalizumab in patients with severe allergic asthma but the treatment period has always been relatively short (4-12 months). In the literature, there are a few data about the long-term omalizumab therapy. We aimed to assess the long-term clinical and functional effectiveness of omalizumab treatment in severe allergic asthmatic patients, Medical records describing the patients' status before the start of treatment, and also having been registered at the end of 4th, 12th, and 36th months from the commencement of treatment, and at the last visit where the patient was evaluated were used for omalizumab effectiveness assessments. Twenty-six patients (female/male: 21/5) with severe allergic asthma, uncontrolled despite GINA 2006 Step 4 therapy, were included in the study. Effectiveness outcomes included spirometry measurements, level of asthma control measured by asthma control test (ACT), systemic glucocorticosteroid (sGCS) use, emergency room (ER) visits, and hospitalizations for severe exacerbations. In addition, the quality of life was assessed using the quality of life questionnaire AQLQ(S) before, 4, and 36 months after treatment, The mean age was 47.6 ± 13.9 and duration of allergic asthma was 22.7 ± 10.1 years. Serum total IgE levels were 322.0 ± 178.1 IU/mL. Mean duration of omalizumab treatment was 40.81 ± 8.2 months. FEV1 improved significantly at all control points versus baseline (p < .05). The level of asthma control as evaluated by ACT improved significantly after treatment (p < .05). We determined significantly reduced numbers of exacerbation, emergency visits, hospitalizations, sGCS, and SABA use by the end of 36 months (p < .05). The proportion of patients with improvements larger than 1.5 points in AQLQ(S) total score was 80.7% at the 4th month and 96.1% at the 36th month of treatment, This study showed that long-term therapy with omalizumab for up to 3 years was well tolerated with significant improvement both in symptoms and lung functions. Accordingly, long-term omalizumab treatment may be recommended for responders.

The Role of the Microbiome in the Relationship of Asthma and Affective Disorders.

PubMed

Trueba, Ana F; Ritz, Thomas; Trueba, Gabriel

2016-01-01

The effect of stress, anxiety and other affective states on inflammatory conditions such as asthma is well documented. Although several immune pathway mechanisms have been proposed and studied, they cannot fully explain the relationship. In this chapter we present a new perspective on asthma development and exacerbation that integrates findings on the role of psychological factors in asthma with the microbiome and the hygiene hypothesis in asthma development.

Nonadherence in the era of severe asthma biologics and thermoplasty

PubMed Central

Lee, Joy; Tay, Tunn Ren; Radhakrishna, Naghmeh; Hore-Lacy, Fiona; Mackay, Anna; Hoy, Ryan; Dabscheck, Eli; O'Hehir, Robyn; Hew, Mark

2018-01-01

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking >75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies. PMID:29519922

The Continuing Problem of Asthma in Very Young Children: A Community-Based Participatory Research Project

ERIC Educational Resources Information Center

Nelson, Belinda Wilburn; Awad, Daniel; Alexander, Jeffrey; Clark, Noreen

2009-01-01

Background: Asthma is a chronic health condition that has a disproportionate effect on low-income minority children who reside in large urban areas. African American children report significantly higher rates than the general population of children and have more-severe asthma and poorer outcomes. This article describes the prevalence of asthma in…

Labial adhesions and outcomes of office management.

PubMed

Granada, Catalina; Sokkary, Nancy; Sangi-Haghpeykar, Haleh; Dietrich, Jennifer E

2015-04-01

To evaluate clinical outcomes of labial adhesions (LA) and to examine the association between LA, lichen sclerosus (LS), eczema (ECZ), or asthma. Retrospective study. Single pediatric and adolescent gynecology clinic, Houston, Texas. 50 girls diagnosed with LA from 2006-2011. Resolution, recurrence, single vs multiple treatments, need for surgery, and conditions such as LS, ECZ, and asthma were reviewed. Mean age was 19.6 months (range 0-84 months), and 48% were Caucasian. Most patients were symptomatic (62%) and all 50 patients chose estrogen treatment. The majority (74%) required multiple treatments, as opposed to a single treatment (26%). Patients with multiple treatments were more likely to be severely agglutinated (P = .05) and to need manual separation after failed topical treatment (P = .08). The prevalence of asthma, LS, and ECZ was 9.8%, 7.8%, and 3.9% respectively. There was no association between LS, ECZ, or asthma, and number of treatments. Both asthma (N = 3; 8%), and LS (N = 2; 5%) were present among the severe agglutinated group; however, this difference was not statistically significant (P values .59 and .99). No association with ECZ was seen in either group. Severe agglutination tends to be associated with need of multiple treatments and manual separation. A concurrent diagnosis of LS, ECZ, or asthma was not associated with number of treatments but there appears to be a trend towards severity of LA in patients with asthma and LS. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

An RGS4-mediated phenotypic switch of bronchial smooth muscle cells promotes fixed airway obstruction in asthma.

PubMed

Damera, Gautam; Druey, Kirk M; Cooper, Philip R; Krymskaya, Vera P; Soberman, Roy J; Amrani, Yassine; Hoshi, Toshinori; Brightling, Christopher E; Panettieri, Reynold A

2012-01-01

In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM) mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4) in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR)-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe asthma.

Implementation of evidence-based asthma interventions in post-Katrina New Orleans: the Head-off Environmental Asthma in Louisiana (HEAL) study.

PubMed

Mitchell, Herman; Cohn, Richard D; Wildfire, Jeremy; Thornton, Eleanor; Kennedy, Suzanne; El-Dahr, Jane M; Chulada, Patricia C; Mvula, Mosanda M; Grimsley, L Faye; Lichtveld, Maureen Y; White, LuAnn E; Sterling, Yvonne M; Stephens, Kevin U; Martin, William J

2012-11-01

Childhood asthma morbidity and mortality in New Orleans, Louisiana, is among the highest in the nation. In August 2005, Hurricane Katrina created an environmental disaster that led to high levels of mold and other allergens and disrupted health care for children with asthma. We implemented a unique hybrid asthma counselor and environmental intervention based on successful National Institutes of Health asthma interventions from the National Cooperative Inner City Asthma (NCICAS) and Inner-City Asthma (ICAS) Studies with the goal of reducing asthma symptoms in New Orleans children after Hurricane Katrina. Children (4-12 years old) with moderate-to-severe asthma (n = 182) received asthma counseling and environmental intervention for approximately 1 year. HEAL was evaluated employing several analytical approaches including a pre-post evaluation of symptom changes over the entire year, an analysis of symptoms according to the timing of asthma counselor contact, and a comparison to previous evidence-based interventions. Asthma symptoms during the previous 2 weeks decreased from 6.5 days at enrollment to 3.6 days at the 12-month symptom assessment (a 45% reduction, p < 0.001), consistent with changes observed after NCICAS and ICAS interventions (35% and 62% reductions in symptom days, respectively). Children whose families had contact with a HEAL asthma counselor by 6 months showed a 4.09-day decrease [95% confidence interval (CI): 3.25 to 4.94-day decrease] in symptom days, compared with a 1.79-day decrease (95% CI: 0.90, 2.67) among those who had not yet seen an asthma counselor (p < 0.001). The novel combination of evidence-based asthma interventions was associated with improved asthma symptoms among children in post-Katrina New Orleans. Post-intervention changes in symptoms were consistent with previous randomized trials of NCICAS and ICAS interventions.

Prevalence, severity and risk factors of asthma, rhinitis and eczema in a large group of Chinese schoolchildren.

PubMed

Song, Ning; Shamssain, Mohammed; Mohammed, Shamssain; Zhang, Jin; Wu, Jianling; Fu, Chunling; Hao, Shuting; Guan, Jitao; Yan, Xixin

2014-04-01

There is a lack of information on the prevalence, severity and risk factors of asthma, rhinitis and eczema in Chinese children. To establish baseline data for a major longitudinal study of factors affecting asthma, rhinitis and eczema in a large group of children from the industrialized city of Shijiazhuang, China. We used the International Study of Asthma and Allergies in Childhood questionnaire and studied 10 338 children, ages 6-18, from Shijiazhuang. The prevalence of childhood asthma, rhinitis and eczema is 1.2%, 13.5% and 11.8%, respectively. Boys had higher prevalence of these conditions than girls and younger children had higher prevalence of asthma and eczema but lower prevalence of rhinitis than older children. Breastfed children had lower prevalence of asthma and rhinitis, but not eczema, than non-breastfed children. Overweight children had higher prevalence of asthma and rhinitis than those who were not overweight. Children exposed to paternal smoking had higher prevalence of rhinitis and eczema than those not exposed; children exposed to pets had higher prevalence of asthma and rhinitis than those not exposed. The prevalence of asthma in this study group is low, but the prevalence of rhinitis is high, and could be considered a major public health problem. The prevalence of asthma, rhinitis and eczema is generally higher in boys and younger children generally have higher prevalence of asthma and eczema but lower prevalence of rhinitis. Exposure to pets is a risk factor for rhinitis, being overweight is a risk factor for asthma and rhinitis, and exposure to parental smoking is a risk factor for asthma, rhinitis and eczema in these children.

Achieving Symptom Control in Patients with Moderate Asthma

PubMed Central

Weir, Nargues A.; Levine, Stewart J.

2012-01-01

Disease severity in asthma can be classified as mild, moderate or severe based upon the frequency of symptoms or the severity of airflow obstruction. This review will focus on the treatment of youths greater than 12 years of age and adults with moderate persistent asthma. Moderate asthmatics may have daily symptoms that cause some limitation with normal daily activities and require use of a rescue inhaled short-acting beta2-agonist inhaler or experience nocturnal awakenings secondary to asthma that occur more than once per week. Furthermore, spirometry may reveal airflow obstruction with a reduction in FEV1 to between 60% and 80% of predicted. Although inhaled corticosteroids (ICS) are the primary controller medication used to modify symptoms in moderate asthmatics, additional controller medications, such as inhaled long-acting beta2-agonists (LABA), leukotriene receptor antagonists (LTRA) or theophylline, are often needed to obtain optimal disease control. While the addition of an inhaled LABA to an ICS is very effective at improving disease control in moderate asthma, concerns have arisen over the safety of LABAs, in particular the risk of asthma-related death. Therefore, consideration may be given to initially adding a LTRA, rather than a LABA, to ICS when asthma symptoms are not adequately controlled by ICS alone. Furthermore, individualization of medication regimens, treatment of co-morbid conditions, and patient education are crucial to optimizing compliance with therapy, improving disease control, and reducing the risk of exacerbations. Lastly, the development of new asthma treatments, perhaps based upon personalized medicine, may revolutionize the future treatment of moderate asthma. PMID:22259262

Organising primary health care for people with asthma: the patient's perspective.

PubMed Central

Paterson, C; Britten, N

2000-01-01

BACKGROUND: The 1993 chronic disease management contract encourages United Kingdom general practices to implement a standardised package of care with an emphasis on regular visits to an asthma clinic. AIM: To explore the views of people with asthma about the organisation of asthma care in general practice. METHOD: Semi-structured interviews with 20 patients registered with one practice with a nurse-run asthma clinic. The sample was selected to provide people with a wide range of ages and disease severity, and included parents of children. RESULTS: The age range of the interviewees was five to 87 years (parents of children were interviewed) and half of the interviewees had attended the asthma clinic at some time. In describing how they managed their asthma, people identified their medical care alongside other important factors, such as avoiding smoking and pollution, and a decision to seek medical help was made in the context of all of life's other priorities. People expressed diverse views about the organisation of care, describing how their needs changed over time and how they balanced up several factors in deciding what was best for them. These factors were encompassed by four themes: the accessibility of care, severity of asthma and dealing with uncertainty, self-knowledge and self-management, and expert knowledge and therapeutic relationships. Interviewees were evenly split between wishing to be seen regularly in the clinic and wishing only to attend when needing help. CONCLUSION: Patients required asthma services that allow individual choice and flexibility, and eight service objectives were identified that would cover most people's needs. PMID:10897514

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

PubMed

Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

2018-03-08

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Summary of the 2008 BTS/SIGN British Guideline on the management of asthma.

PubMed

Levy, Mark L; Thomas, Mike; Small, Iain; Pearce, Linda; Pinnock, Hilary; Stephenson, Paul

2009-01-01

The 2008 BTS/SIGN British Guideline on the management of asthma provides comprehensive updated evidence-based guidance on asthma management for healthcare professionals. This primary care-focussed summary has been produced to aid dissemination and implementation of the key guideline messages into primary care. The section on diagnosis emphasises the new integrated symptom-based approach with clinicians using their deductive skills to determine the probability that the patient has asthma. The various tools used for monitoring asthma are discussed. There are sections on both non-pharmacological and pharmacological management of chronic asthma in adults and children. Treatment options for children are subdivided into the under-5s and children aged 5-12 years. Poor asthma control is manifested by exacerbations and acute asthma. Personalised asthma action plans for guided self management should be provided and used when levels of asthma control change. There are sections on difficult asthma and the treatment of exacerbations and acute severe asthma. Various outcome measures for auditing the quality of asthma care are discussed.

The self-reported quality of life of Lithuanian children with asthma was comparable to Western populations.

PubMed

Taminskiene, Vaida; Vaitkaitiene, Egle; Valiulis, Algirdas; Turner, Steve; Hadjipanayis, Adamos; Stukas, Rimantas; Valiulis, Arunas

2018-02-01

Quality of life (QoL) has been widely researched among children with asthma in Western countries, but there is a lack of data from eastern Europe, where the prevalence is relatively low, but hospital admission rates are higher. We evaluated the overall level and major determinants of QoL in Lithuanian children aged 5-11 years with asthma. This study was carried out in six asthma outpatient clinics in the two largest cities of Lithuania from January 2015 to July 2016. The children's QoL was measured using the Pediatric Quality of Life Inventory (PedsQL) asthma module, which was completed by the child and one parent. We collected questionnaires from 226 children (68% boys) with a mean age of eight (±2) years: 65% had mild asthma, 31% had moderate asthma and 4% had severe asthma. One in 10 had been hospitalised in the preceding 6 months. The mean self-reported QoL score was 74 and the parent-reported QoL score was 73. QoL was associated with asthma severity and control, shortness of breath and the child's general health, but not socioeconomic factors. The overall level and major determinants of QoL in children with asthma in Lithuania were comparable with Western populations. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Multidimensional assessment of severe asthma: A systematic review and meta-analysis.

PubMed

Clark, Vanessa L; Gibson, Peter G; Genn, Grayson; Hiles, Sarah A; Pavord, Ian D; McDonald, Vanessa M

2017-10-01

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes. © 2017 Asian Pacific Society of Respirology.

Pruning of the Pulmonary Vasculature in Asthma: The SARP Cohort.

PubMed

Ash, Samuel Y; Rahaghi, Farbod N; Come, Carolyn E; Ross, James C; Colon, Alysha G; Cardet-Guisasola, Juan Carlos; Dunican, Eleanor M; Bleecker, Eugene R; Castro, Mario; Fahy, John V; Fain, Sean B; Gaston, Benjamin M; Hoffman, Eric A; Jarjour, Nizar N; Mauger, David T; Wenzel, Sally E; Levy, Bruce D; San Jose Estepar, Raul; Israel, Elliot; Washko, George R

2018-04-19

Loss of the peripheral pulmonary vasculature, termed vascular pruning, is associated with disease severity in patients with chronic obstructive pulmonary disease. To determine if pulmonary vascular pruning is associated with asthma severity and exacerbations. We measured the total pulmonary blood vessel volume (TBV) and the blood vessel volume of vessels less than 5mm2 in cross sectional area (BV5) and of vessels less than 10mm2 (BV10) in cross sectional area on non-contrast computed tomographic scans of participants from the Severe Asthma Research Program. Lower values of the BV5 to TBV ratio (BV5/TBV) and the BV10 to TBV ratio (BV10/TBV) represented vascular pruning (loss of the peripheral pulmonary vasculature). Compared to healthy controls, severe asthmatics had more pulmonary vascular pruning. Among asthmatics, those with poor asthma control had more pruning than those well-controlled disease. Pruning of the pulmonary vasculature was also associated with lower percent predicted forced expiratory volume in one second and forced vital capacity, greater peripheral and sputum eosinophilia and higher bronchoalveolar lavage SAA/LXA4, but not with low attenuation area or with sputum neutrophilia. Compared with individuals with less pruning, individuals with the most vascular pruning had a 150% greater odds of reporting an asthma exacerbation (OR 2.50; CI: 1.05, 5.98; p=0.039 for BV10/TBV), and reported 45% more asthma exacerbations during follow-up (IRR 1.45; CI: 1.02, 2.06; p=0.036 for BV10/TBV). Pruning of the peripheral pulmonary vasculature is associated with asthma severity, control and exacerbations, as well as with lung function and eosinophilia.

The impact of gender on asthma in the daily clinical practice.

PubMed

Ciprandi, Giorgio; Gallo, Fabio

2018-03-01

It is up-to-date to consider the potential gender impact on a disease. There are few data about gender difference in asthma. Therefore, the present cross-sectional study tested this hypothesis in a real-life setting to investigate possible difference between genders. This study was cross-sectional, considering 554 consecutive outpatients suspected of asthma, who were referred for a first specialist visit. Clinical and functional parameters were evaluated. Females with asthma could have a worse perception of asthma control, assessed by asthma control test (ACT), and more anxiety than asthmatic males. However, there was no difference regarding asthma control grading, asthma severity, and asthma medication use between genders; the differences in lung function were without clinical relevance. In the daily clinical practice, it is relevant to consider gender in the management of asthma.

Internet Telehealth for Pediatric Asthma Case Management: Integrating Computerized and Case Manager Features for Tailoring a Web-Based Asthma Education Program

PubMed Central

Wise, Meg; Gustafson, David H.; Sorkness, Christine A.; Molfenter, Todd; Staresinic, Anthony; Meis, Tracy; Hawkins, Robert P.; Shanovich, Kathleen Kelly; Walker, Nola P.

2008-01-01

This article reports on the development of a personalized, Web-based asthma-education program for parents whose 4- to 12-year-old children have moderate to severe asthma. Personalization includes computer-based tailored messages and a human coach to build asthma self-management skills. Computerized features include the Asthma Manager, My Calendar/Reminder, My Goals, and a tailored home page. These are integrated with monthly asthma-education phone calls from an asthmanurse case manager. The authors discuss the development process and issues and describe the current randomized evaluation study to test whether the yearlong integrated intervention can improve adherence to a daily asthma controller medication, asthma control, and parent quality of life to reduce asthma-related healthcare utilization. Implications for health education for chronic disease management are raised. PMID:16928987

How should treatment approaches differ depending on the severity of asthma?

PubMed

Kupczyk, Maciej; Kuna, Piotr

2017-12-01

Asthma is nowadays regarded as a syndrome of various overlapping phenotypes with defined clinical characteristics, different underlying inflammatory mechanisms, identifiable genetic background, environmental risk factors and possible biomarkers. There are no doubts that due to the diversity of asthma, a 'one size fits all' management of the disease is no longer valid. Areas covered: Nowadays asthma management is based on the control of the disease, and the goals of asthma treatment are defined as good symptom control, decreased future risk of exacerbations, fixed airflow limitation, and side-effects of treatment. Alternative strategies for adjusting asthma treatment such as sputum or exhaled nitric oxide guided protocols have been evaluated and despite some effectiveness, are regarded as impractical in every-day clinical conditions. Further studies in the field of asthma phenotypes/endotypes and biomarkers are warranted with the main goal to define which of those possible subgroups will be useful in clinical practice in regards to the potential allocation of successful treatment. Expert commentary: Despite the availability of guidelines on the diagnosis and management of asthma, it seems that the disease is still not optimally controlled. Addressing unmet needs in every day care, improving education, adherence/compliance and inhalation technique may significantly improve asthma control across all severities of the disease.

Risk of psoriasis in patients with childhood asthma: a Danish nationwide cohort study.

PubMed

Egeberg, A; Khalid, U; Gislason, G H; Mallbris, L; Skov, L; Hansen, P R

2015-07-01

Psoriasis and asthma are disorders driven by inflammation. Psoriasis may carry an increased risk of asthma, but the reverse relationship has not been investigated. To investigate the risk of psoriasis in subjects with childhood asthma in a nationwide Danish cohort. Data on all Danish individuals aged 6-14 years at study entry between 1 January 1997 and 31 December 2011 (n = 1,478,110) were linked at an individual level in nationwide registers. Incidence rates per 10,000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, concomitant medication and comorbidity were estimated by Poisson regression models. There were 21,725 cases of childhood asthma and 6586 incident cases of psoriasis. There were 5697 and 889 incident cases of mild and severe psoriasis, respectively. The incidence rates of overall, mild and severe psoriasis were 4.49, 3.88 and 0.61 for the reference population, and 5.95, 5.18 and 0.83 for subjects with childhood asthma, respectively. The IRRs for overall, mild and severe psoriasis were 3.94 [95% confidence interval (CI) 2.16-7.17], 5.03 (95% CI 2.48-10.21) and 2.27 (95% CI 0.61-8.42) for patients with childhood asthma. Childhood asthma was associated with a significantly increased risk of psoriasis. Further studies are warranted to determine the clinical significance and effects of therapeutic interventions on this association. © 2015 British Association of Dermatologists.

Aerobic capacity and skeletal muscle function in children with asthma.

PubMed

Villa, Fabiane; Castro, Ana Paula Beltran Moschione; Pastorino, Antonio Carlos; Santarém, José Maria; Martins, Milton Arruda; Jacob, Cristina Miuki Abe; Carvalho, Celso Ricardo

2011-06-01

Peripheral muscle strength and endurance are decreased in patients with chronic pulmonary diseases and seem to contribute to patients' exercise intolerance. However, the authors are not aware of any studies evaluating peripheral muscle function in children with asthma. It seems to be implied that children with asthma have lower aerobic fitness, but there are limited studies comparing the aerobic capacity of children with and without asthma. The present study aimed to evaluate muscle strength and endurance in children with persistent asthma and their association with aerobic capacity and inhaled corticosteroid consumption. Forty children with mild persistent asthma (MPA) or severe persistent asthma (SPA) (N=20 each) and 20 children without asthma (control group) were evaluated. Upper (pectoralis and latissimus dorsi) and lower (quadriceps) muscle strength and endurance were assessed, and cardiopulmonary exercise testing was performed. Inhaled corticosteroid consumption during the last 6 and 24 months was also quantified. Children with SPA presented a reduction in peak oxygen consumption (VO(2)) (28.2±8.1 vs 34.7±6.9 ml/kg/min; p<0.01) and quadriceps endurance (43.1±6.7 vs 80.9±11.9 repetitions; p<0.05) compared with the control group, but not the MPA group (31.5±6.1 ml/kg/min and 56.7±47.7 repetitions respectively; p>0.05). Maximal upper and lower muscle strength was preserved in children with both mild and severe asthma (p>0.05). Finally, the authors observed that lower muscle endurance weakness was not associated with reductions in either peak VO(2) (r=0.22, p>0.05) or corticosteroid consumption (r=-0.31, p>0.05) in children with asthma. The findings suggest that cardiopulmonary exercise and lower limb muscle endurance should be a priority during physical training programs for children with severe asthma.

External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma.

PubMed

Wagener, A H; de Nijs, S B; Lutter, R; Sousa, A R; Weersink, E J M; Bel, E H; Sterk, P J

2015-02-01

Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE(NO) show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation. Quantifying the mutual relationships of blood eosinophils, FE(NO), and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma. The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FENO were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC). In the external validation cohort, ROC AUC for blood eosinophils was 89% (p<0.001) and for FE(NO) level 78% (p<0.001) to detect sputum eosinophilia ≥3%. Serum periostin was not able to distinguish eosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, p<0.001). In patients with mild to moderate asthma, as well as patients with more severe asthma, blood eosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma. NTR1846 and NTR2364. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Impact of coping and socioeconomic factors on quality of life in adults with asthma.

PubMed

Adams, Robert J; Wilson, David; Smith, Brian J; Ruffin, Richard E

2004-03-01

The socioeconomic variables of income, race and employment status have been shown to influence health-related quality of life (HRQL) scores in persons with asthma. However, little is known about the impact of other psychological factors or perceptions of economic hardship on HRQL in asthma, despite the known influence these have on general activity levels and emotional perceptions. The aim of the present study was to assess the relationships between psychological and socioeconomic factors and HRQL and on subsequent changes to HRQL over 12 months. Consecutive adult patients with moderate or severe asthma attending outpatient clinics, emergency departments or who were inpatients at two teaching hospitals, completed surveys of clinical status, psychological and socioeconomic variables, and HRQL instruments (SF-36 and Modified Marks Asthma Quality of Life Questionnaire [MAQLQ-M]), at baseline and over 12-months follow-up. Of 343 eligible subjects, survey responses were received from 293 at baseline and 232 at 12-months. Mean age was 42 years (SD 18), 67% were female, 42% had moderate, and 58% severe current asthma clinical status according to the National Asthma Education and Prevention Program guidelines criteria. In random-effects multiple regression models, after adjusting for age, gender, education, income and hospital, significant independent variables associated with each of total MAQLQ-M, SF-36 Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS) scores were avoidance coping, perceived recent financial difficulties and clinical asthma status. Additional independent associations were, for total MAQLQ-M, patient concerns about costs delaying them from seeking care (overall model r(2) = 0.69); for PCS, active coping (r(2) = 0.69) and for MCS, positive evaluations/satisfaction with illness (r(2) = 0.54). Psychological factors, particularly coping styles, need to be taken into account when considering HRQL scores as outcome measures in asthma. Interventions to improve the coping capabilities of individuals with moderate-to-severe asthma may be potentially important areas for improvement of asthma-related HRQL.

Adipose tissue content and distribution in children and adolescents with bronchial asthma.

PubMed

Umławska, Wioleta

2015-02-01

The excess of adipose tissue and the pattern of adipose tissue distribution in the body seem to play an important role in the complicated dependencies between obesity and risk of developing asthma. The aim of the present study was to determine nutritional status in children and adolescents with bronchial asthma with special emphasis on adipose tissue distribution evaluated on the basis of skin-fold thicknesses, and to determine the relationships between patterns of adipose tissue distribution and the course of the disease. Anthropometric data on height, weight, circumferences and skin-fold thicknesses were extracted from the medical histories of 261 children diagnosed with asthma bronchitis. Values for children with asthma were compared to Polish national growth reference charts. Distribution of subcutaneous adipose tissue was evaluated using principal components analysis (PCA). Multivariate linear regression analyses tested the effect of three factors on subcutaneous adipose tissue distribution: type of asthma, the severity of the disease and the duration of the disease. Mean body height in the children examined in this study was lower than in their healthy peers. Mean BMI and skin-fold thicknesses were significantly higher and lean body mass was lower in the study group. Excess body fat was noted, especially in girls. Adipose tissue was preferentially deposited in the trunk in girls with severe asthma, as well as in those who had been suffering from asthma for a longer time. The type of asthma, atopic or non-atopic, had no observable effect on subcutaneous adipose tissue distribution in children examined. The data suggest that long-treated subjects and those with severe bronchial asthma accumulate more adipose tissue on the trunk. It is important to regularly monitor nutritional status in children with asthma, especially in those receiving high doses of systemic or inhaled glucocorticosteroids, and long-term treatment as well. Copyright © 2014 Elsevier Ltd. All rights reserved.

Asthma management in a specialist setting: Results of an Italian Respiratory Society survey.

PubMed

Braido, Fulvio; Baiardini, Ilaria; Alleri, Pietro; Bacci, Elena; Barbetta, Carlo; Bellocchia, Michela; Benfante, Alida; Blasi, Francesco; Bucca, Caterina; Busceti, Maria Teresa; Centanni, Stefano; Colanardi, Maria Cristina; Contoli, Marco; Corsico, Angelo; D'Amato, Maria; Di Marco, Fabiano; Marco, Dottorini; Ferrari, Marta; Florio, Giovanni; Fois, Alessandro Giuseppe; Foschino Barbaro, Maria Pia; Silvia, Garuti; Girbino, Giuseppe; Grosso, Amelia; Latorre, Manuela; Maniscalco, Sara; Mazza, Francesco; Mereu, Carlo; Molinengo, Giorgia; Ora, Josuel; Paggiaro, Pierluigi; Patella, Vincenzo; Pelaia, Girolamo; Pirina, Pietro; Proietto, Alfio; Rogliani, Paola; Santus, Pierachille; Scichilone, Nicola; Simioli, Francesca; Solidoro, Paolo; Terraneo, Silvia; Zuccon, Umberto; Canonica, Giorgio Walter

2017-06-01

Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources. to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting. A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society. The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients). The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately. Copyright © 2017 Elsevier Ltd. All rights reserved.

Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma.

PubMed

Brazier, Peter; Schauer, Uwe; Hamelmann, Eckard; Holmes, Steve; Pritchard, Clive; Warner, John O

2016-01-01

Chronic asthma is a significant burden for individual sufferers, adversely impacting their quality of working and social life, as well as being a major cost to the National Health Service (NHS). Temperature-controlled laminar airflow (TLA) therapy provides asthma patients at BTS/SIGN step 4/5 an add-on treatment option that is non-invasive and has been shown in clinical studies to improve quality of life for patients with poorly controlled allergic asthma. The objective of this study was to quantify the cost-effectiveness of TLA (Airsonett AB) technology as an add-on to standard asthma management drug therapy in the UK. The main performance measure of interest is the incremental cost per quality-adjusted life year (QALY) for patients using TLA in addition to usual care versus usual care alone. The incremental cost of TLA use is based on an observational clinical study monitoring the incidence of exacerbations with treatment valued using NHS cost data. The clinical effectiveness, used to derive the incremental QALY data, is based on a randomised double-blind placebo-controlled clinical trial comprising participants with an equivalent asthma condition. For a clinical cohort of asthma patients as a whole, the incremental cost-effectiveness ratio (ICER) is £8998 per QALY gained, that is, within the £20 000/QALY cost-effectiveness benchmark used by the National Institute for Health and Care Excellence (NICE). Sensitivity analysis indicates that ICER values range from £18 883/QALY for the least severe patients through to TLA being dominant, that is, cost saving as well as improving quality of life, for individuals with the most severe and poorly controlled asthma. Based on our results, Airsonett TLA is a cost-effective addition to treatment options for stage 4/5 patients. For high-risk individuals with more severe and less well controlled asthma, the use of TLA therapy to reduce incidence of hospitalisation would be a cost saving to the NHS.

IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression.

PubMed

Wenzel, Sally E; Balzar, Silvana; Ampleford, Elizabeth; Hawkins, Gregory A; Busse, William W; Calhoun, William J; Castro, Mario; Chung, K Fan; Erzurum, Serpil; Gaston, Benjamin; Israel, Elliot; Teague, W Gerald; Curran-Everett, Douglas; Meyers, Deborah A; Bleecker, Eugene R

2007-03-15

Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown. Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE. Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE. In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately. SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.

Asthma--it hasn't gone away.

PubMed

Hull, James

2012-10-01

Asthma most definitely hasn't gone away. This article provides a review of the Royal College of Physician's conference in March 2012, which progressed attendees' understanding of both the basic science and clinical aspects of asthma care. The article highlights key clinical messages from the programme for general physicians--e.g., how best to approach the assessment of patients with severe asthma.

Occupational exposures associated with work-related asthma and work-related wheezing among U.S. workers.

PubMed

Arif, Ahmed A; Delclos, George L; Whitehead, Lawrence W; Tortolero, Susan R; Lee, Eun S

2003-10-01

National estimates of occupational asthma (OA) in the United States are sparse. Using data from the Third National Health and Nutrition Examination Survey (NHANES III) 1988-1994, we analyzed associations between occupation and work-related asthma and work-related wheezing among U.S. workers. This study identified several occupations that were at risk of developing work-related asthma and/or wheezing, with cleaners and equipment cleaners showing the highest risks. Other major occupations identified were farm and agriculture; entertainment; protective services; construction; mechanics and repairers; textile; fabricators and assemblers; other transportation and material moving occupations; freight, stock, and material movers; and motor vehicle operators. The population attributable risks for work-related asthma and work-related wheezing were 26% and 27%, respectively. This study adds evidence to the literature that identifies work-related asthma as an important public health problem. Several occupations are targeted for additional evaluation and study. Of particular interest are cleaners, which are being increasingly reported as a risk group for asthma. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace. Copyright 2003 Wiley-Liss, Inc.

Practice makes perfect: self-reported adherence a positive marker of inhaler technique maintenance.

PubMed

Azzi, Elizabeth; Srour, Pamela; Armour, Carol; Rand, Cynthia; Bosnic-Anticevich, Sinthia

2017-04-24

Poor inhaler technique and non-adherence to treatment are major problems in the management of asthma. Patients can be taught how to achieve good inhaler technique, however maintenance remains problematic, with 50% of patients unable to demonstrate correct technique. The aim of this study was to determine the clinical, patient-related and/or device-related factors that predict inhaler technique maintenance. Data from a quality-controlled longitudinal community care dataset was utilized. 238 patients using preventer medications where included. Data consisted of patient demographics, clinical data, medication-related factors and patient-reported outcomes. Mixed effects logistic regression was used to identify predictors of inhaler technique maintenance at 1 month. The variables found to be independently associated with inhaler technique maintenance using logistic regression (Χ 2 (3,n = 238) = 33.24, p < 0.000) were inhaler technique at Visit 1 (OR 7.1), device type (metered dose inhaler and dry powder inhalers) (OR 2.2) and self-reported adherent behavior in the prior 7 days (OR 1.3). This research is the first to unequivocally establish a predictive relationship between inhaler technique maintenance and actual patient adherence, reinforcing the notion that inhaler technique maintenance is more than just a physical skill. Inhaler technique maintenance has an underlying behavioral component, which future studies need to investigate. BEHAVIORAL ELEMENT TO CORRECT LONG-TERM INHALER TECHNIQUES: Patients who consciously make an effort to perfect asthma inhaler technique will maintain their skills long-term. Elizabeth Azzi at the University of Sydney, Australia, and co-workers further add evidence that there is a strong behavioral component to patients retaining correct inhaler technique over time. Poor inhaler technique can limit asthma control, affecting quality of life and increasing the chances of severe exacerbations. Azzi's team followed 238 patients to determine the key predictors of inhaler technique maintenance from factors including age, asthma knowledge and perceived future risks. Correct inhaler technique at initial assessment was the strongest predictor of long-term success, but this was strengthened further when patients reported good adherence to their own medication regimen. This suggests that maintaining correct inhaler technique is more than just a physical skill. Careful guidance towards this 'practice makes perfect' approach may improve patients' long-term technique maintenance.

Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study.

PubMed

Albers, Frank C; Müllerová, Hana; Gunsoy, Necdet B; Shin, Ji-Yeon; Nelsen, Linda M; Bradford, Eric S; Cockle, Sarah M; Suruki, Robert Y

2018-02-01

Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice. This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible. The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31-41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7-21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n = 101), 27-37% were omalizumab-eligible and 18% were reslizumab-eligible. Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.

Trial of a "credit card" asthma self-management plan in a high-risk group of patients with asthma.

PubMed

D'Souza, W; Burgess, C; Ayson, M; Crane, J; Pearce, N; Beasley, R

1996-05-01

The "credit card" asthma self-management plan provides the adult asthmatic patient with simple guidelines for the self-management of asthma, which are based on the self-assessment of peak expiratory flow rate recordings and symptoms. The study was a trial of the clinical efficacy of the credit card plan in a high-risk group of asthmatic patients. In this "before-and-after" trial, patients discharged from the emergency department of Wellington Hospital, after treatment for severe asthma were invited to attend a series of hospital outpatient clinics at which the credit card plan was introduced. Questionnaires were used to compare markers of asthma morbidity, requirement for emergency medical care, and medication use during the 6-month period before and after intervention with the credit card plan. Of the 30 patients with asthma who attended the first outpatient clinic, 26 (17 women and 9 men) completed the program. In these 26 participants, there was a reduction in both morbidity and requirement for acute medical services: specifically, the proportion waking with asthma more than once a week decreased from 65% to 23% (p = 0.005) and the proportion visiting the emergency department for treatment of severe asthma decreased from 58% to 15% (p = 0.004). The patients attending the clinics commented favorably on the plan, in particular on its usefulness as an educational tool for monitoring and treating their asthma. Although the interpretation of this study is limited by the lack of a randomized control group, the findings are consistent with other evidence that the credit card asthma self-management plan can be an effective and acceptable system for improving asthma care in a high-risk group of adult patients with asthma.

CCL11 as a potential diagnostic marker for asthma?

PubMed

Wu, Dandan; Zhou, Ji; Bi, Hui; Li, Lingling; Gao, Wei; Huang, Mao; Adcock, Ian M; Barnes, Peter J; Yao, Xin

2014-10-01

Asthma is an inflammatory airway disease characterized by airway eosinophilia, in which CCL11 (eotaxin) plays a crucial role. The aim of study is to determine the elevation of CCL11 levels in bronchoalveolar lavage fluid (BALF), blood, exhaled breath condensate (EBC) and sputum in asthma patients and to identify which medium yields the most significant change in CCL11 level. The databases of PubMed, Embase and Cochrane Centre Register of Controlled Trials were systematically searched from inception to September 2013. Controlled clinical trials that focused on CCL11 concentrations in asthma patients and controls, and their correlations with other asthma indicators were obtained. Data were analysed using Stata 12.0. Thirty studies were included in this investigation. CCL11 levels in blood, EBC and sputum were significantly higher in asthma patients than in healthy subjects. Sputum CCL11 concentrations were significantly elevated in unstable asthma patients versus stable asthma patients and in uncontrolled asthma patients versus partially controlled asthma patients. CCL11 levels in sputum and blood were negatively correlated with the lung function as measured by FEV1% predicted, and were positively correlated with BALF, EBC and sputum eosinophil counts. Similarly, CCL11 concentrations were positively correlated with eosinophil cationic protein in EBC, blood and sputum as well as with interleukin-5 in sputum and fractional exhaled nitric oxide in EBC. Steroid treatment had no significant effect on CCL11 levels. CCL11 is a potentially useful biomarker for the diagnosis and assessment of asthma severity and control, especially in sputum. CCL11 is crucial in eosinophil chemoattraction and activation in asthma pathogenesis. Further studies using anti-CCL11 approaches are needed to confirm a role for CCL11 in asthma pathogenesis particularly in patients with more severe disease.

Long-term CPAP treatment improves asthma control in patients with asthma and obstructive sleep apnoea.

PubMed

Kauppi, Paula; Bachour, Patrick; Maasilta, Paula; Bachour, Adel

2016-12-01

Both asthma and obstructive sleep apnoea cause sleep disturbance, daytime sleepiness and diminished quality of life. Continuous positive airway pressure (CPAP) is efficient in reducing symptoms related to sleep apnoea. Here we report the impact of long-term use of CPAP on asthma symptoms. A survey questionnaire was distributed to all of our obstructive sleep apnoea patients with CPAP therapy in 2013. We used the Finnish version of the Asthma Control Test™ (ACT) and a visual analogue scale (0 = no symptoms, 100 = severe asthma symptoms). Asthma was defined as self-reported physician-diagnosed disease and a special reimbursement for asthma medication by the Social Insurance Institution. We sent 2577 questionnaires and received 1586 answers (61 %). One hundred ninety-seven patients were asthmatics with a prevalence of asthma among CPAP users of 13 %. We studied 152 patients (58 females) whose CPAP therapy was initiated after starting asthma medication. Their mean (SD) age was 62 (10) years, duration of CPAP 5.7 (4.7) years and their CPAP daily use was 6.3 (2.4) h. Self-reported asthma severity decreased significantly from 48.3 (29.6) to 33.1 (27.4) (p < 0.001), and ACT score increased significantly from 15.35 (5.3) to 19.8 (4.6) (p < 0.001) without a significant change in the body mass index (BMI). The percentage of patients using rescue medication daily reduced from 36 to 8 % with CPAP (P < 0.001). We noticed a significant decrease in asthma symptoms with long-term use of CPAP in patients with both asthma and obstructive sleep apnoea.

GWAS and admixture mapping identify different asthma-associated loci in Latinos: The GALA II Study

PubMed Central

Galanter, Joshua M; Gignoux, Christopher R; Torgerson, Dara G; Roth, Lindsey A; Eng, Celeste; Oh, Sam S; Nguyen, Elizabeth A; Drake, Katherine A; Huntsman, Scott; Hu, Donglei; Sen, Saunak; Davis, Adam; Farber, Harold J.; Avila, Pedro C.; Brigino-Buenaventura, Emerita; LeNoir, Michael A.; Meade, Kelley; Serebrisky, Denise; Borrell, Luisa N; Rodríguez-Cintrón, William; Estrada, Andres Moreno; Mendoza, Karla Sandoval; Winkler, Cheryl A.; Klitz, William; Romieu, Isabelle; London, Stephanie J.; Gilliland, Frank; Martinez, Fernando; Bustamante, Carlos; Williams, L Keoki; Kumar, Rajesh; Rodríguez-Santana, José R.; Burchard, and Esteban G.

2013-01-01

Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations and replication of positive associations has been inconsistent. Objective To identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1,893) and healthy controls (n = 1,881) were recruited from five sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest p-value: rs2523924, p < 5 × 10−6). This association replicates in a meta-analysis of the EVE Asthma Consortium (p = 0.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between the 17q21 asthma in Latinos (IKZF3, lowest p-value: rs90792, OR: 0.67, 95% CI 0.61 – 0.75, p = 6 × 10−13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, while genome-wide association confirms the previously identified locus on 17q21. PMID:24406073

Asthma and Ethnic Minorities: Socioeconomic Status and Beyond

PubMed Central

Forno, Erick; Celedón, Juan C.

2009-01-01

Purpose of review We aim to discuss current insights into our understanding of the mechanisms by which socioeconomic status (SES) influences the prevalence and severity of asthma in ethnic minorities. In addition, we review potential risk factors for ethnic disparities in asthma that are not mediated by SES. Recent findings Exposures and factors correlated with ethnicity through SES (e.g. indoor and outdoor air quality, smoke exposure, and access to healthcare) are likely to explain a significant proportion of the observed ethnic differences in asthma morbidity. However, other factors correlated with ethnicity (e.g., genetic variation) can impact ethnic disparities in asthma independently of and/or interacting with SES-related factors. Summary SES is a rough marker of a variety of environmental/behavioral exposures and a very important determinant of differences in asthma prevalence and severity among ethnic minorities in the U.S. However, SES is unlikely to be the sole explanation for ethnic disparities in asthma, which may also be due to differences in genetic variation and gene-by-environment interactions among ethnic groups. PMID:19326508

Cow milk induced allergies (CMA) and asthma in new born.

PubMed

Wang, W; Wu, H-W; Liu, J-F

2016-01-01

The prevalence of asthma and allergic diseases in childhood has increased in several industrialized countries since the second half of the twentieth century. In some countries, the prevalence is still rising, although in others it seems to have plateaued or even decreased. It has been suggested that environmental factors operating prenatally and in early life affect the development of asthma and allergic diseases. Particularly changes in microbial exposure are proposed to play an important role in the development and maturation of the immune system. Thus, the factors that affect microbial exposure, such as mode of delivery and the use of antibiotics, may influence the development of asthma and allergic diseases. Several studies have explored the associations between perinatal factors and children's use of antibiotics and the risk of asthma, with inconsistent findings. The present review article will be focused on the important findings related with factors responsible for above allergic reactions along with asthma in young infants. Also, the influence of cow milk intake will also be taken in account to cover the aspect of cow milk induced allergies and asthma in infants.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma

PubMed Central

Xie, Yuran; Merkel, Olivia M

2015-01-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues has limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases and costimulatory factors that have been reported as targets of siRNA mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages and dendritic cells, which could potentially be applied in asthma therapy. PMID:26148454

Development of a prototype system for statewide asthma surveillance.

PubMed

Deprez, Ronald D; Asdigian, Nancy L; Oliver, L Christine; Anderson, Norman; Caldwell, Edgar; Baggott, Lee Ann

2002-12-01

We developed and evaluated a statewide and community-level asthma surveillance system. Databases and measures included a community prevalence survey, hospital admissions data, emergency department/outpatient clinic visit records, and a physician survey of diagnosis and treatment practices. We evaluated the system in 5 Maine communities varying in population and income. Asthma hospitalizations were high in the rural/low-socioeconomic-status communities studied, although diagnosed asthma was low. Males were more likely than females to experience asthma symptoms, although they were less likely to have been diagnosed with asthma or to have used hospital-based asthma care. Databases were useful for estimating asthma burden and identifying service needs as well as high-risk groups. They were less useful in estimating severity or in identifying environmental risks.

Usefulness of induced sputum eosinophil count to assess severity and treatment outcome in asthma patients

PubMed Central

Bandyopadhyay, Ankan; Roy, Partha P.; Saha, Kaushik; Chakraborty, Semanti; Jash, Debraj; Saha, Debabrata

2013-01-01

Context: Currently treatment decisions in asthma are governed by clinical assessment and spirometry. Sputum eosinophil, being a marker of airway inflammation, can serve as a tool for assessing severity and response to treatment in asthma patients. Aims: To establish correlation between change in sputum eosinophil count and forced expiratory volume in one second (FEV1)% predicted value of asthma patients in response to treatment. In this study, we also predicted prognosis and treatment outcome of asthma patients from baseline sputum eosinophil count. Settings and Design: A longitudinal study was conducted to determine the treatment outcome among newly diagnosed asthma patients who were classified into A (n = 80) and B (n = 80) groups on the basis of initial sputum eosinophil count (A ≥ 3% and B < 3%). Materials and Methods: After starting treatment according to Global Initiative for Asthma Guideline, both A and B groups were evaluated every 15 days interval for the 1st month and monthly thereafter for a total duration of 12 months. In each follow-up visit detailed history, induced sputum eosinophil count and spirometry were done to evaluate severity and treatment outcome. Results: FEV1% predicted of group A asthma patients gradually increased and sputum eosinophil count gradually decreased on treatment. Longer time was required to achieve satisfactory improvement (FEV1% predicted) in asthma patients with sputum eosinophil count ≥3%. There was statistically significant negative correlation between FEV1% predicted and sputum eosinophil count (%) in of group A patients in each follow-up visit, with most significant negative correlation found in 8th visit (r = −0.9237 and P = < 0.001). Change in mean FEV1% (predicted) from baseline showed strong positive correlation (r = 0.976) with change in reduction of mean sputum eosinophil count at each follow-up visits in group A patients. Conclusions: Sputum eosinophil count, being an excellent biomarker of airway inflammation, can serve as a useful marker to assess disease severity, treatment outcome, and prognosis in asthma patients. PMID:23741092

Problematic Exercise in Anorexia Nervosa: Testing Potential Risk Factors against Different Definitions.

PubMed

Rizk, Melissa; Lalanne, Christophe; Berthoz, Sylvie; Kern, Laurence; Godart, Nathalie

2015-01-01

"Hyperactivity" has a wide prevalence range of 31% to 80% in the anorexia nervosa literature that could be partly due to the plethora of definitions provided by researchers in this field. The purpose of this study was two-fold: 1) To assess the variance across prevalence rates of problematic exercise encountered in patients with anorexia nervosa, in relation to seven different definitions found in the literature. 2) To examine how core eating disorder symptoms and the dimensions of emotional profile are associated with these different definitions and the impact of these definitions on the assessment of patients' quality of life. Exercise was evaluated in terms of duration, intensity, type and compulsion using a semi-structured questionnaire administered to 180 women suffering from severe anorexia nervosa. Seven different definitions of problematic exercise were identified in the literature: three entailing a single dimension of problematic exercise (duration, compulsion or intensity) and four combining these different dimensions. Emotional profile scores, obsessive-compulsive symptoms, eating disorder symptomatology, worries and concerns about body shape, self-esteem and quality of life were assessed using several established questionnaires. The prevalence of problematic exercise varied considerably from, 5% to 54%, depending on the number of criteria used for its definition. The type and level of eating disorder symptomatology was found to be associated with several definitions of problematic exercise. Surprisingly, a better self-reported quality of life was found among problematic exercisers compared to non-problematic exercisers in three of the definitions. The different definitions of problematic exercise explain the broad prevalence ranges and the conflicting associations generally reported in the literature between problematic exercise and eating disorder-related psychological parameters. There is an urgent need for a valid consensus on the definition of problematic exercise in anorexia nervosa. This will support the development of further research on the etiology and treatment of problematic exercise.

Asthma phenotypes modify the impact of environmetnal factors on lung function

EPA Science Inventory

Previous studies have examined the role of childhood asthma phenotypes based on clinical history on asthma severity and symptom aggravation by environmental risk factors. The current study focuses on the associations between lung function in childhood and environmental factors an...

The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children.

PubMed

Arikoglu, Tugba; Kuyucu, Semanur; Karaismailoglu, Eda; Batmaz, Sehra Birgul; Balci, Senay

2015-01-01

Recent evidence about the various effects of vitamin D (vit D) on innate and adaptive immunity has led to a search for the role of vit D in asthma. It is postulated that a decrease in cathelicidin, a multifunctional host defense molecule, production due to low vit D status may predispose to infectious complications in children with asthma. The aim of this study was to determine the association of vit D, vit D-binding protein (VDBP) and cathelicidin with acute asthma attacks among children with allergic asthma. This prospective study included 35 patients with acute asthma attack and 32 children with controlled asthma, and all were matched by sampling season, sensitization to mites, and previous severity of asthma. A comprehensive questionnaire about risk factors, blood sampling for 25-hydroxyvitamin D vit D, VDBP, and cathelicidin levels; spirometric indices were used. Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis. The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group (p < 0.001). The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma (p = 0.002). There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels. Risk factors that may influence vit D levels revealed that body mass index (BMI) (p = 0.038), duration of sun exposure (p < 0.001), and amount of dietary vit D (p < 0.001) independently affected serum vit D levels. Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks (p < 0.001, adjusted odds ratio 16.11). Cathelicidin levels showed a significant positive association with asthma attacks and BMI. Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma.

Prevalence of gastro-esophageal reflux disease in patients with difficult to control asthma and effect of proton pump inhibitor therapy on asthma symptoms, reflux symptoms, pulmonary function and requirement for asthma medications.

PubMed

Sandur, V; Murugesh, M; Banait, V; Rathi, P M; Bhatia, S J; Joshi, J M; Kate, A

2014-01-01

The hypothesis that GER can trigger or exacerbate asthma is supported by several clinical trials that have shown amelioration in asthma symptoms and/or an improvement in pulmonary function after antireflux therapy. To investigate the prevalence of GER in patients with difficult to control asthma and to determine the effect of omeprazole on asthma symptoms, reflux symptoms, pulmonary function and on the requirement of asthma medications. Patients with difficult to control asthma were recruited into the study. All patients underwent esophageal manometry and 24 hour esophageal pH monitoring. Pulmonary function tests were done before and after treatment. The severity of asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and reflux symptom score(RSS) respectively before and after treatment. Those who had an abnormal pH study (pH <4 in the distal esophagus for >5% of the time) underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor (omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted based on severity of asthma. Out of 250 asthmatic patients screened, forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%) were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had no reflux symptoms. On 24 hr pH metry, the percentage time pH <4.0 was 10.81 ± 4.72 and 1.11 ± 1.21; Deemester score was 37.65 ± 14.54 and 4.89 ± 6.39 (p-value is 0.0001) in GERD and non-GERD patients respectively.In GERD group, post treatment reflux symptom score(RSS) improved from 22.39 ± 14.99 to 1.04 ± 1.07, pulmonary symptom score(PSS) improved from 27.14 ± 7.49 to 13.82 ± 4.21 and night time asthma symptom score(NASS) improved from 6.71 ± 1.80 to 3.04 ± 1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 ± 0.57 and 4.14 ± 1.97 to 1.47 ± 0.54 and 5.56 ± 1.72, respectively (p-value 0.00114). PPI therapy improves nocturnal asthma symptoms, daytime asthma symptoms, pulmonary function and decreases requirement of asthma medications in these patients.

Comparison of patterns of allergen sensitization among inner-city Hispanic and African American children with asthma.

PubMed

Rastogi, Deepa; Reddy, Mamta; Neugebauer, Richard

2006-11-01

Among Hispanics, the largest minority ethnic group in the United States, asthma prevalence is increasing, particularly in inner-city neighborhoods. Although allergen sensitization among asthmatic African Americans has been extensively studied, similar details are not available for Hispanic children. To examine patterns of allergen sensitization, including the association with illness severity, in asthmatic children overall and in Hispanic and African American children living in a socioeconomically disadvantaged area of New York City. A retrospective medical record review of asthmatic children attending a community hospital in the South Bronx area of New York City was performed. Information abstracted included demographics, asthma severity classification, reported exposures to indoor allergens, and results of allergy testing. Among 384 children in the analysis, 270 (70.3%) were Hispanic and 114 (29.7%) were African American. Sensitization to indoor and outdoor allergens, respectively, did not differ between Hispanic (58.5% and 27.0%) and African American (58.8% and 32.6%) children. Allergen sensitization exhibited a direct, significant association with asthma severity for indoor allergens for the 2 ethnic groups combined and for Hispanics separately but not between asthma severity and outdoor allergens (P < .01). No correlation was found between self-reported allergen exposure and sensitization. Patterns of allergen sensitization among inner-city Hispanic asthmatic children resemble those among African American children, a finding that is likely explained by the similarity in levels of environmental exposures. With the increasing prevalence of asthma among inner-city Hispanic children, skin testing should be used frequently for objective evaluation of asthma in this ethnic group.

Vitamin D and Bronchial Asthma: An overview of the last five years

PubMed Central

Hall, Sannette C.; Agrawal, Devendra K.

2017-01-01

Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations and overall worse outcomes in patients with asthma. Given the increase in the prevalence of asthma over the last few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Several studies have found that low serum levels of vitamin D (< 20 ng/ml) are associated with increased exacerbations, increased airway inflammation, decreased lung function and poor prognosis in asthmatic patients. Results from the in vitro and in vivo studies in animals and human have suggested that supplementation with vitamin D can ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support the beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women and adults have primarily found little-to-no effect of vitamin D supplementation on improved asthma symptoms, onset or progression of the disease. This could be related to the severity of the disease process and other confounding factors. Despite the conflicting data obtained from clinical trials, vitamin D deficiency does influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce anti-inflammatory effects. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in bronchial asthma. PMID:28449868

Medical emergencies: pulmonary embolism and acute severe asthma.

PubMed

Somasundaram, K; Ball, J

2013-01-01

In this, the second of two articles covering specific medical emergencies, we discuss the definitions, epidemiology, pathophysiology, acute and chronic management of pulmonary embolus and acute severe asthma. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

[Control of asthma symptoms and cellular markers of inflammation in induced sputum in children and adolescents with chronic asthma].

PubMed

Ciółkowski, Janusz; Stasiowska, Barbara; Mazurek, Henryk

2009-03-01

After the GINA 2006 publication, asthma therapy is based on control of symptoms. However there are suggestions of monitoring of airway inflammation. Aim of the study was to compare clinical criteria of asthma control with cellular markers of lower airway inflammation in induced sputum in a group of young asthmatics. To assess relationship between sputum eosinophilia, asthma severity and spirometry. A group of 154 young patients with chronic asthma (8-21 years) underwent sputum induction by inhalation of 4,5% saline solution. Sputum induction was effective in 121 patients (78%), and in this group control of clinical symptoms was assessed according to GINA 2006 criteria. Asthma was controlled in 82 subjects (67.8%) and uncontrolled in 39 (32.2%). Patients with controlled asthma had higher FEV1/FVC (79.8 +/- 7.1% vs 74.2 +/- 9.9%; p = 0.004) and MMEF (80.7 +/- 23.0% vs 65.3 +/- 21.8%; p < 0.001) than those with uncontrolled disease, but the average FEV1 (as percent predicted) did not differ between the two groups. Patients with controlled asthma had lower sputum eosinophil count than those with uncontrolled asthma (3.5 +/- 6.3% vs 7.2 +/- 8.7%; p = 0.01), but difference in neutrophil count was borderline (27.3 +/- 15.5% vs 34.5 +/- 21.0%; p = 0.05). High sputum eosinophil count (> 3%) was observed in 24.4% of patients with controlled asthma and in 61.5% with uncontrolled asthma (p < 0.001). Increased sputum neutrophil count was more frequent in a group of uncontrolled asthma (2.4 vs 15.4%; p = 0.022). Mean sputum eosinophil count was lower in patients with mild astma than in patients with moderate-severe disease (3.1 +/- 5.7% vs 7.1% +/- 8.8; p = 0.006). Patients with high sputum eosinophil count had lower FEV1 (89.4 +/- 14.9% vs 94.9 +/- 13.9%; p = 0.047), FEV1/FVC (74.5 +/- 10.1% vs 79.2 +/- 9.3%; p = 0.01) and MMEF (68.7 +/- 23.3% vs 81.7 +/- 23.1%; p = 0.004). In this study of young asthmatics, control of asthma symptoms was observed in 67.8% of patients. However, cellular markers of lower airway inflammation were present in 1/4 of patients with controlled asthma and in 3/4 with uncontrolled disease. Sputum eosinophilia was related to asthma severity. FEV1/FVC and MMEF were more important that FEV1 for estimating control of asthma. Improvement of asthma control scoring is needed as well as availability of simple methods of inflammation monitoring.

Body mass index and risk of hospitalization among adults presenting with asthma exacerbation to the emergency department.

PubMed

Hasegawa, Kohei; Tsugawa, Yusuke; Lopez, Bernard L; Smithline, Howard A; Sullivan, Ashley F; Camargo, Carlos A

2014-11-01

Studies have linked obesity to incident asthma and worse chronic severity/control. However, the relationship between obesity and acute asthma morbidity remains unclear. To determine whether obese adults presenting to the emergency department (ED) with asthma exacerbation are at higher risk of hospitalization compared with normal-weight adults. Multicenter chart review study of 48 EDs across 23 U.S. states. We identified ED patients aged 18 to 54 years with asthma exacerbation during 2011 to 2012. Primary outcome was hospitalization. The analytic cohort comprised 1,227 patients. Of these, 323 patients (27%) were overweight (body mass index [BMI], 25-29.9 kg/m(2)), and 607 (50%) were obese (BMI ≥ 30 kg/m(2)). Among the 607 obese patients, 364 patients (60%) were severely obese (BMI ≥ 35 kg/m(2)). Several markers of chronic severity/control of asthma and acute severity did not differ across BMI groups. By contrast, compared with normal-weight patients, the risk of hospitalization was higher in patients who were overweight (11 vs. 18%; odds ratio [OR], 1.68; 95% confidence interval [CI], 1.05-2.68; P = 0.03) or obese (11 vs. 23%; OR, 2.30; 95% CI, 1.53-3.49; P < 0.001). In the adjusted analysis with multiple imputation, the association lost statistical significance in overweight patients (OR, 1.56; 95% CI, 0.90-2.71; P = 0.11) but persisted in obese patients (OR, 1.69; 95% CI, 1.02-2.81; P = 0.04). The latter finding was driven by an even higher risk of hospitalization in severely obese patients (OR, 1.95; 95% CI, 1.13-3.34; P = 0.02). In this multicenter study of ED patients with asthma exacerbation, we found that obese adults were at a higher risk of hospitalization compared with normal-weight adults.

Bronchial Thermoplasty – Long Term Safety and Effectiveness in Severe Persistent Asthma

PubMed Central

Wechsler, Michael E.; Laviolette, Michel; Rubin, Adalberto S.; Fiterman, Jussara; Lapa e Silva, Jose R.; Shah, Pallav L.; Fiss, Elie; Olivenstein, Ronald; Thomson, Neil C.; Niven, Robert M.; Pavord, Ian D.; Simoff, Michael; Hales, Jeff B.; McEvoy, Charlene; Slebos, Dirk-Jan; Holmes, Mark; Phillips, Martin J.; Erzurum, Serpil C.; Hanania, Nicola A.; Sumino, Kaharu; Kraft, Monica; Cox, Gerard; Sterman, Daniel H.; Hogarth, Kyle; Kline, Joel N.; Mansur, Adel H.; Louie, Brian E.; Leeds, William M.; Barbers, Richard G.; Austin, John H.M.; Shargill, Narinder S.; Quiring, John; Armstrong, Brian; Castro, Mario

2014-01-01

Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective To assess effectiveness and safety of BT in asthma patients 5 years post therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 (AIR2) Trial (ClinicalTrials.gov NCT01350414) were evaluated annually for 5 years to assess long-term safety of BT and durability of treatment effect. Outcomes assessed post-BT included severe exacerbations, adverse events, healthcare utilization, spirometry data, and high resolution computed tomography (HRCT) scans. Results 162/190 BT-treated subjects (85.3%) from the AIR2 Trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and Emergency Room visits, and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months prior to BT treatment (average 5 year reduction in proportions: 44% for exacerbations and 78% for ER visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in Years 2 through 5 as compared to the first year after BT. Pre-BD FEV1 values remained stable between years 1 and 5 after BT, despite a 17% reduction in average daily inhaled corticosteroid dose. HRCT scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ER visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking ICS (inhaled corticosteroids) and LABA (long-acting-β2-agonists). PMID:23998657

Cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability.

PubMed

van Duijvenbode, Neomi; Didden, Robert; VanDerNagel, Joanne El; Korzilius, Hubert Plm; Engels, Rutger Cme

2018-03-01

We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants ( N = 474) were divided into four groups based on IQ and severity of alcohol use-related problems. IQ was estimated using (a short form of) the Wechsler Adult Intelligence Scale third edition. Severity of alcohol use-related problems was assessed using the Alcohol Use Disorder Identification Test. Overall, there were no significant differences between light and problematic drinkers on estimated VIQ. Within the group without MBID, estimated PIQ was significantly lower. Estimated PIQ was not lower in problematic drinkers with MBID compared to light drinkers with MBID. The results are indicative of cognitive deficits in problematic drinkers without MBID. Screening for cognitive deficits with additional instruments is advised.

Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma and COPD

PubMed Central

Doe, Camille; Bafadhel, Mona; Siddiqui, Salman; Desai, Dhananjay; Mistry, Vijay; Rugman, Paul; McCormick, Margaret; Woods, Joanne; May, Richard; Sleeman, Matthew A.; Anderson, Ian K.

2010-01-01

Background: Asthma and COPD are characterized by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease. The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain. Methods: We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects. Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD. Results: The median (interquartile range) IL-17A cells/mm2 submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P = .04). In COPD, IL-17A+ cells/mm2 submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P = .046). IL-17F+ cells/mm2 submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P = .001) but was not increased in subjects with COPD. IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P = .005). The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P < .0001) and was correlated with post-bronchodilator FEV1% predicted (r = −0.5, P = .008) and FEV1/FVC (r = −0.4, P = .04). Conclusions: Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation. PMID:20538817

Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma.

PubMed

Shi, Yu-heng; Shi, Guo-chao; Wan, Huan-ying; Jiang, Li-hua; Ai, Xiang-yan; Zhu, Hai-xing; Tang, Wei; Ma, Jia-yun; Jin, Xiao-yan; Zhang, Bo-ying

2011-07-05

Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4(+) T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells in patients with allergic asthma. Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Th1, Th2, Th17 and CD4(+)CD25(+) Treg cells were determined by flow cytometry. The expression of cytokines in plasma and in the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay. The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4(+)CD25(+) Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells. Imbalances in Th1/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma.

Problematic smartphone use: A conceptual overview and systematic review of relations with anxiety and depression psychopathology.

PubMed

Elhai, Jon D; Dvorak, Robert D; Levine, Jason C; Hall, Brian J

2017-01-01

Research literature on problematic smartphone use, or smartphone addiction, has proliferated. However, relationships with existing categories of psychopathology are not well defined. We discuss the concept of problematic smartphone use, including possible causal pathways to such use. We conducted a systematic review of the relationship between problematic use with psychopathology. Using scholarly bibliographic databases, we screened 117 total citations, resulting in 23 peer-reviewer papers examining statistical relations between standardized measures of problematic smartphone use/use severity and the severity of psychopathology. Most papers examined problematic use in relation to depression, anxiety, chronic stress and/or low self-esteem. Across this literature, without statistically adjusting for other relevant variables, depression severity was consistently related to problematic smartphone use, demonstrating at least medium effect sizes. Anxiety was also consistently related to problem use, but with small effect sizes. Stress was somewhat consistently related, with small to medium effects. Self-esteem was inconsistently related, with small to medium effects when found. Statistically adjusting for other relevant variables yielded similar but somewhat smaller effects. We only included correlational studies in our systematic review, but address the few relevant experimental studies also. We discuss causal explanations for relationships between problem smartphone use and psychopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Current practice in assessment and treatment of bronchial asthma in young males in Italy.

PubMed

Ferrante, E; Pantaleo, C; Quatela, M; Fuso, L; Basso, S; Pistelli, R

2000-10-01

The aim of the study was to evaluate, in a sample of young asthmatics in Italy, the current practice in assessment and treatment of asthma after the publication of guidelines. Young soldiers who declared bronchial asthma at the beginning of the compulsory military service were evaluated. One-hundred and thirty-eight subjects with confirmed asthma were selected. Sixty-seven subjects (48.5%) had had at last one spirometry, and only one subject had underwent peak flow monitoring at home; most of the subjects (96.8%) had had prick tests. More of the 50% of the subjects with bronchial obstruction or with severe bronchial hyperresponsiveness, with clinical moderate or severe asthma, had used only bronchodilators or no therapy at all in the preceding year. In this sample of young asthmatics, the lung function tests were still underutilized for the diagnosis and follow-up of bronchial asthma; moreover, the inhaled anti-inflammatory drugs were still underutilized.

[The impact of psychological variables on the presentation and progress of asthma and patient's cognitive functions].

PubMed

Talarowska, Monika; Florkowski, Antoni; Gałecki, Piotr; Szemraj, Janusz; Zboralski, Krzysztof; Pietras, Tadeusz; Górski, Paweł

2009-01-01

Chronic respiratory system diseases become serious public health problem all over the world. The most prevalent are obstructive diseases (asthma and COPD). The prevalence of asthma is still high and concern patients representing wide range of age and socio-economic status. Despite progress in diagnostic and therapeutic options several studies showed that asthma has an impact on health-related quality of life and patients' coping. Asthma as chronic condition results in limitations of patients activity and social relations. Thus psychosocial variables, which may have an impact on asthma symptoms presentation and disease progress, should be considered. There are only few reports concerning cognitive functions in asthma. The aim of the study was to assess the potential impact of psychosocial factors on asthma symptoms presentation, and cognitive function in asthma patients.

Acute asthma severity identification of expert system flow in emergency department

NASA Astrophysics Data System (ADS)

Sharif, Nurul Atikah Mohd; Ahmad, Norazura; Ahmad, Nazihah; Desa, Wan Laailatul Hanim Mat

2017-11-01

Integration of computerized system in healthcare management help in smoothening the documentation of patient records, highly accesses of knowledge and clinical practices guideline, and advice on decision making. Exploit the advancement of artificial intelligent such as fuzzy logic and rule-based reasoning may improve the management of emergency department in terms of uncertainty condition and medical practices adherence towards clinical guideline. This paper presenting details of the emergency department flow for acute asthma severity identification with the embedding of acute asthma severity identification expert system (AASIES). Currently, AASIES is still in preliminary stage of system validation. However, the implementation of AASIES in asthma bay management is hope can reduce the usage of paper for manual documentation and be a pioneer for the development of a more complex decision support system to smoothen the ED management and more systematic.

The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

PubMed

Lambert, Katrina A; Prendergast, Luke A; Dharmage, Shyamali C; Tang, Mimi; O'Sullivan, Molly; Tran, Thomas; Druce, Julian; Bardin, Philip; Abramson, Michael J; Erbas, Bircan

2017-10-11

It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

The effect of DPP-4 inhibitors on asthma control: an administrative database study to evaluate a potential pathophysiological relationship.

PubMed

Colice, Gene; Price, David; Gerhardsson de Verdier, Maria; Rabon-Stith, Karma; Ambrose, Christopher; Cappell, Katherine; Irwin, Debra E; Juneau, Paul; Vlahiotis, Anna

2017-01-01

DPP-4 may regulate immunological pathways implicated in asthma. Assessing whether DPP-4 inhibitor (DPP-4i) use might affect asthma control is clinically important because DPP-4i use in type 2 diabetes mellitus management (T2DM) is increasing. This study evaluated associations between DPP-4i use and asthma control. This was a retrospective, observational, matched cohort study using administrative claims in the MarketScan ® Commercial Claims and Encounters (Commercial) and Medicare Supplemental and Coordination of Benefits (Medicare Supplemental) databases. Adult asthma patients initiating an oral DPP-4i or a non-DPP-4i between November 1, 2006 and March 31, 2014 were included. Patients were followed for asthma-related outcomes for 12 months after initiation of the antidiabetes medication. Outcomes included risk-domain asthma control (RDAC), defined as no asthma hospitalizations, no lower respiratory tract infections, and no oral corticosteroid (OCS) prescriptions; overall asthma control (RDAC criteria plus limited short-acting beta agonist use); treatment stability (RDAC criteria plus no increase of ≥50% in inhaled corticosteroid dose or addition of other asthma therapy); and severe asthma exacerbation rates (asthma-related hospitalizations, emergency room visits, or acute treatments with OCS). Comparisons were made between two matched cohorts (DPP-4i vs. non-DPP-4i initiators) using multivariable logistic regression and generalized linear modeling. Covariates included baseline demographic and clinical characteristics related to asthma and T2DM. The adjusted odds of achieving RDAC (odds ratio [OR]: 1.05; 95% CI: 0.964 to 1.147), overall asthma control (OR: 1.04; 95% CI: 0.956 to 1.135), and treatment stability (OR: 1.04; 95% CI: 0.949 to 1.115) did not differ between the DPP-4i and non-DPP-4i cohorts. A difference was not found between cohorts in severe asthma exacerbation rates during the 12 months following initiation of antidiabetes treatment (mean = 0.32 vs. 0.34 exacerbations per subject-year, respectively; p =0.064). Asthma control was similar between patients initiating DPP-4i and non-DPP-4i antidiabetes medications, suggesting no association between DPP-4i use and asthma control.

Insulin resistance, metabolic syndrome, and lung function in US adolescents with and without asthma.

PubMed

Forno, Erick; Han, Yueh-Ying; Muzumdar, Radhika H; Celedón, Juan C

2015-08-01

Obesity increases both the risk of asthma and asthma severity and is a well-known risk factor for insulin resistance and the metabolic syndrome (MS) in children and adolescents. We aimed to examine the association among obesity, insulin sensitivity, MS, and lung function in US adolescents with and without asthma. We performed a cross-sectional study of 1429 adolescents aged 12 to 17 years in the 2007-2010 National Health and Nutrition Examination Survey. Adjusted regression was used to assess the relationships among obesity, insulin sensitivity/resistance, MS, and lung function in children with and without asthma. Insulin resistance was negatively associated with FEV1 and forced vital capacity (FVC) in adolescents with and without asthma, whereas MS was associated with lower FEV1/FVC ratios, with a more pronounced decrease found among asthmatic patients; these associations were driven by overweight/obese adolescents. Higher body mass index was associated with a decrease in FEV1/FVC ratios among adolescents with insulin resistance. Compared with healthy participants, adolescents with MS had an approximately 2% decrease in FEV1/FVC ratios, adolescents with asthma had an approximately 6% decrease, and those with MS and asthma had approximately 10% decreased FEV1/FVC ratios (P < .05). Insulin resistance and MS are associated with worsened lung function in overweight/obese adolescents. Asthma and MS synergistically decrease lung function, as do obesity and insulin resistance. These factors might contribute to the pathogenesis of asthma severity in obese patients and warrant further investigation. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Food allergy and asthma morbidity in children.

PubMed

Simpson, Alyson B; Glutting, Joe; Yousef, Ejaz

2007-06-01

Coexisting food allergy and asthma is a significant problem in the pediatric population. Studies have looked at the association between food sensitization and asthma severity. It is unknown whether specific food allergies are associated with increased asthma morbidity. We studied the independent effect that allergy to egg, milk, fish, and peanut has on the number of hospitalizations and courses of systemic steroids in children with asthma. We performed a medical record review to evaluate the effect food allergy to egg, fish, peanut, and milk has on asthma morbidity. We reviewed the records of 201 children aged 3 months to 14 years with the diagnosis of asthma (ICD-9 codes 493.90, 493.91, and 493.92), of which 88 had coexistent food allergy. All children in the food allergy group had food-specific IgE concentrations greater than the 95% positive predictive value. We compared the rate of hospitalizations and use of systemic steroids between children with asthma and food allergies and those without coexisting food allergy using direct-entry, multiple regression analysis. Patients were adjusted for the severity of their asthma based on symptoms documented at their first visit to the allergist according to the National Asthma Education and Prevention Program guidelines and presence of environmental allergy, eczema, smoke exposure, and gastroesophageal reflux. Peanut and milk allergies were both associated with increased number of hospitalizations (P=0.009, 0.016), and milk allergy was associated with increased use of systemic steroids (P=0.001). Peanut and milk allergies were associated with increased hospitalization and steroid use and may serve as early markers for increased asthma morbidity. (c) 2007 Wiley-Liss, Inc.

Prevalence of childhood asthma in Ulaanbaatar, Mongolia in 2009.

PubMed

Yoshihara, Shigemi; Munkhbayarlakh, Sonomjants; Makino, Sohei; Ito, Clyde; Logii, Narantsetseg; Dashdemberel, Sarangerel; Sagara, Hironori; Fukuda, Takeshi; Arisaka, Osamu

2016-01-01

Bronchial asthma is a common but important chronic disease in children in all over the world. To take measures against prevalence of childhood asthma, many researchers have surveyed the actual statuses of childhood asthma in developed countries, but in most Asia-Pacific developing countries including Mongolia such surveys have never been sufficiently conducted until now. We have thought that this survey, though performed in 2009, will give important and meaningful information even now in taking measures to prevent prevailing bronchial asthma in children in Mongolia or the countries under similar statuses. The asthma prevalence and patient background information in Mongolian children aged 6-7 living in Ulaanbaatar were examined using a written questionnaire modified for their parents from that prepared by the International Study of Asthma and Allergies in Childhood (ISAAC). The estimated prevalence of asthma in Mongolian children was 20.9%. The following 3 risk factors were found to be related to asthma: (1) having allergic rhinitis symptoms, (2) mothers' smoking, and (3) history of severe respiratory infection before 1-year-old. The asthma prevalence in Mongolian children was higher than that in the world and Asia-Pacific countries reported by ISAAC. The higher prevalence was probably attributable to households' (especially mothers) smoking in draft-free houses designed for the cold area and severe air-pollution due to rapid industrialization and urbanization in Mongolia. Smoking prohibition in the mother (including family members) and a reduction of exposure to air pollutants are urgently needed to prevent developing childhood asthma. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Age related IgG subclass concentrations in asthma.

PubMed

Hoeger, P H; Niggemann, B; Haeuser, G

1994-03-01

The prevalence of IgG subclass deficiency in asthma is still controversial. Earlier studies often included patients receiving treatment with systemic steroids which can induce hypogammaglobulinaemia. Concentrations of IgG subclasses were studies in 200 children (aged 2-17 years) with asthma (mean asthma severity score (ASS) 2, range 1-4) who had not received systemic steroids for at least six weeks before investigation, and in 226 healthy age matched controls. The mean concentrations of IgG subclasses in children with asthma were within the 1SD range of those of the control group. In the group with asthma there was a trend towards higher levels of IgG1 and IgG4, whereas the number of children with low concentrations of IgG2 (< 2 SD of control serum samples; absolute concentrations 0.08-1.25 g/l) was slightly greater than in the group who did not have asthma (4.5 v 2.2%). Patients with subnormal concentrations of IgG2 could not be distinguished clinically or on the basis of case history and additional immunological studies did not show further abnormalities. Patients with severe asthma (ASS 3-4) had significantly higher concentrations of IgG4 (mean (SE) 0.53 (0.09) v 0.26 (0.04) g/l) than patients with mild asthma (ASS 1). No significant difference in subclass concentration was found between patients with atopic and those with non-atopic asthma. It is concluded that in an unselected group of children with asthma the mean IgG subclass concentrations do not differ significantly from a group of healthy age matched controls.

Influence of obesity on bone mineral density in postmenopausal asthma patients undergoing treatment with inhaled corticosteroids.

PubMed

Yanik, Burcu; Ayrim, Aylin; Ozol, Duygu; Koktener, Asli; Gokmen, Derya

2009-01-01

The etiology of osteoporosis in asthma is complex as various factors contribute to its pathogenesis. The purpose of our study was to investigate the effects of obesity and inhaled steroids, as well as the severity and duration of asthma, on osteoporosis in postmenopausal asthma patients as compared to healthy controls. A total of 46 patients with asthma and 60 healthy female controls, all postmenopausal, were enrolled in our study. Bone mineral density was assessed at the lumbar spine and hip using a Lunar DPX-L densitometer. Bone mineral density (BMD) scores were comparable between the asthmatic and control groups, with average scores of 0.95 +/- 0.29 and 0.88 +/- 0.14 g/cm(2), respectively. Likewise, osteoporosis was diagnosed in a similar percentage of patients in the asthmatic (39.1%) and control (43.3%) groups. Bone fracture was identified in four patients with asthma (8.6%) and in six patients from the control group (10%). We could not detect any relationship between BMD and duration of asthma, asthma severity, inhaled steroids or body mass index (BMI). There was no difference between the two groups with respect to age or years since menopause. Although asthma patients were more likely to be overweight and presented higher BMD scores on average than the control subjects, these differences were not statistically significant. There is a slight positive protective effect of high BMI against osteoporosis in asthma patients, but this effect is overcome by time and menopause status. Therefore, the protective effect of obesity against osteoporosis in asthma patients seems to not be significant.

Occupational agriculture organic dust exposure and its relationship to asthma and airway inflammation in adults.

PubMed

Wunschel, Javen; Poole, Jill A

2016-06-01

Recent studies have made advances into understanding the complex agriculture work exposure environment in influencing asthma in adults. The objective of this study is to review studies of occupational agricultural exposures including dust, animal, and pesticide exposures with asthma in adult populations. PubMed databases were searched for articles pertaining to farming, agriculture, asthma, occupational asthma, airway inflammation, respiratory disease, lung disease, pesticides, and organic dust. Studies chosen were published in or after 1999 that included adults and asthma and farming/agricultural work or agricultural exposures and airway inflammatory disease measurements. The data remain inconclusive. Several retrospective studies demonstrate agricultural work to be protective against asthma in adults, especially with increased farming exposure over time. In contrast, other studies find increased risk of asthma with farming exposures, especially for the non-atopic adult. Mechanistic and genetic studies have focused on defining the wide variety and abundance of microorganisms within these complex organic dusts that trigger several pattern recognition receptor pathways to modulate the hosts' response. Asthma risk depends on the interplay of genetic factors, gender, atopic predisposition, type of livestock, pesticide exposure, and magnitude and duration of exposure in the adult subject. Longer exposure to occupational farming is associated with decreased asthma risk. However, studies also suggest that agricultural work and multiple types of livestock are independent risk factors for developing asthma. Prospective and longitudinal studies focusing on genetic polymorphisms, objective assessments, and environmental sampling are needed to further delineate the influence of agriculture exposure in the adult worker.

Beginning school with asthma independently predicts low achievement in a prospective cohort of children.

PubMed

Liberty, Kathleen A; Pattemore, Philip; Reid, James; Tarren-Sweeney, Michael

2010-12-01

Concerns about the achievement of children with asthma and respiratory conditions are especially important in New Zealand, which has one of the world's highest rates of childhood asthma. The present study evaluated whether entering school with asthma was associated with low achievement after the first year. A child cohort was recruited to a prospective study at time of first enrollment into randomly selected schools in Christchurch. Parent interviews covered demographics and respiratory status. Physician reports were sought for children with asthma, and all respiratory information was clinically reviewed. The children's achievement in reading and math was individually assessed at school entry and reassessed after 12 months. Schools reported absences. Intelligence subtests were administered. Two hundred ninety-eight children were recruited, including 55 (18.5%) with current asthma. At 1-year follow-up, retention was 93.7%. Children who entered school with asthma were more likely to be ≥ 6 months behind other participants in reading words (P = .023) and books (P = .026), but not in math (P = .167) at the end of the first year of school. Achievement was not related to asthma severity. Entering school with asthma reliably predicted low reading achievement independent of other known covariates of low achievement (high absenteeism, minority status, male gender, single-parent family, poor academic skills at school entry, and low socioeconomic status). Entering school with asthma was a significant predictor of low achievement in reading at 12-month follow-up, independent of asthma severity, high absenteeism, or other covariates of low achievement.

Vitamin D as an adjunctive therapy in asthma. Part 2: A review of human studies.

PubMed

Kerley, Conor P; Elnazir, Basil; Faul, John; Cormican, Liam

2015-06-01

Vitamin D deficiency (VDD) is highly prevalent worldwide, with adverse effects on bone health but also potentially other unfavorable consequences. VDD and asthma-incidence/severity share many common risk factors, including winter season, industrialization, poor diet, obesity, dark skin pigmentation, and high latitude. Multiple anatomical areas relevant to asthma contain both the enzyme responsible for producing activated vitamin D and the vitamin D receptor suggesting that activated vitamin D (1,25-dihydroxyvitamin D) may have important local effects at these sites. Emerging evidence suggests that VDD is associated with increased airway hyperresponsiveness, decreased pulmonary function, worse asthma control, and possibly decreased response to standard anti-asthma therapy. However the effect is inconsistent with preliminary evidence from different studies suggesting vitamin D is both beneficial and detrimental to asthma genesis and severity. Current evidence suggests that supplementation with moderate doses of vitamin D may be appropriate for maintenance of bone health in asthmatics, particularly steroid users. However emerging data from an increasing number of randomized, controlled, intervention studies of vitamin D supplementation in pediatric and adult asthma are becoming available and should help determine the importance, if any of vitamin D for asthma pathogenesis. The purpose of this second of a two-part review is to review the current human literature on vitamin D and asthma, discussing the possible consequences of VDD for asthma and the potential for vitamin D repletion as adjunct therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma.

PubMed

Menezes, Ana Maria B; Montes de Oca, Maria; Pérez-Padilla, Rogelio; Nadeau, Gilbert; Wehrmeister, Fernando César; Lopez-Varela, Maria Victorina; Muiño, Adriana; Jardim, José Roberto B; Valdivia, Gonzalo; Tálamo, Carlos

2014-02-01

Several COPD phenotypes have been described; the COPD-asthma overlap is one of the most recognized. The aim of this study was to evaluate the prevalence of three subgroups (asthma, COPD, and COPD-asthma overlap) in the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) study population, to describe their main characteristics, and to determine the association of the COPD-asthma overlap group with exacerbations, hospitalizations, limitations due to physical health, and perception of general health status (GHS). The PLATINO study is a multicenter population-based survey carried out in five Latin American cities. Outcomes were self-reported exacerbations (defined by deterioration of breathing symptoms that affected usual daily activities or caused missed work), hospitalizations due to exacerbations, physical health limitations, and patients' perception of their GHS obtained by questionnaire. Subjects were classified in three specific groups: COPD--a postbronchodilator (post-BD) FEV₁/FVC ratio of < 0.70; asthma--presence of wheezing in the last year and a minimum post-BD increase in FEV₁ or FVC of 12% and 200 mL; and overlap COPD-asthma--the combination of the two. Out of 5,044 subjects, 767 were classified as having COPD (12%), asthma (1.7%), and COPD-asthma overlap (1.8%). Subjects with COPD-asthma overlap had more respiratory symptoms, had worse lung function, used more respiratory medication, had more hospitalization and exacerbations, and had worse GHS. After adjusting for confounders, the COPD-asthma overlap was associated with higher risks for exacerbations (prevalence ratio [PR], 2.11; 95% CI, 1.08-4.12), hospitalizations (PR, 4.11; 95% CI, 1.45-11.67), and worse GHS (PR, 1.47; 95% CI, 1.18-1.85) compared with those with COPD. The coexisting COPD-asthma phenotype is possibly associated with increased disease severity.

Effect of catastrophic wildfires on asthmatic outcomes in obese children: breathing fire.

PubMed

Tse, Kevin; Chen, Lie; Tse, Mabel; Zuraw, Bruce; Christiansen, Sandra

2015-04-01

Air pollutants from wildfires and obesity independently exacerbate asthma, yet no study has determined the combined effects of these 2 variables on asthma outcomes. To determine the effect of 2 catastrophic wildfires affecting the Southern California region (in 2003 and 2007) on several asthma outcomes in a cohort of children. To investigate the association between wildfire exposure and asthma outcomes, we stratified our study population by body mass index categories (underweight, normal, overweight, and obese) and zip codes (to distinguish individuals who were closer to the fires vs farther away). The primary outcome was the prevalence of physician-dispensed short-acting β-agonist (SABAs). Secondary outcomes included the rate of emergency department visits and/or hospitalizations for asthma, the frequency of oral corticosteroid use for asthma, and number of new diagnoses of asthma. A total of 2,195 and 3,965 asthmatic children were analyzed as part of our retrospective cohort during the 2003 and 2007 wildfires, respectively. SABA dispensing increased the most in the obese group after the 2003 wildfires (P < .05). Increased prevalence of SABA dispensing was also noted in the obese group in 2007, but this was not statistically higher than the increases seen in other body mass index groups. There was no observed increase in emergency department and/or hospitalization rates, oral corticosteroid dispensing frequency, or new asthma diagnoses after either wildfire. Catastrophic wildfires lead to worsening asthma outcomes, particularly in obese individuals. This study gives further evidence of a link between obesity and asthma severity and suggests that air pollutants released during wildfires can have substantial detrimental effects on asthma control. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clinical deterioration in pediatric asthmatic patients after September 11, 2001.

PubMed

Szema, Anthony M; Khedkar, Meera; Maloney, Patrick F; Takach, Patricia A; Nickels, Michael S; Patel, Harshit; Modugno, Francesmary; Tso, Alan Y; Lin, Deborah H

2004-03-01

New York City residents were exposed to a variety of inhaled substances after the collapse of the World Trade Center. Exposure to these substances might lead to an increase in asthma severity, with residential distance from Ground Zero predictive of the degree of change. We sought to assess the effect of the World Trade Center collapse on local pediatric asthmatic patients. We retrospectively reviewed the charts of 205 pediatric patients with established asthma from a clinic in lower Manhattan's Chinatown. Clinical data were obtained for the year before and the year after September 11, 2001. Measurements included numbers of visits, asthma medication prescriptions, oral corticosteroid prescriptions, weekly doses of rescue inhaler, and peak expiratory flow rates. Residential zip codes were used to compare the asthma severity of patients living within and beyond a 5-mile radius of Ground Zero. After September 11, 2001, these children had more asthma-related clinic visits (P = .002) and received more prescriptions for asthma medications (P = .018). No significant differences in oral steroid or rescue inhaler use were noted. Those living within 5 miles had more clinic visits after September 11, 2001 (P = .013); the increase in clinic visits for patients living more than 5 miles from Ground Zero was not significant. Mean percent predicted peak expiratory flow rates decreased solely for those patients living within 5 miles of Ground Zero during the 3 months after September 11, 2001. Asthma severity worsened after September 11, 2001, in pediatric asthmatic patients living near Ground Zero. Residential proximity to Ground Zero was predictive of the degree of decrease in asthma health.

The clinical features of the overlap between COPD and asthma

PubMed Central

2011-01-01

Background The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. Methods We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study. Results 119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness. Conclusion Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history. Trial registration ClinicalTrials.gov: NCT00608764 PMID:21951550

Phenotypes of asthma revisited upon the presence of atopy.

PubMed

Nieves, Ana; Magnan, Antoine; Boniface, Stéphanie; Proudhon, Hervé; Lanteaume, André; Romanet, Stéphanie; Vervloet, Daniel; Godard, Philippe

2005-03-01

Immunological studies claimed that atopic and non-atopic asthma share more similarities than differences. However, these two phenotypes of asthma are considered to be distinguishable upon distinct clinical patterns, which were not systematically assessed before in a large population. We studied characteristics discriminating atopic from non-atopic asthma among 751 asthmatic patients and 80 factors were analysed in univariate and multivariate analysis. Age, age of onset of asthma, female/male ratio were higher in non-atopic (n=200) than in atopic (n=551) asthmatics. Familial asthma, seasonal symptoms, rhinitis, conjunctivitis, allergen-triggered symptoms, improvement in altitude, exercise-induced asthma were associated with atopy. Non-atopic asthmatics displayed lower FEV(1) and FVC. Smoking was more frequent and asthma was more severe in these patients. Younger age, early onset, male sex, rhinitis and smoking were independent factors discriminating atopic from non-atopic asthma. This study establishes in a large population of asthmatics that although similarities exist between atopic and non-atopic asthma, two clinical phenotypes can still distinguish both kinds of asthma.

An international observational prospective study to determine the cost of asthma exacerbations (COAX).

PubMed

Lane, Stephen; Molina, Jesus; Plusa, Tadeusz

2006-03-01

Asthma is a common chronic condition that places substantial burden on patients and healthcare services. Despite the standards of asthma control that international guidelines recommend should be achieved, many patients continue to suffer sub-optimal control of symptoms and experience exacerbations (acute asthma attacks). In addition to being associated with reduced quality of life, asthma exacerbations are a key cost driver in asthma management. Routine clinical practice for the management of asthma exacerbations varies in different healthcare systems, so healthcare providers require local costs to be able to assess the value of therapies that reduce the frequency and severity of exacerbations. This prospective study, conducted in a total of 15 countries, assessed the local cost of asthma exacerbations managed in either primary or secondary care. Healthcare resources used were costed using actual values appropriate to each country in local currency and in Euros. Results are presented for exacerbations managed in primary care in Brazil, Bulgaria, Croatia, Czech Republic, Hungary, Poland, Russia, Slovakia, Slovenia, Spain and Ukraine, and in secondary care in Croatia, Denmark, Ireland, Latvia, Norway, Poland, Russia, Slovakia, Slovenia and Spain. Multiple regression analysis of the 2052 exacerbations included in the economic analysis showed that the cost of exacerbations was significantly affected by country (P<0.0001). Mean costs were significantly higher in secondary care (euro 1349) than primary care (euro 445, P=0.0003). Age was a significant variable (P=0.0002), though the effect showed an interaction with care type (P<0.0001). As severity of exacerbation increased, so did secondary care costs, though primary care costs remained essentially constant. In conclusion, the study showed that asthma exacerbations are costly to manage, suggesting that therapies able to increase asthma control and reduce the frequency or severity of exacerbations may bring economic benefits, as well as improved quality of life.

A review of barriers to effective asthma management in Puerto Ricans: cultural, healthcare system and pharmacogenomic issues.

PubMed

Alicea-Alvarez, Norma; Swanson-Biearman, Brenda; Kelsen, Steven G

2014-02-01

Among the Hispanic community, Puerto Ricans have the highest prevalence of asthma and manifest the worst outcomes. The expected growth of the Hispanic population in the USA in the next several decades make elimination of disparate care in Puerto Rican asthmatics a matter of national importance. The purpose of this review of the literature (ROL) is to examine a variety of health system, genetic and cultural barriers in the Puerto Rican community which have created disparities in asthma care and outcomes among adult and pediatric Hispanic populations. In addition, this ROL describes several culturally sensitive, community-based educational interventions which can be used as a framework for future projects to improved asthma outcomes. Databases searched included Medline, PubMED, EBSCOhost, PsycINFO, CINAHL, Google Scholar and ERIC. Papers published in English from January 1990 to January 2012 were reviewed. Health system policies, insurer compensation patterns, clinician attitudes and cultural values/folk remedies in the Puerto Rican community represent barriers to effective asthma management, the use of controller medication and the implementation of educational interventions. In addition, genetic factors involving the beta-2 adrenergic receptor gene, which impair the response to albuterol, appear to contribute to poorer outcomes in Puerto Rican asthmatics. In contrast, several comprehensive, community-based, culturally sensitive educational interventions such as Controlling Asthma in American Cities Project (CAACP), the Racial and Ethnic Approach to Community Health in the US Program and Healthy Hoops programs (REACH) have been described. We believe that culturally sensitive community-based asthma education programs can serve as models for programs targeted toward Puerto Ricans to help decrease asthma morbidity. Moreover, greater sensitivity to Puerto Rican mores and folk remedies on the part of healthcare providers may improve the patient-clinician rapport and, hence, asthma outcomes. Finally, given ethnically based differences in pharmacogenomics, clinical trials targeting the Puerto Rican population may help to better define optimal asthma medication regimens in this ethnic group.

Functional variants of the sphingosine-1-phosphate receptor 1 gene associate with asthma susceptibility.

PubMed

Sun, Xiaoguang; Ma, Shwu-Fan; Wade, Michael S; Flores, Carlos; Pino-Yanes, Maria; Moitra, Jaideep; Ober, Carole; Kittles, Rick; Husain, Aliya N; Ford, Jean G; Garcia, Joe G N

2010-08-01

The genetic mechanisms underlying asthma remain unclear. Increased permeability of the microvasculature is a feature of asthma, and the sphingosine-1-phosphate receptor (S1PR1) is an essential participant regulating lung vascular integrity and responses to lung inflammation. We explored the contribution of polymorphisms in the S1PR1 gene to asthma susceptibility. A combination of gene resequencing for single nucleotide polymorphism (SNP) discovery, case-control association, functional evaluation of associated SNPs, and protein immunochemistry studies was used. Immunohistochemistry studies demonstrated significantly decreased S1PR1 protein expression in pulmonary vessels in lungs of asthmatic patients compared with those of nonasthmatic subjects (P < .05). Direct DNA sequencing of 27 multiethnic samples identified 39 S1PR1 variants (18 novel SNPs). Association studies were performed based on genotyping results from cosmopolitan tagging SNPs in 3 case-control cohorts from Chicago and New York totaling 1,061 subjects (502 cases and 559 control subjects). The promoter SNP rs2038366 (-1557G/T) was found to be associated with asthma (P = .03) in European Americans. In African Americans an association was found for both asthma and severe asthma for intronic SNP rs3753194 (c.-164+170A/G; P = .006 and P = .040, respectively) and for promoter SNP rs59317557 (-532C/G) with severe asthma (P = .028). Consistent with predicted in silico functionality, alleles of the promoter SNPs rs2038366 (-1557G/T) and rs59317557 (-532C/G) influenced the activity of a luciferase S1PR1 reporter vector in transfected endothelial cells exposed to growth factors (epidermal growth factor, platelet-derived growth factor, and vascular endothelial growth factor) known to be increased in asthmatic airways. These data provide strong support for a role for S1PR1 gene variants in asthma susceptibility and severity. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Decreased FOXP3 mRNA expression in children with atopic asthma and IgE-mediated food allergy.

PubMed

Krogulska, Aneta; Polakowska, Ewa; Wąsowska-Królikowska, Krystyna; Małachowska, Beata; Młynarski, Wojciech; Borowiec, Maciej

2015-11-01

The role of T regulatory lymphocytes has been investigated in various allergic diseases. However, the precise relation between the phenotype and severity of allergic diseases and the changes in FOXP3 mRNA expression are not fully understood. To compare the expression of FOXP3 mRNA in children with asthma with and without concomitant food allergy (FA) with healthy children and children with only FA. The study included 82 children: 15 with atopic asthma and IgE-dependent FA, 27 with atopic asthma without FA, 20 with IgE-dependent FA without asthma, and 20 healthy children without atopy. Reverse transcription was performed using a commercially available High Capacity cDNA Archive Kit (Applied Biosystems, Carlsbad, California). Analysis was carried out with a 7900HT real-time polymerase chain reaction system (Applied Biosystems). The average level of the FOXP3 gene expression in children with allergy was significantly lower compared with healthy children (2.2 ± 1.3 vs 4.2 ± 4.2; P = .014). The lowest mean level of FOXP3 mRNA expression (1.9 ± 1.6) was recorded in children with asthma and FA, and the highest level (4.2 ± 4.2) was recorded in healthy children without atopy (P = .036). A milder course of asthma or the degree of allergic reaction after a food challenge was associated with higher FOXP3 mRNA expression. Significantly lower levels of FOXP3 gene expression, observed more commonly in children with asthma and IgE-dependent FA than in healthy controls, were associated with a more severe clinical course. Therefore, FOXP3 expression could serve as an indicator of severe asthma with concomitant atopic conditions such as IgE-dependent FA. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Poor symptom control is associated with reduced CT scan segmental airway lumen area in smokers with asthma.

PubMed

Thomson, Neil C; Chaudhuri, Rekha; Spears, Mark; Messow, Claudia-Martina; MacNee, William; Connell, Martin; Murchison, John T; Sproule, Michael; McSharry, Charles

2015-03-01

Cigarette smoking is associated with worse symptoms in asthma and abnormal segmental airways in healthy subjects. We tested the hypothesis that current symptom control in smokers with asthma is associated with altered segmental airway dimensions measured by CT scan. In 93 subjects with mild, moderate, and severe asthma (smokers and never smokers), we recorded Asthma Control Questionnaire-6 (ACQ-6) score, spirometry (FEV1; forced expiratory flow rate, midexpiratory phase [FEF(25%-75%)]), residual volume (RV), total lung capacity (TLC), and CT scan measures of the right bronchial (RB) and left bronchial (LB) segmental airway dimensions (wall thickness, mm; lumen area, mm²) in the RB3/LB3, RB6/LB6, and RB10/LB10 (smaller) airways. The CT scan segmental airway (RB10 and LB10) lumen area was reduced in smokers with asthma compared with never smokers with asthma; RB10, 16.6 mm² (interquartile range, 12.4-19.2 mm²) vs 19.6 mm² (14.7-24.2 mm²) (P = .01); LB10, 14.8 mm² (12.1-19.0 mm²) vs 19.9 mm² (14.5-25.0 mm²) (P = .003), particularly in severe disease, with no differences in wall thickness or in larger airway (RB3 and LB3) dimensions. In smokers with asthma, a reduced lumen area in fifth-generation airways (RB10 or LB10) was associated with poor symptom control (higher ACQ-6 score) (-0.463 [-0.666 to -0.196], P = .001, and -0.401 [-0.619 to -0.126], P = .007, respectively) and reduced postbronchodilator FEF(25%-75%) (0.521 [0.292-0.694], P < .001, and [0.471 [0.236-0.654], P = .001, respectively) and higher RV/TLC %. The CT scan segmental airway lumen area is reduced in smokers with asthma compared with never smokers with asthma, particularly in severe disease, and is associated with worse current symptom control and small airway dysfunction.

Health Disparities in Pediatric Asthma: Comprehensive Tertiary Care Center Experience.

PubMed

Holmes, Laurens; Kalle, Fanta; Grinstead, Laura; Jimenez, Maritza; Murphy, Meghan; Oceanic, Pat; Fitzgerald, Diane; Dabney, Kirk

2015-03-01

Study conducted at Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE 19803 BACKGROUND: Although the treatment and management of asthma hasimproved over time, incidence and prevalence among children continues to rise in the United States. Asthma prevalence, health services utilization, and mortality rate demonstrate remarkable disparities. The underlying causes of these disparities are not fully understood. We aimed to examine racial/ethnic variances in pediatric asthma prevalence/admission. We retrospectively reviewed data on 1070 patients and applied a cross-sectional design to assess asthma admission between 2010 and 2011. Information was available on race/ethnicity, sex, insurance status, severity of illness (SOI), and length of stay/hospitalization (LOS).Chi-square statistic was used for the association between race and other variables in an attempt to explain the racial/ethnic variance. The proportionate morbidity of asthma was highest amongCaucasians (40.92%) and African Americans (40.54%), intermediate among others (16.57%), and lowest among Asian (0.56%), American Indian/Alaska Native (0.28%), and Hawaiian Native/Pacific Islander (0.28%). Overall there were disparities by sex, with more boys (61.80%) diagnosed with asthma than girls (38.20%), χ2(7)=20.1, p=0.005. Insurance status, and SOI varied by race/ethnicity, but not LOS. Caucasian children were more likely to have private insurance, while African Americans and Hispanics were more likely to have public insurance (p<0.005). Asthma was more severe among non-Hispanic children, χ2(14)=154.6, p<0.001. While the overall readmission proportion was 2.8%, readmission significantly varied by race/ethnicity. Racial/ethnic disparities in asthma admission exist among children in the Delaware Valley. There were racial/ethnic disparities in insurance status, asthma severity, and sex differed by race/ethnicity, but not in length of hospitalization. © 2015 National Medical Association. Published by Elsevier Inc. All rights reserved.

Impact of Asthma on the Sexual Functioning of Patients. A Case-Control Study.

PubMed

Soto Campos, José Gregorio; Rojas Villegas, Josefa; Padilla Galo, Alicia; Marina Malanda, Nuria; Garcia Rivero, Juan Luis; Pinedo Sierra, Celia; Garcia Salmones, Mercedes; Cabrera Galán, Carmen; Segura Molina, Esperanza; Plaza, Vicente; Pascual Erquicia, Silvia

2017-12-01

Sexual limitations play an important role in the quality of life of patients with chronic diseases. Very limited information is available on the impact of asthma on the sexual functioning of these individuals. Cross-sectional, observational, multicenter study. Asthma patients and healthy individuals were recruited. All subjects participated in an interview in which demographic and clinical data were recorded, and completed the Goldberg Anxiety-Depression Scale (GADS) to evaluate the presence of concomitant psychiatric disease. Men also completed the International Index of Erectile Function (IIEF), and women, the Female Sexual Function Index (FSFI). A total of 276cases were included, comprising 172asthma patients (63 men and 109 women) with a mean age of 42 (±14) years, and 104 controls (52men and 51women) with a mean age of 39 (±12) years. Time since onset of asthma was 15 years and severity distribution was: 6.4% intermittent, 17.9% mild persistent, 47.4% moderate, and 28.2% severe. Disease was considered controlled in 57.7%, partially controlled in 28.2%, and uncontrolled in 14.1%. Women with asthma had greater sexual limitations than women in the control group, with a total FSFI score of 22.1 (±9) compared to 26.5 (±6.8), respectively (P<.005). Men with asthma had significantly more severe erectile dysfunction with a total IIEF score of 59.5 (±12.5) compared to 64.3 (±8.2) in male controls (P<.05). An association was also observed between sexual problems and poorer asthma control. Asthma is associated with a poorer sexual quality of life among patients. These results should arouse the interest of healthcare professionals in detecting and alleviating possible sexual limitations among their asthma patients in routine clinical practice. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma.

PubMed

Turner, M O; Noertjojo, K; Vedal, S; Bai, T; Crump, S; Fitzgerald, J M

1998-06-01

We prospectively recruited patients admitted to the hospital with severe asthma to comprehensively evaluate the association of historical and physiologic features with the risk of near-fatal asthma (NFA). A case-control study design was used. All patients admitted with NFA (cases) were identified prospectively and compared with asthma patients admitted during the same period without respiratory failure (controls). Nineteen cases (age: 40.2 +/- 12.0 yr) (mean +/- SD) and 80 controls (age: 36 +/- 13.5 yr) were enrolled. Duration of asthma, gender, smoking status, ethnicity, and prevalence of atopy were similar in the case and control groups. More than 80% of patients in both groups reported worsening symptoms for more than 48 h before admission, and more than 50% were worse for longer than 7 d. There was no difference in degree of airways obstruction or bronchial hyperresponsiveness (PC20). Perception of dyspnea was similar in the cases and controls, but among cases the males had greater impairment than the females (Borg score: 1.9 +/- 1. 4 versus 3.9 +/- 1.2: p = 0.05). Univariate analysis identified a history of previous mechanical ventilation (OR: 27.5; 95% CI: 6.60 to 113.7), admission to the intensive care unit (ICU) (OR: 9.9; 95% CI: 3.0 to 32.9), history of worse asthma during January and February (OR: 3.5; 95% CI: 1.0 to 11.8), and use of air-conditioning (OR: 15.0; 95% CI: 1.3 to 166) as risk factors for NFA. Of concern was the dependence of most patients (59.8%) on the emergency department (ED) for initial care, and the small number of cases (16%) in which patients visited a physician before admission to the hospital. We have confirmed risk factors identified previously in retrospective studies of fatal and NFA, and have also shown that hospitalized patients with asthma, irrespective of severity of their asthma, share several characteristics, especially in terms of their failure to respond to worsening asthma.

Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.

PubMed

Konno, Satoshi; Taniguchi, Natsuko; Makita, Hironi; Nakamaru, Yuji; Shimizu, Kaoruko; Shijubo, Noriharu; Fuke, Satoshi; Takeyabu, Kimihiro; Oguri, Mitsuru; Kimura, Hirokazu; Maeda, Yukiko; Suzuki, Masaru; Nagai, Katsura; Ito, Yoichi M; Wenzel, Sally E; Nishimura, Masaharu

2015-12-01

Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).

Defining asthma and assessing asthma outcomes using electronic health record data: a systematic scoping review.

PubMed

Al Sallakh, Mohammad A; Vasileiou, Eleftheria; Rodgers, Sarah E; Lyons, Ronan A; Sheikh, Aziz; Davies, Gwyneth A

2017-06-01

There is currently no consensus on approaches to defining asthma or assessing asthma outcomes using electronic health record-derived data. We explored these approaches in the recent literature and examined the clarity of reporting.We systematically searched for asthma-related articles published between January 1, 2014 and December 31, 2015, extracted the algorithms used to identify asthma patients and assess severity, control and exacerbations, and examined how the validity of these outcomes was justified.From 113 eligible articles, we found significant heterogeneity in the algorithms used to define asthma (n=66 different algorithms), severity (n=18), control (n=9) and exacerbations (n=24). For the majority of algorithms (n=106), validity was not justified. In the remaining cases, approaches ranged from using algorithms validated in the same databases to using nonvalidated algorithms that were based on clinical judgement or clinical guidelines. The implementation of these algorithms was suboptimally described overall.Although electronic health record-derived data are now widely used to study asthma, the approaches being used are significantly varied and are often underdescribed, rendering it difficult to assess the validity of studies and compare their findings. Given the substantial growth in this body of literature, it is crucial that scientific consensus is reached on the underlying definitions and algorithms. Copyright ©ERS 2017.

Omalizumab for pediatric asthma.

PubMed

Townley, Robert G; Agrawal, Swati; Sapkota, Kiran

2010-11-01

Omalizumab is of proven efficacy in the treatment of severe allergic bronchial asthma and works through inhibiting the activity of IgE and the allergic immune mechanism IgE mediates. It has been demonstrated to be efficacious in children with asthma but is not approved by the FDA for use in children below 12 years of age. Omalizumab is a 95% humanized monoclonal antibody that binds to circulating IgE at the same site on the Fc domain as the high-affinity IgE receptor, FcϵRI. This blocks the interaction between IgE and mast cells and basophils, thereby preventing the release of inflammatory mediators that cause allergic signs and symptoms. From the review of the literatures and statements from the FDA, Genentec and Novartis, the reader will gain a better appreciation of the value of omalizumab in treatment of severe asthma and the current status of its reported side effects. Omalizumab is of proven efficacy in adults and children with severe asthma and allows a markedly reduced dependence on oral and inhaled corticosteroids and decreased hospitalizations. A potential mechanism of omalizumab's effect on thrombus formation and cardiovascular effect is postulated.

Latent-level relations between DSM-5 PTSD symptom clusters and problematic smartphone use.

PubMed

Contractor, Ateka A; Frankfurt, Sheila B; Weiss, Nicole H; Elhai, Jon D

2017-07-01

Common mental health consequences following the experience of potentially traumatic events include Posttraumatic Stress Disorder (PTSD) and addictive behaviors. Problematic smartphone use is a newer manifestation of addictive behaviors. People with anxiety severity (such as PTSD) may be at risk for problematic smartphone use as a means of coping with their symptoms. Unique to our knowledge, we assessed relations between PTSD symptom clusters and problematic smartphone use. Participants ( N = 347), recruited through Amazon's Mechanical Turk (MTurk), completed measures of PTSD and smartphone addiction. Results of the Wald tests of parameter constraints indicated that problematic smartphone use was more related to PTSD's negative alterations in cognitions and mood (NACM) than to PTSD's avoidance factor, Wald χ 2 (1, N = 347) = 12.51, p = 0.0004; and more to PTSD's arousal compared to PTSD's avoidance factor, Wald χ 2 (1, N = 347) = 14.89, p = 0.0001. Results indicate that problematic smartphone use is most associated with negative affect and arousal among trauma-exposed individuals. Implications include the need to clinically assess problematic smartphone use among trauma-exposed individuals presenting with higher NACM and arousal severity; and targeting NACM and arousal symptoms to mitigate the effects of problematic smartphone use.

Prevalence and effects of multiple chemical sensitivities in Australia.

PubMed

Steinemann, Anne

2018-06-01

Multiple chemical sensitivities (MCS) is a medical condition associated with exposure to common chemical pollutants. The aims of this study are to assess the prevalence of MCS, its overlaps with asthma and fragrance sensitivity, and its health and societal effects in Australia. Data were collected in June 2016 using an on-line survey with a representative national sample (N = 1098) of adults (ages 18-65) in Australia. Results found that, across the country, 6.5% report medically diagnosed MCS, 18.9% report chemical sensitivity (being unusually sensitive to everyday chemicals and chemically formulated products), and 19.9% either or both. Among people with MCS, 74.6% also have diagnosed asthma or an asthma-like condition, and 91.5% have fragrance sensitivity, reporting health problems (such as migraine headaches) when exposed to fragranced consumer products (such as air fresheners and cleaning supplies). In addition, among people with MCS, 77.5% are prevented from access to places because of fragranced products, 52.1% lost workdays or a job in the past year due to fragranced product exposure in the workplace, and 55.4% report health effects considered potentially disabling. Results indicate that MCS is a widespread disease, affecting an estimated 1 million adult Australians, with chemical sensitivity affecting another 2 million. Reducing chemical exposure to problematic sources, such as fragranced consumer products, is critical to reduce adverse effects.

User error with Diskus and Turbuhaler by asthma patients and pharmacists in Jordan and Australia.

PubMed

Basheti, Iman A; Qunaibi, Eyad; Bosnic-Anticevich, Sinthia Z; Armour, Carol L; Khater, Samar; Omar, Muthana; Reddel, Helen K

2011-12-01

Use of inhalers requires accurate completion of multiple steps to ensure effective medication delivery. To evaluate the most problematic steps in the use of Diskus and Turbuhaler for pharmacists and patients in Jordon and Australia. With standardized inhaler-technique checklists, we asked community pharmacists to demonstrate the use of Diskus and Turbuhaler. We asked patients with asthma to demonstrate the inhaler (Diskus or Turbuhaler) they were currently using. Forty-two community pharmacists in Jordan, and 31 in Australia, participated. In Jordan, 51 asthma patients demonstrated use of Diskus, and 40 demonstrated use of Turbuhaler. In Australia, 53 asthma patients demonstrated use of Diskus, and 42 demonstrated use of Turbuhaler. The pharmacists in Australia had received inhaler-technique education more recently than those in Jordan (P = .03). With Diskus, few pharmacists in either country demonstrated correct technique for step 3 (exhale to residual volume) or step 4 (exhale away from the device), although there were somewhat fewer errors in Australia than Jordan (16% vs 0% in step 3, P = .007, and 20% vs 0% in step 4, P = .003 via chi-square test). With Turbuhaler there were significant differences between the pharmacists from Australia and Jordan, mainly in step 2 (hold the device upright while loading, 45% vs 2% correct, P < .001). Few of the patients had received inhaler-technique education in the previous year. The patients made errors similar to those of the pharmacists in individual steps with Diskus and Turbuhaler. The essential steps with Diskus were performed correctly more often by the Jordanian patients, and with Turbuhaler by the Australian patients. Despite differences in Jordan's and Australia's health systems, pharmacists from both Australia and Jordan had difficulty with the same Diskus and Turbuhaler steps. In both countries, the errors made by the asthma patients were similar to those made by the pharmacists.

Identification and characterization of near-fatal asthma phenotypes by cluster analysis.

PubMed

Serrano-Pariente, J; Rodrigo, G; Fiz, J A; Crespo, A; Plaza, V

2015-09-01

Near-fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological features. However, there are no previous studies that identify in a unbiased way--using statistical methods such as clusters analysis--different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis. Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two-steps algorithm was performed from data of 84 of these cases. The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired consciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti-inflammatory treatment and frequent sensitization to Alternaria alternata and soybean. These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence of gastro-oesophageal reflux disease symptoms and reflux-associated respiratory symptoms in asthma.

PubMed

Amarasiri, Lakmali D; Pathmeswaran, Arunasalam; de Silva, H Janaka; Ranasinha, Channa D

2010-09-15

Gastro-oesophageal reflux disease (GORD) symptoms are common in asthma and have been extensively studied, but less so in the Asian continent. Reflux-associated respiratory symptoms (RARS) have, in contrast, been little-studied globally. We report the prevalence of GORD symptoms and RARS in adult asthmatics, and their association with asthma severity and medication use. A cross-sectional analytical study. A validated interviewer-administered GORD scale was used to assess frequency and severity of seven GORD symptoms. Subjects were consecutive asthmatics attending medical clinics. Controls were matched subjects without respiratory symptoms. The mean (SD) composite GORD symptom score of asthmatics was significantly higher than controls (21.8 (17.2) versus 12.0 (7.6); P < 0.001) as was frequency of each symptom and RARS. Prevalence of GORD symptoms in asthmatics was 59.4% (95% CI, 59.1%-59.6%) versus 28.5% in controls (95% CI, 29.0% - 29.4%). 36% of asthmatics experienced respiratory symptoms in association with both typical and atypical GORD symptoms, compared to 10% of controls (P < 0.001). An asthmatic had a 3.5 times higher risk of experiencing a GORD symptom after adjusting for confounders (OR 3.5; 95% CI 2.5-5.3). Severity of asthma had a strong dose-response relationship with GORD symptoms. Asthma medication use did not significantly influence the presence of GORD symptoms. GORD symptoms and RARS were more prevalent in a cohort of Sri Lankan adult asthmatics compared to non-asthmatics. Increased prevalence of RARS is associated with both typical and atypical symptoms of GORD. Asthma disease and its severity, but not asthma medication, appear to influence presence of GORD symptoms.

Prevalence of gastro-oesophageal reflux disease symptoms and reflux-associated respiratory symptoms in asthma

PubMed Central

2010-01-01

Background Gastro-oesophageal reflux disease (GORD) symptoms are common in asthma and have been extensively studied, but less so in the Asian continent. Reflux-associated respiratory symptoms (RARS) have, in contrast, been little-studied globally. We report the prevalence of GORD symptoms and RARS in adult asthmatics, and their association with asthma severity and medication use. Methods A cross-sectional analytical study. A validated interviewer-administered GORD scale was used to assess frequency and severity of seven GORD symptoms. Subjects were consecutive asthmatics attending medical clinics. Controls were matched subjects without respiratory symptoms. Results The mean (SD) composite GORD symptom score of asthmatics was significantly higher than controls (21.8 (17.2) versus 12.0 (7.6); P < 0.001) as was frequency of each symptom and RARS. Prevalence of GORD symptoms in asthmatics was 59.4% (95% CI, 59.1%-59.6%) versus 28.5% in controls (95% CI, 29.0% - 29.4%). 36% of asthmatics experienced respiratory symptoms in association with both typical and atypical GORD symptoms, compared to 10% of controls (P < 0.001). An asthmatic had a 3.5 times higher risk of experiencing a GORD symptom after adjusting for confounders (OR 3.5; 95% CI 2.5-5.3). Severity of asthma had a strong dose-response relationship with GORD symptoms. Asthma medication use did not significantly influence the presence of GORD symptoms. Conclusions GORD symptoms and RARS were more prevalent in a cohort of Sri Lankan adult asthmatics compared to non-asthmatics. Increased prevalence of RARS is associated with both typical and atypical symptoms of GORD. Asthma disease and its severity, but not asthma medication, appear to influence presence of GORD symptoms. PMID:20843346

[Acute asthma attacks introduced by anesthesia before nasal endoscopic surgery].

PubMed

Lü, Xiaofei; Han, Demin; Zhou, Bing; Ding, Bin

2004-05-01

In order to pay our attention to the perioperative treatment before nasal endoscopic surgery. Three patients with asthma accompanied chronic sinusitis were analyzed systemically, who had undergone acute attacks of asthma introduced by anesthesia. Anesthetic drugs and instruments can lead to acute attacks of asthma, because sinusitis with asthma means allergic airway inflammation, broncho-hyperreactivity and lower compensatory pulmonary function. Then all of the 3 cases had missed the preoperative treatment. Anesthetic drugs and instruments can lead to acute attacks of asthma. The perioperative treatment before nasal endoscopic surgery is very important for the prevention of the occurrences of this severe complication. Except emergency, the operation should be can celled for avoiding the acute attack of asthma introduced by anesthesia.

Risk and protective factors for the development of childhood asthma.

PubMed

Ding, Guodong; Ji, Ruoxu; Bao, Yixiao

2015-03-01

Childhood asthma prevalence worldwide has been increasing markedly over several decades. Various theories have been proposed to account for this alarming trend. The disease has a broad spectrum of potential determinants ranging from genetics to lifestyle and environmental factors. Epidemiological observations have demonstrated that several important lifestyle and environmental factors including obesity, urban living, dietary patterns such as food low in antioxidants and fast food, non-breastfeeding, gut flora imbalance, cigarette smoking, air pollution, and viral infection are associated with asthma exacerbations in children. However, only environmental tobacco smoke has been associated with the development of asthma. Despite epidemiological studies indicating that many other factors are probably associated with the development of asthma, the relationships are not considered causal due to the inadequate evidence and inconsistent results from recent studies. This may highlight that sufficient data and exact mechanisms of causality are still in need of further study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Metabolic syndrome and asthma.

PubMed

Garmendia, Jenny V; Moreno, Dolores; Garcia, Alexis H; De Sanctis, Juan B

2014-01-01

Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

[Internalization disorders in children with asthma].

PubMed

Carrera-Bojorges, Xûchitl Beatriz; Pérez-Romero, Luis Francisco; Trujillo-Garcìa, José Ubaldo; Jiménez-Sandoval, Jaime Omar; Machorro-Muñoz, Olga Stephanie

2013-01-01

The presence of asthma may increase the risk for internalizing disorders such as major depression and anxiety. To determine if the diagnosis of asthma in children is associated with other internalizing disorders such as panic disorder, social phobia, separation anxiety, and total anxiety. In this analytical, descriptive and comparative cross sectional study, 144 asthmatic and 144 nonasthmatic patients, with ages between 8 and 17 years, were included. We used the GINA asthma diagnostic criteria. We applied the Hospital Anxiety and Depression Scale for diagnosis of internalizing disorders. Asthmatic children had a significant association with panic disorder P 0.001, RP 2.7; with social phobia P 0.026, RP 2.5; with separation anxiety P 0.002, RP 3.3; and with total anxiety P 0.017, RP 2.3. Nonasthmatic children did not have these associations. Asthma severity was intermittent in 36 cases (12.5%), mild persistent in 86 (29.9%) cases, and moderate persistent in 22 (7.6%) cases. We observed no statistically significant relationship between the severity of asthma and the diagnosis of an internalization disorder. We observed a meaningful association between asthma and internalizing disorders such as panic disorder, social phobia, separation anxiety and total anxiety in children.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma.

PubMed

Xie, Yuran; Merkel, Olivia M

2015-10-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications.

PubMed

Robinson, D; Humbert, M; Buhl, R; Cruz, A A; Inoue, H; Korom, S; Hanania, N A; Nair, P

2017-02-01

Asthma is a complex respiratory disorder characterized by marked heterogeneity in individual patient disease triggers and response to therapy. Several asthma phenotypes have now been identified, each defined by a unique interaction between genetic and environmental factors, including inflammatory, clinical and trigger-related phenotypes. Endotypes further describe the functional or pathophysiologic mechanisms underlying the patient's disease. type 2-driven asthma is an emerging nomenclature for a common subtype of asthma and is characterized by the release of signature cytokines IL-4, IL-5 and IL-13 from cells of both the innate and adaptive immune systems. A number of well-recognized biomarkers have been linked to mechanisms involved in type 2 airway inflammation, including fractional exhaled nitric oxide, serum IgE, periostin, and blood and sputum eosinophils. These type 2 cytokines are targets for pharmaceutical intervention, and a number of therapeutic options are under clinical investigation for the management of patients with uncontrolled severe asthma. Anticipating and understanding the heterogeneity of asthma and subsequent improved characterization of different phenotypes and endotypes must guide the selection of treatment to meet individual patients' needs. © 2017 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Vitamin D and Bronchial Asthma: An Overview of Data From the Past 5 Years.

PubMed

Hall, Sannette C; Agrawal, Devendra K

2017-05-01

Vitamin D is a potent immunomodulator capable of dampening inflammatory signals in several cell types involved in the asthmatic response. Its deficiency has been associated with increased inflammation, exacerbations, and overall poor outcomes in patients with asthma. Given the increase in the prevalence of asthma over the past few decades, there has been enormous interest in the use of vitamin D supplementation as a potential therapeutic option. Here, we critically reviewed the most recent findings from in vitro studies, animal models, and clinical trials regarding the role of vitamin D in treating bronchial asthma. Using the key terms [Vitamin D, asthma, clinical trials, in vivo and in vitro studies], the [PubMed, Google Scholar] databases were searched for [clinical trials, original research articles, meta-analyses, and reviews], English-language articles published from [2012] to the present. Articles that were [Articles that did not meet these criteria were excluded] excluded from the analysis. Several studies have found that low serum levels of vitamin D (< 20 ng/mL) are associated with increased exacerbations, increased airway inflammation, decreased lung function, and poor prognosis in asthmatic patients. Results from in vitro and in vivo studies in animals and humans have suggested that supplementation with vitamin D may ameliorate several hallmark features of asthma. However, the findings obtained from clinical trials are controversial and do not unequivocally support a beneficial role of vitamin D in asthma. Largely, interventional studies in children, pregnant women, and adults have primarily found little to no effect of vitamin D supplementation on improved asthma symptoms, onset, or progression of the disease. This could be related to the severity of the disease process and other confounding factors. Despite the conflicting data obtained from clinical trials, vitamin D deficiency may influence the inflammatory response in the airways. Further studies are needed to determine the exact mechanisms by which vitamin D supplementation may induce antiinflammatory effects. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Families discovering asthma in their high-risk infants and toddlers with severe persistent disease.

PubMed

Koenig, Karel

2006-02-01

Interpretive phenomenology was used to discover the earliest experiences of families of children younger than 4 years hospitalized for severe persistent asthma. The children who were African American or Latino and living in poverty were at highest risk of morbidity and mortality. Three families with distinctly varied responses to early symptoms were chosen from an investigation of 11 families for this study. Each gave three home interviews and participated in home observations. All families experienced life-changing responses to their children's distressed breathing. All had experienced asthma in themselves or others that shaped their beliefs and management patterns. Family experiences prior to and following diagnosis are discussed. Findings suggest that understanding these experiences and respecting families' earliest responses will help clarify established family management patterns for severe asthma in infants and toddlers and will enhance the ability of providers to guide the care of these families and children.

Asthma and school commuting time.

PubMed

McConnell, Rob; Liu, Feifei; Wu, Jun; Lurmann, Fred; Peters, John; Berhane, Kiros

2010-08-01

This study examined associations of asthma with school commuting time. Time on likely school commute route was used as a proxy for on-road air pollution exposure among 4741 elementary school children at enrollment into the Children's Health Study. Lifetime asthma and severe wheeze (including multiple attacks, nocturnal, or with shortness of breath) were reported by parents. In asthmatic children, severe wheeze was associated with commuting time (odds ratio, 1.54 across the 9-minute 5% to 95% exposure distribution; 95% confidence interval, 1.01 to 2.36). The association was stronger in analysis restricted to asthmatic children with commuting times 5 minutes or longer (odds ratio, 1.97; 95% confidence interval, 1.02 to 3.77). No significant associations were observed with asthma prevalence. Among asthmatics, severe wheeze was associated with relatively short school commuting times. Further investigation of effects of on-road pollutant exposure is warranted.

Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines.

PubMed

Brasier, Allan R; Victor, Sundar; Boetticher, Gary; Ju, Hyunsu; Lee, Chang; Bleecker, Eugene R; Castro, Mario; Busse, William W; Calhoun, William J

2008-01-01

Asthma is a heterogeneous clinical disorder. Methods for objective identification of disease subtypes will focus on clinical interventions and help identify causative pathways. Few studies have explored phenotypes at a molecular level. We sought to discriminate asthma phenotypes on the basis of cytokine profiles in bronchoalveolar lavage (BAL) samples from patients with mild-moderate and severe asthma. Twenty-five cytokines were measured in BAL samples of 84 patients (41 severe, 43 mild-moderate) using bead-based multiplex immunoassays. The normalized data were subjected to statistical and informatics analysis. Four groups of asthmatic profiles could be identified on the basis of unsupervised analysis (hierarchical clustering) that were independent of treatment. One group, enriched in patients with severe asthma, showed differences in BAL cellular content, reductions in baseline pulmonary function, and enhanced response to methacholine provocation. Ten cytokines were identified that accurately predicted this group. Classification methods for predicting methacholine sensitivity were developed. The best model analysis predicted hyperresponders with 88% accuracy in 10 trials by using a 10-fold cross-validation. The cytokines that contributed to this model were IL-2, IL-4, and IL-5. On the basis of this classifier, 3 distinct hyperresponder classes were identified that varied in BAL eosinophil count and PC20 methacholine. Cytokine expression patterns in BAL can be used to identify distinct types of asthma and identify distinct subsets of methacholine hyperresponders. Further biomarker discovery in BAL may be informative.

RItA: The Italian severe/uncontrolled asthma registry.

PubMed

Maio, S; Baldacci, S; Bresciani, M; Simoni, M; Latorre, M; Murgia, N; Spinozzi, F; Braschi, M; Antonicelli, L; Brunetto, B; Iacovacci, P; Roazzi, P; Pini, C; Pata, M; La Grasta, L; Paggiaro, P; Viegi, G

2018-03-01

The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, and inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Four hundred and ninety three adult patients from 27 Italian centers (recruited in 2011-2014) were analyzed. Mean age was 53.8 years. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV 1 % pred of 75.1%, median values of 300/mm 3 of blood eosinophil count, 323 kU/L of serum total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3% hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95% CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicenter studies and available registries showed data consistency across European and American populations. An international effort in the implementation of SUA patients' registries could help to better understand the clinical features and to manage severe asthma, representing a non-negligible socioeconomic burden for health services. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Economic analysis of temperature-controlled laminar airflow (TLA) for the treatment of patients with severe persistent allergic asthma

PubMed Central

Brazier, Peter; Schauer, Uwe; Hamelmann, Eckard; Holmes, Steve; Pritchard, Clive; Warner, John O

2016-01-01

Introduction Chronic asthma is a significant burden for individual sufferers, adversely impacting their quality of working and social life, as well as being a major cost to the National Health Service (NHS). Temperature-controlled laminar airflow (TLA) therapy provides asthma patients at BTS/SIGN step 4/5 an add-on treatment option that is non-invasive and has been shown in clinical studies to improve quality of life for patients with poorly controlled allergic asthma. The objective of this study was to quantify the cost-effectiveness of TLA (Airsonett AB) technology as an add-on to standard asthma management drug therapy in the UK. Methods The main performance measure of interest is the incremental cost per quality-adjusted life year (QALY) for patients using TLA in addition to usual care versus usual care alone. The incremental cost of TLA use is based on an observational clinical study monitoring the incidence of exacerbations with treatment valued using NHS cost data. The clinical effectiveness, used to derive the incremental QALY data, is based on a randomised double-blind placebo-controlled clinical trial comprising participants with an equivalent asthma condition. Results For a clinical cohort of asthma patients as a whole, the incremental cost-effectiveness ratio (ICER) is £8998 per QALY gained, that is, within the £20 000/QALY cost-effectiveness benchmark used by the National Institute for Health and Care Excellence (NICE). Sensitivity analysis indicates that ICER values range from £18 883/QALY for the least severe patients through to TLA being dominant, that is, cost saving as well as improving quality of life, for individuals with the most severe and poorly controlled asthma. Conclusions Based on our results, Airsonett TLA is a cost-effective addition to treatment options for stage 4/5 patients. For high-risk individuals with more severe and less well controlled asthma, the use of TLA therapy to reduce incidence of hospitalisation would be a cost saving to the NHS. PMID:27026803

Acute severe asthma: performance of ventilator at simulated altitude.

PubMed

Tourtier, Jean-Pierre; Forsans, Emma; Leclerc, Thomas; Libert, Nicolas; Ramsang, Solange; Tazarourte, Karim; Man, Michel; Borne, Marc

2011-04-01

Exacerbation of asthma can be seen during air transport. Severe patients, not responding to conventional therapy, require ventilator support. We evaluated the performance of two transport ventilators, built with turbine technology, the T-birdVSO2 and the LTV-1000, for use during aeromedical evacuation of acute severe asthma. We have assessed the ability of both the ventilators to deliver to an acute severe asthma model a tidal volume (Vt) set at different simulated altitudes, by changing the ambient air pressure. The simulated cabin altitudes were 1500, 2500, and 3000 m (decompression chamber). Vt was set at 700 and 400 ml in an acute severe asthma lung model. Comparisons of the preset with the actual measured values were accomplished using a t-test. Comparisons between the actual delivered Vt and set Vt showed a significant difference starting at 1500 m for both the ventilators. The T-birdVSO2 showed a decrease in the volume delivered, with a negative variation of more than 10% compared with the Vt set. The LTV-1000 showed mostly an increase in the volume delivered. The delivered Vt remained within 10% of the set Vt. The accuracy of Vt delivery was superior with the LTV-1000 than with the T-birdVSO2, but the higher delivered Vt of the LTV-1000 are likely to be more harmful than lower delivered Vt of the T-birdVSO2.

Emerging mechanisms and novel targets in allergic inflammation and asthma.

PubMed

Weiss, Scott T

2017-12-04

Airway inflammation is key to the severity and persistence of asthma. Recent studies have revealed novel immune mechanisms that target dendritic cells, T helper 2 cytokines, regulatory T cells, and type 2 innate lymphoid cells in allergic inflammation, as well as novel approaches that target airway smooth muscle in asthma. These advances inform the development of new targeted treatments for allergic inflammation and asthma with the potential to provide therapeutic benefit.

Adapting and implementing an evidence-based asthma counseling intervention for resource-poor populations

PubMed Central

Thornton, Eleanor; Kennedy, Suzanne; Hayes-Watson, Claire; Krouse, Rebecca Z.; Mitchell, Herman; Cohn, Richard D.; Wildfire, Jeremy; Mvula, Mosanda M.; Lichtveld, Maureen; Grimsley, Faye; Martin, William J.; Stephens, Kevin U.

2016-01-01

Objective To report implementation strategies and outcomes of an evidence-based asthma counseling intervention. The Head-off Environmental Asthma in Louisiana (HEAL) intervention integrated asthma counseling (AC) capacity and addressed challenges facing children with asthma in post-disaster New Orleans. Methods The HEAL intervention enrolled 182 children (4–12 years) with moderate-to-severe persistent asthma. Recruitment occurred from schools in the Greater New Orleans area for one year. Participants received home environmental assessments and tailored asthma counseling sessions during the study period based on the National Cooperative Inner City Asthma Study and the Inner City Asthma Study. Primary (i.e. asthma symptoms) and secondary outcomes (i.e. healthcare utilization) were captured. During the study, changes were made to meet the demands of a post-hurricane and resource-poor environment which included changes to staffing, training, AC tools, and AC sessions. Results After study changes were made, the AC visit rate increased by 92.3%. Significant improvements were observed across several adherence measures (e.g., running out of medications (p=0.009), financial/insurance problems for appointments (p=0.006), worried about medication side-effects (p=0.01), felt medications did not work (p<0.001)). Additionally, an increasing number of AC visits was modestly associated with a greater reduction in symptoms (test-for-trend p=0.059). Conclusion By adapting to the needs of the study population and setting, investigators successfully implemented a counseling intervention that improved participant behaviors and clinical outcomes. The strategies for implementing the AC intervention may serve as a guide for managing asthma and other chronic conditions in resource-poor settings. PMID:27049234

Effect of catastrophic wildfires on asthmatic outcomes in obese children

PubMed Central

Tse, Kevin; Chen, Lie; Tse, Mabel; Zuraw, Bruce; Christiansen, Sandra

2015-01-01

Background Air pollutants from wildfires and obesity independently exacerbate asthma, yet no study has determined the combined effects of these 2 variables on asthma outcomes. Objective To determine the effect of 2 catastrophic wildfires affecting the Southern California region (in 2003 and 2007) on several asthma outcomes in a cohort of children. Methods To investigate the association between wildfire exposure and asthma outcomes, we stratified our study population by body mass index categories (underweight, normal, overweight, and obese) and zip codes (to distinguish individuals who were closer to the fires vs farther away). The primary outcome was the prevalence of physician-dispensed short-acting β-agonist (SABAs). Secondary outcomes included the rate of emergency department visits and/or hospitalizations for asthma, the frequency of oral corticosteroid use for asthma, and number of new diagnoses of asthma. Results A total of 2,195 and 3,965 asthmatic children were analyzed as part of our retrospective cohort during the 2003 and 2007 wildfires, respectively. SABA dispensing increased the most in the obese group after the 2003 wildfires (P <.05). Increased prevalence of SABA dispensing was also noted in the obese group in 2007, but this was not statistically higher than the increases seen in other body mass index groups. There was no observed increase in emergency department and/or hospitalization rates, oral corticosteroid dispensing frequency, or new asthma diagnoses after either wildfire. Conclusion Catastrophic wildfires lead to worsening asthma outcomes, particularly in obese individuals. This study gives further evidence of a link between obesity and asthma severity and suggests that air pollutants released during wildfires can have substantial detrimental effects on asthma control. PMID:25747784

Inflammation and asthma control in children with comorbid obstructive sleep apnea.

PubMed

Rogers, Valerie E; Bollinger, Mary E; Tulapurkar, Mohan E; Zhu, Shijun; Hasday, Jeffrey D; Pereira, Kevin D; Scharf, Steven M

2018-06-03

A bi-directional relationship exists between asthma and obstructive sleep apnea (OSA) in which presence of one is associated with increased prevalence and severity of the other. Our objective was to determine whether OSA accounted for differences in airway and systemic inflammation in asthmatic children and whether inflammation was associated with asthma control. We hypothesized that greater severity of SDB would correlate with increased upper airway and systemic inflammation and result in reduced asthma control. Non-obese children aged 4-12 years with persistent asthma, with or without OSA were recruited. Asthma control was measured with the Childhood Asthma Control Test. Children underwent polysomnography and blood sampling, and children with OSA underwent clinically indicated adenotonsillectomy. Tonsils and sera were analyzed for 11 cytokines. Twenty-seven children (20 with OSA, seven without OSA) participated, mean age 7.9 years, 55.6% female, 92.6% African American. Levels did not differ for any cytokine between children with and without OSA. Lower nadir oxygen saturation was associated with higher levels of tonsil TNF-α (P < 0.001) and IL-10 (P < 0.05). Higher REM-related apnea-hypopnea index was associated with higher levels of tonsil TNF-α (P < 0.05). Children with uncontrolled asthma had significantly higher levels of serum IL-10, IL-13, and TNF-α, and tonsil TNF-α (all P < 0.05) than well-controlled asthmatic children. There was no association between OSA, or any polysomnography variable, and asthma control. Despite the presence of OSA-associated airway inflammation, and asthma control-associated airway and systemic inflammation, OSA was not related to level of asthma control in this non-obese, largely minority, low income sample. © 2018 Wiley Periodicals, Inc.

Efficacy and Safety of Tiotropium in the Treatment of Severe Persistent Asthma:Meta-analysis.

PubMed

Lou, Li-li; Gong, Hai-hong; Zhang, Ming-qiang; Gao, Jin-ming

2016-02-01

To evaluate the efficacy and safety of tiotropium in treatment of severe persistent asthma. Reports of randomized controlled trials (RCTs) describing tiotropium for treatment of severe persistent asthma published from January 1946 to February 2015 were searched in Cochrane Library, ClinicalTrials.gov, PubMed, Ovid Medline, CNKI, and CSJD. The data of the included RCTs were extracted and the data quality was evaluated. Meta-analyses were performed with Revman 5.3 software. Five RCTs including 1433 patients were analyzed. Meta-analysis of the data showed that compared with the placebo group, tiotropium treatment significantly improved the patients' peak forced expiratory volume in one second (FEV1) [weighted mean difference (WMD): 0.13 L, 95% confidence interval (CI): 0.10-0.16 L, P<0.00001], trough FEV1 (WMD: 0.09 L, 95%CI: 0.06-0.12 L, P<0.00001), peak forced vital capacity (FVC) (WMD: 0.10 L, 95%CI: 0.06-0.14 L, P<0.00001), trough FVC (WMD: 0.12 L, 95%CI: 0.08-0.17 L, P<0.00001), morning peak expiratory flow (PEF) (WMD: 9.21 L/min, 95%CI: 4.2-14.23 L/min, P=0.0003), evening PEF (WMD: 22.06 L/min, 95%CI 13.05-31.08 L/min, P<0.00001). The scores of asthma control questionnaire (ACQ) (WMD: 0.01, 95% CI: -0.07-0.09, P=0.86) or asthma quality of life questionnaire (AQLQ)(WMD: 0.06, 95% CI:-0.18-0.06, P=0.33) were not affected by tiotropium. No significant difference with adverse events between tiotropium group and placebo group were reported in these included studies (P>0.05). Tiotropium for severe persistent asthma treatment can improve FEV1, FVC, and PEF but may not improve the quality of life of the patients. Tiotropium is well tolerated and can be an add-on therapy for severe persistent asthma.

MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2.

PubMed

Kim, Richard Y; Horvat, Jay C; Pinkerton, James W; Starkey, Malcolm R; Essilfie, Ama T; Mayall, Jemma R; Nair, Prema M; Hansbro, Nicole G; Jones, Bernadette; Haw, Tatt Jhong; Sunkara, Krishna P; Nguyen, Thi Hiep; Jarnicki, Andrew G; Keely, Simon; Mattes, Joerg; Adcock, Ian M; Foster, Paul S; Hansbro, Philip M

2017-02-01

Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease. We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches. Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated. Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens. We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of this form of asthma. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle.

PubMed

Austin, Philip J; Tsitsiou, Eleni; Boardman, Charlotte; Jones, Simon W; Lindsay, Mark A; Adcock, Ian M; Chung, Kian Fan; Perry, Mark M

2017-03-01

The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma. Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined. The mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma. lncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Socio-economic disadvantage, quality of medical care and admission for acute severe asthma.

PubMed

Kolbe, J; Vamos, M; Fergusson, W

1997-06-01

In asthma, socio-economic and health care factors may operate by a number of mechanisms to influence asthma morbidity and mortality. To determine the quality of medical care including the patient perception of the doctor-patient relationship, and the level of socio-economic disadvantage in patients admitted to hospital with acute severe asthma. One hundred and thirty-eight patients (15-50 years) admitted to hospital (general ward or intensive care unit) with acute asthma were prospectively assessed using a number of previously validated instruments. The initial subjects had severe asthma on admission (pH = 7.3 +/- 0.2, PaCO2 = 7.1 +/- 5.0 kPa, n = 90) but short hospital stay (3.7 +/- 2.6 days). Although having high morbidity (40% had hospital admission in the last year and 60% had moderate/severe interference with sleep and/or ability to exercise), they had indicators of good ongoing medical care (96% had a regular GP, 80% were prescribed inhaled steroids, 84% had a peak flow meter, GP measured peak flow routinely in 80%, 52% had a written crisis plan and 44% had a supply of steroids at home). However, they were severely economically disadvantaged (53% had experienced financial difficulties in the last year, and for 35% of households the only income was a social security benefit). In the last year 39% had delayed or put off GP visit because of cost. Management of the index attack was compromised by concern about medical costs in 16% and time off work in 20%. Patients admitted to hospital with acute asthma have evidence of good quality on-going medical care, but are economically disadvantaged. If issues such as financial barriers to health care are not acknowledged and addressed, the health care services for asthmatics will not be effectively utilised and the current reductions in morbidity and mortality may not be maintained.

Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.

PubMed

Christenson, Stephanie A; Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S; Postma, Dirkje S; Lenburg, Marc E; Spira, Avrum; Woodruff, Prescott G

2015-04-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.

A Self-Regulation Theory–Based Asthma Management Mobile App for Adolescents: A Usability Assessment

PubMed Central

2017-01-01

Background Self-regulation theory suggests people learn to influence their own behavior through self-monitoring, goal-setting, feedback, self-reward, and self-instruction, all of which smartphones are now capable of facilitating. Several mobile apps exist to manage asthma; however, little evidence exists about whether these apps employ user-centered design processes that adhere to government usability guidelines for mobile apps. Objective Building upon a previous study that documented adolescent preferences for an asthma self-management app, we employed a user-centered approach to assess the usability of a high-fidelity wireframe for an asthma self-management app intended for use by adolescents with persistent asthma. Methods Individual interviews were conducted with adolescents (ages 11-18 years) with persistent asthma who owned a smartphone (N=8). Adolescents were asked to evaluate a PDF app wireframe consisting of 76 screen shots displaying app features, including log in and home screen, profile setup, settings and info, self-management features, and graphical displays for charting asthma control and medication. Preferences, comments, and suggestions for each set of screen shots were assessed using the audio-recorded interviews. Two coders reached consensus on adolescent evaluations of the following aspects of app features: (1) usability, (2) behavioral intentions to use, (3) confusing aspects, and (4) suggestions for improvement. Results The app wireframe was generally well received, and several suggestions for improvement were recorded. Suggestions included increased customization of charts and notifications, reminders, and alerts. Participants preferred longitudinal data about asthma control and medication use to be displayed using line graphs. All participants reported that they would find an asthma management app like the one depicted in the wireframe useful for managing their asthma. Conclusions Early stage usability tests guided by government usability guidelines (usability.gov) revealed areas for improvement for an asthma self-management app for adolescents. Addressing these areas will be critical to developing an engaging and effective asthma self-management app that is capable of improving adolescent asthma outcomes. PMID:28148471

Advances in Pediatric Asthma in 2013: Coordinating Asthma Care

PubMed Central

Szefler, Stanley J.

2014-01-01

Last year’s Advances in Pediatric Asthma: Moving Toward Asthma Prevention concluded that: “We are well on our way to creating a pathway around wellness in asthma care and also to utilize new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.” This year’s summary will focus on recent advances in pediatric asthma on pre- and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding potential therapeutic targets for altering the course of asthma in children as indicated in Journal of Allergy and Clinical Immunology publications in 2013 and early 2014. Recent reports continue to shed light on methods to understand factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention as well as new immunomodulators. It will now be important to carefully assess risk factors for the development of asthma as well as the risk for asthma exacerbations and to improve the way we communicate this information in the health care system. This will allow parents, primary care physicians, specialists and provider systems to more effectively intervene in altering the course of asthma and to further reduce asthma morbidity and mortality. PMID:24581430

Sinus and adenoid inflammation in children with chronic rhinosinusitis and asthma.

PubMed

Anfuso, Antony; Ramadan, Hassan; Terrell, Andrew; Demirdag, Yesim; Walton, Cheryl; Skoner, David P; Piedimonte, Giovanni

2015-02-01

Chronic rhinosinusitis (CRS) and asthma frequently coexist in children and adults. However, the precise pathophysiologic mechanism of this interaction is still poorly understood, especially in children, owing to the lack of direct measurements of mucosal inflammation in the upper airways. To determine the pathophysiologic mechanism by analyzing the expression of a large array of inflammatory cytokines and chemokines in the sinus and adenoid tissues surgically removed from pediatric patients with CRS refractory to medical management. Twenty-eight children 2 to 12 years old diagnosed with CRS with or without asthma and 10 controls were included in this prospective, nonrandomized study. Mucosal expression of 40 inflammatory cytokines was measured with a multiplex assay and was normalized to total tissue protein. Compared with children with CRS and without asthma, children with CRS and asthma had significantly higher sinus levels of tumor necrosis factor-α and adenoid levels of epidermal growth factor, eotaxin, fibroblast growth factor-2, growth-related oncogene, and platelet-derived growth factor-AA. The inflammatory response in the upper airway mucosa of children with asthma and CRS was similar, but more severe, compared with children with CRS without asthma. This observation is consistent with the hypothesis that asthma in these patients is caused or exacerbated by severe upper airway disease and supports the concept that treating sinus disease is paramount in the management of chronic asthma in children using, for the first time, direct measurements of airway inflammation in children. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Th2 cytokine antagonists: potential treatments for severe asthma.

PubMed

Hansbro, Philip M; Scott, Grace V; Essilfie, Ama-Tawiah; Kim, Richard Y; Starkey, Malcolm R; Nguyen, Duc H; Allen, Paul D; Kaiko, Gerard E; Yang, Ming; Horvat, Jay C; Foster, Paul S

2013-01-01

Asthma is a major disease burden worldwide. Treatment with steroids and long acting β-agonists effectively manage symptoms in many patients but do not treat the underlying cause of disease and have serious side effects when used long term and in children. Therapies targeting the underlying causes of asthma are urgently needed. T helper type 2 (Th2) cells and the cytokines they release are clinically linked to the presentation of all forms of asthma. They are the primary drivers of mild to moderate and allergic asthma. They also play a pathogenetic role in exacerbations and more severe asthma though other factors are also involved. Much effort using animal models and human studies has been dedicated to the identification of the pathogenetic roles of these cells and cytokines and whether inhibition of their activity has therapeutic benefit in asthma. We discuss the current status of Th2 cytokine antagonists for the treatment of asthma. We also discuss the potential for targeting Th2-inducing cytokines, Th2 cell receptors and signaling as well as the use of Th2 cell antagonists, small interfering oligonucleotides, microRNAs, and combination therapies. Th2 antagonists may be most effective in particular asthma subtypes/endotypes where specific cytokines are known to be active through the analysis of biomarkers. Targeting common receptors and pathways used by these cytokines may have additional benefit. Animal models have been valuable in identifying therapeutic targets in asthma, however the results from such studies need to be carefully interpreted and applied to appropriately stratified patient cohorts in well-designed clinical studies and trials.

[Changes in the prevalence of asthma in Chilean school age children between 1994 and 2002. International Study of Asthma and Allergies in Childhood (ISAAC)--Chile phases I and III].

PubMed

Mallol, Javier; Aguirre, Viviana; Aguilar, Pedro; Calvo, Mario; Amarales, Lidia; Arellano, Pamela; Palma, Rodrigo

2007-05-01

In developed countries, the prevalence of asthma in children has significantly increased in the last decades. However, there is no information about the trends of asthma in Latin America. To determine changes in asthma prevalence between 1994 and 2002 in Chilean schoolchildren. The prevalence of asthma symptoms in schoolchildren aged 7 (n =18.697) and 13 years (n =18.939), from South Santiago, Valdivia and Punta Arenas, obtained during phases I and III of the ISAAC, carried out in 1994 and 2002, was compared. From 1994 to 2002, the mean national prevalence of "wheezing in the last 12 months" in the group aged 6-7 years, changed from 18.2% to 17.9% (p =NS); "asthma ever" from 12.5% to 10.7% (p =NS), and "severe episode" from 3.2% to 2.8% (p =NS). There was a significant increase of the prevalence of "wheezing in the last 12 months", in children aged 13-14 years, from 9.8% to 15.5% (p =0.01); in "asthma ever" from 10.2% to 14.9% (p =0.01), and for "severe episode" from 2.8% to 3.8% (p =0.01). There was a significant increase in the prevalence of respiratory symptoms related to asthma in children aged 13-14 years that was consistent in all the 3 participating centres of the ISAAC. However, the prevalence of asthma symptoms in children aged 6-7 years remained without significant changes between 1994 and 2002.

Association between Allergic Rhinitis and Asthma Control in Peruvian School Children: A Cross-Sectional Study

PubMed Central

Uceda, Mónica; Ziegler, Otto; Lindo, Felipe; Herrera-Pérez, Eder

2013-01-01

Background. Asthma and allergic rhinitis are highly prevalent conditions that cause major illness worldwide. This study aimed to assess the association between allergic rhinitis and asthma control in Peruvian school children. Methods. A cross-sectional study was conducted among 256 children with asthma recruited in 5 schools from Lima and Callao cities. The outcome was asthma control assessed by the asthma control test. A score test for trend of odds was used to evaluate the association between allergic rhinitis severity and the prevalence of inadequate asthma control. A generalized linear regression model was used to estimate the adjusted prevalence ratios of inadequate asthma control. Results. Allergic rhinitis was present in 66.4% of the population with asthma. The trend analysis showed a positive association between allergic rhinitis and the probability of inadequate asthma control (P < 0.001). It was associated with an increased prevalence of inadequate asthma control, with adjusted prevalence ratios of 1.53 (95% confidence interval: 1.19−1.98). Conclusion. This study indicates that allergic rhinitis is associated with an inadequate level of asthma control, giving support to the recommendation of evaluating rhinitis to improve asthma control in children. PMID:23984414

Relationship of Inhaled Corticosteroid Adherence to Asthma Exacerbations in Patients with Moderate-to-Severe Asthma.

PubMed

Papi, Alberto; Ryan, Dermot; Soriano, Joan B; Chrystyn, Henry; Bjermer, Leif; Rodríguez-Roisin, Roberto; Dolovich, Myrna B; Harris, Mark; Wood, Lucy; Batsiou, Maria; Thornhill, Susannah I; Price, David B

2018-04-05

Patients with asthma and elevated blood eosinophils are at increased risk of severe exacerbations. Management of these patients should consider nonadherence to inhaled corticosteroid (ICS) therapy as a factor for increased exacerbation risk. The objective of this study was to investigate whether poor adherence to ICS therapy explains the occurrence of asthma exacerbations in patients with elevated blood eosinophil levels. This historical cohort study identified patients within the Optimum Patient Care Research Database, aged 18 years or more, at Global Initiative for Asthma step 3 or 4, with 2 or more ICS prescriptions during the year before the clinical review. Patient characteristics and adherence (based on prescription refills and patient self-report) for ICS therapy were analyzed for those with elevated (>400 cells/μL) or normal (≤400 cells/μL) blood eosinophils. We studied 7195 patients (66% female, mean age 60 years) with median eosinophil count of 200 cells/μL and found 81% to be not fully adherent to ICS therapy. A total of 1031 patients (14%) had elevated blood eosinophil counts (58% female, mean age 60 years), 83% of whom were not fully adherent to ICS. An increased proportion of adherent patients in the elevated blood eosinophil group had 2 or more exacerbations (14.0% vs 7.2%; P = .003) and uncontrolled asthma (73% vs 60.8%; P = .004) as compared with non-fully adherent patients. Approximately 1 in 7 patients had elevated eosinophils. Adherence to ICS therapy was not associated with decreased exacerbations for these patients. Additional therapy should be considered for these patients, such as biologics, which have been previously shown to improve control in severe uncontrolled eosinophilic asthma. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Fetal growth and risk of childhood asthma and allergic disease

PubMed Central

Tedner, S G; Örtqvist, A K; Almqvist, C

2012-01-01

Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

Childhood asthma clusters and response to therapy in clinical trials.

PubMed

Chang, Timothy S; Lemanske, Robert F; Mauger, David T; Fitzpatrick, Anne M; Sorkness, Christine A; Szefler, Stanley J; Gangnon, Ronald E; Page, C David; Jackson, Daniel J

2014-02-01

Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial). In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Decreased expression of indolamine 2,3-dioxygenase in childhood allergic asthma and its inverse correlation with fractional concentration of exhaled nitric oxide.

PubMed

Hu, Ying; Chen, Zhiqiang; Jin, Ling; Wang, Mei; Liao, Wei

2017-11-01

The tryptophan metabolic pathway mediated by indolamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays an important role in controlling the development of allergic inflammation. The fractional concentration of exhaled nitric oxide (FeNO) is closely associated with the allergic state and is extensively used for the clinical evaluation of airway allergic inflammation. Clinical trials have rarely assessed the expression of IDO in childhood allergic asthma and its correlation with FeNO. To evaluate the IDO level in children with childhood allergic asthma and the relation between IDO levels and FeNO. Thirty children older than 5 years who were diagnosed the first time with allergic asthma were selected from the pediatric outpatient department. Another 30 healthy children were selected as controls. The subjects were evaluated by complete medical history, pulmonary function test results, skin prick test reaction, FeNO concentration test result, eosinophil count, and a disease severity score. Peripheral venous blood and induced sputum were obtained to measure the concentrations of IDO metabolites (ie, tryptophan and kynurenine). The IDO levels in the peripheral blood and induced sputum were significantly lower in patients with childhood allergic asthma than in children in the control group. The IDO level was negatively correlated with FeNO but was not significantly correlated with age, sex, blood eosinophil count, or disease severity scale. The expression of IDO was significantly lower in childhood allergic asthma, particularly in children with high FeNO levels. There was no significant relation between IDO levels and asthma severity. Chinese Clinical Trial Register (www.chictr.org.cn) Identifier: ChiCTR-COC-15006080. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Secondhand Smoke Exposure Reduction After NICU Discharge: Results of a Randomized Trial.

PubMed

Blaakman, Susan W; Borrelli, Belinda; Wiesenthal, Elise N; Fagnano, Maria; Tremblay, Paul J; Stevens, Timothy P; Halterman, Jill S

2015-01-01

Premature infants are at high risk for respiratory disease, and secondhand smoke (SHS) exposure further increases their risk for developing respiratory illness and asthma. Yet, SHS exposure remains problematic in this vulnerable population. Our objective was to evaluate the effects of brief asthma education plus motivational interviewing counseling on reducing SHS exposure and improving respiratory outcomes in premature infants compared to asthma education alone. Caregivers and their infants ≤32 weeks' gestational age were enrolled after discharge from a neonatal intensive care unit in Rochester, New York, from 2007 to 2011. Participants (N = 165, 61% Medicaid insurance, 35% Black, 19% Hispanic, 59% male) were stratified by infant SHS exposure and randomly assigned to treatment or comparison groups. Caregivers in the treatment group reported significantly more home smoking bans (96% vs 84%, P = .03) and reduced infant contact with smokers after the intervention (40% vs 58%, P = .03), but these differences did not persist long term. At study end (8 months after neonatal intensive care unit discharge), treatment group infants showed significantly greater reduction in salivary cotinine versus comparison (-1.32 ng/mL vs -1.08 ng/mL, P = .04), but no significant differences in other clinical outcomes. A community-based intervention incorporating motivational interviewing and asthma education may be helpful in reducing SHS exposure of premature infants in the short term. Further efforts are needed to support sustained protections for this high-risk group and ultimately, prevent acute and chronic respiratory morbidity. Strategies for successfully engaging families during this stressful period warrant attention. Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

[Environmental tobacco smoke exposure in children and its relationship with the severity of asthma].

PubMed

Suárez López de Vergara, R G; Galván Fernández, C; Oliva Hernández, C; Aguirre-Jaime, A; Aquirre-Jaime, A; Vázquez Moncholí, C

2013-01-01

Environmental tobacco smoke (ETS) exposure produces serious respiratory problems in childhood. The aim of the study was to evaluate if environmental tobacco smoke affects the severity of asthma in asthmatic children. A prospective, multicentre study was conducted on asthmatic children and their parents in 2007-2008, using an exposure questionnaire, pulmonary function, level of cotinine in urine, and evaluation of the severity of asthma according to GEMA guide. The characteristics of the sample are summarised using the appropriate statistical tools, and the comparisons were made using the Pearson chi2 test, Mann-Whitney U test or Studentĭs t, according to the variable and number of groups compared. Four hundred and eighty four households in 7 Autonomous Communities were included. The population included, 61% male children with asthma, 56% with a smoking caregiver in their home, 34% fathers, 31% mothers and 17% both. Home exposure was 37%, with 11% daily and 94% passive smokers since birth. There was 20% with exposure during whole period of pregnancy of 5±1 cigarettes/day. Children exposed to 6±1 cigarettes/day, 27%, up to 10 cigarettes/day, and 10% to more than 10. Severity of asthma during the survey was worse among those exposed (episodic-occasional 47%, episodic-frequent 35% and persistent-moderate 18% versus 59%, 25% and 16%, respectively, P=.040). Severity of asthma in the last year was worse in those exposed (episodic - occasional 22%, episodic - frequent 37% and persistent - moderate 50% versus 38%, 28% and 25% respectively, P=.037). The spirometry was abnormal in 64% of the exposed against to 36% in the non-exposed for FEV(1) (P=.003, 63% vs 38% for FVC (P=.038), and 54% vs 46% for the PEF (P=.050). The cotinine was higher in exposed: 51 (0-524) ng/ml vs 27 (0-116) ng/ml (P=.032). A relationship was observed between cotinine and level of exposure: 120 (0-590) ng/ml for >10 cigarettes/day as opposed to 44 (0-103) ng/ml ≤10 cigarettes/day (P=.035), which corroborates the consistency of the data collected. The exposure of children with asthma to environmental tobacco smoke has a highly negative effect on the severity of their asthma. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier España. All rights reserved.

Bronchial thermoplasty: a novel treatment for severe asthma requiring monitored anesthesia care.

PubMed

Lee, Jamille A; Rowen, David W; Rose, David D

2011-12-01

Dexmedetomidine used in monitored anesthesia care produces a safe and effective technique well documented in research. We report the successful use of dexmedetomidine for sedation during bronchial thermoplasty, a new treatment for patients with severe persistent asthma refractory to inhaled corticosteroids and long-term beta-2 agonists.

Family Relational Factors in Pediatric Depression and Asthma: Pathways of Effect

ERIC Educational Resources Information Center

Wood, Beatrice L.; Miller, Bruce D.; Lim, Jungha; Lillis, Kathleen; Ballow, Mark; Stern, Trudy; Simmens, Samuel

2006-01-01

Objective: This study tested a multilevel biobehavioral family model proposing that negative family emotional climate contributes to child depressive symptoms, which in turn contribute to asthma disease severity. Parent-child relational insecurity is proposed as a mediator. Method: Children with asthma (N = 112; ages 7-18; 55% male) reported…

Difficult‐to‐control asthma management through the use of a specific protocol

PubMed Central

Giavina‐Bianchi, Pedro; Aun, Marcelo Vivolo; Bisaccioni, Carla; Agondi, Rosana; Kalil, Jorge

2010-01-01

The present study is a critical review of difficult‐to‐control asthma, highlighting the characteristics and severity of the disease. It also presents a protocol for the management of patients with this asthma phenotype. The protocol, which was based on relevant studies in the literature, is described and analyzed. PMID:21049219

Asthma and dietary intake: an overview of systematic reviews.

PubMed

Garcia-Larsen, V; Del Giacco, S R; Moreira, A; Bonini, M; Charles, D; Reeves, T; Carlsen, K-H; Haahtela, T; Bonini, S; Fonseca, J; Agache, I; Papadopoulos, N G; Delgado, L

2016-04-01

Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, anti-allergic and anti-inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score ≥32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma. © 2015 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.

Epigenetics in asthma and other inflammatory lung diseases.

PubMed

Durham, Andrew; Chou, Pai-Chien; Kirkham, Paul; Adcock, Ian M

2010-08-01

Asthma is a chronic inflammatory disease of the airways. The causes of asthma and other inflammatory lung diseases are thought to be both environmental and heritable. Genetic studies do not adequately explain the heritability and susceptabilty to the disease, and recent evidence suggests that epigentic changes may underlie these processes. Epigenetics are heritable noncoding changes to DNA and can be influenced by environmental factors such as smoking and traffic pollution, which can cause genome-wide and gene-specific changes in DNA methylation. In addition, alterations in histone acetyltransferase/deacetylase activities can be observed in the cells of patients with lung diseases such as severe asthma and chronic obstructive pulmonary disease, and are often linked to smoking. Drugs such as glucocorticoids, which are used to control inflammation, are dependent on histone deacetylase activity, which may be important in patients with severe asthma and chronic obstructive pulmonary disease who do not respond well to glucocorticoid therapy. Future work targeting specific histone acetyltransferases/deacetylases or (de)methylases may prove to be effective future anti-inflammatory treatments for patients with treatment-unresponsive asthma.

Effect of inhaled corticosteroid use on weight (BMI) in pediatric patients with moderate-severe asthma.

PubMed

Han, Jennifer; Nguyen, John; Kim, Yuna; Geng, Bob; Romanowski, Gale; Alejandro, Lawrence; Proudfoot, James; Xu, Ronghui; Leibel, Sydney

2018-04-19

Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI). A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects. There is a statistically significant increase of 0.369 kg/m 2 in BMI trajectory per year in subjects on high-dose steroids compared to an increase of 0.195 kg/m 2 in the low dose group (p < 0.05). The BMI of subjects initiated on biologic therapy (omalizumab or mepolizumab) had a statistically significant decrease in BMI trajectory of 0.818 kg/m 2 per year (p < 0.05). Subjects with ≥5 ED visits due to asthma exacerbations had a significantly higher BMI trajectory (p < 0.05). The potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.

PubMed

Hose, Alexander J; Depner, Martin; Illi, Sabina; Lau, Susanne; Keil, Thomas; Wahn, Ulrich; Fuchs, Oliver; Pfefferle, Petra Ina; Schmaußer-Hechfellner, Elisabeth; Genuneit, Jon; Lauener, Roger; Karvonen, Anne M; Roduit, Caroline; Dalphin, Jean-Charles; Riedler, Josef; Pekkanen, Juha; von Mutius, Erika; Ege, Markus J

2017-06-01

Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Major Chronic Respiratory Diseases in Chiang Mai: Prevalence, Clinical Characteristics, and Their Correlations.

PubMed

Pothirat, Chaicharn; Phetsuk, Nittaya; Liwsrisakun, Chalerm; Bumroongkit, Chaiwat; Deesomchok, Athavudh; Theerakittikul, Theerakorn

2016-09-01

To identify the prevalence, clinical characteristics, disease severity, and correlations of major chronic respiratory diseases (CRDs) among the adult population living in Chiang Mai. A cross-sectional study was conducted with adults living in municipal areas of Chiang Mai. All clinical relevant data collected by face-to-face interview was confirmed by pulmonologists. The chest radiographic findings and post-bronchodilator spirometry were done in all subjects. The aeroallergen skin test and rhinoscopy were performed in all chronic rhinitis and asthma subjects. Five hundred seventy four subjects with mean age 52.9±10.0 years, 59.6% female, and 37.5% smokers were recruited. The prevalence of overall CRDs was 59.2%. Chronic rhinitis was the most prevalent chronic respiratory disease (n = 239, 41.6%), followed by asthma (n = 58, 10.1%), and chronic obstructive pulmonary disease (COPD) (n = 21, 3.7%). The most common abnormal pulmonary function test was restrictive lung disorders (n = 53, 9.6%). Asthma subjects were determined to be more allergic than chronic rhinitis subjects (58.1% vs. 39.9%, p-value = 0.033). Regarding the disease severity, 14.9% of chronic rhinitis and 10.3% of asthma subjects were classified as moderate to severe degree, whereas 81% of chronic obstructive pulmonary disease subjects were classified as moderate to very severe degrees. In asthma patients, there were positive association with chronic rhinitis (OR 3.9, 95% CI 2.1-7.0, p-value <0.001). The prevalence of major CRDs in adults among Chiang Mai population was significantly high with overlapped respiratory symptoms and varying disease severity. Additionally, chronic rhinitis had correlation with asthma but not with COPD.

IgE-blocking therapy for difficult-to-treat asthma: a brief review.

PubMed

Marshall, Gailen D; Sorkness, Christine A

2004-03-01

To review the characteristics of difficult-to-treat asthma and describe patients who may benefit from therapy with the recently approved humanized monoclonal antiimmunoglobulin E (IgE) antibody, omalizumab. Up to 20 percent of patients have difficult-to-treat asthma. These patients consume a disproportionate share of asthma care resources. Clinical and economic outcomes can be improved via improved self-management, increased adherence to prescribed therapy, and better compliance to national asthma treatment guidelines. These patients also may benefit from therapies that directly target mechanisms responsible for persistent airway inflammation and elicit favorable clinical responses. Effective asthma control remains difficult in a small cohort of patients with persistent, severe airway inflammation. Management strategies that improve asthma control and reduce exacerbations can improve clinical outcomes and minimize health care resource utilization.

Airway smooth muscle: a potential target for asthma therapy.

PubMed

Dowell, Maria L; Lavoie, Tera L; Solway, Julian; Krishnan, Ramaswamy

2014-01-01

Asthma is a major public health problem that afflicts nearly one in 20 people worldwide. Despite available treatments, asthma symptoms remain poorly controlled in a significant minority of asthma patients, especially those with severe disease. Accordingly, much ongoing effort has been directed at developing new therapeutic strategies; these efforts are described in detail below. Although mucus hypersecretion is an important component of asthma pathobiology, the primary mechanism of morbidity and mortality in asthma is excessive narrowing of the airway. The key end- effector of excessive airway narrowing is airway smooth muscle (ASM) contraction; overcoming ASM contraction is therefore a prominent therapeutic strategy. Here, we review exciting new advances aimed at ASM relaxation. Exciting advances in ASM biology have identified new therapeutic targets for the prevention or reversal of bronchoconstriction in asthma.

Adolescent asthma education programs for teens: review and summary.

PubMed

Srof, Brenda; Taboas, Peggy; Velsor-Friedrich, Barbara

2012-01-01

The purpose of this review is to describe and evaluate education programs for teens with asthma. Although asthma educational programs for children are plentiful, this is not the case for adolescents. The developmental tasks of adolescence require asthma education programs that are uniquely tailored to this age group. Although several well-designed studies appear in the literature, further research is needed to evaluate the efficacy of asthma education programs among teens. Although the quality of research varies, demonstrated program benefits include improved asthma self-management, self-efficacy, family support mechanisms, and quality of life. Practice implications point to the need for education programs in schools and camp settings that are consistent with national asthma guidelines. Copyright © 2012 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

Cost-effectiveness of a home-based environmental intervention for inner-city children with asthma.

PubMed

Kattan, Meyer; Stearns, Sally C; Crain, Ellen F; Stout, James W; Gergen, Peter J; Evans, Richard; Visness, Cynthia M; Gruchalla, Rebecca S; Morgan, Wayne J; O'Connor, George T; Mastin, J Patrick; Mitchell, Herman E

2005-11-01

Exposure to indoor allergens contributes to increased asthma morbidity. The Inner-City Asthma Study, a randomized trial involving home environmental allergen and irritant remediation among children aged 6 through 11 years with moderate-to-severe asthma, successfully reduced asthma symptoms. A cost-effectiveness analysis can help stakeholders to evaluate the potential costs and benefits of adopting such a program. We sought to assess the cost-effectiveness of the environmental intervention of the Inner-City Asthma Study. Incremental cost-effectiveness ratios for a 2-year study period were calculated. Health outcome was measured as symptom-free days. Resource use measures included ambulatory visits, hospitalizations, and pharmaceutical use. CIs were obtained by using bootstrapping. The intervention, which cost $1469 per family, led to statistically significant reductions in symptom days, unscheduled clinic visits, and use of beta-agonist inhalers. Over the year of the intervention and a year of follow-up, the intervention cost was $27.57 per additional symptom-free day (95% CI, $7.46-$67.42). Subgroup analysis showed that targeting the intervention to selected high-risk subgroups did not reduce the incremental cost-effectiveness ratio. A targeted home-based environmental intervention improved health and reduced service use in inner-city children with moderate-to-severe asthma. The intervention is cost-effective when the aim is to reduce asthma symptom days and the associated costs.

Oxidative stress biomarkers and asthma characteristics in adults of the EGEA study.

PubMed

Andrianjafimasy, Miora; Zerimech, Farid; Akiki, Zeina; Huyvaert, Helene; Le Moual, Nicole; Siroux, Valérie; Matran, Régis; Dumas, Orianne; Nadif, Rachel

2017-12-01

Asthma is an oxidative stress related disease, but associations with asthma outcomes are poorly studied in adults. We aimed to study the associations between several biomarkers related to oxidative stress and various asthma outcomes.Cross-sectional analyses were conducted in 1388 adults (mean age 43 years, 44% with asthma) from the Epidemiological Study of the Genetics and Environment of Asthma (EGEA2). Three blood antioxidant enzyme activities (biomarkers of response to oxidative stress) and exhaled breath condensate 8-isoprostanes and plasma fluorescent oxidation products (FlOPs) levels (two biomarkers of damage) were measured. Associations between biomarkers and 1) ever asthma and 2) asthma attacks, asthma control and lung function in participants with asthma were evaluated using regression models adjusted for age, sex and smoking.Biomarkers of response were unrelated to asthma outcomes. Higher 8-isoprostane levels were significantly associated with ever asthma (odds ratio for one interquartile range increase 1.28 (95% CI 1.06-1.67). Among participants with asthma, 8-isoprostane levels were negatively associated with adult-onset asthma (0.63, 0.41-0.97) and FlOPs levels were positively associated with asthma attacks (1.33, 1.07-1.65), poor asthma control (1.30, 1.02-1.66) and poor lung function (1.34, 1.04-1.74).Our results suggest that 8-isoprostanes are involved in childhood-onset asthma and FlOPs are linked to asthma expression. Copyright ©ERS 2017.

Insights, attitudes, and perceptions about asthma and its treatment: findings from a multinational survey of patients from Latin America.

PubMed

Maspero, Jorge F; Jardim, Jose R; Aranda, Alvaro; Tassinari C, Paolo; Gonzalez-Diaz, Sandra N; Sansores, Raul H; Moreno-Cantu, Jorge J; Fish, James E

2013-11-04

In 2011 the Latin America Asthma Insight and Management (LA AIM) survey explored the realities of living with asthma. We investigated perception, knowledge, and attitudes related to asthma among Latin American asthma patients. Asthma patients aged ≥12 years from four Latin American countries (Argentina, Brazil, Mexico, Venezuela) and the Commonwealth of Puerto Rico responded to questions during face-to-face interviews. A sample size of 2,169 patients (approximately 400 patients/location) provided an accurate representation of asthma patients' opinions. Questions probed respondents' views on topics such as levels of asthma control, frequency and duration of exacerbations, and current and recent use of asthma medications. A total of 2,169 adults or parents of children with asthma participated in the LA AIM survey. At least 20% of respondents experienced symptoms every day or night or most days or nights. Although 60% reported their disease as well or completely controlled, only 8% met guideline criteria for well-controlled asthma. 47% of respondents reported episodes when their asthma symptoms were more frequent or severe than normal, and 44% reported seeking acute care for asthma in the past year. Asthma patients in Latin America overestimated their degree of asthma control. The LA AIM survey demonstrated the discrepancy between patient perception of asthma control and guideline-mandated criteria. Additional education is required to teach patients that, by more closely following asthma management strategies outlined by current guidelines more patients can achieve adequate asthma control.

Asthma in the United States: burden and current theories.

PubMed

Redd, Stephen C

2002-08-01

Asthma has emerged as a major public health problem in the United States over the past 20 years. Currently, nearly 15 million Americans have asthma, including almost 5 million children. The number of asthma cases has more than doubled since 1980. Approximately 5,500 persons die from asthma each year, and rates have increased over the past 20 years. Rates of death, hospitalization, and emergency department visits are 2-3 times higher among African Americans than among white Americans. The costs of asthma have also increased to 12.7 billion dollars in 1998. Both lifestyle and environmental hypotheses have been invoked to explain the increase in asthma prevalence. Several studies have examined the relationship of obesity and asthma and found associations suggesting that obesity predisposes to the development of asthma. Some studies have found that day care attendance and having older siblings protect against the development of asthma. This observation has led investigators to hypothesize that increased exposure to microbial agents might protect against asthma (the hygiene hypothesis). Environmental exposures found to predispose to asthma include house dust mite allergen and environmental tobacco smoke. Although current knowledge does not permit definitive conclusions about the causes of asthma onset, better adherence to current recommendations for medical therapy and environmental management of asthma would reduce the burden of this disease.

Estimated cost of asthma in outpatient treatment: a real-world study.

PubMed

Costa, Eduardo; Caetano, Rosangela; Werneck, Guilherme Loureiro; Bregman, Maurício; Araújo, Denizar Vianna; Rufino, Rogério

2018-04-09

To estimate the cost of diagnosis and treatment of asthma. We used the perspective of society. We sequentially included for 12 months, in 2011-2012, 117 individuals over five years of age who were treated for asthma in the Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic, Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with a six-month interval for data collection, covering 12 months. The cost units were identified and valued according to defined methods. We carried out a sensitivity analysis and applied statistical methods with a significance level of 5% for cost comparisons between subgroups. The study consisted of 108 patients, and 73.8% of them were women. Median age was 49.5 years. Rhinitis was present in 83.3% of the individuals, and more than half were overweight or obese. Mean family income was U$915.90/month (SD = 879.12). Most workers and students had absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs than non-obese, non-severe, and controlled asthmatics, respectively. Severity and control level were independently associated with higher cost (p = 0.001 and 0.000, respectively). The direct cost accounted for 82.3% of the estimated total cost. The cost of medications for asthma accounted for 62.2% of the direct costs of asthma. Asthma medications, environmental control measures, and long-term health leaves had the greatest potential impact on total cost variation. The results are an estimate of the cost of treating asthma at a secondary level in the Brazilian Unified Health System, assuming that the treatment used represents the ideal approach to the disease.

Estimated cost of asthma in outpatient treatment: a real-world study

PubMed Central

Costa, Eduardo; Caetano, Rosangela; Werneck, Guilherme Loureiro; Bregman, Maurício; Araújo, Denizar Vianna; Rufino, Rogério

2018-01-01

ABSTRACT OBJECTIVE To estimate the cost of diagnosis and treatment of asthma. METHODS We used the perspective of society. We sequentially included for 12 months, in 2011-2012, 117 individuals over five years of age who were treated for asthma in the Pneumology and Allergy-Immunology Services of the Piquet Carneiro Polyclinic, Universidade do Estado do Rio de Janeiro. All of them were interviewed twice with a six-month interval for data collection, covering 12 months. The cost units were identified and valued according to defined methods. We carried out a sensitivity analysis and applied statistical methods with a significance level of 5% for cost comparisons between subgroups. RESULTS The study consisted of 108 patients, and 73.8% of them were women. Median age was 49.5 years. Rhinitis was present in 83.3% of the individuals, and more than half were overweight or obese. Mean family income was U$915.90/month (SD = 879.12). Most workers and students had absenteeism related to asthma. Total annual mean cost was U$1,291.20/patient (SD = 1,298.57). The cost related to isolated asthma was U$1,155.43/patient-year (SD = 1,305.58). Obese, severe, and uncontrolled asthmatic patients had higher costs than non-obese, non-severe, and controlled asthmatics, respectively. Severity and control level were independently associated with higher cost (p = 0.001 and 0.000, respectively). The direct cost accounted for 82.3% of the estimated total cost. The cost of medications for asthma accounted for 62.2% of the direct costs of asthma. CONCLUSIONS Asthma medications, environmental control measures, and long-term health leaves had the greatest potential impact on total cost variation. The results are an estimate of the cost of treating asthma at a secondary level in the Brazilian Unified Health System, assuming that the treatment used represents the ideal approach to the disease. PMID:29641652

Relations of Change in Condition Severity and School Self-Concept To Change in Achievement-Related Behavior in Children with Asthma or Epilepsy.

ERIC Educational Resources Information Center

Huberty, Thomas J.; Austin, Joan K.; Huster, Gertrude A.; Dunn, David W.

2000-01-01

Explores relation of gender, change in condition of severity, and change in school self-concept, to change in teachers' ratings of academic-related behaviors in children with asthma or epilepsy. Tests showed that these children were near population mean in academic-related behaviors, except students with high-severity epilepsy. (Author/JDM)

The Potential for Emerging Microbiome-Mediated Therapeutics in Asthma.

PubMed

Ozturk, Ayse Bilge; Turturice, Benjamin Arthur; Perkins, David L; Finn, Patricia W

2017-08-10

In terms of immune regulating functions, analysis of the microbiome has led the development of therapeutic strategies that may be applicable to asthma management. This review summarizes the current literature on the gut and lung microbiota in asthma pathogenesis with a focus on the roles of innate molecules and new microbiome-mediated therapeutics. Recent clinical and basic studies to date have identified several possible therapeutics that can target innate immunity and the microbiota in asthma. Some of these drugs have shown beneficial effects in the treatment of certain asthma phenotypes and for protection against asthma during early life. Current clinical evidence does not support the use of these therapies for effective treatment of asthma. The integration of the data regarding microbiota with technologic advances, such as next generation sequencing and omics offers promise. Combining comprehensive bioinformatics, new molecules and approaches may shape future asthma treatment.

Diet and asthma: vitamins and methyl donors.

PubMed

Han, Yueh-Ying; Blatter, Josh; Brehm, John M; Forno, Erick; Litonjua, Augusto A; Celedón, Juan C

2013-12-01

Diet changes can partly explain the high burden of asthma in industrialised nations. Findings from experimental studies have stimulated many observational studies of the association between vitamins (A, C, D, and E) or nutrients acting as methyl donors (folate, vitamin B12, and choline) and asthma. However, observational studies are susceptible to several sources of bias; well conducted randomised controlled trials (RCTs) are the gold standard to establish whether diet has an effect on asthma. Evidence from observational studies and a few RCTs strongly justifies ongoing and future RCTs in three areas: vitamin D for the prevention or treatment of asthma, choline supplementation as adjuvant treatment for asthma, and vitamin E to prevent the detrimental effects of air pollution in patients with asthma. At present, insufficient evidence exists to recommend supplementation with any vitamin or nutrient acting as a methyl donor to prevent or treat asthma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Addressing unmet needs in understanding asthma mechanisms: From the European Asthma Research and Innovation Partnership (EARIP) Work Package (WP)2 collaborators.

PubMed

Edwards, Michael R; Saglani, Sejal; Schwarze, Jurgen; Skevaki, Chrysanthi; Smith, Jaclyn A; Ainsworth, Ben; Almond, Mark; Andreakos, Evangelos; Belvisi, Maria G; Chung, Kian Fan; Cookson, William; Cullinan, Paul; Hawrylowicz, Catherine; Lommatzsch, Marek; Jackson, David; Lutter, Rene; Marsland, Benjamin; Moffatt, Miriam; Thomas, Mike; Virchow, J Christian; Xanthou, Georgina; Edwards, Jessica; Walker, Samantha; Johnston, Sebastian L

2017-05-01

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control. Therapeutic advances have been slow despite greater understanding of basic mechanisms and the lack of satisfactory preventative and disease modifying management for asthma constitutes a significant unmet clinical need. Preventing, treating and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which has taken a co-ordinated and integrated approach to analysing the future of asthma research and development. This report aims to identify the mechanistic areas in which investment is required to bring about significant improvements in asthma outcomes. Copyright ©ERS 2017.

Diet and Asthma: Vitamins and Methyl Donors

PubMed Central

Han, Yueh-Ying; Blatter, Josh; Brehm, John M.; Forno, Erick; Litonjua, Augusto A; Celedón, Juan C.

2014-01-01

SUMMARY Dietary changes may partly explain the high burden of asthma in industrialized nations. Experimental studies have motivated a significant number of observational studies of the relation between vitamins (A, C, D, and E) or nutrients acting as methyl donors (folate, vitamin B12, and choline) and asthma. Because observational studies are susceptible to several sources of bias, well-conducted randomized controlled trials (RCTs) remain the “gold standard” to determine whether a vitamin or nutrient has an effect on asthma. Evidence from observational studies and/or relatively few RCTs most strongly justify ongoing and future RCTs of: 1) vitamin D to prevent or treat asthma, 2) choline supplementation as adjuvant treatment for asthma, and 3) vitamin E to prevent the detrimental effects of air pollution in subjects with asthma. At this time, there is insufficient evidence to recommend supplementation with any vitamin or nutrient acting as a methyl donor to prevent or treat asthma. PMID:24461761

Latent-level relations between DSM-5 PTSD symptom clusters and problematic smartphone use

PubMed Central

Contractor, Ateka A.; Frankfurt, Sheila B.; Weiss, Nicole H.; Elhai, Jon D.

2017-01-01

Common mental health consequences following the experience of potentially traumatic events include Posttraumatic Stress Disorder (PTSD) and addictive behaviors. Problematic smartphone use is a newer manifestation of addictive behaviors. People with anxiety severity (such as PTSD) may be at risk for problematic smartphone use as a means of coping with their symptoms. Unique to our knowledge, we assessed relations between PTSD symptom clusters and problematic smartphone use. Participants (N = 347), recruited through Amazon’s Mechanical Turk (MTurk), completed measures of PTSD and smartphone addiction. Results of the Wald tests of parameter constraints indicated that problematic smartphone use was more related to PTSD’s negative alterations in cognitions and mood (NACM) than to PTSD’s avoidance factor, Wald χ2(1, N = 347) = 12.51, p = 0.0004; and more to PTSD’s arousal compared to PTSD’s avoidance factor, Wald χ2(1, N = 347) = 14.89, p = 0.0001. Results indicate that problematic smartphone use is most associated with negative affect and arousal among trauma-exposed individuals. Implications include the need to clinically assess problematic smartphone use among trauma-exposed individuals presenting with higher NACM and arousal severity; and targeting NACM and arousal symptoms to mitigate the effects of problematic smartphone use. PMID:28993716

The application of subset correspondence analysis to address the problem of missing data in a study on asthma severity in childhood.

PubMed

Hendry, G; North, D; Zewotir, T; Naidoo, R N

2014-09-28

Non-response in cross-sectional data is not uncommon and requires careful handling during the analysis stage so as not to bias results. In this paper, we illustrate how subset correspondence analysis can be applied in order to manage the non-response while at the same time retaining all observed data. This variant of correspondence analysis was applied to a set of epidemiological data in which relationships between numerous environmental, genetic, behavioural and socio-economic factors and their association with asthma severity in children were explored. The application of subset correspondence analysis revealed interesting associations between the measured variables that otherwise may not have been exposed. Many of the associations found confirm established theories found in literature regarding factors that exacerbate childhood asthma. Moderate to severe asthma was found to be associated with needing neonatal care, male children, 8- to 9-year olds, exposure to tobacco smoke in vehicles and living in areas that suffer from extreme air pollution. Associations were found between mild persistent asthma and low birthweight, and being exposed to smoke in the home and living in a home with up to four people. The classification of probable asthma was associated with a group of variables that indicate low socio-economic status. Copyright © 2014 John Wiley & Sons, Ltd.

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population

PubMed Central

Kerkhof, Marjan; Tran, Trung N; Soriano, Joan B; Golam, Sarowar; Gibson, Danny; Hillyer, Elizabeth V

2018-01-01

Background Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. Aims We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. Methods This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting β2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. Results Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). Conclusions Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma. PMID:28918400

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population.

PubMed

Kerkhof, Marjan; Tran, Trung N; Soriano, Joan B; Golam, Sarowar; Gibson, Danny; Hillyer, Elizabeth V; Price, David B

2018-02-01

Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×10 9 /L) for patients prescribed long-acting β 2 -agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Post-traumatic Stress Disorder, Bronchodilator Response, and Incident Asthma in World Trade Center Rescue and Recovery Workers

PubMed Central

Jeon, Yunho; Miller, Gregory E.; Wisnivesky, Juan P.

2016-01-01

Rationale: Post-traumatic stress disorder (PTSD) has been associated with asthma in cross-sectional studies. Whether PTSD leads to clinically significant bronchodilator response (BDR) or new-onset asthma is unknown. Objectives: We sought to determine the relationship between probable PTSD and both BDR and incident asthma in a high-risk cohort of World Trade Center workers in New York (NY). Methods: This study was conducted on data from a high-risk cohort of 11,481 World Trade Center workers in New York, including 6,133 never smokers without a previous diagnosis of asthma. Of the 6,133 never smokers without asthma, 3,757 (61.3%) completed a follow-up visit several years later (mean = 4.95 yr, interquartile range = 3.74–5.90 yr). At the baseline visit, probable PTSD was defined as a score 44 points or greater in the PTSD Checklist questionnaire, and BDR was defined as both a change of 12% or greater and an increment of 200 ml or greater in FEV1 after bronchodilator administration. Incident asthma was defined as a self-report of new physician-diagnosed asthma after the baseline visit. Multivariable logistic regression was used for the analysis of probable PTSD and baseline BDR or incident asthma. Measurements and Main and Results: At baseline, probable PTSD was associated with BDR among all participants (adjusted odds ratio = 1.43; 95% confidence interval = 1.19–1.72), with similar results among never smokers without asthma. Among 3,757 never smokers, probable PTSD at baseline was associated with incident asthma, even after adjustment for baseline BDR (odds ratio = 2.41; 95% confidence interval = 1.85–3.13). This association remained significant in a confirmatory analysis after excluding 195 subjects with baseline BDR. Conclusions: In a cohort of adult workers exposed to a severe traumatic event, probable PTSD is significantly associated with BDR at baseline and predicts incident asthma. PMID:27548615

Post-traumatic Stress Disorder, Bronchodilator Response, and Incident Asthma in World Trade Center Rescue and Recovery Workers.

PubMed

de la Hoz, Rafael E; Jeon, Yunho; Miller, Gregory E; Wisnivesky, Juan P; Celedón, Juan C

2016-12-01

Post-traumatic stress disorder (PTSD) has been associated with asthma in cross-sectional studies. Whether PTSD leads to clinically significant bronchodilator response (BDR) or new-onset asthma is unknown. We sought to determine the relationship between probable PTSD and both BDR and incident asthma in a high-risk cohort of World Trade Center workers in New York (NY). This study was conducted on data from a high-risk cohort of 11,481 World Trade Center workers in New York, including 6,133 never smokers without a previous diagnosis of asthma. Of the 6,133 never smokers without asthma, 3,757 (61.3%) completed a follow-up visit several years later (mean = 4.95 yr, interquartile range = 3.74-5.90 yr). At the baseline visit, probable PTSD was defined as a score 44 points or greater in the PTSD Checklist questionnaire, and BDR was defined as both a change of 12% or greater and an increment of 200 ml or greater in FEV 1 after bronchodilator administration. Incident asthma was defined as a self-report of new physician-diagnosed asthma after the baseline visit. Multivariable logistic regression was used for the analysis of probable PTSD and baseline BDR or incident asthma. Measurements and Main and Results: At baseline, probable PTSD was associated with BDR among all participants (adjusted odds ratio = 1.43; 95% confidence interval = 1.19-1.72), with similar results among never smokers without asthma. Among 3,757 never smokers, probable PTSD at baseline was associated with incident asthma, even after adjustment for baseline BDR (odds ratio = 2.41; 95% confidence interval = 1.85-3.13). This association remained significant in a confirmatory analysis after excluding 195 subjects with baseline BDR. In a cohort of adult workers exposed to a severe traumatic event, probable PTSD is significantly associated with BDR at baseline and predicts incident asthma.

Asthma–COPD Overlap. Clinical Relevance of Genomic Signatures of Type 2 Inflammation in Chronic Obstructive Pulmonary Disease

PubMed Central

Steiling, Katrina; van den Berge, Maarten; Hijazi, Kahkeshan; Hiemstra, Pieter S.; Postma, Dirkje S.; Lenburg, Marc E.; Spira, Avrum; Woodruff, Prescott G.

2015-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids. Objectives: To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features. Methods: We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89). Measurements and Main Results: The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD. Conclusions: These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and “asthma-like” features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma. PMID:25611785

Anxiety and depression in asthma patients: impact on asthma control.

PubMed

Vieira, Aline Arlindo; Santoro, Ilka Lopes; Dracoulakis, Samir; Caetano, Lilian Ballini; Fernandes, Ana Luisa Godoy

2011-01-01

There is evidence that asthma is associated with an increase in psychiatric symptoms and mental disorders. This association can make it difficult to achieve asthma control. The purpose of this study was to determine whether the level of asthma control is associated with anxiety and depression. A crosssectional study involving 78 patients with confirmed moderate or severe asthma and under regular treatment at the Asthma Outpatient Clinic of the Federal University of São Paulo Hospital São Paulo, in the city of São Paulo, Brazil. The patients were divided into two groups by asthma control status, as assessed by the asthma control test, and were subsequently compared in terms of demographic, clinical, and spirometric data, as well as scores for asthma quality of life and hospital anxiety/depression. The sample was predominantly female. Of the 78 patients, 49 (63%) were classified as having uncontrolled asthma. The prevalence of anxiety and of anxiety+depression was significantly higher among patients with uncontrolled asthma than among those with controlled asthma (78% and 100%; p = 0.04 and p = 0.02, respectively), whereas there were no differences between the two groups in terms of the prevalence of depression, spirometry results, or quality of life score. In this sample, the prevalence of anxiety symptoms was higher in the patients with uncontrolled asthma than in those with controlled asthma.In the evaluation of asthma patients, the negative impact of mood states ought to be taken into consideration when asthma control strategies are being outlined.

Tobacco Control Laws and Pediatric Asthma.

PubMed

Hatoun, Jonathan; Davis-Plourde, Kendra; Penti, Brian; Cabral, Howard; Kazis, Lewis

2018-01-01

Exposure to environmental tobacco smoke increases pediatric asthma severity. Strict, state-level tobacco control reduces smoking. The Child Asthma Call-Back Survey (Child ACBS) is a nationally representative survey of the guardians of children with asthma. The American Lung Association's annual State of Tobacco Control report grades tobacco control laws in each state including a tax grade (cigarette excise tax relative to the national mean), and a smoke-free air grade (number of locations where smoking is prohibited). We joined Child ACBS data from 2006 to 2010 with corresponding state and year tobacco grades. In the primary analysis, we investigated the effect of state tax grades on a child's asthma severity by using a logistic regression model adjusting for year. A secondary analysis assessed the impact of smoke-free air grades on in-home smoking. Our analysis included 12 860 Child ACBS interviews from 35 states over 5 years, representing over 24 million individuals. We merged 112 unique State of Tobacco Control grades with patient data by state and year. A higher tax grade was associated with reduced severity (adjusted odds ratio = 1.40; P = .007, 95% confidence interval: 1.10-1.80). A better smoke-free air grade was not associated with decreased in-home smoking after adjusting for confounding by income and type of residence. A stronger tobacco tax is associated with reduced asthma severity. Further study is needed to determine the effect of smoke-free air laws on in-home environmental. This work supports ongoing efforts to strengthen tobacco control through federal and state regulations. Copyright © 2018 by the American Academy of Pediatrics.

Influence of two different geo-climatic zones on the prevalence and time trends of asthma symptoms among Spanish adolescents and schoolchildren

NASA Astrophysics Data System (ADS)

García-Marcos, Luis; Batllés-Garrido, José; Blanco-Quirós, Alfredo; García-Hernández, Gloria; Guillén-Grima, Francisco; González-Díaz, Carlos; García-Merino, Águeda; Arnedo-Pena, Alberto; Busquets-Monge, Rosa M.; Morales-Suárez-Varela, María; López-Silvarrey-Varela, Ángel; García-Andoin, Nekane

2009-01-01

Few studies have focused on the long-term influence of the climate on the prevalence of asthma. The aim of this study is to establish the influence of geo-climatic conditions on the prevalence of asthma symptoms both in adolescents and schoolchildren, and to discover if this influence is associated with their time trends. Eight centres in Spain performed both ISAAC phases I (1994) and III (2002) in children 13-14 years old. Six of them also surveyed children 6-7 years old. For each age group and phase, about 3,000 children were surveyed per centre. This study examines the prevalence of current wheeze and severe current wheeze in two different geo-climatic zones, coast and plateau, considering their relative humidity and temperature range. In both age groups, the mean asthma prevalence on the coast, for phase I and III, was significantly higher than on the plateau. Living on the plateau was an independent protective factor for current wheeze and severe current wheeze for the two age groups. Within the coastal centres, the increase of the annual relative humidity was a statistical significant risk factor for current wheeze, the same trend existing for current severe wheeze. These effects were independent of the sex and of the phase of the study. The prevalence of asthma and severe asthma symptoms is more frequent on the coast of Spain as compared to the inner plateau. This finding was repeated both in 1994 and in 2002.

Problematic internet usage in US college students: a pilot study

PubMed Central

2011-01-01

Background Internet addiction among US college students remains a concern, but robust estimates of its prevalence are lacking. Methods We conducted a pilot survey of 307 college students at two US universities. Participants completed the Internet Addiction Test (IAT) as well as the Patient Health Questionnaire. Both are validated measures of problematic Internet usage and depression, respectively. We assessed the association between problematic Internet usage and moderate to severe depression using a modified Poisson regression approach. In addition, we examined the associations between individual items in the IAT and depression. Results A total of 224 eligible respondents completed the survey (73% response rate). Overall, 4% of students scored in the occasionally problematic or addicted range on the IAT, and 12% had moderate to severe depression. Endorsement of individual problematic usage items ranged from 1% to 70%. In the regression analysis, depressive symptoms were significantly associated with several individual items. Relative risk could not be estimated for three of the twenty items because of small cell sizes. Of the remaining 17 items, depressive symptoms were significantly associated with 13 of them, and three others had P values less than 0.10. There was also a significant association between problematic Internet usage overall and moderate to severe depression (relative risk 24.07, 95% confidence interval 3.95 to 146.69; P = 0.001). Conclusion The prevalence of problematic Internet usage among US college students is a cause for concern, and potentially requires intervention and treatment amongst the most vulnerable groups. The prevalence reported in this study is lower than that which has been reported in other studies, however the at-risk population is very high and preventative measures are also recommended. PMID:21696582

Serum decoy receptor 3 is a biomarker for disease severity in nonatopic asthma patients.

PubMed

Chen, Ming-Han; Kan, Hung-Tsai; Liu, Chun-Yu; Yu, Wen-Kuang; Lee, Shinn-Shing; Wang, Jia-Horng; Hsieh, Shie-Liang

2017-01-01

Decoy receptor 3 (DcR3), a soluble receptor of the tumor necrosis factor receptor superfamily, is a pleiotropic immunomodulator. The aim of this study was to investigate serum DcR3 levels in atopic and nonatopic asthma patients. The serum DcR3 levels of 70 adults with asthma and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). The asthma patients were divided into atopic and nonatopic subgroups, based on the presence or absence of immunoglobulin E (IgE) specific to allergen. Correlations between serum DcR3 levels and blood total-eosinophil counts, forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and Asthma Control Test (ACT) scores were analyzed. The mean serum DcR3 level was significantly higher in asthma patients than in healthy controls (266.1 ± 60.6 pg/mL vs. 63.7 ± 21.9 pg/mL, p = 0.003), but there was no significant difference between the mean serum DcR3 level of asthma patients with atopy (37 patients) and patients without atopy (33 patients; 298.7 ± 111.2 pg/mL vs. 230.6 ± 38.5 pg/mL, p = 0.064). However, the serum DcR3 level was positively correlated with the total eosinophil count (r = 0.448, p = 0.012) and inversely correlated with the percentages of predicted FEV1, FEV1/FVC, and ACT score (r = 0.409, p = 0.018; r = -0.399, p = 0.021; and r = -0.505, p = 0.003, respectively) in nonatopic asthma patients, but not in atopic patients. High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma. Copyright © 2016. Published by Elsevier B.V.

Advances in pediatric asthma and atopic dermatitis.

PubMed

Foroughi, Shabnam; Thyagarajan, Ananth; Stone, Kelly D

2005-10-01

Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.

Single-inhaler combination therapy for maintenance and relief of asthma: a new strategy in disease management.

PubMed

Peters, Matthew

2009-01-01

When an adequate standard of asthma control is not achieved with maintenance treatment of inhaled corticosteroids, the addition of a long-acting beta(2)-adrenergic receptor agonist (LABA) bronchodilator is recommended. Using a combination product, salmeterol/fluticasone propionate (Seretide or Advair) or budesonide/formoterol (Symbicort) is preferred for convenience and avoids any risk that LABA might be used as monotherapy. As formoterol has a rapid onset of bronchodilator effect, the budesonide/formoterol combination can be used for both the maintenance and reliever components of asthma treatment (Symbicort SMART) and this is endorsed as an effective treatment by the Global Initiative for Asthma. The efficacy of this approach has been evaluated in a series of well conducted, controlled studies. Current control of asthma symptoms is improved or achieved with reduced total dose administration with Symbicort SMART compared with any reasonable alternate option. In every study, the risk of severe exacerbations was lower with Symbicort SMART than comparator treatment. Patients who benefit to the greatest extent are those with evidence of more severe asthma and greater exacerbation risk. When initiated in suitable patients in conjunction with appropriate education, Symbicort SMART is dominant in pharmacoeconomic terms. Symbicort SMART delivers improved asthma outcomes with lower treatment and social costs than any alternative.

African Ancestry Is Associated with Asthma Risk in African Americans

PubMed Central

Pino-Yanes, María; Wade, Michael S.; Pérez-Méndez, Lina; Kittles, Rick A.; Wang, Deli; Papaiahgari, Srinivas; Ford, Jean G.; Kumar, Rajesh; Garcia, Joe G. N.

2012-01-01

Background Asthma is a common complex condition with clear racial and ethnic differences in both prevalence and severity. Asthma consultation rates, mortality, and severe symptoms are greatly increased in African descent populations of developed countries. African ancestry has been associated with asthma, total serum IgE and lower pulmonary function in African-admixed populations. To replicate previous findings, here we aimed to examine whether African ancestry was associated with asthma susceptibility in African Americans. In addition, we examined for the first time whether African ancestry was associated with asthma exacerbations. Methodology/Principal Findings After filtering for self-reported ancestry and genotype data quality, samples from 1,117 self-reported African-American individuals from New York and Baltimore (394 cases, 481 controls), and Chicago (321 cases followed for asthma exacerbations) were analyzed. Genetic ancestry was estimated based on ancestry informative markers (AIMs) selected for being highly divergent among European and West African populations (95 AIMs for New York and Baltimore, and 66 independent AIMs for Chicago). Among case-control samples, the mean African ancestry was significantly higher in asthmatics than in non-asthmatics (82.0±14.0% vs. 77.8±18.1%, mean difference 4.2% [95% confidence interval (CI):2.0–6.4], p<0.0001). This association remained significant after adjusting for potential confounders (odds ratio: 4.55, 95% CI: 1.69–12.29, p = 0.003). African ancestry failed to show an association with asthma exacerbations (p = 0.965) using a model based on longitudinal data of the number of exacerbations followed over 1.5 years. Conclusions/Significance These data replicate previous findings indicating that African ancestry constitutes a risk factor for asthma and suggest that elevated asthma rates in African Americans can be partially attributed to African genetic ancestry. PMID:22235241

Concordance of opinions between patients and physicians and their relationship with symptomatic control and future risk in patients with moderate-severe asthma.

PubMed

Crespo-Lessmann, Astrid; Plaza, Vicente; González-Barcala, Francisco-Javier; Fernández-Sánchez, Toni; Sastre, Joaquín

2017-01-01

Differences between the opinions of patients and physicians on the impact of asthma are common. We hypothesised that patient-physician discordance may negatively affect asthma outcome. A total of 2902 patients (61% women, mean age 47 years) with moderate-severe asthma and 231 physicians participated in a prospective study. At the baseline visit, data on demographics, clinical variables, degree of asthma control according to the Asthma Control Test (ACT), basic spirometry and the Hospital Anxiety and Depression Scale (HADS) were collected and an ad hoc questionnaire was completed that allowed the degree of concordance between doctors and patients to be assessed. A scheduled telephone call after 3 months was used to elicit the ACT score and the future risk of asthma. At the final visit at 6 months, the following data were recorded: ACT score, spirometry, HADS score and an ad hoc questionnaire to assess the agreement between the doctor and the patient. Changes in study variables according to patient-physician concordance or discordance were analysed. The rate of patient-physician discordance was 27.2%, with overestimation of disease impact by the physician in 12.3% and underestimation in 14.9%. Patient-physician opinion discordance, particularly in the case of physicians underestimating the impact of asthma, showed worse results with statistically significant differences in ACT score, a higher percentage of patients with poor asthma control and lower HADS scores. The need for hospital and emergency department admissions was also higher. Patient-physician opinion discordance may be contributing to lower symptomatic control and increased future risk, with a higher impact when physicians underestimate the impact of asthma on their patients.

Radiographic Evidence of Sinonasal Inflammation in Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: An Underrecognized Association.

PubMed

Hamada, Satoshi; Tatsumi, Shuji; Kobayashi, Yoshiki; Matsumoto, Hisako; Yasuba, Hirotaka

Sinonasal inflammation on both clinical examinations and imaging significantly impacts both asthma and chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the association between sinonasal inflammation and asthma-COPD overlap syndrome (ACOS). A total of 112 patients with a ratio of forced expiratory volume in 1 s to forced vital capacity of less than 70% were enrolled. COPD, asthma, and ACOS were clinically diagnosed according to the 2014 Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Sinonasal inflammatory condition was evaluated using sinus computed tomography, and its severity was assessed according to the Lund-Mackay staging (LMS) system. Ethmoid sinus-dominant shadow was defined as the presence of greater LMS scores for the anterior and posterior ethmoid sinuses than for the maxillary sinus. COPD, asthma, and ACOS were diagnosed in 55 (49.1%), 39 (34.8%), and 18 patients (16.1%), respectively. The frequency of radiographic evidence of sinonasal inflammation in patients with COPD, asthma, ACOS was 60.0%, 94.9%, and 72.2%, respectively. Patients with ACOS and COPD had only mild radiographic evidence of sinonasal inflammation (LMS score, 1-7), whereas moderate (LMS score, 8-11) and severe (LMS score, ≥12) radiographic evidence of sinonasal inflammation were detected only in patients with asthma. Furthermore, the frequency of ethmoid sinus-dominant shadow was significantly higher in patients with asthma than in those with COPD and ACOS. Radiographic evidence of sinonasal inflammation was a common comorbidity in ACOS. Future studies are required to examine the role of sinonasal inflammation in ACOS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A Mechanistic Role for Type III IFN-λ1 in Asthma Exacerbations Mediated by Human Rhinoviruses

PubMed Central

Miller, E. Kathryn; Hernandez, Johanna Zea; Wimmenauer, Vera; Shepherd, Bryan E.; Hijano, Diego; Libster, Romina; Serra, M. Elina; Bhat, Niranjan; Batalle, Juan P.; Mohamed, Yassir; Reynaldi, Andrea; Rodriguez, Andrea; Otello, Monica; Pisapia, Nestor; Bugna, Jimena; Bellabarba, Miguel; Kraft, David; Coviello, Silvina; Ferolla, F. Martin; Chen, Aaron; London, Stephanie J.; Siberry, George K.; Williams, John V.

2012-01-01

Rationale: Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear. Objectives: To determine the role of HRV in pediatric asthma exacerbations and the mechanisms mediating wheezing. Methods: We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma. Measurements and Main Results: HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21–2.99; P = 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-λ1 levels were higher in wheezing children infected with HRV compared with nonwheezing (P < 0.001) and increased with worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-λ1, children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57–2.46; P = 0.66). Conclusions: Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-λ1 responses mediate exacerbations caused by HRV. Modulation of IFN- λ1 should be studied as a therapeutic target for exacerbations caused by HRV. PMID:22135341

[Comparison Study of Oropharyngeal Microbiota in Case of Bronchial Asthma and Chronic Obstructive Pulmonary Disease in Different Severity Levels].

PubMed

Ogorodova, L M; Fedosenko, S V; Popenko, A S; Petrov, V A; Tyakht, A V; Saltykova, I V; Deev, I A; Kulikov, E S; Kirillova, N A; Govorun, V M; Kostryukova, E S

2015-01-01

The result of comparative study of oropharyngeal microbiota taxonomic composition in patients with different severity level of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is presented in this paper. To compare oropharyngeal microbiota composition in case of bronchial asthma and chronic obstructive pulmonary disease in different severity levels. 138 patients, 50 with BA and 88 with COPD were studied. For each patient was collected anamnesis vitae, swab from the back of the throat and performed physical examination. High-throughput 16S ribosomal RNA gene sequencing and bioinformatic analysis was employed to characterize the microbial communities. As a result of the study wasfound a number of differences on various taxonomic levels in microbiota's composition within group of patients with different severity level of BA and group of patients with different severity level of COPD and between those groups. COPD patients with GOLD 1-2 in comparison with GOLD 3-4 patiens are marked by prevalence of species Brevibacterium aureum, genus Scardovia, Coprococcus, Haemophilus, Moryella, Dialister, Paludibacter and decrease of Prevotella melaninogenica species. BA patients with severe uncontrolled asthma in comparison with patients which have mild persistent asthma are marked by decrease of Prevotella and increase of species Bifidobacterium longum, Prevotella nanceiensis, Neisseria cinerea, Aggregatibacter segnis and genus Odoribacter, Alloiococcus, Lactobacillus, Megasphaera, Parvimonas, Sneathia. Patient's microbiota in BA group in comparison with COPD group is characterized by the prevalence of Prevotella melaninogenica and genus Selenomonas, Granulicatella u Gemella, and decrease of Prevotella nigrescens, Haemophilus influenza and genus Aggregatibacter, Alloiococcus, Catonella, Mycoplasma, Peptoniphilus u Sediminibacterium. There are no differences between microbiota composition in case of severe uncontrolled BA and very severe COPD. Lack of differences in oropharyngeal microbiota taxonomic composition between patients with severe uncontrolled BA and very severe COPD allow us to suggest a similarity of bronchopulmonary system condition in case of diseases' severe stages.

Rural Asthma: Current Understanding of Prevalence, Patterns, and Interventions for Children and Adolescents.

PubMed

Estrada, Robin Dawson; Ownby, Dennis R

2017-06-01

Asthma is the most common chronic illness of children and adolescents in the USA. While asthma has been understood to disproportionately affect urban dwellers, recent investigations have revealed rural pediatric asthma prevalence to be very similar to urban and to be more closely correlated with socioeconomic and environmental factors than geographic location or population density. Rural children experience factors unique to location that impact asthma development and outcomes, including housing quality, cigarette smoke exposure, and small/large-scale farming. Additionally, there are challenging barriers to appropriate asthma care that frequently are more severe for those living in rural areas, including insurance status, lack of primary care providers and pulmonary specialists, knowledge deficits (both patient and provider), and a lack of culturally tailored asthma interventions. Interventions designed to address rural pediatric asthma disparities are more likely to be successful when targeted to specific challenges, such as the use of school-based services or telemedicine to mitigate asthma care access issues. Continued research on understanding the complex interaction of specific rural environmental factors with host factors can inform future interventions designed to mitigate asthma disparities.

Influence of chronic azithromycin treatment on the composition of the oropharyngeal microbial community in patients with severe asthma.

PubMed

Lopes Dos Santos Santiago, Guido; Brusselle, Guy; Dauwe, Kenny; Deschaght, Pieter; Verhofstede, Chris; Vaneechoutte, Dries; Deschepper, Ellen; Jordens, Paul; Joos, Guy; Vaneechoutte, Mario

2017-05-10

This study of the oropharyngeal microbiome complements the previously published AZIthromycin in Severe ASThma (AZISAST) clinical trial, where the use of azithromycin was assessed in subjects with exacerbation-prone severe asthma. Here, we determined the composition of the oropharyngeal microbial community by means of deep sequencing of the amplified 16S rRNA gene in oropharyngeal swabs from patients with exacerbation-prone severe asthma, at baseline and during and after 6 months treatment with azithromycin or placebo. A total of 1429 OTUs were observed, of which only 59 were represented by more than 0.02% of the reads. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria and Actinobacteria were the most abundant phyla and Streptococcus and Prevotella were the most abundant genera in all the samples. Thirteen species only accounted for two thirds of the reads and two species only, i.e. Prevotella melaninogenica and Streptococcus mitis/pneumoniae, accounted for one fourth of the reads. We found that the overall composition of the oropharyngeal microbiome in patients with severe asthma is comparable to that of the healthy population, confirming the results of previous studies. Long term treatment (6 months) with azithromycin increased the species Streptococcus salivarius approximately 5-fold and decreased the species Leptotrichia wadei approximately 5-fold. This was confirmed by Boruta feature selection, which also indicated a significant decrease of L. buccalis/L. hofstadtii and of Fusobacterium nucleatum. Four of the 8 treated patients regained their initial microbial composition within one month after cessation of treatment. Despite large diversity of the oropharyngeal microbiome, only a few species predominate. We confirm the absence of significant differences between the oropharyngeal microbiomes of people with and without severe asthma. Possibly, long term azithromycin treatment may have long term effects on the composition of the oropharygeal microbiome in half of the patients.

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

PubMed Central

Vijayakanthi, Nandini; Greally, John M.

2016-01-01

The burden of obesity-related asthma among children, particularly among ethnic minorities, necessitates an improved understanding of the underlying disease mechanisms. Although obesity is an independent risk factor for asthma, not all obese children develop asthma. Several recent studies have elucidated mechanisms, including the role of diet, sedentary lifestyle, mechanical fat load, and adiposity-mediated inflammation that may underlie the obese asthma pathophysiology. Here, we review these recent studies and emerging scientific evidence that suggest metabolic dysregulation may play a role in pediatric obesity-related asthma. We also review the genetic and epigenetic factors that may underlie susceptibility to metabolic dysregulation and associated pulmonary morbidity among children. Lastly, we identify knowledge gaps that need further exploration to better define pathways that will allow development of primary preventive strategies for obesity-related asthma in children. PMID:27244776

Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma.

PubMed

Castro, Mario; Corren, Jonathan; Pavord, Ian D; Maspero, Jorge; Wenzel, Sally; Rabe, Klaus F; Busse, William W; Ford, Linda; Sher, Lawrence; FitzGerald, J Mark; Katelaris, Constance; Tohda, Yuji; Zhang, Bingzhi; Staudinger, Heribert; Pirozzi, Gianluca; Amin, Nikhil; Ruddy, Marcella; Akinlade, Bolanle; Khan, Asif; Chao, Jingdong; Martincova, Renata; Graham, Neil M H; Hamilton, Jennifer D; Swanson, Brian N; Stahl, Neil; Yancopoulos, George D; Teper, Ariel

2018-05-21

Background Dupilumab is a fully human anti-interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma. Methods We randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV 1 ) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV 1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed. Results The annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P<0.001); similar results were seen with the dupilumab dose of 300 mg every 2 weeks. At week 12, the FEV 1 had increased by 0.32 liters in patients assigned to the lower dose of dupilumab (difference vs. matched placebo, 0.14 liters; P<0.001); similar results were seen with the higher dose. Among patients with a blood eosinophil count of 300 or more per cubic millimeter, the annualized rate of severe asthma exacerbations was 0.37 (95% CI, 0.29 to 0.48) among those receiving lower-dose dupilumab and 1.08 (95% CI, 0.85 to 1.38) among those receiving a matched placebo (65.8% lower rate with dupilumab than with placebo; 95% CI, 52.0 to 75.6); similar results were observed with the higher dose. Blood eosinophilia occurred after the start of the intervention in 52 patients (4.1%) who received dupilumab as compared with 4 patients (0.6%) who received placebo. Conclusions In this trial, patients who received dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. Greater benefits were seen in patients with higher baseline levels of eosinophils. Hypereosinophilia was observed in some patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA QUEST ClinicalTrials.gov number, NCT02414854 .).

Wheezing or Breezing through Exercise-Induced Asthma.

ERIC Educational Resources Information Center

McCarthy, Paul

1989-01-01

Several physicians discuss the tests they use to diagnose exercise-induced asthma (EIA), the medications they typically prescribe and why, and the importance of properly educating athletes about EIA. (JD)

Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community.

PubMed

Armour, Carol; Bosnic-Anticevich, Sinthia; Brillant, Martha; Burton, Debbie; Emmerton, Lynne; Krass, Ines; Saini, Bandana; Smith, Lorraine; Stewart, Kay

2007-06-01

Despite national disease management plans, optimal asthma management remains a challenge in Australia. Community pharmacists are ideally placed to implement new strategies that aim to ensure asthma care meets current standards of best practice. The impact of the Pharmacy Asthma Care Program (PACP) on asthma control was assessed using a multi-site randomised intervention versus control repeated measures study design. Fifty Australian pharmacies were randomised into two groups: intervention pharmacies implemented the PACP (an ongoing cycle of assessment, goal setting, monitoring and review) to 191 patients over 6 months, while control pharmacies gave their usual care to 205 control patients. Both groups administered questionnaires and conducted spirometric testing at baseline and 6 months later. The main outcome measure was asthma severity/control status. 186 of 205 control patients (91%) and 165 of 191 intervention patients (86%) completed the study. The intervention resulted in improved asthma control: patients receiving the intervention were 2.7 times more likely to improve from "severe" to "not severe" than control patients (OR 2.68, 95% CI 1.64 to 4.37; p<0.001). The intervention also resulted in improved adherence to preventer medication (OR 1.89, 95% CI 1.08 to 3.30; p = 0.03), decreased mean daily dose of reliever medication (difference -149.11 microg, 95% CI -283.87 to -14.36; p=0.03), a shift in medication profile from reliever only to a combination of preventer, reliever with or without long-acting beta agonist (OR 3.80, 95% CI 1.40 to 10.32; p=0.01) and improved scores on risk of non-adherence (difference -0.44, 95% CI -0.69 to -0.18; p=0.04), quality of life (difference -0.23, 95% CI -0.46 to 0.00; p=0.05), asthma knowledge (difference 1.18, 95% CI 0.73 to 1.63; p<0.01) and perceived control of asthma questionnaires (difference -1.39, 95% CI -2.44 to -0.35; p<0.01). No significant change in spirometric measures occurred in either group. A pharmacist-delivered asthma care programme based on national guidelines improves asthma control. The sustainability and implementation of the programme within the healthcare system remains to be investigated.

Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

PubMed

Aguirre-Valencia, David; Posso-Osorio, Iván; Bravo, Juan-Carlos; Bonilla-Abadía, Fabio; Tobón, Gabriel J; Cañas, Carlos A

2017-09-01

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

The Effects of Meal Schedule and Quantity on Problematic Behavior.

ERIC Educational Resources Information Center

Wacker, David P.; And Others

1996-01-01

Two case examples (a toddler with severe developmental delays and a 7-year old with severe mental retardation) illustrating effects of meal schedule and food quantity on displays of problematic behavior are offered. Brief functional analyses of aberrant behavior provided useful information for interpreting distinct patterns of behavior. (DB)

Effects of Triple P parenting intervention on child health outcomes for childhood asthma and eczema: Randomised controlled trial.

PubMed

Morawska, Alina; Mitchell, Amy E; Burgess, Scott; Fraser, Jennifer

2016-08-01

Childhood chronic health conditions have considerable impact on children. We aimed to test the efficacy of a brief, group-based parenting intervention for improving illness-related child behaviour problems, parents' self-efficacy, quality of life, parents' competence with treatment, and symptom severity. A 2 (intervention vs. care as usual) by 3 (baseline, post-intervention, 6-month follow-up) design was used, with random group assignment. Participants were 107 parents of 2- to 10-year-old children with asthma and/or eczema. Parents completed self-report questionnaires, symptom diaries, and home observations were completed. The intervention comprised two 2-h group discussions based on Triple P. Parents in the intervention group reported (i) fewer eczema-related, but not asthma-related, child behaviour problems; (ii) improved self-efficacy for managing eczema, but not asthma; (iii) better quality of life for parent and family, but not child; (iv) no change in parental treatment competence; (v) reduced symptom severity, particularly for children prescribed corticosteroid-based treatments. Results demonstrate the potential for brief parenting interventions to improve childhood chronic illness management, child health outcomes, and family wellbeing. Effects were stronger for eczema-specific outcomes compared to asthma-specific outcomes. Effects on symptom severity are very promising, and further research examining effects on objective disease severity and treatment adherence is warranted. ACTRN12611000558921. Copyright © 2016 Elsevier Ltd. All rights reserved.

Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome.

PubMed

Lötvall, Jan; Akdis, Cezmi A; Bacharier, Leonard B; Bjermer, Leif; Casale, Thomas B; Custovic, Adnan; Lemanske, Robert F; Wardlaw, Andrew J; Wenzel, Sally E; Greenberger, Paul A

2011-02-01

It is increasingly clear that asthma is a complex disease made up of number of disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is possibly the greatest obstacle in understanding the causes of asthma and improving treatment and can explain the failure to identify consistent genetic and environmental correlations to asthma. Here we describe a hypothesis whereby the asthma syndrome is divided into distinct disease entities with specific mechanisms, which we have called "asthma endotypes." An "endotype" is proposed to be a subtype of a condition defined by a distinct pathophysiological mechanism. Criteria for defining asthma endotypes on the basis of their phenotypes and putative pathophysiology are suggested. Using these criteria, we identify several proposed asthma endotypes and propose how these new definitions can be used in clinical study design and drug development to target existing and novel therapies to patients most likely to benefit. This PRACTALL (PRACtical ALLergy) consensus report was produced by experts from the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Children's illness drawings and asthma symptom awareness.

PubMed

Gabriels, R L; Wamboldt, M Z; McCormick, D R; Adams, T L; McTaggart, S R

2000-01-01

This study examines the relationship between children's abilities to perceive their symptoms of asthma via several previously researched subjective and objective procedures compared with their performance on a standardized children's drawing task and scale criteria. Results indicated that girls verbalized significantly more emotions about their drawings and were better able to detect airflow changes in their small airways than boys. The Gabriels Asthma Perception Drawing Scales (GAPDS) is a promising clinical tool for assessing children's perceptions and emotions about asthma via nonverbal methods. Varying methods of measuring asthma symptom awareness are not highly correlated; thus, more than one methodology is appropriate for use with children.

Bronchial Thermoplasty in Severe Asthma: Best Practice Recommendations from an Expert Panel.

PubMed

Bonta, Peter I; Chanez, Pascal; Annema, Jouke T; Shah, Pallav L; Niven, Robert

2018-01-01

Bronchial thermoplasty (BT) is a bronchoscopic treatment for patients with severe asthma who remain symptomatic despite optimal medical therapy. In this "expert best practice" paper, the background and practical aspects of BT are highlighted. Randomized, controlled clinical trials have shown BT to be safe and effective in reducing severe exacerbations, improving quality of life, and decreasing emergency department visits. Five-year follow-up studies have provided evidence of the functional stability of BT-treated patients with persistence of a clinical benefit. The Global Initiative for Asthma (GINA) guidelines state that BT can be considered as a treatment option for adult asthma patients at step 5. Patient selection for BT requires close collaboration between interventional pulmonologists and severe asthma specialists. Key patient selection criteria for BT will be reviewed. BT therapy is delivered in 3 separate bronchoscopy sessions at least 3 weeks apart, covering different regions of the lung separately. Patients are treated with 50 mg/day of prednisolone or equivalent for 5 days, starting treatment 3 days prior to the procedure. The procedure is performed under moderate-to-deep sedation or general anesthesia. At bronchos-copy a single-use catheter with a basket design is inserted through the instrument channel and the energy is delivered by a radiofrequency (RF) generator (AlairTM Bronchial Thermoplasty System). BT uses temperature-controlled RF energy to impact airway remodeling, including a reduction of excessive airway smooth muscle within the airway wall, which has been recognized as a predominant feature of asthma. The treatment should be performed in a systemic manner, starting at the most distal part of the (sub)segmental airway, then moving proximally to the main bronchi, ensuring that the majority of the airways are treated. In general, 40-70 RF activations are provided in the lower lobes, and between 50 and 100 activations in the upper lobes combined. The main periprocedural adverse events are exacerbation of asthma symptoms and increased cough and sputum production. Occasionally, atelectasis has been observed following the procedure. The long-term safety of BT is excellent. An optimized BT responder profile - i.e., which specific asthma phenotype benefits most - is a topic of current research. © 2018 S. Karger AG, Basel.

Costs associated with workdays lost and utilization of health care resources because of asthma in daily clinical practice in Spain.

PubMed

Ojeda, P; Sanz de Burgoa, V

2013-01-01

Asthma is associated with high indirect costs due to lower work productivity and higher absenteeism and presenteeism. To study loss of productivity measured using the lost workday equivalent (LWDE) index and health care utilization in asthmatics depending on age, geographical location, time period, severity, and level of asthma control. In this cross-sectional, observational, epidemiological multicenter study, 120 allergists nationwide were asked to select asthmatic patients aged 18 to 65 years who were evenly distributed according to the 4 levels of asthma severity (Global Initiative on Asthma) during 3 different seasons. The participants collected sociodemographic data, spirometry values, Asthma Control Test (ACT) score, health care utilization data, perceived stress according to the Impact on Work Productivity Index (IMPALA, indice del Impacto de la Enfermedad en la Productividad Laboral), and score on the Sheehan disability scale. The LWDE index was used to measure the number of workdays lost and the number of workdays with asthma symptoms combined with the percentage for average performance at work. The study sample comprised 1098 patients (58.7% females; 48.5% aged 18-40 and 51.5% aged 41-65). According to the ACT score, disease was uncontrolled in 57.6% of patients, well controlled in 32.8%, and totally controlled in 9.6%. The mean cost due to workdays lost was Euro 285.81/patient/mo (95% CI, Euro 252.71-318.92). Indirect costs were significantly higher in older patients (41-65 years, Euro 405.08; 95% CI, 348.97-461.19), patients with more severe disease (Euro 698.95; 95% CI, 588.63-809.27), and patients with more poorly controlled asthma (Euro 466.86; 95% CI, Euro 414.39-519.33). The average cost of health care units per patient for each 3-month period was Euro1317.30 (95% CI, Euro 1151.34-Euro 1483.26). Indirect costs were significantly higher in older patients (Euro 2104.00 in patients aged 18-40 vs Euro 3301.55 in patients aged 41-65), in northern and central regions, in severe disease (Euro 2921.63), and in more poorly controlled asthma (Euro 1799.42). Our findings could prove useful for physicians and health care providers.

Asthma Exacerbations and Unconventional Natural Gas Development in the Marcellus Shale

PubMed Central

Rasmussen, Sara G.; Ogburn, Elizabeth L.; McCormack, Meredith; Casey, Joan A.; Bandeen-Roche, Karen; Mercer, Dione G.; Schwartz, Brian S.

2017-01-01

Importance Asthma is common and can be exacerbated by air pollution and stress. Unconventional natural gas development (UNGD) has community and environmental impacts. In Pennsylvania, development began in 2005 and by 2012, 6,253 wells were drilled. There are no prior studies of UNGD and objective respiratory outcomes. Objective To evaluate associations between UNGD and asthma exacerbations. Design A nested case-control study comparing asthma patients with exacerbations to asthma patients without exacerbations from 2005–12. Setting The Geisinger Clinic, which provides primary care services to over 400,000 patients in Pennsylvania. Participants Asthma patients aged 5–90 years (n = 35,508) were identified in electronic health records; those with exacerbations were frequency-matched on age, sex, and year of event to those without. Exposure(s) On the day before each patient’s index date (cases: date of event or medication order; controls: contact date), we estimated UNGD activity metrics for four phases (pad preparation, drilling, stimulation [“fracking”], and production) using distance from the patient’s home to the well, well characteristics, and the dates and durations of phases. Main Outcome(s) and Measure(s) We identified mild, moderate, and severe asthma exacerbations (new oral corticosteroid medication order, emergency department encounter, and hospitalization, respectively). Results We identified 20,749 mild, 1,870 moderate, and 4,782 severe asthma exacerbations, and frequency-matched these to 18,693, 9,350, and 14,104 control index dates, respectively. In three-level adjusted models, there was an association between the highest group of the activity metric for each UNGD phase compared to the lowest group for 11 out of 12 UNGD-outcome pairs (odds ratios [95% CI] ranged from 1.5 [1.2–1.7] for the association of the pad metric with severe exacerbations to 4.4 [3.8–5.2] for the association of the production metric with mild exacerbations). Six of the 12 UNGD-outcome associations had increasing odds ratios across quartiles. Our findings were robust to increasing levels of covariate control and in sensitivity analyses that included evaluation of some possible sources of unmeasured confounding. Conclusions and Relevance Residential UNGD activity metrics were statistically associated with increased odds of mild, moderate, and severe asthma exacerbations. Whether these associations are causal awaits further investigation, including more detailed exposure assessment. PMID:27428612

A Self-Regulation Theory-Based Asthma Management Mobile App for Adolescents: A Usability Assessment.

PubMed

Sage, Adam; Roberts, Courtney; Geryk, Lorie; Sleath, Betsy; Tate, Deborah; Carpenter, Delesha

2017-02-01

Self-regulation theory suggests people learn to influence their own behavior through self-monitoring, goal-setting, feedback, self-reward, and self-instruction, all of which smartphones are now capable of facilitating. Several mobile apps exist to manage asthma; however, little evidence exists about whether these apps employ user-centered design processes that adhere to government usability guidelines for mobile apps. Building upon a previous study that documented adolescent preferences for an asthma self-management app, we employed a user-centered approach to assess the usability of a high-fidelity wireframe for an asthma self-management app intended for use by adolescents with persistent asthma. Individual interviews were conducted with adolescents (ages 11-18 years) with persistent asthma who owned a smartphone (N=8). Adolescents were asked to evaluate a PDF app wireframe consisting of 76 screen shots displaying app features, including log in and home screen, profile setup, settings and info, self-management features, and graphical displays for charting asthma control and medication. Preferences, comments, and suggestions for each set of screen shots were assessed using the audio-recorded interviews. Two coders reached consensus on adolescent evaluations of the following aspects of app features: (1) usability, (2) behavioral intentions to use, (3) confusing aspects, and (4) suggestions for improvement. The app wireframe was generally well received, and several suggestions for improvement were recorded. Suggestions included increased customization of charts and notifications, reminders, and alerts. Participants preferred longitudinal data about asthma control and medication use to be displayed using line graphs. All participants reported that they would find an asthma management app like the one depicted in the wireframe useful for managing their asthma. Early stage usability tests guided by government usability guidelines (usability.gov) revealed areas for improvement for an asthma self-management app for adolescents. Addressing these areas will be critical to developing an engaging and effective asthma self-management app that is capable of improving adolescent asthma outcomes. ©Adam Sage, Courtney Roberts, Lorie Geryk, Betsy Sleath, Deborah Tate, Delesha Carpenter. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 01.02.2017.

Future biologic therapies in asthma.

PubMed

Quirce, Santiago; Bobolea, Irina; Domínguez-Ortega, Javier; Barranco, Pilar

2014-08-01

Despite the administration of appropriate treatment, a high number of patients with asthma remain uncontrolled. This suggests the need for alternative treatments that are effective, safe and selective for the established asthma phenotypes, especially in patients with uncontrolled severe asthma. The most promising options among the new asthma treatments in development are biological therapies, particularly those monoclonal antibodies directed at selective targets. It should be noted that the different drugs, and especially the new biologics, act on very specific pathogenic pathways. Therefore, determination of the individual profile of predominant pathophysiological alterations of each patient will be increasingly important for prescribing the most appropriate treatment in each case. The treatment of severe allergic asthma with anti-IgE monoclonal antibody (omalizumab) has been shown to be effective in a large number of patients, and new anti-IgE antibodies with improved pharmacodynamic properties are being investigated. Among developing therapies, biologics designed to block certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13 (lebrikizumab), have a greater chance of being used in the clinic. Perhaps blocking more than one cytokine pathway (such as IL-4 and IL-13 with dulipumab) might confer increased efficacy of treatment, along with acceptable safety. Stratification of asthma based on the predominant pathogenic mechanisms of each patient (phenoendotypes) is slowly, but probably irreversibly, emerging as a tailored medical approach to asthma, and is becoming a key factor in the development of drugs for this complex respiratory syndrome. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Urban-Rural Differences in School Nurses' Asthma Training Needs and Access to Asthma Resources.

PubMed

Carpenter, Delesha M; Estrada, Robin Dawson; Roberts, Courtney A; Elio, Alice; Prendergast, Melissa; Durbin, Kathy; Jones, Graceann Clyburn; North, Steve

Few studies have examined school nurses preferences' for asthma training. Our purpose was to: 1) assess school nurses' perceived asthma training needs, 2) describe nurses' access to asthma educational resources, and 3) identify urban-rural differences in training needs and access to resources in southern states. A convenience sample of school nurses (n=162) from seven counties (two urban and five rural) in North Carolina and South Carolina completed an online, anonymous survey. Chi-square tests were used to examine urban-rural differences. Although most nurses (64%) had received asthma training within the last five years, urban nurses were more likely to have had asthma training than rural nurses (χ 2 =10.84, p=0.001). A majority of nurses (87%) indicated they would like to receive additional asthma training. Approximately half (45%) of nurses reported access to age-appropriate asthma education materials, but only 16% reported that their schools implemented asthma education programs. Urban nurses were more likely than rural nurses to have access to asthma education programs (χ 2 =4.10, p=0.04) and age-appropriate asthma education materials (χ 2 =8.86, p=0.003). Few schools are implementing asthma education programs. Rural nurses may be disadvantaged in terms of receiving asthma training and having access to asthma education programs and materials. Schools are an ideal setting for delivering age-appropriate asthma education. By providing school nurses with access to age-appropriate asthma education resources and additional asthma training, we can help them overcome several of the barriers that impede their ability to deliver asthma care to their students. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting key proximal drivers of type 2 inflammation in disease.

PubMed

Gandhi, Namita A; Bennett, Brandy L; Graham, Neil M H; Pirozzi, Gianluca; Stahl, Neil; Yancopoulos, George D

2016-01-01

Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is emerging as a unifying feature of both classically defined allergic diseases, such as asthma, and a range of other inflammatory diseases. Rather than reducing inflammation with broad-acting immunosuppressants or narrowly targeting downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and IL-13 - represent a promising strategy to achieve therapeutic benefit across multiple diseases. After several initial disappointing clinical results with therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized approach achieved therapeutic benefit in an asthma subtype exhibiting an 'allergic' phenotype. More recently, efficacy was extended into a broad population of people with asthma. This argues that the Type 2 inflammation is broadly relevant across the severe asthma population if the key upstream drivers are properly blocked. Moreover, the simultaneous inhibition of IL-4 and IL-13 has shown significant clinical activity in diseases that are often co-morbid with asthma - atopic dermatitis and chronic sinusitis with nasal polyps - supporting the hypothesis that targeting a central 'driver pathway' could benefit multiple allergic diseases.

Improving childcare staff management of acute asthma exacerbation - An Australian pilot study.

PubMed

Soo, Yien Yien; Luckie, Kate Helen; Saini, Bandana; Kritikos, Vicky; Brannan, John D; Moles, Rebekah Jane

2017-09-01

This study aimed to evaluate the effectiveness of an asthma first-aid training tool for childcare staff in Australia. The effects of training on both asthma knowledge and skills were assessed. A pre/post-study design was utilised to assess changes in asthma knowledge and asthma first-aid skills in childcare staff before and after an educational intervention. Asthma first-aid skills were assessed from the participant's response to two scenarios in which a child was having a severe exacerbation of asthma. Asthma knowledge and asthma skills scores were collected at base-line and 3 weeks post the education session, which involved feedback on each individual's skills and a brief lecture on asthma delivered via PowerPoint presentation. There was a significant improvement after intervention in asthma knowledge (Z = -3.638, p < 0.001) and asthma first-aid skills for both scenario 1 (Z = -6.012, p < 0.001) and scenario 2 (Z = -6.018, p < 0.001). In scenario 1 and 2, first-aid skills improved by 65% (p < 0.001) and 57% (p < 0.001), respectively. Asthma knowledge was high at baseline (79%) and increased by 7% (p < 0.001) after the educational intervention. These asthma knowledge results were not significant when adjusted for prior knowledge. Results suggest that knowledge assessment alone may not predict the practical skills needed for asthma first-aid. Skills assessment is a useful adjunct to knowledge assessment when gauging the ability of childcare staff to manage acute asthma exacerbation. Skills assessment could be considered for incorporation into future educational interventions to improve management of acute asthma exacerbation.

Internet-based self-management offers an opportunity to achieve better asthma control in adolescents.

PubMed

van der Meer, Victor; van Stel, Henk F; Detmar, Symone B; Otten, Wilma; Sterk, Peter J; Sont, Jacob K

2007-07-01

Internet and short message service are emerging tools for chronic disease management in adolescents, but few data exist on the barriers to and benefits of internet-based asthma self-management. Our objective was to reveal the barriers and benefits perceived by adolescents with well-controlled and poorly controlled asthma to current and internet-based asthma management. Ninety-seven adolescents with mild-to-moderate persistent asthma monitored their asthma control on a designated Web site. After 4 weeks, 35 adolescents participated in eight focus groups. Participants were stratified in terms of age, gender, and asthma control level. We used qualitative and quantitative methods to analyze the written focus group transcripts. Limited self-efficacy to control asthma was a significant barrier to current asthma management in adolescents with poor asthma control (65%) compared to adolescents with good asthma control (17%; p < 0.01). The former group revealed the following several benefits from internet-based asthma self-management: feasible electronic monitoring; easily accessible information; e-mail communication; and use of an electronic action plan. Personal benefits included the ability to react to change and to optimize asthma control. Patients with poor asthma control were able and ready to incorporate internet-based asthma self-management for a long period of time (65%), whereas patients with good control were not (11%; p < 0.01). Our findings reveal a need for the support of self-management in adolescents with poorly controlled asthma that can be met by the application of novel information and communication technologies. Internet-based self-management should therefore target adolescents with poor asthma control.

Patients' expectations of asthma treatment.

PubMed

Mancuso, Carol A; Rincon, Melina; Robbins, Laura; Charlson, Mary E

2003-12-01

A multicomponent model has been developed to explain patients' unmet expectations of medical care. The model proposes that expectations are related to patients' personal experiences with illness, perceived vulnerability to disease, transmitted knowledge, and perceived severity of disease. The objective of this cross-sectional study was to determine whether this model can be applied to patients' unrealistic expectations of treatment outcomes, specifically expecting to be cured of asthma. In total, 230 patients observed in a primary care practice in New York City were interviewed in person with open-ended questions about their expectations of asthma treatment. Responses were analyzed with qualitative techniques to generate categories of expectations. Patients had a mean age of 41 +/- 11 years, 21% were white, 30% African American, 42% Latino, and 7% other groups. Major categories of expectations were generated from patients' responses and included symptom relief (expected by 52%), cure (36%), improved physical function (21%), and improved psychological well-being (15%). The category of expecting a cure was assessed with patients' responses to the following items representing components of the model: 1) resource utilization and medication requirements for asthma (representing severity of disease); 2) perceived quality of asthma care and satisfaction with care (representing past asthma experiences); 3) the Asthma Self-Efficacy Scale (representing perceived vulnerability to exacerbations); and 4) experiences of social network contacts with asthma and the Check Your Asthma IQ survey (representing transmitted knowledge). In bivariate analysis, patients who expected a cure were more likely to be Latino or Native American or Asian (p = 0.02), to have never required oral corticosteroids (p = 0.004), to be dissatisfied with the status of their asthma (p = 0.008), to know others who were limited by asthma (p = 0.03), to have worse Asthma Self-Efficacy Scale scores (p = 0.002), to have worse Check Your Asthma IQ scores (p = 0.04), and to currently be taking inhaled corticosteroids (p = 0.03). In multivariate analysis, worse asthma self-efficacy (p = 0.008), never having required oral corticosteroids (p = 0.005), and currently taking inhaled corticosteroids (p = 0.05) remained associated with expecting a cure. As a result of this study, we found that patients have multiple expectations of asthma treatment, including realistic expectations such as symptom relief and improved function, as well as unrealistic expectations, specifically to be cured of asthma. A multicomponent model of patient and disease characteristics was associated with this unrealistic expectation. These findings indicate that clinicians can intervene in diverse areas to foster realistic expectations of treatment outcomes among asthma patients.

[Management of patients with bronchial asthma received general anesthesia and surgical intervention].

PubMed

To, Masako; Tajima, Makoto; Ogawa, Cyuhei; Otomo, Mamoru; Suzuki, Naohito; Sano, Yasuyuki

2002-01-01

Stimulation to bronchial mucosa is one of the major risk factor of asthma attack. When patients receive surgical intervention and general anesthesia, they are always exposed to stimulation to bronchial mucosa. Prevention method of bronchial asthma attack during surgical intervention is not established yet. We investigated that clinical course of patients with bronchial asthma who received general anesthesia and surgical intervention. Seventy-six patients with bronchial asthma were received general anesthesia and surgical intervention from 1993 to 1998. Twenty-four patients were mild asthmatic patients, 39 were moderate asthmatic patients and 13 were severe asthmatic patients. Preoperative treatment for preventing asthma attack was as follows; Eight patients were given intravenous infusion of aminophylline before operation. Fifty-two patients were given intravenous infusion of aminophylline and hydrocortisone before operation. Three patients were given intravenous infusion of hydrocortisone for consecutive 3 days before operation. Thirteen patients were given no treatment for preventing asthma attack. One patient was suffered from asthma attack during operation. She was given no preventing treatment for asthma attack before operation. Three patients were suffered from asthma attack after operation. No wound dehiscence was observed in all patients. To prevent asthma attack during operation, intravenous infusion of steroid before operation is recommended, when patients with asthma receive general anesthesia and surgical intervention.

Development, implementation, and evaluation of a community pharmacy-based asthma care model.

PubMed

Saini, Bandana; Krass, Ines; Armour, Carol

2004-11-01

Pharmacists are uniquely placed in the healthcare system to address critical issues in asthma management in the community. Various programs have shown the benefits of a pharmacist-led asthma care program; however, no such programs have previously been evaluated in Australia. To measure the impact of a specialized asthma service provided through community pharmacies in terms of objective patient clinical, humanistic, and economic outcomes. A parallel controlled design, where 52 intervention patients and 50 control patients with asthma were recruited in 2 distinct locations, was used. In the intervention area, pharmacists were trained and delivered an asthma care model, with 3 follow-up visits over 6 months. This model was evaluated based on clinical, humanistic, and economic outcomes compared between and within groups. There was a significant reduction in asthma severity in the intervention group, 2.6 +/- 0.5 to 1.6 +/- 0.7 (mean +/- SD; p < 0.001) versus the control group, 2.3 +/- 0.7 to 2.4 +/- 0.5. In the intervention group, peak flow indices improved from 82.7% +/- 8.2% at baseline to 87.4% +/- 8.9% (p < 0.001) at the final visit, and there was a significant reduction in the defined daily dose of albuterol used by patients, from 374.8 +/- 314.8 microg at baseline to 198.4 +/- 196.9 microg at the final visit (p < 0.015). There was also a statistically significant improvement in perceived control of asthma and asthma-related knowledge scores in the intervention group compared with the control group between baseline and the final visit. Annual savings of $132.84(AU) in medication costs per patient and $100,801.20 for the whole group, based on overall severity reduction, were demonstrated. Based on the results of this study, it appears that a specialized asthma care model offers community pharmacists an opportunity to contribute toward improving asthma management in the Australian community.

Unmet needs in asthma treatment in a resource-limited setting: findings from the survey of adult asthma patients and their physicians in Nigeria.

PubMed

Desalu, Olufemi Olumuyiwa; Onyedum, Cajetan Chigozie; Adeoti, Adekunle Olatayo; Ozoh, Obianuju Beatrice; Fadare, Joseph Olusesan; Salawu, Fatai Kunle; Danburam, Ali; Fawibe, Ademola Emmanuel; Adewole, Olanisun Olufemi

2013-01-01

The prevalence of asthma in our society is rising and there is need for better understanding of the asthma patients' perception and treatment practice of physicians. The study was aimed at determining asthma attitudes and treatment practices among adult physicians and patients in Nigeria, with the goal of identifying barriers to optimal management. To assess asthma attitudes, treatment practices and limitations among adult physicians and patients in Nigeria, a questionnaire survey was conducted among 150 patients and 70 physicians. Majority (66.7%) of the patients reported their asthma as moderate to severe, 42.7% had emergency room visit and 32% had admission due to asthma in the previous 12 months. Physicians and patients perceptions significantly differed in the time devoted to educational issues (31.4% vs.18.7%) and its contents: individual management plan (64.3% vs.33.3%), correct inhaler technique (84.0% vs.71.0%), medication side effects (80.0% vs.60.0%) and compliance 100% of time (5.7% vs. 18.7%). Patients reported that non-compliance with medication causes increased symptoms (67.0%), exacerbations (60.0%), bronchodilator use (56.0%), urgent physician visit (52.0%) and hospitalizations /ER visits (38.7%). Asthma medication in patients caused short term (10.7%) and long term side effects (20.0%). Due to side effects, 28.0% skipped and stopped their medications. Most physicians (85.7%) and patients (56.0%) agreed on the need for new medication options. The need for new medication in patients was strongly related to asthma severity, limitation of activities, side effects, cost and lack of satisfaction with current medication. With the exception of pulmonologists, physicians did not readily prescribe ICS and their prescriptions were not in line with treatment guidelines. This study has highlighted the gaps and barriers to asthma treatment which need to be addressed to improve the quality of care in Nigeria.

Associations Between Asthma Control and Airway Obstruction and Performance of Activities of Daily Living in Older Adults with Asthma.

PubMed

Woods, Eric C; O'Conor, Rachel; Martynenko, Melissa; Wolf, Michael S; Wisnivesky, Juan P; Federman, Alex D

2016-05-01

To determine the effect of asthma on functional limitations of older adults in the United States. Analyses were conducted with data from the Asthma Beliefs and Literacy in the Elderly study, a prospective cohort study of people aged 60 and older with asthma. Participants were recruited from urban primary care and pulmonary specialty practices in New York City and Chicago between 2010 and 2012. Individuals aged 60 and older with asthma (380 women, 72 men, mean age 67.5 ± 6.8 (range 60-98), 40% Latino, 30% black). Characteristics of participants with and without activity of daily living (ADL) limitations were compared using the chi-square test. Generalized estimating equations were used to model the relationships between poor asthma control (Asthma Control Questionnaire (ACQ) score >1.5) and severity of airway obstruction (forced expiratory volume in 1-second (FEV1 )) and number of ADL limitations. Participants with one or more ADL limitations were more likely to be female (90% vs 81%, P = .02) and Latino (58% vs 32%, P < .001), have less than a high school education (53% vs 27%, P < .001) and an income of $1,350 per month or less (79% vs 46%, P < .001), and be unmarried (78% vs 64%, P = .003). In the adjusted analysis, poorer ACQ scores (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.0-2.4; P = .05) but not severity of airway obstruction (OR = 1.1, 95% CI = 0.6-1.9) was associated with greater ADL limitations. Older adults reporting poor asthma control are more likely to have ADL limitations than those with controlled asthma, although one-time spirometry may not adequately identify those at risk of physical impairment from asthma. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Improved asthma control in patients with severe, persistent allergic asthma after 12 months of nightly temperature-controlled laminar airflow: an observational study with retrospective comparisons

PubMed Central

Schauer, Uwe; Bergmann, Karl-Christian; Gerstlauer, Michael; Lehmann, Sylvia; Gappa, Monika; Brenneken, Amelie; Schulz, Christian; Ahrens, Peter; Schreiber, Jens; Wittmann, Michael; Hamelmann, Eckard

2015-01-01

Introduction Continuous or episodic allergen exposure is a major risk factor of frequent symptoms and exacerbations for patients with allergic asthma. It has been shown that temperature-controlled laminar airflow (TLA) significantly reduced allergen exposure and airway inflammation and improved quality of life of patients with poorly controlled allergic asthma. Objective The objective was to evaluate the effects of nighttime TLA when used during real-life conditions for 12 consecutive months in addition to the patients’ regular medication. Methods This multicenter, pre- and postretrospective observational study included patients with inadequately controlled moderate-to-severe allergic asthma who received add-on treatment with TLA for 12 consecutive months. Data on medication use, asthma control, asthma symptoms, lung function, use of hospital resources, and exacerbations were collected after 4 and 12 months and compared with corresponding data collected retrospectively from medical records during the year prior to inclusion in the study. Results Data from 30 patients (mean age 28; range 8–70) completing 4 months and 27 patients completing 12 months of TLA use are presented. The mean number of exacerbations was reduced from 3.6 to 1.3 (p<0.0001), and the ratio of asthma-related emergency room visits or hospitalizations diminished from 72.4 to 23.3% (p=0.001) or from 44.8 to 20.0% (p<0.05), respectively, after 12 months of TLA use. The Asthma Control Test index increased from 14.1 to 18.5 (p<0.0001). After 4 months of TLA use, clear improvements can be shown for most variables in line with the data collected after 12 months. Conclusions The addition of TLA to the patients’ regular medication significantly reduced exacerbations, asthma symptoms, and the utilization of hospital resources. The data support that TLA may be an important new non-pharmacological approach in the management of poorly controlled allergic asthma. PMID:26557252

Improved asthma control in patients with severe, persistent allergic asthma after 12 months of nightly temperature-controlled laminar airflow: an observational study with retrospective comparisons.

PubMed

Schauer, Uwe; Bergmann, Karl-Christian; Gerstlauer, Michael; Lehmann, Sylvia; Gappa, Monika; Brenneken, Amelie; Schulz, Christian; Ahrens, Peter; Schreiber, Jens; Wittmann, Michael; Hamelmann, Eckard

2015-01-01

Continuous or episodic allergen exposure is a major risk factor of frequent symptoms and exacerbations for patients with allergic asthma. It has been shown that temperature-controlled laminar airflow (TLA) significantly reduced allergen exposure and airway inflammation and improved quality of life of patients with poorly controlled allergic asthma. The objective was to evaluate the effects of nighttime TLA when used during real-life conditions for 12 consecutive months in addition to the patients' regular medication. This multicenter, pre- and postretrospective observational study included patients with inadequately controlled moderate-to-severe allergic asthma who received add-on treatment with TLA for 12 consecutive months. Data on medication use, asthma control, asthma symptoms, lung function, use of hospital resources, and exacerbations were collected after 4 and 12 months and compared with corresponding data collected retrospectively from medical records during the year prior to inclusion in the study. Data from 30 patients (mean age 28; range 8-70) completing 4 months and 27 patients completing 12 months of TLA use are presented. The mean number of exacerbations was reduced from 3.6 to 1.3 (p<0.0001), and the ratio of asthma-related emergency room visits or hospitalizations diminished from 72.4 to 23.3% (p=0.001) or from 44.8 to 20.0% (p<0.05), respectively, after 12 months of TLA use. The Asthma Control Test index increased from 14.1 to 18.5 (p<0.0001). After 4 months of TLA use, clear improvements can be shown for most variables in line with the data collected after 12 months. The addition of TLA to the patients' regular medication significantly reduced exacerbations, asthma symptoms, and the utilization of hospital resources. The data support that TLA may be an important new non-pharmacological approach in the management of poorly controlled allergic asthma.

Safety of Adding Salmeterol to Fluticasone Propionate in Children with Asthma.

PubMed

Stempel, David A; Szefler, Stanley J; Pedersen, Søren; Zeiger, Robert S; Yeakey, Anne M; Lee, Laurie A; Liu, Andrew H; Mitchell, Herman; Kral, Kenneth M; Raphiou, Ibrahim H; Prillaman, Barbara A; Buaron, Kathleen S; Yun Kirby, Suyong; Pascoe, Steven J

2016-09-01

Long-acting beta-agonists (LABAs) have been shown to increase the risk of asthma-related death among adults and the risk of asthma-related hospitalization among children. It is unknown whether the concomitant use of inhaled glucocorticoids with LABAs mitigates those risks. This trial prospectively evaluated the safety of the LABA salmeterol, added to fluticasone propionate, in a fixed-dose combination in children. We randomly assigned, in a 1:1 ratio, children 4 to 11 years of age who required daily asthma medications and had a history of asthma exacerbations in the previous year to receive fluticasone propionate plus salmeterol or fluticasone alone for 26 weeks. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization), as assessed in a time-to-event analysis. The statistical design specified that noninferiority would be shown if the upper boundary of the 95% confidence interval of the hazard ratio for the primary safety end point was less than 2.675. The main efficacy end point was the first severe asthma exacerbation that led to treatment with systemic glucocorticoids, as assessed in a time-to-event analysis. Among the 6208 patients, 27 patients in the fluticasone-salmeterol group and 21 in the fluticasone-alone group had a serious asthma-related event (all were hospitalizations); the hazard ratio with fluticasone-salmeterol versus fluticasone alone was 1.28 (95% confidence interval [CI], 0.73 to 2.27), which showed the noninferiority of fluticasone-salmeterol (P=0.006). A total of 265 patients (8.5%) in the fluticasone-salmeterol group and 309 (10.0%) in the fluticasone-alone group had a severe asthma exacerbation (hazard ratio, 0.86; 95% CI, 0.73 to 1.01). In this trial involving children with asthma, salmeterol in a fixed-dose combination with fluticasone was associated with the risk of a serious asthma-related event that was similar to the risk with fluticasone alone. (Funded by GlaxoSmithKline; VESTRI ClinicalTrials.gov number, NCT01462344 .).

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study

PubMed Central

Li, Jing; Kang, Jian; Wang, Changzheng; Yang, Jing; Wang, Linda; Kottakis, Ioannis; Humphries, Michael

2016-01-01

Purpose Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. Methods This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). Results A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. Conclusions Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile. PMID:27126725

Omalizumab Improves Quality of Life and Asthma Control in Chinese Patients With Moderate to Severe Asthma: A Randomized Phase III Study.

PubMed

Li, Jing; Kang, Jian; Wang, Changzheng; Yang, Jing; Wang, Linda; Kottakis, Ioannis; Humphries, Michael; Zhong, Nanshan

2016-07-01

Omalizumab is the preferred add-on therapy for patients with moderate-to-severe persistent allergic asthma and has demonstrated efficacy and safety in various ethnicities. This study evaluated the efficacy and safety of omalizumab in Chinese patients with moderate-to-severe allergic asthma. This randomized, double-blind, parallel-group, placebo-controlled, phase III study assessed lung function, quality of life, asthma control, and safety of omalizumab after 24-week therapy in Chinese patients (18-75 years of age). A total of 616 patients were randomized (1:1) to omalizumab or placebo. The primary endpoint, least squares mean treatment difference (LSM-TD) in morning peak expiratory flow (PEF) (omalizumab vs placebo), at Weeks >20-24 was 8.85 L/min (Full analysis set; P=0.062). Per-protocol analysis set showed significant improvements with LSM-TD of 11.53 L/min in mean mPEF at Weeks >20-24 (P=0.022). The FEV1 % predicted was significantly improved with omalizumab vs placebo from 8 to 24 weeks (after 24-week treatment: LSM-TD=4.12%; P=0.001). At Week 24, a higher proportion of omalizumab-treated patients achieved clinically relevant improvements in standardized AQLQ (58.2% vs 39.3%; LSM=0.51 vs 0.10; P<0.001) and ACQ (49.5% vs 35.5%; LSM=-0.51 vs -0.34; P=0.002) scores vs placebo. Total and nighttime symptom scores reduced significantly with omalizumab vs placebo (LSM-TD=-0.21, P=0.048 and -0.12, P=0.011, respectively). Although the study was not powered to study differences in exacerbation rates (P=0.097), exacerbations in winter months were less frequent in the omalizumab vs placebo group (2 vs 21). Adverse event and severe adverse event rates were comparable between omalizumab and placebo. Omalizumab improves lung function, quality of life, and asthma control in Chinese patients with moderate-to-severe persistent allergic asthma and has a good safety profile.

Fungal Exposure and Asthma: IgE and Non-IgE-Mediated Mechanisms.

PubMed

Zhang, Zhonghua; Reponen, Tiina; Hershey, Gurjit K Khurana

2016-11-01

Fungi are ubiquitous in indoor and outdoor environments and have been associated with respiratory disease including childhood and adult asthma. A growing body of evidence from human and animal studies has revealed a link between fungal exposure, especially indoor fungal exposure, with asthma initiation, persistence, and exacerbation. Despite the overwhelming evidence linking mold exposure and asthma, the mechanistic basis for the association has remained elusive. It is now clear that fungi need not be intact to impart negative health effects. Fungal components and fungal fragments are biologically active and contribute to asthma development and severity. Recent mechanistic studies have demonstrated that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. This paper will review the connection between fungal exposure and asthma with a focus on the immunological mechanisms underlying this relationship.

Asthma phenotypes in childhood.

PubMed

Reddy, Monica B; Covar, Ronina A

2016-04-01

This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

Thunderstorm asthma: an overview of the evidence base and implications for public health advice.

PubMed

Dabrera, G; Murray, V; Emberlin, J; Ayres, J G; Collier, C; Clewlow, Y; Sachon, P

2013-03-01

Thunderstorm asthma is a term used to describe an observed increase in acute bronchospasm cases following the occurrence of thunderstorms in the local vicinity. The roles of accompanying meteorological features and aeroallergens, such as pollen grains and fungal spores, have been studied in an effort to explain why thunderstorm asthma does not accompany all thunderstorms. Despite published evidence being limited and highly variable in quality due to thunderstorm asthma being a rare event, this article reviews this evidence in relation to the role of aeroallergens, meteorological features and the impact of thunderstorm asthma on health services. This review has found that several thunderstorm asthma events have had significant impacts on individuals' health and health services with a range of different aeroallergens identified. This review also makes recommendations for future public health advice relating to thunderstorm asthma on the basis of this identified evidence.

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation.

PubMed

Vijayakanthi, Nandini; Greally, John M; Rastogi, Deepa

2016-05-01

The burden of obesity-related asthma among children, particularly among ethnic minorities, necessitates an improved understanding of the underlying disease mechanisms. Although obesity is an independent risk factor for asthma, not all obese children develop asthma. Several recent studies have elucidated mechanisms, including the role of diet, sedentary lifestyle, mechanical fat load, and adiposity-mediated inflammation that may underlie the obese asthma pathophysiology. Here, we review these recent studies and emerging scientific evidence that suggest metabolic dysregulation may play a role in pediatric obesity-related asthma. We also review the genetic and epigenetic factors that may underlie susceptibility to metabolic dysregulation and associated pulmonary morbidity among children. Lastly, we identify knowledge gaps that need further exploration to better define pathways that will allow development of primary preventive strategies for obesity-related asthma in children. Copyright © 2016 by the American Academy of Pediatrics.

Psychological treatment of Comorbid Asthma and Panic Disorder: A Pilot Study

PubMed Central

Lehrer, Paul M.; Karavidas, Maria Katsamanis; Lu, Shou-En; Feldman, Jonathan; Kranitz, Linda; Abraham, Smrithy; Sanderson, William; Reynolds, Russ

2008-01-01

We evaluated two protocols for treating adults with comorbid asthma and panic disorder. The protocols included elements of Barlow’s “panic control therapy” and several asthma education programs, as well as modules designed to teach participants how to differentiate asthma and panic symptoms, and how to apply specific home management strategies for each. Fifty percent of subjects dropped out of a 14-session protocol by the eighth session; however, 83% of patients were retained in an eight-session protocol. Clinical results were mostly equivalent: significant decreases of >50% in panic symptoms, clinically significant decreases in asthma symptoms, improvement in asthma quality of life, and maintenance of clinical stability in asthma. Albuterol use decreased significantly in the 14-session protocol and at a borderline level in the 8-session protocol, while pulmonary function was maintained. A controlled evaluation of this procedure is warranted. PMID:17693054

Hypnosis and asthma: a critical review.

PubMed

Hackman, R M; Stern, J S; Gershwin, M E

2000-02-01

Asthma is among the most common chronic diseases of the western world and has significant effects on patients' health and quality of life. Asthma is typically treated with pharmaceutical products, but there is interest in finding nonpharmaceutical therapies for this condition. Hypnosis has been used clinically to treat a variety of disorders that are refractive to pharmaceutical-based therapies, including asthma, but relatively little attention has been given recently to the use of clinical hypnosis as a standard treatment for asthma. Significant data suggest that hypnosis may be an effective treatment for asthma, but it is premature to conclude that hypnosis is unequivocally effective. Studies conducted to date have consistently demonstrated an effect of hypnosis with asthma. More and larger randomized, controlled studies are needed. Existing data suggest that hypnosis efficacy is enhanced in subjects who are susceptible to the treatment modality, with experienced investigators, when administered over several sessions, and when reinforced by patient autohypnosis. Children in particular appear to respond well to hypnosis as a tool for improving asthma symptoms.

Parental preference for short- versus long-course corticosteroid therapy in children with asthma presenting to the pediatric emergency department.

PubMed

Williams, Kelli W; Andrews, Annie L; Heine, Daniel; Russell, W Scott; Titus, M Olivia

2013-01-01

Asthma is the most common chronic condition affecting children and a prominent chief complaint in pediatric emergency departments (ED). We aimed to determine parental preference between short- and long-term courses of oral corticosteroids for use in children with mild to moderate asthma presenting to our pediatric ED with acute asthma exacerbations. We surveyed parents of asthmatic children who presented to our pediatric ED from August 2011 to April 2012. Questions characterized each patient's asthma severity, assessed parental preference among systemic steroid and inhaled medication delivery options for acute asthma management, and inquired about compliance, medication costs, and intention to follow up. The majority of our parents prefer the use of 1 to 2 days of steroids to 5 days for acute asthma exacerbations in the ED. Thus, dexamethasone is an attractive alternative to prednisone/prednisolone and should be considered in the management of acute asthma exacerbations in the ED.

Psychosocial functioning and stress-processing of children with asthma in the school context: differences and similarities with children without asthma.

PubMed

Röder, Irma; Kroonenberg, Pieter M; Boekaerts, Monique

2003-01-01

To characterize children with asthma by their stress processing at school and their psychosocial functioning. To establish similarities and differences between children with and without asthma. Participants were 79 children with asthma and 359 children without asthma (ages 8-12). Children completed questionnaires on stress processing and their well-being at school. Parents filled in a questionnaire on behavior problems, and teachers provided data on school performance and absence rate. Children with asthma had higher scores on absence rates, teacher-rated well-being, internalizing behavior problems, occurrence of "rejection by peers," and use of aggression when coping with "problems with school work." However, using discriminant analyses, the groups could not reliably be distinguished from one another by these variables. Children with asthma are similar to other children with regard to their stress processing at school and their psychosocial functioning. The value of conducting multivariate analysis over several univariate tests is underscored.

The Tennessee Children's Respiratory Initiative: Objectives, design and recruitment results of a prospective cohort study investigating infant viral respiratory illness and the development of asthma and allergic diseases.

PubMed

Hartert, Tina V; Carroll, Kecia; Gebretsadik, Tebeb; Woodward, Kimberly; Minton, Patricia

2010-05-01

The 'attack rate' of asthma following viral lower respiratory tract infections (LRTI) is about 3-4 fold higher than that of the general population; however, the majority of children who develop viral LRTI during infancy do not develop asthma, and asthma incidence has been observed to continuously decrease with age. Thus, we do not understand how viral LRTI either predispose or serve as a marker of children to develop asthma. The Tennessee Children's Respiratory Initiative has been established as a longitudinal prospective investigation of infants and their biological mothers. The primary goals are to investigate both the acute and the long-term health consequences of varying severity and aetiology of clinically significant viral respiratory tract infections on early childhood outcomes. Over four respiratory viral seasons, 2004–2008, term, predominantly non-low weight previously healthy infants and their biological mothers were enrolled during an infant's acute viral respiratory illness.Longitudinal follow up to age 6 years is ongoing [corrected]. This report describes the study objectives, design and recruitment results of the over 650 families enrolled in this longitudinal investigation. The Tennessee Children's Respiratory Initiative is additionally unique because it is designed in parallel with a large retrospective birth cohort of over 95,000 mother-infant dyads with similar objectives to investigate the role of respiratory viral infection severity and aetiology in the development of asthma. Future reports from this cohort will help to clarify the complex relationship between infant respiratory viral infection severity, aetiology, atopic predisposition and the subsequent development of early childhood asthma and atopic diseases.

Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

PubMed

Meert, Kathleen L; Clark, Jeff; Sarnaik, Ashok P

2007-11-01

1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. Retrospective medical record review. University-affiliated children's hospital. All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. None. Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH <7.35, Pco2 <35 torr [4.6 kPa], and base excess < or = -7 mmol/L) during their hospital course. Of these, lactic acid was assessed in four patients and was elevated in each; all had hyperglycemia (blood glucose >120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.

Predictive factors for moderate or severe exacerbations in asthma patients receiving outpatient care.

PubMed

Gutiérrez, Francisco Javier Álvarez; Galván, Marta Ferrer; Gallardo, Juan Francisco Medina; Mancera, Marta Barrera; Romero, Beatriz Romero; Falcón, Auxiliadora Romero

2017-05-02

Asthma exacerbations are important events that affect disease control, but predictive factors for severe or moderate exacerbations are not known. The objective was to study the predictive factors for moderate (ME) and severe (SE) exacerbations in asthma patients receiving outpatient care. Patients aged > 12 years with asthma were included in the study and followed-up at 4-monthly intervals over a 12-month period. Clinical (severity, level of control, asthma control test [ACT]), atopic, functional, inflammatory, SE and ME parameters were recorded. Univariate analysis was used to compare data from patients presenting at least 1 SE or ME during the follow-up period vs no exacerbations. Statistically significant (p <0.1) factors were then subjected to multiple analysis by binary logistic regression. A total of 330 patients completed the study, most of whom were atopic (76%), women (nearly 70%), with moderate and mild persistent asthma (>80%). Twenty-seven patients (8%) had a SE and 183 had a ME (58.5%) during follow-up. In the case of SEs, the only predictive factor identified in the multiple analysis was previous SE (baseline visit OR 4.218 95% CI 1.53-11.58, 4-month follow-up OR 6.88 95% CI 2.018-23.51) and inhalation technique (OR 3.572 95% CI 1.324-9.638). In the case of MEs, the only predictive factor found in the multiple analysis were previous ME (baseline visit OR 2.90 95% CI 1.54-5.48, 4-month follow- up OR 1.702 95% CI 1.146-2.529). The primary predictive factor for SE or ME is prior SE or ME, respectively. SEs seem to constitute a specific patient "phenotype", in which the sole predictive factor is prior SEs.

326 Lung Age/Chronological Age Index as Indicator of Clinical Improvement or Severity in Asthma Patients

PubMed Central

Castrejon-Vázquez, Isabel; Vargas, Maria Eugenia; Sabido, Raúl Cicero; Tapía, Jorge Galicia

2012-01-01

Background Spirometry is a very useful clinical test to evaluate pulmonary function in asthma. However pulmonary function could be affected by the sex, time of clinical evolution, lung age (LA) and chronological age (CA). The aim of this study was to evaluate LA/CA as index of clinical improvement or severity in asthma patients. Methods The tenets of the Declaration of Helsinki were followed, and all patients gave their informed consent to participate in this study. Asthma severity was evaluated according with GINA classification. Spirometry was performed at the beginning of this study, at 46 days, 96 days, 192 days and after 8 months. Statistical analysis was performed using t test, 2-way ANOVA test, correlation and multiple regression models as well as ROC curves were also performed, a P < 0.05 was considered as significant. Results 70 asthma patients were included (22 male and 48 female), mean CA was 35-years old; mean LA was 48-years with a LA/CA index = 1.4, time of clinical evolution was 13 years. A LA/CA index = 1 (range 0.5 to 0.9) was observed in asymptomatic patients. LA/CA index over 1 were related with airway inflammation, and a LA/CA index more than 2 correlated with GINA step 3. Interestingly when we analyzed CA and LA, we observed that in female group more than 10 years of difference between CA and LA, (GINA Step2 and 3); while in male we observed (GINA Step1, Step2 and Step3). LA/CA index ≤ 1 was considered as normal. Conclusions LA/CA index is a good as clinical indicator of clinical improvement or severity in asthma patients in with excellent correlation of pulmonary function and age.

Early administration of systemic corticosteroids reduces hospital admission rates for children with moderate and severe asthma exacerbation.

PubMed

Bhogal, Sanjit K; McGillivray, David; Bourbeau, Jean; Benedetti, Andrea; Bartlett, Susan; Ducharme, Francine M

2012-07-01

The variable effectiveness of clinical asthma pathways to reduce hospital admissions may be explained in part by the timing of systemic corticosteroid administration. We examine the effect of early (within 60 minutes [SD 15 minutes] of triage) versus delayed (>75 minutes) administration of systemic corticosteroids on health outcomes. We conducted a prospective observational cohort of children aged 2 to 17 years presenting to the emergency department with moderate or severe asthma, defined as a Pediatric Respiratory Assessment Measure (PRAM) score of 5 to 12. The outcomes were hospital admission, relapse, and length of active treatment; they were analyzed with multivariate logistic and linear regressions adjusted for covariates and potential confounders. Among the 406 eligible children, 88% had moderate asthma; 22%, severe asthma. The median age was 4 years (interquartile range 3 to 8 years); 64% were male patients. Fifty percent of patients received systemic corticosteroids early; in 33%, it was delayed; 17% of children failed to receive any. Overall, 36% of patients were admitted to the hospital. Compared with delayed administration, early administration reduced the odds of admission by 0.4 (95% confidence interval 0.2 to 0.7) and the length of active treatment by 0.7 hours (95% confidence interval -1.3 to -0.8 hours), with no significant effect on relapse. Delayed administration was positively associated with triage priority and negatively with PRAM score. In this study of children with moderate or severe asthma, administration of systemic corticosteroids within 75 minutes of triage decreased hospital admission rate and length of active treatment, suggesting that early administration of systemic corticosteroids may allow for optimal effectiveness. Copyright © 2012 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood

PubMed Central

Strachan, D P; Aït-Khaled, N; Foliaki, S; Mallol, J; Odhiambo, J; Pearce, N; Williams, H C

2015-01-01

Background Associations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries. Methods Questionnaire data for 210 200 children aged 6–7 years from 31 countries, and 337 226 children aged 13–14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence. Results In both age groups, inverse trends (P < 0.0001) were observed for reported ‘hay fever ever’ and ‘eczema ever’ with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita. Conclusions These global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the ‘hygiene hypothesis’ for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread. PMID:24912652

Global analysis of breast feeding and risk of symptoms of asthma, rhinoconjunctivitis and eczema in 6-7 year old children: ISAAC Phase Three.

PubMed

Björkstén, B; Aït-Khaled, N; Innes Asher, M; Clayton, T O; Robertson, C

2011-01-01

In Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC), we investigated the relationship between breast feeding in infancy and symptoms of asthma, rhinoconjunctivitis and eczema in 6-7 year old children. Parents or guardians of 6-7 year old children completed written questionnaires on current symptoms of asthma, rhinoconjunctivitis and eczema, and on a range of possible asthma risk factors including a history of breast feeding ever. Prevalence odds ratios were estimated using logistic regression, adjusted for gender, region of the world, language, per capita gross national income, and other risk factors. In all 206,453 children from 72 centres in 31 countries participated in the study. Reported breast feeding ever was not associated with current wheeze, with an odds ratio (adjusted for gender, region of the world, language, per capita gross national income, and factors encountered in infancy) of 0.99 (95% CI 0.92-1.05), current rhinoconjunctivitis (OR 1.00, 95% CI 0.93-1.08), current eczema (OR 1.05, 95% CI 0.97-1.12), or symptoms of severe asthma (OR 0.95, 95% CI 0.87-1.05). Breast feeding was however associated with a reduced risk of severe rhinoconjunctivitis (OR 0.74, 95% CI 0.59-0.94) and severe eczema (OR 0.79, 95% CI 0.66-0.95). There was no consistent association between breast feeding use in the first year of life and either a history or current symptoms of wheezing, rhinoconjunctivitis or eczema in 6-7 year old children, but possibly an effect on severe symptoms of the latter two conditions. Copyright © 2011 SEICAP. Published by Elsevier Espana. All rights reserved.

Real-life Efficacy of Omalizumab After 9 Years of Follow-up.

PubMed

Menzella, Francesco; Galeone, Carla; Formisano, Debora; Castagnetti, Claudia; Ruggiero, Patrizia; Simonazzi, Anna; Zucchi, Luigi

2017-07-01

Omalizumab is frequently used as add-on treatment to inhaled corticosteroids (ICS) and long-acting β2-agonists in patients with suboptimal control of severe asthma. Patients with severe asthma will typically require chronic treatment, although due to the limited amount of data available there are still some concerns about the safety and efficacy of long-term therapy with omalizumab. Herein, in an extension of a previous 4-year study, we report disease-related outcomes of 8 patients with severe persistent allergic asthma who have been followed for a total of 9 years in a real-life setting. Both quality of life (QoL) (evaluated using the Juniper Asthma-Related QoL Questionnaire [AQLQ]) and forced expiratory volume in 1 second (FEV1) showed sustained improvement at 9 years. The median values of AQLQ and FEV1 at 4 years were 5.5 and 82.0% compared to 5.9 and 85.5%, respectively, at 9 years, which were all significantly increased from baseline. After 9 years, the mean annual number of severe exacerbations was 0.63 compared to 5 at baseline. There also appeared to be a trend toward use of a lower dose of ICS at longer follow-up times. After 9 years, there were no safety concerns for continued use of omalizumab, and no asthma-related hospitalizations or emergency department visits were documented over the last 5 years. The present analysis is the longest reported clinical follow-up of omalizumab. Long-term maintenance treatment with omalizumab for up to 9 years is associated with continued benefits in reducing symptoms, exacerbations, and medication burden without any safety concerns. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.

Advances in pediatric asthma in 2014: Moving toward a population health perspective.

PubMed

Szefler, Stanley J

2015-03-01

Last year's "Advances in pediatric asthma in 2013: Coordinating asthma care" concluded that, "Enhanced communication systems will be necessary among parents, clinicians, health care providers and the pharmaceutical industry so that we continue the pathway of understanding the disease and developing new treatments that address the unmet needs of patients who are at risk for severe consequences of unchecked disease persistence or progression." This year's summary will focus on further advances in pediatric asthma related to prenatal and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding the management of asthma in children as indicated in Journal of Allergy and Clinical Immunology publications in 2014. A major theme of this review is how new research reports can be integrated into medical communication in a population health perspective to assist clinicians in asthma management. The asthma specialist is in a unique position to convey important messages to the medical community related to factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention, as well as new immunomodulators. By enhancing communication among patients, parents, primary care physicians, and specialists within provider systems, the asthma specialist can provide timely information that can help to reduce asthma morbidity and mortality. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma

PubMed Central

Johnson, Martin; Nikolos, Christina; Jester, William; Klanderman, Barbara; Litonjua, Augusto A.; Tantisira, Kelan G.; Truskowski, Kevin; MacDonald, Kevin; Panettieri, Reynold A.; Weiss, Scott T.

2015-01-01

Globally, asthma is a chronic inflammatory respiratory disease affecting over 300 million people. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. Vitamin D, as an adjunct therapy, may improve disease control in severe asthma patients since vitamin D enhances glucocorticoid responsiveness and mitigates airway smooth muscle (ASM) hyperplasia. We sought to characterize differences in transcriptome responsiveness to vitamin D between fatal asthma- and non-asthma-derived ASM by using RNA-Seq to measure ASM transcript expression in five donors with fatal asthma and ten non-asthma-derived donors at baseline and with vitamin D treatment. Based on a Benjamini-Hochberg corrected p-value <0.05, 838 genes were differentially expressed in fatal asthma vs. non-asthma-derived ASM at baseline, and vitamin D treatment compared to baseline conditions induced differential expression of 711 and 867 genes in fatal asthma- and non-asthma-derived ASM, respectively. Functional gene categories that were highly represented in all groups included extracellular matrix, and responses to steroid hormone stimuli and wounding. Genes differentially expressed by vitamin D also included cytokine and chemokine activity categories. Follow-up qPCR and individual analyte ELISA experiments were conducted for four cytokines (i.e. CCL2, CCL13, CXCL12, IL8) to measure TNFα-induced changes by asthma status and vitamin D treatment. Vitamin D inhibited TNFα-induced IL8 protein secretion levels to a comparable degree in fatal asthma- and non-asthma-derived ASM even though IL8 had significantly higher baseline levels in fatal asthma-derived ASM. Our findings identify vitamin D-specific gene targets and provide transcriptomic data to explore differences in the ASM of fatal asthma- and non-asthma-derived donors. PMID:26207385

Acetaminophen use and asthma in children.

PubMed

Sakulchit, Teeranai; Goldman, Ran D

2017-03-01

Question A child with a history of asthma came to my clinic with acute fever. I have heard that acetaminophen might be associated with exacerbation of asthma. Is it safe if I recommend acetaminophen for this child? Answer Most studies suggest an association between acetaminophen use in children and development of asthma later in childhood. However, several confounding factors in study design might contribute to this positive correlation, and without a prospective controlled trial, confirming this finding is challenging. If children have a known history of asthma, it is likely safe to administer a single dose of acetaminophen without concern of precipitating adverse respiratory symptoms. Regular use of acetaminophen to relieve fever or pain does not seem to exacerbate asthma in children more than ibuprofen does. Copyright© the College of Family Physicians of Canada.

[The Chinese experts' consensus on the evaluation and management of asthma exacerbation].

PubMed

2018-01-01

Asthma exacerbations can do a lot of harm to the patients and consume large amounts of medical resources. This consensus is based on the domestic and foreign guidelines and literatures to standardize the evaluation and management of asthma exacerbations in China. Asthma exacerbations are characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing or chest tightness and progressive decrease in lung function, and usually require modification of treatment. Recognizing risk factors and triggering factors of asthma exacerbations is helpful for the prevention and long-term management. Evaluation of asthma exacerbations is based on symptoms, lung function, and arterial blood gas. Management is stratified according to the severity of disease. Different regimens to treat asthma exacerbations are discussed in this consensus. Glucocorticoids should be used properly. Overuse of antibiotics should be avoided. Management of life-threatening asthma is discussed separately. Special attention should be paid in some special respects, such as asthma during peri-operation period, gestation period, and childhood. Diagnosis and management of complications are also of great significance and are discussed in details.

Self-hypnosis for anxiety associated with severe asthma: a case report

PubMed Central

Anbar, Ran D

2003-01-01

Background Management of asthma can be complicated by both medical and psychiatric conditions, such as gastroesophageal reflux, chronic sinusitis, and anxiety. When symptoms of asthma are interpreted without regard to such conditions treatment may yield a suboptimal outcome. For example, anxiety-associated dyspnea, tachypnea, and chest tightness can be mistakenly interpreted as resulting from an exacerbation of asthma. Medical treatment directed only for asthma may thus lead to overuse of asthma medications and increased hospitalizations. Case Presentation The described case illustrates how a systemic steroid-dependent patient with asthma benefited from receiving care from a pediatric pulmonologist who also was well versed in the diagnosis and treatment of anxiety. By using self-hypnosis, the patient was able to reduce her dependence on bronchodilators. Following modification of her medical therapy under supervision of the pulmonologist, and regular use of hypnosis, the patient ultimately was weaned off her systemic steroid therapy. Conclusions This report emphasizes that anxiety must be considered as a comorbid condition in the treatment of asthma. Self-hypnosis can be a useful skill in the treatment of a patient with anxiety and asthma. PMID:12875663

Self-hypnosis for anxiety associated with severe asthma: a case report.

PubMed

Anbar, Ran D

2003-07-22

Management of asthma can be complicated by both medical and psychiatric conditions, such as gastroesophageal reflux, chronic sinusitis, and anxiety. When symptoms of asthma are interpreted without regard to such conditions treatment may yield a suboptimal outcome. For example, anxiety-associated dyspnea, tachypnea, and chest tightness can be mistakenly interpreted as resulting from an exacerbation of asthma. Medical treatment directed only for asthma may thus lead to overuse of asthma medications and increased hospitalizations. The described case illustrates how a systemic steroid-dependent patient with asthma benefited from receiving care from a pediatric pulmonologist who also was well versed in the diagnosis and treatment of anxiety. By using self-hypnosis, the patient was able to reduce her dependence on bronchodilators. Following modification of her medical therapy under supervision of the pulmonologist, and regular use of hypnosis, the patient ultimately was weaned off her systemic steroid therapy. This report emphasizes that anxiety must be considered as a comorbid condition in the treatment of asthma. Self-hypnosis can be a useful skill in the treatment of a patient with anxiety and asthma.

Gene polymorphisms of tumor necrosis factor alpha-308 and interleukin-10-1082 among asthmatic Egyptian children.

PubMed

Zedan, Magdy; Settin, Ahmed; Farag, Mohammad K; El-Bayoumi, Mohammed; El Regal, Mohammed Ezz; El Baz, Rizk; Osman, Engy

2008-01-01

Tumor necrosis factor (TNF) alpha-308 and interleukin (IL)-10(-1082) have potent inflammatory responses in the process of airway inflammation in asthma. The purpose of this study was to check for association of polymorphisms related to cytokine genes with susceptibility and severity of bronchial asthma in Egyptian children. Blood samples of 69 asthmatic children receiving treatment and follow-up at the Allergy and Respiratory Medicine Unit, Mansoura University Children Hospital, Mansoura, Egypt, were subjected to DNA extraction and amplification using polymerase chain reaction with sequence-specific primers for detection of single nucleotide polymorphisms in the promoter regions of cytokine genes TNF-alpha(-308(G-->A)), IL-10(-1082(G-->A)). Compared with normal controls, Egyptian asthmatic children showed a significant higher frequency of IL-10(-1082) G/G homozygosity genotype (p < 0.001; odds ratio [OR] = 7) with lower frequency of G/A heterozygosity genotype among cases. This finding also was detected in cases with persistent asthma and eczema. These cases showed significant lower frequency of TNF-alpha-308 G/A heterozygosity (p < 0.05; OR = 0.44). Also, male cases, cases with positive family history, and those patients with persistent types of asthma showed a higher frequency of TNF-alpha-308 G/G homozygosity. IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G may be a contributing factor in susceptibility as well as severity of asthma among Egyptian children. Separate studies should be specified relating these cytokine genotypes to response to various modalities in asthma therapy. This study reports that IL-10(-1082(G-->A)) G/G and TNF-alpha-308(G-->A) G/G genotypes may be contributing factors in susceptibility as well as in severity of asthma among Egyptian children. Separate studies may be specified relating these cytokine genotypes to response to various modalities in asthma therapy.

Therapeutic interventions in severe asthma.

PubMed

Canonica, Giorgio Walter; Senna, Gianenrico; Mitchell, Patrick D; O'Byrne, Paul M; Passalacqua, Giovanni; Varricchi, Gilda

2016-01-01

The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospitalizations and Emergency Department accesses as well as expensive treatments. The recent identification of different endotypes of asthma, based on the inflammatory pattern, has led to the development of tailored treatments that target different inflammatory mediators. These are major achievements in the perspective of Precision Medicine: a leading approach to the modern treatment strategy. Omalizumab, an anti-IgE antibody, has been the only biologic treatment available on the market for severe asthma during the last decade. It prevents the linkage of the IgE and the receptors, thereby inhibiting mast cell degranulation. In clinical practice omalizumab significantly reduced the asthma exacerbations as well as the concomitant use of oral glucocorticoids. In the "Th2-high asthma" phenotype, the hallmarks are increased levels of eosinophils and other markers (such as periostin). Because anti-IL-5 in this condition plays a crucial role in driving eosinophil inflammation, this cytokine or its receptors on the eosinophil surface has been studied as a potential target for therapy. Two different anti-IL-5 humanized monoclonal antibodies, mepolizumab and reslizumab, have been proven effective in this phenotype of asthma (recently they both came on the market in the United States), as well as an anti-IL-5 receptor alpha (IL5Rα), benralizumab. Other monoclonal antibodies, targeting different cytokines (IL-13, IL-4, IL-17 and TSLP) are still under evaluation, though the preliminary results are encouraging. Finally, AIT, Allergen Immunotherapy, a prototype of Precision Medicine, is considered, also in light of the recent evidences of Sublingual Immunotherapy (SLIT) tablet efficacy and safety in mite allergic asthma patients. Given the high costs of these therapies, however, there is an urgent need to identify biomarkers that can predict the clinical responders.

Asthma exacerbations: risk factors for hospital readmissions.

PubMed

Gonzalez-Barcala, F-J; Calvo-Alvarez, U; Garcia-Sanz, M-T; Garcia-Couceiro, N; Martin-Lancharro, P; Pose, A; Carreira, J-M; Moure-Gonzalez, J-D; Valdes-Cuadrado, L; Muñoz, X

2018-02-01

The aim of our study is to analyse hospital readmissions due to asthma, as well as the factors associated with their increase. We carried out a retrospective study including all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The data were gathered by two members of the research team, by reviewing the clinical records. The first hospital admission of each patient was included for this study. An early readmission (ER) was defined as that which occurred in the following 15 days after hospital discharge and late readmission (LR) to that occurring from 16 days after discharge. This study included 2166 hospital admissions and 1316 patients, with a mean age of 62.6 years. Of the 1316 patients analysed, 36 (2.7%) had one ER and 313 (23.8%) one LR. The only factor independently associated with a higher probability of an ER was poor lung function. A higher probability of LR was associated with a greater severity of the asthma (OR: 17.8, for severe asthma versus intermittent asthma), to have had any hospital admission in the previous year (OR: 3.5) and the use of a combination of ICS-LABA as maintenance treatment. About 25% of the patients in our area admitted to hospital due to asthma exacerbation had repeat episodes of hospitalisation.

Active Video Game Exercise Training Improves the Clinical Control of Asthma in Children: Randomized Controlled Trial.

PubMed

Gomes, Evelim L F D; Carvalho, Celso R F; Peixoto-Souza, Fabiana Sobral; Teixeira-Carvalho, Etiene Farah; Mendonça, Juliana Fernandes Barreto; Stirbulov, Roberto; Sampaio, Luciana Maria Malosá; Costa, Dirceu

2015-01-01

The aim of the present study was to determine whether aerobic exercise involving an active video game system improved asthma control, airway inflammation and exercise capacity in children with moderate to severe asthma. A randomized, controlled, single-blinded clinical trial was carried out. Thirty-six children with moderate to severe asthma were randomly allocated to either a video game group (VGG; N = 20) or a treadmill group (TG; n = 16). Both groups completed an eight-week supervised program with two weekly 40-minute sessions. Pre-training and post-training evaluations involved the Asthma Control Questionnaire, exhaled nitric oxide levels (FeNO), maximum exercise testing (Bruce protocol) and lung function. No differences between the VGG and TG were found at the baseline. Improvements occurred in both groups with regard to asthma control and exercise capacity. Moreover, a significant reduction in FeNO was found in the VGG (p < 0.05). Although the mean energy expenditure at rest and during exercise training was similar for both groups, the maximum energy expenditure was higher in the VGG. The present findings strongly suggest that aerobic training promoted by an active video game had a positive impact on children with asthma in terms of clinical control, improvement in their exercise capacity and a reduction in pulmonary inflammation. Clinicaltrials.gov NCT01438294.

Fragrance materials in asthma: a pilot study using a surrogate aerosol product.

PubMed

Vethanayagam, Dilini; Vliagoftis, Harissios; Mah, Dennell; Beach, Jeremy; Smith, Ladd; Moqbel, Redwan

2013-11-01

Many household products contain fragrances. Little is known about exposure to fragrances on human health, particularly within the airways. This study aimed to evaluate how common household fragrance products (i.e. air fresheners, cleaning products) affect people with asthma, who frequently report sensitivity to these products. Many of these products have volatile organic compounds or semi-volatile organic compounds. This study evaluated nine fragrance materials in an aerosol formulation to assess effects on airway physiology, airway inflammation and symptom perception in normal controls and those with asthma. The effects of fragrances were evaluated in people without asthma, people with mild asthma and people with moderate asthma in a four-way crossover placebo-controlled study. Subjects were exposed twice to a fragranced aerosol and twice to a placebo aerosol (15 and 30 min each). Subjects completed a questionnaire for 29 symptoms during and up to 3 h after each exposure scenario. Spirometry was performed prior to and 3 h post-exposure; sputum induction was conducted 3 h post-exposure. Nasal symptoms showed the greatest frequency of response in all three subject groups, and moderate asthmatics reported the greatest symptom severity and symptom types. No significant differences were noted in physiology or cellular inflammation. A trend for increased symptoms was noted in moderate asthmatics, suggesting that asthma severity may play a factor in fragrance sensitivity.