Clinical and Immunological Efficacy of Aspirin Desensitization in Nasal Polyp Patients with Aspirin-Exacerbated Respiratory Disease

PubMed Central

Mortazavi, Negar; Esmaeilzadeh, Hossein; Abbasinazari, Mohammad; Babaie, Delara; Alyasin, Soheila; Nabavizadeh, Hesamodin; Esmailzadeh, Elmira

2017-01-01

This study aimed to investigate the efficacy and the underlining mechanism of aspirin desensitization among patients with Aspirin Exacerbated Respiratory Disease (AERD). Thirty-eight patients, who had undergone an aspirin challenge test and were diagnosed as having AERD, were engaged in a double-blind randomized clinical trial. They were divided into two groups—an active group of patients who went through aspirin desensitization, and the control group, receiving placebo. Clinical symptoms and the quality of life of the patients—in addition to the levels of interleukin 4 and 5 (IL4), (IL5)—were documented at the beginning of the study and again after six months of aspirin desensitization. The quality of life of the patients was significantly higher in the active group after six months (P = 0.001). Medication requirements and symptom score were manifested to be significantly lower in the active group after six months than at the beginning of the study (P = 0.005, 0.017 respectively). Forced expiratory volume in the second one (FEV1) was, also, significantly higher in the active group after six months of the study (P = 0.032). IL5 was found to be significantly lower in the active group after six months (P = 0.019). However, no significant difference was observed in the levels of IL4 between the two groups (P = 0.152). The study revealed that aspirin desensitization can improve the quality of life of patients with AERD, lessen their symptoms and medication requirements, lower their levels of IL5, and improve some pulmonary function tests such as FEV1. PMID:29552073

The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population.

PubMed

Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

2012-01-01

Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17-7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene.

The IL1B-511 Polymorphism (rs16944 AA Genotype) Is Increased in Aspirin-Exacerbated Respiratory Disease in Mexican Population

PubMed Central

Falfán-Valencia, Ramcés; Pavón-Romero, Gandhi F.; Camarena, Angel; García, María de la Luz; Galicia-Negrete, Gustavo; Negrete-García, María Cristina; Teran, Luis Manuel

2012-01-01

Aspirin exacerbated respiratory disease (AERD) is characterized by chronic hyperplastic rhinosinusitis, nasal polyposis, asthma, and aspirin sensitivity. The mechanisms which produce these manifestations of intolerance are not fully defined, current research focuses on cyclooxygenase 1 (COX-1) inhibition, metabolism of arachidonic acid, and the COX pathway to the lipoxygenase (LO) route, inducing increased synthesis of leukotrienes (LT). The biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis, such as IL1B and IL8. We performed a genetic association study between IL8-251 (rs4073) and IL1B-511 (rs16944) polymorphisms in AERD, aspirin-tolerant asthma (ATA), and healthy control subjects. Using allelic discrimination by real-time PCR, we found statistically nonsignificant associations between AERD, ATA, and healthy control subjects for the GG and GA genotypes of IL1B (rs16944). Interestingly, the AA genotype showed an increased frequency in the AERD patients versus the ATA group (GF = 0.19 versus 0.07, p = 0.018, OR 2.98, and 95% CI 1.17–7.82). This is the first observation that IL1B polymorphisms are involved in AERD. Thus, future studies must investigate whether interleukin-1β is released in the airways of AERD patients and whether it relates to genetic polymorphisms in the IL1B gene. PMID:22132000

Aspirin challenge and desensitization: how, when and why.

PubMed

Cortellini, Gabriele; Caruso, Cristiano; Romano, Antonino

2017-08-01

To investigate the current approach to aspirin challenge (drug provocation) and/or desensitization in patients with histories of hypersensitivity reactions to it, particularly in those with cardiovascular diseases. The literature indicates that patients with coronary artery disease (CAD), including those with an acute coronary syndrome, may safely undergo low-dose aspirin challenge and/or desensitization. Recently, flowcharts regarding challenge/desensitization procedures with aspirin in patients with CAD and histories of aspirin hypersensitivity reactions have become available. Aspirin desensitization and continuous aspirin therapy constitute an effective option in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory diseases (NERD) who have suboptimally controlled asthma or rhinosinusitis, or require multiple revision polypectomies. The use of aspirin has proven to reduce morbidity and mortality associated with CAD. There is a general consensus on aspirin's effectiveness in secondary prevention of CAD. Therefore, aspirin desensitization is necessary in patients with CAD and histories of hypersensitivity reactions to it. The effectiveness of aspirin desensitization and continuous therapy in patients with NERD has been shown in numerous studies. However, shared selection criteria of candidates for aspirin challenge/desensitization procedures, and simple and homogeneous protocols are necessary. Moreover, preventive safety measures are still needed in order to reduce the potential risks of these procedures.

Frequency and severity of reactions to a 325-mg aspirin dose during desensitization.

PubMed

Schuler, Charles F; Baldwin, James L; Baptist, Alan P

2017-03-01

The frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. To determine the rate and type of reaction at 325 mg of aspirin during desensitization. A retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20-40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. Eighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0-10.3; P = .05). During aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations.

PubMed

Lal, Devyani; Jategaonkar, Ameya A; Borish, Larry; Chambliss, Linda R; Gnagi, Sharon H; Hwang, Peter H; Rank, Matthew A; Stankiewicz, James A; Lund, Valerie J

2016-06-01

Management of rhinosinusitis during pregnancy requires special considerations. 1. Conduct a systematic literature review for acute and chronic rhinosinusitis (CRS) management during pregnancy. 2. Make evidence-based recommendations. The systematic review was conducted using MEDLINE and EMBASE databases and relevant search terms. Title, abstract and full manuscript review were conducted by two authors independently. A multispecialty panel with expertise in management of Rhinological disorders, Allergy-Immunology, and Obstetrics-Gynecology was invited to review the systematic review. Recommendations were sought on use of following for CRS management during pregnancy: oral corticosteroids; antibiotics; leukotrienes; topical corticosteroid spray/irrigations/drops; aspirin desensitization; elective surgery for CRS with polyps prior to planned pregnancy; vaginal birth versus planned Caesarian for skull base erosions/ prior CSF rhinorrhea. Eighty-eight manuscripts underwent full review after screening 3052 abstracts. No relevant level 1, 2, or 3 studies were found. Expert panel recommendations for rhinosinusitis management during pregnancy included continuing nasal corticosteroid sprays for CRS maintenance, using pregnancy-safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspirin desensitization for aspirin exacerbated respiratory disease. The manuscript presents detailed recommendations. The lack of evidence pertinent to managing rhinosinusitis during pregnancy warrants future trials. Expert recommendations constitute the current best available evidence.

Management of rhinosinusitis during pregnancy: systematic review and expert panel recommendations

PubMed Central

Lal, Devyani; Jategaonkar, Ameya A.; Borish, Larry; Chambliss, Linda R.; Gnagi, Sharon H.; Hwang, Peter H.; Rank, Matthew A.; Stankiewicz, James A.; Lund, Valerie J.

2018-01-01

Background Management of rhinosinusitis during pregnancy requires special considerations. Objectives 1. Conduct a systematic literature review for acute and chronic rhinosinusitis (CRS) management during pregnancy. 2. Make evidence-based recommendations. Methods The systematic review was conducted using MEDLINE and EMBASE databases and relevant search terms. Title, abstract and full manuscript review were conducted by two authors independently. A multispecialty panel with expertise in management of Rhinological disorders, Allergy-Immunology, and Obstetrics-Gynecology was invited to review the systematic review. Recommendations were sought on use of following for CRS management during pregnancy: oral corticosteroids; antibiotics; leukotrienes; topical corticosteroid spray/irrigations/drops; aspirin desensitization; elective surgery for CRS with polyps prior to planned pregnancy; vaginal birth versus planned Caesarian for skull base erosions/ prior CSF rhinorrhea. Results Eighty-eight manuscripts underwent full review after screening 3052 abstracts. No relevant level 1, 2, or 3 studies were found. Expert panel recommendations for rhinosinusitis management during pregnancy included continuing nasal corticosteroid sprays for CRS maintenance, using pregnancy-safe antibiotics for acute rhinosinusitis and CRS exacerbations, and discontinuing aspirin desensitization for aspirin exacerbated respiratory disease. The manuscript presents detailed recommendations. Conclusions The lack of evidence pertinent to managing rhinosinusitis during pregnancy warrants future trials. Expert recommendations constitute the current best available evidence. PMID:26800862

No significant detectable anti-infection effects of aspirin and statins in chronic obstructive pulmonary disease.

PubMed

Yayan, Josef

2015-01-01

Past studies have shown that aspirin and statins decrease the rate and severity of exacerbation, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). Although these studies are relatively new, there is evidence that new therapeutic strategies could prevent exacerbation of COPD. This article examines retrospectively the possibility of using aspirin and statins to prevent exacerbation and infection in patients with COPD. All patients with COPD were identified from hospital charts in the Department of Internal Medicine, Saarland University Medical Center, Germany, between 2004 and 2014. The study examined 514 medical reports and secured a study population of 300 with COPD. The mean age was 69 ± 10 years (206 men, 68.7%, 95% CI, 63.4-73.9; 94 women, 31.3%, 95% CI, 26.1-36.6). The study results did not show a causal relationship between aspirin and statins and prevention of exacerbation and infection in patients with COPD. In contrast, in this study, the exacerbation and infection rates increased under medication with aspirin and statins (p = 0.008).

Safety risks for patients with aspirin-exacerbated respiratory disease after acute exposure to selective nonsteroidal anti-inflammatory drugs and COX-2 inhibitors: Meta-analysis of controlled clinical trials.

PubMed

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

2014-07-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause bronchospasm in susceptible patients with asthma, often termed aspirin-exacerbated respiratory disease (AERD), with the risk being greatest after acute exposure. Selective NSAIDs that preferentially inhibit COX-2 might be safer. We sought to systematically evaluate changes in symptoms and pulmonary function after acute selective NSAID or COX-2 inhibitor exposure in patients with the AERD phenotype. A systematic review of databases was performed to identify all blinded, placebo-controlled clinical trials evaluating acute selective NSAID or COX-2 inhibitor exposure in patients with AERD. Effect estimates for changes in respiratory function and symptoms were pooled by using fixed-effects meta-analysis, with heterogeneity investigated. No significant difference in respiratory symptoms (risk difference, -0.01; 95% CI, -0.03 to 0.01; P = .57), decrease in FEV1 of 20% or greater (RD, 0.00; 95% CI, -0.02 to 0.02; P = .77), or nasal symptoms (RD, -0.01; 95% CI, -0.04 to 0.02; P = .42) occurred with COX-2 inhibitors (eg, celecoxib). Selective NSAID exposure caused respiratory symptoms in approximately 1 in 13 patients with AERD (RD, 0.08; 95% CI, 0.02 to 0.14; P = .01). No significant differences were found according to leukotriene antagonist exposure or whether NSAIDs were randomly allocated. According to clinical trial evidence in patients with stable mild-to-moderate asthma with AERD, acute exposure to COX-2 inhibitors is safe, and selective NSAIDs exhibit a small risk. Thus COX-2 inhibitors could be used in patients with AERD or in patients with general asthma unwilling to risk nonselective NSAID exposure when oral challenge tests are unavailable. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.

PubMed

Mastalerz, Lucyna; Januszek, Rafał; Kaszuba, Marek; Wójcik, Krzysztof; Celejewska-Wójcik, Natalia; Gielicz, Anna; Plutecka, Hanna; Oleś, Krzysztof; Stręk, Paweł; Sanak, Marek

2015-09-01

Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC). EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge. Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027). A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease.

PubMed

Stevens, Whitney W; Peters, Anju T; Hirsch, Annemarie G; Nordberg, Cara M; Schwartz, Brian S; Mercer, Dione G; Mahdavinia, Mahboobeh; Grammer, Leslie C; Hulse, Kathryn E; Kern, Robert C; Avila, Pedro; Schleimer, Robert P

Aspirin-exacerbated respiratory disease (AERD) comprises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to inhibitors of the cyclooxygenase-1 (COX-1) enzyme. The prevalence of AERD remains unclear, and few studies have compared the clinical characteristics of patients with AERD to those with CRSwNP alone, asthma alone, or both CRSwNP and asthma. To determine the prevalence of AERD within a tertiary care setting, and to identify unique clinical features that could distinguish these patients from those with both CRSwNP and asthma or with CRSwNP alone. Electronic medical records of patients at Northwestern in Chicago, Illinois, were searched by computer algorithm and then manual chart review to identify 459 patients with CRSwNP alone, 412 with both CRSwNP and asthma, 171 with AERD, and 300 with asthma only. Demographic and clinical features including sex, atopy, and sinus disease severity were characterized. The prevalence of AERD among patients with CRSwNP was 16%. Patients with AERD had undergone 2-fold more sinus surgeries (P < .001) and were significantly younger at the time of their first surgery (40 ± 13 years) than were patients with CRSwNP (43 ± 14 years; P < .05). Atopy was significantly more prevalent in patients with AERD (84%) or asthma (85%) than in patients with CRSwNP (66%, P < .05). More patients with AERD (13%) had corticosteroid-dependent disease than patients with both CRSwNP and asthma (4%, P < .01) or asthma (1%, P < .001). AERD is common among patients with CRSwNP; even though patients with AERD have CRSwNP and asthma, the clinical course of their disease is not the same as of patients who have CRSwNP and asthma but are tolerant to COX-1 inhibitors. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

PubMed Central

Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

2014-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

PubMed

Seemungal, T; Harper-Owen, R; Bhowmik, A; Moric, I; Sanderson, G; Message, S; Maccallum, P; Meade, T W; Jeffries, D J; Johnston, S L; Wedzicha, J A

2001-11-01

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

PubMed

Friedman, H; Seckman, C; Stubbs, C; Oster, H; Royer, G

1990-01-01

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Viruses in bronchiectasis: a pilot study to explore the presence of community acquired respiratory viruses in stable patients and during acute exacerbations.

PubMed

Mitchell, Alicia B; Mourad, Bassel; Buddle, Lachlan; Peters, Matthew J; Oliver, Brian G G; Morgan, Lucy C

2018-05-22

Bronchiectasis is a chronic respiratory condition. Persistent bacterial colonisation in the stable state with increased and sometimes altered bacterial burden during exacerbations are accepted as key features in the pathophysiology. The extent to which respiratory viruses are present during stable periods and in exacerbations is less well understood. This study aimed to determine the incidence of respiratory viruses within a cohort of bronchiectasis patients with acute exacerbations at a teaching hospital and, separately, in a group of patients with stable bronchiectasis. In the group of stable patients, a panel of respiratory viruses were assayed for using real time quantitative PCR in respiratory secretions and exhaled breath. The Impact of virus detection on exacerbation rates and development of symptomatic infection was evaluated. Routine hospital-based viral PCR testing was only requested in 28% of admissions for an exacerbation. In our cohort of stable bronchiectasis patients, viruses were detected in 92% of patients during the winter season, and 33% of patients during the summer season. In the 2-month follow up period, 2 of 27 patients presented with an exacerbation. This pilot study demonstrated that respiratory viruses are commonly detected in patients with stable bronchiectasis. They are frequently detected during asymptomatic viral periods, and multiple viruses are often present concurrently.

Association between respiratory impedance measured by forced oscillation technique and exacerbations in patients with COPD.

PubMed

Yamagami, Hitomi; Tanaka, Akihiko; Kishino, Yasunari; Mikuni, Hatsuko; Kawahara, Tomoko; Ohta, Shin; Yamamoto, Mayumi; Suzuki, Shintaro; Ohnishi, Tsukasa; Sagara, Hironori

2018-01-01

It is well known that increased airflow limitation as measured by spirometry is associated with the risk of exacerbation in patients with COPD. The forced oscillation technique (FOT) is a noninvasive method used to assess respiratory impedance (resistance and reactance) with minimal patient cooperation required. The clinical utility of the FOT in assessing the risk of exacerbations of COPD is yet to be determined. We examined the relationship between respiratory impedance as measured by FOT and exacerbations in patients with COPD. Among 310 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages I-IV) who presented at the outpatient clinic of the Showa University Hospital from September 2014 through January 2015, 119 were collected and assigned into 2 groups according to their history of exacerbation: exacerbators and nonexacerbators. Respiratory resistance components and respiratory reactance components, as measured by FOT, were compared between the two groups. Exacerbators were significantly older and had a higher white blood cell count than nonexacerbators. Resistance at 20 Hz, reactance at 5 Hz (X5), resonant frequency (Fres), and area of low reactance (ALX) differed significantly between the two groups. In addition, among patients with stage II COPD, there were significant differences in X5, Fres, and ALX between the two groups despite no significant differences in respiratory function as assessed by spirometry. Finally, receiver operating characteristic curve analysis revealed that the reactance components rather than the resistance components were associated with the risk of exacerbation. There were significant differences in respiratory impedance between exacerbators and nonexacerbators in patients with moderate COPD. FOT is a promising tool for assessing future exacerbations in patients with COPD.

Significance of Medication History at the Time of Entry into the COPDGene Study: Relationship with Exacerbation and CT Metrics

PubMed Central

Park, Seoung Ju; Make, Barry; Hersh, Craig P.; Bowler, Russell P.

2015-01-01

Background Despite the importance of respiratory medication use in COPD, relatively little is known about which clinical phenotypes were associated with respiratory medications. Methods To determine the association between respiratory medication use and exacerbations or quantitative CT metrics, we analyzed medication history from 4,484 COPD subjects enrolled in the COPDGene Study. Results 2,941 (65.6%) subjects were receiving one or more respiratory medications; this group experienced more frequent exacerbations in the year before study entry and had increased gas trapping, emphysema, and subsegmental airway wall area, compared to the patients who were on no respiratory medication. In subgroup analysis, subjects who were on triple therapy (long-acting beta2-agonist [LABA], long-acting muscarinic antagonist [LAMA], and inhaled corticosteroids [ICS]) had the highest frequencies of exacerbations and severe exacerbations and tended to have increased quantitative measures of emphysema and gas trapping on CT compared to other five groups. After adjustment for confounding variables, the triple therapy group experienced more exacerbations and severe exacerbations compared with other five groups. In addition, the LABA+LAMA+ICS group was more likely to have emphysema and gas trapping on CT than other groups in multivariable logistic analysis. Interestingly, the total number of respiratory medications was significantly associated with not only the frequency of exacerbations but also gas trapping and airway wall thickness as assessed by CT scan in multivariable analysis. Conclusions These results suggest that the use of respiratory medications, especially the number of medications, may identify a more severe phenotype of COPD that is highly susceptible to COPD exacerbations. PMID:25254928

Impact of exacerbations on respiratory system impedance measured by a forced oscillation technique in COPD: a prospective observational study.

PubMed

Kamada, Takahiro; Kaneko, Masahiro; Tomioka, Hiromi

2017-01-01

Forced oscillation technique (FOT) has been reported to be useful in the evaluation and management of obstructive lung disease, including COPD. To date, no data are available concerning long-term changes in respiratory system impedance measured by FOT. Additionally, although exacerbations have been reported to be associated with excessive lung function decline in COPD, the impact of exacerbations on the results of FOT has not been demonstrated. The aim of this study was to investigate the longitudinal changes in respiratory system impedance and the influence of exacerbations thereon. Between March 2011 and March 2012, outpatients who attended Kobe City Medical Center West Hospital with a diagnosis of COPD were assessed for eligibility. Baseline patient characteristics (age, sex, body mass index, smoking history, current smoking status, COPD stage), lung function (post-bronchodilator forced expiratory volume in 1 second [FEV 1 ]), blood tests (neutrophils and eosinophils), FOT, and COPD assessment test results were collected at enrollment. Lung function and FOT were examined every 6 months until March 2016. Annual changes in FEV 1 and FOT parameters were obtained from the slope of the linear regression curve. The patients were divided into 2 groups based on exacerbation history. Fifty-one of 58 patients with COPD were enrolled in this study. The median follow-up period was 57 (52-59) months. Twenty-five (49%) patients experienced exacerbations. A significant annual decline in FEV 1 and respiratory system impedance were shown. Additionally, annual changes in FEV 1 , respiratory system resistance at 5 Hz, respiratory system reactance at 5 Hz, and resonant frequency were greater in patients with exacerbations than in those without exacerbations. Exacerbations of COPD lead not only to a decline in lung function but also to an increase in respiratory system impedance.

Respiratory Infections and Antibiotic Usage in Common Variable Immunodeficiency.

PubMed

Sperlich, Johannes M; Grimbacher, Bodo; Workman, Sarita; Haque, Tanzina; Seneviratne, Suranjith L; Burns, Siobhan O; Reiser, Veronika; Vach, Werner; Hurst, John R; Lowe, David M

Patients with common variable immunodeficiency (CVID) suffer frequent respiratory tract infections despite immunoglobulin replacement and are prescribed significant quantities of antibiotics. The clinical and microbiological nature of these exacerbations, the symptomatic triggers to take antibiotics, and the response to treatment have not been previously investigated. To describe the nature, frequency, treatment, and clinical course of respiratory tract exacerbations in patients with CVID and to describe pathogens isolated during respiratory tract exacerbations. We performed a prospective diary card exercise in 69 patients with CVID recruited from a primary immunodeficiency clinic in the United Kingdom, generating 6210 days of symptom data. We collected microbiology (sputum microscopy and culture, atypical bacterial PCR, and mycobacterial culture) and virology (nasopharyngeal swab multiplex PCR) samples from symptomatic patients with CVID. There were 170 symptomatic exacerbations and 76 exacerbations treated by antibiotics. The strongest symptomatic predictors for commencing antibiotics were cough, shortness of breath, and purulent sputum. There was a median delay of 5 days from the onset of symptoms to commencing antibiotics. Episodes characterized by purulent sputum responded more quickly to antibiotics, whereas sore throat and upper respiratory tract symptoms responded less quickly. A pathogenic virus was isolated in 56% of respiratory exacerbations and a potentially pathogenic bacteria in 33%. Patients with CVID delay and avoid treatment of symptomatic respiratory exacerbations, which could result in structural lung damage. However, viruses are commonly represented and illnesses dominated by upper respiratory tract symptoms respond poorly to antibiotics, suggesting that antibiotic usage could be better targeted. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

The Role of the Microbiome in Exacerbations of Chronic Lung Diseases

PubMed Central

Dickson, Robert P.; Martinez, Fernando J.; Huffnagle, Gary B.

2014-01-01

Summary Culture-independent microbiological techniques have revealed a previously unappreciated complexity to the bacterial microbiome of the respiratory tract, forcing reconsideration of the interactions between host, bacteria and the pathogenesis of exacerbations of chronic lung disease. The composition of the lung microbiome is determined by microbial immigration, elimination, and the relative growth rates of its members; all of these change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack key features of bacterial infections, including increased bacterial burden and decreased community diversity. We propose instead that exacerbations are occasions of respiratory dysbiosis: a disordered respiratory microbial ecosystem with negative effects on host biology. Respiratory dysbiosis provokes a dysregulated host immune response, which in turn alters microbial growth conditions in patient airways, further promoting dysbiosis and perpetuating a coupled cycle of inflammation and disordered microbiota. Differences in baseline respiratory microbiota may help explain the “frequent-exacerbator” phenotype observed across multiple disease states, and may provide novel targets for therapeutic intervention. PMID:25152271

Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

PubMed

Makowska, Joanna S; Olszewska-Ziąber, Agnieszka; Bieńkiewicz, Barbara; Lewandowska-Polak, Anna; Kurowski, Marcin; Woźniakowski, Bartłomiej; Rotkiewicz, Arkadiusz; Kowalski, Marek L

2016-05-01

Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Sensitivity to non-acetylated salicylates in a patient with asthma, nasal polyps, and rheumatoid arthritis.

PubMed

Chudwin, D S; Strub, M; Golden, H E; Frey, C; Richmond, G W; Luskin, A T

1986-08-01

A woman experienced exacerbations of bronchial asthma after taking aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis. On oral challenges, she developed an urticarial reaction after tartrazine; urticarial and bronchospastic reactions after salicylsalicylic acid; and urticarial and bronchospastic reactions after choline magnesium trisalicylate. Non-acetylated salicylates have been recommended for use in aspirin- and/or tartrazine-sensitive patients. The results of sensitivity studies of our patient indicates that such patients may also be sensitive to non-acetylated salicylates.

Prevalence and Risk Factors of Respiratory Viral Infections in Exacerbations of Chronic Obstructive Pulmonary Disease.

PubMed

Kwak, Hyun Jung; Park, Dong Won; Kim, Jee Eun; Park, Min Kyung; Koo, Gun Woo; Park, Tai Sun; Moon, Ji-Yong; Kim, Tae Hyung; Sohn, Jang Won; Yoon, Ho Joo; Shin, Dong Ho; Kim, Sang-Heon

2016-10-01

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations.

Management of acute exacerbations of chronic obstructive pulmonary disease (COPD). Guidelines from the Société de pneumologie de langue française (summary).

PubMed

Jouneau, S; Dres, M; Guerder, A; Bele, N; Bellocq, A; Bernady, A; Berne, G; Bourdin, A; Brinchault, G; Burgel, P R; Carlier, N; Chabot, F; Chavaillon, J M; Cittee, J; Claessens, Y E; Delclaux, B; Deslée, G; Ferré, A; Gacouin, A; Girault, C; Ghasarossian, C; Gouilly, P; Gut-Gobert, C; Gonzalez-Bermejo, J; Jebrak, G; Le Guillou, F; Léveiller, G; Lorenzo, A; Mal, H; Molinari, N; Morel, H; Morel, V; Noel, F; Pégliasco, H; Perotin, J M; Piquet, J; Pontier, S; Rabbat, A; Revest, M; Reychler, G; Stelianides, S; Surpas, P; Tattevin, P; Roche, N

2017-04-01

Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

[Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

PubMed

Du, X B; Ma, X; Gao, Y; Wen, L F; Li, J; Wang, Z Z; Liu, S

2017-04-12

Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95% CI 1.51-16.48, P =0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.

Aspirin-induced chemoprevention and response kinetics are enhanced by PIK3CA mutations in colorectal cancer cells

PubMed Central

Zumwalt, Timothy J; Wodarz, Dominik; Komarova, Natalia L; Toden, Shusuke; Turner, Jacob; Cardenas, Jacob; Burn, John; Chan, Andrew T; Boland, C Richard; Goel, Ajay

2017-01-01

This study was designed to determine how aspirin influences the growth kinetics and characteristics of cultured colorectal cancer (CRC) cells that harbor a variety of different mutational backgrounds, including PIK3CA and KRAS activating mutations and the presence or absence of microsatellite instability. CRC cell lines (HCT116, HCT116+Chr3/5, RKO, SW480, HCT15, CACO2, HT29, and SW48) were treated with pharmacologically relevant doses of aspirin (0.5–10 mM) and evaluated for proliferation and cell cycle distribution. These parameters were fitted to a mathematical model to quantify the effects and understand the mechanism(s) by which aspirin modifies growth in CRC cells. We also evaluated the effects of aspirin on key G0/G1 cell cycle genes that are regulated by PI3K-Akt pathway. Aspirin decelerated growth rates and disrupted cell cycle dynamics more profoundly in faster growing CRC cell lines, which tended to be PIK3CA-mutants. Additionally, microarray analysis of 151 CRC cell lines identified important cell cycle regulatory genes downstream targets of PIK3, which were dysregulated by aspirin treatment cycle genes (PCNA and RB1, p<0.01). Our study demonstrated what clinical trials have only speculated, that PIK3CA-mutant CRCs are more sensitive to aspirin. Aspirin inhibited cell growth in all CRC cell lines regardless of mutational background, but the effects were exacerbated in cells with PIK3CA mutations. Mathematical modeling combined with bench science revealed that cells with PIK3CA mutations experience significant G0/G1 arrest and explains why patients with PIK3CA-mutant CRCs may benefit from aspirin use after diagnosis. PMID:28154202

Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial.

PubMed

Chang, Anne B; Grimwood, Keith; Wilson, Andrew C; van Asperen, Peter P; Byrnes, Catherine A; O'Grady, Kerry-Ann F; Sloots, Theo P; Robertson, Colin F; Torzillo, Paul J; McCallum, Gabrielle B; Masters, Ian B; Buntain, Helen M; Mackay, Ian M; Ungerer, Jacobus; Tuppin, Joanne; Morris, Peter S

2013-02-20

Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879.

Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879 PMID:23421781

The role of respiratory viruses in adult patients with cystic fibrosis receiving intravenous antibiotics for a pulmonary exacerbation.

PubMed

Etherington, C; Naseer, R; Conway, S P; Whitaker, P; Denton, M; Peckham, D G

2014-01-01

Respiratory viruses have become increasingly recognised as important agents in pulmonary exacerbations in infants and children with CF. The aim of this study was to determine the prevalence of respiratory viruses during acute pulmonary exacerbations in adults and compare the severity of these exacerbations with non-viral associated exacerbations. This was a retrospective case control study. Viral throat swabs were taken from all patients presenting with an acute pulmonary exacerbation requiring intravenous antibiotic treatment over a 12 month period. There were 432 pulmonary exacerbations in 180 adults. A positive viral PCR in 42 exacerbations indicated a prevalence of 9.7%. The commonest virus isolated was rhinovirus (n = 29, 69%) with influenza A/H1N1 in seven patients (16.7%). Exacerbations associated with a positive viral PCR had a greater fall in lung function at presentation with higher levels of inflammatory markers. They received more days of intravenous antibiotics, showed less response to treatment and had a shorter time to next pulmonary exacerbation compared to matched controls. Viral associated pulmonary exacerbations in adults with CF are associated with more severe pulmonary involvement and respond less well to standard treatment. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

[Family study of patients with aspirin intolerance and rhinosinusitis].

PubMed

May, A; Wagner, D; Langenbeck, U; Weber, A

2000-09-01

The high prevalence of aspirin intolerance in asthmatics and patients with nasal polyps as well as reports of familial clustering suggest a genetic disposition of this disease. Our study aimed at obtaining further evidence of hereditary factors in this disease. We included 33 unselected patients from 28 families with aspirin intolerance and rhinosinusitis in this study. Controls were recruited from individuals treated in our ENT clinic for diseases other than aspirin intolerance (n = 52). A questionnaire focused on family histories as well as reports on diseases of the upper respiratory tract or allergies. ASS intolerance was verified either by bronchial or nasal provocation tests. We found cases of aspirin intolerance among parents, siblings, and children of ASS intolerant probands. The children of probands had nasal polyps and rhinosinusitis more often than the children of controls. We propose that ASS intolerance with nasal polyps and asthma represents a complex phenotype, with genetic and environmental factors contributing to its manifestation.

Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review.

PubMed

Zheng, Xue-Yan; Xu, Yan-Jun; Guan, Wei-Jie; Lin, Li-Feng

2018-04-01

Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. We also examined the prevalence of viral infection stratified by age, geographic region, type of respiratory secretion, and detection method. Sixty articles were included in the final analysis. During asthma exacerbations, the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%, respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV, BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major virus detected globally, except in Africa. RV could be detected in both the upper and lower airway. Polymerase chain reaction was the most sensitive method for detecting viral infection. Our findings indicate the need to develop prophylactic polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce herd immunity and reduce the healthcare burden associated with virus-induced asthma exacerbations.

Incidence and clinical impact of respiratory viruses in adults with cystic fibrosis.

PubMed

Flight, William G; Bright-Thomas, Rowland J; Tilston, Peter; Mutton, Kenneth J; Guiver, Malcolm; Morris, Julie; Webb, A Kevin; Jones, Andrew M

2014-03-01

Viral respiratory infection (VRI) is a common cause of pulmonary exacerbations in children with cystic fibrosis (CF). The importance of VRI in adult CF populations is unclear. To determine the incidence and clinical impact of VRI among adults with CF. One hundred adults with CF were followed up prospectively for 12 months. Sputum, nose swabs and throat swabs were collected every 2 months and at onset of pulmonary exacerbation. PCR assays for adenovirus, influenza A&B, human metapneumovirus, parainfluenza 1-3, respiratory syncytial virus and human rhinovirus were performed on each sample. Symptom scores, spirometry and inflammatory markers were measured at each visit. One or more respiratory viruses were detected in 191/626 (30.5%) visits. Human rhinovirus accounted for 72.5% of viruses. Overall incidence of VRI was 1.66 (95% CI 1.39 to 1.92) cases/patient-year. VRI was associated with increased risk of pulmonary exacerbation (OR=2.19; 95% CI 1.56 to 3.08; p<0.001) and prescription of antibiotics (OR=2.26; 95% CI 1.63 to 3.13; p<0.001). Virus-positive visits were associated with higher respiratory symptom scores and greater C-reactive protein levels. Virus-positive exacerbations had a lower acute fall in FEV1 than virus-negative exacerbations (12.7% vs 15.6%; p=0.040). The incidence of exacerbations, but not VRI, was associated with greater lung function decline over 12 months (-1.79% per pulmonary exacerbation/year; 95% CI -3.4 to -0.23; p=0.025). VRI is common in adults with CF and is associated with substantial morbidity. Respiratory viruses are a potential therapeutic target in CF lung disease.

Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age.

PubMed

Byrnes, Catherine Ann; Vidmar, Suzanna; Cheney, Joyce L; Carlin, John B; Armstrong, David S; Cooper, Peter J; Grimwood, Keith; Moodie, Marj; Robertson, Colin F; Rosenfeld, Margaret; Tiddens, Harm A; Wainwright, Claire E

2013-07-01

Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years. Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry. 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient -0.39, 95% CI -0.74 to -0.05). Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.

Drug-disease interactions: narrative review of aspirin in gastric ulcer.

PubMed

Nwose, Ezekiel Uba; Yee, Kwang Choon

2016-09-01

Drug-disease interactions include the impact of a drug and a particular disease condition on each other. However, the current practice in addressing drug-disease interaction is unbalanced and mostly limited to how the drug worsens the disease or health condition. Aspirin and gastric ulcer interaction are used as an example to illustrate this concept, especially the narration of how disease affects drug efficacy. The number of molecules that make up 100 mg of aspirin is identified with a view to discuss the pharmacokinetics, especially in terms of absorption and distribution. Using hypothetical scenarios, the pharmacodynamics in co-morbidities that could involve gastric ulcer and aspirin are also discussed. There seems to be oversight in definition and description of drug-disease interaction, which is often limited to 'how drug exacerbates disease'. The implication of this limited definition is that the discussions, research and teaching of the topic either lacks information, or are not clear on 'how disease affects drug efficacy'. For example, gastric ulcer has the potential to enhance absorption, bioavailability and therapeutic effects of aspirin, but this is rarely discussed in preference to the probability of gastro-intestinal bleeding side-effect.

Sodium Cromoglycate Prevents Exacerbation of IgE-Mediated Food-Allergic Reaction Induced by Aspirin in a Rat Model of Egg Allergy.

PubMed

Yokooji, Tomoharu; Matsuo, Hiroaki

2015-01-01

Aspirin (ASP)-facilitated absorption of ingested allergens is considered an exacerbating factor in the development of food allergy. Sodium cromoglycate (SCG) is used for the treatment of atopic dermatitis with food allergy, but the efficacy of SCG in ASP-exacerbated food-allergy reactions is unclear. In this study, we evaluated the effect of SCG on ASP-exacerbated food-allergic reactions, as well as allergen absorption, in egg-allergic model rats. Plasma concentrations of ovalbumin (OVA) and fluorescein isothiocyanate-labeled dextran (FD-40), a marker for nonspecific-absorption pathways, were measured after oral administration of mixtures of OVA and FD-40 in OVA-unsensitized and OVA-sensitized rats. IgE-mediated allergic reactions were evaluated by measuring changes in rectal temperature and Evans blue dye (EBD) extravasation in the intestine and liver after oral challenge with OVA. The effects of ASP and SCG on such absorption and allergic reactions were also evaluated kinetically. In OVA-sensitized rats, plasma concentrations of OVA and FD-40 were significantly higher than those in unsensitized rats after oral administration. ASP increased the intestinal absorption of OVA and FD-40 via the paracellular pathway, and a lower rectal temperature and higher EBD extravasation were detected in the intestine and liver of OVA-sensitized rats. SCG ameliorated these ASP-facilitated absorptions and allergic reactions in a dose-dependent manner. In particular, high-dose SCG (195.2 μmol/kg) completely inhibited these absorptions and reactions. SCG can prevent ASP-exacerbated allergic reactions in patients with food allergy resulting from inhibition of increases in allergen absorption. © 2015 S. Karger AG, Basel.

Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age

PubMed Central

Byrnes, Catherine Ann; Vidmar, Suzanna; Cheney, Joyce L; Carlin, John B; Armstrong, David S; Cooper, Peter J; Grimwood, Keith; Moodie, Marj; Robertson, Colin F; Rosenfeld, Margaret; Tiddens, Harm A; Wainwright, Claire E

2013-01-01

Background Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years. Methods Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry. Results 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospital-managed exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient −0.39, 95% CI −0.74 to −0.05). Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group. PMID:23345574

The similarities and differences of epidemic cycles of chronic obstructive pulmonary disease and asthma exacerbations.

PubMed

Johnston, Neil W

2007-12-01

The majority of chronic obstructive pulmonary disease (COPD) and asthma exacerbations in both children and adults are associated with respiratory viral infections and are cyclic in nature. Some variation in these cycles is associated with the timing of the appearance of respiratory viruses, particularly influenza and respiratory syncytial virus. Much more, however, is associated with signal events that are of either fixed or predictable timing. In children, asthma exacerbations reach epidemic levels following school return after the summer vacation and these are predominantly associated with rhinovirus infections. Although younger adults experience a rise in asthma exacerbations at this time, these are secondary to the epidemic in children. Older adults with either COPD or asthma experience only a slightly elevated risk of exacerbations after school return, and hospital presentations for pneumonia in any age group show only marginal increases at that time. Exacerbations of both COPD and adult asthma, with increasing risk with age, are at their highest average annual levels during the Christmas period. This effect appears to be independent of the timing of above average levels of influenza, RSV, parainfluenza, or adenovirus detections; however, hospitalization for respiratory tract infections in all age groups reaches high levels at the same time. Both the post-summer vacation asthma epidemic and the Christmas epidemic of COPD, asthma, and pneumonia are synchronous with the timing of signal events, the day of school return for the former and Christmas Day for the latter, and have been for several years. The agents responsible for the Christmas epidemic of respiratory diseases have not yet been identified. The differences between age and disease exacerbation patterns after school return and at Christmas suggest that either different agents are involved or that the response to a common agent is different between the two signal events.

Use of aspirin, non-steroidal anti-inflammatory drugs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis: a cohort study.

PubMed

Wu, Shaowei; Han, Jiali; Qureshi, Abrar A

2015-02-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, non-aspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women, the Nurses' Health Study II (1991-2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95,540 participants during the follow-up. During 1,321,280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios of 3.60 [95% confidence interval (CI): 2.02-6.41] and 2.10 (95% CI: 1.11-3.96) for PsA, respectively. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs for long-term periods.

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

PubMed

Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

2013-11-01

Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

The Christmas season as a risk factor for chronic obstructive pulmonary disease exacerbations

PubMed Central

Johnston, Neil W; McIvor, Andrew; N, Kim Lambert Reg; Greene, Justina M; Hussac, Pat; de Verdier, Maria Gerhardsson; Higenbottam, Tim; Lewis, Jonathan; Newbold, Paul; Herath, Athula; Jenkins, Martin

2010-01-01

BACKGROUND Epidemics of hospitalization for chronic obstructive pulmonary disease (COPD) occur annually during the Christmas holidays, and COPD exacerbations commonly coincide with respiratory viral infections. OBJECTIVE To compare the incidence and determinants of COPD exacerbations occurring between the Christmas holiday period and the remainder of the winter season. METHODS Seventy-one subjects with COPD of mixed severity faxed daily symptom diaries to a computer monitoring system from December 1, 2006, to April 30, 2007. Possible exacerbations prompted a home visit for assessment, spirometry and specimen collection for virological testing. RESULTS Study subjects submitted a total of 95.4% of possible daily symptom diary sheets by fax. Of 114 possible COPD exacerbations detected using the faxed diaries, 110 met the Anthonisen criteria for true exacerbations. A total of 47 exacerbations (mean 6.7/week) occurred during the Christmas holiday period, while 63 exacerbations (mean 4.3/week) occurred during the remainder of winter. Of the Christmas period exacerbations and of those in the balance of winter, 21 (44%) and 20 (32%), respectively, coincided with respiratory viral infections. CONCLUSIONS The incidence of COPD exacerbations during the Christmas period was greater than during the rest of winter in 2006/2007 and peaked immediately before Christmas – in contrast to hospital presentation for COPD, which peaked during the Christmas week. No clear role of respiratory viral infections in the increased rate of exacerbations during the Christmas period was established in the present study. COPD patients were highly compliant with daily symptom reporting using faxed daily diaries, which permitted nearly complete detection of all exacerbations that occurred at incidence. PMID:21165349

Pathogenic Mechanisms and In Vitro Diagnosis of AERD

PubMed Central

Schäfer, Dirk; Maune, Steffen

2012-01-01

Aspirin-exacerbated respiratory disease (AERD) refers to chronic rhinosinusitis, nasal polyposis, bronchoconstriction, and/or eosinophilic inflammation in asthmatics following the exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A key pathogenic mechanism associated with AERD is the imbalance of eicosanoid metabolism focusing on prostanoid and leukotriene pathways in airway mucosa as well as blood cells. Genetic and functional metabolic studies on vital and non-vital cells pointed to the variability and the crucial role of lipid mediators in disease susceptibility and their response to medication. Eicosanoids, exemplified by prostaglandin E2 (PGE2) and peptidoleukotrienes (pLT), are potential metabolic biomarkers contributing to the AERD phenotype. Also other mediators are implicated in the progress of AERD. Considering the various pathogenic mechanisms of AERD, a multitude of metabolic and genetic markers is suggested to be implicated and were introduced as potential biomarkers for in vitro diagnosis during the past decades. Deduced from an eicosanoid-related pathogenic mechanism, functional tests balancing PGE2 and pLT as well as other eicosanoids from preferentially vital leukocytes demonstrated their applicability for in vitro diagnosis of AERD. PMID:22654920

The Likelihood of Preventing Respiratory Exacerbations in Children and Adolescents with either Chronic Suppurative Lung Disease or Bronchiectasis

PubMed Central

O’Grady, Kerry-Ann F; Grimwood, Keith

2017-01-01

Chronic suppurative lung disease (CSLD) and bronchiectasis in children and adolescents are important causes of respiratory morbidity and reduced quality of life (QoL), also leading to subsequent premature death during adulthood. Acute respiratory exacerbations in pediatric CSLD and bronchiectasis are important markers of disease control clinically, given that they impact upon QoL and increase health-care-associated costs and can adversely affect future lung functioning. Preventing exacerbations in this population is, therefore, likely to have significant individual, familial, societal, and health-sector benefits. In this review, we focus on therapeutic interventions, such as drugs (antibiotics, mucolytics, hyperosmolar agents, bronchodilators, corticosteroids, non-steroidal anti-inflammatory agents), vaccines and physiotherapy, and care-planning, such as post-hospitalization management and health promotion strategies, including exercise, diet, and reducing exposure to environmental toxicants. The review identified a conspicuous lack of moderate or high-quality evidence for preventing respiratory exacerbations in children and adolescents with CSLD or bronchiectasis. Given the short- and long-term impact of exacerbations upon individuals, their families, and society as a whole, large studies addressing interventions at the primary and tertiary prevention phases are required. This research must include children and adolescents in both developing and developed countries and address long-term health outcomes. PMID:28393062

Aspirin does not affect exercise performance.

PubMed

Roi, G S; Garagiola, U; Verza, P; Spadari, G; Radice, D; Zecca, L; Cerretelli, P

1994-07-01

A single-blind, cross-over study was carried out to evaluate the effects of acetylsalicylic acid (ASA) on cardiorespiratory performance during exercise. Eighteen young men, 9 athletes and 9 untrained but active subjects, performed a progressive maximal exercise test on a cycle ergometer (30 watt, 3 min steps, starting at 60 watt) on three different occasions, after a single administration of plain aspirin (1000mg of ASA), chewable buffered aspirin (1000mg of ASA and 600 mg of calcium carbonate) and placebo. Continuous measurement of breath-by-breath ventilation, oxygen consumption, carbon dioxide output, respiratory frequency and heart rate was carried-out at rest and during the exercise test. Blood lactate concentration was measured just before the start of exercise and at the third minute of each step in order to detect the anaerobic threshold. The pharmacokinetics of aspirin during exercise was also investigated in ten of the eighteen participants. The analysis of all investigated variables did not show any statistically significant difference between treatments, suggesting that a single dose of 1000mg of aspirin does not affect physical performance during submaximal and maximal exercise.

Pneumococcal vaccination and chronic respiratory diseases.

PubMed

Froes, Filipe; Roche, Nicolas; Blasi, Francesco

2017-01-01

Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases.

Genetic associations with viral respiratory illnesses and asthma control in children

PubMed Central

Loisel, Dagan A; Du, Gaixin; Ahluwalia, Tarunveer Singh; Tisler, Christopher J.; Evans, Michael D.; Myers, Rachel A.; Gangnon, Ronald E.; Kreiner-Møller, Eskil; Bønnelykke, Klaus; Bisgaard, Hans; Jackson, Daniel J.; Lemanske, Robert F.; Nicolae, Dan L.; Gern, James E.; Ober, Carole

2015-01-01

Background Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. Objective We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. Methods The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2,128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma birth cohort study (COAST). Results A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. Conclusions We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma. PMID:26399222

Salicylate pre-treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin-intolerant patients.

PubMed

Nizankowska, E; Dworski, R; Soja, J; Szczeklik, A

1990-11-01

Aspirin (ASA) and other non-steroidal anti-inflammatory drugs, which are cyclooxygenase (COX) inhibitors, precipitate asthmatic attacks in ASA-intolerant patients, while sodium salicylate, hardly active on COX by itself, is well tolerated by these patients. However, salicylate moiety appears to interfere with aspirin inhibitory action on platelets and vascular COX. Such interaction, if present at the level of respiratory tract, may be of interest to pathogenesis of ASA-induced asthma. We performed a double-blind, placebo-controlled, randomized cross-over study on the effect of choline magnesium trisalicylate (CMT, trilisate) pre-treatment on ASA-induced adverse reactions in nine patients. Pulmonary function tests, nasal symptoms score, PNIF and serum salicylate levels were monitored following challenges with threshold doses of ASA. Trilisate administered at a dose of 3000 mg daily for 3 days, offered a moderate protection against ASA-induced symptoms; it diminished the severity and/or delayed the appearance of FEV1 fall. Maximal decreases in FEV1 as well as reaction intensity indexes were significantly lower (P less than 0.02 and P less than 0.002, respectively) after trilisate pre-treatment as compared to placebo. Trilisate also attenuated nasal symptoms in three out of five patients. Although the precise mechanism of the protective action of trilisate is unknown, our data support the possibility of interaction between salicylate and ASA on cyclo-oxygenase locus in the respiratory tract in ASA-intolerant patients.

Chronic aspirin via dose-dependent and selective inhibition of cardiac proteasome possibly contributed a potential risk to the ischemic heart.

PubMed

Tan, Chunjiang; Chen, Wenlie; Wu, Yanbin; Lin, Jiumao; Lin, Ruhui; Tan, Xuerui; Chen, Songming

2013-08-01

Impaired cardiac proteasome has been reported in ischemic heart and heart failure. Recent data highlighted aspirin as an inhibitor of the ubiquitin-proteasome system, however, it's unclear whether it affects cardiac proteasome functions. Myocardial infarction (MI), sham or normal male SD rats were injected intraperitoneally with high (300 mg/kg), low (5 mg/kg) aspirin or saline (control) once a day for seven weeks. Parallel experiments were performed in the hypoxia/reoxygenated human ventricular myocytes. Dose-related increases in heart and ventricular weight, and impaired cardiac functions, were found more exacerbated in the aspirin-treated MI rat hearts than the saline-treated MI counterparts. The activity of 26S, 20S and 19S declined by about 30%, or the 20S proteasome subunits β5, β2 and β1 decreased by 40%, 20% and 30%, respectively, in the MI rats compared with the non-MI rats (P<0.05). Compared with the saline-treated MI rats, 26S and 20S in high or low dose aspirin-treated MI rats further decreased by 30% and 20%, β5 by 30% and 12%, and β1 by 40% and 30%, respectively, and the lost activity was correlated with the compromised cardiac functions or the decreased cell viability. The dose-related and selective inhibition of 26S and 20S proteasome, or the 20S proteasome subunits β5 and β1 by aspirin was comparable to their protein expressions in the MI rats and in the cultured cells. The impaired cardiac proteasome, enhanced by chronic aspirin treatment, attenuated the removal of oxidative and ubiquitinated proteins, and chronic aspirin treatment via selective and dose-dependent inhibition of cardiac proteasome possibly constituted a potential risk to ischemic heart. Copyright © 2013 Elsevier Inc. All rights reserved.

Chronic Sinusitis

MedlinePlus

... connected to chronic sinusitis Aspirin sensitivity that causes respiratory symptoms An immune system disorder, such as HIV/AIDS or cystic fibrosis Hay fever or another allergic condition that affects your sinuses Regular exposure to pollutants such as cigarette smoke Complications Chronic ...

Clinical presentation of metabolic alkalosis in an adult patient with cystic fibrosis.

PubMed

Sweetser, Lisel J; Douglas, James A; Riha, Renata L; Bell, Scott C

2005-03-01

In subtropical and tropical climates, dehydration is common in cystic fibrosis patients with respiratory exacerbations. This may lead to a clinical presentation of metabolic alkalosis with associated hyponatraemia and hypochloraemia. An adult cystic fibrosis patient who presented with a severe respiratory exacerbation accompanied by metabolic alkalosis is presented and the effects of volume correction are reported.

Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats.

PubMed

Masuda, Takahiro; Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2018-01-01

Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). The aim of this study was to clarify the effect of LDA on chronic RE in rats. Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p < 0.05). The grade of severity correlated with the depth of inflammation (r s  = 0.492, p < 0.001). Maximal dose aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults

PubMed Central

Gold, Diane R; Litonjua, Augusto A.; Carey, Vincent J.; Manson, JoAnn E.; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

2016-01-01

Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial—the VITamin D and OmegA-3 TriaL (VITAL)—to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2×2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA] +docosahexaenoic acid [DHA], 1 g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. PMID:26784651

Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults.

PubMed

Gold, Diane R; Litonjua, Augusto A; Carey, Vincent J; Manson, JoAnn E; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

2016-03-01

Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial-the VITamin D and OmegA-3 TriaL (VITAL)--to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. Copyright © 2016 Elsevier Inc. All rights reserved.

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

PubMed

Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

2017-11-01

Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the prevention and treatment of ARDS. NCT01659307 Results. 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/.

Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations.

PubMed

Vilaró, Jordi; Ramirez-Sarmiento, Alba; Martínez-Llorens, Juana M A; Mendoza, Teresa; Alvarez, Miguel; Sánchez-Cayado, Natalia; Vega, Angeles; Gimeno, Elena; Coronell, Carlos; Gea, Joaquim; Roca, Josep; Orozco-Levi, Mauricio

2010-12-01

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. A multicentre study was carried out in 121 COPD patients (92% males, 63 ± 11 yr, FEV(1), 49 ± 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PI(max)), and expiratory (PE(max)) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses. Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV(1) (PE(max), OR = 6.8, p < 0.01; PI(max), OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV(1), was associated with current acute exacerbations. Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Preoperative Aspirin Use and Lung Injury After Aortic Valve Replacement Surgery: A Retrospective Cohort Study.

PubMed

Mazzeffi, Michael; Kassa, Woderyelesh; Gammie, James; Tanaka, Kenichi; Roman, Philip; Zhan, Min; Griffith, Bartley; Rock, Peter

2015-08-01

Acute respiratory distress syndrome (ARDS) occurs uncommonly after cardiac surgery but has a mortality rate as high as 80%. Aspirin may prevent lung injury in at-risk patients by reducing platelet-neutrophil aggregates in the lung. We hypothesized that preoperative aspirin use would be associated with a decreased risk of ARDS after aortic valve replacement surgery. We performed a retrospective single-center cohort study that included all adult patients who had aortic valve replacement surgery during a 5-year period. The primary outcome variable was postoperative ARDS. The secondary outcome variable was nadir PaO2/FIO2 ratio during the first 72 hours after surgery. Both crude and propensity score-adjusted logistic regression analyses were performed to estimate the odds ratio for developing ARDS in aspirin users. Subgroups were analyzed to determine whether preoperative aspirin use might be associated with improved oxygenation in patients with specific risk factors for lung injury. Of the 375 patients who had aortic valve replacement surgery during the study period, 181 patients took aspirin preoperatively (48.3%) with most taking a dose of 81 mg (72.0%). There were 22 cases of ARDS in the cohort (5.5%). There was no significant difference in the rate of ARDS between aspirin users and nonusers (5.0% vs 6.7%, P = 0.52). There was also no significant difference in the nadir PaO2/FIO2 ratio between aspirin users and nonusers (P = 0.12). The crude odds ratio for ARDS in aspirin users was 0.725 (99% confidence interval, 0.229-2.289; P = 0.47), and the propensity score-adjusted odds ratio was 0.457 (99% confidence interval, 0.120-1.730; P = 0.13). Within the constraints of this analysis that included only 22 affected patients, preoperative aspirin use was not associated with a decreased incidence of ARDS after aortic valve replacement surgery or improved oxygenation.

Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts

PubMed Central

Keene, Jason D.; Jacobson, Sean; Kechris, Katerina; Kinney, Gregory L.; Foreman, Marilyn G.; Doerschuk, Claire M.; Make, Barry J.; Curtis, Jeffrey L.; Rennard, Stephen I.; Barr, R. Graham; Bleecker, Eugene R.; Kanner, Richard E.; Kleerup, Eric C.; Hansel, Nadia N.; Woodruff, Prescott G.; Han, MeiLan K.; Paine, Robert; Martinez, Fernando J.; O’Neal, Wanda K.

2017-01-01

Rationale: Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux. Objectives: To determine the value of adding blood biomarkers to clinical variables to predict exacerbations. Methods: Subjects from the SPIROMICS (Subpopulations and Intermediate Outcomes Measures in COPD Study) (n = 1,544) and COPDGene (Genetic Epidemiology of COPD) (n = 602) cohorts had 90 plasma or serum candidate proteins measured on study entry using Myriad-RBM multiplex panels. We defined total exacerbations as subject-reported worsening in respiratory health requiring therapy with corticosteroids and/or antibiotics, and severe exacerbations as those leading to hospitalizations or emergency room visits. We assessed retrospective exacerbations during the 12 months before enrollment and then documented prospective exacerbations in each cohort. Exacerbations were modeled for biomarker associations with negative binomial regression including clinical covariates (age, sex, percent predicted FEV1, self-reported gastroesophageal reflux, St. George’s Respiratory Questionnaire score, smoking status). We used the Stouffer-Liptak test to combine P values for metaanalysis. Measurements and Main Results: Between the two cohorts, 3,471 total exacerbations (1,044 severe) were reported. We identified biomarkers within each cohort that were significantly associated with a history of exacerbation and with a future exacerbation, but there was minimal replication between the cohorts. Although established clinical features were predictive of exacerbations, of the blood biomarkers only decorin and α2-macroglobulin increased predictive value for future severe exacerbations. Conclusions: Blood biomarkers were significantly associated with the occurrence of exacerbations but were not robust between cohorts and added little to the predictive value of clinical covariates for exacerbations. PMID:27579823

Frequency of self-reported COPD exacerbation and airflow obstruction in five Latin American cities: the Proyecto Latinoamericano de Investigacion en Obstruccion Pulmonar (PLATINO) study.

PubMed

Montes de Oca, Maria; Tálamo, Carlos; Halbert, Ronald J; Perez-Padilla, Rogelio; Lopez, Maria Victorina; Muiño, Adriana; Jardim, José Roberto B; Valdivia, Gonzalo; Pertuzé, Julio; Moreno, Dolores; Menezes, Ana Maria B

2009-07-01

Recurrent exacerbations are common in COPD patients. Limited information exists regarding exacerbation frequency in COPD patients from epidemiologic studies. We examined the frequency of self-reported exacerbations and the factors influencing exacerbation frequency among COPD patients in a population-based study conducted in Latin America. We used a post-bronchodilator FEV(1)/FVC ratio of < 0.70 to define COPD. Exacerbation was self-reported and defined by symptoms (deterioration of breathing symptoms that affected usual daily activities or caused missed work). Spirometry was performed in 5,314 subjects. There were 759 subjects with airflow limitation; of these, 18.2% reported ever having had an exacerbation, 7.9% reported having an exacerbation, and 6.2% reported having an exacerbation requiring at least a doctor visit within the past year. The proportion of individuals with an exacerbation significantly increased by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, from 4.2% in stage 1 to 28.9% in stages 3 and 4. The self-reported exacerbation rate was 0.58 exacerbations per year. The rate of exacerbations requiring at least a doctor visit and length of stay in hospital due to exacerbations also increased as COPD severity progressed. The factors associated with having an exacerbation in the past year were dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and disease severity of GOLD stages 3 and 4. The proportion of individuals with airflow limitation and self-reported exacerbation increases as the disease severity progresses. Dyspnea, prior asthma diagnosis, receiving any respiratory therapy, and more severe obstruction were significantly associated with having an exacerbation in the past year.

Respiratory symptoms, sleep-disordered breathing and biomarkers in nocturnal gastroesophageal reflux.

PubMed

Emilsson, Össur Ingi; Benediktsdóttir, Bryndís; Ólafsson, Ísleifur; Cook, Elizabeth; Júlíusson, Sigurður; Björnsson, Einar Stefán; Guðlaugsdóttir, Sunna; Guðmundsdóttir, Anna Soffía; Mirgorodskaya, Ekaterina; Ljungström, Evert; Arnardóttir, Erna Sif; Gíslason, Þórarinn; Janson, Christer; Olin, Anna-Carin

2016-09-20

Nocturnal gastroesophageal reflux (nGER) is associated with respiratory symptoms and sleep-disordered breathing (SDB), but the pathogenesis is unclear. We aimed to investigate the association between nGER and respiratory symptoms, exacerbations of respiratory symptoms, SDB and airway inflammation. Participants in the European Community Respiratory Health Survey III in Iceland with nGER symptoms (n = 48) and age and gender matched controls (n = 42) were studied by questionnaires, exhaled breath condensate (EBC), particles in exhaled air (PEx) measurements, and a home polygraphic study. An exacerbation of respiratory symptoms was defined as an episode of markedly worse respiratory symptoms in the previous 12 months. Asthma and bronchitis symptoms were more common among nGER subjects than controls (54 % vs 29 %, p = 0.01; and 60 % vs 26 %, p < 0.01, respectively), as were exacerbations of respiratory symptoms (19 % vs 5 %, p = 0.04). Objectively measured snoring was more common among subjects with nGER than controls (snores per hour of sleep, median (IQR): 177 (79-281) vs 67 (32-182), p = 0.004). Pepsin (2.5 ng/ml (0.8-5.8) vs 0.8 ng/ml (0.8-3.6), p = 0.03), substance P (741 pg/ml (626-821) vs 623 pg/ml (562-676), p < 0.001) and 8-isoprostane (3.0 pg/ml (2.7-3.9) vs 2.6 pg/ml (2.2-2.9), p = 0.002) in EBC were higher among nGER subjects than controls. Albumin and surfactant protein A in PEx were lower among nGER subjects. These findings were independent of BMI. In a general population sample, nGER is associated with symptoms of asthma and bronchitis, as well as exacerbations of respiratory symptoms. Also, nGER is associated with increased respiratory effort during sleep. Biomarker measurements in EBC, PEx and serum indicate that micro-aspiration and neurogenic inflammation are plausible mechanisms.

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

[Early exercise training after exacerbation in patients with chronic respiratory failure].

PubMed

Takahashi, Hiromitsu; Molleyres, Sandrine; Dousse, Nicolas; Contal, Olivier; Janssens, Jean-Paul

2011-11-23

Patients who suffered from an exacerbation of a chronic respiratory disorder are often very limited in terms of their exercise capacity because of severe dyspnea and amyotrophy of peripheral muscles. Early implementation of pulmonary rehabilitation may help these patients to avoid the complications of a prolonged bedridden period, and increase more rapidly their mobility. Early rehabilitation has become more frequent, but requires special skills from the care givers (chest therapists). Techniques which enhance muscular performance and motility of patients who are recovering from an exacerbation such as electromoystimulation or mobilisation under non-invasive ventilation, give encouraging results; their impact on length of hospital stay requires further studies.

High-resolution computed tomography findings of acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis.

PubMed

Ichikado, Kazuya

2014-02-01

Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. © 2013 Published by Elsevier Inc.

Early Intravascular Events are Associated with Development of ARDS.

PubMed

Abdulnour, Raja-Elie E; Gunderson, Tina; Barkas, Ioanna; Timmons, Jack Y; Barnig, Cindy; Gong, Michelle; Kor, Daryl J; Gajic, Ognjen; Talmor, Daniel; Carter, Rickey E; Levy, Bruce D

2018-05-21

The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. To determine select peripheral blood lipid mediator and leukocyte responses in patients at-risk for ARDS. Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin or placebo. Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, 9 subjects developed ARDS after randomization yet prior to study drug initiation, including 7 subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio. Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.

Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis.

PubMed

Holland, Anne E; Wilson, John W; Kotsimbos, Thomas C; Naughton, Matthew T

2003-08-01

and study objectives: Patients with end-stage cystic fibrosis (CF) develop respiratory failure and hypercapnia. In contrast to COPD patients, altered electrolyte transport and malnutrition in CF patients may predispose them to metabolic alkalosis and, therefore, may contribute to hypercapnia. The aim of this study was to determine the prevalence of metabolic alkalosis in adults with hypercapnic respiratory failure in the setting of acute exacerbations of CF compared with COPD. Levels of arterial blood gases, plasma electrolytes, and serum albumin from 14 consecutive hypercapnic CF patients who had been admitted to the hospital with a respiratory exacerbation were compared with 49 consecutive hypercapnic patients with exacerbations of COPD. Hypercapnia was defined as a PaCO(2) of > or = 45 mm Hg. Despite similar PaCO(2) values, patients in the CF group were significantly more alkalotic than were those in the COPD group (mean [+/- SD] pH, 7.43 +/- 0.03 vs 7.37 +/- 0.05, respectively; p < 0.01). A mixed respiratory acidosis and metabolic alkalosis was evident in 71% of CF patients and 22% of COPD patients (p < 0.01). The mean concentrations of plasma chloride (95.1 +/- 4.9 vs 99.8 +/- 5.2 mmol/L, respectively; p < 0.01) and sodium (136.5 +/- 2.8 vs 140.4 +/- 4.5 mmol/L, respectively; p < 0.01) were significantly lower in the CF group, and the levels of serum albumin were significantly reduced (27.4 +/- 5.8 vs 33.7 +/- 4.8 mmol/L, respectively; p < 0.01). Metabolic alkalosis contributes to hypercapnic respiratory failure in adults with acute exacerbations of CF. This acid-base disturbance occurs in conjunction with reduced total body salt levels and hypoalbuminemia.

Daily activity during stability and exacerbation of chronic obstructive pulmonary disease.

PubMed

Alahmari, Ayedh D; Patel, Anant R C; Kowlessar, Beverly S; Mackay, Alex J; Singh, Richa; Wedzicha, Jadwiga A; Donaldson, Gavin C

2014-06-02

During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134-353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = -0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030).Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time.

To investigate the prevention of OM-85 on bronchiectasis exacerbations (iPROBE) in Chinese patients: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Non-cystic fibrosis bronchiectasis is characterized by the irreversible dilatation of the medium-sized bronchi as a result of airway injury from recurrent or chronic inflammation and lower respiratory tract infections. Bronchiectasis airways are commonly colonized with bacterial species. Infections of the airways play important role in bronchiectasis exacerbations. The non-specific prevention of recurrent airway infections by immunostimulating agents has gained growing interest. OM-85, consisting of extracts of eight kinds of bacteria important in respiratory infections, could support the respiratory tract resistance to the pathogens. OM-85 has been shown to be a benefit by decreasing the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) in several perspective clinical trials. Exacerbation of bronchiectasis substantially contributes to a more rapid decline in lung function, reduced quality of life, and healthcare costs. In this context, we plan to conduct a clinical trial to investigate the PReventive effect of OM-85 on Bronchiectasis Exacerbation in Chinese patients (iPROBE). Methods/Design This study is designed as a prospective, randomized, double blind, placebo-controlled multicenter trial. A total of 244 patients with bronchiectasis, who have had at least one exacerbation of bronchiectasis in the previous year, will be included. The subjects will randomly receive two courses of 7 mg of OM-85 or a matching placebo. The treatment dose of OM-85 will be one daily capsule taken orally for 10 days each month for 3 consecutive months at the beginning of the study, followed by 3 months of no drug. This schedule will repeat until the patient has been seen for one year. Discussion We will investigate whether long-term treatment with an oral immunostimulant (OM-85) could decrease exacerbations of bronchiectasis over a one-year period. We will also assess other relevant outcomes, including the rate of event-based exacerbation, lung function parameters, and total scores judged by the St George’s respiratory questionnaire, Leicester cough questionnaire, and inflammatory index. We hope that this study will provide new information on the preventive effects of OM-85 on bronchiectasis exacerbations and will address a knowledge gap for this understudied disease. Trial registration This study is registered at http://www.clinicaltrials.gov (identifier NCT01968421) on 19 October 2013. PMID:24773830

[Epidemiological profile of respiratory diseases in children hospitalized at the Rabat Children's Hospital, Morocco].

PubMed

Benchekroun, Ilham; Boubkraoui, Mohamed El Mahdi; Mekaoui, Nour; Karboubi, Lamia; Mahraoui, Chafiq; Dakhama, Badr Sououd Benjelloun

2017-01-01

Respiratory diseases are a common cause of pediatric hospitalization. This study aimed to evaluate the epidemiological profile of respiratory diseases among children at the Rabat Children's Hospital, Morocco. We conducted an observational-cross sectional study of all children aged 3 months to 15 years hospitalized for respiratory disease at the Department of Pneumoallergology and Pediatric Infectious Diseases at the Rabat Children's Hospital, Morocco over a one-year period, from 1 January 2014 to 31 December 2014. Out of 3537 hospitalized patients, 2493 (70.5%) had respiratory disease. Hospitalizations due to asthmatic exacerbation (p < 0.001), acute bronchiolitis (p < 0.001) and laryngeal dyspnoea (p = 0.004) were more frequent among boys, while hospitalizations due to acute pneumonia (p = 0.005), inhalation of a foreign body (p = 0.007) and pertussis (p = 0.020) were frequent among girls. Hospitalizations due to acute pneumonia (p < 0.001), exacerbation of serious viral disease sequelae (p < 0.001) and pertussis (p < 0.001) were more frequent among infants. Hospitalizations due to acute pneumonia (p < 0.001) and pertussis (p = 0.015) were more frequent during the autumn-winter period. The causes of hospitalization were dominated by asthmatic exacerbations and acute bronchiolitis, which were more frequent among boys. Respiratory infections, such as acute pneumonitis and pertussis, were more frequent during the autumn-winter period and mainly affected the infants.

Respiratory Viruses and Treatment Failure in Children With Asthma Exacerbation.

PubMed

Merckx, Joanna; Ducharme, Francine M; Martineau, Christine; Zemek, Roger; Gravel, Jocelyn; Chalut, Dominic; Poonai, Naveen; Quach, Caroline

2018-06-04

: media-1vid110.1542/5771275574001PEDS-VA_2017-4105 Video Abstract OBJECTIVES: Respiratory pathogens commonly trigger pediatric asthma exacerbations, but their impact on severity and treatment response remains unclear. We performed a secondary analysis of the Determinants of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY) study, a prospective cohort study of children (aged 1-17 years) presenting to the emergency department with moderate or severe exacerbations. Nasopharyngeal specimens were analyzed by RT-PCR for 27 respiratory pathogens. We investigated the association between pathogens and both exacerbation severity (assessed with the Pediatric Respiratory Assessment Measure) and treatment failure (hospital admission, emergency department stay >8 hours, or relapse) of a standardized severity-specific treatment. Logistic multivariate regressions were used to estimate average marginal effects (absolute risks and risk differences [RD]). Of 958 participants, 61.7% were positive for ≥1 pathogen (rhinovirus was the most prevalent [29.4%]) and 16.9% experienced treatment failure. The presence of any pathogen was not associated with higher baseline severity but with a higher risk of treatment failure (20.7% vs 12.5%; RD = 8.2% [95% confidence interval: 3.3% to 13.1%]) compared to the absence of a pathogen. Nonrhinovirus pathogens were associated with an increased absolute risk (RD) of treatment failure by 13.1% (95% confidence interval: 6.4% to 19.8%), specifically, by 8.8% for respiratory syncytial virus, 24.9% for influenza, and 34.1% for parainfluenza. Although respiratory pathogens were not associated with higher severity on presentation, they were associated with increased treatment failure risk, particularly in the presence of respiratory syncytial virus, influenza, and parainfluenza. This supports influenza prevention in asthmatic children, consideration of pathogen identification on presentation, and exploration of treatment intensification for infected patients at higher risk of treatment failure. Copyright © 2018 by the American Academy of Pediatrics.

Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation.

PubMed

Terzano, Claudio; Di Stefano, Fabio; Conti, Vittoria; Di Nicola, Marta; Paone, Gregorino; Petroianni, Angelo; Ricci, Alberto

2012-01-01

Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO(2) and PaCO(2) and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis-metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1 ± 9.8, 36.2 ± 8.9 and 53.3 ± 4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis-metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.

Mixed Acid-Base Disorders, Hydroelectrolyte Imbalance and Lactate Production in Hypercapnic Respiratory Failure: The Role of Noninvasive Ventilation

PubMed Central

Terzano, Claudio; Di Stefano, Fabio; Conti, Vittoria; Di Nicola, Marta; Paone, Gregorino; Petroianni, Angelo; Ricci, Alberto

2012-01-01

Background Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure. Methods Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO2 and PaCO2 and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV. Results Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder. Conclusions Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated. PMID:22539963

Respiratory exacerbation in a young adult with cystic fibrosis and tricuspid atresia.

PubMed

Wood, Jamie; Sawyer, Abbey; Mulrennan, Siobhain; Bullock, Andrew

2018-07-01

Tricuspid atresia (TAt) is a complex congenital heart defect (CHD) characterized by the absence of the tricuspid valve and right ventricular hypoplasia requiring surgery in childhood, the Fontan procedure. We present a case of a 21-year-old male with TAt and cystic fibrosis (CF), who underwent a Fontan procedure in childhood, presenting to an adult CF clinic with severe deterioration in his respiratory status and multi-organ dysfunction associated with CF. This report describes problems associated with the management of a CF respiratory exacerbation and extrapulmonary manifestations of CF in the unique situation of a Fontan circulation, a circulation with absence of a subpulmonary ventricle and pulsatile pulmonary arterial blood flow where maintenance of systemic cardiac output is totally dependent on good respiratory function and low pulmonary artery pressures.

Bacterial lysate in the prevention of acute exacerbation of COPD and in respiratory recurrent infections

PubMed Central

Braido, F; Tarantini, F; Ghiglione, V; Melioli, G; Canonica, G W

2007-01-01

Respiratory tract infections (RTIs) represent a serious problem because they are one of the most common cause of human death by infection. The search for the treatment of those diseases has therefore a great importance. In this study we provide an overview of the currently available treatments for RTIs with particular attention to chronic obstructive pulmonary diseases exacerbations and recurrent respiratory infections therapy and a description of bacterial lysate action, in particular making reference to the medical literature dealing with its clinical efficacy. Those studies are based on a very large number of clinical trials aimed to evaluate the effects of this drug in maintaining the immune system in a state of alert, and in increasing the defences against microbial infections. From this analysis it comes out that bacterial lysates have a protective effect, which induce a significant reduction of the symptoms related to respiratory infections. Those results could be very interesting also from an economic point of view, because they envisage a reduction in the number of acute exacerbations and a shorter duration of hospitalization. The use of bacterial lysate could therefore represent an important means to achieve an extension of life duration in patients affected by respiratory diseases. PMID:18229572

Computerised Analysis of Telemonitored Respiratory Sounds for Predicting Acute Exacerbations of COPD.

PubMed

Fernandez-Granero, Miguel Angel; Sanchez-Morillo, Daniel; Leon-Jimenez, Antonio

2015-10-23

Chronic obstructive pulmonary disease (COPD) is one of the commonest causes of death in the world and poses a substantial burden on healthcare systems and patients' quality of life. The largest component of the related healthcare costs is attributable to admissions due to acute exacerbation (AECOPD). The evidence that might support the effectiveness of the telemonitoring interventions in COPD is limited partially due to the lack of useful predictors for the early detection of AECOPD. Electronic stethoscopes and computerised analyses of respiratory sounds (CARS) techniques provide an opportunity for substantial improvement in the management of respiratory diseases. This exploratory study aimed to evaluate the feasibility of using: (a) a respiratory sensor embedded in a self-tailored housing for ageing users; (b) a telehealth framework; (c) CARS and (d) machine learning techniques for the remote early detection of the AECOPD. In a 6-month pilot study, 16 patients with COPD were equipped with a home base-station and a sensor to daily record their respiratory sounds. Principal component analysis (PCA) and a support vector machine (SVM) classifier was designed to predict AECOPD. 75.8% exacerbations were early detected with an average of 5 ± 1.9 days in advance at medical attention. The proposed method could provide support to patients, physicians and healthcare systems.

Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study.

PubMed

Hayden, Lystra P; Hardin, Megan E; Qiu, Weiliang; Lynch, David A; Strand, Matthew J; van Beek, Edwin J; Crapo, James D; Silverman, Edwin K; Hersh, Craig P

2018-02-01

Previous investigations in adult smokers from the COPDGene Study have shown that early-life respiratory disease is associated with reduced lung function, COPD, and airway thickening. Using 5-year follow-up data, we assessed disease progression in subjects who had experienced early-life respiratory disease. We hypothesized that there are alternative pathways to reaching reduced FEV 1 and that subjects who had childhood pneumonia, childhood asthma, or asthma-COPD overlap (ACO) would have less lung function decline than subjects without these conditions. Subjects returning for 5-year follow-up were assessed. Childhood pneumonia was defined by self-reported pneumonia at < 16 years. Childhood asthma was defined as self-reported asthma diagnosed by a health professional at < 16 years. ACO was defined as subjects with COPD who self-reported asthma diagnosed by a health-professional at ≤ 40 years. Smokers with and those without these early-life respiratory diseases were compared on measures of disease progression. Follow-up data from 4,915 subjects were examined, including 407 subjects who had childhood pneumonia, 323 subjects who had childhood asthma, and 242 subjects with ACO. History of childhood asthma or ACO was associated with an increased exacerbation frequency (childhood asthma, P < .001; ACO, P = .006) and odds of severe exacerbations (childhood asthma, OR, 1.41; ACO, OR, 1.42). History of childhood pneumonia was associated with increased exacerbations in subjects with COPD (absolute difference [β], 0.17; P = .04). None of these early-life respiratory diseases were associated with an increased rate of lung function decline or progression on CT scans. Subjects who had early-life asthma are at increased risk of developing COPD and of having more active disease with more frequent and severe respiratory exacerbations without an increased rate of lung function decline over a 5-year period. ClinicalTrials.gov; No. NCT00608764; https://clinicaltrials.gov. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The role of NIV in chronic hypercapnic COPD following an acute exacerbation: the importance of patient selection?

PubMed

Duiverman, Marieke L; Windisch, Wolfram; Storre, Jan H; Wijkstra, Peter J

2016-04-01

Recently, clear benefits have been shown from long-term noninvasive ventilation (NIV) in stable chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure. In our opinion, these benefits are confirmed and nocturnal NIV using sufficiently high inspiratory pressures should be considered in COPD patients with chronic hypercapnic respiratory failure in stable disease, preferably combined with pulmonary rehabilitation. In contrast, clear benefits from (continuing) NIV at home after an exacerbation in patients who remain hypercapnic have not been shown. In this review we will discuss the results of five trials investigating the use of home nocturnal NIV in patients with prolonged hypercapnia after a COPD exacerbation with acute hypercapnic respiratory failure. Although some uncontrolled trials might have shown some benefits of this therapy, the largest randomized controlled trial did not show benefits in terms of hospital readmission or death. However, further studies are necessary to select the patients that optimally benefit, select the right moment to initiate home NIV, select the optimal ventilatory settings, and to choose optimal follow up programmes. Furthermore, there is insufficient knowledge about the optimal ventilatory settings in the post-exacerbation period. Finally, we are not well informed about exact reasons for readmission in patients on NIV, the course of the exacerbation and the treatment instituted. A careful follow up might probably be necessary to prevent deterioration on NIV early. © The Author(s), 2016.

Treatment adherence and health outcomes in patients with bronchiectasis.

PubMed

McCullough, Amanda R; Tunney, Michael M; Quittner, Alexandra L; Elborn, J Stuart; Bradley, Judy M; Hughes, Carmel M

2014-07-01

We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as "adherent" to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted. Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies.

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

PubMed Central

Larcombe, Alexander N.; Foong, Rachel E.; Boylen, Catherine E.; Zosky, Graeme R.

2012-01-01

Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background  Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre‐existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives  To assess the physiological consequences of an acute DEP exposure during the peak of influenza‐induced illness. Methods  We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results  Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions  A single dose of DEP is not sufficient to physiologically exacerbate pre‐existing respiratory disease caused by influenza infection in mice. PMID:22994877

AIRWAY EPITHELIAL EFFECTS OF PARTICULATE POLLUTANTS: ROLE OF METAL INTERACTIONS

EPA Science Inventory

Numerous epidemiologic studies have demonstrated positive associations with particulate matter (PM) air pollution and daily respiratory morbidity - including exacerbations of asthma. Data are needed to elucidate which PM subcomponents may be mediating disease exacerbation in ind...

Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae

PubMed Central

Finney, Lydia J; Ritchie, Andrew; Pollard, Elizabeth; Johnston, Sebastian L; Mallia, Patrick

2014-01-01

Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. PMID:25342897

Changes of Respiratory Mechanics in COPD Patients from Stable State to Acute Exacerbations with Respiratory Failure.

PubMed

Ceriana, Piero; Vitacca, Michele; Carlucci, Annalisa; Paneroni, Mara; Pisani, Lara; Nava, Stefano

2017-04-01

Symptoms, clinical course, functional and biological data during an exacerbation of chronic obstructive pulmonary disease (EXCOPD) have been investigated, but data on physiological changes of respiratory mechanics during a severe exacerbation with respiratory acidosis requiring noninvasive mechanical ventilation (NIMV) are scant. The aim of this study was to evaluate changes of respiratory mechanics in COPD patients comparing data observed during EXCOPD with those observed during stable state in the recovery phase. In 18 COPD patients having severe EXCOPD requiring NIMV for global respiratory failure, we measured respiratory mechanics during both EXCOPD (T0) and once the patients achieved a stable state (T1). The diaphragm and inspiratory muscles effort was significantly increased under relapse, as well as the pressure-time product of the diaphragm and the inspiratory muscle (PTPdi and PTPes). The resistive loads to breathe (i.e., PEEPi,dyn, compliance and inspiratory resistances) were also markedly increased, while the maximal pressures generated by the diaphragm and the inspiratory muscles, together with forced expired volumes were decreased. All these indices statistically improved but with a great intrasubject variability in stable condition. Moreover, tension-time index (TTdi) significantly improved from the EXCOPD state to the condition of clinical stability (0.156 ± 0.04 at T0 vs. 0.082 ± 0.02 at T1 p < 0.001). During an EXCOPD, the load/capacity of the respiratory pump is impaired, and although the patients exhibit a rapid shallow breathing pattern, this does not necessarily correlate with a TTdi ≥ 0.15. These changes are reverted once they recover from the EXCOPD, despite a large variability between patients.

In-home air pollution is linked to respiratory morbidity in former smokers with chronic obstructive pulmonary disease.

PubMed

Hansel, Nadia N; McCormack, Meredith C; Belli, Andrew J; Matsui, Elizabeth C; Peng, Roger D; Aloe, Charles; Paulin, Laura; Williams, D'Ann L; Diette, Gregory B; Breysse, Patrick N

2013-05-15

The effect of indoor air pollutants on respiratory morbidity among patients with chronic obstructive pulmonary disease (COPD) in developed countries is uncertain. The first longitudinal study to investigate the independent effects of indoor particulate matter (PM) and nitrogen dioxide (NO(2)) concentrations on COPD morbidity in a periurban community. Former smokers with COPD were recruited and indoor air was monitored over a 1-week period in the participant's bedroom and main living area at baseline, 3 months, and 6 months. At each visit, participants completed spirometry and questionnaires assessing respiratory symptoms. Exacerbations were assessed by questionnaires administered at clinic visits and monthly telephone calls. Participants (n = 84) had moderate or severe COPD with a mean FEV1 of 48.6% predicted. The mean (± SD) indoor PM(2.5) and NO(2) concentrations were 11.4 ± 13.3 µg/m(3) and 10.8 ± 10.6 ppb in the bedroom, and 12.2 ± 12.2 µg/m(3) and 12.2 ± 11.8 ppb in the main living area. Increases in PM(2.5) concentrations in the main living area were associated with increases in respiratory symptoms, rescue medication use, and risk of severe COPD exacerbations. Increases in NO(2) concentrations in the main living area were independently associated with worse dyspnea. Increases in bedroom NO(2) concentrations were associated with increases in nocturnal symptoms and risk of severe COPD exacerbations. Indoor pollutant exposure, including PM(2.5) and NO(2), was associated with increased respiratory symptoms and risk of COPD exacerbation. Future investigations should include intervention studies that optimize indoor air quality as a novel therapeutic approach to improving COPD health outcomes.

Changes in the respiratory microbiome during acute exacerbations of idiopathic pulmonary fibrosis.

PubMed

Molyneaux, Philip L; Cox, Michael J; Wells, Athol U; Kim, Ho Cheol; Ji, Wonjun; Cookson, William O C; Moffatt, Miriam F; Kim, Dong Soon; Maher, Toby M

2017-02-01

Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) have been defined as events of clinically significant respiratory deterioration with an unidentifiable cause. They carry a significant mortality and morbidity and while their exact pathogenesis remains unclear, the possibility remains that hidden infection may play a role. The aim of this pilot study was to determine whether changes in the respiratory microbiota occur during an AE-IPF. Bacterial DNA was extracted from bronchoalveolar lavage from patients with stable IPF and those experiencing an AE-IPF. A hyper-variable region of the 16S ribosomal RNA gene (16S rRNA) was amplified, quantified and pyrosequenced. Culture independent techniques demonstrate AE-IPF is associated with an increased BAL bacterial burden compared to stable disease and highlight shifts in the composition of the respiratory microbiota during an AE-IPF.

Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample.

PubMed

Clark, Tristan W; Medina, Marie-jo; Batham, Sally; Curran, Martin D; Parmar, Surendra; Nicholson, Karl G

2014-11-01

Many adult patients hospitalised with acute respiratory illness have viruses detected but the overall importance of viral infection compared to bacterial infection is unclear. Patients were recruited from two acute hospital sites in Leicester (UK) over 3 successive winters. Samples were taken for viral and bacterial testing. Of the 780 patients hospitalised with acute respiratory illness 345 (44%) had a respiratory virus detected. Picornaviruses were the most commonly isolated viruses (detected in 23% of all patients). Virus detection rates exceeded 50% in patients with exacerbation of asthma (58%), acute bronchitis and Influenza-like-illness (64%), and ranged from 30 to 50% in patients with an exacerbation of COPD (38%), community acquired pneumonia (36%) and congestive cardiac failure (31%). Bacterial detection was relatively frequent in patients with exacerbation of COPD and pneumonia (25% and 33% respectively) but was uncommon in all other groups. Antibiotic use was high across all clinical groups (76% overall) and only 21% of all antibiotic use occurred in patients with detectable bacteria. Respiratory viruses are the predominant detectable aetiological agents in most hospitalised adults with acute respiratory illness. Antibiotic usage in hospital remains excessive including in clinical conditions associated with low rates of bacterial detection. Efforts at reducing excess antibiotic use should focus on these groups as a priority. Registered International Standard Controlled Trial Number: 21521552. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Daily activity during stability and exacerbation of chronic obstructive pulmonary disease

PubMed Central

2014-01-01

Background During most COPD exacerbations, patients continue to live in the community but there is little information on changes in activity during exacerbations due to the difficulties of obtaining recent, prospective baseline data. Methods Patients recorded on daily diary cards any worsening in respiratory symptoms, peak expiratory flow (PEF) and the number of steps taken per day measured with a Yamax Digi-walker pedometer. Exacerbations were defined by increased respiratory symptoms and the number of exacerbations experienced in the 12 months preceding the recording of daily step count used to divide patients into frequent (> = 2/year) or infrequent exacerbators. Results The 73 COPD patients (88% male) had a mean (±SD) age 71(±8) years and FEV1 53(±16)% predicted. They recorded pedometer data on a median 198 days (IQR 134–353). At exacerbation onset, symptom count rose by 1.9(±1.3) and PEF fell by 7(±13) l/min. Mean daily step count fell from 4154(±2586) steps/day during a preceding baseline week to 3673(±2258) step/day during the initial 7 days of exacerbation (p = 0.045). Patients with larger falls in activity at exacerbation took longer to recover to stable level (rho = −0.56; p < 0.001). Recovery in daily step count was faster (median 3.5 days) than for exacerbation symptoms (median 11 days; p < 0.001). Recovery in step count was also faster in untreated compared to treated exacerbation (p = 0.030). Daily step count fell faster over time in the 40 frequent exacerbators, by 708 steps/year, compared to 338 steps/year in 33 infrequent exacerbators (p = 0.002). Conclusions COPD exacerbations reduced physical activity and frequent exacerbations accelerate decline in activity over time. PMID:24885188

High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus-induced exacerbations: A prospective cohort study.

PubMed

Bjerregaard, A; Laing, I A; Backer, V; Sverrild, A; Khoo, S-K; Chidlow, G; Sikazwe, C; Smith, D W; Le Souëf, P; Porsbjerg, C

2017-08-01

The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown. To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma. Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI: 1.6-35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1-10.4, P=.033). Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies. © 2017 John Wiley & Sons Ltd.

Health Effects of Exposure to Water-Damaged New Orleans Homes Six Months After Hurricanes Katrina and Rita

PubMed Central

Cummings, Kristin J.; Cox-Ganser, Jean; Riggs, Margaret A.; Edwards, Nicole; Hobbs, Gerald R.; Kreiss, Kathleen

2008-01-01

Objectives. We investigated the relation between respiratory symptoms and exposure to water-damaged homes and the effect of respirator use in posthurricane New Orleans, Louisiana. Methods. We randomly selected 600 residential sites and then interviewed 1 adult per site. We created an exposure variable, calculated upper respiratory symptom (URS) and lower respiratory symptom (LRS) scores, and defined exacerbation categories by the effect on symptoms of being inside water-damaged homes. We used multiple linear regression to model symptom scores (for all participants) and polytomous logistic regression to model exacerbation of symptoms when inside (for those participating in clean-up). Results. Of 553 participants (response rate=92%), 372 (68%) had participated in clean-up; 233 (63%) of these used a respirator. Respiratory symptom scores increased linearly with exposure (P<.05 for trend). Disposable-respirator use was associated with lower odds of exacerbation of moderate or severe symptoms inside water-damaged homes for URS (odds ratio (OR)=.51; 95% confidence interval (CI)=0.24, 1.09) and LRS (OR=0.33; 95% CI=0.13, 0.83). Conclusions. Respiratory symptoms were positively associated with exposure to water-damaged homes, including exposure limited to being inside without participating in clean-up. Respirator use had a protective effect and should be considered when inside water-damaged homes regardless of activities undertaken. PMID:18381997

[Preanesthetic evaluation, preparation and prognostic prediction for bronchial asthma].

PubMed

Shinozaki, Katsuhiro; Kawamae, Kaneyuki

2010-07-01

The most important matter in preanesthetic evaluation of patients with bronchial asthma is recognition of its severity and the state controlled by drugs. We should judge them generally by history taking, physical examination and respiratory functional examination in each individual patient, and should take care not to induce attack. The use of anodyne such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) may cause violent bronchospasm, shock, loss of consciousness and even respiratory arrest. When we use such drugs, we have to be careful especially in perioperative period.

Extracorporeal carbon dioxide removal in acute exacerbations of chronic obstructive pulmonary disease

PubMed Central

Pettenuzzo, Tommaso; Fan, Eddy

2018-01-01

Extracorporeal carbon dioxide removal (ECCO2R) has been proposed as an adjunctive intervention to avoid worsening respiratory acidosis, thereby preventing or shortening the duration of invasive mechanical ventilation (IMV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD). This review will present a comprehensive summary of the pathophysiological rationale and clinical evidence of ECCO2R in patients suffering from severe COPD exacerbations. PMID:29430448

The association of lung function and St. George's respiratory questionnaire with exacerbations in COPD: a systematic literature review and regression analysis.

PubMed

Martin, Amber L; Marvel, Jessica; Fahrbach, Kyle; Cadarette, Sarah M; Wilcox, Teresa K; Donohue, James F

2016-04-16

This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St. George's Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations. A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations. These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance. Sixty-seven trials were included in the analysis. Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024). Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant. The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations. Even in cases of non-significant relationships, results were in the expected direction with few exceptions. The results of this analysis offer health care providers and payers a broader picture of the relationship between exacerbations and mean change in FEV1 as well as SGRQ score, and will help inform clinical and formulary-making decisions while stimulating new research questions for future prospective studies.

Comprehensive self management and routine monitoring in chronic obstructive pulmonary disease patients in general practice: randomised controlled trial.

PubMed

Bischoff, Erik W M A; Akkermans, Reinier; Bourbeau, Jean; van Weel, Chris; Vercoulen, Jan H; Schermer, Tjard R J

2012-11-28

To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients' management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice. 24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial. 15 general practices in the eastern part of the Netherlands. Patients with COPD confirmed by spirometry and treated in general practice. Patients with very severe COPD or treated by a respiratory physician were excluded. A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients' own initiative). The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score. Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients' management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale. 165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55). At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant. Secondary outcomes did not differ, except for exacerbation management. Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58). Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice. Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group. Clinical trials NCT00128765.

Treatment adherence and health outcomes in patients with bronchiectasis

PubMed Central

2014-01-01

Background We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. Methods Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as “adherent” to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. Results Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with FEV1 % predicted. Conclusions Treatment adherence is low in bronchiectasis and affects important health outcomes including pulmonary exacerbations. Adherence should be measured as part of bronchiectasis management and future research should evaluate bronchiectasis-specific adherence strategies. PMID:24980161

Influenza enhances caspase-1 in bronchial epithelial cells from asthmatic volunteers and is associated with pathogenesis

EPA Science Inventory

Background: The leading cause of asthma exacerbation is respiratory viral infection. Innate antiviral defense pathways are altered in the asthmatic epithelium, yet involvement of inflammasome signaling in virus-induced asthma exacerbation is not known. Objective: This study com...

Long-acting muscarinic antagonist use in adults with asthma: real-life prescribing and outcomes of add-on therapy with tiotropium bromide.

PubMed

Price, David; Kaplan, Alan; Jones, Rupert; Freeman, Daryl; Burden, Anne; Gould, Shuna; von Ziegenweidt, Julie; Ali, Muzammil; King, Christine; Thomas, Mike

2015-01-01

Randomized controlled trials indicate that addition of a long-acting muscarinic antagonist (LAMA) such as tiotropium may improve asthma control and reduce exacerbation risk in patients with poorly controlled asthma, but broader clinical studies are needed to investigate the effectiveness of LAMA in real-life asthma care. Medical records of adults with asthma (aged ≥18 years) prescribed tiotropium were obtained from the UK Optimum Patient Care Research Database for the period 2001-2013. Patients diagnosed with chronic obstructive pulmonary disease were excluded, but no other clinical exclusions were applied. Two primary outcomes were compared in the year before (baseline) and the year after (outcome) addition of tiotropium: exacerbations (asthma-related hospital emergency department attendance or inpatient admission, or acute oral corticosteroid course) and acute respiratory events (exacerbation or antibiotic prescription with lower respiratory consultation). Secondary outcomes included lung function test results and short-acting β2 agonist usage. The Wilcoxon signed-rank test was used for variables measured on the interval scale, the marginal homogeneity test for categorized variables, and the paired t-test for lung function indices. Of the 2,042 study patients, 83% were prescribed an inhaled corticosteroid and 68% a long-acting β2 agonist during the baseline year; 67% were prescribed both. Comparing baseline and outcome years, the percentage of patients having at least one exacerbation decreased from 37% to 27% (P<0.001) and the percentage having at least one acute respiratory event decreased from 58% to 47% (P<0.001). There were no significant changes in lung function, and usage of short-acting β2 agonists (in salbutamol/albuterol equivalents) increased from a median (interquartile range) of 274 (110, 548) to 329 (110, 603) μg/day (P=0.01). In this real-life asthma population, addition of LAMA therapy was associated with significant decreases in the incidence of exacerbations and antibiotic prescriptions for lower respiratory tract infections in the following year.

What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

PubMed

Kim, Deog Kyeom; Lee, Jungsil; Park, Ju Hee; Yoo, Kwang Ha

2018-04-01

Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is reported that it was also effective in reducing intubation in AECOPD with hypercapnic respiratory failure. Despite the apparent need for more supporting evidence, efforts to improve efficacy of NIV have continued unabated. It is anticipated that these efforts will, over time, serve toprogressively decrease the risk of intubation and invasive mechanical ventilation in cases of AECOPD with acute respiratory failure. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan.

PubMed

Santus, Pierachille; Russo, Antonio; Madonini, Enzo; Allegra, Luigi; Blasi, Francesco; Centanni, Stefano; Miadonna, Antonio; Schiraldi, Gianfranco; Amaducci, Sandro

2012-10-18

Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy. We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0-2 and lag 3-5 in both single and multi-pollutant models, adjusted for daily weather variables. An increase in ozone (O(3)) levels at lag 3-5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0-2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO(2)), CO, nitrate dioxide (NO(2)), and particulate matter (PM(10) and PM(2.5)). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0-2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association. Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.

Streptococcal Upper Respiratory Tract Infections and Exacerbations of Tic and Obsessive-Compulsive Symptoms: A Prospective Longitudinal Study

ERIC Educational Resources Information Center

Leckman, James F.; King, Robert A.; Gilbert, Donald L.; Coffey, Barbara J.; Singer, Harvey S.; Dure, Leon S., IV; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J.; Kawikova, Ivana; Johnson, Dwight R.; Kurlan, Roger M.; Kaplan, Edward L.

2011-01-01

Objective: The objective of this blinded, prospective, longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders…

Non-invasive ventilation (NIV) as an aid to rehabilitation in acute respiratory disease.

PubMed

Dyer, Fran; Flude, Lizzie; Bazari, Farid; Jolley, Caroline; Englebretsen, Catherine; Lai, Dilys; Polkey, Michael I; Hopkinson, Nicholas S

2011-12-16

Non-invasive ventilation (NIV) can increase exercise tolerance, reduce exercise induced desaturation and improve the outcome of pulmonary rehabilitation in patients with chronic respiratory disease. It is not known whether it can be applied to increase exercise capacity in patients admitted with non-hypercapnic acute exacerbations of COPD (AECOPD). We investigated the acceptability and feasibility of using NIV for this purpose. On a single occasion, patients admitted with an acute exacerbation of chronic respiratory disease who were unable to cycle for five minutes at 20 watts attempted to cycle using NIV and their endurance time (T(lim)) was recorded. To determine feasibility of this approach in clinical practice patients admitted with AECOPD were screened for participation in a trial of regular NIV assisted rehabilitation during their hospital admission. In 12 patients tested on a single occasion NIV increased T(lim) from 184(65) seconds to 331(229) seconds (p = 0.04) and patients desaturated less (median difference = 3.5%, p = 0.029). In the second study, 60 patients were admitted to hospital during a three month period of whom only 18(30)% were eligible to participate and of these patients, only four (7%) consented to participate. NIV improves exercise tolerance in patients with acute exacerbations of chronic respiratory disease but the applicability of this approach in routine clinical practice may be limited. http://www.controlled-trials.com/ISRCTN35692743.

Recurrent haematomas of the thigh: a case of von Willebrand's disease presenting to a sports clinic

PubMed Central

Owens, S.; Baglin, T.

2000-01-01

Von Willebrand's disease is a relatively common mild form of haemophilia. It should be suspected in assessing sports injuries when excessive bleeding occurs in response to relatively mild trauma. Those with the disease should remain active but avoid contact sports. They should not take aspirin or non-steroidal anti-inflammatory drugs, which may exacerbate bleeding, and should be given supportive treatment to cover dental extraction, surgery, or significant bleeding episodes. Key Words: von Willebrand's disease; haemophilia; haematoma; sports clinic PMID:10786868

[Costs of hospitalisation for exacerbations of COPD in patients receiving domiciliary rehabilitation].

PubMed

Romain, D; Bernady, A; Etchamendy, E; Barokas, T; Pignede, P

2011-09-01

The aim of this study was to estimate the costs related to hospitalisation for exacerbations of COPD in patients who received domiciliary rehabilitation. The hospital costs (obtained from the health insurance office of Bayonne) of 31 patients suffering from COPD of all stages, were analysed for the year of rehabilitation and for the preceding year. All the patients had access to the same management programme in a health care system: domiciliary bicycle ergometry, collective gymnastics, dietary advice, psychological support and education. The analysis of the costs of respiratory care revealed two populations: a minority in whom costs were increased (two end of life situations requiring palliative care and two severe episodes requiring intensive care), and a majority in whom domiciliary rehabilitation led to a reduction of over 60% in the costs related to hospitalisation. Respiratory rehabilitation reduces the costs of hospitalisation secondary to exacerbations in patients suffering from COPD but does not reduce the high costs related to severe episodes of respiratory failure or terminal care. It is important that rehabilitation is adapted to the needs of each patient until the end of his life. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Moxifloxacin in respiratory tract infections.

PubMed

Miravitlles, Marc

2005-02-01

Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including Gram-positive (Streptococcus pneumoniae), Gram-negative (Haemophilus influenzae, Moraxella catarrhalis), and atypical strains (Chlamydia pneumoniae, Mycoplasma pneumoniae), as well as multi-drug resistant S. pneumoniae, including strains resistant to penicillin, macrolides, tetracyclines, trimethoprim/sulfamethoxazole and some fluoroquinolones. Moxifloxacin is highly concentrated in lung tissue, and has demonstrated rapid eradication rates. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400mg/day. The ratio of the area under the concentration-time curve to MIC of moxifloxacin is the highest among the fluoroquinolones against S. pneumoniae. The clinical efficacy of moxifloxacin has been shown in controlled studies of community-acquired pneumonia (CAP), exacerbations of chronic bronchitis (CB) and acute bacterial rhinosinusitis. Moxifloxacin has demonstrated a faster resolution of symptoms in CAP and exacerbations of CB patients compared with first-line therapy. It has also demonstrated better eradication in exacerbations of CB compared with standard therapy, in particular the macrolides. Treatment guidelines should take into account the results of clinical trials with moxifloxacin in order to establish the role of this antimicrobial in the therapeutic arsenal against respiratory tract infections.

Bacillus licheniformis in geogenic dust induces inflammation in respiratory epithelium.

PubMed

Pickering, Janessa; Teo, Teck Hui; Thornton, Ruth B; Kirkham, Lea-Ann; Zosky, Graeme R; Clifford, Holly D

2018-07-01

Exposure to environmental geogenic (or earth-derived) dust can lead to more frequent and severe infections in the human airway. Particulate matter < 10 µm (PM 10 ) is the component of air pollution that is commonly associated with the exacerbation of respiratory diseases. We have previously demonstrated that mice exposed to geogenic dust PM 10 experienced an exacerbation of inflammatory responses to influenza A virus. Whether geogenic dust PM 10 also exacerbates respiratory bacterial infection is not yet known, nor are the components of the dust that drive these responses. We treated airway bronchial epithelial cells (NuLi-1) with UV-irradiated geogenic dust PM 10 from six remote Western Australian towns. High levels of IL-6 and IL-8 production were observed, as well as persistent microbial growth. 16 S rRNA sequencing of the growth identified the microbe as Bacillus licheniformis, a spore-forming, environmentally abundant bacterium. We next investigated the interaction of B. licheniformis with respiratory epithelium in vitro to determine whether this exacerbated infection with a bacterial respiratory pathogen (non-typeable Haemophilus influenzae, NTHi). Heat treatment (100 °C) of all PM 10 samples eliminated B. licheniformis contamination and reduced epithelial inflammatory responses, suggesting that heat-labile and/or microbial factors were involved in the host response to geogenic dust PM 10 . We then exposed NuLi-1 epithelium to increasing doses of the isolated Bacillus licheniformis (multiplicity of infection of 10:1, 1:1 or 0.1:1 bacteria: cells) for 1, 3, and 24 h. B. licheniformis and NTHi infection (association and invasion) was assessed using a standard gentamicin survival assay, and epithelial release of IL-6 and IL-8 was measured using a bead based immunoassay. B. licheniformis was cytotoxic to NuLi-1 cells at 24 h. At 3 h post-challenge, B. licheniformis elicited high IL-6 and IL-8 inflammatory responses from NuLi-1 cells compared with cells treated with heat-treated geogenic dust PM 10 (p < 0.0001). Whilst treatment of cells with B. licheniformis increased inflammation, this did not make the cells more susceptible to NTHi infection. This study highlights that geogenic dust PM 10 can harbour viable bacterial spores that induce inflammation in respiratory epithelium. The impact on respiratory health from inhalation of bacterial spores in PM 10 in arid environments may be underestimated. Further investigation into the contribution of B. licheniformis and the wider dust microbiome to respiratory infection is warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Majority of never-smokers with airflow limitation do not have asthma: the Copenhagen General Population Study.

PubMed

Çolak, Yunus; Afzal, Shoaib; Nordestgaard, Børge G; Lange, Peter

2016-07-01

A substantial proportion of individuals with airflow limitation are never-smokers. However, whether never-smokers with airflow limitation have undiagnosed asthma is unknown. We hypothesised that the majority of never-smokers with respiratory symptoms and airflow limitation but without known asthma have undiagnosed asthma by comparing characteristics and prognosis in never-smokers with airflow limitation and asthma (NS+AFL+A) with never-smokers with airflow limitation but without asthma (NS+AFL-A). Among 94 079 participants aged 20-100 years from the general population, 39 102 (42%) were never-smokers. In this group, 13 719 (35%) reported to have respiratory symptoms of whom 1610 (12%) had airflow limitation. We investigated characteristics and risk of complications (asthma or COPD exacerbations, pneumonias and all-cause mortality) and comorbidities (lung cancer, ischaemic heart disease, myocardial infarction, deep venous thrombosis and PE) during 4.5 years median follow-up. NS+AFL-A compared with NS+AFL+A reported less allergy and respiratory symptoms, and had higher FEV1 and lower levels of eosinophils and IgE in peripheral blood. NS+AFL+A had increased risk of asthma and COPD exacerbations, but not of pneumonias; adjusted HRs in NS+AFL+A compared with NS+AFL-A were 16 (95% CI 3.7 to 73) for asthma exacerbations and 15 (2.8 to 80) for COPD exacerbations. Still, NS+AFL-A had increased risk of COPD exacerbations and pneumonias, but not of asthma exacerbations; adjusted HRs in NS+AFL-A compared with never-smokers without airflow limitation or asthma (NS-AFL-A) were 7.7 (2.8 to 21) for COPD exacerbations and 1.7 (1.3 to 2.3) for pneumonias. Risk of comorbidities or all-cause mortality was not increased in NS+AFL-A or NS+AFL+A compared with NS-AFL-A. Majority of NS+AFL-A do not seem to have undiagnosed asthma and may instead have airflow limitation caused by other risk factors. 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/

Rhinovirus viremia in children with respiratory infections.

PubMed

Xatzipsalti, Maria; Kyrana, Serena; Tsolia, Mariza; Psarras, Stelios; Bossios, Apostolos; Laza-Stanca, Vasile; Johnston, Sebastian L; Papadopoulos, Nikolaos G

2005-10-15

Viremia has been implicated in many viral infections; however, viremia due to rhinovirus (RV; rhinoviremia) has been considered not to occur in normal individuals. To evaluate whether RV enters the bloodstream and identify the possible risk factors. Nasopharyngeal washes (NPWs) of 221 children with respiratory infections were examined for the presence of RV by reverse transcription-polymerase chain reaction. Blood from 88 children, whose NPW was RV-positive, and 31 of RV-negative control subjects was subsequently examined for the presence of RV in the blood by semi-nested reverse transcription-polymerase chain reaction. Rhinoviremia was then correlated with clinical characteristics of the disease. RV was detected in the blood of 10 out of 88 NPW RV-positive cases (11.4%): 7 of 28 children with asthma exacerbations (25.0%), 2 of 26 with common cold (7.7%), 1 of 25 with bronchiolitis (4.0%), and 0 of 9 with pneumonia (0%). All NPW RV-negative cases were negative in the blood. The proportion of rhinoviremia in children with asthma exacerbation was significantly higher compared with children suffering from the other diseases (25 vs. 5%, p = 0.01). Significant risk factors were: sampling

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.

A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis

ClinicalTrials.gov

2017-10-12

Lung Diseases; Pulmonary Disease; Cystic Fibrosis; Cystic Fibrosis Lung; Cystic Fibrosis Pulmonary Exacerbation; Cystic Fibrosis With Exacerbation; Respiratory Tract Disease; Pulmonary Inflammation; Multi-antibiotic Resistance; Antibiotic Resistant Infection; Lung Infection; Lung Infection Pseudomonal; Lung; Infection, Atypical Mycobacterium; Burkholderia Infections; Burkholderia Cepacia Infection; Lung Inflammation

Novel tools for blood inflammatory markers detection in monitoring air pollution-induced cardio-respiratory symptoms.

PubMed

Coccini, Teresa; Manzo, Luigi; De Simone, Uliana; Acerbi, Davide; Roda, Elisa

2012-01-01

There is strong epidemiological evidence that air pollution exposure (short- and long-term, i.e. < 24 hr to 3 weeks, and year/s) is related to exacerbation of cardiovascular and respiratory diseases. Data from toxicological and basic science/molecular studies, controlled animal and human exposures and human panel studies have demonstrated several mechanisms by which particle exposure may both trigger acute events as well as prompt the chronic development of cardiovascular diseases. These pollutant-mediated biological mechanisms are supporting the potential use of haematic (inflammation/coagulation/oxidative stress) markers of effects in cardio-respiratory diseases. Various examples from in vitro, in vivo and epidemiological investigations are reported, together with some novel technologies that should provide with new tools for research in these diseases and improve the knowledge about any linkage of local and systemic inflammation and clinical features of these diseases (in particular COPD), including lung function, exacerbations, disease progression, and mortality.

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial

PubMed Central

Papi, A; Dokic, D; Tzimas, W; Mészáros, I; Olech-Cudzik, A; Koroknai, Z; McAulay, K; Mersmann, S; Dalvi, PS; Overend, T

2017-01-01

Purpose To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD. Patients and methods COPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations. Results In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077). There were more St George’s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066). Acute β2-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups. Conclusion FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments. PMID:28740376

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial.

PubMed

Papi, A; Dokic, D; Tzimas, W; Mészáros, I; Olech-Cudzik, A; Koroknai, Z; McAulay, K; Mersmann, S; Dalvi, P S; Overend, T

2017-01-01

To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD. COPD patients with forced expiratory volume in 1 s (FEV 1 ) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations. In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P ≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P =0.084). Pre- and post-dose FEV 1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM ( P ≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P =0.077). There were more St George's Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P ≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM ( P ≤0.066). Acute β 2 -agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups. FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.

Predicting high risk of exacerbations in bronchiectasis: the E-FACED score.

PubMed

Martinez-Garcia, M A; Athanazio, R A; Girón, R; Máiz-Carro, L; de la Rosa, D; Olveira, C; de Gracia, J; Vendrell, M; Prados-Sánchez, C; Gramblicka, G; Corso Pereira, M; Lundgren, F L; Fernandes De Figueiredo, M; Arancibia, F; Rached, S Z

2017-01-01

Although the FACED score has demonstrated a great prognostic capacity in bronchiectasis, it does not include the number or severity of exacerbations as a separate variable, which is important in the natural history of these patients. Construction and external validation of a new index, the E-FACED, to evaluate the predictive capacity of exacerbations and mortality. The new score was constructed on the basis of the complete cohort for the construction of the original FACED score, while the external validation was undertaken with six cohorts from three countries (Brazil, Argentina, and Chile). The main outcome was the number of annual exacerbations/hospitalizations, with all-cause and respiratory-related deaths as the secondary outcomes. A statistical evaluation comprised the relative weight and ideal cut-off point for the number or severity of the exacerbations and was incorporated into the FACED score (E-FACED). The results obtained after the application of FACED and E-FACED were compared in both the cohorts. A total of 1,470 patients with bronchiectasis (819 from the construction cohorts and 651 from the external validation cohorts) were followed up for 5 years after diagnosis. The best cut-off point was at least two exacerbations in the previous year (two additional points), meaning that the E-FACED has nine points of growing severity. E-FACED presented an excellent prognostic capacity for exacerbations (areas under the receiver operating characteristic curve: 0.82 for at least two exacerbations in 1 year and 0.87 for at least one hospitalization in 1 year) that was statistically better than that of the FACED score (0.72 and 0.78, P <0.05, respectively). The predictive capacities for all-cause and respiratory mortality were 0.87 and 0.86, respectively, with both being similar to those of the FACED. E-FACED score significantly increases the FACED capacity to predict future yearly exacerbations while maintaining the score's simplicity and prognostic capacity for death.

Predicting high risk of exacerbations in bronchiectasis: the E-FACED score

PubMed Central

Martinez-Garcia, MA; Athanazio, RA; Girón, R; Máiz-Carro, L; de la Rosa, D; Olveira, C; de Gracia, J; Vendrell, M; Prados-Sánchez, C; Gramblicka, G; Corso Pereira, M; Lundgren, FL; Fernandes De Figueiredo, M; Arancibia, F; Rached, SZ

2017-01-01

Background Although the FACED score has demonstrated a great prognostic capacity in bronchiectasis, it does not include the number or severity of exacerbations as a separate variable, which is important in the natural history of these patients. Objective Construction and external validation of a new index, the E-FACED, to evaluate the predictive capacity of exacerbations and mortality. Methods The new score was constructed on the basis of the complete cohort for the construction of the original FACED score, while the external validation was undertaken with six cohorts from three countries (Brazil, Argentina, and Chile). The main outcome was the number of annual exacerbations/hospitalizations, with all-cause and respiratory-related deaths as the secondary outcomes. A statistical evaluation comprised the relative weight and ideal cut-off point for the number or severity of the exacerbations and was incorporated into the FACED score (E-FACED). The results obtained after the application of FACED and E-FACED were compared in both the cohorts. Results A total of 1,470 patients with bronchiectasis (819 from the construction cohorts and 651 from the external validation cohorts) were followed up for 5 years after diagnosis. The best cut-off point was at least two exacerbations in the previous year (two additional points), meaning that the E-FACED has nine points of growing severity. E-FACED presented an excellent prognostic capacity for exacerbations (areas under the receiver operating characteristic curve: 0.82 for at least two exacerbations in 1 year and 0.87 for at least one hospitalization in 1 year) that was statistically better than that of the FACED score (0.72 and 0.78, P<0.05, respectively). The predictive capacities for all-cause and respiratory mortality were 0.87 and 0.86, respectively, with both being similar to those of the FACED. Conclusion E-FACED score significantly increases the FACED capacity to predict future yearly exacerbations while maintaining the score’s simplicity and prognostic capacity for death. PMID:28182132

European Respiratory Society guidelines for the management of adult bronchiectasis.

PubMed

Polverino, Eva; Goeminne, Pieter C; McDonnell, Melissa J; Aliberti, Stefano; Marshall, Sara E; Loebinger, Michael R; Murris, Marlene; Cantón, Rafael; Torres, Antoni; Dimakou, Katerina; De Soyza, Anthony; Hill, Adam T; Haworth, Charles S; Vendrell, Montserrat; Ringshausen, Felix C; Subotic, Dragan; Wilson, Robert; Vilaró, Jordi; Stallberg, Bjorn; Welte, Tobias; Rohde, Gernot; Blasi, Francesco; Elborn, Stuart; Almagro, Marta; Timothy, Alan; Ruddy, Thomas; Tonia, Thomy; Rigau, David; Chalmers, James D

2017-09-01

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes. Copyright ©ERS 2017.

Can a school-based hand hygiene program reduce asthma exacerbations among elementary school children?

PubMed Central

Gerald, Joe K.; Zhang, Bin; McClure, Leslie A.; Bailey, William C.; Harrington, Kathy F.

2012-01-01

Background Viral upper respiratory infections have been implicated as a major cause of asthma exacerbations among school age children. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections but, effective hand washing practices are difficult to establish in schools. Objectives This randomized controlled trial evaluated whether a standardized regimen of hand washing plus alcohol-based hand sanitizer could reduce asthma exacerbations more than schools’ usual hand hygiene practices. Methods This was a two year, community-based, randomized controlled crossover trial. Schools were randomized to usual care then intervention (Sequence 1) or intervention then usual care (Sequence 2). Intervention schools were provided with alcohol-based hand sanitizer, hand soap, and hand hygiene education. The primary outcome was the proportion of students experiencing an asthma exacerbation each month. Generalized estimating equations were used to model the difference in the marginal rate of exacerbations between sequences while controlling for individual demographic factors and the correlation within each student and between students within each school. Results 527 students with asthma were enrolled among 31 schools. The hand hygiene intervention did not reduce the number of asthma exacerbations as compared to the schools’ usual hand hygiene practices (p=0.132). There was a strong temporal trend as both sequences experienced fewer exacerbations during Year 2 as compared to Year 1 (p<0.001). Conclusions While the intervention was not found to be effective, the results were confounded by the H1N1 influenza pandemic that resulted in substantially increased hand hygiene behaviors and resources in usual care schools. Therefore, these results should be viewed cautiously. PMID:23069487

A Respiratory Therapist Disease Management Program for Subjects Hospitalized With COPD.

PubMed

Silver, Patty C; Kollef, Marin H; Clinkscale, Darnetta; Watts, Peggy; Kidder, Robin; Eads, Brittany; Bennett, Debbie; Lora, Carolyn; Quartaro, Michael

2017-01-01

Patients with COPD often require repeated emergency department visits and hospitalizations for COPD exacerbations. Such readmissions increase health-care costs and expose COPD patients to the added risks of nosocomial infections and increased mortality. To determine whether a respiratory therapist (RT) disease management program could reduce re-hospitalization and emergency department visits, a prospective, single-center, unblinded, randomized trial was performed. We enrolled 428 subjects (214 intervention, 214 control). The primary outcome (combined non-hospitalized emergency department visits and hospital readmissions for a COPD exacerbation during the 6-month follow-up) was similar for the study groups (91 vs 159, P = .08). When the 2 components of the primary end point were analyzed individually, the percentage of subjects with non-hospitalized emergency department visits for COPD exacerbations was similar between groups (15.0% vs 15.9%, P = .79). Readmission for a COPD exacerbation was significantly lower in the intervention group (20.1% vs 28.5%, P = .042). The median (interquartile range) duration of hospitalization for a COPD exacerbation was less for the intervention group (5 [3-11] d vs 8 [4-18.5] d, P = .045). In-patient hospital days (306 d vs 523 d, P = .02) and ICU days (17 d vs 53 d, P = .02) due to COPD exacerbations were significantly less for the intervention group. Mortality was similar for both groups (1.4% vs 0.9%, P > .99). Our RT disease management program was associated with less readmission, fewer ICU days, and shorter hospital stays due to COPD exacerbations. Further studies are needed to determine the optimal utilization of RT disease management teams for patients with COPD to optimize outcomes and prevent return hospital visits. (ClinicalTrials.gov registration NCT01543217.). Copyright © 2017 by Daedalus Enterprises.

Expiratory flow limitation relates to symptoms during COPD exacerbations requiring hospital admission.

PubMed

Jetmalani, Kanika; Timmins, Sophie; Brown, Nathan J; Diba, Chantale; Berend, Norbert; Salome, Cheryl M; Wen, Fu-Qiang; Chen, Peng; King, Gregory G; Farah, Claude S

2015-01-01

Expiratory flow limitation (EFL) is seen in some patients presenting with a COPD exacerbation; however, it is unclear how EFL relates to the clinical features of the exacerbation. We hypothesized that EFL when present contributes to symptoms and duration of recovery during a COPD exacerbation. Our aim was to compare changes in EFL with symptoms in subjects with and without flow-limited breathing admitted for a COPD exacerbation. A total of 29 subjects with COPD were recruited within 48 hours of admission to West China Hospital for an acute exacerbation. Daily measurements of post-bronchodilator spirometry, resistance, and reactance using the forced oscillation technique and symptom (Borg) scores until discharge were made. Flow-limited breathing was defined as the difference between inspiratory and expiratory respiratory system reactance (EFL index) greater than 2.8 cmH2O·s·L(-1). The physiological predictors of symptoms during recovery were determined by mixed-effect analysis. Nine subjects (31%) had flow-limited breathing on admission despite similar spirometry compared to subjects without flow-limited breathing. Spirometry and resistance measures did not change between enrolment and discharge. EFL index values improved in subjects with flow-limited breathing on admission, with resolution in four patients. In subjects with flow-limited breathing on admission, symptoms were related to inspiratory resistance and EFL index values. In subjects without flow-limited breathing, symptoms related to forced expiratory volume in 1 second/forced vital capacity. In the whole cohort, EFL index values at admission was related to duration of stay (Rs=0.4, P=0.03). The presence of flow-limited breathing as well as abnormal respiratory system mechanics contribute independently to symptoms during COPD exacerbations.

The complexity of managing COPD exacerbations: a grounded theory study of European general practice

PubMed Central

Risør, Mette Bech; Spigt, Mark; Iversen, R; Godycki-Cwirko, M; Francis, N; Altiner, A; Andreeva, E; Kung, K; Melbye, H

2013-01-01

Objectives To understand the concerns and challenges faced by general practitioners (GPs) and respiratory physicians about primary care management of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Design 21 focus group discussions (FGDs) were performed in seven countries with a Grounded Theory approach. Each country performed three rounds of FGDs. Setting Primary and secondary care in Norway, Germany, Wales, Poland, Russia, The Netherlands, China (Hong Kong). Participants 142 GPs and respiratory physicians were chosen to include urban and rural GPs as well as hospital-based and out patient-clinic respiratory physicians. Results Management of acute COPD exacerbations is dealt with within a scope of concerns. These concerns range from ‘dealing with comorbidity’ through ‘having difficult patients’ to ‘confronting a hopeless disease’. The first concern displays medical uncertainty regarding diagnosis, medication and hospitalisation. These clinical processes become blurred by comorbidity and the social context of the patient. The second concern shows how patients receive the label ‘difficult’ exactly because they need complex attention, but even more because they are time consuming, do not take responsibility and are non-compliant. The third concern relates to the emotional reactions by the physicians when confronted with ‘a hopeless disease’ due to the fact that most of the patients do not improve and the treatment slows down the process at best. GPs and respiratory physicians balance these concerns with medical knowledge and practical, situational knowledge, trying to encompass the complexity of a medical condition. Conclusions Knowing the patient is essential when dealing with comorbidities as well as with difficult relations in the consultations on exacerbations. This study suggests that it is crucial to improve the collaboration between primary and secondary care, in terms of, for example, shared consultations and defined work tasks, which may enhance shared knowledge of patients, medical decision-making and improved management planning. PMID:24319274

A new mode of community continuing care service for COPD patients in China: participation of respiratory nurse specialists.

PubMed

Li, Pingdong; Gong, Yucui; Zeng, Guangqiao; Ruan, Liang; Li, Guifen

2015-01-01

This study explored a community nursing service mode in which respiratory nurse specialists cared for patients with chronic obstructive pulmonary disease (COPD) in a 12-week period after hospital discharge, with the aim of better preventing acute exacerbations, improving health-related quality of life (HRQOL) and reducing medical expenses in these patients. We carried out a prospective randomized controlled study in which 68 COPD patients discharged were recruited from a general hospital in Guangzhou, China, were randomized divided into two groups. The control group underwent conventional nursing care, and the intervention group received community continuing care by respiratory nurse specialists. The observation period was 12 weeks. The results of intervention were evaluated using the Seattle Obstructive Lung Disease Questionnaire (SOLDQ) and the COPD Self-Efficacy Scale (CSES). In addition, the frequency of acute exacerbations, emergency treatments or hospitalizations, and medical expenses were recorded in the 12-week observation period. After six weeks, the total and subscale scores (P < 0.05) of SOLDQ and CSES significantly improved compared to the baseline ones in the intervention group. The control group had significantly higher scores in the treatment satisfaction (TS) of SOLDQ, the total score, and the weather/environment and behavioral risk factors of CSES. After 12 weeks, the total and subscale scores of SOLDQ and CSES showed a sustained and significant growth in the intervention group (P < 0.05). The control group had significantly higher scores only in the weather/environment risk factor of CSES. During the 12-week observation, the intervention group had significantly fewer acute exacerbations, emergency treatments or re-hospitalizations and significantly lower average medical expenses than the control group (P < 0.05). Community continuing care by respiratory nurse specialists may improve HRQOL, increase self-efficacy, reduce incidence of acute exacerbation, and lower medical expenses in patients with COPD after hospital discharge.

A new mode of community continuing care service for COPD patients in China: participation of respiratory nurse specialists

PubMed Central

Li, Pingdong; Gong, Yucui; Zeng, Guangqiao; Ruan, Liang; Li, Guifen

2015-01-01

Objective: This study explored a community nursing service mode in which respiratory nurse specialists cared for patients with chronic obstructive pulmonary disease (COPD) in a 12-week period after hospital discharge, with the aim of better preventing acute exacerbations, improving health-related quality of life (HRQOL) and reducing medical expenses in these patients. Methods: We carried out a prospective randomized controlled study in which 68 COPD patients discharged were recruited from a general hospital in Guangzhou, China, were randomized divided into two groups. The control group underwent conventional nursing care, and the intervention group received community continuing care by respiratory nurse specialists. The observation period was 12 weeks. The results of intervention were evaluated using the Seattle Obstructive Lung Disease Questionnaire (SOLDQ) and the COPD Self-Efficacy Scale (CSES). In addition, the frequency of acute exacerbations, emergency treatments or hospitalizations, and medical expenses were recorded in the 12-week observation period. Results: After six weeks, the total and subscale scores (P < 0.05) of SOLDQ and CSES significantly improved compared to the baseline ones in the intervention group. The control group had significantly higher scores in the treatment satisfaction (TS) of SOLDQ, the total score, and the weather/environment and behavioral risk factors of CSES. After 12 weeks, the total and subscale scores of SOLDQ and CSES showed a sustained and significant growth in the intervention group (P < 0.05). The control group had significantly higher scores only in the weather/environment risk factor of CSES. During the 12-week observation, the intervention group had significantly fewer acute exacerbations, emergency treatments or re-hospitalizations and significantly lower average medical expenses than the control group (P < 0.05). Conclusions: Community continuing care by respiratory nurse specialists may improve HRQOL, increase self-efficacy, reduce incidence of acute exacerbation, and lower medical expenses in patients with COPD after hospital discharge. PMID:26629091

Immune Responses in Rhinovirus-Induced Asthma Exacerbations.

PubMed

Steinke, John W; Borish, Larry

2016-11-01

Acute asthma exacerbations are responsible for urgent care visits and hospitalizations; they interfere with school and work productivity, thereby driving much of the morbidity and mortality associated with asthma. Approximately 80 to 85 % of asthma exacerbations in children, adolescents, and less frequently adults are associated with viral upper respiratory tract viral infections, and rhinovirus (RV) accounts for ∼60-70 % of these virus-associated exacerbations. Evidence suggests that it is not the virus itself but the nature of the immune response to RV that drives this untoward response. In particular, evidence supports the concept that RV acts to exacerbate an ongoing allergic inflammatory response to environmental allergens present at the time of the infection. The interaction of the ongoing IgE- and T cell-mediated response to allergen superimposed on the innate and adaptive immune responses to the virus and how this leads to triggering of an asthma exacerbation is discussed.

Assessing the Potential of Land Use Modification to Mitigate Ambient NO₂ and Its Consequences for Respiratory Health.

PubMed

Rao, Meenakshi; George, Linda A; Shandas, Vivek; Rosenstiel, Todd N

2017-07-10

Understanding how local land use and land cover (LULC) shapes intra-urban concentrations of atmospheric pollutants-and thus human health-is a key component in designing healthier cities. Here, NO₂ is modeled based on spatially dense summer and winter NO₂ observations in Portland-Hillsboro-Vancouver (USA), and the spatial variation of NO₂ with LULC investigated using random forest, an ensemble data learning technique. The NO 2 random forest model, together with BenMAP, is further used to develop a better understanding of the relationship among LULC, ambient NO₂ and respiratory health. The impact of land use modifications on ambient NO₂, and consequently on respiratory health, is also investigated using a sensitivity analysis. We find that NO₂ associated with roadways and tree-canopied areas may be affecting annual incidence rates of asthma exacerbation in 4-12 year olds by +3000 per 100,000 and -1400 per 100,000, respectively. Our model shows that increasing local tree canopy by 5% may reduce local incidences rates of asthma exacerbation by 6%, indicating that targeted local tree-planting efforts may have a substantial impact on reducing city-wide incidence of respiratory distress. Our findings demonstrate the utility of random forest modeling in evaluating LULC modifications for enhanced respiratory health.

Respiratory Conditions Associated with Tracheobronchomegaly (Mounier-Kuhn Syndrome): A Study of Seventeen Cases.

PubMed

Schmitt, Pierre; Dalar, Levent; Jouneau, Stéphane; Toublanc, Bénédicte; Camuset, Juliette; Chatte, Gérard; Cellerin, Laurent; Dutau, Hervé; Sanchez, Stéphane; Sauvage, Maxime; Vergnon, Jean-Michel; Dury, Sandra; Deslée, Gaetan; Lebargy, François

2016-01-01

Mounier-Kuhn syndrome (MKS) is a rare disorder characterized by enlargement of the trachea and main bronchi and associated with recurrent respiratory tract infections. This multicenter, retrospective study was carried out to describe respiratory conditions associated with tracheobronchomegaly. Nine institutions involved in the 'Groupe d'Endoscopie de Langue Française' (GELF) participated in this study. A standard form was used to record patient characteristics, treatments and follow-up from medical charts. Seventeen patients, 53% male, aged 58 ± 18 years at diagnosis were included. Recurrent infections revealed MKS in 88% of cases. Main comorbid conditions were diffuse bronchiectasis in 88% of patients and tracheobronchomalacia in 67% of cases. The exacerbation rate was 1.5 exacerbations/patient/year. The main non-respiratory morbid condition was gastroesophageal reflux disease in 29% of cases. Interventional bronchoscopy was performed in seven patients (41%), consisting of laser (n = 2) and tracheal stenting (n = 5). Complications related to stents were observed in 80% of cases with a mean stent duration of 8 months. Four deaths, including three due to respiratory causes, occurred during follow-up. This is the largest series of MKS reported in the literature, showing that bronchiectasis and tracheobronchomalacia are the main associated morbid conditions that constitute a challenge for treatment. © 2016 S. Karger AG, Basel.

Association between respiratory prescribing, air pollution and deprivation, in primary health care.

PubMed

Sofianopoulou, Eleni; Rushton, Stephen P; Diggle, Peter J; Pless-Mulloli, Tanja

2013-12-01

We investigated the association between respiratory prescribing, air quality and deprivation in primary health care. Most previous studies have used data from secondary and tertiary care to quantify air pollution effects on exacerbations of asthma and chronic obstructive pulmonary disease (COPD). However, these outcomes capture patients who suffer from relatively severe symptoms. This is a population-based ecological study. We analysed respiratory medication (salbutamol) prescribed monthly by 63 primary care practices, UK. Firstly, we captured the area-wide seasonal variation in prescribing. Then, using the area-wide variation in prescribing as an offset, we built a mixed-effects model to assess the remaining variation in relation to air quality and demographic variables. An increase of 10 μg/m(3) in ambient PM10 was associated with an increase of 1% (95% CI: 0.1-2%) in salbutamol prescribing. An increase of 1 SD in income and employment deprivation was associated with an increase of 20.5% (95% CI: 8.8-33.4%) and 14.7% (95% CI: 4.3-26.2%) in salbutamol prescribing rate, respectively. The study provides evidence that monthly respiratory prescribing in primary care is a useful indicator of the extent to which air pollution exacerbates asthma and COPD symptoms. Respiratory prescribing was higher on deprived populations.

Gene-Environment Interactions in Asthma: Genetic and Epigenetic Effects.

PubMed

Lee, Jong-Uk; Kim, Jeong Dong; Park, Choon-Sik

2015-07-01

Over the past three decades, a large number of genetic studies have been aimed at finding genetic variants associated with the risk of asthma, applying various genetic and genomic approaches including linkage analysis, candidate gene polymorphism studies, and genome-wide association studies (GWAS). However, contrary to general expectation, even single nucleotide polymorphisms (SNPs) discovered by GWAS failed to fully explain the heritability of asthma. Thus, application of rare allele polymorphisms in well defined phenotypes and clarification of environmental factors have been suggested to overcome the problem of 'missing' heritability. Such factors include allergens, cigarette smoke, air pollutants, and infectious agents during pre- and post-natal periods. The first and simplest interaction between a gene and the environment is a candidate interaction of both a well known gene and environmental factor in a direct physical or chemical interaction such as between CD14 and endotoxin or between HLA and allergens. Several GWAS have found environmental interactions with occupational asthma, aspirin exacerbated respiratory disease, tobacco smoke-related airway dysfunction, and farm-related atopic diseases. As one of the mechanisms behind gene-environment interaction is epigenetics, a few studies on DNA CpG methylation have been reported on subphenotypes of asthma, pitching the exciting idea that it may be possible to intervene at the junction between the genome and the environment. Epigenetic studies are starting to include data from clinical samples, which will make them another powerful tool for re-search on gene-environment interactions in asthma.

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.

Risk of death and readmission of hospital-admitted COPD exacerbations: European COPD Audit.

PubMed

Hartl, Sylvia; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Castro-Acosta, Ady; Studnicka, Michael; Kaiser, Bernhard; Roberts, C Michael

2016-01-01

Studies report high in-hospital and post-discharge mortality of chronic obstructive pulmonary disease (COPD) exacerbations varying depending upon patient characteristics, hospital resources and treatment standards. This study aimed to investigate the patient, resource and organisational factors associated with in-hospital and 90-day post-discharge mortality and readmission of COPD exacerbations within the European COPD Audit. The audit collected data of COPD exacerbation admissions from 13 European countries.On admission, only 49.7% of COPD patients had spirometry results available and only 81.6% had blood gases taken. Using logistic regression analysis, the risk associated with in-hospital and post-discharge mortality was higher age, presence of acidotic respiratory failure, subsequent need for ventilatory support and presence of comorbidity. In addition, the 90-day risk of COPD readmission was associated with previous admissions. Only the number of respiratory specialists per 1000 beds, a variable related to hospital resources, decreased the risk of post-discharge mortality.The European COPD Audit identifies risk factors associated with in-hospital and post-discharge mortality and COPD readmission. Addressing the deficiencies in acute COPD care such as making spirometry available and measuring blood gases and providing noninvasive ventilation more regularly would provide opportunities to improve COPD outcomes. Copyright ©ERS 2016.

Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica

USDA-ARS?s Scientific Manuscript database

Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovi...

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness.

PubMed

Edwards, Michael R; Strong, Katherine; Cameron, Aoife; Walton, Ross P; Jackson, David J; Johnston, Sebastian L

2017-10-01

Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with T H 2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and T H 2 mediators. With the renewed interest in anti-T H 2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Human Metapneumovirus (hMPV) associated to severe bronchial asthmatic crisis].

PubMed

López, M A; Kusznierz, G F; Imaz, M S; Cociglio, R; Tedeschi, F A; Zalazar, F E

2006-01-01

Human Metapneumovirus (hMPV) is a recently reported agent of acute infection in the respiratory tract. It has been found in children as well as in young adults and elders. The clinical manifestations produced by hMPV are indistinguishable from those by common respiratory virus, and can evolve from asymptomatic infection into severe pneumonia. On the other hand, some authors have described cases of bronchial asthma exacerbation associated with hMPV infection. In this work we report a case of a child who presented a severe bronchial asthmatic crisis with a suspected viral associated infection. Immunofluorescence tests yielded negative results for sincitial respiratory virus, adenovirus, a-b influenza virus and parainfluenza 1, 2, 3, virus. In an attempt to detect the presence of hMPV, a RT-PCR was carried out to amplify sequences from both N and F genes. Using this approach, a positive result for hMPV was obtained. To our knowledge, this is the first description of a case of asthma exacerbation associated to hMPV in our region. In addition, these results are similar to previous reports where it was hypothesized that, like RSV, hMPV can trigger a respiratory chronic disease as asthma.

Managing Pseudomonas aeruginosa respiratory infections in cystic fibrosis.

PubMed

Langan, Katherine M; Kotsimbos, Tom; Peleg, Anton Y

2015-12-01

The current guidelines and recent clinical research in the management of Pseudomonas aeruginosa respiratory infections in cystic fibrosis (CF) are reviewed. Areas where further research is required will also be highlighted. P. aeruginosa is a key respiratory pathogen in CF. Inhaled tobramycin or colistin is recommended for early eradication to prevent establishment of chronic infection. Other antibiotic options are currently being investigated. The long-term success of eradication strategies is also now being assessed. The use of inhaled antibiotics in the management of chronic P. aeruginosa infection is an area of active investigation. Acute pulmonary exacerbations are still a major cause of morbidity and mortality. Guidelines continue to recommend combination intravenous therapy but further research is required to clarify the advantage of this approach. Multidrug resistance is common and potentially more effective antipseudomonal antibiotics may soon become available. The management of P. aeruginosa respiratory infection in CF remains a challenging area, especially in the setting of multidrug resistance. The role of inhaled antibiotics continues to be expanded. Further research is required in the key areas of eradication and management of chronic infection and acute pulmonary exacerbations to identify those treatments that optimize long-term, clinical benefits.

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.

Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

PubMed Central

Mesquita, Carolina Bonfanti; Caram, Laura M. O.; Dourado, Victor Zuniga; de Godoy, Irma; Tanni, Suzana Erico

2017-01-01

Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years) agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT). Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg (p = 0.004) and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm (p = 0.008) and pulse oximetry (SpO2) decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (p < 0.001). Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (p = 0.092), and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe. PMID:28265180

Differences in baseline factors and survival between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation: A pilot study.

PubMed

Lun, Chung-Tat; Tsui, Miranda S N; Cheng, Suet-Lai; Chan, Veronica L; Leung, Wah-Shing; Cheung, Alice P S; Chu, Chung-Ming

2016-01-01

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute exacerbation (AE-COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. However, the outcomes of AE-COPD patients with compensated respiratory acidosis are not known. We performed a 1-year prospective, single-centre, cohort study in patients surviving the index admission for AE-COPD to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life-threatening events and death. A total of 250 patients fulfilling the inclusion and exclusion criteria were recruited and 245 patients were analysed. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % (P < 0.001), higher GOLD stage (P = 0.003, <0.001) and higher BODE index (P = 0.038, 0.001) and a shorter time to life-threatening events (P < 0.001). Comparing compensated and decompensated respiratory acidosis, there was no difference in FEV1 (% predicted) (P = 0.15), GOLD stage (P = 0.091), BODE index (P = 0.158) or time to life-threatening events (P = 0.301). High PaCO2 level (P = 0.002) and previous use of non-invasive ventilation (NIV) in acute setting (P < 0.001) are predictive factors of future life-threatening events by multivariate analysis. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with poorer lung function and higher risk of future life-threatening events. High PaCO2 level and past history of NIV use in acute settings were predictive factors for future life-threatening events. Compensated respiratory acidosis warrants special attention and optimization of medical therapy as it poses risk of life-threatening events. © 2015 Asian Pacific Society of Respirology.

/sup 125/I-Clq-binding and specific antibodies as indicators of pulmonary disease activity in cystic fibrosis

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

Moss, R.B.; Hsu, Y.P.; Lewiston, N.J.

1981-08-01

We studied the incidence and levels of circulating immune complexes by the /sup 125/I-Clq-binding assay in patients with cystic fibrosis in relation to clinical respiratory status and specific IgG and IgE antibodies to Pseudomonas aeruginosa. Staphylococcus aureus, Aspergillus fumigatus, and Candida albicans. Overall prevalence of CIC was 43%, but 86% of serially studied patients had evidence of CIC at some time. Patients with acute respiratory exacerbations and deteriorating pulmonary function had a higher incidence of CIC (76%) as compared to stable patients (36%, P less than 0.01), as well as significantly higher levels of CIC. Acute exacerbations were also associatedmore » with significant increases in IgG antibody to Pseudomonas (P less than 0.005) but not in other antibodies. CIC did not correlate with Pseudomonas-specific IgG nor with any other specific antibody studied. A variety of age-related differences in specific antibody levels were seen. The episodic appearance of CIC is common in CF and is usually associated with exacerbation of lung disease.« less

Is there a threshold concentration of cat allergen exposure on respiratory symptoms in adults?

PubMed

Chen, Chih-Mei; Thiering, Elisabeth; Zock, Jan-Paul; Villani, Simona; Olivieri, Mario; Modig, Lars; Jarvis, Deborah; Norbäck, Dan; Verlato, Giuseppe; Heinrich, Joachim

2015-01-01

Cat allergen concentrations higher than 8 μg/g in settled house dust, have been suggested to provoke exacerbation of allergic respiratory symptoms. However, whether the 8 μg/g of indoor cat allergen concentration is indeed the minimal exposure required for triggering the asthma related respiratory symptoms or the development of sensitization has not yet been confirmed. We studied the associations between domestic cat allergen concentrations and allergic symptoms in the European Community Respiratory Health Survey II, with the aim of confirming this suggested threshold. Cat allergen concentrations were measured in the mattress dust of 3003 participants from 22 study centres. Levels of specific immunoglobulin E to cat allergens were measured in serum samples using an immunoassay. Information on allergic symptoms, medication use, home environment and smoking was obtained from a face-to-face interview. Domestic cat allergen concentrations were not associated with allergic/ asthmatic symptoms in the entire study population, nor in the subset sensitized to cat allergen. We also found no association among individuals exposed to concentrations higher than 8 μg/g. However, exposure to medium cat allergen concentrations (0.24-0.63 μg/g) was positively associated with reported asthmatic respiratory symptoms in subjects who have experienced allergic symptoms when near animals. The proposed 8 μg/g threshold of cat allergen concentrations for the exacerbation of allergic/ respiratory symptoms was not confirmed in a general European adult population. Potential biases attributable to avoidance behaviours and an imprecise exposure assessment cannot be excluded.

Selective inhibition by aspirin and naproxen of mainstream cigarette smoke-induced genotoxicity and lung tumors in female mice.

PubMed

Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Micale, Rosanna T; La Maestra, Sebastiano; D'Oria, Chiara; Steele, Vernon E; De Flora, Silvio

2016-05-01

The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in smoke-related lung carcinogenesis is still controversial. We have developed and validated a murine model for evaluating the tumorigenicity of mainstream cigarette smoke (MCS) and its modulation by chemopreventive agents. In the present study, the protective effects of the nonselective cyclooxygenase inhibitors aspirin and naproxen were investigated by using a total of 277 Swiss H neonatal mice of both genders. Groups of mice were exposed whole-body to MCS during the first 4 months of life, followed by an additional 3.5 months in filtered air in order to allow a better growth of tumors. Aspirin (1600 mg/kg diet) and naproxen (320 mg/kg diet) were given after weanling until the end of the experiment. After 4 months of exposure, MCS significantly enhanced the frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice, and naproxen prevented such systemic genotoxic damage in female mice. After 7.5 months, exposure of mice to MCS resulted in the formation of lung tumors, both benign and malignant, and in several other histopathological lesions detectable both in the respiratory tract and in the urinary tract. Aspirin and, even more sharply, naproxen significantly inhibited the formation of lung tumors in MCS-exposed mice, but this protective effect selectively occurred in female mice only. These results lend support to the views that estrogens are involved in smoke-related pulmonary carcinogenesis and that NSAIDs have antiestrogenic properties. The two NSAIDs proved to be safe and efficacious in the experimental model used.

Assessing the Potential of Land Use Modification to Mitigate Ambient NO2 and Its Consequences for Respiratory Health

PubMed Central

Rao, Meenakshi; George, Linda A.; Shandas, Vivek; Rosenstiel, Todd N.

2017-01-01

Understanding how local land use and land cover (LULC) shapes intra-urban concentrations of atmospheric pollutants—and thus human health—is a key component in designing healthier cities. Here, NO2 is modeled based on spatially dense summer and winter NO2 observations in Portland-Hillsboro-Vancouver (USA), and the spatial variation of NO2 with LULC investigated using random forest, an ensemble data learning technique. The NO2 random forest model, together with BenMAP, is further used to develop a better understanding of the relationship among LULC, ambient NO2 and respiratory health. The impact of land use modifications on ambient NO2, and consequently on respiratory health, is also investigated using a sensitivity analysis. We find that NO2 associated with roadways and tree-canopied areas may be affecting annual incidence rates of asthma exacerbation in 4–12 year olds by +3000 per 100,000 and −1400 per 100,000, respectively. Our model shows that increasing local tree canopy by 5% may reduce local incidences rates of asthma exacerbation by 6%, indicating that targeted local tree-planting efforts may have a substantial impact on reducing city-wide incidence of respiratory distress. Our findings demonstrate the utility of random forest modeling in evaluating LULC modifications for enhanced respiratory health. PMID:28698523

Eosinophilic and non-eosinophilic COPD patients with chronic respiratory failure: neutrophil-to-lymphocyte ratio as an exacerbation marker.

PubMed

Acartürk Tunçay, Eylem; Karakurt, Zuhal; Aksoy, Emine; Saltürk, Cuneyt; Gungor, Sinem; Ciftaslan, Nezihe; Irmak, İlim; Yavuz, Dilek; Ocakli, Birsen; Adıgüzel, Nalan

2017-01-01

Increased dyspnea, sputum volume, and purulence are subjective symptoms in COPD patients. To diagnose COPD exacerbations with chronic respiratory failure (CRF) and to assess the requirement for antibiotic treatment, physicians require more objective criteria. We aimed to investigate whether neutrophil-to-lymphocyte ratio (NLR) can be used as an infectious exacerbation marker in COPD patients with CRF. This retrospective cross-sectional study was performed in the intensive care outpatient clinic of a tertiary training hospital between 2014 and 2015. Patients admitted with CRF due to COPD and who had complete blood count (CBC) results were enrolled. CBC results and C-reactive protein (CRP) levels were obtained from the hospital online database. The "modified exacerbation model (MEM)" was defined as follows: exacerbation A, leukocytes ≥12,000/mm 3 , CRP >10 mg/dL; exacerbation B, leukocytes ≥10,000/mm 3 , CRP >10 mg/dL; exacerbation C, leukocytes ≥10,000/mm 3 , CRP >8 mg/dL; exacerbation D, leukocytes ≥10,000/mm 3 , CRP >5 mg/dL. The cutoff value of NLR was defined for each model. Patients were split into two groups based on the NLR cutoff value according to the "NLR exacerbation model" and further subgrouped according to peripheral eosinophil percentage (eosinophils ≥2% and <2%) and compared with the MEM. A total of 1,066 COPD patients (430 females, 40.3%), with a mean age of 66±13 years, were included. A NLR cutoff value of 3.54 (NLR ≥3.54, n=366, 34%) showed the highest sensitivity and specificity for model A (78%, 69%), model B (63%, 71%), model C (61%, 72%), and model D (58%, 72%). Peripheral eosinophilia (PE ≥2%) was present in 48 patients (4.5%). The ratio of patients with PE <2% in the NLR ≥3.54 group was significantly higher in the MEM ( P <0.001). The NLR presents an attractive option as an exacerbation marker in COPD patients with CRF due to its simplicity and cost-effectiveness. In COPD patients with CRF, where the NLR is ≥3.54, PE levels are <2%, and subjective symptoms are present, antibiotic treatment should be considered.

Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model.

PubMed

Eggo, Rosalind M; Scott, James G; Galvani, Alison P; Meyers, Lauren Ancel

2016-02-23

Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses--the "common cold" viruses--are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41-49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17-21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the "back-to-school" asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics.

Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model

PubMed Central

Scott, James G.; Galvani, Alison P.; Meyers, Lauren Ancel

2016-01-01

Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses—the “common cold” viruses—are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41–49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17–21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the “back-to-school” asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics. PMID:26858436

Hazardous air pollutants and asthma.

PubMed

Leikauf, George D

2002-08-01

Asthma has a high prevalence in the United States, and persons with asthma may be at added risk from the adverse effects of hazardous air pollutants (HAPs). Complex mixtures (fine particulate matter and tobacco smoke) have been associated with respiratory symptoms and hospital admissions for asthma. The toxic ingredients of these mixtures are HAPs, but whether ambient HAP exposures can induce asthma remains unclear. Certain HAPs are occupational asthmagens, whereas others may act as adjuncts during sensitization. HAPs may exacerbate asthma because, once sensitized, individuals can respond to remarkably low concentrations, and irritants lower the bronchoconstrictive threshold to respiratory antigens. Adverse responses after ambient exposures to complex mixtures often occur at concentrations below those producing effects in controlled human exposures to a single compound. In addition, certain HAPs that have been associated with asthma in occupational settings may interact with criteria pollutants in ambient air to exacerbate asthma. Based on these observations and past experience with 188 HAPs, a list of 19 compounds that could have the highest impact on the induction or exacerbation of asthma was developed. Nine additional compounds were identified that might exacerbate asthma based on their irritancy, respirability, or ability to react with biological macromolecules. Although the ambient levels of these 28 compounds are largely unknown, estimated exposures from emissions inventories and limited air monitoring suggest that aldehydes (especially acrolein and formaldehyde) and metals (especially nickel and chromium compounds) may have possible health risk indices sufficient for additional attention. Recommendations for research are presented regarding exposure monitoring and evaluation of biologic mechanisms controlling how these substances induce and exacerbate asthma.

Hazardous air pollutants and asthma.

PubMed Central

Leikauf, George D

2002-01-01

Asthma has a high prevalence in the United States, and persons with asthma may be at added risk from the adverse effects of hazardous air pollutants (HAPs). Complex mixtures (fine particulate matter and tobacco smoke) have been associated with respiratory symptoms and hospital admissions for asthma. The toxic ingredients of these mixtures are HAPs, but whether ambient HAP exposures can induce asthma remains unclear. Certain HAPs are occupational asthmagens, whereas others may act as adjuncts during sensitization. HAPs may exacerbate asthma because, once sensitized, individuals can respond to remarkably low concentrations, and irritants lower the bronchoconstrictive threshold to respiratory antigens. Adverse responses after ambient exposures to complex mixtures often occur at concentrations below those producing effects in controlled human exposures to a single compound. In addition, certain HAPs that have been associated with asthma in occupational settings may interact with criteria pollutants in ambient air to exacerbate asthma. Based on these observations and past experience with 188 HAPs, a list of 19 compounds that could have the highest impact on the induction or exacerbation of asthma was developed. Nine additional compounds were identified that might exacerbate asthma based on their irritancy, respirability, or ability to react with biological macromolecules. Although the ambient levels of these 28 compounds are largely unknown, estimated exposures from emissions inventories and limited air monitoring suggest that aldehydes (especially acrolein and formaldehyde) and metals (especially nickel and chromium compounds) may have possible health risk indices sufficient for additional attention. Recommendations for research are presented regarding exposure monitoring and evaluation of biologic mechanisms controlling how these substances induce and exacerbate asthma. PMID:12194881

Digging through the Obstruction: Insight into the Epithelial Cell Response to Respiratory Virus Infection in Patients with Cystic Fibrosis.

PubMed

Hendricks, Matthew R; Bomberger, Jennifer M

2016-05-01

Respiratory virus infections are common but generally self-limiting infections in healthy individuals. Although early clinical studies reported low detection rates, the development of molecular diagnostic techniques by PCR has led to an increased recognition that respiratory virus infections are associated with morbidity and acute exacerbations of chronic lung diseases, such as cystic fibrosis (CF). The airway epithelium is the first barrier encountered by respiratory viruses following inhalation and the primary site of respiratory viral replication. Here, we describe how the airway epithelial response to respiratory viral infections contributes to disease progression in patients with CF and other chronic lung diseases, including the role respiratory viral infections play in bacterial acquisition in the CF patient lung. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Impact of air pollution on respiratory diseases in children with recurrent wheezing or asthma.

PubMed

Esposito, Susanna; Galeone, Carlotta; Lelii, Mara; Longhi, Benedetta; Ascolese, Beatrice; Senatore, Laura; Prada, Elisabetta; Montinaro, Valentina; Malerba, Stefano; Patria, Maria Francesca; Principi, Nicola

2014-08-07

Air pollution has many negative health effects on the general population, especially children, subjects with underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering from asthma or wheezing compared with healthy subjects and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms. This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma and 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about respiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants. Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed follow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p=0.005) and cough (p<0.001), episodes of rhinitis (p=0.04) and tracheitis (p=0.01), asthma attacks (p<0.001), episodes of pneumonia (p<0.001) and hospitalizations (p=0.02). In the wheezing/asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR]=1.79; 95% confidence interval [CI], 1.13-2.84), whereas living near green areas was found to be protective (OR=0.50; 95% CI, 0.31 -0.80). An increase of 10 μg/m3 of particulates less than 10 microns in diameter (PM10) and nitrogen dioxide (NO2) increased the onset of pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR]=1.08, 95% CI: 1.00-1.17 for PM10; continuous RR=1.08, 95% CI: 1.01-1.17 for NO2). There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent wheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in children with underlying respiratory disease.

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease--2003.

PubMed

O'Donnell, Denis E; Aaron, Shawn; Bourbeau, Jean; Hernandez, Paul; Marciniuk, Darcy; Balter, Meyer; Ford, Gordon; Gervais, Andre; Goldstein, Roger; Hodder, Rick; Maltais, Francois; Road, Jeremy

2003-01-01

Chronic obstructive pulmonary disease (COPD) is a common cause of disability and death in Canada. Moreover, morbidity and mortality from COPD continue to rise, and the economic burden is enormous. The main goal of the Canadian Thoracic Society (CTS) Evidence-Based Guidelines is to optimize early diagnosis, prevention and management of COPD in Canada. Targeted spirometry is strongly recommended to expedite early diagnosis in smokers and exsmokers who develop respiratory symptoms, and who are at risk for COPD. Smoking cessation remains the single most effective intervention in accordance with the increasing severity of symptoms and disability. Long-acting anticholinergics and beta2-agonist inhalers should be prescribed for patients who remain symptomatic despite short-acting bronchodilatory therapy. Inhaled steroids should not be used as first-line therapy in COPD but have a role in preventing exacerbations in patients with more advanced disease who suffer recurrent exacerbations. Management strategies consisting of combined modern pharmacotherapy and nonpharmacotherapeutic interventions (eg, pulmonary rehabilitation/exercise training) can effectively improve symptoms, activity levels and quality of life, even in patients with severe COPD. Acute exacerbations of COPD cause significant morbidity and mortality and should be treated promptly with bronchodilators and a short course of oral steroids; antibiotics should be prescribed for purulent exacerbations. Patients with advanced COPD and respiratory failure require a comprehensive management plan that incorporates structured end-of-life care.

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

Respiratory viral infections in children with asthma: do they matter and can we prevent them?

PubMed Central

2012-01-01

Background Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. Discussion While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. Summary Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children. PMID:22974166

Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study.

PubMed

van Geffen, Wouter H; Bruins, Marcel; Kerstjens, Huib A M

2016-06-16

Respiratory infections, viral or bacterial, are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A rapid, point-of-care, and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care. An electronic nose (e-nose) could fit this profile but has never been tested in this setting before. In a single-center registered trial (NTR 4601) patients admitted with AECOPD were tested with the Aeonose(®) electronic nose, and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs. A neural network with leave-10%-out cross-validation was used to assess the e-nose data. Forty three patients were included. In the bacterial infection model, 22 positive cases were tested versus the negatives; and similarly 18 positive cases were tested in the viral infection model. The Aeonose was able to distinguish between COPD-subjects suffering from a viral infection and COPD patients without infection, showing an area under the curve (AUC) of 0.74. Similarly, for bacterial infections, an AUC of 0.72 was obtained. The Aeonose e-nose yields promising results in 'smelling' the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD. Validation of these results using a new and large cohort is required before introduction into clinical practice.

Lactic Acidosis with Chloramphenicol Treatment in a Child with Cystic Fibrosis.

PubMed

Goyer, Isabelle; Iseppon, Massimiliano; Thibault, Céline; Abaji, Rachid; Krajinovic, Maja; Autmizguine, Julie

2017-01-30

Children with cystic fibrosis are commonly colonized with multi-resistant bacteria. In such patients, infectious exacerbation may require salvage therapy with uncommonly used antimicrobials, including chloramphenicol. Chloramphenicol is rarely used nowadays because of the associated severe adverse events. We describe the case of a 15-year-old female with terminal cystic fibrosis who required intravenous (IV) chloramphenicol treatment for a Burkholderia cepacia (B. cepacia) exacerbation. The child subsequently developed lactic acidosis and secondary respiratory compensation adding to her baseline respiratory distress. Based on the Naranjo scale, the probability of chloramphenicol being the cause of the hyperlactatemia and associated respiratory distress was rated as probable, as the adverse effects resolved upon discontinuation of the drug. Subsequent genotyping for mitochondrial polymorphism (G3010A) confirmed a possible susceptibility to lactic acidosis from mitochondrial RNA-inhibiting agents such as chloramphenicol. Hyperlactatemia is a rare but life threatening adverse effect that has been previously reported with chloramphenicol exposure, but is not generally thought of. Clinicians should be aware of this potentially life threatening, but reversible adverse event. Lactate should be monitored under chloramphenicol and it should be discontinued as soon as this complication is suspected, especially in patients with low respiratory reserve. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Is There a Threshold Concentration of Cat Allergen Exposure on Respiratory Symptoms in Adults?

PubMed Central

Zock, Jan-Paul; Villani, Simona; Olivieri, Mario; Modig, Lars; Jarvis, Deborah; Norbäck, Dan; Verlato, Giuseppe; Heinrich, Joachim

2015-01-01

Background and Objective Cat allergen concentrations higher than 8 μg/g in settled house dust, have been suggested to provoke exacerbation of allergic respiratory symptoms. However, whether the 8μg/g of indoor cat allergen concentration is indeed the minimal exposure required for triggering the asthma related respiratory symptoms or the development of sensitization has not yet been confirmed. We studied the associations between domestic cat allergen concentrations and allergic symptoms in the European Community Respiratory Health Survey II, with the aim of confirming this suggested threshold. Methods Cat allergen concentrations were measured in the mattress dust of 3003 participants from 22 study centres. Levels of specific immunoglobulin E to cat allergens were measured in serum samples using an immunoassay. Information on allergic symptoms, medication use, home environment and smoking was obtained from a face-to-face interview. Results Domestic cat allergen concentrations were not associated with allergic/ asthmatic symptoms in the entire study population, nor in the subset sensitized to cat allergen. We also found no association among individuals exposed to concentrations higher than 8 μg/g. However, exposure to medium cat allergen concentrations (0.24-0.63 μg/g) was positively associated with reported asthmatic respiratory symptoms in subjects who have experienced allergic symptoms when near animals. Conclusions The proposed 8 μg/g threshold of cat allergen concentrations for the exacerbation of allergic/ respiratory symptoms was not confirmed in a general European adult population. Potential biases attributable to avoidance behaviours and an imprecise exposure assessment cannot be excluded. PMID:26035304

The clinical and integrated management of COPD. An official document of AIMAR (Interdisciplinary Association for Research in Lung Disease), AIPO (Italian Association of Hospital Pulmonologists), SIMER (Italian Society of Respiratory Medicine), SIMG (Italian Society of General Medicine)

PubMed Central

2014-01-01

COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60% predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2 < 88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with "severe" or "very severe" COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneously published in Sarcoidosis Vasc Diffuse Lung Dis 2014, 31(Suppl. 1);3-21. PMID:25057359

Management of Acute Exacerbation of Asthma and Chronic Obstructive Pulmonary Disease in the Emergency Department.

PubMed

Suau, Salvador J; DeBlieux, Peter M C

2016-02-01

Acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations are the most common respiratory diseases requiring emergent medical evaluation and treatment. Asthma and COPD are chronic, debilitating disease processes that have been differentiated traditionally by the presence or absence of reversible airflow obstruction. Asthma and COPD exacerbations impose an enormous economic burden on the US health care budget. In daily clinical practice, it is difficult to differentiate these 2 obstructive processes based on their symptoms, and on their nearly identical acute treatment strategies; major differences are important when discussing anatomic sites involved, long-term prognosis, and the nature of inflammatory markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Leukotriene E4 induces airflow obstruction and mast cell activation through the cysteinyl leukotriene type 1 receptor.

PubMed

Lazarinis, Nikolaos; Bood, Johan; Gomez, Cristina; Kolmert, Johan; Lantz, Ann-Sofie; Gyllfors, Pär; Davis, Andy; Wheelock, Craig E; Dahlén, Sven-Erik; Dahlén, Barbro

2018-03-05

Leukotriene (LT) E 4 is the final active metabolite among the cysteinyl leukotrienes (CysLTs). Animal studies have identified a distinct LTE 4 receptor, suggesting that current cysteinyl leukotriene type 1 (CysLT 1 ) receptor antagonists can provide incomplete inhibition of CysLT responses. We tested this hypothesis by assessing the influence of the CysLT 1 antagonist montelukast on responses induced by means of inhalation of LTE 4 in asthmatic patients. Fourteen patients with mild intermittent asthma and 2 patients with aspirin-exacerbated respiratory disease received 20 mg of montelukast twice daily and placebo for 5 to 7 days in a randomized, double-blind, crossover study (NCT01841164). The PD 20 value was determined at the end of each treatment period based on an increasing dose challenge. Measurements included lipid mediators in urine and sputum cells 4 hours after LTE 4 challenge. Montelukast completely blocked LTE 4 -induced bronchoconstriction. Despite tolerating an at least 10 times higher dose of LTE 4 after montelukast, there was no difference in the percentage of eosinophils in sputum. Urinary excretion of all major lipid mediators increased after LTE 4 inhalation. Montelukast blocked release of the mast cell product prostaglandin (PG) D 2 , as well as release of PGF 2α and thromboxane (Tx) A 2 , but not increased excretion of PGE 2 and its metabolites or isoprostanes. LTE 4 induces airflow obstruction and mast cell activation through the CysLT 1 receptor. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Acute spinal cord compression: a rare complication of dual antiplatelet therapy

PubMed Central

Iskandar, Muhammad Zaid; Chong, Victor; Hutcheon, Stuart

2015-01-01

A 73-year-old woman presented with acute shortness of breath and exacerbation of chronic back pain. She was diagnosed with pulmonary oedema and a non-ST-elevation myocardial infarction following chest X-ray, ECG and high sensitivity troponin levels. She subsequently underwent coronary angioplasty with deployment of drug-eluting stents to her circumflex and left anterior descending arteries and was started on aspirin and clopidogrel for her dual antiplatelet therapy. Unfortunately, following the procedure, she gradually lost power and sensation in both lower limbs. MRI of her spine confirmed an extradural haematoma causing thoracic cord compression. She was managed conservatively following discussions with neurosurgeons and developed further complications secondary to her immobility. PMID:26202314

Hemicrania Continua: Beneficial Effect of Non-Invasive Vagus Nerve Stimulation in a Patient With a Contraindication for Indomethacin.

PubMed

Eren, Ozan; Straube, Andreas; Schöberl, Florian; Schankin, Christoph

2017-02-01

Hemicrania continua (HC) is a primary chronic headache disorder, characterized by a continuous and strictly unilateral headache, with possible cranial autonomic symptoms during episodes of pain exacerbation. The unilateral headache generally responds well to indomethacin; however, continuous indomethacin intake is often not tolerated due to severe adverse effects, like hypertension, gastrointestinal discomfort (especially if combined with aspirin), slightly increased risk of vascular events, and bronchial spasms. Therefore, alternative treatment options are desperately needed. Non-invasive vagus nerve stimulation (nVNS) has been shown to be effective in patients with cluster headache, another trigeminal autonomic cephalalgia (TAC), with cranial parasympathetic autonomic activation during the attacks. © 2016 American Headache Society.

Host DNA released by NETosis promotes rhinovirus-induced type 2 allergic asthma exacerbation

PubMed Central

Toussaint, Marie; Jackson, David J; Swieboda, Dawid; Guedán, Anabel; Tsourouktsoglou, Theodora-Dorita; Ching, Yee Man; Radermecker, Coraline; Makrinioti, Heidi; Aniscenko, Julia; Edwards, Michael R; Solari, Roberto; Farnir, Frédéric; Papayannopoulos, Venizelos; Bureau, Fabrice; Marichal, Thomas; Johnston, Sebastian L

2018-01-01

Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of type 2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type 2 responses is poorly understood. We report a significant correlation between release of host double stranded DNA (dsDNA) following rhinovirus infection and exacerbation of type 2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with neutrophil extracellular traps (NETs) formation (NETosis). We further demonstrate that inhibiting NETosis by blocking neutrophil elastase, or degrading NETs with DNase protects mice from type 2 immunopathology. Furthermore, injection of mouse genomic DNA alone is sufficient to recapitulate many features of rhinovirus-induced type 2 immune responses and asthma pathology. Thus, NETosis and its associated extracellular dsDNA contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations. PMID:28459437

Hyperventilation of pregnancy presenting with flaccid quadriparesis due to hypokalaemia secondary to respiratory alkalosis.

PubMed

Santra, Gouranga; Paul, Rudrajit; Das, Shubhabrata; Pradhan, Sourav

2014-06-01

Hyperventilation in pregnancy is a cause of chronic respiratory alkalosis. Alkalosis either metabolic or respiratory may cause intracellular shift of potassium ions that may lead to hypokalaemia. However, the resultant hypokalaemia in respiratory alkalosis is usually mild and does not cause much clinical features. A five-months-pregnant female of the age 25 years presented with sudden onset flaccid weakness of both lower limbs associated with thigh muscle pain followed by weakness of both upper limbs within three days. Subsequent investigation revealed severe hypokalaemia due to acute exacerbation of chronic respiratory alkalosis secondary to hyperventilation of pregnancy, other causes of hypokalaemia being ruled out. Respiratory alkalosis causes tetany and other clinical manifestations. But hypokalaemia and such weakness is rarely found. Thisis probably the first report of this type from India.

Biventricular non-compaction hypertrophic cardiomyopathy in association with congenital complete heart block and type I mitochondrial complex deficiency.

PubMed

Dhar, Ranjana; Reardon, William; McMahon, Colin J

2015-06-01

We report a baby girl with an antenatal diagnosis of biventricular non-compaction and complete heart block detected at 22 weeks' gestation. Postnatal echocardiography confirmed severe biventricular non-compaction hypertrophic cardiomyopathy, multiple muscular ventricular septal defects, and mild-moderate pulmonary valve stenosis. Skeletal muscle biopsy confirmed complex 1 mitochondrial respiratory chain deficiency. An epicardial VVI pacemaker was implanted on day 3 of life and revised at 7 years of age. She remains stable at 8 years of age following pacing and medical treatment with carvedilol, aspirin, co-enzyme Q10, and carnitine. This represents the first report of biventricular non-compaction hypertrophic phenotype in association with congenital complete heart block and complex 1 mitochondrial respiratory chain deficiency in a child.

Detection of adenovirus and respiratory syncytial virus in patients with chronic obstructive pulmonary disease: Exacerbation versus stable condition.

PubMed

Kokturk, Nurdan; Bozdayi, Gulendam; Yilmaz, Senay; Doğan, Bora; Gulbahar, Ozlem; Rota, Seyyal; Tatlicioglu, Turkan

2015-08-01

Latent infection with adenovirus and respiratory syncytial virus (RSV) is associated with chronic obstructive pulmonary disease (COPD). The role of respiratory viral infections are emerging in COPD exacerbations. The present study aimed to investigate the prevalence of adenovirus and RSV serotypes A and B in individuals with acute exacerbations of COPD (COPD-AE) and stable COPD. Twenty seven patients with COPD-AE were evaluated using a prospective longitudinal study design. Induced sputum, sera and nasal smears were sampled from patients experiencing COPD-AE and those in a stable condition. Adenoplex® multiplex polymerase chain reaction (PCR) kits and Invitek RTP® DNA/RNA Virus Mini kits were used for PCR assays of adenovirus and RSV, respectively. Eighteen patients who experienced a COPD-AE were also evaluated while in a stable condition. The results showed that three sputum samples were positive for adenovirus in patients experiencing an exacerbation, while one was positive among the patients in a stable condition. RSV serotype A was detected in 17/27 (63%) patients with COPD-AE and 10/18 (55.6%) patients in a stable condition. RSV serotype B was not detected. Patients with COPD-AE, who were positive for RSV serotype A exhibited higher serum fibrinogen levels than those who were negative (438.60 ± 126.08 mg/dl compared with 287.60 ± 85.91 mg/dl; P=0.004). Eight/ten patients who were positive for RSV serotype A while in a stable condition, were also positive during COPD-AE. The results of the present study suggested that RSV infection may be prevalent in patients with COPD-AE and in those in a stable condition. Therefore, chronic RSV infection may occur in COPD. The detection and prevention of RSV may be useful in the management of COPD.

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

Aerosolized recombinant human DNase I for the treatment of cystic fibrosis.

PubMed

Shak, S

1995-02-01

Respiratory symptoms, recurrent infectious exacerbations, and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. Purulent secretions contain high concentrations of extracellular DNA, a viscous material released by leukocytes. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase or Pulmozyme), the human enzyme was cloned, sequenced, and expressed. In in vitro studies, rhDNase has been shown to reduce the viscoelasticity, reduce the adhesiveness, and improve the mucociliary transportability of cystic fibrosis sputum. In short-term phase 1 and phase 2 clinical trials, rhDNase has been shown to be safely tolerated and to improve the FEV1, FVC, and symptoms of dyspnea. A long-term placebo-controlled phase 3 study was performed in 968 adults and children (> or = 5 years) with cystic fibrosis to determine the effect of rhDNase on the risk of respiratory exacerbations requiring parenteral antibiotics and on the FEV1. Compared with placebo-treated patients, patients treated with rhDNase once daily or twice daily experienced a reduced risk of respiratory exacerbations by 28% (p = 0.04) and 37% (p = 0.01), respectively, and had a mean improvement in FEV1 of 5.8% (p < 0.01) and 5.6% (p < 0.01), respectively. Compared with placebo-treated patients, patients treated with rhDNase spent 2.7 fewer days receiving parenteral antibiotics (p = 0.04) and spent 1.3 fewer days in the hospital (p = 0.06) over the 6-month treatment period. Inhalation of rhDNase did not cause anaphylaxis but was associated with upper airway symptoms (ie, voice alteration, hoarseness, pharyngitis) that were generally mild and transient. In conclusion, aerosol administration of rhDNase was safely tolerated, reduced the risk of infectious exacerbations requiring parenteral antibiotics, and improved pulmonary function and patient well-being.

Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation.

PubMed

Soler, N; Torres, A; Ewig, S; Gonzalez, J; Celis, R; El-Ebiary, M; Hernandez, C; Rodriguez-Roisin, R

1998-05-01

We carried out a comprehensive microbiological study of the upper and lower airways in patients with severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation in order to describe microbial patterns and analyze their clinical significance. Quantitative cultures of tracheobronchial aspirates (TBAs), bronchoscopically retrieved protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) at admission to the ICU and after 72 h, as well as serology for bacteria and respiratory viruses were performed. Fifty patients (mean age 68 +/- 8, 46 males) were studied prospectively. Potentially pathogenic microorganisms (PPMs) and/or a positive serology were present in 36 of 50 (72%) patients, including 12 (33%) polymicrobial cases. Only six (12%) had no pathogen in any sample in the absence of antimicrobial pretreatment. Microbial patterns corresponded to community-acquired pathogens (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) in 19 of 34 (56%) and to gram-negative enteric bacilli (GNEB), Pseudomonas, and Stenotrophomonas spp. in 15 of 34 (44%) of isolates. Chlamydia pneumoniae and respiratory viruses were found in 18% and 16% of investigations, respectively. Repeated investigation after 72 h in 19 patients with PPMs in the initial investigation revealed eradication of virtually all isolates of community-acquired pathogens and GNEB but persistence of three of five Pseudomonas spp. and both Stenotrophomonas spp. as well as the emergence of new GNEB, Pseudomonas and Stenotrophomonas spp. Clinical parameters neither predicted the presence of PPMs nor of GNEB and Pseudomonas/Stenotrophomonas spp. Nevertheless, severe pneumonia attributable to initially isolated pathogens occurred in two patients with severe COPD exacerbation. We conclude that pathogens were more frequently present than previously reported. The rate of GNEB and Pseudomonas/Stenotrophomonas spp. isolates was high. The presence of pathogens was clinically unpredictable. Thus, in this population of patients with severe exacerbations of COPD, it may be advisable to obtain respiratory samples and to treat according to diagnostic results. Further studies are warranted to clarify this issue.

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD)

PubMed Central

Gadre, Shruti K.; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-01-01

Abstract There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation. A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure. We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2–7); the median duration for ICU length of stay (LOS) was 5 (IQR 2–9) days and the median duration of hospital LOS was 12 (IQR 7–22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute exacerbation of severe COPD were lower than those with other etiologies of acute respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated with a 45% decrease in ICU survival (P < .001). A discharge home at the time of index admission was associated an increased overall survival compared with any other discharge location (P < .001). We report good early outcomes, but significant long-term morbidity in patients with severe COPD requiring invasive mechanical ventilation for acute respiratory failure. A higher APACHE score and presence of active malignancy are associated with a decrease in ICU survival, whereas a discharge home is associated with an increase in the overall survival. PMID:29703009

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD).

PubMed

Gadre, Shruti K; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-04-01

There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P < .001), and the hospital mortality (17% vs 32%; P = .004) for mechanically ventilated patients with an acute exacerbation of severe COPD were lower than those with other etiologies of acute respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated with a 45% decrease in ICU survival (P < .001). A discharge home at the time of index admission was associated an increased overall survival compared with any other discharge location (P < .001).We report good early outcomes, but significant long-term morbidity in patients with severe COPD requiring invasive mechanical ventilation for acute respiratory failure. A higher APACHE score and presence of active malignancy are associated with a decrease in ICU survival, whereas a discharge home is associated with an increase in the overall survival.

Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations

PubMed Central

Lambert, Christophe; Clarke, Stuart C; Kim, Viktoriya L; Magid-Slav, Michal; Miller, Bruce E; Patel, Ruchi; Sathe, Ganesh; Simola, Daniel F; Sung, Ruby; Tal-Singer, Ruth; Tuck, Andrew C; Van Horn, Stephanie; Weynants, Vincent; Williams, Nicholas P; Devaster, Jeanne-Marie; Wilkinson, Tom M A

2018-01-01

Background Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD. Objective To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes. Methods We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes. Results The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies. Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated. We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis. Conclusions Subtypes of COPD have distinct bacterial compositions and stabilities over time. Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future. This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient. Trial registration number Results, NCT01360398. PMID:29386298

A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure

PubMed Central

Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun

2016-01-01

Background COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. Objective We evaluated pressure-regulated volume control (PRVC) ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Patients and methods Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation – volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2–4 hours and 48 hours. Results Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2), and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2) levels. The pH and PaCO2 levels at 2–4 hours were lower and higher, respectively, in the test group than those in the control group (P<0.05 for both); after 48 hours, blood gas analyses showed no statistical difference in any marker (P>0.05). Vital signs during 2–4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05). The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2–4 hours and 48 hours was significantly lower than that in the control group (P<0.05), while other variables were not significantly different between groups (P>0.05). Conclusion Among elderly COPD patients with respiratory failure, application of PRVC resulted in rapid improvement in arterial blood gas analyses while maintaining a low peak inspiratory pressure. PRVC can reduce pulmonary barotrauma risk, making it a safer protective ventilation mode than synchronized intermittent mandatory ventilation – volume control. PMID:27274223

A comparison of synchronized intermittent mandatory ventilation and pressure-regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure.

PubMed

Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun

2016-01-01

COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. We evaluated pressure-regulated volume control (PRVC) ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation - volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2-4 hours and 48 hours. Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2), and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2) levels. The pH and PaCO2 levels at 2-4 hours were lower and higher, respectively, in the test group than those in the control group (P<0.05 for both); after 48 hours, blood gas analyses showed no statistical difference in any marker (P>0.05). Vital signs during 2-4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05). The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2-4 hours and 48 hours was significantly lower than that in the control group (P<0.05), while other variables were not significantly different between groups (P>0.05). Among elderly COPD patients with respiratory failure, application of PRVC resulted in rapid improvement in arterial blood gas analyses while maintaining a low peak inspiratory pressure. PRVC can reduce pulmonary barotrauma risk, making it a safer protective ventilation mode than synchronized intermittent mandatory ventilation - volume control.

Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function.

PubMed

Woodruff, Prescott G; Barr, R Graham; Bleecker, Eugene; Christenson, Stephanie A; Couper, David; Curtis, Jeffrey L; Gouskova, Natalia A; Hansel, Nadia N; Hoffman, Eric A; Kanner, Richard E; Kleerup, Eric; Lazarus, Stephen C; Martinez, Fernando J; Paine, Robert; Rennard, Stephen; Tashkin, Donald P; Han, MeiLan K

2016-05-12

Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms. We conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score, <10) and whether those with symptoms had different findings from the asymptomatic group with respect to the 6-minute walk distance, lung function, or high-resolution computed tomographic (HRCT) scan of the chest. Respiratory symptoms were present in 50% of current or former smokers with preserved pulmonary function. The mean (±SD) rate of respiratory exacerbations among symptomatic current or former smokers was significantly higher than the rates among asymptomatic current or former smokers and among controls who never smoked (0.27±0.67 vs. 0.08±0.31 and 0.03±0.21 events, respectively, per year; P<0.001 for both comparisons). Symptomatic current or former smokers, regardless of history of asthma, also had greater limitation of activity, slightly lower FEV1, FVC, and inspiratory capacity, and greater airway-wall thickening without emphysema according to HRCT than did asymptomatic current or former smokers. Among symptomatic current or former smokers, 42% used bronchodilators and 23% used inhaled glucocorticoids. Although they do not meet the current criteria for COPD, symptomatic current or former smokers with preserved pulmonary function have exacerbations, activity limitation, and evidence of airway disease. They currently use a range of respiratory medications without any evidence base. (Funded by the National Heart, Lung, and Blood Institute and the Foundation for the National Institutes of Health; SPIROMICS ClinicalTrials.gov number, NCT01969344.).

Respiratory and Allergic Health Effects of Dampness, Mold, and Dampness-Related Agents: A Review of the Epidemiologic Evidence

PubMed Central

Mendell, Mark J.; Mirer, Anna G.; Cheung, Kerry; Tong, My; Douwes, Jeroen

2011-01-01

Objectives Many studies have shown consistent associations between evident indoor dampness or mold and respiratory or allergic health effects, but causal links remain unclear. Findings on measured microbiologic factors have received little review. We conducted an updated, comprehensive review on these topics. Data sources We reviewed eligible peer-reviewed epidemiologic studies or quantitative meta-analyses, up to late 2009, on dampness, mold, or other microbiologic agents and respiratory or allergic effects. Data extraction We evaluated evidence for causation or association between qualitative/subjective assessments of dampness or mold (considered together) and specific health outcomes. We separately considered evidence for associations between specific quantitative measurements of microbiologic factors and each health outcome. Data synthesis Evidence from epidemiologic studies and meta-analyses showed indoor dampness or mold to be associated consistently with increased asthma development and exacerbation, current and ever diagnosis of asthma, dyspnea, wheeze, cough, respiratory infections, bronchitis, allergic rhinitis, eczema, and upper respiratory tract symptoms. Associations were found in allergic and nonallergic individuals. Evidence strongly suggested causation of asthma exacerbation in children. Suggestive evidence was available for only a few specific measured microbiologic factors and was in part equivocal, suggesting both adverse and protective associations with health. Conclusions Evident dampness or mold had consistent positive associations with multiple allergic and respiratory effects. Measured microbiologic agents in dust had limited suggestive associations, including both positive and negative associations for some agents. Thus, prevention and remediation of indoor dampness and mold are likely to reduce health risks, but current evidence does not support measuring specific indoor microbiologic factors to guide health-protective actions. PMID:21269928

Incidence, Prevalence, and Clinical Course of Idiopathic Pulmonary Fibrosis

PubMed Central

Daniels, Craig E.; Schroeder, Darrell R.; St. Sauver, Jennifer; Hartman, Thomas E.; Bartholmai, Brian J.; Yi, Eunhee S.; Ryu, Jay H.

2010-01-01

Background: Limited data exist regarding the population-based epidemiology of idiopathic pulmonary fibrosis (IPF). The objective of the study was to describe the trends in the incidence, prevalence, and clinical course of IPF in the community. Methods: We conducted a population-based study of adult patients with IPF in Olmsted County, Minnesota, from 1997 to 2005. Two methods were used to identify IPF cases, as defined by the 2002 American Thoracic Society/European Respiratory Society consensus statement: (1) usual interstitial pneumonia (UIP) on a surgical lung biopsy specimen or a definite UIP pattern on a high-resolution CT image (narrow criteria) and (2) UIP on a surgical lung biopsy specimen or a definite or possible UIP pattern on CT image (broad criteria). Results: Of 596 patients screened for the possibility of pulmonary disease or pulmonary fibrosis over 9 years of follow-up, 47 cases had IPF. Of these, 24 met the narrow criteria. The age- and sex-adjusted incidence was 8.8/100,000 and 17.4/100,000 person-years, for narrow and broad criteria, respectively. The age-adjusted incidence was higher in men than in women, and among patients aged 70-79 years. During the study period, the incidence of IPF decreased (P < .001). On December 31, 2005, the age- and sex-adjusted prevalence was 27.9/100,000 and 63/100,000 persons by narrow and broad criteria, respectively. Thirty-seven patients experienced a total of 53 respiratory exacerbations (26 IPF related, 27 non-IPF related), and 34 (72%) patients died. The primary cause of death was IPF related in 16 (47%) patients. Median survival for narrow-criteria and broad-criteria incidence cases was 3.5 and 4.4 years, respectively. Conclusions: The incidence of IPF in Olmsted County decreased over the study period. Nonprimary IPF respiratory exacerbations are as frequent as primary IPF respiratory exacerbations and an important cause of death. PMID:19749005

Association between environmental factors and hospitalisations for bronchiectasis in Badalona, Barcelona, Spain (2007-2015).

PubMed

Garcia-Olivé, Ignasi; Radua, Joaquim; Sánchez-Berenguer, Dan; Hernández-Biette, Agnes; Raya-Márquez, Patricia; Stojanovic, Zoran; Martínez-Rivera, Carlos; Fernandez Serrano, Silvia; Ruiz Manzano, Juan

2018-04-13

The relationship between environmental factors and the exacerbation of respiratory diseases has been widely studied. However, there are no studies examining the relationship between these factors and bronchiectasis exacerbations. Our objective was to analyse the association between various environmental factors and hospitalisation for bronchiectasis. This was a retrospective observational study conducted at two hospitals in Badalona (Barcelona). The number of hospital admissions for exacerbation of bronchiectasis between 2007 and 2015 was obtained. Through multiple regression we analysed the relationship between the number of exacerbations and mean monthly values of temperature, SO 2 , NO, NO 2 , O 3 and CO. Temperature, SO 2 , NO, NO 2 , O 3 and CO were significantly associated with an increase in admissions due to exacerbation of bronchiectasis. By controlling the effect of temperature on the pollution variables, only SO 2 maintained statistical significance (P=.008). We have detected an increase in hospital admissions for exacerbation of bronchiectasis with increases in the atmospheric concentration of SO 2 and the decrease in temperature. Prospective studies with different geographical locations to confirm these results are needed. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

PubMed

Brill, Simon E; Patel, Anant R C; Singh, Richa; Mackay, Alexander J; Brown, Jeremy S; Hurst, John R

2015-02-07

Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described. This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values. At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset. Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.

Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats.

EPA Science Inventory

Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We...

Respiratory Effects and Systemic Stress Response Following Acute Acrolein Inhalation in Rats

EPA Science Inventory

Previous studies have demonstrated that exposure to ozone, a pulmonary irritant, causes myriad systemic metabolic and pulmonary effects that are attributed to neuronal and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically-impaired models...

AGE AND STRAIN INFLUENCES ON LUNG RESPONSES TO CONCENTRATED AIR PARTICULATES (CAPS) IN RODENTS

EPA Science Inventory

Asthma, an inflammatory airways disease, is an urgent health problem. Recent epidemiologic studies have demonstrated positive associations between ambient air particulate matter concentrations and daily respiratory morbidity ? including exacerbations of asthma. Of note, elderly i...

AB033. Assessing the appropriateness of pharmacological prescriptions for COPD to clinical guidelines: EPOCONSUL study

PubMed Central

Alcázar, Bernardino; Calle, Myrian; Soler, Juan José; López-Campos, José Luis; Rodriguez, José-Maria; Soriano, Joan

2016-01-01

Background Adherence to clinical practice guidelines is far from optimal for most of the chronic diseases. Spain has implemented a phenotype based chronic obstructive pulmonary disease (COPD) guideline and there is scarce data about the follow-up of this guideline. The aim of this study is to evaluate the suitability of the pharmacological treatment for COPD to the Spanish Guidelines (GesEPOC) recommendations in patients with COPD recruited at respiratory clinics around Spain. Methods EPOCONSUL study is a observational, multicentre, cross-sectional study aimed to audit clinical histories from stable COPD patients attended at respiratory offices. Patients were recruited prospectively from 62 centres around Spain along June 2014 to June 2015. Results The EPOCONSUL study audited 4,501 medical histories from patients with COPD. Characteristics of study population showed 86.0% males, with a mean age (± SD) of 69.77±9.79 years. In 76.9% of the cases patients were attended at general respiratory offices. Baseline FEV1 values were 52.3%±18.4% of predicted. A COPD diagnosis using GesEPOC guidelines was performed in 2,087 patients (46.3%). The most preferred treatment option was the association of ICS/LABA in fixed-dose combination and LAMA, that was used in 2,450 patients of the whole sample. Among patients with a diagnosis of COPD according to GesEPOC guidelines, the preferred form of treatment was: non-exacerbators (LAMA/LABA 37.8%, LAMA/LABA/ICS 36.6%, LAMA 15.9% and LABA/ICS 4.9%), Asthma-COPD overlap syndrome (LAMA/LABA/ICS 61.9%, LABA/ICS 21.9%, LAMA/LABA 10.3% and LAMA 2.9%), frequent exacerbator with emphysema (LAMA/LABA/ICS 69.2%, LAMA/LABA 18.3%, LABA/ICS 6.4%, and LAMA 3.2%) and finally frequent exacerbator with chronic bronchitis (LAMA/LABA/ICS 77.0%, LAMA/LABA 14.0%, LABA/ICS 5.9% and LAMA 1.1%). Conclusions According to EPOCONSUL study data, the most used pharmacological option for COPD in Spain is triple therapy, which is prescribed in more than half of the patients. There are many appropriate prescriptions in patients with frequent exacerbations but not so in patients without frequent exacerbations.

Murine respiratory mycoplasmosis (MRM) in C57BL/6N and C3H/HeN mice: strain differences in early host responses and exacerbation by nitrogen dioxide

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

Parker, R.F.

1987-01-01

The studies reported here used genetic differences in susceptibility of C57BL/6N and C3H/HeN mice and exacerbation of the disease by nitrogen dioxide (NO/sub 2/) as tools in assessing the role of early host responses in the pathogenesis of MRM. The two strains did not differ in susceptibility to infection, but C3H/HeN mice were more susceptible to and had increased severity of lung lesions 14 days after intranasal inoculation as determined by 50% biological endpoints and morphometric analysis of tissues. Exposure to NO/sub 2/ for 4 hours prior to exposure to infectious aerosols exacerbated murine respiratory mycoplasmosis (MRM) by 7 daysmore » after exposure in both mouse strains. NO/sub 2/ appeared to affect host lung defense mechanisms responsible for limiting mycoplasmal growth in the lungs. The NO/sub 2/ exposure concentration required for this effect varied with the genetic background of the host, the dose of mycoplasmas administered, and the endpoint measured. Pulmonary clearance of radiolabeled M. pulmonis was determined in both mouse strains, and in C57BL/6N mice exposed to NO/sub 2/.« less

Acute spinal cord compression: a rare complication of dual antiplatelet therapy.

PubMed

Iskandar, Muhammad Zaid; Chong, Victor; Hutcheon, Stuart

2015-07-22

A 73-year-old woman presented with acute shortness of breath and exacerbation of chronic back pain. She was diagnosed with pulmonary oedema and a non-ST-elevation myocardial infarction following chest X-ray, ECG and high sensitivity troponin levels. She subsequently underwent coronary angioplasty with deployment of drug-eluting stents to her circumflex and left anterior descending arteries and was started on aspirin and clopidogrel for her dual antiplatelet therapy. Unfortunately, following the procedure, she gradually lost power and sensation in both lower limbs. MRI of her spine confirmed an extradural haematoma causing thoracic cord compression. She was managed conservatively following discussions with neurosurgeons and developed further complications secondary to her immobility. 2015 BMJ Publishing Group Ltd.

The diagnosis and management of respiratory viral infections in cystic fibrosis.

PubMed

Flight, William; Jones, Andrew

2017-03-01

Respiratory viruses, such as those that cause influenza and the common cold, are a regular feature of life for the entire human population. Among people with CF, these viruses are associated with prolonged respiratory illness and show a clear association with pulmonary exacerbations which in turn are associated with lung function decline and risk of death. Human rhinovirus is the most commonly encountered respiratory viral pathogen in CF although adenovirus, bocavirus, coronavirus, influenza, parainfluenza, metapneumovirus and respiratory syncytial virus are all also responsible for infections in this population. Areas covered: This article reviews the epidemiology, clinical impact and therapeutic options for respiratory virus infection in both children and adults with CF. Expert commentary: The management of CF to date has largely focused on airway clearance strategies, nutritional support and aggressive antibacterial therapy. We highlight the significant role that respiratory viruses play in CF lung disease and argue that these pathogens represent an under-exploited target in the battle to control patients' symptoms and disease progression.

Occurrence of virus-induced COPD exacerbations during four seasons.

PubMed

Djamin, Remco S; Uzun, Sevim; Snelders, Eveline; Kluytmans, Jan J W; Hoogsteden, Henk C; Aerts, Joachim G J V; Van Der Eerden, Menno M

2015-02-01

In this study, we investigated the occurrence of viral infections in acute exacerbations of chronic obstructive pulmonary disease (COPD) during four seasons. Viral infections were detected by the use of real-time reverse transcriptase polymerase chain reaction on pharyngeal swabs. During a 12-month period pharyngeal swabs were obtained in 136 exacerbations of 63 patients. In 35 exacerbations (25.7%) a viral infection was detected. Most viral infections occurred in the winter (n = 14, 40.0%), followed by summer (n = 9, 25.7%), autumn (n = 6, 17.1%), and spring (n = 6, 17.1%). Rhinovirus was the most frequently isolated virus (n = 19, 51.4%), followed by respiratory syncytial virus (n = 6, 16.2%), human metapneumovirus (n = 5, 13.5%), influenza A (n = 4, 10.8%), parainfluenza 4 (n = 2, 5.4%), and parainfluenza 3 (n = 1, 2.7%). This study showed that virus-induced COPD exacerbations occur in all four seasons with a peak in the winter months. However, the distribution of rhinovirus infections showed a different pattern, with most infections occurring in July.

Lyophilized aspirin with trehalose may decrease the incidence of gastric injuries in healthy dogs.

PubMed

Lin, Lee-Shuan; Kayasuga, Yuko; Shimohata, Nobuyuki; Kamata, Hiroyuki; Suzuki, Shigeki; Echigo, Ryosuke; Mochizuki, Manabu; Chung, Ung-Il; Sasaki, Nobuo

2012-11-01

Trehalose has several novel anti-inflammatory and cell-protective functions. We hypothesized that lyophilized aspirin/trehalose could decrease the severity of aspirin-induced gastropathy. Thirteen dogs were assigned into aspirin, lyophilized aspirin/trehalose, and control groups, and the gastric lesions were assessed on gastroscopy with the modified Lanza scale. Another 6 dogs were used to measure the plasma aspirin concentration by high-performance liquid chromatography after aspirin or lyophilized aspirin/trehalose administration. The results indicated that lyophilized aspirin/trehalose induced less gastric ulceration than aspirin despite maintaining therapeutic concentrations of plasma aspirin in both the groups. Lyophilized aspirin/trehalose might be a solution to decrease aspirin-induced gastropathy.

Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations.

PubMed

Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Lin, Zhi-Ya; Tang, Yan; Li, Hui-Min; Lin, Zhi-Min; Jiang, Mei; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

2015-08-01

Bronchiectasis exacerbations are critical events characterized by worsened symptoms and signs (ie, cough frequency, sputum volume, malaise). Our goal was to examine variations in airway and systemic inflammation, spirometry, and quality of life during steady state, bronchiectasis exacerbations, and convalescence (1 week following a 2-week antibiotic treatment) to determine whether potentially pathogenic microorganisms, including Pseudomonas aeruginosa, were associated with poorer conditions during bronchiectasis exacerbations. Peripheral blood and sputum were sampled to detect inflammatory mediators and bacterial densities. Spirometry and quality of life (St George Respiratory Questionnaire [SGRQ]) were assessed during the 3 stages. Forty-eight subjects with bronchiectasis (43.2 ± 14.2 y of age) were analyzed. No notable differences in species and density of potentially pathogenic microorganisms were found during bronchiectasis exacerbations. Except for CXCL8 and tumor necrosis factor alpha (TNF-α), serum inflammation was heightened during bronchiectasis exacerbations and recovered during convalescence. Even though sputum TNF-α was markedly higher during bronchiectasis exacerbations and remained heightened during convalescence, the variations in miscellaneous sputum markers were unremarkable. Bronchiectasis exacerbations were associated with notably higher SGRQ symptom and total scores, which recovered during convalescence. FVC, FEV1, and maximum mid-expiratory flow worsened during bronchiectasis exacerbations (median change from baseline of -2.2%, -0.8%, and -1.3%) and recovered during convalescence (median change from baseline of 0.6%, 0.7%, and -0.7%). Compared with no bacterial isolation, potentially pathogenic microorganism or P. aeruginosa isolation at baseline did not result in poorer clinical condition during bronchiectasis exacerbations. Bronchiectasis exacerbations are characterized by heightened inflammatory responses and poorer quality of life and spirometry, but not by increased bacterial density, which applies for subjects with and without potentially pathogenic microorganism isolation when clinically stable. (ClinicalTrials.gov registration NCT01761214.). Copyright © 2015 by Daedalus Enterprises.

Acute respiratory and cardiovascular admissions after a public smoking ban in Geneva, Switzerland.

PubMed

Humair, Jean-Paul; Garin, Nicolas; Gerstel, Eric; Carballo, Sebastian; Carballo, David; Keller, Pierre-Frédéric; Guessous, Idris

2014-01-01

Many countries have introduced legislations for public smoking bans to reduce the harmful effects of exposure to tobacco smoke. Smoking bans cause significant reductions in admissions for acute coronary syndromes but their impact on respiratory diseases is unclear. In Geneva, Switzerland, two popular votes led to a stepwise implementation of a state smoking ban in public places, with a temporary suspension. This study evaluated the effect of this smoking ban on hospitalisations for acute respiratory and cardiovascular diseases. This before and after intervention study was conducted at the University Hospitals of Geneva, Switzerland, across 4 periods with different smoking legislations. It included 5,345 patients with a first hospitalisation for acute coronary syndrome, ischemic stroke, acute exacerbation of chronic obstructive pulmonary disease, pneumonia and acute asthma. The main outcomes were the incidence rate ratios (IRR) of admissions for each diagnosis after the final ban compared to the pre-ban period and adjusted for age, gender, season, influenza epidemic and secular trend. Hospitalisations for acute exacerbation of chronic obstructive pulmonary disease significantly decreased over the 4 periods and were lowest after the final ban (IRR=0.54 [95%CI: 0.42-0.68]). We observed a trend in reduced admissions for acute coronary syndromes (IRR=0.90 [95%CI: 0.80-1.00]). Admissions for ischemic stroke, asthma and pneumonia did not significantly change. A legislative smoking ban was followed by a strong decrease in hospitalisations for acute exacerbation of chronic obstructive pulmonary disease and a trend for reduced admissions for acute coronary syndrome. Smoking bans are likely to be very beneficial for patients with chronic obstructive pulmonary disease.

Acute Respiratory and Cardiovascular Admissions after a Public Smoking Ban in Geneva, Switzerland

PubMed Central

Humair, Jean-Paul; Garin, Nicolas; Gerstel, Eric; Carballo, Sebastian; Carballo, David; Keller, Pierre-Frédéric; Guessous, Idris

2014-01-01

Background Many countries have introduced legislations for public smoking bans to reduce the harmful effects of exposure to tobacco smoke. Smoking bans cause significant reductions in admissions for acute coronary syndromes but their impact on respiratory diseases is unclear. In Geneva, Switzerland, two popular votes led to a stepwise implementation of a state smoking ban in public places, with a temporary suspension. This study evaluated the effect of this smoking ban on hospitalisations for acute respiratory and cardiovascular diseases. Methods This before and after intervention study was conducted at the University Hospitals of Geneva, Switzerland, across 4 periods with different smoking legislations. It included 5,345 patients with a first hospitalisation for acute coronary syndrome, ischemic stroke, acute exacerbation of chronic obstructive pulmonary disease, pneumonia and acute asthma. The main outcomes were the incidence rate ratios (IRR) of admissions for each diagnosis after the final ban compared to the pre-ban period and adjusted for age, gender, season, influenza epidemic and secular trend. Results Hospitalisations for acute exacerbation of chronic obstructive pulmonary disease significantly decreased over the 4 periods and were lowest after the final ban (IRR = 0.54 [95%CI: 0.42–0.68]). We observed a trend in reduced admissions for acute coronary syndromes (IRR = 0.90 [95%CI: 0.80–1.00]). Admissions for ischemic stroke, asthma and pneumonia did not significantly change. Conclusions A legislative smoking ban was followed by a strong decrease in hospitalisations for acute exacerbation of chronic obstructive pulmonary disease and a trend for reduced admissions for acute coronary syndrome. Smoking bans are likely to be very beneficial for patients with chronic obstructive pulmonary disease. PMID:24599156

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts

PubMed Central

McDonnell, M J; Aliberti, S; Goeminne, P C; Dimakou, K; Zucchetti, S C; Davidson, J; Ward, C; Laffey, J G; Finch, S; Pesci, A; Dupont, L J; Fardon, T C; Skrbic, D; Obradovic, D; Cowman, S; Loebinger, M R; Rutherford, R M; De Soyza, A; Chalmers, J D

2016-01-01

Introduction Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. Methods We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. Results The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in ‘severe’ patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. Conclusion The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity. PMID:27516225

Effects of long-term azithromycin therapy on airway oxidative stress markers in non-cystic fibrosis bronchiectasis.

PubMed

Diego, Afredo De; Milara, Javier; Martinez-Moragón, Eva; Palop, Marta; León, Montse; Cortijo, Julio

2013-10-01

To explore the effect of long-term therapy with azithromycin in regards to airway oxidative stress markers in exhaled breath condensate (EBC) of adult patients with stable non-cystic fibrosis (CF) bronchiectasis. Open-label prospective study of 30 patients randomized to azithromycin 250 mg three times per week during 3 months (16 patients) or control (14 patients). Primary outcome were changes in nitric oxide, 8-isoprostane, pH, nitrites and nitrates in EBC. Secondary outcomes were changes in exacerbation rates, dyspnoea (Borg scale), sputum volume (cc), sputum colour (15-point scale), bacterial infection, health-related quality of life (St George's Respiratory Questionnaire), lung function and radiological extension. Azithromycin produced a significant decrease in sputum volume (8.9 (1.8) mL vs 2.1 (3.4) mL) and number of exacerbations (0.1 (0.6) vs 1.2 (0.9)). Dyspnoea (0.4 (0.1) vs 0.1 (0.2)) and health-related quality of life also improved after therapy. However, oxidative stress markers in EBC, systemic inflammatory markers as well as functional respiratory tests did not differ from the control group after therapy. A post-hoc analysis comparing patients infected or not with Pseudomonas aeruginosa revealed that these effects were more pronounced in infected patients. In this subgroup, treatment was followed by a significant reduction in sputum volume, number of exacerbations, dyspnoea and St George's Respiratory Questionnaire total score. Of all airway oxidative stress markers, only nitrates in EBC were reduced after therapy. Long-term azythromicin treatment has some clinical benefits in patients with non-CF stable bronchiectasis, but it does not affect airway oxidative stress markers. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

[Chronic Rhinosinusitis - EPOS 2012 Part I].

PubMed

Riechelmann, H

2013-03-01

An expert group of the European Academy of Allergy and Clinical Immunology (EAACI) and the European Rhinologic Society (ERS) has recently published the revised position paper for acute and chronic rhinosinusitis (EPOS 2012). In the following article, the most important aspects of the EPOS 2012 paper concerning chronic rhinosinusitis (CRS) are referenced. Every 10th European is suffering from a chronic inflammation of the nose and paranasal sinuses.2 EPOS key messages according CRS are: 1. CRS is an inflammatory disease, not an infection. 2. CRS comes in 2 different subtypes, namely CRS without polyps (CRSsNP) and CRS with polyps (CRSwNP). CRSwNP is diagnosed, when nasal polyps are visible at an appropriate nasal endoscopic examination. Otherwise CRSsNP is classified. In the EPOS 2012 paper the current pathogenetic knowledge of these 2 different CRS subtypes are discussed. Current research focuses on epithelial/immune cell interactions, the biofilm hypothesis and the superantigen hypothesis. Both CRS subtypes may be associated with different frequencies with other diseases, especially allergies, asthma and aspirin exacerbated respiratory disease (AERD). These comorbidities should be recorded and treated. The standard diagnostic procedures include medical history, nasal endoscopy, CT-scans of the paranasal sinus, and allergy test of common inhalant allergens. The classification of disease severity in mild, moderate and severe was complemented with a concept of symptom control in controlled, partly controlled and uncontrolled. Also, a 'difficult-to-treat-CRS' was defined. The choice of therapy depends upon symptom intensity. In patients with moderate and severe symptoms, usually several weeks of conservative treatment including topical steroids are administered. In non-responders, surgical treatment (functional endonasal sinus surgery) is indicated. The EPOS Group offers evidence-based treatment algorithms for general practitioners and ENT-specialists. © Georg Thieme Verlag KG Stuttgart · New York.

[Impacts of airborne particulate matter and its components on respiratory system health].

PubMed

Cao, L M; Zhou, Y; Zhang, Z; Sun, W W; Mu, G; Chen, W H

2016-12-06

Nowadays, particulate air pollution has been a global environmental problem. Numerous studies has shown that long-term exposure to high level of airborne particulate matter (PM) can damage human health. Respiratory system, as a direct portal to contact with particulate matter, can be more susceptible to airborne particulates. Summarizing latest five-year epidemiological research, the present review is focused on the effects of PM on respiratory system health in different age groups. In detail, we investigated the harmful effect of PM, or its components on three common respiratory diseases, including lung function decline, chronic obstructive pulmonary disease (COPD) and asthma. The result showed that, to a certain degree, PM could induce the decline of lung function, the development and the exacerbation of COPD and asthma by oxidative stress and inflammatory reaction. And it may prompt that exposure to PM can be an improtant risk factor for the respiratory system health.

The effects of ambient particulate matter on human alveolar machrophage oxidative and inflammatory responses

EPA Science Inventory

Epidemiologic and occupational studies demonstrate that ambient PM and DEP have deleterious effects on human cardiopulmonary health including exacerbation of pre-existing lung disease and development of respiratory infections. The effects of ambient PM on lung cell responsivenes...

Floor Health

ERIC Educational Resources Information Center

High, Jacalyn

2010-01-01

Poor indoor air quality (IAQ) in schools and universities contributes to absenteeism and reduced performance. The American Lung Association estimates that U.S. students miss more than 14 million school days a year because of asthma, allergies and other respiratory problems exacerbated by poor IAQ. Fortunately, maintenance departments in education…

Indoor Air Quality and Asthma

PubMed Central

Holm, Stewart

2017-01-01

Numerous contaminants in indoor air and their potential to cause or exacerbate asthma continue to be a subject of public health concern. Many agents are causally associated with or can exacerbate asthma, particularly in children. For formaldehyde, an established respiratory irritant based on numerous studies, the evidence for an association with asthma is still considered only limited or suggestive. However, there is no evidence that indicates increased sensitivity to sensory irritation to formaldehyde in people often regarded as susceptible such as asthmatics. Acrolein, but not formaldehyde, was significantly associated with asthma in a large cohort of children. This prompted an evaluation of this highly irritating chemical that had never previously been considered in the context of the indoor air/childhood asthma issue. Because acrolein is more potent than formaldehyde as a respiratory irritant and ubiquitous in indoor air, it is plausible that previous studies on potential risk factors and childhood asthma may be confounded by formaldehyde acting as an unrecognized proxy for acrolein. PMID:28250718

Enteroviruses as major cause of microbiologically unexplained acute respiratory tract infections in hospitalized pediatric patients.

PubMed

Renois, Fanny; Lévêque, Nicolas; Deliège, Pierre-Guillaume; Fichel, Caroline; Bouin, Alexis; Abely, Michel; N'guyen, Yohan; Andréoletti, Laurent

2013-06-01

To assess the etiological role and the clinical characteristics of HRV and HEV infections in pediatric patients hospitalized for acute respiratory tract infections (ARTIs). RT-qPCR assays and molecular sequencing methods were used to identify HRV and HEV strains in nasopharyngeal aspirates of 309 hospitalized pediatric patients with microbiologically unexplained ARTIs and in 210 hospitalized pediatric patients without respiratory symptoms from September 2009 to June 2010 in France. Among the 309 ARTI cases, 15 HEV and 172 HRV strains were identified whereas only 1 HEV and 37 HRV strains were observed in control patients (187 vs. 38: P < 10(-3)). HRV strains were identified in 150 of the 164 lower ARTIs whereas HEV strains were identified in only 14 of these cases. Among bronchiolitis and asthma exacerbation cases (n = 133), HEV infected cases were older (Median age (months) 36 vs. 11, P = 0.003) and were more frequently associated with a respiratory distress (P = 0.01) and a need for oxygen supply at the time of admission (P = 0.01) than cases infected by HRV strains. HRV and HEV strains were identified as potential etiological causes of 60.5% of microbiologically unexplained ARTIs diagnosed in hospitalized pediatric cases. A higher clinical severity was observed in HEV infected bronchiolitis or asthma exacerbation cases in comparison to HRV infected cases. Copyright © 2013 The British Infection Association. Published by 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

Validation of a Quality of Life Questionnaire for Bronchiectasis: psychometric analyses of the Spanish QOL-B-V3.0.

PubMed

Olveira, Casilda; Olveira, Gabriel; Espildora, Francisco; Giron, Rosa-Maria; Muñoz, Gerard; Quittner, Alexandra L; Martinez-Garcia, Miguel-Angel

2014-05-01

Bronchiectasis is a chronic disease, leading to worsening of health-related quality of life. This study evaluated the psychometric properties of a new patient-reported outcome for non-cystic fibrosis bronchiectasis, the Quality of Life Questionnaire Bronchiectasis, translated into Spanish (QOL-B-Sp-V3.0). This prospective study recruited clinically stable patients with non-cystic fibrosis bronchiectasis at 4 Spanish centers. Health status was assessed with multiple indicators (dyspnea, exacerbations, bronchorrhea, etc.), microbiological, radiological, spirometric, and anthropometric parameters plus St-George Respiratory Questionnaire (SGRQ). Psychometric analyses included internal consistency, test-retest reliability, convergent validity, predictive validity, and responsivity to change. The 207 stable patients (mean age 57.2 years) had a Bhalla score of 11.53 ± 7.39 and FEV1% of 68.3 ± 22.2 %. One hundred and sixty-one stable patients repeated the test 2 weeks later, and 80 patients who had an exacerbation within 6 months of the assessment also repeated it. Internal consistency was high across all scales (Cronbach's alpha >0.70). Thirty-six of 37 items correlated more strongly with their assigned scale than a competing scale. Test-retest coefficients were strong (intraclass correlations r = 0.68-0.88). All scales, except Treatment Burden, discriminated significantly between patients with mild, moderate, and severe disease according to FEV1% and other respiratory parameters. Strong convergence was found between the QOL-B-Sp-V3.0 and SGRQ. Significant correlations were found between QOL-B-Sp-V3.0 and various clinical, spirometric, radiological, and anthropometric variables. Significant differences were found on all QOL-B-Sp-V3.0 scales, except emotional functioning, between the baseline responses and onset of an exacerbation; robust sensitivity to change was observed on the Respiratory Symptoms scale. The QOL-B-Sp-V3.0 questionnaire demonstrated strong reliability and validity. Scores were reproducible after 2 weeks, and it discriminated between patients who varied in severity and was responsive to changes related to exacerbation.

When should acute exacerbations of COPD be treated with systemic corticosteroids and antibiotics in primary care: a systematic review of current COPD guidelines.

PubMed

Laue, Johanna; Reierth, Eirik; Melbye, Hasse

2015-02-19

Not all patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) benefit from treatment with systemic corticosteroids and antibiotics. The aim of the study was to identify criteria recommended in current COPD guidelines for treating acute exacerbations with systemic corticosteroids and antibiotics and to assess the underlying evidence. Current COPD guidelines were identified by a systematic literature search. The most recent guidelines as per country/organisation containing recommendations about treating acute exacerbations of COPD were included. Guideline development and criteria for treating acute exacerbations with systemic corticosteroids and antibiotics were appraised. Randomised controlled trials directly referred to in context with the recommendations were evaluated in terms of study design, setting, and study population. A total of 19 COPD guidelines were included. Systemic corticosteroids were often universally recommended to all patients with acute exacerbations. Criteria for treatment with antibiotics were mainly an increase in respiratory symptoms. Objective diagnostic tests or clinical examination were only rarely recommended. Only few criteria were directly linked to underlying evidence, and the trial patients represented a highly specific group of COPD patients. Current COPD guidelines are of little help in primary care to identify patients with acute exacerbations probably benefitting from treatment with systemic corticosteroids and antibiotics in primary care, and might contribute to overuse or inappropriate use of either treatment.

A smartphone application for reporting symptoms in adults with cystic fibrosis: protocol of a randomised controlled trial.

PubMed

Wood, Jamie; Jenkins, Sue; Putrino, David; Mulrennan, Siobhain; Morey, Sue; Cecins, Nola; Hill, Kylie

2018-04-21

In people with cystic fibrosis (CF), exacerbations have been shown to have profound and prolonged negative effects such as reducing physical activity and health-related quality of life, increasing the rate of decline of lung function and healthcare costs, and ultimately increasing the risk of mortality. Delayed initiation of treatment following the signs of an exacerbation has been shown to be associated with failure to recover to baseline. Therefore, the late identification and treatment of an exacerbation due to delayed presentation will potentially worsen short-term and long-term outcomes. We have developed a smartphone application, containing questions which require yes or no responses relating to symptoms suggestive of a respiratory exacerbation. Its use is intended to facilitate the early identification of symptoms suggestive of a respiratory exacerbation, and allow the CF team to initiate treatment sooner, thereby potentially reducing the risk of severe exacerbations which require intravenous antibiotics (IVAB) and often a hospital admission. We will undertake a randomised controlled trial. 60 adults with CF will be recruited and randomised to either the intervention or control group. The intervention group will use the smartphone application weekly for 12 months, or earlier than the next weekly reporting time if they feel their symptoms have worsened. The control group will continue to receive usual care, involving regular (approximately 3 monthly) CF outpatient clinic appointments. The primary outcome measure will be courses and days of IVAB. Approval was obtained from the Sir Charles Gairdner Group Human Research Ethics Committee for WA Health (2015-030) and Curtin University Human Research Ethics Committee (HR212/2015), and has been registered with the Australian and New Zealand Clinical Trials Registry. Results of this study will be presented at international conferences and published in peer-reviewed journals in accordance with the Consolidated Standards of Reporting Trials statement. ACTRN12615000599572. © 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.

Day-to-day measurement of patient-reported outcomes in exacerbations of chronic obstructive pulmonary disease

PubMed Central

Kocks, Jan Willem H; van den Berg, Jan Willem K; Kerstjens, Huib AM; Uil, Steven M; Vonk, Judith M; de Jong, Ynze P; Tsiligianni, Ioanna G; van der Molen, Thys

2013-01-01

Background Exacerbations of chronic obstructive pulmonary disease (COPD) are a major burden to patients and to society. Little is known about the possible role of day-to-day patient-reported outcomes during an exacerbation. This study aims to describe the day-to-day course of patient-reported health status during exacerbations of COPD and to assess its value in predicting clinical outcomes. Methods Data from two randomized controlled COPD exacerbation trials (n = 210 and n = 45 patients) were used to describe both the feasibility of daily collection of and the day-to-day course of patient-reported outcomes during outpatient treatment or admission to hospital. In addition to clinical parameters, the BORG dyspnea score, the Clinical COPD Questionnaire (CCQ), and the St George’s Respiratory Questionnaire were used in Cox regression models to predict treatment failure, time to next exacerbation, and mortality in the hospital study. Results All patient-reported outcomes showed a distinct pattern of improvement. In the multivariate models, absence of improvement in CCQ symptom score and impaired lung function were independent predictors of treatment failure. Health status and gender predicted time to next exacerbation. Five-year mortality was predicted by age, forced expiratory flow in one second % predicted, smoking status, and CCQ score. In outpatient management of exacerbations, health status was found to be less impaired than in hospitalized patients, while the rate and pattern of recovery was remarkably similar. Conclusion Daily health status measurements were found to predict treatment failure, which could help decision-making for patients hospitalized due to an exacerbation of COPD. PMID:23766644

Responses to tiotropium in African-American and Caucasian patients with chronic obstructive pulmonary disease.

PubMed

Rice, Kathryn L; Leimer, Inge; Kesten, Steven; Niewoehner, Dennis E

2008-08-01

Sparse information exists about chronic obstructive pulmonary disease (COPD) outcomes among different ethnic groups. To determine whether the effect of tiotropium on COPD exacerbation differs between African Americans and Caucasians, we performed a post hoc analysis of African-American (n = 150) and Caucasian (n = 1670) subgroups from a previously reported 6-month trial of tiotropium in patients with moderate-to-very-severe COPD. Compared with placebo, tiotropium reduced the likelihood of having at least 1 exacerbation in the entire group (RR, 0.81; 95% CI, 0.66-0.99, P = 0.037) with no statistically significant difference between African-American and Caucasian subgroups (P = 0.34). For African Americans, tiotropium significantly reduced the number of antibiotic days for COPD, hospitalizations for exacerbations, and hospitalization days for COPD. For Caucasians, tiotropium significantly reduced the number of exacerbations, exacerbation days, unscheduled clinic visits for COPD, and hospitalizations for exacerbations. Tiotropium reduced the frequencies of antibiotic days and of COPD hospital days to a significantly greater extent in African Americans compared with Caucasians (P = 0.027 and P = 0.025, respectively). No statistically significant ethnic-related differences were observed in the effect of tiotropium on the frequencies of exacerbations, exacerbation days, systemic corticosteroid days, unscheduled clinic visits, or COPD hospitalizations. Spirometry improved to a similar extent in both subgroups for the entire duration of the 6-month trial. African Americans used fewer respiratory medications than Caucasians in this study. We conclude that tiotropium reduces COPD exacerbations and associated health-care use to a similar extent in African Americans compared with Caucasians.

The effect of transcutaneous electrical nerve stimulation in patients with acute exacerbation of chronic obstructive pulmonary disease: randomised controlled trial.

PubMed

Öncü, Emine; Zincir, Handan

2017-07-01

The aim of the present study was to assess the efficacy of transcutaneous electrical nerve stimulation in patients with acute exacerbation of chronic obstructive pulmonary disease. In patients with stable chronic obstructive pulmonary disease, transcutaneous electrical nerve stimulation has been known to attain improvement in forced expiratory volume in 1 seconds, physical activity, and quality of life. However, information about the effects of transcutaneous electrical nerve stimulation on acute exacerbation of chronic obstructive pulmonary disease is quite limited. A single-blind, randomised controlled trial. Data were collected between August 2013-May 2014. Eighty-two patients who were hospitalised with a diagnosis of acute exacerbation of chronic obstructive pulmonary disease were randomly assigned to a transcutaneous electrical nerve stimulation group receiving transcutaneous electrical nerve stimulation treatment for 20 seance over the acupuncture points with pharmacotherapy or placebo group receiving the same treatment without electrical current output from the transcutaneous electrical nerve stimulation device. Pulmonary functional test, six-minute walking distance, dyspnoea and fatigue scale, and St. George's Respiratory Questionnaire scores were assessed pre- and postprogram. The program started at the hospital by the researcher was sustained in the patient's home by the caregiver. All patients were able to complete the program, despite the exacerbation. The 20 seance transcutaneous electrical nerve stimulation program provided clinically significant improvement in forced expiratory volume in 1 seconds 21 ml, 19·51% but when compared with the placebo group, the difference was insignificant (p > 0·05). The six-minute walking distance increased by 48·10 m more in the placebo group (p < 0·05). There were no significant differences between the two groups' St. George's Respiratory Questionnaire, dyspnoea and fatigue score (p > 0·05). Adding transcutaneous electrical nerve stimulation therapy to pharmacotherapy in patients with acute exacerbation of chronic obstructive pulmonary disease provided clinical improvement in forced expiratory volume in 1 seconds and add benefit in exercise capacity, but no significant effect on the other outcomes measured. Transcutaneous electrical nerve stimulation can be used as a non-invasive complementary therapy due to its beneficial effects on forced expiratory volume in 1 seconds and exercise capacity in patients with acute exacerbation of chronic obstructive pulmonary disease. © 2016 John Wiley & Sons Ltd.

Depression and anxiety symptoms in bronchiectasis: associations with health-related quality of life.

PubMed

Olveira, Casilda; Olveira, Gabriel; Gaspar, Inmaculada; Dorado, Antonio; Cruz, Ivette; Soriguer, Federico; Quittner, Alexandra L; Espildora, Francisco

2013-04-01

Bronchiectasis causes pulmonary infections and loss of lung function, resulting in chronic respiratory symptoms and worsening health-related quality of life. The aims of this study were to measure symptoms of depression and anxiety in a sample of patients with bronchiectasis and evaluate their relationship to health outcomes and health-related quality of life. This cross-sectional study included adolescents and adults with bronchiectasis. Patients completed the hospital anxiety and depression scale and the St. George respiratory questionnaire. Health outcome data, including clinical, radiological and spirometric values, were recorded from medical charts. Ninety-three participants with bronchiectasis of any aetiology were recruited: 20 % had elevated depression-related scores and 38 % had elevated anxiety-related scores. Increased symptoms of depression and anxiety were significantly associated with age; anxiety was associated with more frequent exacerbations. Regression analyses indicated that after controlling for demographic (gender and age) and clinical variables (exacerbations frequency, daily sputum, aetiology and spirometry), both depression and anxiety symptoms predicted significantly worse health-related quality of life. In comparison with other predictors, psychological symptoms explained the largest amount of variance in health-related quality of life. Symptoms of depression and anxiety were significant predictors of health-related quality of life in patients with bronchiectasis, independently of respiratory involvement, gender, age or other variables.

Comparison of increased aspirin dose versus combined aspirin plus clopidogrel therapy in patients with diabetes mellitus and coronary heart disease and impaired antiplatelet response to low-dose aspirin.

PubMed

Duzenli, Mehmet Akif; Ozdemir, Kurtulus; Aygul, Nazif; Soylu, Ahmet; Tokac, Mehmet

2008-08-15

The effects of therapy with aspirin 300 mg/day and with combined aspirin 100 mg/day plus clopidogrel 75 mg/day on platelet function were compared in patients with diabetes mellitus and coronary artery disease and impaired antiplatelet responses to aspirin 100 mg/day. The study population consisted of 151 outpatients with type II diabetes mellitus and coronary artery disease who were taking aspirin 100 mg/day. Of the 151 patients, a subgroup of subjects with impaired aspirin response were selected on the basis of the results of platelet aggregometry. Nonresponsiveness to aspirin was defined as mean aggregation > or =69% with 3 micromol/L adenosine diphosphate and mean aggregation > or =70% with 2 micromol/L collagen. Aspirin semiresponders were defined as meeting 1 but not both of these criteria. Nonresponders and semiresponders were randomized equally to aspirin 300 mg/day and aspirin 100 mg/day plus clopidogrel 75 mg/day, and aggregation tests were repeated after 2 weeks. Sixty of the 151 patients with diabetes (40%) were found to respond to aspirin inadequately. Platelet aggregation induced by adenosine diphosphate and collagen decreased significantly after aspirin 300 mg/day or combined therapy. Combined treatment was found to have a stronger inhibitory effect on platelet aggregation induced by adenosine diphosphate than aspirin 300 mg/day (p = 0.002). Impaired aspirin response was resolved by increasing the aspirin dose or adding clopidogrel to aspirin (p <0.0001 for each). However, desired platelet inhibition was achieved in significantly more patients by combined treatment than by aspirin 300 mg/day (p <0.05). In conclusion, aspirin 100 mg/day does not inhibit platelet function adequately in a significant number of patients with diabetes mellitus and coronary artery disease. Increasing the aspirin dose to 300 mg/day or adding clopidogrel to aspirin can provide adequate platelet inhibition in a significant number of those patients with impaired responses to low-dose aspirin.

A Persistent and Diverse Airway Microbiota Present during Chronic Obstructive Pulmonary Disease Exacerbations

PubMed Central

Huang, Yvonne J.; Kim, Eugenia; Cox, Michael J.; Brodie, Eoin L.; Brown, Ron; Wiener-Kronish, Jeanine P.

2010-01-01

Abstract Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases. PMID:20141328

Antibiotic treatment of exacerbations of COPD in general practice: long-term impact on health-related quality of life

PubMed Central

Miravitlles, Marc; Llor, Carles; Molina, Jesús; Naberan, Karlos; Cots, Josep M; Ros, Fernando

2010-01-01

Objective: To investigate the impact of exacerbations in health-related quality of life (HRQL) of patients with COPD and to compare the effect of treatment of COPD exacerbations with moxifloxacin (400 mg/day for 5 days) and amoxicillin/clavulanate (500/125 mg 3 times a day for 10 days) on HRQL. Methods: 229 outpatients with stable COPD (mean age 68.2 years; mean FEV1 % predicted 49.3%) participated in a prospective, observational study of 2 years’ duration. The St George’s Respiratory Questionnaire (SGRQ) was completed at baseline and every 6 months thereafter. Results: COPD exacerbations (mean 2.7 episodes/patient) occurred in 136 patients (124 patients received the study medications [amoxicillin/clavulanate 54, moxifloxacin 70]). Differences between baseline and the final visit were higher for moxifloxacin compared with amoxicillin/clavulanate for total SGRQ score (−2.60 [13.1] vs 4.21 [16.2], P = 0.05) and “Symptoms” subscale (−5.64 [16.7] vs 8.27 [21], P = 0.02). The same findings were observed in patients with two or more exacerbations. Conclusions: In COPD outpatients, treatment of exacerbations with moxifloxacin had a more favorable long-term effect on quality of life than amoxicillin/clavulanate. PMID:20368907

Air pollution and acute respiratory infections among children 0-4 years of age: an 18-year time-series study.

PubMed

Darrow, Lyndsey A; Klein, Mitchel; Flanders, W Dana; Mulholland, James A; Tolbert, Paige E; Strickland, Matthew J

2014-11-15

Upper and lower respiratory infections are common in early childhood and may be exacerbated by air pollution. We investigated short-term changes in ambient air pollutant concentrations, including speciated particulate matter less than 2.5 μm in diameter (PM2.5), in relation to emergency department (ED) visits for respiratory infections in young children. Daily counts of ED visits for bronchitis and bronchiolitis (n = 80,399), pneumonia (n = 63,359), and upper respiratory infection (URI) (n = 359,246) among children 0-4 years of age were collected from hospitals in the Atlanta, Georgia, area for the period 1993-2010. Daily pollutant measurements were combined across monitoring stations using population weighting. In Poisson generalized linear models, 3-day moving average concentrations of ozone, nitrogen dioxide, and the organic carbon fraction of particulate matter less than 2.5 μm in diameter (PM2.5) were associated with ED visits for pneumonia and URI. Ozone associations were strongest and were observed at low (cold-season) concentrations; a 1-interquartile range increase predicted a 4% increase (95% confidence interval: 2%, 6%) in visits for URI and an 8% increase (95% confidence interval: 4%, 13%) in visits for pneumonia. Rate ratios tended to be higher in the 1- to 4-year age group compared with infants. Results suggest that primary traffic pollutants, ozone, and the organic carbon fraction of PM2.5 exacerbate upper and lower respiratory infections in early life, and that the carbon fraction of PM2.5 is a particularly harmful component of the ambient particulate matter mixture. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects.

PubMed

Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

2014-08-01

Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2 , and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. © 2014 The British Pharmacological Society.

Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects

PubMed Central

Floyd, Christopher N; Goodman, Timothy; Becker, Silke; Chen, Nan; Mustafa, Agnesa; Schofield, Emma; Campbell, James; Ward, Malcolm; Sharma, Pankaj; Ferro, Albert

2014-01-01

Aims Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects. Methods Ninety-three healthy subjects received aspirin 300 mg daily for 28 days. Before and at the end of treatment, urine was taken to determine 11-dehydrothromboxane B2, and blood was taken to measure arachidonic acid (AA)-induced aggregation of platelet-rich plasma and to interrogate the platelet proteome by mass spectrometric analysis with further confirmation of findings using Western blotting. Results In two of the 93 subjects, neither AA-induced aggregation nor urinary 11-dehydrothromboxane B2 was effectively suppressed by aspirin, despite measurable plasma salicylate concentrations, suggesting the presence of true aspirin resistance. Despite no detectable differences in the platelet proteome at baseline, following aspirin a marked increase was seen in platelet glycoprotein IIIa expression in the aspirin-resistant but not aspirin-sensitive subjects. An increase in platelet glycoprotein IIIa expression with aspirin resistance was confirmed in a separate cohort of 17 patients with stable coronary artery disease on long term aspirin treatment, four of whom exhibited aspirin resistance. Conclusions In a healthy population, true aspirin resistance is uncommon but exists. Resistance is associated with an increase in platelet glycoprotein IIIa expression in response to aspirin. These data shed new light on the mechanism of aspirin resistance, and provide the potential to identify aspirin-resistant subjects using a novel biomarker. PMID:25099258

Environmental triggers of COPD symptoms: a case cross-over study.

PubMed

Sama, Susan R; Kriebel, David; Gore, Rebecca J; DeVries, Rebecca; Rosiello, Richard

2017-01-01

This study investigated the hypothesis that common environmental chemical exposures with known irritant or sensitising properties trigger exacerbations for patients with chronic obstructive pulmonary disease (COPD). We conducted a case cross-over study in 168 patients with COPD who were members of a disease management group in central Massachusetts. Participants completed a baseline health survey and several short exposure surveys. Exposure surveys were administered by a nurse when a participant telephoned to report an exacerbation (case periods) and at a maximum of three randomly identified control periods when they were not experiencing an exacerbation. We compared exposures in the week preceding an exacerbation with exposures in normal (non-exacerbation) weeks. The questionnaire assessed short-term (1 week) home, community and workplace activities and exposures that may be associated with COPD exacerbation. Self-reported exercise was negatively associated with exacerbation (OR=0.59, 95% CI: 0.35 to 1.00). Among the environmental chemical exposures, car and truck exhaust (OR=4.36, 95% CI: 1.76 to 10.80) and use of scented laundry products (OR=2.69, 95% CI: 1.31 to 5.52) showed strong positive effects. Self-reported respiratory infections were strongly associated with exacerbation (OR=7.90, 95% CI 4.29 to 14.50). Variations in outdoor temperature were associated with COPD exacerbation risk (moderate versus cold temperature OR=1.95, 95% CI 1.09 to 3.49 and warm versus cold OR=0.43, 95% CI: 0.26 to 0.70). These results suggest that some environmental chemical exposures may play a role in triggering COPD exacerbations. If confirmed, they may provide useful guidance for patients with COPD to better manage their disease.

Environmental triggers of COPD symptoms: a case cross-over study

PubMed Central

Sama, Susan R; Kriebel, David; Gore, Rebecca J; DeVries, Rebecca; Rosiello, Richard

2017-01-01

Introduction This study investigated the hypothesis that common environmental chemical exposures with known irritant or sensitising properties trigger exacerbations for patients with chronic obstructive pulmonary disease (COPD). Methods We conducted a case cross-over study in 168 patients with COPD who were members of a disease management group in central Massachusetts. Participants completed a baseline health survey and several short exposure surveys. Exposure surveys were administered by a nurse when a participant telephoned to report an exacerbation (case periods) and at a maximum of three randomly identified control periods when they were not experiencing an exacerbation. We compared exposures in the week preceding an exacerbation with exposures in normal (non-exacerbation) weeks. The questionnaire assessed short-term (1 week) home, community and workplace activities and exposures that may be associated with COPD exacerbation. Results Self-reported exercise was negatively associated with exacerbation (OR=0.59, 95% CI: 0.35 to 1.00). Among the environmental chemical exposures, car and truck exhaust (OR=4.36, 95% CI: 1.76 to 10.80) and use of scented laundry products (OR=2.69, 95% CI: 1.31 to 5.52) showed strong positive effects. Self-reported respiratory infections were strongly associated with exacerbation (OR=7.90, 95% CI 4.29 to 14.50). Variations in outdoor temperature were associated with COPD exacerbation risk (moderate versus cold temperature OR=1.95, 95% CI 1.09 to 3.49 and warm versus cold OR=0.43, 95% CI: 0.26 to 0.70). Conclusions These results suggest that some environmental chemical exposures may play a role in triggering COPD exacerbations. If confirmed, they may provide useful guidance for patients with COPD to better manage their disease. PMID:29071071

Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial.

PubMed

Bilton, Diana; Tino, Gregory; Barker, Alan F; Chambers, Daniel C; De Soyza, Anthony; Dupont, Lieven J A; O'Dochartaigh, Conor; van Haren, Eric H J; Vidal, Luis Otero; Welte, Tobias; Fox, Howard G; Wu, Jian; Charlton, Brett

2014-12-01

Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (-2.4 units, p=0.046). Adverse events were similar between groups. Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. NCT00669331. 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.

An exploration of how nurse prescribing is being used for patients with respiratory conditions across the east of England

PubMed Central

2014-01-01

Background There is a need to reduce symptoms, exacerbations and improve quality of life for patients with respiratory diseases. Across the world, increasing numbers of nurses are adopting the prescribing role and can potentially enhance service provision. Evidence suggests improved quality of care and efficiencies occur when nurses adopt the prescribing role. No evidence is available on the views of nurse prescribers who care for respiratory patients. The aim was to explore how nurse prescribing is being used for patients with respiratory conditions in different care settings across one strategic health authority, and whether this has benefited patients, healthcare professionals and the National Health Service. Methods A qualitative study involving semi-structured interviews with a purposive sample of 40 nurses who prescribed for respiratory patients across the six counties in the East of England Strategic Health Authority. Data were collected in 2011 and subject to thematic analysis. Results Disease management, including treatment and prevention of exacerbations, emergency episodes and minor illness, optimising and co-ordinating care were key aspects of care provided. Findings are reported under three themes: access, adherence and risk management and impact on nurses. Prescribing enabled nurses overcome existing problems in service provision to improve access, efficiency and patient convenience, reducing hospital admissions and length of stay. It also enabled patient centered consultations, which encouraged self-management, improved adherence, helped manage expectations, and reduced inappropriate service use. While participants experienced increased job satisfaction, knowledge and confidence, concerns were raised about increased responsibility, support, governance and future commissioning of services in line with planned major changes to the National Health Service. Conclusions This study provides new knowledge about how nurse prescribers provide care to patients with respiratory diseases. Despite a lack of consensus over the most effective model of respiratory care, prescribing was reported to have improved and extended points of access to treatment, and supported management of complex patients, particularly vulnerable groups. Given the high burden of chronic respiratory disease to patients and families this has important implications that need to be considered by those responsible for commissioning services in the United Kingdom and other countries. PMID:24443796

[Pleural procedures in patients treated by platelet aggregation inhibitors: An opinion survey].

PubMed

Dangers, L; Similowski, T; Chenivesse, C

2016-01-01

When pleural procedures (thoracocentesis, blind pleural biopsies and chest tube insertion) are required in patients taking long-term platelet aggregation inhibitors, the risk of bleeding must be balanced against the risk of arterial thrombosis. Currently, the bleeding risk of pleural procedures is poorly understood. The objective of the survey was to gather the opinion of respiratory physicians regarding the bleeding risk of pleural procedures in patients taking platelet aggregation inhibitors. We emailed a standardized questionnaire designed by the French National Authority for Health to 2697 French respiratory physicians. One hundred and eighty-eight of the 2697 questionnaires were returned (response rate: 7 %). The respiratory physicians declared that they performed an average of 8 pleural procedures per month. One hundred and seventy-five responders (95 %) practised pleural procedures in patients receiving platelet aggregation inhibitors; 68 of them (39 %) reported experiencing haemorrhagic complications. The bleeding risk associated with thoracentesis and chest tube insertion was considered minor by 97.8 and 65 % of responders respectively, whereas it was considered major for blind pleural biopsies by 73.4 %. Respiratory physicians were more reticent about performing pleural procedures in patients treated with clopidogrel than in those taking aspirin. This study provides an overview of how respiratory physicians perceive the bleeding risk associated with pleural procedures in patients taking platelet aggregation inhibitors. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

Virus/allergen interactions in asthma.

PubMed

Gavala, Monica L; Bashir, Hiba; Gern, James E

2013-06-01

Understanding the underlying mechanisms that cause and exacerbate allergic asthmatic disease is of great clinical interest. Clinical studies have revealed that allergies and viral respiratory illnesses are strongly linked to the inception and exacerbation of asthma, and suggest the possibility that there are interactive inflammatory mechanisms. Recent work has revealed a number of mechanisms of virus and allergen cross-talk that may play a role in the pathophysiology of allergic asthma, including (1) deficiency in virus-induced interferon responses, (2) defective epithelial barrier function, (3) increased release of epithelium-derived cytokines (e.g., thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, IL-33), (4) dysregulation of lymphocytes [e.g., innate lymphoid cells (ILCs), regulatory T cells (Tregs)], and (5) altered activation of purinergic receptors. One or more of these processes may provide targets for new therapeutics to treat allergic asthma and prevent disease exacerbation.

How close are we to definitively identifying the respiratory health effects of e-cigarettes?

PubMed

Ratajczak, Alexsandra; Feleszko, Wojciech; Smith, Danielle M; Goniewicz, Maciej

2018-07-01

Use of electronic cigarettes (e-cigarettes) is frequently promoted as a less harmful alternative to cigarette smoking. The impact of repeated inhalation of e-cigarette aerosols on respiratory health is not well understood. Areas covered: Using results from laboratory, observational, and clinical studies, we synthesize evidence relevant to potential respiratory health effects that may result from inhalation of e-cigarette aerosols. Expert commentary: Chemical analyses reveal that e-cigarette aerosols contain numerous respiratory irritants and toxicants. There are documented cytotoxic effects of e-cigarette constituents on lung tissue. Studies among ex-smokers who switched to e-cigarettes note reduced exposure to numerous respiratory toxicants, reduced asthma exacerbations, and chronic obstructive pulmonary disease symptoms. Regular exposure to e-cigarette aerosols is associated with impaired respiratory functioning. Potential respiratory health risks resulting from secondhand e-cigarette aerosol exposure have not been sufficiently evaluated. Current evidence indicates that although e-cigarettes are not without risk, these products seemingly pose fewer respiratory health harms issues compared to tobacco cigarettes. Data from prospective studies and randomized controlled trials examining the impact of e-cigarette use on lung health are needed to better understand respiratory health risks tied to use of these products.

Safety and feasibility of liver resection with continued antiplatelet therapy using aspirin.

PubMed

Monden, Kazuteru; Sadamori, Hiroshi; Hioki, Masayoshi; Ohno, Satoshi; Saneto, Hiromi; Ueki, Toru; Yabushita, Kazuhisa; Ono, Kazumi; Sakaguchi, Kousaku; Takakura, Norihisa

2017-07-01

Aspirin is widely used for the secondary prevention of ischemic stroke and cardiovascular disease. Perioperative aspirin may decrease thrombotic morbidity, but may also increase hemorrhagic morbidity. In particular, liver resection carries risks of bleeding, leading to higher risks of hemorrhagic morbidity. Our institution has continued aspirin therapy perioperatively in patients undergoing liver resection. This study examined the safety and feasibility of liver resection while continuing aspirin. We retrospectively evaluated 378 patients who underwent liver resection between January 2010 and January 2016. Patients were grouped according to preoperative aspirin prescription: patients with aspirin therapy (aspirin users, n = 31); and patients without use of aspirin (aspirin non-users, n = 347). Aspirin users were significantly older (P < 0.001), with a higher proportion of males (P < 0.001) and higher frequencies of hypertension (P  = 0.004) and diabetes mellitus (P < 0.001). No significant differences were observed in intraoperative parameters. Although the frequency of major morbidity tended to be higher among aspirin users than among aspirin non-users, no significant difference was identified. No postoperative hemorrhage was seen among aspirin users. Liver resection can be safely performed while continuing aspirin therapy without increasing hemorrhagic morbidity. Our results suggest that interruption of aspirin therapy is unnecessary for patients undergoing liver resection. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Exposure to Indoor Particulate Matter Worsens the Symptoms and Acute Exacerbations in Chronic Obstructive Pulmonary Disease Patients of Southwestern Taiwan: A Pilot Study

PubMed Central

Chi, Miao-Ching; Guo, Su-Er; Hwang, Su-Lun; Chou, Chiang-Ting; Lin, Chieh-Mo; Lin, Yu-Ching

2016-01-01

Ambient particulate matter (PM) can trigger adverse reactions in the respiratory system, but less is known about the effect of indoor PM. In this longitudinal study, we investigated the relationships between indoor PM and clinical parameters in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Indoor air quality (PM2.5 and PM10 levels) was monitored in the patients’ bedroom, kitchen, living room, and front door at baseline and every two months for one year. At each home visit, the patients were asked to complete spirometry and questionnaire testing. Exacerbations were assessed by chart review and questionnaires during home visits. Generalized estimating equation (GEE) analysis (n = 83) showed that the level of wheezing was significantly higher in patients whose living room and kitchen had abnormal (higher than ambient air quality standards in Taiwan) PM2.5 and PM10 levels. Patients who lived in houses with abnormal outdoor PM2.5 levels had higher COPD Assessment Test scores (physical domain), and those who lived in houses with abnormal PM10 levels in the living room and kitchen had higher London Chest Activity of Daily Living scores. Increased PM levels were associated with worse respiratory symptoms and increased risk of exacerbation in patients with moderate to very severe COPD. PMID:28025521

Mathematical modeling of postcoinfection with influenza A virus and Streptococcus pneumoniae, with implications for pneumonia and COPD-risk assessment.

PubMed

Cheng, Yi-Hsien; You, Shu-Han; Lin, Yi-Jun; Chen, Szu-Chieh; Chen, Wei-Yu; Chou, Wei-Chun; Hsieh, Nan-Hung; Liao, Chung-Min

2017-01-01

The interaction between influenza and pneumococcus is important for understanding how coinfection may exacerbate pneumonia. Secondary pneumococcal pneumonia associated with influenza infection is more likely to increase respiratory morbidity and mortality. This study aimed to assess exacerbated inflammatory effects posed by secondary pneumococcal pneumonia, given prior influenza infection. A well-derived mathematical within-host dynamic model of coinfection with influenza A virus and Streptococcus pneumoniae (SP) integrated with dose-response relationships composed of previously published mouse experimental data and clinical studies was implemented to study potentially exacerbated inflammatory responses in pneumonia based on a probabilistic approach. We found that TNFα is likely to be the most sensitive biomarker reflecting inflammatory response during coinfection among three explored cytokines. We showed that the worst inflammatory effects would occur at day 7 SP coinfection, with risk probability of 50% (likely) to develop severe inflammatory responses. Our model also showed that the day of secondary SP infection had much more impact on the severity of inflammatory responses in pneumonia compared to the effects caused by initial virus titers and bacteria loads. People and health care workers should be wary of secondary SP infection on day 7 post-influenza infection for prompt and proper control-measure implementation. Our quantitative risk-assessment framework can provide new insights into improvements in respiratory health especially, predominantly due to chronic obstructive pulmonary disease (COPD).

Role of long term antibiotics in chronic respiratory diseases.

PubMed

Suresh Babu, K; Kastelik, J; Morjaria, J B

2013-06-01

Antibiotics are commonly used in the management of respiratory disorders such as cystic fibrosis (CF), non-CF bronchiectasis, asthma and COPD. In those conditions long-term antibiotics can be delivered as nebulised aerosols or administered orally. In CF, nebulised colomycin or tobramycin improve lung function, reduce number of exacerbations and improve quality of life (QoL). Oral antibiotics, such as macrolides, have acquired wide use not only as anti-microbial agents but also due to their anti-inflammatory and pro-kinetic properties. In CF, macrolides such as azithromycin have been shown to improve the lung function and reduce frequency of infective exacerbations. Similarly macrolides have been shown to have some benefits in COPD including reduction in a number of exacerbations. In asthma, macrolides have been reported to improve some subjective parameters, bronchial hyperresponsiveness and airway inflammation; however have no benefits on lung function or overall asthma control. Macrolides have also been used with beneficial effects in less common disorders such as diffuse panbronchiolitis or post-transplant bronchiolitis obliterans syndrome. In this review we describe our current knowledge the use of long-term antibiotics in conditions such as CF, non-CF bronchiectasis, asthma and COPD together with up-to-date clinical and scientific evidence to support our understanding of the use of antibiotics in those conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of the effectiveness of manual chest physiotherapy techniques on quality of life at six months post exacerbation of COPD (MATREX): a randomised controlled equivalence trial

PubMed Central

2012-01-01

Background Manual chest physiotherapy (MCP) techniques involving chest percussion, vibration, and shaking have long been used in the treatment of respiratory conditions. However, methodological limitations in existing research have led to a state of clinical equipoise with respect to this treatment. Thus, for patients hospitalised with an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), clinical preference tends to dictate whether MCP is given to assist with sputum clearance. We standardised the delivery of MCP and assessed its effectiveness on disease-specific quality of life. Methods In this randomised, controlled trial powered for equivalence, 526 patients hospitalised with acute COPD exacerbation were enrolled from four centres in the UK. Patients were allocated to receive MCP plus advice on airway clearance or advice on chest clearance alone. The primary outcome was a COPD specific quality of life measure, the Saint Georges Respiratory Questionnaire (SGRQ) at six months post randomisation. Analyses were by intention to treat (ITT). This study was registered, ISRCTN13825248. Results All patients were included in the analyses, of which 372 (71%) provided evaluable data for the primary outcome. An effect size of 0·3 standard deviations in SGRQ score was specified as the threshold for superiority. The ITT analyses showed no significant difference in SGRQ for patients who did, or did not receive MCP (95% CI −0·14 to 0·19). Conclusions These data do not lend support to the routine use of MCP in the management of acute exacerbation of COPD. However, this does not mean that MCP is of no therapeutic value to COPD patients in specific circumstances. PMID:22748085

Differences in care between general medicine and respiratory specialists in the management of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease.

PubMed

Wijayaratne, Kurugamage; Wilson, Jessica; Sivakumaran, Pathmanathan; Sriram, Krishna B

2013-10-01

Hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) may be managed by either respiratory specialists (RS) or general medicine physicians (GMP). While previous studies have audited the hospital AECOPD management of RS, only a small number of studies have evaluated the management of GMP. The aims of this study were to firstly examine the differences in AECOPD management of GMP and RS and secondly compare their care to national COPD guidelines. A retrospective review was undertaken of consecutive AECOPD patients admitted to two hospitals (one hospital where all AECOPD patients were managed by RS and another where all AECOPD patients were managed by GMP) over a 3-month period. Electronic medical records, medical case notes, pathology and radiology data for the admission were reviewed. There were 201 COPD exacerbations in 169 patients (49.7% male, mean age 72.3). GMP managed 84 (41.7%) exacerbations. In comparison to RS, GMP performed fewer spirometry tests, blood gas analysis and less frequently treated patients with guideline-recommended medications. Referral to pulmonary rehabilitation was poor for both groups of clinicians. Median length of stay was shorter in GMP patients versus RS patients (3 days vs. 5 days, P = 0.001). There were no differences in the 12-month re-admission (41.7% vs. 38.5%, P = 0.664) and mortality rates (10.7% vs. 6%, P = 0.292) between both groups of patients. Our study found differences in the hospital AECOPD management of GMP and RS, but these did not translate into different clinical outcomes between their patients. We also found suboptimal adherence to national COPD guidelines, suggesting that there is scope for improvement in the AECOPD management of both groups of clinicians.

State of the Art Compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease.

PubMed

O'Donnell, Denis E; Aaron, Shawn; Bourbeau, Jean; Hernandez, Paul; Marciniuk, Darcy; Balter, Meyer; Ford, Gordon; Gervais, Andre; Goldstein, Roger; Hodder, Rick; Maltais, Francois; Road, Jeremy; McKay, Valoree; Schenkel, Jennifer; Ariel, Annon; Day, Anna; Lacasse, Yves; Levy, Robert; Lien, Dale; Miller, John; Rocker, Graeme; Sinuff, Tasmin; Stewart, Paula; Voduc, Nha; Abboud, Raja; Ariel, Amnon; Becklake, Margo; Borycki, Elizabeth; Brooks, Dina; Bryan, Shirley; Calcutt, Luanne; Chapman, Ken; Choudry, Nozhat; Couet, Alan; Coyle, Steven; Craig, Arthur; Crawford, Ian; Dean, Mervyn; Grossman, Ronald; Haffner, Jan; Heyland, Daren; Hogg, Donna; Holroyde, Martin; Kaplan, Alan; Kayser, John; Lein, Dale; Lowry, Josiah; McDonald, Les; MacFarlane, Alan; McIvor, Andrew; Rea, John; Reid, Darlene; Rouleau, Michel; Samis, Lorelei; Sin, Don; Vandemheen, Katherine; Wedzicha, J A; Weiss, Karl

2004-01-01

Chronic obstructive pulmonary disease (COPD) is a common cause of disability and death in Canada. Moreover, morbidity and mortality from COPD continue to rise, and the economic burden is enormous. The main goal of the Canadian Thoracic Society's evidence-based guidelines is to optimize early diagnosis, prevention and management of COPD in Canada. The main message of the guidelines is that COPD is a preventable and treatable disease. Targeted spirometry is strongly recommended to expedite early diagnosis in smokers and former smokers who develop respiratory symptoms, and who are at risk for COPD. Smoking cessation remains the single most effective intervention to reduce the risk of COPD and to slow its progression. Education, especially self-management plans, are key interventions in COPD. Therapy should be escalated on an individual basis in accordance with the increasing severity of symptoms and disability. Long-acting anticholinergics and beta-2-agonist inhalers should be prescribed for patients who remain symptomatic despite short-acting bronchodilator therapy. Inhaled steroids should not be used as first line therapy in COPD, but have a role in preventing exacerbations in patients with more advanced disease who suffer recurrent exacerbations. Acute exacerbations of COPD cause significant morbidity and mortality and should be treated promptly with bronchodilators and a short course of oral steroids; antibiotics should be prescribed for purulent exacerbations. Patients with advanced COPD and respiratory failure require a comprehensive management plan that incorporates structured end-of-life care. Management strategies, consisting of combined modern pharmacotherapy and nonpharmacotherapeutic interventions (eg, pulmonary rehabilitation and exercise training) can effectively improve symptoms, activity levels and quality of life, even in patients with severe COPD.

Quality of Life Questionnaire-Bronchiectasis: final psychometric analyses and determination of minimal important difference scores.

PubMed

Quittner, Alexandra L; O'Donnell, Anne E; Salathe, Matthias A; Lewis, Sandra A; Li, Xiaoming; Montgomery, A Bruce; O'Riordan, Thomas G; Barker, Alan F

2015-01-01

The Quality of Life-Bronchiectasis (QOL-B), a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis (CF) bronchiectasis, contains 37 items on 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden). Psychometric analyses of QOL-B V.3.0 used data from two double-blind, multicentre, randomised, placebo-controlled, phase III trials of aztreonam for inhalation solution (AZLI) in 542 patients with non-CF bronchiectasis and Gram-negative endobronchial infection. Excellent internal consistency (Cronbach's α ≥0.70) and 2-week test-retest reliability (intraclass correlation coefficients ≥0.72) were demonstrated for each scale. Convergent validity with 6 min walk test was observed for Physical and Role Functioning scores. No floor or ceiling effects (baseline scores of 0 or 100) were found for the Respiratory Symptoms scale (primary endpoint of trials). Baseline Respiratory Symptoms scores discriminated between patients based on baseline FEV₁% predicted in only one trial. The minimal important difference score for the Respiratory Symptoms scale was 8.0 points. AZLI did not show efficacy in the two phase III trials. QOL-B responsivity to treatment was assessed by examining changes from baseline QOL-B scores at study visits at which protocol-defined pulmonary exacerbations were reported. Mean Respiratory Symptoms scores decreased 14.0 and 14.2 points from baseline for placebo-treated and AZLI-treated patients with exacerbations, indicating that worsening respiratory symptoms were reflected in clinically meaningful changes in QOL-B scores. Previously established content validity, reliability and responsivity of the QOL-B are confirmed by this final validation study. The QOL-B is available for use in clinical trials and routine clinical practice. 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.

Aspirin resistance in cerebrovascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients.

PubMed

Derle, Eda; Öcal, Ruhsen; Kibaroğlu, Seda; Çelikkol, Ceyda; Bayraktar, Nilüfer; Verdi, Hasibe; Ataç, Belgin F; Can, Ufuk

2016-03-01

Aspirin resistance occurs in 5-45% of high-risk patients, with various mechanisms proposed for its development. This study aimed to determine the relationships among aspirin resistance, aspirin dosage, type of aspirin and glycoprotein IIIa P1A1/A2 polymorphism in patients with vascular risk factors. Two hundred and eight (75 symptomatic, 133 asymptomatic) patients with vascular risk factors who were using aspirin for primary or secondary prevention were prospectively included. The symptomatic group was further classified into two groups according to aspirin use at the time of stroke. Aspirin resistance was measured by the PFA-100 system (collagen/epinephrine cartridge) and glycoprotein IIIa P1A1/A2 polymorphism was determined by PCR. The overall prevalence of aspirin resistance was 32.2%. The mean age of patients with aspirin resistance was significantly higher than that in those who did not have resistance (P = 0.009). The prevalence of aspirin resistance was similar for the symptomatic and asymptomatic under aspirin therapy groups. The resistance rate was found to be highest with 100 mg enteric-coated preparation use (39.3%). Increasing the aspirin dosage and/or shifting to uncoated preparations caused a change in aspirin sensitivity of 36-60%. Repeated measurements showed development of aspirin resistance in 14% of patients who were sensitive to aspirin in previous measurements. Glycoprotein IIIaP1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke were not significantly related. The effect of aspirin can change by time, dosage and type of preparation used. There are no relationships among glycoprotein IIIa P1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke.

Aspirin use and the incidence of breast, colon, ovarian, and pancreatic cancers in elderly women in the Iowa Women's Health Study.

PubMed

Vaughan, Lisa E; Prizment, Anna; Blair, Cindy K; Thomas, William; Anderson, Kristin E

2016-11-01

Few studies have evaluated the chemopreventive effect of aspirin on the cancer risk in elderly women. We examined associations between frequency, dose, and duration of aspirin use with incidence of 719 aspirin-sensitive cancers (cancers of colon, pancreas, breast, and ovaries) in the Iowa Women's Health Study (IWHS), a prospective cohort of women over 70 years old. Aspirin frequency, dose, and duration were self-reported in the 2004 IWHS questionnaire. Women were followed-up to 2011. Cancer cases were ascertained by linkage to the Iowa State Health Registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CI). Among the 14,386 women, 30 % were nonusers of aspirin; 34 % used low-dose aspirin, and 36 % used regular- or high-dose aspirin. Compared with nonuse of aspirin, the HRs (95 % CI) for incidence of aspirin-sensitive cancers were 0.87 (0.72-1.06) for regular to high doses of aspirin use, 0.95 (0.80-1.13) for aspirin use 6+ times per week, and 0.93 (0.74-1.17) for aspirin use for 10+ years. For cumulative aspirin use, HR (95 % CI) was 0.87 (0.70-1.09) for >60,000 mg of aspirin per year and 0.95 (0.75-1.21) for >280,000 mg of aspirin in their lifetime, versus nonuse of aspirin. Results were similar for the all-cause cancer death as an endpoint, with a significant inverse association observed between lifetime aspirin dose and cancer mortality [<95,000 mg vs nonuser HR 0.76 (0.61-0.95)]. These findings suggest that aspirin use may prevent incident breast, colon, pancreatic, and ovarian cancer in elderly women.

Community-Based Decision-Making: Application of Web-Based Near-Road Modeling System to Newport News, Virginia

EPA Science Inventory

Living, working, and going to school near roadways has been associated with a number of adverse health effects, including asthma exacerbation, cardiovascular impairment, and respiratory symptoms. In the United States, 30% - 45% of urban populations live or work in the near-road e...

Diesel, children and respiratory disease.

PubMed

Liu, Norrice M; Grigg, Jonathan

2018-01-01

Air pollution generated in urban areas is a global public health burden since half of the world's population live in either cities, megacities or periurban areas. Its direct effects include initiating and exacerbating disease, with indirect effects on health mediated via climate change putting the basic needs of water, air and food at risk.

Subclinical and Overt Adverse Cardiac Effects with Ozone Inhalation in Rats: Potentially Dire Implications of Low Exposures

EPA Science Inventory

Ozone is a ubiquitous smog-associated photochemical oxidant with deleterious health effects. While most of the adverse effects described to date involve the respiratory system (i.e, decrements in lung function, airway injury and inflammation, exacerbation of asthma, and compromis...

Complex roles of the old drug aspirin in cancer chemoprevention and therapy.

PubMed

Hua, Hui; Zhang, Hongying; Kong, Qingbin; Wang, Jiao; Jiang, Yangfu

2018-06-01

The nonsteroidal anti-inflammatory agent aspirin is widely used for preventing and treating cardiovascular and cerebrovascular diseases. In addition, epidemiologic evidences reveal that aspirin may prevent a variety of human cancers, while data on the association between aspirin and some kinds of cancer are conflicting. Preclinical studies and clinical trials also reveal the therapeutic effect of aspirin on cancer. Although cyclooxygenase is a well-known target of aspirin, recent studies uncover other targets of aspirin and its metabolites, such as AMP-activated protein kinase, cyclin-dependent kinase, heparanase, and histone. Accumulating evidence demonstrate that aspirin may act in different cell types, such as epithelial cell, tumor cell, endothelial cell, platelet, and immune cell. Therefore, aspirin acts on diverse hallmarks of cancer, such as sustained tumor growth, metastasis, angiogenesis, inflammation, and immune evasion. In this review, we focus on recent progress in the use of aspirin for cancer chemoprevention and therapy, and integratively analyze the mechanisms underlying the anticancer effects of aspirin and its metabolites. We also discuss mechanisms of aspirin resistance and describe some derivatives of aspirin, which aim to overcome the adverse effects of aspirin. © 2018 Wiley Periodicals, Inc.

Effects of seasonal smog on asthma and COPD exacerbations requiring emergency visits in Chiang Mai, Thailand.

PubMed

Pothirat, Chaicharn; Tosukhowong, Apiwat; Chaiwong, Warawut; Liwsrisakun, Chalerm; Inchai, Juthamas

2016-12-01

Seasonal smog produces particulate matters that are less than 10 microns in diameter (PM₁₀), which are known to have several impacts on the respiratory system. This study was to determine the association of an increased PM10 level due to seasonal smog in Chiang Mai and emergency visits for asthma and chronic obstructive pulmonary disease (COPD) exacerbations. A retrospective cross-sectional study was conducted between the months of January and March from 2006 until 2009. The association of an increased PM₁₀ level and the daily number of asthma and COPD exacerbations were analyzed using a generalized linear model; a Poisson regression model was fit to the number of daily emergency visits using predictor variables: lags of PM10, day of the week, and time. There were a total of 917 emergency visits for acute exacerbations of asthma and COPD, with a median of 2 visits per day (range 0-10). The median PM₁₀ level during the same interval was 64.5 microgram per cubic meter (μg/m3) (16-304). For every 10 μg/m3 rise in PM10 concentration, there was a lag time of 6 days for asthma exacerbations [Adjusted relative risk (RR)=1.020; 95% confident interval (CI), 1.001-1.040; (p=0.014)], 7 days for COPD exacerbations [RR=1.030; 95%CI, 1.010-1.050 (p=0.024)] and 7 days for all exacerbations [RR=1.030 95%CI, 1.010-1.040 (p<0.001)]. This study confirms the effect of increasing PM₁₀ concentrations from seasonal smog on asthma and COPD exacerbations. However, there was an approximately 1 week lag time between the elevated PM₁₀ levels and time to emergency visits due to disease exacerbation.

Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥40 Years: Data from the National Health and Nutrition Examination Survey, 2011–2012

PubMed Central

Dillon, Charles F.; Eberhardt, Mark S.; Wright, Jacqueline D.; Burt, Vicki L.

2015-01-01

Objective We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. Methods We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged ≥40 years from the National Health and Nutrition Examination Survey, 2011–2012. Results In 2011–2012, one-third of U.S. adults aged ≥40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40–49 years to 54% of those ≥80 years of age, p<0.001). Non-Hispanic white (35%) and black (30%) adults were more likely to take preventive aspirin than non-Hispanic Asian (20%, p<0.001) and Hispanic (22%, p=0.013) adults. Adults with, compared with those without health insurance, and adults with ≥2 doctor visits in the past year, diagnosed diabetes, hypertension, or high cholesterol were twice as likely to take preventive aspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. Conclusion The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use. PMID:26556936

Enteric Coating and Aspirin Nonresponsiveness in Patients With Type 2 Diabetes Mellitus.

PubMed

Bhatt, Deepak L; Grosser, Tilo; Dong, Jing-Fei; Logan, Douglas; Jeske, Walter; Angiolillo, Dominick J; Frelinger, Andrew L; Lei, Lanyu; Liang, Juan; Moore, Jason E; Cryer, Byron; Marathi, Upendra

2017-02-14

A limitation of aspirin is that some patients, particularly those with diabetes, may not have an optimal antiplatelet effect. The goal of this study was to determine if oral bioavailability mediates nonresponsiveness. The rate and extent of serum thromboxane generation and aspirin pharmacokinetics were measured in 40 patients with diabetes in a randomized, single-blind, triple-crossover study. Patients were exposed to three 325-mg aspirin formulations: plain aspirin, PL2200 (a modified-release lipid-based aspirin), and a delayed-release enteric-coated (EC) aspirin. Onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B 2 (TXB 2 ) generation. Aspirin nonresponsiveness was defined as a level of residual serum TXB 2 associated with elevated thrombotic risk (<99.0% inhibition or TXB 2 >3.1 ng/ml) within 72 h after 3 daily aspirin doses. The rate of aspirin nonresponsiveness was 15.8%, 8.1%, and 52.8% for plain aspirin, PL2200, and EC aspirin, respectively (p < 0.001 for both comparisons vs. EC aspirin; p = 0.30 for comparison between plain aspirin and PL2200). Similarly, 56% of EC aspirin-treated subjects had serum TXB 2 levels >3.1 ng/ml, compared with 18% and 11% of subjects after administration of plain aspirin and PL2200 (p < 0.0001). Compared with findings for plain aspirin and PL2200, this high rate of nonresponsiveness with EC aspirin was associated with lower exposure to acetylsalicylic acid (63% and 70% lower geometric mean maximum plasma concentration [C max ] and 77% and 82% lower AUC 0-t [area under the curve from time 0 to the last time measured]) and 66% and 72% lower maximum decrease of TXB 2 , with marked interindividual variability. A high proportion of patients treated with EC aspirin failed to achieve complete inhibition of TXB 2 generation due to incomplete absorption. Reduced bioavailability may contribute to "aspirin resistance" in patients with diabetes. (Pharmacodynamic Evaluation of PL2200 Versus Enteric-Coated and Immediate Release Aspirin in Diabetic Patients; NCT01515657). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population

PubMed Central

Leidy, Nancy K; Kim, Katherine; Bacci, Elizabeth D; Yawn, Barbara P; Mannino, David M; Thomashow, Byron M; Barr, R Graham; Rennard, Stephen I; Houfek, Julia F; Han, Meilan K; Meldrum, Catherine A; Make, Barry J; Bowler, Russ P; Steenrod, Anna W; Murray, Lindsey T; Walsh, John W; Martinez, Fernando

2015-01-01

Background: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations. Aims: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care. Methods: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care). Phase I: Eight focus groups and six telephone interviews were conducted to elicit descriptions of risk factors for COPD, recent or historical acute respiratory events, and symptoms to inform the development of candidate items for the new questionnaire. Phase II: A new cohort of subjects participated in cognitive interviews to assess and modify candidate items. Two peak expiratory flow (PEF) devices (electronic, manual) were assessed for use in screening. Results: Of 77 subjects, 50 participated in Phase I and 27 in Phase II. Six themes informed item development: exposure (smoking, second-hand smoke); health history (family history of lung problems, recurrent chest infections); recent history of respiratory events (clinic visits, hospitalisations); symptoms (respiratory, non-respiratory); impact (activity limitations); and attribution (age, obesity). PEF devices were rated easy to use; electronic values were significantly higher than manual (P<0.0001). Revisions were made to the draft items on the basis of cognitive interviews. Conclusions: Forty-eight candidate items are ready for quantitative testing to select the best, smallest set of questions that, together with PEF, can efficiently identify patients in need of diagnostic evaluation for clinically significant COPD. PMID:26028486

Gastroesophageal reflux disease in COPD: links and risks.

PubMed

Lee, Annemarie L; Goldstein, Roger S

2015-01-01

COPD is a long-term condition associated with considerable disability with a clinical course characterized by episodes of worsening respiratory signs and symptoms associated with exacerbations. Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal conditions in the general population and has emerged as a comorbidity of COPD. GERD may be diagnosed by both symptomatic approaches (including both typical and atypical symptoms) and objective measurements. Based on a mix of diagnostic approaches, the prevalence of GERD in COPD ranges from 17% to 78%. Although GERD is usually confined to the lower esophagus in some individuals, it may be associated with pulmonary microaspiration of gastric contents. Possible mechanisms that may contribute to GERD in COPD originate from gastroesophageal dysfunction, including altered pressure in the lower esophageal sphincter (which normally protect against GERD) and changes in esophageal motility. Proposed respiratory contributions to the development of GERD include respiratory medications that may alter esophageal sphincter tone and changes in respiratory mechanics, with increased lung hyperinflation compromising the antireflux barrier. Although the specific cause and effect relationship between GERD and COPD has not been fully elucidated, GERD may influence lung disease severity and has been identified as a significant predictor of acute exacerbations of COPD. Further clinical effects could include a poorer health-related quality of life and an increased cost in health care, although these factors require further clarification. There are both medical and surgical options available for the treatment of GERD in COPD and while extensive studies in this population have not been undertaken, this comorbidity may be amenable to treatment.

Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015.

PubMed

Romero-Espinoza, Jose A; Moreno-Valencia, Yazmin; Coronel-Tellez, Rodrigo H; Castillejos-Lopez, Manuel; Hernandez, Andres; Dominguez, Aaron; Miliar-Garcia, Angel; Barbachano-Guerrero, Arturo; Perez-Padilla, Rogelio; Alejandre-Garcia, Alejandro; Vazquez-Perez, Joel A

2018-01-01

Acute asthma exacerbations and pneumonia are important causes of morbidity and mortality in children and may coexist in the same children, although symptom overlap may lead to difficulties in diagnosis. Microbial and viral diversity and differential abundance of either may play an important role in infection susceptibility and the development of acute and chronic respiratory diseases. To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. During the winter seasons of 2013-2014 and 2014-2015, 134 nasopharyngeal swabs samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were selected based on clinical diagnosis of asthma or pneumonia. The virome and bacteriome were characterized using Whole Genome Sequencing (WGS) and in-house bioinformatics analysis pipeline. The Asthma group was represented mainly by RV-C, BoV-1 and RSV-B and the pneumonia group by Bacteriophage EJ-1 and TTMV. TTV was found in both groups with a similar amount of reads. About bacterial composition Moraxella catarrhalis, Propionibacterium acnes and Acinetobacter were present in asthma and Veillonella parvula and Mycoplasma pneumoniae in pneumonia. Streptococcus pneumoniae and Haemophilus influenzae were mostly found with both asthma and pneumonia. Our results show a complex viral and bacterial composition in asthma and pneumonia groups with a strong association of RV-C presence in asthmatic children. We observed Streptococcus pneumoniae and Haemophilus influenzae concurrently in both groups.

Gastroesophageal reflux disease in COPD: links and risks

PubMed Central

Lee, Annemarie L; Goldstein, Roger S

2015-01-01

COPD is a long-term condition associated with considerable disability with a clinical course characterized by episodes of worsening respiratory signs and symptoms associated with exacerbations. Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal conditions in the general population and has emerged as a comorbidity of COPD. GERD may be diagnosed by both symptomatic approaches (including both typical and atypical symptoms) and objective measurements. Based on a mix of diagnostic approaches, the prevalence of GERD in COPD ranges from 17% to 78%. Although GERD is usually confined to the lower esophagus in some individuals, it may be associated with pulmonary microaspiration of gastric contents. Possible mechanisms that may contribute to GERD in COPD originate from gastroesophageal dysfunction, including altered pressure in the lower esophageal sphincter (which normally protect against GERD) and changes in esophageal motility. Proposed respiratory contributions to the development of GERD include respiratory medications that may alter esophageal sphincter tone and changes in respiratory mechanics, with increased lung hyperinflation compromising the antireflux barrier. Although the specific cause and effect relationship between GERD and COPD has not been fully elucidated, GERD may influence lung disease severity and has been identified as a significant predictor of acute exacerbations of COPD. Further clinical effects could include a poorer health-related quality of life and an increased cost in health care, although these factors require further clarification. There are both medical and surgical options available for the treatment of GERD in COPD and while extensive studies in this population have not been undertaken, this comorbidity may be amenable to treatment. PMID:26392769

Epidemiology of NIV for Acute Respiratory Failure in COPD Patients: Results from the International Surveys vs. the "Real World".

PubMed

Ozsancak Ugurlu, Aylin; Habesoglu, Mehmet Ali

2017-08-01

Non-invasive ventilation (NIV) has been recommended as the  first-line ventilation modality for acute respiratory failure (ARF) due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) based on strong evidence. However, everyday clinical practice may differ from findings of multiple randomized controlled trials. Physicians and respiratory therapists involved in NIV management have been queried about its utilization and effectiveness. In addition to these estimates, cohort studies and analysis of large inpatient dataset of patients with AECOPD and ARF managed with NIV have been extensively published over the last two decades. This review summarizes the perception of medical staff vs. the "real life" data about NIV use for ARF in AECOPD patients.

Serum inflammatory biomarkers and clinical outcomes of COPD exacerbation caused by different pathogens.

PubMed

Kawamatawong, Theerasuk; Apiwattanaporn, Apitch; Siricharoonwong, Warisara

2017-01-01

COPD exacerbation is characterized by worsening of symptoms, warranting change in treatment. Systemic and airway inflammation play roles in the pathogenesis of COPD exacerbation. We hypothesized whether increased serum inflammatory biomarkers are associated with the clinical outcomes of COPD exacerbation caused by different infectious pathogens. COPD patients with exacerbation were recruited from a hospital emergency department during 2014-2015. Serum procalcitonin (PCT) and C-reactive protein (CRP) were measured. Dyspnea, eosinopenia, consolidation, acidemia, and atrial fibrillation (DECAF) score was calculated for predicting mortality. Multiplex polymerase chain reaction was carried out for respiratory viral assay from nasopharyngeal swabs, and sputum bacterial culture was also performed. Hospital mortality, invasive mechanical ventilation requirement, and length of hospital stay (LOS) were evaluated, and their associations with clinical characteristics, DECAF score, and serum biomarkers were examined. A total of 62 COPD patients were enrolled. These patients were classified as Global Initiative for Obstructive Lung Disease (GOLD) stage 2, 3, and 4 in 12.9%, 6.4%, and 80.7% of cases, respectively. Isolated bacterial exacerbation was recovered in 30.6% of exacerbation episodes: Klebsiella pneumoniae was the most commonly identified bacteria. Viral pathogens and coinfections were noted in 9.6% and 16.1% of exacerbated patients, respectively. Influenza was the most commonly detected viral pathogen. Serum biomarkers and DECAF score for viruses, bacteria, coinfection, and noninfectious causes of exacerbations were similar. Neither DECAF score nor serum biomarkers were able to differentiate patients with and without mortality or requiring mechanical ventilation. Increased serum PCT was noted in patients with LOS ≥7 days when compared with those with LOS <7 days (0.38 ng/mL vs 0.1 ng/mL; P =0.035). Increased serum PCT is associated with longer LOS in COPD exacerbation. However, CRP and DECAF score play limited roles in predicting clinical outcome and lack an association with causes of exacerbation.

Resource Use Study In COPD (RUSIC): A prospective study to quantify the effects of COPD exacerbations on health care resource use among COPD patients

PubMed Central

FitzGerald, J Mark; Haddon, Jennifer M; Bradley-Kennedy, Carole; Kuramoto, Lisa; Ford, Gordon T

2007-01-01

BACKGROUND: There is increasing interest in health care resource use (HRU) in Canada, particularly in resources associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). OBJECTIVE: To identify HRU due to exacerbations of COPD. METHODS: A 52-week, multicentre, prospective, observational study of HRU due to exacerbations in patients with moderate to severe COPD was performed. Patients were recruited from primary care physicians and respirologists in urban and rural centres in Canada. RESULTS: In total, 524 subjects (59% men) completed the study. Their mean age was 68.2±9.4 years, with a forced expiratory volume in 1 s of 1.01±0.4 L. Patients had significant comorbidities. There were 691 acute exacerbations of COPD, which occurred in 53% of patients: 119 patients (23%) experienced one acute exacerbation, 70 patients (13%) had two acute exacerbations and 89 patients (17%) had three or more acute exacerbations. Seventy-five patients were admitted to hospital, with an average length of stay of 13.2 days. Fourteen of the patients spent time in an intensive care unit (average length of stay 5.6 days). Factors associated with acute exacerbations of COPD included lower forced expiratory volume in 1 s (P<0.001), high number of respiratory medications prescribed (P=0.037), regular use of oral corticosteroids (OCSs) (P=0.008) and presence of depression (P<0.001). Of the 75 patients hospitalized, only 53 received OCSs, four received referral for rehabilitation and 15 were referred for home care. CONCLUSIONS: The present study showed a high prevalence of COPD exacerbations, which likely impacted on HRU. There was evidence of a lack of appropriate management of exacerbations, especially with respect to use of OCSs, and referral for pulmonary rehabilitation and home care. PMID:17464378

Risk factors for COPD exacerbations in inhaled medication users: the COPDGene study biannual longitudinal follow-up prospective cohort.

PubMed

Busch, Robert; Han, MeiLan K; Bowler, Russell P; Dransfield, Mark T; Wells, J Michael; Regan, Elizabeth A; Hersh, Craig P

2016-02-10

Despite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the COPDGene Study taking inhaled medications. 2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta-agonist/inhaled-corticosteroid (ICS ± LABA), tiotropium alone, ICS ± LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS ± LABA. In separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS ± LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 [95 % CI 0.45, 1.06], p = 0.09) compared with ICS ± LABA users, especially in subjects without comorbid asthma (OR = 0.56 [95% CI 0.31, 1.00], p = 0.05). Each common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS ± LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma. ClinicalTrials.gov NCT00608764, first received 1/28/2008.

Detecting COPD exacerbations early using daily telemonitoring of symptoms and k-means clustering: a pilot study.

PubMed

Sanchez-Morillo, Daniel; Fernandez-Granero, Miguel Angel; Jiménez, Antonio León

2015-05-01

COPD places an enormous burden on the healthcare systems and causes diminished health-related quality of life. The highest proportion of human and economic cost is associated with admissions for acute exacerbation of respiratory symptoms (AECOPD). Since prompt detection and treatment of exacerbations may improve outcomes, early detection of AECOPD is a critical issue. This pilot study was aimed to determine whether a mobile health system could enable early detection of AECOPD on a day-to-day basis. A novel electronic questionnaire for the early detection of COPD exacerbations was evaluated during a 6-months field trial in a group of 16 patients. Pattern recognition techniques were applied. A k-means clustering algorithm was trained and validated, and its accuracy in detecting AECOPD was assessed. Sensitivity and specificity were 74.6 and 89.7 %, respectively, and area under the receiver operating characteristic curve was 0.84. 31 out of 33 AECOPD were early identified with an average of 4.5 ± 2.1 days prior to the onset of the exacerbation that was considered the day of medical attendance. Based on the findings of this preliminary pilot study, the proposed electronic questionnaire and the applied methodology could help to early detect COPD exacerbations on a day-to-day basis and therefore could provide support to patients and physicians.

[The use of fenspiride for the combined treatment of exacerbation of chronic laryngitis].

PubMed

Ryabova, M A

The present study was carried out based at the Department of Otorhinolaryngology of I.P. Pavlov First State Medical University of Saint-Petersburg. The objective of this work was to elucidate the efficacy and safety of fenspiride therapy for the treatment of exacerbation of chronic laryngitis associated with an acute respiratory infection. The patients comprising the main group received fenspiride (Eurespal, 'Servier', France) at the standard dose in addition to the conventional therapy with the use of antibiotics, inhalation, and voice rest. The patients in the group of comparison were treated following the conventional protocol without fenspiride. The clinical symptoms evaluated based on the scoring system, the results of videolaryngoscopy, and computer-assisted analysis of the voice were compared before and after treatment in the patients of both groups. The results of the study have confirmed the high effectiveness and safety of fenspiride therapy of exacerbation of chronic laryngitis.

Pathophysiology of viral-induced exacerbations of COPD

PubMed Central

Alfredo, Potena; Gaetano, Caramori; Paolo, Casolari; Marco, Contoli; Johnston, Sebastian L; Alberto, Papi

2007-01-01

Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD). Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors. In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner. Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation. Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations. In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation. PMID:18268922

[Gastro-esophageal reflux and chronic respiratory diseases].

PubMed

Dirou, S; Germaud, P; Bruley des Varannes, S; Magnan, A; Blanc, F-X

2015-12-01

Gastroesophageal reflux disease (GERD) frequently occurs in association with chronic respiratory diseases although the casual link is not always clear. Several pathophysiological and experimental factors are considered to support a role for GERD in respiratory disease. Conversely, respiratory diseases and bronchodilator treatment can themselves exacerbate GERD. When cough or severe asthma is being investigated, GERD does not need to be systematically looked for and a therapeutic test with proton pump inhibitors is not always recommended. pH impedance monitoring is now the reference diagnostic tool to detect non acid reflux, a form of reflux for which proton pump inhibitor treatment is ineffective. Recent data have shown a potential role of GERD in idiopathic pulmonary fibrosis and bronchiolitis obliterans following lung transplantation, leading to discussions about the place of surgery in this context. However, studies using pH impedance monitoring are still needed to better understand and manage the association between GERD and chronic respiratory diseases. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Anti-Aspergillus Activities of the Respiratory Epithelium in Health and Disease.

PubMed

Bertuzzi, Margherita; Hayes, Gemma E; Icheoku, Uju J; van Rhijn, Norman; Denning, David W; Osherov, Nir; Bignell, Elaine M

2018-01-08

Respiratory epithelia fulfil multiple roles beyond that of gaseous exchange, also acting as primary custodians of lung sterility and inflammatory homeostasis. Inhaled fungal spores pose a continual antigenic, and potentially pathogenic, challenge to lung integrity against which the human respiratory mucosa has developed various tolerance and defence strategies. However, respiratory disease and immune dysfunction frequently render the human lung susceptible to fungal diseases, the most common of which are the aspergilloses, a group of syndromes caused by inhaled spores of Aspergillus fumigatus . Inhaled Aspergillus spores enter into a multiplicity of interactions with respiratory epithelia, the mechanistic bases of which are only just becoming recognized as important drivers of disease, as well as possible therapeutic targets. In this mini-review we examine current understanding of Aspergillus -epithelial interactions and, based upon the very latest developments in the field, we explore two apparently opposing schools of thought which view epithelial uptake of Aspergillus spores as either a curative or disease-exacerbating event.

[Specific aspects and care of lung involvement in adults with cystic fibrosis].

PubMed

Pin, I; Grenet, D; Scheid, P; Domblides, P; Stern, M; Hubert, D

2000-08-01

Respiratory impairment is present in almost all adult cystic fibrosis patients and makes the prognosis. Viscous, infected and abundant secretions, inflammation and bronchial oedema, bronchoconstriction and respiratory muscle fatigue lead to airway obstruction, bronchiectasis and respiratory failure. The disease is preferentially located in the upper lobes. Exacerbations of the disease are due to bronchial infections and are often responsible for drops of the respiratory function. Regular spirometric surveillance is fundamental for the prognosis and the assessment of the effects of the treatment. Among adult patients chronic colonisation with mucoid and often multiresistant strains of Pseudomonas Aeruginosa are common. It is treated with i.v. high doses antibiotic courses and nebulized antibiotics between i.v. courses. Respiratory failure may require long term oxygen and non invasive mechanical ventilation. Systemic hypervascularization around the bronchiectasis may lead to moderate to severe hemoptysis, which may require embolization. Pneumothorax are associated with poor prognosis and are treated by pleural drainage and if failure by thoracoscopy.

Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a Rational Approach.

PubMed

Dugani, Sagar; Ames, Jeffrey M; Manson, JoAnn E; Mora, Samia

2018-02-21

The role of aspirin in secondary cardiovascular prevention is well understood; however, the role in primary prevention is less clear, and requires careful balancing of potential benefits with risks. Here, we summarize the evidence base on the benefits and risks of aspirin therapy, discuss clinical practice guidelines and decision support tools to assist in initiating aspirin therapy, and highlight ongoing trials that may clarify the role of aspirin in cardiovascular disease prevention. In 2016, the USPSTF released guidelines on the use of aspirin for primary prevention. Based on 11 trials (n = 118,445), aspirin significantly reduced all-cause mortality and nonfatal myocardial infarction, and in 7 trials that evaluated aspirin ≤ 100 mg/day, there was significant reduction in nonfatal stroke. The USPSTF recommends individualized use of aspirin based on factors including age, 10-year atherosclerotic cardiovascular disease risk score, and bleeding risk. Several ongoing trials are evaluating the role of aspirin in primary prevention, secondary prevention, and in combination therapy for atrial fibrillation. Evidence-based approaches to aspirin use should consider the anti-ischemic benefits and bleeding risks from aspirin. In this era of precision medicine, tools that provide the personalized benefit to risk assessment, such as the freely available clinical decision support tool (Aspirin-Guide), can be easily incorporated into the electronic health record and facilitate more informed decisions about initiating aspirin therapy for primary prevention. Aspirin has a complex matrix of benefits and risks, and its use in primary prevention requires individualized decision-making. Results from ongoing trials may guide healthcare providers in identifying appropriate candidates for aspirin therapy.

The difference in association between aspirin use and other thrombocyte aggregation inhibitors and survival in patients with colorectal cancer.

PubMed

Frouws, M A; Rademaker, E; Bastiaannet, E; van Herk-Sukel, M P P; Lemmens, V E; Van de Velde, C J H; Portielje, J E A; Liefers, G J

2017-05-01

Several studies have suggested that the association between aspirin and improved cancer survival is mediated through the mechanism of aspirin as thrombocyte aggregation inhibitors (TAI). The aim of this study was to provide epidemiological evidence for this mechanism assessing the association between overall survival and the use of aspirin and non-aspirin TAI in patients with colorectal cancer. In this observational study, data from the Netherlands Comprehensive Cancer Organisation were linked to PHARMO Database Network. Patients using aspirin or aspirin in combination with non-aspirin TAI (dual users) were selected and compared with non-users. The association between overall survival and the use of (non-)aspirin TAI was analysed using Cox regression models with the use of (non-)aspirin TAI as a time-varying covariate. In total, 9196 patients were identified with colorectal cancer and 1766 patients used TAI after diagnosis. Non-aspirin TAI were mostly clopidogrel and dipyridamole. Aspirin use was associated with a significant increased overall survival and hazard ratio (HR) 0.41 (95% confidence interval [CI] 0.37-0.47), and the use of non-aspirin TAI was not associated with survival of HR 0.92 (95% CI 0.70-1.22). Dual users did not have an improved overall survival when compared with patients using solely aspirin. Aspirin use after diagnosis of colorectal cancer was associated with significantly lower mortality rates and this effect remained significant after adjusting for potential confounders. No additional survival benefit was observed in patients using both aspirin and another TAI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preparation and analysis of deuterium-labeled aspirin: application to pharmacokinetic studies

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

Pedersen, A.K.; FitzGerald, G.A.

Inhibition of endogenous prostacyclin and thromboxane biosynthesis by aspirin is critically dose-dependent in humans. Gastrointestinal and hepatic hydrolysis may limit systemic availability of aspirin, especially in low doses, perhaps contributing to the biochemical selectivity of aspirin. Existing analytical methods do not permit determination of systemic bioavailability when low (less than 100 mg) doses of aspirin are administered. Deuterium-labeled aspirin (2-acetoxy(3,4,5,6-/sup 2/H4)benzoic acid) was synthesized from salicylic acid by catalytic exchange and subsequent acetylation. Analysis of the compounds as benzyl esters by GC-MS followed extractive alkylation from plasma. Heptadeuterated compounds were used as internal standards. Simultaneous administration of tetradeuterated aspirin intravenouslymore » with native aspirin orally to anesthetized dogs permitted kinetic studies of both aspirin and salicylic acid. The sensitivity of the method is superior to published methods using HPLC and, thus, more applicable to studies of low dose aspirin. Pulse administration of stable isotope-labeled aspirin permits detailed and repeated studies of dose-related aspirin pharmacokinetics in humans.« less

Health effects of the Federal Bureau of Prisons tobacco ban

PubMed Central

2012-01-01

Background Tobacco smoking remains the leading cause of preventable death in America, claiming 450,000 lives annually. Chronic Obstructive Pulmonary Disease, caused by smoking in the vast majority of cases, became the third leading cause of death in the U.S. in 2008. The burden of asthma, often exacerbated by tobacco exposure, has widespread clinical and public health impact. Despite this considerable harm, we know relatively little about the natural history of lung disease and respiratory impairment in adults, especially after smoking cessation. Methods/Design Our paper describes the design and rationale for using the 2004 Federal Bureau of Prisons tobacco ban to obtain insights into the natural history of respiratory diseases in adult men and women of different races/ethnicities who are imprisoned in federal medical facilities. We have developed a longitudinal study of new prison arrivals, with data to be collected from each participant over the course of several years, through the use of standardized questionnaires, medical chart reviews, lung function tests, six-minute walk tests, and stored serum for the analysis of present and future biomarkers. Our endpoints include illness exacerbations, medication and health services utilization, lung function, serum biomarkers, and participants’ experience with their health and nicotine addiction. Discussion We believe the proposed longitudinal study will make a substantial contribution to the understanding and treatment of respiratory disease and tobacco addiction. PMID:23067295

Host response to secondary bacterial infection associated with antecedent influenza virus infection in pigs – exacerbation associated with vaccination

USDA-ARS?s Scientific Manuscript database

The increasing number of annual influenza (IAV) cases, coupled with the recent IAV pandemic, has amplified concerns about its impact on human and animal health. It is appreciated that Flu is complicated by bacterial pneumonia. Vaccine-associated enhanced respiratory disease (VAERD) can occur followi...

Diesel, children and respiratory disease

PubMed Central

Liu, Norrice M

2018-01-01

Air pollution generated in urban areas is a global public health burden since half of the world’s population live in either cities, megacities or periurban areas. Its direct effects include initiating and exacerbating disease, with indirect effects on health mediated via climate change putting the basic needs of water, air and food at risk. PMID:29862329

Indoor Molds and Respiratory Hypersensitivity: A Comparison of Selected Molds and House Dust Mite Induced Responses in a Mouse Model**

EPA Science Inventory

Molds are ubiquitous in the environment and exposures to molds contribute to various human diseases. Damp/moldy environments have been associated with asthma exacerbation, but mold's role in allergic asthma induction is less clear. The molds selected for these studies are commonl...

Modeling asthma: Pitfalls, promises, and the road ahead.

PubMed

Rosenberg, Helene F; Druey, Kirk M

2018-02-16

Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource. ©2018 Society for Leukocyte Biology.

Pulmonary gas exchange in acute respiratory failure.

PubMed

Rodriguez-Roisin, R

1994-01-01

The principal function of the lung is to facilitate the exchange of the respiratory gases, oxygen (O2) and carbon dioxide (CO2). When the lung fails as a gas exchanger respiratory failure ensues. Clinically, it is generally accepted that an arterial oxygen tension (PaO2) of less than 60 mmHg or a PaCO2 of greater than 50 mmHg, or both, whilst breathing room air are values consistent with the concept of respiratory failure. This article will deal, firstly, with some basic aspects of the physiology of pulmonary gas exchange and more specifically on the measurement of ventilation-perfusion (VA/Q) relationships, the most influential factor determining hypoxaemia. The second part highlights the most important findings on pulmonary gas exchange in the adult respiratory distress syndrome (ARDS) and other common acute respiratory failure conditions, such as pneumonia, acute exacerbation of chronic obstructive pulmonary disease (COPD) and status asthmaticus, based on the data obtained by means of the multiple inert gas elimination approach, a technique which gives a detailed picture of VA/Q ratio distributions.

Tobacco use among designated air pollution victims and its association with lung function and respiratory symptoms: a retrospective cross-sectional study

PubMed Central

Kotaki, Kenji; Senjyu, Hideaki; Tanaka, Takako; Yano, Yudai; Miyamoto, Naomi; Nishinakagawa, Tsuyoshi; Yanagita, Yorihide; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Sawai, Terumitsu; Honda, Sumihisa

2014-01-01

Objectives We sought to elucidate the long-term association of tobacco use and respiratory health in designated pollution victims with and without obstructive pulmonary defects. Design A retrospective cross-sectional study. Setting The register of pollution victims in Kurashiki, Japan. Participants 730 individuals over 65 years of age previously diagnosed with pollution-related respiratory disease. Patients were classified into four groups according to their smoking status and whether they had obstructive pulmonary disease. We then compared the prevalence of respiratory symptoms and lung function over time between groups. Primary outcome measures Spirometry was performed and a respiratory health questionnaire completed in the same season each year for up to 30 years. Results Rates of smoking and respiratory disease were high in our sample. Although respiratory function in non-smoking patients did not completely recover, the annual rate of change in lung function was within the normal range (p<0.01). However, smokers had worse lung function and were more likely to report more severe pulmonary symptoms (p<0.01). Conclusions Patients’ respiratory function did not fully recover despite improved air quality. Our results suggest that, in the context of exposure to air pollution, tobacco use causes additional loss of lung function and exacerbates respiratory symptoms. PMID:25082419

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.

Approaches to the diagnosis and management of patients with a history of nonsteroidal anti-inflammatory drug-related urticaria and angioedema.

PubMed

Kowalski, Marek L; Woessner, Katharine; Sanak, Marek

2015-08-01

Nonsteroidal anti-inflammatory drug (NSAID)-induced urticarial and angioedema reactions are among the most commonly encountered drug hypersensitivity reactions in clinical practice. Three major clinical phenotypes of NSAID-induced acute skin reactions manifesting with angioedema, urticaria, or both have been distinguished: NSAID-exacerbated cutaneous disease, nonsteroidal anti-inflammatory drug-induced urticaria/angioedema (NIUA), and single NSAID-induced urticaria and angioedema. In some patients clinical history alone might be sufficient to establish the diagnosis of a specific type of NSAID hypersensitivity, whereas in other cases oral provocation challenges are necessary to confirm the diagnosis. Moreover, classification of the type of cutaneous reaction is critical for proper management. For example, in patients with single NSAID-induced reactions, chemically nonrelated COX-1 inhibitors can be safely used. However, there is cross-reactivity between the NSAIDs in patients with NSAID-exacerbated cutaneous disease and NIUA, and thus only use of selective COX-2 inhibitors can replace the culprit drug if the chronic treatment is necessary, although aspirin desensitization will allow for chronic treatment with NSAIDs in some patients with NIUA. In this review we present a practical clinical approach to the patient with NSAID-induced urticaria and angioedema. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Is there an ideal way to initiate antiplatelet therapy with aspirin? A crossover study on healthy volunteers evaluating different dosing schemes with whole blood aggregometry

PubMed Central

2011-01-01

Background Guidelines recommend an early initiation of aspirin treatment in patients with acute cerebral ischemia. Comparative studies on the best starting dose for initiating aspirin therapy to achieve a rapid antiplatelet effect do not exist. This study evaluated the platelet inhibitory effect in healthy volunteers by using three different aspirin loading doses to gain a model for initiating antiplatelet treatment in acute strokes patients. Methods Using whole blood aggregometry, this study with a prospective, uncontrolled, open, crossover design examined 12 healthy volunteers treated with three different aspirin loading doses: intravenous 500 mg aspirin, oral 500 mg aspirin, and a course of 200 mg aspirin on two subsequent days followed by a five-day course of 100 mg aspirin. Aspirin low response was defined as change of impedance exceeding 0 Ω after stimulation with arachidonic acid. Results Sufficient antiplatelet effectiveness was gained within 30 seconds when intravenous 500 mg aspirin was used. The mean time until antiplatelet effect was 74 minutes for 500 mg aspirin taken orally and 662 minutes (11.2 hours) for the dose scheme with 200 mg aspirin with a high inter- and intraindividual variability in those two regimes. Platelet aggregation returned to the baseline range during the wash-out phase within 4 days. Conclusion Our study reveals that the antiplatelet effect differs significantly between the three different aspirin starting dosages with a high inter- and intraindividual variability of antiplatelet response in our healthy volunteers. To ensure an early platelet inhibitory effect in acute stroke patients, it could be advantageous to initiate the therapy with an intravenous loading dose of 500 mg aspirin. However, clinical outcome studies must still define the best way to initiate antiplatelet treatment with aspirin. PMID:21466682

Dipyrone comedication in aspirin treated stroke patients impairs outcome.

PubMed

Dannenberg, Lisa; Erschoff, Vladimir; Bönner, Florian; Gliem, Michael; Jander, Sebastian; Levkau, Bodo; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias; Polzin, Amin

2016-12-01

>50% of stroke patients rely on analgesic medication to control pain. Aspirin is the mainstay of medical treatment of stroke patients; however analgesic medication with dipyrone impairs aspirin antiplatelet effects ex-vivo. The clinical impact of this impairment is unknown. Therefore, we aimed to determine aspirin antiplatelet effects and neurological outcome in stroke patients with aspirin and dipyrone comedication. We conducted a prospective cohort study in 41 patients with stroke. Primary outcome was pharmacodynamic response to aspirin in dipyrone treated stroke patients. Secondary outcome was neurological recovery after stroke. Pharmacodynamic response to aspirin was measured using arachidonic acid induced aggregation in light-transmission aggregometry. Neurological outcome was determined three months after stroke onset by telephone interview. Patient's characteristics were similar in the aspirin-alone group and the aspirin+dipyrone group. Impaired pharmacodynamic response to aspirin occurred in 62% (14/21) of patients with aspirin and dipyrone co-medication. Only 10% (2/20) of aspirin treated patients without analgesic comedication displayed residual platelet reactivity (P=0.001; odds ratio [OR], 18 [95% CI, 3.2-100]). Excellent neurological recovery (measured by three months follow-up modified Rankin Scale<2) was observed in 80% (16/20) of patients in the aspirin-alone group and 48% (10/21) of patients in the aspirin+dipyrone group (P=0.037; OR, 4.4 [95% CI, 1.1-17.7]). Dipyrone comedication in patients with stroke impairs pharmacodynamic response to aspirin. This is associated with worse clinical outcome. Therefore dipyrone should be used with caution in aspirin treated stroke patients. https://clinicaltrials.gov/show/NCT02148939; Identifier: NCT02148939. Copyright © 2016 Elsevier Inc. All rights reserved.

AMPK-mediated up-regulation of mTORC2 and MCL-1 compromises the anti-cancer effects of aspirin

PubMed Central

Hua, Hui; Yin, Yancun; Wang, Jiao; Luo, Ting; Jiang, Yangfu

2016-01-01

AMP-activated protein kinase (AMPK) is an important energy sensor that may inhibit cell proliferation or promote cell survival during stresses. Besides cyclooxygenase, AMPK is another target of the nonsteroid anti-inflammatory agent aspirin. Preclinical and clinical investigations demonstrate that aspirin can inhibit several types of cancer such as colorectal adenomas and hepatocellular carcinoma (HCC). However, little is known about the cellular response to aspirin that may lead to aspirin resistance. Here, we show that aspirin induces the expression of MCL-1 in HepG2 and SW480 cells through AMPK-mTOR-Akt/ERK axis. Treatment of HepG2 and SW480 cells with aspirin leads to increased MCL-1 expression, Akt and ERK1/2 phosphorylation. Inhibition of Akt/MEK abrogates the induction of MCL-1 by aspirin. Aspirin activates AMPK, which in turn up-regulates mTORC2 activity, Akt, ERK1/2 phosphorylation and MCL-1 expression. MCL-1 knockdown sensitizes cancer cells to aspirin-induced apoptosis. Combination of aspirin and AMPK, Akt or MEK inhibitor results in more significant inhibition of cell proliferation and induction of apoptosis than single agent. Moreover, sorafenib blocks aspirin-induced MCL-1 up-regulation. Combination of aspirin and sorafenib leads to much more cell death and less cell proliferation than each drug alone. Treatment of HCC and colon cancer xenografts with both aspirin and sorafenib results in more significant tumor suppression than single agent. These data demonstrate that AMPK-mediated up-regulation of mTORC2 and MCL-1 may compromise the anticancer effects of aspirin. Combination of aspirin and sorafenib may be an effective regimen to treat HCC and colon cancer. PMID:26918349

Clinical and Immunological Benefits of OM-85 Bacterial Lysate in Patients with Allergic Rhinitis, Asthma, and COPD and Recurrent Respiratory Infections.

PubMed

Koatz, Ana M; Coe, Noemí A; Cicerán, Alberto; Alter, Adriana J

2016-08-01

The aim of this study was to evaluate the efficacy of OM-85 in reducing the incidence of respiratory tract infections (RTIs) in patients with allergic rhinitis, asthma, or chronic obstructive pulmonary disease (COPD), and its effect on immunological parameters, namely serum and secretory IgA levels. This was an open-label, prospective, sequential study which included 84 consecutive patients aged 16-65 years, who presented with recurrent (three or more) respiratory infections during the year prior to study entry. In the first year of the study, patients received standard optimized care (SOC), according to their underlying disease condition (asthma, allergic rhinitis, or COPD). In the following year, patients received treatment with OM-85 oral bacterial lysate (one 7 mg capsule daily for ten consecutive days per month, for 3 months), with a 6-month follow-up. Medical history, clinical symptoms, serum, and secretory IgA levels, and the number of infections and exacerbations were evaluated before and after treatment. There was a decrease in the total number of RTIs before the OM-85 treatment period (SOC only) compared to the year before the study start [69/266 (corresponding to a 74 % reduction)] and an additional decrease [38/69 (corresponding to a 45 % reduction)] after OM-85 treatment; p < 0.05. There was also a significant reduction in the total number of exacerbations related to the patients' underlying medical conditions, which decreased from 55 to 35 during OM-85 (+SOC) treatment, corresponding to a reduction of 36 %. In addition, an increase in serum and secretory IgA levels which coincided with the administration of OM-85 was observed. Our results showed the clinical benefits of OM-85 in reducing RTIs and exacerbations of the underlying medical condition, in patients with allergic rhinitis, asthma, or COPD.

Epidemiologic evidence for asthma and exposure to air toxics: linkages between occupational, indoor, and community air pollution research.

PubMed Central

Delfino, Ralph J

2002-01-01

Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma. However, the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures. Occupational exposures associated with asthma may yield clues to causal components in ambient air pollution because such exposures are often identifiable as single-chemical agents (e.g., metal compounds). However, translating occupational to community exposure-response relationships is limited. Of the air toxics found to cause occupational asthma, only formaldehyde has been frequently investigated in epidemiologic studies of allergic respiratory responses to indoor air, where general consistency can be shown despite lower ambient exposures. The specific volatile organic compounds (VOCs) identified in association with occupational asthma are generally not the same as those in studies showing respiratory effects of VOC mixtures on nonoccupational adult and pediatric asthma. In addition, experimental evidence indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to diesel exhaust particles (DEPs) have proinflammatory effects on airways, but there is insufficient supporting evidence from the occupational literature of effects of DEPs on asthma or lung function. In contrast, nonoccupational epidemiologic studies have frequently shown associations between allergic responses or asthma with exposures to ambient air pollutant mixtures with PAH components, including black smoke, high home or school traffic density (particularly truck traffic), and environmental tobacco smoke. Other particle-phase and gaseous co-pollutants are likely causal in these associations as well. Epidemiologic research on the relationship of both asthma onset and exacerbation to air pollution is needed to disentangle effects of air toxics from monitored criteria air pollutants such as particle mass. Community studies should focus on air toxics expected to have adverse respiratory effects based on biological mechanisms, particularly irritant and immunological pathways to asthma onset and exacerbation. PMID:12194890

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts.

PubMed

McDonnell, M J; Aliberti, S; Goeminne, P C; Dimakou, K; Zucchetti, S C; Davidson, J; Ward, C; Laffey, J G; Finch, S; Pesci, A; Dupont, L J; Fardon, T C; Skrbic, D; Obradovic, D; Cowman, S; Loebinger, M R; Rutherford, R M; De Soyza, A; Chalmers, J D

2016-12-01

Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of 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/.

Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

PubMed Central

Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A.; Propert, Kathleen J.; Diamond, Scott L.; Blair, Ian A.; FitzGerald, Garret A.; Grosser, Tilo

2014-01-01

The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

Prevention of respiratory tract infections with bacterial lysate OM-85 bronchomunal in children and adults: a state of the art

PubMed Central

2013-01-01

Respiratory tract infections (RTIs) are a leading cause of morbidity and also represent a cause of death in some parts of the world. The treatment of RTIs implies a continuous search for stronger therapies and represents an economical burden for health services and society. In this context the prevention of infections is absolutely required. The use of bacterial lysates as immuno-modulators to boost immunological response is widely debated. Aim of this review is to summarize the main clinical studies on the effect of the bacterial lysate OM-85 in treating RTIs in susceptible subjects - namely children and chronic obstructive pulmonary disease (COPD)-affected adults. Results from clinical trials and recent systematic reviews are reported. The results show that mean number of RTIs decreases upon treatment with OM-85, as measured by frequency of exacerbations or number of antibiotic courses. Data from systematic reviews indicated that OM-85 is particularly beneficial in children at high risk of RTIs. In COPD-affected adults, clinical studies showed that treatment with OM-85 reduced exacerbations, although systematic reviews did not legitimate the protective effect of OM-85 toward COPD as significant. The use of OM-85 could be efficacious in reducing exacerbation frequency of RTIs in children and adults at risk. However further high-quality studies are needed to better explain the mechanism of action and confirm the beneficial results of OM85. PMID:23692890

Protein tyrosine phosphatase 1B negatively regulates S100A9-mediated lung damage during respiratory syncytial virus exacerbations.

PubMed

Foronjy, R F; Ochieng, P O; Salathe, M A; Dabo, A J; Eden, E; Baumlin, N; Cummins, N; Barik, S; Campos, M; Thorp, E B; Geraghty, P

2016-09-01

Protein tyrosine phosphatase 1B (PTP1B) has anti-inflammatory potential but PTP1B responses are desensitized in the lung by prolonged cigarette smoke exposure. Here we investigate whether PTP1B expression affects lung disease severity during respiratory syncytial viral (RSV) exacerbations of chronic obstructive pulmonary disease (COPD). Ptp1b(-/-) mice infected with RSV exhibit exaggerated immune cell infiltration, damaged epithelial cell barriers, cytokine production, and increased apoptosis. Elevated expression of S100A9, a damage-associated molecular pattern molecule, was observed in the lungs of Ptp1b(-/-) mice during RSV infection. Utilizing a neutralizing anti-S100A9 IgG antibody, it was determined that extracellular S100A9 signaling significantly affects lung damage during RSV infection. Preexposure to cigarette smoke desensitized PTP1B activity that coincided with enhanced S100A9 secretion and inflammation in wild-type animals during RSV infection. S100A9 levels in human bronchoalveolar lavage fluid had an inverse relationship with lung function in healthy subjects, smokers, and COPD subjects. Fully differentiated human bronchial epithelial cells isolated from COPD donors cultured at the air liquid interface secreted more S100A9 than cells from healthy donors or smokers following RSV infection. Together, these findings show that reduced PTP1B responses contribute to disease symptoms in part by enhancing S100A9 expression during viral-associated COPD exacerbations.

Pneumonia as comorbidity in chronic obstructive pulmonary disease (COPD). Differences between acute exacerbation of COPD and pneumonia in patients with COPD.

PubMed

Boixeda, Ramon; Bacca, Sandra; Elias, Lorena; Capdevila, Josep Anton; Vilà, Xavier; Mauri, Montserrat; Almirall, Jordi

2014-12-01

Pneumonia is considered an independent entity in chronic obstructive pulmonary disease (COPD), to be distinguished from an infectious exacerbation of COPD. The aim of this study was to analyze the clinical characteristics and progress of the exacerbation of COPD (ECOPD) compared to pneumonia in COPD (PCOPD) patients requiring hospitalization. Prospective, longitudinal, observational cohort study including 124 COPD patients requiring hospital admission for lower respiratory tract infection. Patients were categorized according to presence of ECOPD (n=104) or PCOPD (n=20), depending on presence of consolidation on X-ray. Demographic, clinical, laboratory, microbiological and progress variables were collected. Patients with ECOPD showed more severe respiratory disease according to the degree of obstruction (P<.01) and need for oxygen therapy (P<.05). PCOPD patients showed increased presence of fever (P<.05), lower blood pressure (P<.001), more laboratory abnormalities (P<.05; leukocytosis, elevated CRP, low serum albumin) and increased presence of crepitus (P<.01). Microbiological diagnosis was achieved in 30.8% of cases of ECOPD and 35% of PCOPD; sputum culture yielded the highest percentage of positive results, predominantly Pseudomonas aeruginosa. Regarding the progress of the episode, no differences were found in hospital stay, need for ICU or mechanical ventilation. Our data confirm clinical and analytical differences between ECOPD and PCOPD in patients who require hospital admission, while there were no differences in subsequent progress. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

The effect of aspirin dosing on platelet function in diabetic and nondiabetic patients: an analysis from the aspirin-induced platelet effect (ASPECT) study.

PubMed

DiChiara, Joseph; Bliden, Kevin P; Tantry, Udaya S; Hamed, Miruais S; Antonino, Mark J; Suarez, Thomas A; Bailon, Oscar; Singla, Anand; Gurbel, Paul A

2007-12-01

Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients. Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients. We examined the effect of aspirin (81, 162, and 325 mg/day for 4 weeks each) on platelet aspirin responsiveness in 120 stable outpatients (30 diabetic patients and 90 nondiabetic patients) with coronary artery disease (CAD) using light transmittance aggregometry (LTA), VerifyNow, platelet function analyzer (PFA)-100, and levels of urinary 11-dehydro-thromboxane B(2) (11-dh-TxB(2)). In the total group, a low prevalence (0-2%) of aspirin resistance was observed with all aspirin doses as determined by arachidonic acid-induced LTA. Aspirin resistance was higher at the 81-mg dose in diabetic versus nondiabetic patients using collagen-induced LTA (27 vs. 4%, P = 0.001), VerifyNow (13 vs. 3%, P = 0.05), and urinary 11-dh-TxB(2) (37 vs. 17%, P = 0.03). Diabetic patients treated with 81 mg exhibited higher platelet function measured by VerifyNow, collagen- and ADP-induced LTA, and 11-dh-TxB(2) levels (P

Combination antiplatelet therapy with aspirin and clopidogrel: the role of antecedent and concomitant doses of aspirin. An analysis of 711 patients.

PubMed

Serebruany, Victor L; Malinin, Alex I; Atar, Dan

2007-01-01

Numerous randomized studies have shown that the combination of clopidogrel with aspirin yields better clinical outcomes than monotherapy in patients with acute vascular events. However, the impact of the aspirin dose on the antiplatelet potency of clopidogrel is unclear. We sought to compare the antiplatelet profile of aspirin 81 mg (n = 252) versus aspirin 325 mg (n = 459) before and during conventional clopidogrel loading (300 mg), and/or clopidogrel maintenance (75 mg/daily) therapy. Secondary post hoc analysis of an existing dataset consisting of 711 patients after coronary stenting (n = 601) and ischemic stroke (n = 110) treated previously with aspirin for at least 1 month, and then with aspirin + clopidogrel for at least 7 days was performed. Platelet assessments include conventional and whole blood aggregometry, rapid cartridge-based analyzers, and expression of platelet/endothelial cell adhesion molecule-1, P-selectin, and GPIIb/IIIa activity by flow cytometry measured before and after addition of clopidogrel. There was a small but consistent yet non-significant trend towards more potent platelet inhibition with aspirin 325 mg compared to aspirin 81 mg for every platelet activation parameter before addition of clopidogrel. However, after loading and/or 1 week of chronic treatment with clopidogrel + aspirin, measured platelet parameters became very similar between the groups, and identical for collagen-induced aggregation and PFA-100 analyzer readings. Before addition of clopidogrel, aspirin 325 mg has a tendency to provide stronger platelet inhibition than aspirin 81 mg. However, when clopidogrel and aspirin are used in combination, the higher aspirin dose does not translate into superior antiplatelet action. Given that the existing body of evidence supports the comparable efficacy and, particularly, superior safety of lower versus higher doses of aspirin, aspirin 81 mg should be the dose used in combination with clopidogrel. 2007 S. Karger AG, Basel

Research priorities for respiratory nursing: a UK-wide Delphi study.

PubMed

Kelly, Carol Ann; Kirkcaldy, Andrew J; Pilkington, Melissa; Hodson, Matthew; Welch, Lindsay; Yorke, Janelle; Knighting, Katherine

2018-04-01

Respiratory nurses make a significant contribution to the delivery of respiratory healthcare, but there is a dearth of nurse-led, practice-focused, published research. Using a modified three-round Delphi, this study sought to identify research priorities for respiratory nursing to inform a national research strategy. Study information and the survey link were sent electronically to members of UK professional respiratory organisations. Round 1 had 78 items across 16 topics, informed by a systematic literature review. Respondents suggested additional items which were content analysed to inform Round 2. Respondents rated all items and ranked the topics in all rounds. To ensure rigour, rounds had an explicit focus with pre-determined criteria for consensus (70%). In total, 363 responses were received across Rounds 1, 2 and 3 (n=183, 95 and 85, respectively). The top five research priorities were: 1) "Patient understanding of asthma control"; 2) "The clinical and cost-effectiveness of respiratory nurse interventions"; 3) "The impact of nurse-led clinics on patient care"; 4) "Inhaler technique"; and 5) two topics jointly scored: "Prevention of exacerbations" and "Symptom management". With potential international significance, this is the first UK study to identify research priorities for respiratory nursing, providing direction for those planning or undertaking research.

Non-ST-segment elevation syndromes. Pharmacologic management, conservative versus early invasive approach.

PubMed

Santiago, Patrick; Tadros, Peter

2002-07-01

Many advances have been made in the treatment of acute coronary syndromes. Patients with intermediate-risk or high-risk features should receive treatment with the newer pharmacologic agents--enoxaparin, statins and, in selected cases, clopidogrel--in addition to established standard therapies (i.e., aspirin, beta-blockers, nitroglycerin, and oxygen). Use of GpIIb-IIIa inhibitors should also be strongly considered, especially in an early invasive approach. However, there is no substitute for a good physician who has the big picture and knows the individual patient in totality. This physician can best judge the dangers of the patient's acute cardiac condition against the comorbidities that may be exacerbated by revascularization procedures. The ability to weigh the risks of the patient's acute coronary syndrome against the risks of an aggressive invasive approach ultimately provides the best care for each patient.

Taking Aspirin to Protect Your Heart

MedlinePlus

Toolkit No. 23 Taking Aspirin to Protect Your Heart What can taking aspirin do for me? If you are at high risk for or if you have heart disease, taking a low dose aspirin every day may help. Aspirin can also help ...

Efficacy and Safety of Ticagrelor in Relation to Aspirin Use Within the Week Before Randomization in the SOCRATES Trial.

PubMed

Wong, K S Lawrence; Amarenco, Pierre; Albers, Gregory W; Denison, Hans; Easton, J Donald; Evans, Scott R; Held, Peter; Himmelmann, Anders; Kasner, Scott E; Knutsson, Mikael; Ladenvall, Per; Minematsu, Kazuo; Molina, Carlos A; Wang, Yongjun; Johnston, S Claiborne

2018-07-01

SOCRATES (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), comparing ticagrelor with aspirin in patients with acute cerebral ischemia, found a nonsignificant 11% relative risk reduction for stroke, myocardial infarction, or death ( P =0.07). Aspirin intake before randomization could enhance the effect of ticagrelor by conferring dual antiplatelet effect during a high-risk period for subsequent stroke. Therefore, we explored the efficacy and safety of ticagrelor versus aspirin in the patients who received any aspirin the week before randomization. A prespecified subgroup analysis in SOCRATES (n=13 199), randomizing patients with acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤5) or transient ischemic attack (ABCD 2 score of ≥4) to 90-day treatment with ticagrelor or aspirin. Patients in the prior-aspirin group had received any aspirin within the week before randomization. Primary end point was time to stroke, myocardial infarction, or death. Safety end point was PLATO (Study of Platelet Inhibition and Patient Outcomes) major bleeding. The 4232 patients in the prior-aspirin group were older, had more vascular risk factors, and vascular disease than the other patients. In the prior-aspirin group, the primary end point occurred in 138/2130 (6.5%) of patients on ticagrelor and in 177/2102 (8.3%) on aspirin (hazard ratio, 0.76; 95% confidence interval, 0.61-0.95; P =0.02); in patients with no prior-aspirin usage an event occurred in 304/4459 (6.9%) and 320/4508 (7.1%) on ticagrelor and aspirin, respectively (hazard ratio, 0.96; 95% confidence interval, 0.82-1.12; P =0.59). The treatment-by-prior-aspirin interaction was not statistically significant ( P =0.10). In the prior-aspirin group, major bleeding occurred in 0.7% and 0.4% of patients on ticagrelor and aspirin, respectively (hazard ratio, 1.58; 95% confidence interval, 0.68-3.65; P =0.28). In this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction. A new study will investigate the benefit-risk of combining ticagrelor and aspirin in patients with acute cerebral ischemia (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429). URL: https://www.clinicaltrials.gov. Unique identifier: NCT01994720. © 2018 American Heart Association, Inc.

Effects of Low-Dose Aspirin and Fish Oil on Platelet Function and NF-kappaB in Adults with Diabetes Mellitus

PubMed Central

Block, Robert C; Abdolahi, Amir; Smith, Brian; Meednu, N; Thevenet-Morrison, Kelly; Cai, Xueya; Cui, Huadong; Mousa, Shaker; Brenna, J. Thomas; Georas, S

2013-01-01

SUMMARY Introduction Many diabetics are insensitive to aspirin’s platelet anti-aggregation effects. The possible modulating effects of coadministration of aspirin and fish oil in subjects with diabetes are poorly characterized. Participants and Methods Thirty adults with type 2 diabetes mellitus were treated with aspirin 81 mg/d for 7 days, then with fish oil 4g/day for 28 days, then the combination of fish oil and aspirin for another 7 days. Results Aspirin alone and in combination with fish oil reduced platelet aggregation in most participants. Five of 7 participants classified as aspirin insensitive 1 week after daily aspirin ingestion were sensitive after the combination. Although some platelet aggregation measures correlated positively after aspirin and fish oil ingestion alone and (in combination) in all individuals, correlation was only observed in those who were aspirin insensitive after ingestion of the combination. Conclusions Co-adminstration of aspirin and fish oil may reduce platelet aggregation more than aspirin alone in adults with diabetes mellitus. PMID:23664596

Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: A prospective longitudinal study

PubMed Central

Leckman, James F.; King, Robert A.; Gilbert, Donald L.; Coffey, Barbara J.; Singer, Harvey S.; Dure, Leon S.; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J.; Kawikova, Ivana; Johnson, Dwight R.; Kurlan, Roger M.; Kaplan, Edward L.

2010-01-01

Objective The objective of this blinded, prospective longitudinal study was to determine whether new group A beta hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or obsessive-compulsive disorder without a PANDAS history served as the (non-PANDAS) comparison group. Method Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25 month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results. Results No group differences were observed in either the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions out of a total of 51 (12%) a newly diagnosed GABHS infection was followed, within two months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group. Conclusions This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria. PMID:21241948

Particularities of COPD exacerbations in different phenotypes of the disease in Tunisia.

PubMed

Zendah, Ines; Ayed, Khadija; Kwas, Hamida; Khattab, Amel; Ghédira, Habib

2016-03-01

Chronic Obstructive Pulmonary Disease is defined by a limitation of airflow. This disease is characterized by exacerbations that threaten the patient's life and worsens his prognosis. Moreover, COPD patients are different according to many parameters that define different phenotypes. Characteristics of exacerbations may depend on these phenotypes according to few recent studies. To determine the characteristics and the prognosis of the exacerbations in each phenotype of COPD patients phenotype in Tunisia. Retrospective study including 153 male patients hospitalized for COPD exacerbation from January 2009 to June 2012. Patients were classified into 4 phenotypes according to Burgel's classification. Patients were divided into four phenotypes: phenotype (PH)1: (n=68), PH2: (n=33), PH3: (n=25) and PH4: (n=27). Mean age for PH1, 2, 3 and 4 was: 61, 74, 56 and 72 years. The number of exacerbations per year was higher in PH1. Dyspnea was more important in PH1 and 4. Hypercapnia on admission was higher in PH4. Non invasive ventilation and transfer to resuscitation unit were more frequently mandatory in PH3 and 4.   Death occurred 2% of PH1 and 5% of PH4. Hospitalization duration was more important in PH4. COPD patients are heterogenous and belong to different phenotypes. The characteristics of the exacerbations and their prognosis widely differ according to these different groups. In Tunisia, it seems that patients who had moderate respiratory functional tests impairment are the lowest responders to treatment with a higher frequency of resuscitation unit transfer.

Platelet Inhibition by 81 and 325 mg Aspirin Daily in Men vs. Women without Clinically Apparent Cardiovascular Disease

PubMed Central

Qayyum, Rehan; Becker, Diane M.; Yanek, Lisa R.; Moy, Taryn F.; Becker, Lewis C.; Faraday, Nauder; Vaidya, Dhananjay

2011-01-01

Compared to men, women have greater platelet aggregation before and after low-dose aspirin. It is not known whether high-dose aspirin therapy brings residual platelet aggregation in women closer to men. Our objective was to compare the inhibition of platelet aggregation in women and men after low and high-dose aspirin. We enrolled healthy subjects (N=106) in a trial of 14 days of aspirin 81 mg/day followed by 14 days of 325 mg/day. Platelet function was measured at baseline and following both aspirin doses. Women had greater baseline platelet activation measures. After both aspirin doses, both sexes had near complete suppression of platelet aggregation to arachidonic acid in whole blood and in platelet-rich plasma (PRP), the direct cyclooxygenase-1 (COX-1) pathway affected by aspirin. For indirect pathways, women had significantly greater residual platelet activation to collagen and adenosine diphosphate (ADP) in whole blood after both aspirin doses and in response to collagen and ADP in PRP after aspirin 325 mg/day only. After aspirin 325 mg/day, women continued to have greater residual platelet aggregation compared to men after aspirin 81 mg/day in response to collagen (p=0.016 in whole blood and p=0.037 in PRP), ADP (p<0.001 in whole blood and p=0.012 in PRP), and epinephrine (p=0.03 in PRP). Excretion of urinary thromboxane metabolite (urinary 11-dehydro thromboxane B2) decreased after aspirin to a similar extent in both sexes. In conclusion, women continue to have greater residual platelet activity after high-dose aspirin even when compared to men treated with a lower dose of aspirin. PMID:18435972

Anti-tumor and Anti-angiogenic Effects of Aspirin-PC in Ovarian Cancer

PubMed Central

Huang, Yan; Lichtenberger, Lenard M.; Taylor, Morgan; Bottsford-Miller, Justin N.; Haemmerle, Monika; Wagner, Michael J.; Lyons, Yasmin; Pradeep, Sunila; Hu, Wei; Previs, Rebecca A.; Hansen, Jean M.; Fang, Dexing; Dorniak, Piotr L.; Filant, Justyna; Dial, Elizabeth J.; Shen, Fangrong; Hatakeyama, Hiroto; Sood, Anil K.

2016-01-01

To determine the efficacy of a novel and safer (for gastrointestinal tract) aspirin (aspirin-PC) in preclinical models of ovarian cancer, in vitro dose-response studies were performed to compare the growth-inhibitory effect of aspirin-PC vs. aspirin on 3 human (A2780, SKOV3ip1, HeyA8), and a mouse (ID8) ovarian cancer cell line over an 8-day culture period. In the in vivo studies, the aspirin test drugs were studied alone and in the presence of a VEGF-A inhibitor (bevacizumab or B20), due to an emerging role for platelets in tumor growth following anti-angiogenic therapy, and we examined their underlying mechanisms. Aspirin-PC was more potent (vs. aspirin) in blocking the growth of both human and mouse ovarian cancer cells in monolayer culture. Using in vivo model systems of ovarian cancer, we found that aspirin-PC significantly reduced ovarian cancer growth by 50–90% (depending on the ovarian cell line/density). The efficacy was further enhanced in combination with Bevacizumab or B20. The growth-inhibitory effect on ovarian tumor mass and number of tumor nodules was evident, but less pronounced for aspirin and the VEGF inhibitors alone. There was no detectable gastrointestinal toxicity. Both aspirin and aspirin-PC also inhibited cell proliferation, angiogenesis and increased apoptosis of ovarian cancer cells. In conclusion, PC-associated aspirin markedly inhibits the growth of ovarian cancer cells, which exceeds that of the parent drug, in both cell culture and in mouse model systems. We also found that both aspirin-PC and aspirin have robust anti-neoplastic action in the presence of VEGF blocking drugs. PMID:27638860

Evaluation of nitrate-substituted pseudocholine esters of aspirin as potential nitro-aspirins.

PubMed

Gilmer, John F; Moriarty, Louise M; Clancy, John M

2007-06-01

Herein we explore some designs for nitro-aspirins, compounds potentially capable of releasing both aspirin and nitric oxide in vivo. A series of nitrate-bearing alkyl esters of aspirin were prepared based on the choline ester template preferred by human plasma butyrylcholinesterase. The degradation kinetics of the compounds were followed in human plasma solution. All compounds underwent hydrolysis rapidly (t(1/2) approximately 1min) but generating exclusively the corresponding nitro-salicylate. The one exception, an N-propyl, N-nitroxyethyl aminoethanol ester produced 9.2% aspirin in molar terms indicating that the nitro-aspirin objective is probably achievable if due cognisance can be paid to the demands of the activating enzyme. Even at this low level of aspirin release, this compound is the most successful nitro-aspirin reported to date in the key human plasma model.

Aspirin resistance in systemic lupus erythematosus. A pilot study.

PubMed

Akdogan, A; Kilic, L; Akman, U; Dogan, I; Karadag, O; Bilgen, S A; Buyukasik, Y; Kiraz, S; Ertenli, I

2013-07-01

Systemic lupus erythematosus (SLE) patients are at increased risk of thrombosis and cardiovascular diseases. Aspirin is an effective treatment option for these patients. The aim of this study was to investigate the presence of aspirin resistance in SLE patients. We studied aspirin resistance in 33 SLE patients and nine healthy controls by using a Multiplate® impedance aggregometer (Dynabyte GmbH, Munich, Germany). Twenty-six SLE patients were on regular aspirin treatment. Aspirin resistance was found in five (19.2%) out of 26 patients who were on aspirin treatment. When the tests were repeated by adding acetylsalicylic acid in the medium, all of these patients became responsive to the aspirin. SLE disease activity, body mass index, smoking status, and the presence of anticardiolipin antibodies or positive lupus anticoagulant test results were no different in patients with or without aspirin resistance. (p>0.05 for all). Our results suggest that there may be a considerable number of SLE patients with aspirin resistance.

Clinical and biochemical aspirin resistance in patients with recurrent cerebral ischemia.

PubMed

El-Mitwalli, Ashraf; Azzam, Hanan; Abu-Hegazy, Mohammad; Gomaa, Mohamed; Wasel, Yasser

2013-07-01

Stroke recurrence is an important public health concern. One half of survivors remain disabled, and one seventh requires institutional care. Aspirin remains the cornerstone of primary and secondary stroke prevention; meanwhile, aspirin resistance is one of the possible causes of stroke recurrence. We aimed to evaluate the clinical and biochemical aspirin resistance in patients with recurrent ischemic stroke. We studied demographic characteristics, vascular risk factors, stroke subtypes, radiologic findings and biochemical aspirin resistance tests using both arachidonic acid (AA) and adenosine diphosphate (ADP)-induced light transmittance aggregometry (LTA) on admission and 24 h after observed aspirin ingestion. Of the 82 patients with recurrent cerebral ischemia included in this study, 37 (45%) patients were poor compliant with aspirin. There were no statistically significant differences between the two groups regarding the demographic characteristics, stroke severity, laboratory tests, radiological findings or vascular risk factors. On admission, 19.6% and 4.8% of patients showed aspirin resistance, while 24 h after supervised 300 mg single aspirin dose ingestion, it was 9.8% and 2.4% using ADP and AA-induced LTA respectively. Of the eight aspirin resistant patients, two only showed resistance using both AA and ADP. Aspirin resistance was statistically significantly higher in the male gender, older age, hyperlipidemia, smokers and in all lacunar strokes using AA. Biochemical aspirin resistance in one's series was rather rare (2.4%) and was more prevalent in patients with lacunar strokes. Clinical aspirin failure may often be contributed to poor compliance with aspirin intake. Copyright © 2012 Elsevier B.V. All rights reserved.

PFA-100-measured aspirin resistance is the predominant risk factor for hospitalized cardiovascular events in aspirin-treated patients: A 5-year cohort study.

PubMed

Chen, H Y; Chou, P

2018-04-01

Aspirin therapy is the clinical gold standard for the prevention of cardiovascular events. However, cardiovascular events still develop in some patients undergoing aspirin therapy. Many laboratory methods exist for measuring aspirin resistance. Using the platelet Function Analyzer (PFA)-100 system, we aimed to determine the effect of aspirin resistance on hospitalized cardiovascular events (hCVE) in a 5-year follow-up cohort. We also sought to determine the impact of aspirin resistance on the relationship between common cardiovascular risk factors and cardiovascular hospitalization. Aspirin resistance was evaluated in aspirin-treated patients from the outpatient department. A total of 465 patients during a 5-year follow-up period were included in this study. The primary endpoint of the study was hospitalization for any acute cardiovascular event. The prevalence and associated risk factors of acute cardiovascular events were evaluated. Aspirin resistance was prevalent in 91 (20.0%) of 465 patients. Prior hospitalization history of cardiovascular events was highly associated with aspirin resistance (P = .001). At the 5-year follow-up, cardiovascular events were found to have developed in 11 patients (8 stroke and 3 myocardial infarction) who exhibited aspirin resistance (12.1%) and in 9 (4 stroke and 5 myocardial infarction) patients who did not exhibit aspirin resistance (2.4%) (P < .001). At the 5-year follow-up, multivariate logistic regression analysis results showed a strong association between aspirin resistance and cardiovascular events (adjusted odds ratio 4.28; 95% CI: 1.64-11.20; P = .03). PFA-100 measurements of aspirin resistance correlate with hCVE, as evidenced by both the past medical history and the 5-year follow-up. The logistic regression analysis results showed that aspirin resistance plays a larger role in hospitalized cardiovascular disease than do other cardiovascular risk factors. © 2017 John Wiley & Sons Ltd.

Acute exacerbation of idiopathic pulmonary fibrosis triggered by Aspergillus empyema.

PubMed

Suzuki, Atsushi; Kimura, Tomoki; Kataoka, Kensuke; Matsuda, Toshiaki; Yokoyama, Toshiki; Mori, Yuta; Kondoh, Yasuhiro

2018-01-01

Acute exacerbation (AE) is a severe and life-threatening complication of idiopathic pulmonary fibrosis (IPF). In 2016, the definition and diagnostic criteria for AE-IPF were updated by an international working group. The new definition includes any acute, clinically significant respiratory deterioration (both idiopathic and triggered events) characterized by evidence of new widespread alveolar abnormality in patients with IPF. There are no currently proven beneficial management strategies for idiopathic and triggered AE-IPF. This is the first report describing AE-IPF triggered by Aspergillus empyema, which was improved by a combination of corticosteroid, systemic antifungal therapy, local antifungal therapy, and additional pharmacological therapies. Future research may reveal optimal strategies for both idiopathic and triggered AE-IPF.

Virome and bacteriome characterization of children with pneumonia and asthma in Mexico City during winter seasons 2014 and 2015

PubMed Central

Romero-Espinoza, Jose A.; Moreno-Valencia, Yazmin; Coronel-Tellez, Rodrigo H.; Castillejos-Lopez, Manuel; Hernandez, Andres; Dominguez, Aaron; Miliar-Garcia, Angel; Barbachano-Guerrero, Arturo; Perez-Padilla, Rogelio; Alejandre-Garcia, Alejandro

2018-01-01

Background Acute asthma exacerbations and pneumonia are important causes of morbidity and mortality in children and may coexist in the same children, although symptom overlap may lead to difficulties in diagnosis. Microbial and viral diversity and differential abundance of either may play an important role in infection susceptibility and the development of acute and chronic respiratory diseases. Objectives To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. Methods During the winter seasons of 2013–2014 and 2014–2015, 134 nasopharyngeal swabs samples of children <15 years of age with ARI hospitalized at a referral hospital for respiratory diseases were selected based on clinical diagnosis of asthma or pneumonia. The virome and bacteriome were characterized using Whole Genome Sequencing (WGS) and in-house bioinformatics analysis pipeline. Results The Asthma group was represented mainly by RV-C, BoV-1 and RSV-B and the pneumonia group by Bacteriophage EJ-1 and TTMV. TTV was found in both groups with a similar amount of reads. About bacterial composition Moraxella catarrhalis, Propionibacterium acnes and Acinetobacter were present in asthma and Veillonella parvula and Mycoplasma pneumoniae in pneumonia. Streptococcus pneumoniae and Haemophilus influenzae were mostly found with both asthma and pneumonia. Conclusions Our results show a complex viral and bacterial composition in asthma and pneumonia groups with a strong association of RV-C presence in asthmatic children. We observed Streptococcus pneumoniae and Haemophilus influenzae concurrently in both groups. PMID:29447223

Perspectives on advance care planning among patients recently requiring non-invasive ventilation for acute respiratory failure: A qualitative study using thematic analysis.

PubMed

Smith, Tracy A; Disler, Rebecca T; Jenkins, Christine R; Ingham, Jane M; Davidson, Patricia M

2017-06-01

Patients requiring non-invasive ventilation for acute-on-chronic respiratory failure due to chronic obstructive pulmonary disease or heart failure exacerbations may have a poor prognosis underscoring the importance of advance care planning. We aimed to describe attitudes to, and experiences of, discussing the future among patients recently treated with non-invasive ventilation. Qualitative research using thematic analysis. Tertiary teaching hospital. Patients with acute hypercapnic respiratory failure requiring non-invasive ventilation. Individuals recently treated with non-invasive ventilation describe feeling the future is beyond their control and instead controlled by their illness. Participants often recognised their poor prognosis but avoided discussing some difficult topics. The majority preferred not to undergo cardiopulmonary resuscitation but most had not discussed this with healthcare professionals. When participants voiced concerns about their future health to family members, they were met with polarised responses. Some encountered willingness for further discussion, while others met deflection, deterring further conversation. An overarching narrative of 'Looking through my illness to an uncertain but concerning future' unites these themes. This study suggests opportunities and barriers for advance care planning in individuals with chronic disease. Patients' understanding of their prognosis and their attitudes to cardiopulmonary resuscitation suggests an opportunity for advance care planning. Structuring discussions around patients' preferences for care during future exacerbations may foster a sense of control over the future despite illness. The diversity of familial responses to patients' concerns about their future health has implications for advance care planning. These findings have the potential to improve care for patients with respiratory failure and suggest an important ongoing research agenda.

Respiratory Syncytial Virus Inhibits Ciliagenesis in Differentiated Normal Human Bronchial Epithelial Cells: Effectiveness of N-Acetylcysteine

PubMed Central

Mata, Manuel; Sarrion, Irene; Armengot, Miguel; Carda, Carmen; Martinez, Isidoro; Melero, Jose A.; Cortijo, Julio

2012-01-01

Persistent respiratory syncytial virus (RSV) infections have been associated with the exacerbation of chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). This virus infects the respiratory epithelium, leading to chronic inflammation, and induces the release of mucins and the loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. These alterations involve reactive oxygen species-dependent mechanisms. The antioxidant N-acetylcysteine (NAC) has proven useful in the management of COPD, reducing symptoms, exacerbations, and accelerated lung function decline. NAC inhibits RSV infection and mucin release in human A549 cells. The main objective of this study was to analyze the effects of NAC in modulating ciliary activity, ciliagenesis, and metaplasia in primary normal human bronchial epithelial cell (NHBEC) cultures infected with RSV. Our results indicated that RSV induced ultrastructural abnormalities in axonemal basal bodies and decreased the expression of β-tubulin as well as two genes involved in ciliagenesis, FOXJ1 and DNAI2. These alterations led to a decrease in ciliary activity. Furthermore, RSV induced metaplastic changes to the epithelium and increased the number of goblet cells and the expression of MUC5AC and GOB5. NAC restored the normal functions of the epithelium, inhibiting ICAM1 expression, subsequent RSV infection through mechanisms involving nuclear receptor factor 2, and the expression of heme oxygenase 1, which correlated with the restoration of the antioxidant capacity, the intracellular H2O2 levels and glutathione content of NHBECs. The results presented in this study support the therapeutic use of NAC for the management of chronic respiratory diseases, including COPD. PMID:23118923

Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica

PubMed Central

McGill, Jodi L.; Rusk, Rachel A.; Guerra-Maupome, Mariana; Briggs, Robert E.; Sacco, Randy E.

2016-01-01

Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and γδ T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing γδ T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and γδ T cells in the pathogenesis of BRDC. PMID:26942409

The hemodynamic effects of prolonged respiratory alkalosis in anesthetized newborn piglets.

PubMed

Jundi, K; Barrington, K J; Henderson, C; Allen, R G; Finer, N N

2000-04-01

To test the hypothesis that prolonged alkalosis decreases cardiac output and, furthermore, exacerbates hypoxic pulmonary vasoconstriction, as respiratory alkalosis is frequently induced as a therapy for persistent pulmonary hypertension of the newborn despite a lack of controlled evidence of improved outcomes. Potential adverse effects of prolonged alkalosis have been demonstrated. Two groups (control, n = 6, and hypocapnic alkalosis, n = 6) of 1-3 day old fentanyl-anesthetized, vecuronium-paralyzed piglets were instrumented to measure cardiac index (CI) and mean systemic (MAP) and pulmonary (PAP) arterial pressures. Baseline values were recorded. Alveolar hypoxia was then induced to achieve an arterial oxygen saturation of between 50 and 60% for 15 min. Respiratory alkalosis was then induced, by increasing ventilation to achieve a pH between 7.55-7.60, and was continued for 240 min. Inspired carbon dioxide was used with hyperventilation in the control group to maintain pressure of arterial carbon dioxide (PaCO2) at 35-45 mmHg and pH of 7.35-7.45. Hypoxia was induced again at 15 and 240 min. Pulmonary and systemic vascular resistances (PVR and SVR) were calculated. Prolonged alkalosis led to a significant and progressive fall in mean MAP from 61 (SD 7) mmHg at the start of the study falling to 50 (SD 6.9, p = 0.043), with no effect on CI. Calculated SVR decreased (0.45 SD 0.03 vs 0.36 SD 0.05). There were no statistically significant changes in any of the variables in the control group. Neither acute nor prolonged respiratory alkalosis had a significant effect on hypoxic pulmonary vasoconstriction. Prolonged hyperventilation leads to systemic hypotension, however it does not exacerbate hypoxic pulmonary vasoconstriction.

Different pattern of viral infections and clinical outcomes in patient with acute exacerbation of chronic obstructive pulmonary disease and chronic obstructive pulmonary disease with pneumonia.

PubMed

Kim, Ho-Cheol; Choi, Sang-Ho; Huh, Jin-Won; Sung, Heungsup; Hong, Sang Bum; Lim, Chae-Man; Koh, Younsuck

2016-12-01

Respiratory viruses are well-known causes of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) and also important pathogens for concomitant pneumonia in COPD (CP-COPD). However, the differences in a viral infection pattern and clinical impacts of respiratory viruses between the two groups have not been well investigated. The clinical and microbiological data from COPD patients admitted with AE-COPD (n = 281) or CP-COPD (n = 284) between January 2010 and December 2012 were reviewed. After excluding 88 patients (40 with AE-COPD and 48 with CP-COPD) who did not undergo a multiplex RT-PCR test for respiratory viruses, the demographic characteristics, identified viruses, and clinical outcomes of the AE-COPD and CP-COPD groups were compared. Respiratory viruses were identified in 41.9% of AE-COPD group and 33.5% of the CP-COPD groups. The most common virus was influenza virus in the AE-COPD group (33.7%) versus human coronavirus (24.1%) in the CP-COPD group. Influenza virus was significantly more common in the AE-ACOPD group than in the CP-COPD group (P < 0.01). In-hospital mortality of AE-COPD and CP-COPD were 1.2% and 12.3%, respectively (P < 0.01). Among CP-COPD patients, in-hospital mortality of patients with only viral infection group, only bacterial infection group, and viral-bacterial co-infection were 2.6%, 25.8%, and 17.5%, respectively (P = 0.01). Respiratory viruses were commonly identified in both AE-COPD and CP-COPD, influenza virus and human coronavirus were the most common viruses identified in AE-COPD and CP-COPD patients, respectively. The mortality rates of only viral infection group was significantly lower than only bacterial infection or viral-bacterial co-infection group in CP-COPD patients. J. Med. Virol. 88:2092-2099, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Metformin-associated respiratory alkalosis.

PubMed

Bryant, Sean M; Cumpston, Kirk; Lipsky, Martin S; Patel, Nirali; Leikin, Jerrold B

2004-01-01

We present an 84-year-old man with a history of chronic obstructive pulmonary disease, type 2 diabetes, hypertension, glaucoma, and bladder cancer who presented to the emergency department after the police found him disoriented and confused. Metformin therapy began 3 days before, and he denied any overdose or suicidal ideation. Other daily medications included glipizide, fluticasone, prednisone, aspirin, furosemide, insulin, and potassium supplements. In the emergency department, his vital signs were significant for hypertension (168/90), tachycardia (120 bpm), and Kussmaul respirations at 24 breaths per minute. Oxygen saturation was 99% on room air, and a fingerstick glucose was 307 mg/dL. He was disoriented to time and answered questions slowly. Metformin was discontinued, and by day 3, the patient's vital signs and laboratory test results normalized. He has been asymptomatic at subsequent follow-up visits. Metformin-associated lactic acidosis is a well-known phenomenon. Respiratory alkalosis may be an early adverse event induced by metformin prior to the development of lactic acidosis.

No Breathing in the Aisles: Diesel Exhaust inside School Buses.

ERIC Educational Resources Information Center

Solomon, Gina M.; Campbell, Todd R.; Feuer, Gail Ruderman; Masters, Julie; Samkian, Artineh; Paul, Kavita Ann

There is evidence that diesel exhaust causes cancer and premature death, and also exacerbates asthma and other respiratory illness. Noting that the vast majority of the nation's school buses run on diesel fuel, this report details a study examining the level of diesel exhaust to which children are typically exposed as they travel to and from…

Aspirin Desensitization

MedlinePlus

... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Aspirin Desensitization Kevin C. Welch, MD Zara Patel, MD Introduction The term "aspirin-sensitive asthma" (also known as "aspirin triad" or " ...

Surgical treatment of aspirin triad sinusitis.

PubMed

McFadden, E A; Woodson, B T; Fink, J N; Toohill, R J

1997-01-01

Aspirin sensitivity, asthma, and chronic sinusitis with polyposis comprises the syndrome of Aspirin Triad (AT). The sinusitis associated with this disease is often fulminate and difficult to treat. In order to evaluate the surgical treatment of chronic sinusitis of AT a 17-year retrospective study of 80 patients was performed. Friedman Class III or IV sinus CT scans were present in 73 patients (90%) preoperatively. Twenty-five patients (30.1%) had steroid-dependent asthma and an additional 40 (50%) required intermittent oral steroids for asthma control. All patients underwent bilateral sinus surgery by either a conservative or a radical approach. Patients were followed from 3 weeks to 16 years postoperatively, with an average followup of 3 years. Sixty-eight patients (85%) had significant improvement in their sinus symptoms and 67 (83%) had relief of their asthma. The eight patients (10%) who remained steroid dependent required smaller doses of steroids. Seven patients (8.8%) had nonoperative orbital complications. There was a significant incidence of revision surgery after both conservative and radical sinus procedures. We conclude that surgical treatment by either a conservative or a radical approach controlled the sinusitis in the majority of AT patients, but neither was effective in eliminating the need for subsequent sinus surgery in a significant number of patients with severe sinus disease (Classes III and IV). Control of the sinus disease has a definite beneficial effect on steroid dependency and the need for intermittent oral steroids in managing the asthma in AT. We recommend conservative surgery in the surgical treatment of these patients. AT patients also require close long-term followup with intense medical management of their chronic respiratory inflammation that appears to put them at increased risk for nonoperative complications of their severe sinusitis.

The use of aspirin and opiates by Dumfries and Galloway general practitioners in the management of acute myocardial infarction.

PubMed

Strachan, D A; Robertson, S

1995-10-01

In March 1994 a study in the British Medical Journal indicated a low rate of administration of aspirin and opiates by general practitioners in cases of suspected myocardial infarction. A retrospective analysis was made of 120 consecutive admissions to the medical intensive care unit of Dumfries and Galloway Royal Infirmary, by general practitioners, with a primary diagnosis of acute myocardial infarction. Of these 120 cases, 24% were given aspirin by their G.P. prior to admission and 64% were given opiate (IV or IM). Thirty-three percent were already on regular aspirin and of these 18% received further aspirin prior to admission. These figures were considerably better than those previously quoted and they showed that prior regular aspirin therapy did influence the GPs' decision on further administration of aspirin in the acute event. A questionnaire sent to all GPs in Dumfries and Galloway revealed that 100% carried aspirin in their medical bags, 62% claimed to give aspirin to patients with suspected MI, 95% used a British Heart Foundation approved dose of aspirin and 83.3% administered the aspirin using one of the approved methods.

[Long-term effect of policosanol on the functional recovery of non-cardioembolic ischemic stroke patients: a one year study].

PubMed

Sanchez, J; Illnait, J; Mas, R; Mendoza, S; Fernandez, L; Mesa, M; Vega, H; Fernandez, J; Reyes, P; Ruiz, D

2017-02-16

Stroke is a leading cause of mortality and disability. Policosanol has been effective in brain ischemia models. The aim of this study is to investigate whether policosanol, added to aspirin therapy within 30 days of stroke onset, is better than placebo + aspirine for the long-term recovery of non-cardioembolic ischemic stroke subjects. Randomized, double-blind, placebo-controlled study. Eighty patients (mean age: 69 years) within 30 days of onset, with a modified Rankin Scale score (mRS) 2 to 4, were included. They were randomized in two groups (policosanol + aspirine or placebo + aspirine) for 12 months. Policosanol + aspirine decreased significantly mean mRS from the first interim check-up (1.5 months). The treatment even improved after long-term therapy. More policosanol + aspirin (87.5%) than placebo + aspirine (0%) patients achieved mRSs <= 1. Policosanol + aspirine increased significantly Barthel Index, lowered LDL-cholesterol and increased HDL-cholesterol versus placebo + aspirin. Long-term (12 months) administration of policosanol + aspirin given after suffering non-cardioembolic ischemic stroke was shown to be better than placebo + aspirin in improving functional outcomes when used among patients with non-cardioembolic ischemic stroke of moderate severity.

Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study

PubMed Central

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Jinnouchi, Hideaki; Waki, Masako; Akai, Yasuhiro; Ishii, Hitoshi; Saito, Yoshihiko

2016-01-01

Background Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes. Methods We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR). Results Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995–1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92–1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, −0.8 ± 2.9; no aspirin, −0.9 ± 2.5 ml/min/1.73m2/year). Conclusion Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes. PMID:26808136

Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study.

PubMed

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Jinnouchi, Hideaki; Waki, Masako; Akai, Yasuhiro; Ishii, Hitoshi; Saito, Yoshihiko

2016-01-01

Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes. We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR). Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995-1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92-1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, -0.8 ± 2.9; no aspirin, -0.9 ± 2.5 ml/min/1.73 m(2)/year). Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes.

Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypaSS occlusion After off-pump procedures) randomised study.

PubMed

Mannacio, Vito Antonio; Di Tommaso, Luigi; Antignan, Anita; De Amicis, Vincenzo; Vosa, Carlo

2012-12-01

To determine the individual variability in the response to aspirin and/or clopidogrel and its impact on graft patency after off-pump coronary artery bypass grafting. A single-centre prospective randomised controlled study designed according to the Consolidated Standards of Reporting Trials statement. Randomisation was obtained by a computer-generated algorithm. University medical school in Italy. 300 patients who underwent off-pump coronary artery bypass grafting were randomised to receive aspirin (n=150) or aspirin plus clopidogrel (n=150). Aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily was initiated when postoperative chest tube drainage was ≤ 50 ml/h for 2 h and patients were followed up for 12 months. Qualitative and quantitative assessment of platelet function, angiographic evaluation of coronary revascularisation by 64-slice CT and clinical outcome. In the aspirin group, 49 patients (32.6%) were aspirin resistant and, in the aspirin-clopidogrel group, 19 patients (12.6%) were aspirin and clopidogrel resistant. The platelet response to aspirin was similar in all aspirin responders despite the study arm (Aspirin Reaction Units 313.2 ± 44.8 vs 323.6 ± 53.6; p=0.07). The platelet response to clopidogrel was enhanced by aspirin in patients responsive to both aspirin and clopidogrel (synergistic effect) compared with responders to clopidogrel only (P2Y12 Reaction Units 139.9 ± 15.5 vs 179.4 ± 18.5; p<0.001). Combined therapy was associated with a reduced vein graft occlusion rate (7.4% vs 13.1%; p=0.04). Antiplatelet resistance was a predictor of graft occlusion (RR 3.6, 95% CI 2.5 to 6.9; p<0.001). Synergistic aspirin and clopidogrel activity was a strong predictor of vein graft patency (RR 5.1, 95% CI 1.4 to 16.3; p<0.01). Combined clopidogrel and aspirin overcome single drug resistances, are safe for bleeding and improve venous graft patency.

Multiple electrode whole blood aggregometry, PFA-100, and in vivo bleeding time for the point-of-care assessment of aspirin-induced platelet dysfunction in the preoperative setting.

PubMed

Jámbor, Csilla; von Pape, Klaus-Werner; Spannagl, Michael; Dietrich, Wulf; Giebl, Andreas; Weisser, Heike

2011-07-01

Acquired platelet dysfunction due to aspirin ingestion may increase bleeding tendency during surgery. Thus, we examined the diagnostic accuracy of in vivo bleeding time (BT) and 2 platelet function assays for the preoperative assessment of a residual antiplatelet effect in patients treated with aspirin. Consecutive patients scheduled for surgery were prospectively enrolled in this study. The patients' last aspirin ingestion had occurred within the previous 48 hours before blood sampling in the "full aspirin effect" group, between 48 and 96 hours before in the "variable aspirin effect" group, and >96 hours before in the "recovered aspirin effect" group. The control group had not taken any aspirin. Multiple electrode aggregometry, platelet function analyzer (PFA)-100, and in vivo BT were performed to assess the effects of aspirin. One-way analysis of variance on ranks with a post hoc multiple-comparison procedure (Dunn) was used to detect differences among the groups. Categorical data were compared using the z test. Receiver operating characteristic (ROC) curves were created to determine the diagnostic accuracy of the platelet function assays investigated. The area under the ROC curve (AUC), sensitivity, and specificity of the assays were calculated. The level of statistical significance was set at P < 0.05. Three hundred ninety-four patients were included in the analysis (133 control and 261 aspirin-treated patients). All 3 methods were able to detect the antiplatelet effect of aspirin in the full aspirin effect group. Furthermore, no difference in the measurement values between the recovered aspirin effect and control group was found, irrespective of the assay performed. Measurement values in the variable aspirin effect group were different from those of the control group in the ASPItest using multiple electrode aggregometry and COL-EPI using PFA-100 but not in BT. ROC analysis showed the highest diagnostic accuracy in excluding the residual aspirin effect in the ASPItest (AUC 0.81, P < 0.001), followed by COL-EPI (AUC 0.78, P < 0.001) and BT (AUC 0.56, P = 0.05). The cutoff value of 53 U in the ASPItest excluded the effect of aspirin with a sensitivity of 88% and specificity of 71%. The full therapeutic antiplatelet effects of aspirin can be expected within 48 hours of the patient's last aspirin ingestion. Platelet function recovered in our study if aspirin cessation occurred >96 hours (4 days) before; thus, in these patients, preoperative platelet function testing is not useful. To quantify any residual aspirin effect in patients who ceased their intake of aspirin between 48 and 96 hours before surgery, the ASPItest might have the highest diagnostic accuracy.

Impact of bronchiectasis and trapped air on quality of life and exacerbations in cystic fibrosis.

PubMed

Tepper, Leonie A; Utens, Elisabeth M W J; Caudri, Daan; Bos, Aukje C; Gonzalez-Graniel, Karla; Duivenvoorden, Hugo J; van der Wiel, Els C W; Quittner, Alexandra L; Tiddens, Harm A W M

2013-08-01

Cystic fibrosis (CF) is primarily characterised by bronchiectasis and trapped air on chest computed tomography (CT). The revised Cystic Fibrosis Questionnaire respiratory symptoms scale (CFQ-R RSS) measures health-related quality of life. To validate bronchiectasis, trapped air and CFQ-R RSS as outcome measures, we investigated correlations and predictive values for pulmonary exacerbations. CF patients (aged 6-20 years) underwent CT, CFQ-R RSS and 1-year follow-up. Bronchiectasis and trapped air were scored using the CF-CT scoring system. Correlation coefficients and backward multivariate modelling were used to identify predictors of pulmonary exacerbations. 40 children and 32 adolescents were included. CF-CT bronchiectasis (r = -0.38, p<0.001) and CF-CT trapped air (r = -0.35, p = 0.003) correlated with CFQ-R RSS. Pulmonary exacerbations were associated with: bronchiectasis (rate ratio 1.10, 95% CI 1.02-1.19; p = 0.009), trapped air (rate ratio 1.02, 95% CI 1.00-1.05; p = 0.034) and CFQ-R RSS (rate ratio 0.95, 95% CI 0.91-0.98; p = 0.002). The CFQ-R RSS was an independent predictor of pulmonary exacerbations (rate ratio 0.96, 95% CI 0.94-0.97; p<0.001). Bronchiectasis, trapped air and CFQ-R RSS were associated with pulmonary exacerbations. The CFQ-R RSS was an independent predictor. This study further validated bronchiectasis, trapped air and CFQ-R RSS as outcome measures in CF.

Preoperative aspirin use and acute kidney injury after cardiac surgery: A propensity-score matched observational study.

PubMed

Hur, Min; Koo, Chang-Hoon; Lee, Hyung-Chul; Park, Sun-Kyung; Kim, Minkyung; Kim, Won Ho; Kim, Jin-Tae; Bahk, Jae-Hyon

2017-01-01

The association between preoperative aspirin use and postoperative acute kidney injury (AKI) in cardiovascular surgery is unclear. We sought to evaluate the effect of preoperative aspirin use on postoperative AKI in cardiac surgery. A total of 770 patients who underwent cardiovascular surgery under cardiopulmonary bypass were reviewed. Perioperative clinical parameters including preoperative aspirin administration were retrieved. We matched 108 patients who took preoperative aspirin continuously with patients who stopped aspirin more than 7 days or did not take aspirin for the month before surgery. The parameters used in the matching included variables related to surgery type, patient's demographics, underlying medical conditions and preoperative medications. In the first seven postoperative days, 399 patients (51.8%) developed AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and 128 patients (16.6%) required hemodialysis. Most patients took aspirin 100 mg once daily (n = 195, 96.5%) and the remaining 75 mg once daily. Multivariable analysis showed that preoperative maintenance of aspirin was independently associated with decreased incidence of postoperative AKI (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21-0.98, P = 0.048; after propensity score matching: OR 0.39, 95% CI 0.22-0.67, P = 0.001). Preoperative maintenance of aspirin was associated with less incidence of AKI defined by KDIGO both in the entire and matched cohort (n = 44 [40.7%] vs. 69 [63.9%] in aspirin and non-aspirin group, respectively in matched sample, relative risk [RR] 0.64, 95% CI 0.49, 0.83, P = 0.001). Preoperative aspirin was associated with decreased postoperative hospital stay after matching (12 [9-18] days vs. 16 [10-25] in aspirin and non-aspirin group, respectively, P = 0.038). Intraoperative estimated or calculated blood loss using hematocrit difference and estimated total blood volume showed no difference according to aspirin administration in both entire and matched cohort. Preoperative low dose aspirin administration without discontinuation was protective against postoperative AKI defined by KDIGO criteria independently in both entire and matched cohort. Preoperative aspirin was also associated with decreased hemodialysis requirements and decreased postoperative hospital stay without increasing bleeding. However, differences in AKI and hospital stay were not associated with in-hospital mortality.

Evaluation of health care providers’ role transition and satisfaction in hospital-at-home for chronic obstructive pulmonary disease exacerbations: a survey study

PubMed Central

2013-01-01

Background Hospital-at-home is an accepted alternative for usual hospital treatment for patients with a Chronic Obstructive Pulmonary Disease (COPD) exacerbation. The introduction of hospital-at-home may lead to changes in health care providers’ roles and responsibilities. To date, the impact on providers’ roles is unknown and in addition, little is known about the satisfaction and acceptance of care providers involved in hospital-at-home. Methods Objective of this survey study was to investigate the role differentiation, role transitions and satisfaction of professional care providers (i.e. pulmonologists, residents, hospital respiratory nurses, generic and specialised community nurses and general practitioners) from 3 hospitals and 2 home care organisations, involved in a community-based hospital-at-home scheme. A combined multiple-choice and open-end questionnaire was administered in study participants. Results Response rate was 10/17 in pulmonologists, 10/23 in residents, 9/12 in hospital respiratory nurses, 15/60 in generic community nurses, 6/10 in specialised community nurses and 25/47 in general practitioners. For between 66% and 100% of respondents the role in early discharge was clear and between 57% and 78% of respondents was satisfied with their role in early discharge. For nurses the role in early discharge was different compared to their role in usual care. 67% of generic community nurses felt they had sufficient knowledge and skills to monitor patients at home, compared to 100% of specialised community nurses. Specialised community nurses felt they should monitor patients. 60% of generic community nurses responded they should monitor patients at home. 78% of pulmonologists, 12% of general practitioners, 55% of hospital respiratory nurses and 48 of community nurses was satisfied with early discharge in general. For coordination of care 29% of community nurses had an unsatisfied response. For continuity of care this was 12% and 10% for hospital respiratory nurses and community nurses, respectively. Conclusion A community-based early assisted discharge for COPD exacerbations is possible and well accepted from the perspective of health care providers’ involved. Satisfaction with the different aspects is good and the transfer of patients in the community while supervised by generic community nurses is possible. Attention should be paid to coordination and continuity of care, especially information transfer between providers. PMID:24074294

Prevalence of Aspirin Resistance in Diabetic Patients and its Associated Factors

PubMed Central

HABIZAL, Nor Halwani; ABDUL HALIM, Sanihah; BHASKAR, Shalini; WAN BEBAKAR, Wan Mohamed; ABDULLAH, Jafri Malin

2015-01-01

Background: Aspirin resistance has posed a major dilemma in the prevention of cardiovascular disease and stroke. There have been many factors that have been associated with aspirin resistance. Among these factors, the inflammatory processes of diabetes and glycaemic control have been significantly associated with aspirin resistance. Our study evaluated the prevalence of aspirin resistance and its associated factors. Methods: This was a cross-sectional, interventional study, which was implemented from October to November 2012 at the Hospital Universiti Sains Malaysia (HUSM). Sixty-nine patients with diabetes who were taking aspirin were enrolled. The glycosylated haemoglobin (HbA1c) and C-reactive protein (CRP) levels were measured in these patients. The thromboelastography (TEG) level was measured using a TEG machine by a trained technician employing standard methods. The variables obtained were analysed for prevalence of aspirin resistance, HbA1c, CRP, and TEG level. The Chi-square test (and Fisher exact test where applicable) were used to evaluate the associations between aspirin resistance with glycaemic control (HbA1c) and inflammatory markers (CRP). Results: The prevalence of aspirin resistance was 17.4% (95%; CI 9.3, 28.4). Glycaemic control (HbA1c) and inflammatory markers (CRP) were not associated with aspirin resistance. Aspirin resistance was prevalent in our study population and was comparable to other studies. The mean HbA1c in the aspirin-resistant group was 8.9%, whereas the mean HbA1c in the aspirin-sensitive group was 8.6%. Conclusion: There was no significant difference in HbA1c between the two groups. There was no significant association between CRP levels and aspirin resistance. PMID:25892950

Effects of daily vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients: a pilot trial.

PubMed

Rafiq, Rachida; Prins, Hendrik J; Boersma, Wim G; Daniels, Johannes Ma; den Heijer, Martin; Lips, Paul; de Jongh, Renate T

2017-01-01

Although vitamin D is well known for its function in calcium homeostasis and bone mineralization, several studies have shown positive effects on muscle strength and physical function. In addition, vitamin D has been associated with pulmonary function and the incidence of airway infections. As vitamin D deficiency is highly prevalent in chronic obstructive pulmonary disease (COPD) patients, supplementation might have a beneficial effect in these patients. To assess the effect of vitamin D supplementation on respiratory muscle strength and physical performance in vitamin D-deficient COPD patients. Secondary outcomes are pulmonary function, handgrip strength, exacerbation rate, and quality of life. We performed a randomized, double-blind, placebo-controlled pilot trial. Participants were randomly allocated to receive 1,200 IU vitamin D3 per day (n=24) or placebo (n=26) during 6 months. Study visits were conducted at baseline, and at 3 and 6 months after randomization. During the visits, blood was collected, respiratory muscle strength was measured (maximum inspiratory and expiratory pressure), physical performance and 6-minute walking tests were performed, and handgrip strength and pulmonary function were assessed. In addition, participants kept a diary card in which they registered respiratory symptoms. At baseline, the mean (standard deviation [SD]) serum 25-hydroxyvitamin D (25(OH)D) concentration (nmol/L) was 42.3 (15.2) in the vitamin D group and 40.6 (17.0) in the placebo group. Participants with vitamin D supplementation had a larger increase in serum 25(OH)D compared to the placebo group after 6 months (mean difference (SD): +52.8 (29.8) vs +12.3 (25.1), P <0.001). Primary outcomes, respiratory muscle strength and physical performance, did not differ between the groups after 6 months. In addition, no differences were found in the 6-minute walking test results, handgrip strength, pulmonary function, exacerbation rate, or quality of life. Vitamin D supplementation did not affect (respiratory) muscle strength or physical performance in this pilot trial in vitamin D-deficient COPD patients.

Aspirin desensitization in patients undergoing percutaneous coronary intervention: a survey of current practice.

PubMed

Chapman, Andrew R; Rushworth, Gordon F; Leslie, Stephen J

2013-01-01

Aspirin remains the mainstay of anti-platelet therapy in cardiac patients. However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated - such as with percutaneous coronary intervention (PCI), then there is no clear guidance. One possibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization of patients with aspirin allergy. The aim of this survey was to assess current knowledge and practice regarding aspirin desensitization in the UK. We conducted a UK wide survey of all UK 116 PCI centers and obtained complete responses from 40 (35.4%) centers. Of these, just 7 (17.5%) centers had previously desensitised patients; 29 (87.9%) centers suggested a lack of a local protocol prevented them from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization. Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25 (64.1%) units had a clinical strategy for dealing with aspirin allergy; the majority (72%) giving higher doses of thienopyridine class drugs. In the UK, there appears to be no consistent approach to patients with aspirin allergy. Patients undergoing PCI benefit from dual anti-platelet therapy (including aspirin), and aspirin desensitization in those with known allergy may facilitate this. Sustained effort should be placed on encouraging UK centers to use desensitization as a treatment modality prior to PCI rather than avoiding aspirin altogether.

In vivo prostacyclin biosynthesis and effects of different aspirin regimens in patients with essential thrombocythaemia.

PubMed

Cavalca, V; Rocca, B; Squellerio, I; Dragani, A; Veglia, F; Pagliaccia, F; Porro, B; Barbieri, S S; Tremoli, E; Patrono, C

2014-07-03

Essential thrombocythaemia (ET) is characterised by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1α (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials.

Long-term treatment with aspirin desensitization: a prospective clinical trial comparing 100 and 300 mg aspirin daily.

PubMed

Rozsasi, A; Polzehl, D; Deutschle, T; Smith, E; Wiesmiller, K; Riechelmann, H; Keck, T

2008-09-01

The daily dose of aspirin in desensitization in aspirin-sensitive asthmatics with nasal polyps is still a matter of debate. To compare two doses of aspirin during the first year of desensitization and to evaluate long-term effects on nasal/pulmonary symptoms. Patients with positive aspirin provocation test were treated with either 100 or 300 mg aspirin daily. In all patients taking 100 mg aspirin (n = 7) recurrent nasal polyps were observed. No patient experienced reduction of asthma medication or improvement of pulmonary function. In the 300 mg group no recurrent nasal polyps were seen. Asthma medication could be reduced in three patients, pulmonary function was improved in five patients. Thirty-nine consecutively desensitized patients, taking 300 mg aspirin, showed significant improvement of olfaction and polyp-free nasal passages during the first year of therapy. After a median follow-up of 27 months no sinus revision surgery was necessary. Aspirin desensitization followed by 300 mg aspirin daily is efficacious and results in polyp-free nasal airways, improvement of sense of smell, and reduction of the need for sinus revision surgery for recurrent nasal polyps. Aspirin in a dose of 100 mg daily is not sufficient to effectively reduce nasal and bronchial or pulmonary symptoms and to prevent recurrent nasal polyps by at least the first 12 months of treatment.

Up-regulation of Ciliary Neurotrophic Factor in Astrocytes by Aspirin

PubMed Central

Modi, Khushbu K.; Sendtner, Michael; Pahan, Kalipada

2013-01-01

Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor, and the mechanisms by which CNTF expression could be increased in the brain are poorly understood. Acetylsalicylic acid (aspirin) is one of the most widely used analgesics. Interestingly, aspirin increased mRNA and protein expression of CNTF in primary mouse and human astrocytes in a dose- and time-dependent manner. Aspirin induced the activation of protein kinase A (PKA) but not protein kinase C (PKC). H-89, an inhibitor of PKA, abrogated aspirin-induced expression of CNTF. The activation of cAMP-response element-binding protein (CREB), but not NF-κB, by aspirin, the abrogation of aspirin-induced expression of CNTF by siRNA knockdown of CREB, the presence of a consensus cAMP-response element in the promoter of CNTF, and the recruitment of CREB and CREB-binding protein to the CNTF promoter by aspirin suggest that aspirin increases the expression of the Cntf gene via the activation of CREB. Furthermore, we demonstrate that aspirin-induced astroglial CNTF was also functionally active and that supernatants of aspirin-treated astrocytes of wild type, but not Cntf null, mice increased myelin-associated proteins in oligodendrocytes and protected oligodendrocytes from TNF-α insult. These results highlight a new and novel myelinogenic property of aspirin, which may be of benefit for multiple sclerosis and other demyelinating disorders. PMID:23653362

77 FR 3777 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-25

... Potassium (multiple RLDs) Aripiprazole Aspirin; Butalbital; Caffeine (multiple RLDs) Aspirin; Dipyridamole Aspirin; Oxycodone Aspirin; Butalbital; Caffeine; Codeine Phosphate Atovaquone Auranofin Azelaic Acid...

Aspirin

MedlinePlus

... of the American Heart Association Cardiology Patient Page Aspirin Jeremy S. Paikin , John W. Eikelboom Download PDF https:// ... treatment of heart attack and stroke. How Does Aspirin Work? Aspirin reduces the risk of heart attacks ...

Aspirin overdose

MedlinePlus

... this page: //medlineplus.gov/ency/article/002542.htm Aspirin overdose To use the sharing features on this page, please enable JavaScript. An overdose of aspirin means you have too much aspirin in your ...

Localized unilateral periorbital edema induced by aspirin.

PubMed

Price, K S; Thomson, D M

1997-11-01

Aspirin intolerance manifested as bronchospasm or urticaria/angioedema has been observed since the beginning of this century. To report a novel case of intolerance to aspirin ingestion. Case report; routine skin testing; pulmonary function testing; aspirin challenge. A 30-year-old man with a history of left ocular trauma at the age of 10 noted a 3-year history of left periorbital angioedema after aspirin but not other nonsteroidal anti-inflammatory drugs. Incremental oral aspirin challenge resulted in this unilateral symptomatology at a dose of 673 mg. To the best of our knowledge, this is the first reported case of unilateral periorbital edema following aspirin ingestion.

The Impact of Ambient Air Pollution on Daily Hospital Visits for Various Respiratory Diseases and the Relevant Medical Expenditures in Shanghai, China.

PubMed

Zhang, Hao; Niu, Yue; Yao, Yili; Chen, Renjie; Zhou, Xianghong; Kan, Haidong

2018-02-28

The evidence concerning the acute effects of ambient air pollution on various respiratory diseases was limited in China, and the attributable medical expenditures were largely unknown. From 2013 to 2015, we collected data on the daily visits to the emergency- and outpatient-department for five main respiratory diseases and their medical expenditures in Shanghai, China. We used the overdispersed generalized additive model together with distributed lag models to fit the associations of criteria air pollutants with hospital visits, and used the linear models to fit the associations with medical expenditures. Generally, we observed significant increments in emergency visits (8.81-17.26%) and corresponding expenditures (0.33-25.81%) for pediatric respiratory diseases, upper respiratory infection (URI), and chronic obstructive pulmonary disease (COPD) for an interquartile range increase of air pollutant concentrations over four lag days. As a comparison, there were significant but smaller increments in outpatient visits (1.36-4.52%) and expenditures (1.38-3.18%) for pediatric respiratory diseases and upper respiratory infection (URI). No meaningful changes were observed for asthma and lower respiratory infection. Our study suggested that short-term exposure to outdoor air pollution may induce the occurrences or exacerbation of pediatric respiratory diseases, URI, and COPD, leading to considerable medical expenditures upon the patients.

Aspirin increases mitochondrial fatty acid oxidation

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

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse themore » mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. - Highlights: • Aspirin increases mitochondrial—but inhibits peroxisomal—fatty acid oxidation. • Aspirin acetylates mitochondrial proteins including fatty acid oxidation enzymes. • SIRT3 does not influence the effect of aspirin on fatty acid oxidation. • Increased fatty acid oxidation is likely due to altered mitochondrial morphology and respiration.« less

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

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

Sung, Jin Young; Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr

Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effectsmore » via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.« less

Differences in care between general medicine and respiratory specialists in the management of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease

PubMed Central

Wijayaratne, Kurugamage; Wilson, Jessica; Sivakumaran, Pathmanathan; Sriram, Krishna B.

2013-01-01

CONTEXT: Hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) may be managed by either respiratory specialists (RS) or general medicine physicians (GMP). While previous studies have audited the hospital AECOPD management of RS, only a small number of studies have evaluated the management of GMP. AIMS: The aims of this study were to firstly examine the differences in AECOPD management of GMP and RS and secondly compare their care to national COPD guidelines. METHODS: A retrospective review was undertaken of consecutive AECOPD patients admitted to two hospitals (one hospital where all AECOPD patients were managed by RS and another where all AECOPD patients were managed by GMP) over a 3-month period. Electronic medical records, medical case notes, pathology and radiology data for the admission were reviewed. RESULTS: There were 201 COPD exacerbations in 169 patients (49.7% male, mean age 72.3). GMP managed 84 (41.7%) exacerbations. In comparison to RS, GMP performed fewer spirometry tests, blood gas analysis and less frequently treated patients with guideline-recommended medications. Referral to pulmonary rehabilitation was poor for both groups of clinicians. Median length of stay was shorter in GMP patients versus RS patients (3 days vs. 5 days, P = 0.001). There were no differences in the 12-month re-admission (41.7% vs. 38.5%, P = 0.664) and mortality rates (10.7% vs. 6%, P = 0.292) between both groups of patients. CONCLUSION: Our study found differences in the hospital AECOPD management of GMP and RS, but these did not translate into different clinical outcomes between their patients. We also found suboptimal adherence to national COPD guidelines, suggesting that there is scope for improvement in the AECOPD management of both groups of clinicians. PMID:24250732

Perioperative aspirin management after POISE-2: some answers, but questions remain.

PubMed

Gerstein, Neal Stuart; Carey, Michael Christopher; Cigarroa, Joaquin E; Schulman, Peter M

2015-03-01

Aspirin constitutes important uninterrupted lifelong therapy for many patients with cardiovascular (CV) disease or significant (CV) risk factors. However, whether aspirin should be continued or withheld in patients undergoing noncardiac surgery is a common clinical conundrum that balances the potential of aspirin for decreasing thrombotic risk with its possibility for increasing perioperative blood loss. In this focused review, we describe the role of aspirin in treating and preventing cardiovascular disease, summarize the most important literature on the perioperative use of aspirin (including the recently published PeriOperative ISchemic Evaluation [POISE]-2 trial), and offer current recommendations for managing aspirin during the perioperative period. POISE-2 suggests that aspirin administration during the perioperative period does not change the risk of a cardiovascular event and may result in increased bleeding. However, these findings are tempered by a number of methodological issues related to the study. On the basis of currently available literature, including POISE-2, aspirin should not be administered to patients undergoing surgery unless there is a definitive guideline-based primary or secondary prevention indication. Aside from closed-space procedures, intramedullary spine surgery, or possibly prostate surgery, moderate-risk patients taking lifelong aspirin for a guideline-based primary or secondary indication may warrant continuation of their aspirin throughout the perioperative period.

Proteome-wide prediction of targets for aspirin: new insight into the molecular mechanism of aspirin

PubMed Central

Dai, Shao-Xing; Li, Wen-Xing

2016-01-01

Besides its anti-inflammatory, analgesic and anti-pyretic properties, aspirin is used for the prevention of cardiovascular disease and various types of cancer. The multiple activities of aspirin likely involve several molecular targets and pathways rather than a single target. Therefore, systematic identification of these targets of aspirin can help us understand the underlying mechanisms of the activities. In this study, we identified 23 putative targets of aspirin in the human proteome by using binding pocket similarity detecting tool combination with molecular docking, free energy calculation and pathway analysis. These targets have diverse folds and are derived from different protein family. However, they have similar aspirin-binding pockets. The binding free energy with aspirin for newly identified targets is comparable to that for the primary targets. Pathway analysis revealed that the targets were enriched in several pathways such as vascular endothelial growth factor (VEGF) signaling, Fc epsilon RI signaling and arachidonic acid metabolism, which are strongly involved in inflammation, cardiovascular disease and cancer. Therefore, the predicted target profile of aspirin suggests a new explanation for the disease prevention ability of aspirin. Our findings provide a new insight of aspirin and its efficacy of disease prevention in a systematic and global view. PMID:26989626

Proteome-wide prediction of targets for aspirin: new insight into the molecular mechanism of aspirin.

PubMed

Dai, Shao-Xing; Li, Wen-Xing; Li, Gong-Hua; Huang, Jing-Fei

2016-01-01

Besides its anti-inflammatory, analgesic and anti-pyretic properties, aspirin is used for the prevention of cardiovascular disease and various types of cancer. The multiple activities of aspirin likely involve several molecular targets and pathways rather than a single target. Therefore, systematic identification of these targets of aspirin can help us understand the underlying mechanisms of the activities. In this study, we identified 23 putative targets of aspirin in the human proteome by using binding pocket similarity detecting tool combination with molecular docking, free energy calculation and pathway analysis. These targets have diverse folds and are derived from different protein family. However, they have similar aspirin-binding pockets. The binding free energy with aspirin for newly identified targets is comparable to that for the primary targets. Pathway analysis revealed that the targets were enriched in several pathways such as vascular endothelial growth factor (VEGF) signaling, Fc epsilon RI signaling and arachidonic acid metabolism, which are strongly involved in inflammation, cardiovascular disease and cancer. Therefore, the predicted target profile of aspirin suggests a new explanation for the disease prevention ability of aspirin. Our findings provide a new insight of aspirin and its efficacy of disease prevention in a systematic and global view.

Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products

MedlinePlus

updated 3/10/08 Medications Containing Aspirin (Acetylsalicylate) and Aspirin-Like Products © National Reye's Syndrome Foundation Inc. 2008 Epidemiologic research has shown an association between the development of Reye's ...

Enoxaparin and Aspirin Compared With Aspirin Alone to Prevent Placenta-Mediated Pregnancy Complications: A Randomized Controlled Trial.

PubMed

Haddad, Bassam; Winer, Norbert; Chitrit, Yvon; Houfflin-Debarge, Véronique; Chauleur, Céline; Bages, Karine; Tsatsaris, Vassilis; Benachi, Alexandra; Bretelle, Florence; Gris, Jean-Christophe; Bastuji-Garin, Sylvie

2016-11-01

To evaluate whether daily enoxaparin, added to low-dose aspirin, started before 14 weeks of gestation reduces placenta-mediated complications in pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation. In this open-label multicenter randomized trial, we enrolled consenting pregnant women with previous severe preeclampsia diagnosed before 34 weeks of gestation, gestational age at randomization of 7-13 weeks, singleton pregnancy, and no plan for anticoagulation. Eligible patients were randomly assigned to a one-to-one ratio to receive daily either 4,000 international units enoxaparin plus 100 mg aspirin or 100 mg aspirin alone. Randomization was done by a web-based randomization system. The primary composite outcome comprised maternal death, perinatal death, preeclampsia, small for gestational age (less than the 10th percentile), and placental abruption. A sample size of 232 women equally divided into two groups was needed to detect a significant reduction in primary outcome from 55% in the aspirin group to 36.7% in the enoxaparin-aspirin group (α: 0.05, β: 0.8, two-sided). Between November 14, 2009, and February 21, 2015, 257 participants were enrolled. Baseline demographic and clinical factors were similar between groups. Eight women were excluded after randomization (six in the enoxaparin-aspirin group and two in the aspirin group), leaving 124 participants assigned to enoxaparin-aspirin and 125 to aspirin. Five participants were lost to follow-up (two in the enoxaparin-aspirin group and three in the aspirin group). There was no significant difference between the groups in the primary outcome: enoxaparin-aspirin 42 of 122 (34.4%) compared with aspirin alone 50 of 122 (41%) (relative risk 0.84, 95% confidence interval 0.61-1.16, P=.29). The occurrence of complications did not differ between the two groups. Antepartum prophylactic enoxaparin does not significantly reduce placenta-mediated complications in women receiving low-dose aspirin for previous severe preeclampsia diagnosed before 34 weeks of gestation. ClinicalTrials.gov, https://clinicaltrials.gov, NCT00986765.

Effectiveness of Healthcare Coordination in Patients with Chronic Respiratory Diseases.

PubMed

Kurpas, Donata; Szwamel, Katarzyna; Lenarcik, Dorota; Guzek, Marika; Prusaczyk, Artur; Żuk, Paweł; Michalowska, Jolanta; Grzeda, Agnieszka; Mroczek, Bożena

2017-08-12

Coordination of healthcare effectively prevents exacerbations and reduces the number of hospitalizations, emergency visits, and the mortality rate in patients with chronic respiratory diseases. The purpose of this study was to determine clinical effectiveness of ambulatory healthcare coordination in chronic respiratory patients and its effect on the level of healthcare services as an indicator of direct medical costs. We conducted a retrospective health record survey, using an online database of 550 patients with chronic respiratory diseases. There were decreases in breathing rate, heart rate, and the number of cigarettes smoked per day, and forced vital capacity (FVC) and forced expired volume in 1 s (FEV1) increased after the implementation of the coordinated healthcare structure. These benefits were accompanied by increases in the number of visits to the pulmonary outpatient clinic (p < 0.001), diagnostic costs (p < 0.001), and referrals to other outpatient clinics (p < 0.003) and hospitals (p < 0.001). The advantageous effects of healthcare coordination on clinical status of respiratory patients above outlined persisted over a 3-year period being reviewed.

[Undernutrition in chronic respiratory diseases].

PubMed

Zielonka, Tadeusz M; Hadzik-Błaszczyk, Małgorzata

2015-01-01

Respiratory diseases such as asthma, COPD, lung cancer, infections, including also tuberculosis constitute the most frequent diseases in the word. Undernutrition frequently accompanies these diseases. Early diagnosis of malnutrition and implementation of appropriate treatment is very important. A nutritional interview and anthropometric examinations, such as body mass index, fat free mass and fat mass are used to diagnose it. Nutritional therapy affects the course and prognosis of these diseases. Diet should be individually adjusted to the calculated caloric intake that increases during exacerbation of disease, because of increased respiratory effort. Too large supply of energy can cause increase metabolism, higher oxygen consumption and PaCO2 increase each dangerous for patients with respiratory insufficiency. Main source of carbohydrates for these patients should be products with low glycemic index and with high dietary fiber contents. Large meals should be avoided since they cause rapid satiety, abdominal discomfort and have negative impact on the work of the respiratory muscles, especially of the diaphragm. Dietary supplements can be used in case of ineffectiveness of diet or for the patients with severe undernutrition.

Antiplatelet effects of aspirin with phytosterols: comparison with non-enteric coated aspirin alone.

PubMed

Antonino, Mark J; Coppolecchia, Rosa; Mahla, Elisabeth; Bliden, Kevin P; Tantry, Udaya S; Gurbel, Paul A

2010-11-01

The novel combination of aspirin and phytosterols may be a potential strategy to treat patients with cardiovascular disease. We sought to determine if the antiplatelet effects of a combination caplet of 81 mg aspirin with 400 mg phytosterols differed from the antiplatelet effects of non-enteric coated aspirin. The first five days of aspirin therapy alone (T1) produced marked reductions in collagen-induced, ADP-induced, and archidonic acid- induced platelet aggregation, and in serum and urine TxB(2) compared to baseline. Five days after randomization to aspirin alone versus aspirin+phytosterols (T2), there were no differences in any measurement of platelet function within each group compared to T1 or between groups. The present study suggests that the antiplatelet effect of non-enteric coated 81 mg twice-daily aspirin therapy alone is not affected by the addition of phytosterols in a combination product. Copyright © 2009 Elsevier Ltd. All rights reserved.

Salicylic acid plasma levels following multiple doses of Norgesic Forte and aspirin.

PubMed

Harrison, L I; Kehe, C R; Goldlust, M B; Kvam, D C; Bianchine, J R

1983-01-01

Plasma salicyclic acid levels from the recommended multiple dose regimen of Norgesic Forte (orphenadrine citrate, aspirin, and caffeine) were compared to those from an equivalent multiple dose regimen of aspirin alone in 24 volunteers. The drugs were administered double-blind so that side effects could also be compared. No statistically significant differences were found between Norgesic Forte and aspirin in peak or trough levels, time to peak level, area under the curve, or mean steady-state level of salicylic acid. Mean steady-state levels averaged 154 +/- 46 (+/- SD) and 152 +/- 49 micrograms/ml on days 5 and 10 following Norgesic Forte versus 161 +/- 49 and 154 +/- 47 micrograms/ml following aspirin. Thus, the aspirin in Norgesic Forte provides an anti-inflammatory amount of salicylic acid equivalent to that of plain aspirin. There was no evidence that the combination of orphenadrine citrate, caffeine, and aspirin in Norgesic Forte caused increased or unusual side effects compared with aspirin alone.

Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

PubMed

Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

2007-12-01

Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

PubMed

Głobińska, Anna; Kowalski, Marek L

2017-10-01

Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

Effects of different doses, enteric-coated preparation of aspirin, and sex on urinary 11-dehydrothromboxane B2 in healthy volunteers.

PubMed

Dharmasaroja, Pornpatr A; Sae-Lim, Suvaraporn

2010-10-01

There is scarce information about the effects of different doses and enteric-coated preparation of aspirin on platelet function, especially in Asian people, evaluated by the measurement of urinary 11-dehydrothromboxane B2 (dTXB2). The objective of the present study was to assess the effects of different doses, enteric-coated preparation of aspirin, sex and also the effects of timing of urine collection on urinary dTXB2 level in healthy volunteers. Thirty healthy volunteers were included. Each volunteer took three preparations of aspirin (aspirin 81 mg, enteric-coated aspirin 300 mg and aspirin 300 mg) for 7 days. Urine dTXB2 level was measured at baseline, day 3, and day 7 after taking each preparation of aspirin. There was no significant difference in the effects of different doses of aspirin (81 vs. 300 mg, 50.7 vs. 61.8 ng/mmol creatinine, P = 0.248), preparations (enteric-coated vs. nonenteric-coated aspirin, 61.8 vs. 67.9 ng/mmol creatinine, P = 0.527) and time of urine collection (day 3 vs. day 7, 51.7 vs. 49.9 ng/mmol creatinine, P = 0.448). Female volunteers showed a trend to have higher urinary dTXB2 than male volunteers at baseline and after taking aspirin. This study showed no significant difference in urinary dTXB2 level after taking different doses and enteric-coated preparation of aspirin in healthy volunteers.

[Long-term clinical course of sequelae in patients with neonatal anoxic encephalopathy resulting in profound mental retardation and motor disturbance].

PubMed

Ishizaki, A; Kubota, M; Fueki, N; Shinozaki, M; Kurata, K; Takei, M; Sakamoto, K

1993-01-01

A long-term observation has been made in 58 patients (30 males and 28 females) with severe sequelae of neonatal anoxic encephalopathy. They aged from 8 months to 65 years. All of them had motor disturbances and profound mental retardation. Motor function was improved in 4 patients with aging. In contrast, motor activity deteriorated in 11 cases, of which 4 showed a mental regression. Among them, patients who had originally better motor ability than sitting were likely to deteriorate by uncontrollable epilepsy and/or excessive administration of anticonvulsants. Regression of the patients with worse motor ability like bedridden appeared to attributable hypertonia of muscles and bodily deformation. Fifteen cases showed an exacerbation of general condition which originated predominantly to respiratory distress. Twelve patients died including 6 exacerbated cases. Exacerbation or death may have occurred frequently in specific periods of infancy, adolescence and youth with the patients who showed very low motor function such as bedridden and no locomotion.

[Clinical studies on flomoxef in respiratory tract infections].

PubMed

Kanegae, H; Yamada, H; Yamaguchi, T; Kuroki, S; Katoh, O

1987-10-01

Flomoxef (FMOX, 6315-S) is a new oxacephem with a broad spectrum of antimicrobial activity. We used FMOX for treatment of 13 patients with respiratory tract infections including 4 cases of pneumonia, 5 of lung abscess and 4 of exacerbation of the chronic airway diseases. FMOX showed excellent in vitro antimicrobial activities against clinical isolates including 4 strains of Streptococcus pneumoniae, 2 strains of Haemophilus influenzae and each one strain of Escherichia coli and Klebsiella pneumoniae. Clinical responses were excellent in 3 cases, good in 7 and fair or poor in 3. No side effect was observed, but abnormal laboratory findings caused by FMOX administration were found in 2 cases; hypertransaminasemia and eosinophilia. However, neither of them was severe. From the above results, it is considered that FMOX will be useful for treatment of patients with respiratory tract infections.

The expression of Mirc1/Mir17-92 cluster in sputum samples correlates with pulmonary exacerbations in cystic fibrosis patients.

PubMed

Krause, Kathrin; Kopp, Benjamin T; Tazi, Mia F; Caution, Kyle; Hamilton, Kaitlin; Badr, Asmaa; Shrestha, Chandra; Tumin, Dmitry; Hayes, Don; Robledo-Avila, Frank; Hall-Stoodley, Luanne; Klamer, Brett G; Zhang, Xiaoli; Partida-Sanchez, Santiago; Parinandi, Narasimham L; Kirkby, Stephen E; Dakhlallah, Duaa; McCoy, Karen S; Cormet-Boyaka, Estelle; Amer, Amal O

2018-07-01

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17-92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17-92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment. Mirc1/Mir17-92 cluster expression was measured in human CF and non-CF plasma, blood-derived neutrophils, and sputum samples. Values were correlated with pulmonary function, exacerbations and use of CFTR modulators. Mirc1/Mir17-92 cluster expression was not significantly elevated in CF neutrophils nor plasma when compared to the non-CF cohort. Cluster expression in CF sputum was significantly higher than its expression in plasma. Elevated CF sputum Mirc1/Mir17-92 cluster expression positively correlated with pulmonary exacerbations and negatively correlated with lung function. Patients with CF undergoing treatment with the CFTR modulator Ivacaftor/Lumacaftor did not demonstrate significant change in the expression Mirc1/Mir17-92 cluster after six months of treatment. Mirc1/Mir17-92 cluster expression is a promising biomarker of respiratory status in patients with CF including pulmonary exacerbation. Published by Elsevier B.V.

Gastro-esophageal reflux disease and exacerbations in chronic obstructive pulmonary disease.

PubMed

Ingebrigtsen, Truls S; Marott, Jacob L; Vestbo, Jørgen; Nordestgaard, Børge G; Hallas, Jesper; Lange, Peter

2015-01-01

We tested the hypothesis that gastro-esophageal reflux disease is a risk factor for exacerbations in individuals with chronic obstructive pulmonary disease (COPD). Among 9622 participants in the Copenhagen City Heart Study, we identified 1259 individuals with COPD and information on gastro-esophageal reflux disease and the regular use of acid inhibitory treatment. These individuals were followed for 5 years with regard to medically treated COPD exacerbations, which we defined as a short course treatment with oral corticosteroids alone or in combination with antibiotics. We applied a multivariable Cox regression analysis with adjustment for well-established risk factors associated with COPD exacerbations or gastro-esophageal reflux disease, including COPD severity, and symptoms. Individuals with COPD and gastro-esophageal reflux disease had more chronic bronchitis (31 vs 21%, P = 0.004), more breathlessness (39 vs 22%, P < 0.001), and more of them had a history of respiratory infections (6.8 vs 1.4%, P < 0.001) than individuals with COPD but without gastro-esophageal reflux disease. Among individuals with COPD and gastro-esophageal reflux disease, those who did not use acid inhibitory treatment regularly had an increased risk of COPD exacerbations during follow-up, hazards ratio (HR): HR = 2.7 (1.3-5.4, P = 0.006). Individuals with gastro-esophageal reflux disease, using acid inhibitory treatment regularly did not have an increased risk of exacerbations, HR = 1.2 (0.6-2.7, P = 0.63). Gastro-esophageal reflux disease was associated with an increased risk of medically treated exacerbations of COPD, but only in those individuals who did not use acid inhibitory treatment regularly. © 2014 Asian Pacific Society of Respirology.

The effect of positive expiratory pressure (PEP) therapy on symptoms, quality of life and incidence of re-exacerbation in patients with acute exacerbations of chronic obstructive pulmonary disease: a multicentre, randomised controlled trial.

PubMed

Osadnik, Christian R; McDonald, Christine F; Miller, Belinda R; Hill, Catherine J; Tarrant, Ben; Steward, Ranjana; Chao, Caroline; Stodden, Nicole; Oliveira, Cristino C; Gagliardi, Nadia; Holland, Anne E

2014-02-01

Positive expiratory pressure (PEP) is a technique used to enhance sputum clearance during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The impact of PEP therapy during acute exacerbations on clinically important outcomes is not clear. This study sought to determine the effect of PEP therapy on symptoms, quality of life and future exacerbations in patients with AECOPD. 90 inpatients (58 men; mean age 68.6 years, FEV(1) 40.8% predicted) with AECOPD and sputum expectoration were randomised to receive usual care (including physical exercise)±PEP therapy. The Breathlessness, Cough and Sputum Scale (BCSS), St George's Respiratory Questionnaire (SGRQ) and BODE index (Body mass index, airflow Obstruction, Dyspnoea, Exercise tolerance) were measured at discharge, 8 weeks and 6 months following discharge, and analysed via linear mixed models. Exacerbations and hospitalisations were recorded using home diaries. There were no significant between-group differences over time for BCSS score [mean (SE) at discharge 5.2 (0.4) vs 5.0 (0.4) for PEP and control group, respectively; p=0.978] or SGRQ total score [41.6 (2.6) vs 40.8 (2.8) at 8 weeks, p=0.872]. Dyspnoea improved more rapidly in the PEP group over the first 8 weeks (p=0.006), however these benefits were not observed at 6 months. Exacerbations (p=0.986) and hospitalisations (p=0.359) did not differ between groups. We found no evidence that PEP therapy during AECOPD improves important short-term or long-term outcomes. There does not appear to be a routine role for PEP therapy in the management of such individuals.

Characteristics of a COPD population categorised using the GOLD framework by health status and exacerbations.

PubMed

Jones, Paul W; Nadeau, Gilbert; Small, Mark; Adamek, Lukasz

2014-01-01

GOLD proposed a COPD assessment framework focussed on symptoms measured by the COPD Assessment Test™ (CAT) or the mMRC and on exacerbation risk based on poor lung function (FEV1 <50%) or a history of ≥2 exacerbations in the previous year. This analysis examined the characteristics of COPD patients recruited from routine clinical settings and classified using the GOLD framework. 1041 European COPD patients (38.5% from primary care) from the Adelphi Respiratory Disease Specific Programme with information on CAT, mMRC, spirometry and exacerbation history in the previous year were analysed. Their mean age was 64.9 ± 9.9 years and mean FEV1 was 62.5 ± 17.8% predicted; 80% were in GOLD 2 spirometric grade or milder. CAT and mMRC cut points identified different groups of patients; using CAT, the composition was: Group A 9.3%, Group B 48.5%, Group C 0.7% and Group D 41.5%. 80% were classified as high risk based on exacerbation history and 25% of patients in a low risk category (GOLD A and B) had 1 exacerbation in the previous year. The incidence of diabetes, hypertension and hyperlipidaemia rose with worsening GOLD group (all p < 0.0001); diabetes GOLD A 4%, GOLD B 16%, GOLD D 29%; hypertension GOLD A 38%, GOLD B 55%, GOLD D 65%; hyperlipidaemia GOLD A 13%, GOLD B 30%, GOLD D 37%. In patients seen in routine clinical settings, 25% of GOLD low risk patients had one exacerbation per year and the incidence of cardio-vascular and metabolic diseases increases with worsening GOLD group. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Streptococcal upper respiratory tract infections and exacerbations of tic and obsessive-compulsive symptoms: a prospective longitudinal study.

PubMed

Leckman, James F; King, Robert A; Gilbert, Donald L; Coffey, Barbara J; Singer, Harvey S; Dure, Leon S; Grantz, Heidi; Katsovich, Liliya; Lin, Haiqun; Lombroso, Paul J; Kawikova, Ivana; Johnson, Dwight R; Kurlan, Roger M; Kaplan, Edward L

2011-02-01

The objective of this blinded, prospective, longitudinal study was to determine whether new group A β hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or OC disorder without a PANDAS history served as the comparison (non-PANDAS) group. Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25-month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results. No group differences were observed in the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions of a total of 51 (12%), a newly diagnosed GABHS infection was followed, within 2 months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group. This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Effect of Air Pollution on Exacerbations of Bronchiectasis in Badalona, Spain, 2008-2016.

PubMed

Garcia-Olivé, Ignasi; Stojanovic, Zoran; Radua, Joaquim; Rodriguez-Pons, Laura; Martinez-Rivera, Carlos; Ruiz Manzano, Juan

2018-05-17

Air pollution has been widely associated with respiratory diseases. Nevertheless, the association between air pollution and exacerbations of bronchiectasis has been less studied. To analyze the effect of air pollution on exacerbations of bronchiectasis. This was a retrospective observational study conducted in Badalona. The number of daily hospital admissions and emergency room visits related to exacerbation of bronchiectasis (ICD-9 code 494.1) between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, SO2, NO2, CO, and PM10 levels on bronchiectasis-related emergencies and hospitalizations on the same day and 1-4 days after. All p values were corrected for multiple comparisons. SO2 was significantly associated with an increase in the number of hospitalizations (lags 0, 1, 2, and 3). None of these associations remained significant after correcting for multiple comparisons. The number of emergency room visits was associated with higher levels of SO2 (lags 0-4). After correcting for multiple comparisons, the association between emergency room visits and SO2 levels was statistically significant for lag 0 (p = 0.043), lag 1 (p = 0.018), and lag 3 (p = 0.050). The number of emergency room visits for exacerbation of bronchiectasis is associated with higher levels of SO2. © 2018 S. Karger AG, Basel.

Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD.

PubMed

Soler, Néstor; Esperatti, Mariano; Ewig, Santiago; Huerta, Arturo; Agustí, Carlos; Torres, Antoni

2012-12-01

In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) needing hospitalisation, sputum purulence is associated with bacteria in the lower respiratory tract. We performed a prospective non-randomised interventional pilot study applying a sputum purulence-guided strategy of antibiotic treatment and investigating the relationship between sputum purulence and biomarkers. In hospitalised patients with acute exacerbation of COPD antibiotics were restricted to those with purulent sputum. The primary end-point was rate of therapeutic failure during hospitalisation. Secondary end-points were parameters reflecting short- and long-term outcomes. We included 73 patients, 34 with non-purulent sputum. No differences were observed on therapeutic failure criteria (9% non-purulent versus 10% purulent (p=0.51)). Serum C-reactive protein (CRP) was significantly increased in the purulent group at admission (11.6 versus 5.3, p=0.006) and at day 3 (2.7 versus 1.2, p=0.01). Serum procalcitonin (PCT) was similar between the groups. No differences were found in short-term outcomes. The exacerbation rate at 180 days was higher in the purulent group. These results support the hypothesis of performing a randomised trial using a sputum purulence-guided antibiotic treatment strategy in patients with acute exacerbations of COPD. CRP, but not PCT, may be a useful parameter to increase confidence of the absence of bacterial bronchial infection.

Aspirin Increases Mitochondrial Fatty Acid Oxidation

PubMed Central

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.; Bharathi, Sivakama S.; Zhang, Yuxun; Stolz, Donna B.; Goetzman, Eric S.

2016-01-01

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 hr incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. PMID:27856258

A Proteomic Approach to Analyze the Aspirin-mediated Lysine Acetylome*

PubMed Central

Tatham, Michael H.; Cole, Christian; Scullion, Paul; Wilkie, Ross; Westwood, Nicholas J.; Stark, Lesley A.; Hay, Ronald T.

2017-01-01

Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences of nonspecific chemical acetylations. PMID:27913581

Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets

PubMed Central

Massimi, Isabella; Guerriero, Raffaella; Lotti, Lavinia Vittoria; Lulli, Valentina; Borgognone, Alessandra; Romani, Federico; Barillà, Francesco; Gaudio, Carlo; Gabbianelli, Marco; Frati, Luigi; Pulcinelli, Fabio M

2014-01-01

Aim The aim of the study was to investigate whether human megakaryocytic cells have an adaptive response to aspirin treatment, leading to an enhancement of multidrug resistance protein-4 (MRP4) expression in circulating platelets responsible for a reduced aspirin action. We recently found that platelet MRP4 overexpression has a role in reducing aspirin action in patients after by-pass surgery. Aspirin enhances MRP4-mRNA levels in rat liver and drug administration transcriptionally regulates MRP4 gene expression through peroxisome proliferator-activated receptor-α (PPARα). Methods The effects induced by aspirin or PPARα agonist (WY14643) on MRP4 modulation were evaluated in vitro in a human megakaryoblastic DAMI cell line, in megakaryocytes (MKs) and in platelets obtained from human haematopoietic progenitor cell (HPC) cultures, and in vivo platelets obtained from aspirin treated healthy volunteers (HV). Results In DAMI cells, aspirin and WY14643 treatment induced a significant increase in MRP4 and PPARα expression. In human MKs grown in the presence of either aspirin or WY14643, MRP4 and PPARα-mRNA were higher than in control cultures and derived platelets showed an enhancement in MRP4 protein expression. The ability of aspirin to modulate MRP4 expression in MKs and to transfer it to platelets was also confirmed in vivo. In fact, we found the highest MRP4 mRNA and protein expression in platelets obtained from HV after 15 days' aspirin treatment. Conclusions The present study provides evidence, for the first time, that aspirin treatment affects the platelet protein pattern through MK genomic modulation. This work represents an innovative and attractive approach, useful both to identify patients less sensitive to aspirin and to improve pharmacological treatment in cardiovascular high-risk patients. PMID:24902864

Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials.

PubMed

Flaker, Greg C; Gruber, Michael; Connolly, Stuart J; Goldman, Steven; Chaparro, Sandra; Vahanian, Alec; Halinen, Matti O; Horrow, Jay; Halperin, Jonathan L

2006-11-01

Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available. We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines. The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year). Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

Long-Term Low-Dose Aspirin Use Reduces Gastric Cancer Incidence: A Nationwide Cohort Study.

PubMed

Kim, Young-Il; Kim, So Young; Kim, Ji Hyun; Lee, Jun Ho; Kim, Young-Woo; Ryu, Keun Won; Park, Jong-Hyock; Choi, Il Ju

2016-04-01

The aim of this study was to investigate whether aspirin use can reduce the incidence of gastric cancer in patients with hypertension or type 2 diabetes. A total of 200,000 patients with hypertension or type 2 diabetes were randomly selected from the Korean National Health Insurance claim database. Of these, 3,907 patients who used 100 mg of aspirin regularly (regular aspirin users) and 7,808 patients who did not use aspirin regularly (aspirin non-users) were selected at a frequency of 1:2, matched by age, sex, comorbid illnesses (type 2 diabetes and hypertension), and observation periods. The incidence of gastric cancer in this cohort was then assessed during the observation period of 2004 to 2010. In the matched cohort, the incidence rates of gastric cancer were 0.8% (31/3,907) for regular aspirin users and 1.1% (86/7,808) for aspirin non-users, but the cumulative incidence rates were not significantly different between groups (p=0.116, log-rank test). However, in multivariate analysis, regular aspirin users had a reduced risk of gastric cancer (adjusted hazard ratio [aHR], 0.71; 95% confidential interval [CI], 0.47 to 1.08; p=0.107). Duration of aspirin use showed significant association with reduction of gastric cancer risk (aHR for each year of aspirin use, 0.85; 95% CI, 0.73 to 0.99; p=0.044), particularly in patients who used aspirin for more than 3 years (aHR, 0.40; 95% CI, 0.16 to 0.98; p=0.045). Long-term low-dose aspirin use was associated with reduced gastric cancer risk in patients with hypertension or type 2 diabetes.

Long-Term Low-Dose Aspirin Use Reduces Gastric Cancer Incidence: A Nationwide Cohort Study

PubMed Central

Kim, Young-Il; Kim, So Young; Kim, Ji Hyun; Lee, Jun Ho; Kim, Young-Woo; Ryu, Keun Won; Park, Jong-Hyock; Choi, Il Ju

2016-01-01

Purpose The aim of this study was to investigate whether aspirin use can reduce the incidence of gastric cancer in patients with hypertension or type 2 diabetes. Materials and Methods A total of 200,000 patients with hypertension or type 2 diabetes were randomly selected from the Korean National Health Insurance claim database. Of these, 3,907 patients who used 100 mg of aspirin regularly (regular aspirin users) and 7,808 patients who did not use aspirin regularly (aspirin non-users) were selected at a frequency of 1:2, matched by age, sex, comorbid illnesses (type 2 diabetes and hypertension), and observation periods. The incidence of gastric cancer in this cohort was then assessed during the observation period of 2004 to 2010. Results In the matched cohort, the incidence rates of gastric cancer were 0.8% (31/3,907) for regular aspirin users and 1.1% (86/7,808) for aspirin non-users, but the cumulative incidence rates were not significantly different between groups (p=0.116, log-rank test). However, in multivariate analysis, regular aspirin users had a reduced risk of gastric cancer (adjusted hazard ratio [aHR], 0.71; 95% confidential interval [CI], 0.47 to 1.08; p=0.107). Duration of aspirin use showed significant association with reduction of gastric cancer risk (aHR for each year of aspirin use, 0.85; 95% CI, 0.73 to 0.99; p=0.044), particularly in patients who used aspirin for more than 3 years (aHR, 0.40; 95% CI, 0.16 to 0.98; p=0.045). Conclusion Long-term low-dose aspirin use was associated with reduced gastric cancer risk in patients with hypertension or type 2 diabetes. PMID:26194372

The use of preoperative aspirin in cardiac surgery: A systematic review and meta-analysis.

PubMed

Aboul-Hassan, Sleiman Sebastian; Stankowski, Tomasz; Marczak, Jakub; Peksa, Maciej; Nawotka, Marcin; Stanislawski, Ryszard; Kryszkowski, Bartosz; Cichon, Romuald

2017-12-01

Despite the fact that aspirin is of benefit to patients following coronary artery bypass grafting (CABG), continuation or administration of preoperative aspirin before CABG or any cardiac surgical procedure remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the influence of preoperative aspirin administration on patients undergoing cardiac surgery. Medline database was searched using OVID SP interface. Similar searches were performed separately in EMBASE, PubMed, and Cochrane Central Registry of Controlled Trials. Twelve randomized controlled trials and 28 observational studies met our inclusion criteria and were included in the meta-analysis. The use of preoperative aspirin in patients undergoing CABG at any dose is associated with reduced early mortality as well as a reduced incidence of postoperative acute kidney injury (AKI). Low-dose aspirin (≤160 mg/d) is associated with a decreased incidence of perioperative myocardial infarction (MI). Administration of preoperative aspirin at any dose in patients undergoing cardiac surgery increases postoperative bleeding. Despite this effect of preoperative aspirin, it did not increase the rates of surgical re-exploration due to excessive postoperative bleeding nor did it increase the rates of packed red blood cell transfusions (PRBC) when preoperative low-dose aspirin (≤160 mg/d) was administered. Preoperative aspirin increases the risk for postoperative bleeding. However, this did not result in an increased need for chest re-exploration and did not increase the rates of PRBC transfusion when preoperative low-dose (≤160 mg/d) aspirin was administered. Aspirin at any dose is associated with decreased mortality and AKI and low-dose aspirin (≤160 mg/d) decreases the incidence of perioperative MI. © 2017 Wiley Periodicals, Inc.

Aspirin and Omeprazole

MedlinePlus

The combination of aspirin and omeprazole is used to reduce the risk of stroke or heart attack in patients who have had or ... risk of developing a stomach ulcer when taking aspirin. Aspirin is in a class of medications called ...

Perception of breathlessness by a 3-minute respiratory exerciser test predicts asthma exacerbations: a prospective cohort study.

PubMed

Loh, Li-Cher; Teh, Pek-Ngor

2009-08-01

We prospectively evaluated the use of a simple 3-Minute Respiratory Exerciser Test (3MRET) that estimates perception of dyspnea to identify patients at risk of asthma exacerbations. A total of 146 stable asthmatics (42 under-perceivers, 69 normal perceivers, and 35 over-perceivers) received follow-up for 12 months. The mean (SD) unscheduled visits to doctors among under-, normal, and over-perceivers were 1.8 (1.2), 2.2 (1.8), and 3.1 (2.3), respectively (p = 0.008). The mean (SD) hospital admissions among the groups were 1.3 (0.5), 1.2 (0.6), and 1.7 (1.3), respectively (p = 0.026). Compared to normal perceivers, over-perceivers had increased risks of unscheduled visits (OD: 5.12; 95% CI = 1.59 to 16.47) and hospital admissions (OD: 0.31; 95% CI = 0.23 to 0.41), defined as > or =2 events in 12 months. The association between over-perceiver and unscheduled visits remained significant after adjusting for forced expiratory volume in 1 second (FEV(1)). Sensitivity and specificity of over-perceivers are 77% and 47%, respectively, for unscheduled visits and 37% and 78%, respectively, for hospital admissions, with significantly better area under ROC for unscheduled visits (0.67 [95% CI = 0.56 to 0.77]; p = 0.003) than for hospital admissions (0.58 [0.471 to 0.70]; p = 0.127). We conclude that the 3MRET may have a role in identifying asthmatic patients with over-perception of dyspnea at risk of clinically important asthma exacerbations.

Productivity losses in chronic obstructive pulmonary disease: a population-based survey.

PubMed

Erdal, Marta; Johannessen, Ane; Askildsen, Jan Erik; Eagan, Tomas; Gulsvik, Amund; Grønseth, Rune

2014-01-01

We aimed to estimate incremental productivity losses (sick leave and disability) of spirometry-defined chronic obstructive pulmonary disease (COPD) in a population-based sample and in hospital-recruited patients with COPD. Furthermore, we examined predictors of productivity losses by multivariate analyses. We performed four quarterly telephone interviews of 53 and 107 population-based patients with COPD and controls, as well as 102 hospital-recruited patients with COPD below retirement age. Information was gathered regarding annual productivity loss, exacerbations of respiratory symptoms and comorbidities. Incremental productivity losses were estimated by multivariate quantile median regression according to the human capital approach, adjusting for sex, age, smoking habits, education and lung function. Main effect variables were COPD/control status, number of comorbidities and exacerbations of respiratory symptoms. Altogether 55%, 87% and 31% of population-based COPD cases, controls and hospital patients, respectively, had a paid job at baseline. The annual incremental productivity losses were 5.8 (95% CI 1.4 to 10.1) and 330.6 (95% CI 327.8 to 333.3) days, comparing population-recruited and hospital-recruited patients with COPD to controls, respectively. There were significantly higher productivity losses associated with female sex and less education. Additional adjustments for comorbidities, exacerbations and FEV1% predicted explained all productivity losses in the population-based sample, as well as nearly 40% of the productivity losses in hospital-recruited patients. Annual incremental productivity losses were more than 50 times higher in hospital-recruited patients with COPD than that of population-recruited patients with COPD. To ensure a precise estimation of societal burden, studies on patients with COPD should be population-based.

GOLD Stage and Treatment in COPD: A 500 Patient Point Prevalence Study.

PubMed

Safka, Katherine A; Wald, Joshua; Wang, Hongyu; McIvor, Luke; McIvor, Andrew

2016-12-22

Background and Objective: The Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines recommend using a combination of spirometry, symptoms and exacerbation history to classify patients into 4 categories (A, B, C, D) to guide treatment decisions along with a stepwise increase in therapy. Our objectives were to identify the GOLD stage of patients in respiratory outpatient clinics and assess how treatment compares to guideline recommendations. Methods: This was a point prevalence study using a convenience sample of 500 patients with chronic obstructive pulmonary disease (COPD) from a single tertiary care outpatient respiratory clinic. Results: Patients' GOLD classification was determined based on symptoms (modified Medical Research Council [mMRC] dyspnea scale, COPD Assessment Test [CAT]), spirometry and self-reported exacerbation history. A total of 8.2% of patients were in the GOLD group A, 28.3% in group B, 4.2% in group C and 59.2% in group D. Conclusions: In this 500 patient point prevalence study we report a low proportion of patients in GOLD group C and a high level of inhaled corticosteroids (ICS)/ long-acting beta2-agonist (LABA) and triple therapy use throughout all GOLD categories. Clinical Implications: The GOLD guidelines have attempted to provide direction to practitioners by grouping patients into 4 groups based on symptoms and exacerbations however, the low prevalence of GOLD group C may indicate that not all of these groupings are clinically relevant. Future research is needed to better identify clinically relevant phenotypes that predict benefit from ICS and methods to promote guideline concordant management in COPD.

Use of helium-oxygen mixture in adult patients presenting with exacerbations of asthma and chronic obstructive pulmonary disease: a systematic review.

PubMed

Colebourn, C L; Barber, V; Young, J D

2007-01-01

We examined systematically all controlled and cross-over randomised trials in patients with acute exacerbations of asthma and chronic obstructive pulmonary disease comparing Heliox against air-oxygen mixtures. Fourteen studies were identified. In asthma studies, peak expiratory flow rate (PEFR) was increased by an average of 29.6% (95% CI 16.6-42.6) by Heliox-driven nebulisers, or by 13.3 l.min(-1) (95% CI 3.71-22.81) absolute. In studies of patients with chronic obstructive pulmonary disease receiving non-invasive ventilation the arterial carbon dioxide tension (P(a)co(2)) and respiratory rate were unchanged: weighted mean difference for P(a)co(2)-0.29kPa (95% CI - 0.64-0.07) favoured Heliox, and for respiratory rate 1.6 breaths.min(-1) (95% CI - 0.93, 4.14) favoured control. Heliox minimally reduced the work of breathing in intubated patients, and reduced intrinsic positive end expiratory pressure (iPEEP). The use of Heliox to drive nebulisers in patients with acute asthma slightly improves airflow measures. We were unable to determine whether this improved recovery.

[Physical therapy intervention during hospitalization in patients with acute exacerbation of chronic obstructive pulmonary disease and pneumonia: A randomized clinical trial].

PubMed

Martín-Salvador, Adelina; Colodro-Amores, Gloria; Torres-Sánchez, Irene; Moreno-Ramírez, M Paz; Cabrera-Martos, Irene; Valenza, Marie Carmen

2016-04-01

Respiratory infections involve not only hospitalization due to pneumonia, but also acute exacerbations of COPD (AECOPD). The objective of the present study was to evaluate the effectiveness of a physical therapy intervention during hospitalization in patients admitted due to community-acquired pneumonia (CAP) and AECOPD. Randomized clinical trial, 44 patients were randomized into 2 groups: a control group which received standard medical therapy (oxygen therapy and pharmacotherapy) and an experimental group that received standard treatment and a physical therapy intervention (breathing exercises, electrostimulation, exercises with elastic bands and relaxation). Between-groups analysis showed that after the intervention (experimental vs. control) significant differences were found in perceived dyspnoea (P=.041), and right and left quadriceps muscle strength (P=.008 and P=.010, respectively). In addition, the subscale of "domestic activities" of the functional ability related to respiratory symptoms questionnaire showed significant differences (P=.036). A physical therapy intervention during hospitalization in patients with AECOPD and CAP can generate skeletal muscle level gains that exceed the deterioration caused by immobilization during hospitalization. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Localized periorbital edema induced by aspirin.

PubMed

Katz, Y; Goldberg, N; Kivity, S

1993-07-01

We documented localized periorbital edema in two patients with aspirin sensitivity without underlying chronic urticaria. The reaction developed 30 min after ingestion of 62.5 and 125 mg of aspirin, respectively. No systemic symptoms were observed. Other NSAIDs did not induce symptoms. These patients were able to tolerate doses of aspirin after pretreatment with terfenadine. These observations suggest that histamine plays a central role in aspirin-induced skin reaction. Despite the fact that terfenadine blocks the drug-induced reaction, this protocol should be used with caution and only where there is no feasible alternative to aspirin.

A headache not to be sneezed at.

PubMed

Garry, D; Forrest-Hay, A

2009-05-01

A 32-year-old male patient presented to the emergency department (ED) complaining of a headache and vertigo precipitated by sneezing. He had a recent history of neck trauma. Examination revealed horizontal nystagmus and a gait that veered to the left, exacerbated by heel to toe walking. A diagnosis of vertebral artery dissection (VAD) was suspected. A bleed was ruled out in the ED by computerised tomography, after which the patient was loaded with aspirin. The diagnosis was confirmed by magnetic resonance imaging and magnetic resonance angiography. Although optimal treatment for VAD is unknown, the Cervical Artery Dissection in Stroke Study (CADISS) is an ongoing randomised multicentre prospective study comparing antiplatelet therapy with anticoagulation for patients with both carotid artery dissection and VAD. Headache is a very common presentation to the ED and a full neurological examination is essential if rarer causes are not to be missed.

Identifying and Describing the Impact of Cyclone, Storm and Flood Related Disasters on Treatment Management, Care and Exacerbations of Non-communicable Diseases and the Implications for Public Health.

PubMed

Ryan, Benjamin; Franklin, Richard C; Burkle, Frederick M; Aitken, Peter; Smith, Erin; Watt, Kerrianne; Leggat, Peter

2015-09-28

Over the last quarter of a century the frequency of natural disasters and the burden of non-communicable diseases (NCD) across the globe have been increasing. For individuals susceptible to, or chronically experiencing, NCDs this has become a significant risk. Disasters jeopardize access to essential treatment, care, equipment, water and food, which can result in an exacerbation of existing conditions or even preventable death. Consequently, there is a need to expand the public health focus of disaster management to include NCDs. To provide a platform for this to occur, this article presents the results from a systematic review that identifies and describes the impact of cyclone, flood and storm related disasters on those susceptible to, or experiencing, NCDs. The NCDs researched were: cardiovascular diseases; cancers; chronic respiratory diseases; and diabetes.   Four electronic publication databases were searched with a date limit of 31 December 2014. The data was analyzed through an aggregation of individual papers to create an overall data description. The data was then grouped by disease to describe the impact of a disaster on treatment management, exacerbation, and health care of people with NCDs. The PRISMA checklist was used to guide presentation of the research.   The review identified 48 relevant articles. All studies represented developed country data. Disasters interrupt treatment management and overall care for people with NCDs, which results in an increased risk of exacerbation of their illness or even death. The interruption may be caused by a range of factors, such as damaged transport routes, reduced health services, loss of power and evacuations. The health impact varied according to the NCD. For people with chronic respiratory diseases, a disaster increases the risk of acute exacerbation. Meanwhile, for people with cancer, cardiovascular diseases and diabetes there is an increased risk of their illness exacerbating, which can result in death.      Cyclone, flood and storm related disasters impact on treatment management and care for people with NCDs. Possible consequences include exacerbation of illness, complications or even death. There is now a need to expand traditional disaster approaches by public health to incorporate NCDs. This must be guided by the major NCDs identified by the World Health Organization and implemented in-line with the Sendai Framework for Disaster Risk Reduction: 2015-2030. This includes understanding all the factors that influence both direct and indirect (preventable) morbidity and mortality related to NCDs during and after disasters. Once achieved, disaster planners and public health professionals will be in a position to develop and implement effective mitigation strategies.

A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone.

PubMed

Schleinitz, Mark D; Heidenreich, Paul A

2005-02-15

Although clopidogrel plus aspirin is more effective than aspirin alone in preventing subsequent vascular events in patients with unstable angina, the cost-effectiveness of this combination has yet to be examined in this high-risk population. To determine the cost-effectiveness of clopidogrel plus aspirin compared with aspirin alone. Cost-utility analysis. Published literature. Patients with unstable angina and electrocardiographic changes or non-Q-wave myocardial infarction. time horizon: Lifetime. Societal. Combination therapy with clopidogrel, 75 mg/d, plus aspirin, 325 mg/d, for 1 year, followed by aspirin monotherapy, was compared with lifelong aspirin therapy, 325 mg/d. Lifetime costs, life expectancy in quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. Patients treated with aspirin alone lived 9.51 QALYs after their initial event and incurred expenses of 127,700 dollars; the addition of clopidogrel increased life expectancy to 9.61 QALYs and costs to 129,300 dollars. The incremental cost-effectiveness ratio for clopidogrel plus aspirin compared with aspirin alone was 15,400 dollars per QALY. The analysis of 1 year of therapy was robust to all sensitivity analyses. In the probabilistic sensitivity analysis, fewer than 3% of simulations resulted in cost-effectiveness ratios over 50,000 dollars per QALY. The cost-effectiveness of longer combination therapy depends critically on the balance of thrombotic event rates, durable efficacy, and the increased bleeding rate in patients taking clopidogrel. This analysis may not apply to patients with severe heart failure, those undergoing long-term anticoagulant therapy, those recently managed with revascularization, or those undergoing short-term treatment with glycoprotein IIb/IIIa inhibitors. In patients with high-risk acute coronary syndromes, 1 year of therapy with clopidogrel plus aspirin results in greater life expectancy than aspirin alone, at a cost within the traditional limits of cost-effectiveness. The durable efficacy of clopidogrel relative to the risk for hemorrhage should be further explored before more protracted therapy can be recommended.

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling

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

Yang, Guang; Wang, Yuan; Feng, Jinyan

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. Inmore » addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. - Highlights: • Aspirin inhibits the levels of liquid droplets, triglyceride and cholesterol in HCC cells. • Aspirin is able to down-regulate ACSL1 in HCC cells. • NF-κB inhibitor PDTC can down-regulate ACSL1 and reduces lipogenesis in HCC cells. • Aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling.« less

Impact of aspirin resistance on outcomes among patients following coronary artery bypass grafting: exploratory analysis from randomized controlled trial (NCT01159639).

PubMed

Petricevic, Mate; Kopjar, Tomislav; Gasparovic, Hrvoje; Milicic, Davor; Svetina, Lucija; Zdilar, Boris; Boban, Marko; Mihaljevic, Martina Zrno; Biocina, Bojan

2015-05-01

Individual variability in the response to aspirin, has been established by various platelet function assays, however, the clinical relevance of aspirin resistance (AR) in patients undergoing coronary artery bypass grafting (CABG) has to be evaluated. Our working group conducted a randomized controlled trial (NCT01159639) with the aim to assess impact of dual antiplatelet therapy (APT) on outcomes among patients with AR following CABG. Patients that were aspirin resistant on fourth postoperative day (POD 4) were randomly assigned to receive either dual APT with clopidogrel (75 mg) plus aspirin (300 mg)-intervention arm or monotherapy with aspirin (300 mg)-control arm. This exploratory analysis compares clinical outcomes between aspirin resistant patients allocated to control arm and patients that have had adequate platelet inhibitory response to aspirin at POD 4. Both groups were treated with 300 mg of aspirin per day following surgery. We sought to evaluate the impact of early postoperative AR on outcomes among patients following CABG. Exploratory analysis included a total number of 325 patients. Of those, 215 patients with adequate response to aspirin and 110 patients with AR allocated to aspirin monotherapy following randomization protocol. The primary efficacy end point (MACCEs-major adverse cardiac and cardiovascular events) occurred in 10 and 6 % of patients with AR and with adequate aspirin response, respectively (p = 0.27). Non-significant differences were observed in bleeding events occurrence. Subgroup analysis of the primary end point revealed that aspirin resistant patients with BMI > 30 kg/m(2) tend to have a higher occurrence of MACCEs 18 versus 5 % (relative risk 0.44 [95 % CI 0.16-1.16]; p = 0.05). This exploratory analysis did not reveal significant impact of aspirin resistance on outcomes among patients undergoing CABG. Further, sufficiently powered studies are needed in order to evaluate clinical relevance of AR in patients undergoing CABG.

Effectiveness and predictors of failure of noninvasive mechanical ventilation in acute respiratory failure.

PubMed

Martín-González, F; González-Robledo, J; Sánchez-Hernández, F; Moreno-García, M N; Barreda-Mellado, I

2016-01-01

To assess the effectiveness and identify predictors of failure of noninvasive ventilation. A retrospective, longitudinal descriptive study was made. Adult patients with acute respiratory failure. A total of 410 consecutive patients with noninvasive ventilation treated in an Intensive Care Unit of a tertiary university hospital from 2006 to 2011. Noninvasive ventilation. Demographic variables and clinical and laboratory test parameters at the start and two hours after the start of noninvasive ventilation. Evolution during admission to the Unit and until hospital discharge. The failure rate was 50%, with an overall mortality rate of 33%. A total of 156 patients had hypoxemic respiratory failure, 87 postextubation respiratory failure, 78 exacerbation of chronic obstructive pulmonary disease, 61 hypercapnic respiratory failure without chronic obstructive pulmonary disease, and 28 had acute pulmonary edema. The failure rates were 74%, 54%, 27%, 31% and 21%, respectively. The etiology of respiratory failure, serum bilirubin at the start, APACHEII score, radiological findings, the need for sedation to tolerate noninvasive ventilation, changes in level of consciousness, PaO2/FIO2 ratio, respiratory rate and heart rate from the start and two hours after the start of noninvasive ventilation were independently associated to failure. The effectiveness of noninvasive ventilation varies according to the etiology of respiratory failure. Its use in hypoxemic respiratory failure and postextubation respiratory failure should be assessed individually. Predictors of failure could be useful to prevent delayed intubation. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma cells to temozolomide therapy

PubMed Central

Li, Ziwei; Lin, Lin; Meng, Xiangqi; Han, Bo; Wang, Ruijia; Wu, Pengfei; Li, Jianlong; Cai, Jinquan; Jiang, Chuanlu

2017-01-01

Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin. Aspirin acted as the glioma growth-inhibitory and pro-apoptosis roles by inhibiting the SHH/GLI1 pathway and reprogramming the epithelial to mesenchymal transition (EMT). The immunofluorescence assay showed aspirin could prevent the nuclear translocation of GLI1 to inhibit its transcriptional regulation. The stable lentiviral overexpression of GLI1 reversed the DNA double strand breaks (DSBs) caused by the GANT61 and TMZ. Furthermore, aspirin combined with TMZ enhanced chemosensitivity and GLI1-induced chemoprotection was partly blocked by aspirin in vitro and in vivo. Collectively, aspirin has a therapeutic potential for SHH/GLI1 targeted therapy against glioma cells. Acquired activation of GLI1 protects glioma cells against TMZ therapy. Impairment of DNA DSBs repair activity might be involved in the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a promising strategy against malignant glioma. PMID:28446712

Aspirin use and head and neck cancer survival: an observational study of 11,623 person-years follow-up.

PubMed

Kim, Shin-Ae; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

2018-02-01

Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risks for certain human cancers. However, the effects of aspirin and NSAIDs on head and neck squamous cell carcinoma (HNSCC) remain controversial, and the prognostic effects of these drugs in patients with HNSCC are largely unknown. This study examined the clinical impact of aspirin and NSAIDs on disease recurrence and survival in patients with HNSCC. This study analysed a cohort of 1392 consecutive patients who received definitive treatment for previously untreated HNSCC at our tertiary referral center. Aspirin or NSAID use was considered positive if the patients were receiving aspirin or NSAID medication from HNSCC diagnosis to at least 1 year after treatment initiation. Cox proportional hazard models were utilised to determine the association of aspirin and/or NSAID use with recurrence, survival, and second primary cancer occurrence. Of 1392 patients, 81 (5.8%) and 89 (6.4%) received post-diagnosis treatment with aspirin and NSAIDs, respectively. After controlling for clinical factors, aspirin and NSAIDs were not significantly associated with recurrence, survival, or second cancer occurrence (P > 0.05). The cumulative dose of aspirin or NSAIDs did not alter survival outcomes (P > 0.05). Our data illustrated that the use of aspirin or NSAIDs has no effect on survival or recurrence in patients with HNSCC.

Should This Patient Receive Aspirin?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

PubMed

Burns, Risa B; Graham, Kelly; Sawhney, Mandeep S; Reynolds, Eileen E

2017-12-05

Aspirin exerts antiplatelet effects through irreversible inhibition of cyclooxygenase-1, whereas its anticancer effects may be due to inhibition of cyclooxygenase-2 and other pathways. In 2009, the U.S. Preventive Services Task Force endorsed aspirin for primary prevention of cardiovascular disease. However, aspirin's role in cancer prevention is still emerging, and no groups currently recommend its use for this purpose. To help physicians balance the benefits and harms of aspirin in primary disease prevention, the Task Force issued a guideline titled, "Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer" in 2016. In the evidence review conducted for the guideline, cardiovascular disease mortality and colorectal cancer mortality were significantly reduced among persons taking aspirin. However, there was no difference in nonfatal stroke, cardiovascular disease mortality, or all-cause mortality, nor in total cancer mortality, among those taking aspirin. Aspirin users were found to be at increased risk for major gastrointestinal bleeding. In this Beyond the Guidelines, the guideline is reviewed and 2 experts discuss how they would apply it to a 57-year-old man considering starting aspirin for primary prevention. Our experts review the data on which the guideline is based, discuss how they would balance the benefits and harms of aspirin therapy, and explain how they would incorporate shared decision making into clinical practice.

Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma cells to temozolomide therapy.

PubMed

Ming, Jianguang; Sun, Bo; Li, Ziwei; Lin, Lin; Meng, Xiangqi; Han, Bo; Wang, Ruijia; Wu, Pengfei; Li, Jianlong; Cai, Jinquan; Jiang, Chuanlu

2017-04-01

Aberrant activation of sonic hedgehog (SHH)/glioma-associated oncogene homolog 1 (GLI1) pathway plays an important role in the tumorigenicity of malignant glioma cells and resistance to temozolomide (TMZ). Here we investigated the aspirin's antineoplastic molecular route by targeting SHH/GLI1 pathway and examined the feasibility of aspirin combined with TMZ therapy. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) revealed that the activity of the SHH/GLI1 pathway was strongly inhibited by aspirin. Aspirin acted as the glioma growth-inhibitory and pro-apoptosis roles by inhibiting the SHH/GLI1 pathway and reprogramming the epithelial to mesenchymal transition (EMT). The immunofluorescence assay showed aspirin could prevent the nuclear translocation of GLI1 to inhibit its transcriptional regulation. The stable lentiviral overexpression of GLI1 reversed the DNA double strand breaks (DSBs) caused by the GANT61 and TMZ. Furthermore, aspirin combined with TMZ enhanced chemosensitivity and GLI1-induced chemoprotection was partly blocked by aspirin in vitro and in vivo . Collectively, aspirin has a therapeutic potential for SHH/GLI1 targeted therapy against glioma cells. Acquired activation of GLI1 protects glioma cells against TMZ therapy. Impairment of DNA DSBs repair activity might be involved in the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a promising strategy against malignant glioma.

Talk with Your Doctor about Taking Aspirin Every Day

MedlinePlus

... En español Talk with Your Doctor about Taking Aspirin to Prevent Disease Browse Sections The Basics Overview ... and Risks What are the benefits of taking aspirin regularly? Low-dose aspirin can reduce your risk ...

Aspirin Use Prior to Coronary Artery Bypass Grafting Surgery: a Systematic Review.

PubMed

Elbadawi, Ayman; Saad, Marwan; Nairooz, Ramez

2017-02-01

Aspirin use before coronary artery bypass graft (CABG) surgery has been a puzzling question for years. Controversy existed regarding the overall benefits vs. risk of pre-operative aspirin use and was translated to conflicting guidelines from major societies. Observational studies have suggested a reduced mortality with pre-operative aspirin use. A meta-analysis of randomized controlled trials showed increased risk of post-operative bleeding with aspirin, with no associated increased mortality risk. A recent large randomized controlled trial did not find a significant difference in bleeding risk or post-operative mortality with pre-CABG aspirin use. The results of available studies showed a beneficial effect with pre-CABG aspirin use by decreasing thrombotic complications and perioperative myocardial infarction, with an associated adverse risk of bleeding that did not affect mortality rates. Given overall benefit-risk assessment, we are in favor of pre-operative aspirin use in CABG patients.

Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease.

PubMed

Eikelboom, John W; Connolly, Stuart J; Bosch, Jackie; Dagenais, Gilles R; Hart, Robert G; Shestakovska, Olga; Diaz, Rafael; Alings, Marco; Lonn, Eva M; Anand, Sonia S; Widimsky, Petr; Hori, Masatsugu; Avezum, Alvaro; Piegas, Leopoldo S; Branch, Kelley R H; Probstfield, Jeffrey; Bhatt, Deepak L; Zhu, Jun; Liang, Yan; Maggioni, Aldo P; Lopez-Jaramillo, Patricio; O'Donnell, Martin; Kakkar, Ajay K; Fox, Keith A A; Parkhomenko, Alexander N; Ertl, Georg; Störk, Stefan; Keltai, Matyas; Ryden, Lars; Pogosova, Nana; Dans, Antonio L; Lanas, Fernando; Commerford, Patrick J; Torp-Pedersen, Christian; Guzik, Tomek J; Verhamme, Peter B; Vinereanu, Dragos; Kim, Jae-Hyung; Tonkin, Andrew M; Lewis, Basil S; Felix, Camilo; Yusoff, Khalid; Steg, P Gabriel; Metsarinne, Kaj P; Cook Bruns, Nancy; Misselwitz, Frank; Chen, Edmond; Leong, Darryl; Yusuf, Salim

2017-10-05

We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Effect of Prior Aspirin Treatment on Patients With Acute Coronary Syndromes: Insights From the PROSPECT Study.

PubMed

Brener, Sorin J; Maehara, Akiko; Mintz, Gary S; Weisz, Giora; de Bruyne, Bernard; Serruys, Patrick W; Stone, Gregg W

2015-12-01

Prior aspirin treatment is considered a risk factor for adverse outcomes in acute coronary syndrome (ACS) patients. The relationships between aspirin pretreatment and findings on quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS), as well as clinical outcomes, are not well understood. In the PROSPECT trial, QCA and triple-vessel IVUS imaging were performed after successful percutaneous coronary intervention (PCI) of the culprit lesion(s) in ACS patients. We compared patients receiving aspirin within 7 days of enrollment to those naive to aspirin. Propensity score matching was performed to adjust for differences in baseline characteristics. Aspirin-pretreated patients (n = 236; 35%) were older and more likely to have known coronary disease than those without pretreatment (P≤.01 for all). Pretreated patients had more untreated non-culprit lesions with angiographic and IVUS characteristics predictive of future events (53.1% vs 38.6%; P<.001). There were no significant differences in overall major adverse cardiac event (MACE) rates at 3 years between the aspirin and no-aspirin groups (23.6% vs 18.8%, respectively; P=.17) in unadjusted or propensity-adjusted analyses. Prior aspirin use was not an independent predictor of MACE at 3 years (hazard ratio, 1.21; 95% confidence interval, 0.73-2.01; P=.45). In the PROSPECT trial, aspirin pretreatment identifies an older population with more advanced coronary disease. Aspirin pretreatment was not an independent predictor of MACE in ACS patients treated with an early invasive strategy. The extent to which aspirin pretreatment is a risk factor for adverse events after PCI in ACS should be revisited.

Aspirin inhibits the growth of Helicobacter pylori and enhances its susceptibility to antimicrobial agents

PubMed Central

Wang, W H; Wong, W M; Dailidiene, D; Berg, D E; Gu, Q; Lai, K C; Lam, S K; Wong, B C Y

2003-01-01

Background and aim: The role of Helicobacter pylori and aspirin in peptic ulcer formation and recurrence remains an important clinical topic. The interaction between aspirin and H pylori in vitro is also not clear. We investigated the effect of aspirin on the growth of H pylori and on the susceptibility of H pylori to antimicrobials. Methods: Time killing studies of H pylori were performed with different concentrations of aspirin and salicylate. Growth of bacteria was assessed spectrophotometrically and by viable colony count. The effects of aspirin on the efficiency of colony formation and on metronidazole induced mutation to rifampicin resistance in H pylori were determined. Minimal inhibitory concentrations (MICs) of aspirin and metronidazole were tested by the standard agar dilution method. MICs of amoxycillin and clarithromycin were determined by the E test method. Results: Aspirin and salicylate inhibited the growth of H pylori in a dose dependent manner and bactericidal activity was due to cell lysis. Aspirin 400 μg/ml caused a 2 logs decrease in colony forming units/ml at 48 hours, and suppressed the normal ability of metronidazole to induce new mutations to rifampicin. The IC90 of aspirin was 512 μg/ml. Increased susceptibility of amoxycillin, clarithromycin, and metronidazole to H pylori was observed at 1 mM (180 μg/ml) aspirin. Conclusions: Aspirin inhibited the growth of H pylori, suppressed the mutagenic effect of metronidazole, and enhanced the susceptibility of H pylori to antimicrobial agents. This mechanism is important in future drug development for effective clearing and overcoming resistance. PMID:12631656

Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial.

PubMed

Alexander, John H; Lopes, Renato D; Thomas, Laine; Alings, Marco; Atar, Dan; Aylward, Philip; Goto, Shinya; Hanna, Michael; Huber, Kurt; Husted, Steen; Lewis, Basil S; McMurray, John J V; Pais, Prem; Pouleur, Hubert; Steg, Philippe Gabriel; Verheugt, Freek W A; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars

2014-01-01

We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91%, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10% vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78%, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.

Preoperative Aspirin Does Not Increase Transfusion or Reoperation in Isolated Valve Surgery.

PubMed

Goldhammer, Jordan E; Herman, Corey R; Berguson, Mark W; Torjman, Marc C; Epstein, Richard H; Sun, Jian-Zhong

2017-10-01

Preoperative aspirin has been studied in patients undergoing isolated coronary artery bypass graft surgery. However, there is a paucity of clinical data available evaluating perioperative aspirin in other cardiac surgical procedures. This study was designed to investigate the effects of aspirin on bleeding and transfusion in patients undergoing non-emergent, isolated, heart valve repair or replacement. Retrospective, cohort study. Academic medical center. A total of 694 consecutive patients having non-emergent, isolated, valve repair or replacement surgery at an academic medical center were identified. Of the 488 patients who met inclusion criteria, 2 groups were defined based on their preoperative use of aspirin: those taking (n = 282), and those not taking (n = 206) aspirin within 5 days of surgery. Binary logistic regression was used to examine relationships among demographic and clinical variables. No significant difference was found between the aspirin and non-aspirin groups with respect to the percentage receiving red blood cell (RBC) transfusion, mean RBC units transfused in those who required transfusion, massive transfusion of RBC, or amounts of fresh frozen plasma, cryoprecipitate, or platelets. Aspirin was not associated with an increase in the rate of re-exploration for bleeding (5.3% v 6.3%, p = 0.478). Major adverse cardiocerebral events (MACE), 30-day mortality, and 30-day readmission rates were not statistically different between the aspirin-and non-aspirin-treated groups. Preoperative aspirin therapy in elective, isolated, valve surgery did not result in an increase in transfusion or reoperation for bleeding and was not associated with reduced readmission rate, MACE, or 30-day mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuous Aspirin Use Does Not Increase Bleeding Risk of Split-Thickness Skin Transplantation Repair to Chronic Wounds.

PubMed

Sun, Yanwei; Wang, Yibing; Li, Liang; Zhang, Zheng; Wang, Ning; Wu, Dan

Discontinuation of aspirin therapy before cutaneous surgery may cause serious complications. The aim of this prospective study was to evaluate the bleeding risk of split-thickness skin transplantation repair to chronic wounds in patients on aspirin therapy. A total of 97 patients who underwent split-thickness skin transplantation surgery of chronic wounds during a 2-year period were enrolled. They were categorized on the basis of aspirin therapies. The primary outcome was postoperative bleeding and bleeding complications. Univariate analysis was performed to examine the association between aspirin and bleeding complications. Among the 26 patients taking aspirin continuously in group A, there were 5 bleeding complications (19.23%). Among the 55 nonusers in group B, there were 10 bleeding complications (18.18%). Among the 16 discontinuous patients in group C, there were 3 bleeding complications (18.75%). No statistical differences were found among the groups ( P = .956). Univariate analysis showed that continuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.933; 95% confidence interval, 0.283-3.074; P = .910 in the aspirin and control groups) and that discontinuous aspirin use was not significantly associated with bleeding complications (odds ratio, 0.963; 95% confidence interval, 0.230-4.025; P = .959 in the aspirin and control groups; odds ratio, 0.969; 95% confidence interval, 0.198-4.752; P = .969 in the aspirin and discontinuous groups). Continuous aspirin use does not produce an additional bleeding risk in patients who undergo split-thickness skin transplantation repair of chronic wounds.

Review of pharmacokinetic and pharmacodynamic modeling and safety of proton pump inhibitors and aspirin.

PubMed

Gesheff, Martin G; Franzese, Christopher J; Bliden, Kevin P; Contino, Chase J; Rafeedheen, Rahil; Tantry, Udaya S; Gurbel, Paul A

2014-09-01

The efficacy of aspirin in primary and secondary prevention of cardiovascular diseases has been convincingly demonstrated. Gastrointestinal (GI) adverse effects with aspirin may lead to poor adherence and/or discontinuation of treatment. Proton pump inhibitors (PPIs) have been used for more than 20 years as the first choice for treating peptic ulcers and their bleeding complications, gastroesophageal reflux disease, non-steroidal anti-inflammatory drug-induced GI lesions and dyspepsia. Adherence becomes a major concern when aspirin is co-prescribed with PPIs to prevent GI adverse effects. Combining aspirin and PPIs into one tablet is an effective approach to address aspirin-related GI adverse effects and increase adherence to aspirin therapy for the prevention of cardiovascular diseases.

The Aspirin Foundation Scientific Conference: the history, the present state and the future of aspirin prophylaxis

PubMed Central

Smith, Tom; Elwood, Peter; Keating, Conrad; Rothwell, Peter; Detering, Elmar; Freedman, Andrew; Langley, Ruth; Logan, Richard; Phillips, Ceri; DeCensi, Andrea

2014-01-01

The 2013 Aspirin Foundation Conference covered a range of topics from clinical and medical history, epidemiology, health economics, and the current uses of aspirin in general practice and in the treatment and prevention of cancer. The use of aspirin as primary prevention in people at risk of atherosclerotic events is now well known, but its use as a preventative agent in some cancer types is still under discussion, and data on colorectal and lung cancer were presented at this meeting. The potential use of aspirin in preventing vascular disease in HIV patients was also discussed. The cost effectiveness of aspirin as a primary prevention strategy was discussed for the first time in this series of meetings. PMID:24678343

Localized periorbital edema as a clinical manifestation of sulfite sensitivity.

PubMed

Park, H S; Nahm, D

1996-08-01

Sulfite is commonly used in pharmaceuticals as a preservative. We report a unique clinical presentation of localized periorbital edema on the left eye after administration of sulfite-containing dexamethasone. The patient's sulfite sensitivity was confirmed by sulfite oral provocation test: periorbital edema on the same site developed after ingestion of 200 mg sodium bisulfite. She was non-atopic and did not complain of any respiratory symptoms. Allergy skin prick test with 100 mg/ml sodium bisulfite showed a negative result. She also has aspirin-sensitive urticaria which was confirmed by oral provocation test. In conclusion, sulfite can induce a localized periorbital edema, an uncommon manifestation in sensitive patients. Further investigations are needed to clarify the pathogenetic mechanisms.

Aspirin disrupts the mTOR-Raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition.

PubMed

Sun, Danni; Liu, Hongchun; Dai, Xiaoyang; Zheng, Xingling; Yan, Juan; Wei, Rongrui; Fu, Xuhong; Huang, Min; Shen, Aijun; Huang, Xun; Ding, Jian; Geng, Meiyu

2017-10-10

Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we revealed the mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described a mechanism-based rationale for the use of aspirin in cancer therapy. We found that aspirin inhibited mTORC1 signaling through AMPK-dependent and -independent manners. Aspirin inhibited the AMPK-TSC pathway, thus resulting in the suppression of mTORC1 activity. In parallel, it directly disrupted the mTOR-raptor interaction. Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Aspirin and sorafenib showed synergetic anticancer efficacy in the SMMC-7721 model. Our study provides mechanistic insights and a mechanism-based rationale for the roles of aspirin in cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of chronic aspirin ingestion on epithelial proliferation in rat fundus, antrum, and duodenum

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

Eastwood, G.L.; Quimby, G.F.

We studied the effect of chronic aspirin ingestion on gastroduodenal epithelial proliferation by feeding rats aspirin in the drinking water. A control group of rats received plain water. At the end of 4 wk, (3H)-thymidine was given intravenously to label proliferating cells, and the rats were killed 1 h later. Sections of fundus, antrum, and proximal duodenum were processed for light autoradiography. We found that chronic aspirin ingestion stimulated epithelial proliferation in fundic mucosa but had no effect in the antrum. In the duodenum, aspirin increased proliferation in the lowest four crypt-cell positions, which most likely indicates an increase inmore » stem-cell production. None of the tissues contained evidence of inflammation or ulceration. The proliferative effects of aspirin may help explain the previously observed phenomenon of mucosal adaptation in the rat after repeated exposure to aspirin. Further, if human gastroduodenal epithelium responds in a similar manner to chronic aspirin exposure, the effects on proliferation may explain in part the distribution of aspirin-associated ulcers.« less

Comparative effects of aspirin and enteric-coated aspirin on loss of chromium 51-labeled erythrocytes from the gastrointestinal tract

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

Robbins, D.C.; Schwartz, R.S.; Kutny, K.

Sodium chromate Cr 51 was used to label red blood cells of 19 healthy male volunteers, whose stools were collected for four days before and four days during oral administration of either uncoated (N . 9) or enteric-coated (N . 10) aspirin. Each subject received 2.925 gm/day of aspirin, in three equal doses separated by eight-hour intervals, for a total of seven days. During drug use, stools were collected on days 4 through 7. Fecal blood content, estimated by measuring radioactivity in the stools, was significantly higher (P less than 0.001) during use of either type of aspirin than atmore » baseline, but losses measured during use of the coated aspirin (mean, 1.54 ml/day) were significantly lower (P less than 0.001) than those measured during use of the uncoated aspirin (mean, 4.33 ml/day). The two types of aspirin produced equivalent serum concentrations of salicylates. We conclude that enteric-coated aspirin reduces gastrointestinal blood loss.« less

Utility of brief questionnaires of health-related quality of life (Airways Questionnaire 20 and Clinical COPD Questionnaire) to predict exacerbations in patients with asthma and COPD

PubMed Central

2013-01-01

Background There is some evidence that quality of life measured by long disease-specific questionnaires may predict exacerbations in asthma and COPD, however brief quality of life tools, such as the Airways Questionnaire 20 (AQ20) or the Clinical COPD Questionnaire (CCQ), have not yet been evaluated as predictors of hospital exacerbations. Objectives To determine the ability of brief specific health-related quality of life (HRQoL) questionnaires (AQ20 and CCQ) to predict emergency department visits (ED) and hospitalizations in patients with asthma and COPD, and to compare them to longer disease-specific questionnaires, such as the St George´s Respiratory Questionnaire (SGRQ), the Chronic Respiratory Disease Questionnaire (CRQ) and the Asthma Quality of Life Questionnaire (AQLQ). Methods We conducted a two-year prospective cohort study of 208 adult patients (108 asthma, 100 COPD). Baseline sociodemographic, clinical, functional and psychological variables were assessed. All patients completed the AQ20 and the SGRQ. COPD patients also completed the CCQ and the CRQ, while asthmatic patients completed the AQLQ. We registered all exacerbations that required ED or hospitalizations in the follow-up period. Differences between groups (zero ED visits or hospitalizations versus ≥ 1 ED visits or hospitalizations) were tested with Pearson´s X2 or Fisher´s exact test for categorical variables, ANOVA for normally distributed continuous variables, and Mann–Whitney U test for non-normally distributed variables. Logistic regression analyses were performed to estimate the predictive ability of each HRQoL questionnaire. Results In the first year of follow-up, the AQ20 scores predicted both ED visits (OR: 1.19; p = .004; AUC 0.723) and hospitalizations (OR: 1.21; p = .04; AUC 0.759) for asthma patients, and the CCQ emerged as independent predictor of ED visits in COPD patients (OR: 1.06; p = .036; AUC 0.651), after adjusting for sociodemographic, clinical, and psychological variables. Among the longer disease-specific questionnaires, only the AQLQ emerged as predictor of ED visits in asthma patients (OR: 0.9; p = .002; AUC 0.727). In the second year of follow-up, none of HRQoL questionnaires predicted exacerbations. Conclusions AQ20 predicts exacerbations in asthma and CCQ predicts ED visits in COPD in the first year of follow-up. Their predictive ability is similar to or even higher than that of longer disease-specific questionnaires. PMID:23706146

Acute respiratory distress syndrome.

PubMed

Confalonieri, Marco; Salton, Francesco; Fabiano, Francesco

2017-06-30

Since its first description, the acute respiratory distress syndrome (ARDS) has been acknowledged to be a major clinical problem in respiratory medicine. From July 2015 to July 2016 almost 300 indexed articles were published on ARDS. This review summarises only eight of them as an arbitrary overview of clinical relevance: definition and epidemiology, risk factors, prevention and treatment. A strict application of definition criteria is crucial, but the diverse resource-setting scenarios foster geographic variability and contrasting outcome data. A large international multicentre prospective cohort study including 50 countries across five continents reported that ARDS is underdiagnosed, and there is potential for improvement in its management. Furthermore, epidemiological data from low-income countries suggest that a revision of the current definition of ARDS is needed in order to improve its recognition and global clinical outcome. In addition to the well-known risk-factors for ARDS, exposure to high ozone levels and low vitamin D plasma concentrations were found to be predisposing circumstances. Drug-based preventive strategies remain a major challenge, since two recent trials on aspirin and statins failed to reduce the incidence in at-risk patients. A new disease-modifying therapy is awaited: some recent studies promised to improve the prognosis of ARDS, but mortality and disabling complications are still high in survivors in intensive care. Copyright ©ERS 2017.

The effect of helium-oxygen-assisted mechanical ventilation on chronic obstructive pulmonary disease exacerbation: A systemic review and meta-analysis.

PubMed

Wu, Xu; Shao, Chuan; Zhang, Liang; Tu, Jinjing; Xu, Hui; Lin, Zhihui; Xu, Shuguang; Yu, Biyun; Tang, Yaodong; Li, Shanqun

2018-03-01

Chronic obstructive pulmonary disease (COPD) is often accompanied by acute exacerbations. Patients of COPD exacerbation suffering from respiratory failure often need the support of mechanical ventilation. Helium-oxygen can be used to reduce airway resistance during mechanical ventilation. The aim of this study is to evaluate the effect of helium-oxygen-assisted mechanical ventilation on COPD exacerbation through a meta-analysis. A comprehensive literature search through databases of Pub Med (1966∼2016), Ovid MEDLINE (1965∼2016), Cochrane EBM (1991∼2016), EMBASE (1974∼2016) and Ovid MEDLINE was performed to identify associated studies. Randomized clinical trials met our inclusion criteria that focus on helium-oxygen-assisted mechanical ventilation on COPD exacerbation were included. The quality of the papers was evaluated after inclusion and information was extracted for meta-analysis. Six articles and 392 patients were included in total. Meta-analysis revealed that helium-oxygen-assisted mechanical ventilation reduced Borg dyspnea scale and increased arterial PH compared with air-oxygen. No statistically significant difference was observed between helium-oxygen and air-oxygen as regards to WOB, PaCO 2 , OI, tracheal intubation rates and mortality within hospital. Our study suggests helium-oxygen-assisted mechanical ventilation can help to reduce Borg dyspnea scale. In terms of the tiny change of PH, its clinical benefit is negligible. There is no conclusive evidence indicating the beneficial effect of helium-oxygen-assisted mechanical ventilation on clinical outcomes or prognosis of COPD exacerbation. © 2017 John Wiley & Sons Ltd.

Cost-effectiveness of antibiotics for COPD management: observational analysis using CPRD data.

PubMed

Ronaldson, Sarah J; Raghunath, Anan; Torgerson, David J; Van Staa, Tjeerd

2017-04-01

It is often difficult to determine the cause of chronic obstructive pulmonary disease (COPD) exacerbations, and antibiotics are frequently prescribed. This study conducted an observational cost-effectiveness analysis of prescribing antibiotics for exacerbations of COPD based on routinely collected data from patient electronic health records. A cohort of 45 375 patients aged 40 years or more who attended their general practice for a COPD exacerbation during 2000-2013 was identified from the Clinical Practice Research Datalink. Two groups were formed ("immediate antibiotics" or "no antibiotics") based on whether antibiotics were prescribed during the index general practice (GP) consultation, with data analysed according to subsequent healthcare resource use. A cost-effectiveness analysis was undertaken from the perspective of the UK National Health Service, using a time horizon of 4 weeks in the base case. The use of antibiotics for COPD exacerbations resulted in cost savings and an improvement in all outcomes analysed; i.e. GP visits, hospitalisations, community respiratory team referrals, all referrals, infections and subsequent antibiotics prescriptions were lower for the antibiotics group. Hence, the use of antibiotics was dominant over no antibiotics. The economic analysis suggests that use of antibiotics for COPD exacerbations is a cost-effective alternative to not prescribing antibiotics for patients who present to their GP, and remains cost-effective when longer time horizons of 3 months and 12 months are considered. It would be useful for a definitive trial to be undertaken in this area to determine the cost-effectiveness of antibiotics for COPD exacerbations.

Cost-effectiveness of antibiotics for COPD management: observational analysis using CPRD data

PubMed Central

Raghunath, Anan; Torgerson, David J.; Van Staa, Tjeerd

2017-01-01

It is often difficult to determine the cause of chronic obstructive pulmonary disease (COPD) exacerbations, and antibiotics are frequently prescribed. This study conducted an observational cost-effectiveness analysis of prescribing antibiotics for exacerbations of COPD based on routinely collected data from patient electronic health records. A cohort of 45 375 patients aged 40 years or more who attended their general practice for a COPD exacerbation during 2000–2013 was identified from the Clinical Practice Research Datalink. Two groups were formed (“immediate antibiotics” or “no antibiotics”) based on whether antibiotics were prescribed during the index general practice (GP) consultation, with data analysed according to subsequent healthcare resource use. A cost-effectiveness analysis was undertaken from the perspective of the UK National Health Service, using a time horizon of 4 weeks in the base case. The use of antibiotics for COPD exacerbations resulted in cost savings and an improvement in all outcomes analysed; i.e. GP visits, hospitalisations, community respiratory team referrals, all referrals, infections and subsequent antibiotics prescriptions were lower for the antibiotics group. Hence, the use of antibiotics was dominant over no antibiotics. The economic analysis suggests that use of antibiotics for COPD exacerbations is a cost-effective alternative to not prescribing antibiotics for patients who present to their GP, and remains cost-effective when longer time horizons of 3 months and 12 months are considered. It would be useful for a definitive trial to be undertaken in this area to determine the cost-effectiveness of antibiotics for COPD exacerbations. PMID:28656132

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.

Effect of low-dose aspirin use on survival of patients with gastrointestinal malignancies; an observational study

PubMed Central

Frouws, M A; Bastiaannet, E; Langley, R E; Chia, W K; van Herk-Sukel, M P P; Lemmens, V E P P; Putter, H; Hartgrink, H H; Bonsing, B A; Van de Velde, C J H; Portielje, J E A; Liefers, G J

2017-01-01

Background: Previous studies suggested a relationship between aspirin use and mortality reduction. The mechanism for the effect of aspirin on cancer outcomes remains unclear. The aim of this study was to evaluate aspirin use and survival in patients with gastrointestinal tract cancer. Methods: Patients with gastrointestinal tract cancer diagnosed between 1998 and 2011 were included. The population-based Eindhoven Cancer Registry was linked to drug-dispensing data from the PHARMO Database Network. The association between aspirin use after diagnosis and overall survival was analysed using Cox regression models. Results: In total, 13 715 patients were diagnosed with gastrointestinal cancer. A total of 1008 patients were identified as aspirin users, and 8278 patients were identified as nonusers. The adjusted hazard ratio for aspirin users vs nonusers was 0.52 (95% CI 0.44–0.63). A significant association between aspirin use and survival was observed for patients with oesophageal, hepatobiliary and colorectal cancer. Conclusions: Post-diagnosis use of aspirin in patients with gastrointestinal tract malignancies is associated with increased survival in cancers with different sites of origin and biology. This adds weight to the hypothesis that the anti-cancer effects of aspirin are not tumour-site specific and may be modulated through the tumour micro-environment. PMID:28072768

Nullification of aspirin induced gastrotoxicity and hepatotoxicity by prior administration of wheat germ oil in Mus musculus: histopathological, ultrastructural and molecular studies.

PubMed

Mohamed, H R H; Hamad, S R

2017-08-30

Aspirin (acetyl salicylic acid) is used worldwide to treat various inflammatory conditions and prevent cardiovascular disease, along with reducing the risk of cancer. However, administration of aspirin causes toxic effects, especially in the stomach and liver. Thus, our study examined the protective effect of wheat germ oil on aspirin-induced toxicity in the stomach and liver tissues of Swiss albino mice. Administration of wheat germ oil before aspirin has restored normal hepatic and gastric tissue architecture and DNA integrity has become better than that of a negative health control group compared with the aspirin only treated group. The elevated gastric nitric oxide content in the aspirin only treated group was significantly decreased by wheat germ oil prior administration as a result of reduced the expression of inducible nitric synthase and increased the expression of endothelial nitric oxide synthase compared to their expression in the aspirin administered group. Wheat germ oil pre-administration significantly reduced the level of malondialdehyde, increased the level of glutathione and catalase and superoxide dismutase activities compared with those in aspirin only treated group. We conclude that wheat germ oil has a potential protective effect against aspirin induced gastro- and hepato-toxicity because of its free radical scavenging ability.

Chronic Use of Aspirin and Total White Matter Lesion Volume: Results from the Women's Health Initiative Memory Study of Magnetic Resonance Imaging Study.

PubMed

Holcombe, Andrea; Ammann, Eric; Espeland, Mark A; Kelley, Brendan J; Manson, JoAnn E; Wallace, Robert; Robinson, Jennifer

2017-10-01

To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women. Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis. The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen. There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women. Published by Elsevier Inc.

Exacerbation-related impairment of quality of life and work productivity in severe and very severe chronic obstructive pulmonary disease.

PubMed

Solem, Caitlyn T; Sun, Shawn X; Sudharshan, Lavanya; Macahilig, Cynthia; Katyal, Monica; Gao, Xin

2013-01-01

Exacerbation-associated health-related quality of life (HRQoL) in patients with severe and very severe chronic obstructive pulmonary disease (COPD) is ill-defined. This study describes patterns, HRQoL, and the work productivity impact of COPD-related moderate and SEV exacerbations in patients with SEV/VSEV COPD, focusing on the chronic bronchitis subtype. A US sample of SEV and VSEV COPD patients with recent moderate or SEV exacerbation was recruited. Along with the demographic and clinical data collected from medical records, patients reported on exacerbation frequency, health-related quality of life (HRQoL) (using the St George's Respiratory Questionnaire for COPD [SGRQ-C] and the European Quality of Life-5 Dimensions [EQ-5D]™ index), and work productivity and activity impairment (using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem [WPAI-SHP]). The HRQoL-related impacts of exacerbation frequency, time since exacerbation, and last exacerbation severity were evaluated via linear regressions. A total of 314 patients (190 SEV/124 VSEV, mean age =68.0 years, 51% male, 28% current smokers) were included. In the previous 12 months, patients reported an average of 1.8 moderate exacerbations and 0.9 SEV exacerbations. Overall, 16% of patients were employed and reported a high percentage of overall work impairment (42.4% ± 31.1%). Activity impairment was positively associated with recent exacerbation severity (SEV 64.6% ± 26.8% versus moderate 55.6% ± 28.2%) (P=0.006). The HRQoL was significantly worse for SEV versus VSEV COPD (EQ-5D: 0.62 ± 0.23 versus 0.70 ± 0.17, respectively, and SGRQ-C: 70.1 ± 21.3 versus 61.1 ± 19.0, respectively) (P<0.001). Worse current HRQoL was reported by patients with a SEV versus moderate recent exacerbation (EQ-5D: 0.63 ± 0.21 versus 0.70 ± 0.20, respectively) (P=0.003); SGRQ-C: 70.3 ± 19.9 versus 61.7 ± 20.1, respectively (P<0.001). One additional exacerbation in the previous 12 months was associated with a 2.4-point SGRQ-C increase and a 0.02-point EQ-5D index decrease. The severity and frequency of COPD-related moderate/SEV exacerbations in SEV and VSEV COPD patients were positively associated with poor HRQoL and work productivity and activity impairment.

Resistance to low-dose aspirin therapy among patients with acute coronary syndrome in relation to associated risk factors.

PubMed

Salama, M M; Morad, A-R Mohamed; Saleh, M A; Sabri, N A; Zaki, M M; ElSafady, L A

2012-12-01

A substantial proportion of patients have recurrence of vascular events despite daily intake of low-dose aspirin therapy. Therefore, different patients may require different aspirin dosages to achieve complete inhibition of platelet function. The aim of this work was to measure the response to low-dose aspirin therapy (150 mg/day) among patients with unstable angina or non-ST-segment elevation myocardial infarction and to find out whether titrating aspirin dosage to 300 mg/day, would provide a better therapeutic response in the resistant cases. Moreover, we also aimed to study any association between aspirin non-responsiveness and atherothrombotic risk factors. The antiplatelet effect of 150 mg/day aspirin was studied prospectively in 50 consecutive patients with unstable angina or non-ST-segment elevation myocardial infarction. Platelet aggregation was measured using optical platelet aggregometry and serum thromboxane B(2) level. Aspirin resistance was defined as collagen (1 μg/mL) and adenosine diphosphate (ADP) (5 μmol/L)-induced platelet aggregation of ≥ 40% when compared with control values. Twenty healthy age- and sex-matched individuals were taken as a control group. All patients were subjected to complete medical history (risk factors, medications), thorough clinical examination, ECG, coronary angiography and laboratory investigations including: complete haemogram, coagulation, kidney, liver and lipid profiles, fasting blood glucose and glycated haemoglobin (HbA(1C) ). Eleven of 50 patients (22%) were found to be aspirin resistant. A highly significant difference was found between the mean values of ADP, collagen-induced platelet aggregation percentage and thromboxane B(2) level after aspirin 150 mg/day when compared with the corresponding mean values after aspirin 300 mg/day among the resistant patients (66 ± 7.01%, 62 ± 4.34% and 620 ± 64.58 pg/mL, respectively, vs. 26.87 ± 2.85%, 16.5 ± 3.8% and 77 ± 11.3 pg/mL) indicating enhanced response to aspirin after escalating the dose. The presence of atherothrombotic risk factors (hypertension, smoking, family history of ischaemic heart disease and previous MI) were not statistically different between aspirin-resistant and aspirin-sensitive patients. However, there was a highly significant difference between the aspirin sensitive and the resistant patients regarding the other risk factors (diabetes mellitus and dyslipidaemia) (P < 0.01). There is inter-individual variability in response to the antiplatelet effect of standard doses of aspirin (150, 300 mg/day). The response to aspirin 300 mg/day is enhanced in resistant patients when compared to 150 mg/day. There was a significant association between aspirin resistance and atherothrombotic risk factors (diabetes, hyperlipidaemia and obesity). © 2009 Blackwell Publishing Ltd.

Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial.

PubMed

Kor, Daryl J; Carter, Rickey E; Park, Pauline K; Festic, Emir; Banner-Goodspeed, Valerie M; Hinds, Richard; Talmor, Daniel; Gajic, Ognjen; Ware, Lorraine B; Gong, Michelle Ng

2016-06-14

Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear. To evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS. A multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 16 US academic hospitals. Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score ≥4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified intention-to-treat analysis cohort. Administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death. The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A final α level of .0737 (α = .10 overall) was required for statistical significance of the primary outcome. Among 390 analyzed patients (median age, 57 years; 187 [48%] women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively; odds ratio, 1.24 [92.6% CI, 0.67 to 2.31], P = .53). No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days (mean [90% CI] difference, -0.26 [-1.46 to 0.94] days; P = .72); ICU length of stay, mean (SD), 5.2 (7.0) days vs 5.4 (7.0) days (mean [90% CI] difference, -0.16 [-1.75 to 1.43] days; P = .87); hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days (mean [90% CI] difference, -0.27 [-1.96 to 1.42] days; P = .79); or 28-day survival, 90% vs 90% (hazard ratio [90% CI], 1.03 [0.60 to 1.79]; P = .92) or 1-year survival, 73% vs 75% (hazard ratio [90% CI], 1.06 [0.75 to 1.50]; P = .79). Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%; odds ratio [90% CI], 2.27 [0.92 to 5.61]; P = .13). Among 390 analyzed patients (median age, 57 years; 187 [48%] women), median (IQR) hospital length of stay was 6 (3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (OR, 1.24; 92.6%CI, 0.67-2.31). No significant differences were seen in secondary outcomes or adverse events. [table: see text] Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial. clinicaltrials.gov Identifier: NCT01504867.

Aspirin in the 21st century-common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK.

PubMed

Smith, Tom; Hutchison, Pippa; Schrör, Karsten; Clària, Joan; Lanas, Angel; Patrignani, Paola; Chan, Andrew T; Din, Farhat; Langley, Ruth; Elwood, Peter; Freedman, Andrew; Eccles, Ron

2015-01-01

Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti-inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long-term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long-term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV.

Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

PubMed

Polzin, Amin; Richter, Stefan; Schrör, Karsten; Rassaf, Tienush; Merx, Marc W; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias

2015-07-01

We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1.

Platelet response to aspirin 50 and 100 mg in patients with coronary heart disease over a five-year period.

PubMed

Berent, Robert; Auer, Johann; Franklin, Barry; Schmid, Peter; von Duvillard, Serge P

2011-09-01

Aspirin has been shown to decrease cardiovascular (CV) events by ∼25%. Despite aspirin therapy 10% to 20% of patients with arterial vascular disease develop atherothrombotic events. A meta-analysis of antiplatelet therapy showed a progressive decrease in clinical efficacy of aspirin after 2 years. Whether this is due to a decreased sensitivity to aspirin during long-term therapy remains unclear. A prospective randomized clinical trial with serial monitoring over 5 years was conducted in 100 patients with documented coronary heart disease. We investigated whether long-term treatment with aspirin 50 and 100 mg affects platelet response similarly. Occurrence of CV events was documented. Platelet sensitivity to aspirin, prostacyclin, and adenosine diphosphate-, collagen-, and epinephrine-induced platelet aggregation were evaluated over time. In addition, β-thromboglobulin and inflammatory markers were measured. Four patients were lost to follow-up and 10 patients died. Eleven patients developed nonfatal CV events. In the 2 groups platelet response to aspirin and the referenced variables remained unchanged over 5 years. In patients who developed CV events, the last monitoring interval revealed no difference in platelet response to aspirin. However, patients with nonfatal and fatal CV events showed increased inflammatory markers versus patients without CV events independent of aspirin 50 or 100 mg intake. In conclusion, our study revealed no difference in antiplatelet response to aspirin 50 versus 100 mg or CV events over 5 years in patients with coronary heart disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Indacaterol/glycopyrronium versus salmeterol/fluticasone in Asian patients with COPD at a high risk of exacerbations: results from the FLAME study

PubMed Central

Wedzicha, Jadwiga A; Zhong, Nanshan; Ichinose, Masakazu; Humphries, Michael; Fogel, Robert; Thach, Chau; Patalano, Francesco; Banerji, Donald

2017-01-01

Background The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting β2-agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study. Patients and methods Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included. IND/GLY was compared versus SFC for effects on exacerbations, lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), health status (St George’s Respiratory Questionnaire [SGRQ]), rescue medication use, and safety. Results A total of 510 Asian patients (IND/GLY, n=250 or SFC, n=260) were included. Compared to the overall FLAME population, the Asian cohort had more males, a shorter duration of COPD, fewer patients using inhaled corticosteroid (ICS) at screening, fewer current smokers, and more patients with very severe COPD. IND/GLY significantly reduced the rate of moderate/severe exacerbations (rate ratio: 0.75; 95% confidence interval: 0.58–0.97; P=0.027) and prolonged time to first moderate/severe exacerbation versus SFC (hazard ratio: 0.77; 95% confidence interval: 0.59–1.01; P=0.055). Predose trough FEV1 and FVC significantly improved in Asian patients (P<0.001). IND/GLY improved SGRQ for COPD (SGRQ-C score; P=0.006) and reduced rescue medication use (P=0.058) at week 52. Pneumonia incidence was 3.6% with IND/GLY and 7.7% with SFC (P=0.046). Conclusion In exacerbating Asian COPD patients, IND/GLY was more effective than SFC. PMID:28176893

Indacaterol/glycopyrronium versus salmeterol/fluticasone in Asian patients with COPD at a high risk of exacerbations: results from the FLAME study.

PubMed

Wedzicha, Jadwiga A; Zhong, Nanshan; Ichinose, Masakazu; Humphries, Michael; Fogel, Robert; Thach, Chau; Patalano, Francesco; Banerji, Donald

2017-01-01

The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting β 2 -agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study. Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included. IND/GLY was compared versus SFC for effects on exacerbations, lung function (forced expiratory volume in 1 second [FEV 1 ] and forced vital capacity [FVC]), health status (St George's Respiratory Questionnaire [SGRQ]), rescue medication use, and safety. A total of 510 Asian patients (IND/GLY, n=250 or SFC, n=260) were included. Compared to the overall FLAME population, the Asian cohort had more males, a shorter duration of COPD, fewer patients using inhaled corticosteroid (ICS) at screening, fewer current smokers, and more patients with very severe COPD. IND/GLY significantly reduced the rate of moderate/severe exacerbations (rate ratio: 0.75; 95% confidence interval: 0.58-0.97; P =0.027) and prolonged time to first moderate/severe exacerbation versus SFC (hazard ratio: 0.77; 95% confidence interval: 0.59-1.01; P =0.055). Predose trough FEV 1 and FVC significantly improved in Asian patients ( P <0.001). IND/GLY improved SGRQ for COPD (SGRQ-C score; P =0.006) and reduced rescue medication use ( P =0.058) at week 52. Pneumonia incidence was 3.6% with IND/GLY and 7.7% with SFC ( P =0.046). In exacerbating Asian COPD patients, IND/GLY was more effective than SFC.

Prevention of exacerbations in patients with stable non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis of pharmacological and non-pharmacological therapies.

PubMed

Abu Dabrh, Abd Moain; Hill, Adam T; Dobler, Claudia C; Asi, Noor; Farah, Wigdan H; Haydour, Qusay; Wang, Zhen; Benkhadra, Khalid; Prokop, Larry J; Murad, Mohammad Hassan

2018-04-20

Several pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology. We conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations. Multiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model. 30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV 1 ) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD -0.90 (95% CI -1.58 to -0.22)) and improving quality of life scores assessed by the St George's Respiratory Questionnaire (WMD -6.07 (95% CI -10.7 to -1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy. Moderate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations. © 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.

Exacerbation frequency and course of COPD.

PubMed

Halpin, David M G; Decramer, Marc; Celli, Bartolome; Kesten, Steven; Liu, Dacheng; Tashkin, Donald P

2012-01-01

Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial. This retrospective analysis of data from the 4-year UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo. Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2). Spirometry and the St George's Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry). In total, 5992 patients (mean age 65 years, 75% male) were randomized. Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV(1)) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units). Corresponding rates of decline in postbronchodilator FEV(1) (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium). Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium). The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium). The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations. Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD. Increasing rates of hospitalized exacerbations are associated with increasing risk of death.

The anti-tumor effect of aspirin: What we know and what we expect.

PubMed

Ma, Ji; Cai, Zhonglin; Wei, Hongliang; Liu, Xinlan; Zhao, Qingli; Zhang, Tao

2017-11-01

Aspirin has been widely used as an antipyretic analgesic drug. More and more evidences have shown that aspirin may be play some role on anti-tumor. In this article, we reviewed the research history of aspirin in the treatment and prevention of cancer. Many epidemiological and clinical studies have shown that aspirin can reduce the risk of a variety of malignant tumors and reduce cancer mortality. In addition, we discuss the specific mechanisms of aspirin in the anti-tumor effects. It has been found that aspirin mainly depends on the COX pathway and non-COX pathway to inhibit tumor cell growth and to curb tumor development. In this article, clinical studies and anti-tumor mechanism studies published in recent years are reviewed. Copyright © 2017. Published by Elsevier Masson SAS.

The Role of Aspirin in the Prevention of Cardiovascular Disease

PubMed Central

Ittaman, Sunitha V.; VanWormer, Jeffrey J.; Rezkalla, Shereif H.

2014-01-01

Aspirin therapy is well-accepted as an agent for the secondary prevention of cardiovascular events and current guidelines also define a role for aspirin in primary prevention. In this review, we describe the seminal trials of aspirin use in the context of current guidelines, discuss factors that may influence the effectiveness of aspirin therapy for cardiovascular disease prevention, and briefly examine patterns of use. The body of evidence supports a role for aspirin in both secondary and primary prevention of cardiovascular events in selected population groups, but practice patterns may be suboptimal. As a simple and inexpensive prophylactic measure for cardiovascular disease, aspirin use should be carefully considered in all at-risk adult patients, and further measures, including patient education, are necessary to ensure its proper use. PMID:24573704

Aspirin suppresses neuronal apoptosis, reduces tissue inflammation, and restrains astrocyte activation by activating the Nrf2/HO-1 signaling pathway.

PubMed

Wei, Wang; Shurui, Chen; Zipeng, Zhou; Hongliang, Dai; Hongyu, Wang; Yuanlong, Li; Kang, Zhou; Zhaoliang, Shen; Yue, Guo; Chang, Liu; Mei, Xifan

2018-05-02

The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element signaling pathway plays a substantial role in preventing oxidative stress-related diseases. Aspirin has been shown to exert several pharmacological effects by inducing the expression of the heme oxygenase-1 (HO-1) protein. However, the effects of aspirin on spinal cord injury (SCI) have rarely been studied. Therefore, we sought to investigate the neuroprotective effects of aspirin after SCI. We employed a spinal cord contusion model in Sprague-Dawley rats, and aspirin was administered intraperitoneally for 7 days. Nissl staining showed that the aspirin treatment significantly reduced the loss of motor neurons after SCI compared with vehicle-treated animals. The expression of Nrf2, quinine oxidoreductase 1, and HO-1 proteins was increased in aspirin-treated animals after SCI compared with the vehicle group. In addition, aspirin simultaneously decreased the expression of inflammation-related proteins, such as tumor necrosis factor-α and interleukin-6 after SCI. Moreover, the ratio of apoptotic neurons in the anterior horn and the levels of the apoptosis-related proteins caspase-3, cleaved caspase-3, and Bax were significantly decreased in the aspirin group compared with the vehicle group. Immunofluorescence staining was used to detect the colocalization of NeuN and HO-1, and the results showed that aspirin significantly increased expression of the HO-1 protein in neurons. In addition, western blots and immunofluorescence staining showed aspirin restrained astrocyte activation. In conclusion, aspirin induces neuroprotective effects by inhibiting astrocyte activation and apoptosis after SCI through the activation of the Nrf2/HO-1 signaling pathway.

Association of gastric acid and mucus secretion level with low-dose aspirin-induced gastropathy.

PubMed

Iijima, Katsunori; Ara, Nobuyuki; Abe, Yasuhiko; Koike, Tomoyuki; Iwai, Wataru; Iwabuchi, Toshimitsu; Ichikawa, Takafumi; Kamata, Yayoi; Ishihara, Kazuhiko; Shimosegawa, Tooru

2012-02-01

Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy. In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy. While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy. Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication.

Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year results of the APACC randomised trial.

PubMed

Benamouzig, Robert; Uzzan, Bernard; Deyra, Jacques; Martin, Antoine; Girard, Bernard; Little, Julian; Chaussade, Stanislas

2012-02-01

Aspirin inhibits colorectal carcinogenesis. In a randomised double-blind placebo-controlled trial, daily soluble aspirin significantly reduced recurrence of colorectal adenomas at 1-year follow-up. In this study the results of daily intake of low-dose aspirin on polyp recurrence at 4-year follow-up are presented. 272 patients (naive for chronic aspirin use) with colorectal adenomas were randomly assigned to treatment with lysine acetylsalicylate 160 mg/day (n=73) or 300 mg/day (n=67) or placebo (n=132) for 4 years. The primary endpoints were adenoma recurrence and adenomatous polyp burden at year 4, comparing aspirin at either dose with placebo. The same endpoints were also assessed at year 1 or 4 (last colonoscopy performed for each patient). At the final year 4 colonoscopy the analysis included 185 patients (55 receiving aspirin 160 mg/day, 47 aspirin 300 mg/day and 83 placebo). There was no difference in the proportion of patients with at least one recurrent adenoma between patients receiving aspirin at either dose and those treated with placebo (42/102 (41%) vs 33/83 (40%); NS) or in the adenomatous polyp burden (3.1 ± 5.8 mm vs 3.4 ± 6.2 mm; NS). Also, the proportion of patients with at least one advanced recurrent adenoma did not differ (10/102 [corrected] (10%) in the aspirin group vs 7/83 (8.4%) [corrected] in the placebo group; NS). Daily low-dose aspirin decreased adenoma recurrence significantly at 1 year but not at year 4. This discrepancy might be explained by a differential effect of aspirin according to the natural history of the polyp. NCT 00224679.

Early aspirin use and the development of cardiac allograft vasculopathy.

PubMed

Kim, Miae; Bergmark, Brian A; Zelniker, Thomas A; Mehra, Mandeep R; Stewart, Garrick C; Page, Deborah S; Woodcome, Erica L; Smallwood, Jennifer A; Gabardi, Steven; Givertz, Michael M

2017-12-01

Cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Little is known about the influence of aspirin on clinical expression of CAV. We followed 120 patients with OHT at a single center for a median of 7 years and categorized them by the presence or absence of early aspirin therapy post-transplant (aspirin treatment ≥6 months in the first year). The association between aspirin use and time to the primary end-point of angiographic moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) was investigated. Propensity scores for aspirin treatment were estimated using boosting models and applied by inverse probability of treatment weighting (IPTW). Despite a preponderance of risk factors for CAV among patients receiving aspirin (male sex, ischemic heart disease as the etiology of heart failure, and smoking), aspirin therapy was associated with a lower rate of moderate or severe CAV at 5 years. Event-free survival was 95.9% for patients exposed to aspirin compared with 79.6% for patients without aspirin exposure (log-rank p = 0.005). IPTW-weighted Cox regression revealed a powerful inverse association between aspirin use and moderate to severe CAV (adjusted hazard ratio 0.13; 95% confidence interval 0.03-0.59), which was directionally consistent for CAV of any severity (adjusted hazard ratio 0.50; 95% confidence interval 0.23-1.08). This propensity score-based comparative observational analysis suggests that early aspirin exposure may be associated with a reduced risk of development of moderate to severe CAV. These findings warrant prospective validation in controlled investigations. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Use of Low-dose Aspirin as Secondary Prevention of Atherosclerotic Cardiovascular Disease Among US Adults (From the National Health Interview Survey, 2012)

PubMed Central

Fang, Jing; George, Mary G.; Gindi, Renee M.; Hong, Yuling; Yang, Quanhe; Ayala, Carma; Ward, Brian W.; Loustalot, Fleetwood

2015-01-01

Current guidelines recommend that adults with atherosclerotic cardiovascular disease take low-dose aspirin or other antiplatelet medications as secondary prevention of recurrent cardiovascular events. Yet, no national level assessment of low-dose aspirin use for secondary prevention of cardiovascular disease has been reported among a community-based population. Using data from the 2012 National Health Interview Survey, we assessed low-dose aspirin use among those with atherosclerotic cardiovascular disease. We estimated the prevalence ratios of low-dose aspirin use, adjusting for sociodemographic status, health insurance, and cardiovascular risk factors. Among those with atherosclerotic cardiovascular disease (n=3,068), 76% had been instructed to take aspirin, and 88% of those were following this advice. Of those not advised, 11% took aspirin on this own. Overall, 70% were taking aspirin (including those who followed their health care provider's advice and those who were not advised but took aspirin on their own). Logistic regression models showed that women, non-Hispanic blacks and Hispanics, those aged 40–64 years, with a high school education or with some college, or with fewer cardiovascular disease risk factors were less likely to take aspirin than men, non-Hispanic whites, those aged ≥65 years, with a college education or higher, or with all four selected cardiovascular disease risk factors, respectively. Additional analyses conducted among those with coronary heart disease only (n=2,007) showed similar patterns. In conclusion, use of low-dose aspirin for secondary prevention was 70%, with high reported adherence to health care providers' advice to take low-dose aspirin (88%), and significant variability within subgroups. PMID:25670639

Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

PubMed

Hong, Keun-Sik; Lee, Seung-Hoon; Kim, Eung Gyu; Cho, Ki-Hyun; Chang, Dae Il; Rha, Joung-Ho; Bae, Hee-Joon; Lee, Kyung Bok; Kim, Dong Eog; Park, Jong-Moo; Kim, Hahn-Young; Cha, Jae-Kwan; Yu, Kyung-Ho; Lee, Yong-Seok; Lee, Soo Joo; Choi, Jay Chol; Cho, Yong-Jin; Kwon, Sun U; Kim, Gyeong-Moon; Sohn, Sung-Il; Park, Kwang-Yeol; Kang, Dong-Wha; Sohn, Chul-Ho; Lee, Jun; Yoon, Byung-Woo

2016-09-01

In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268. © 2016 American Heart Association, Inc.

Aspirin and incident depressive symptoms: A longitudinal cohort study over 8 years.

PubMed

Veronese, Nicola; Koyanagi, Ai; Stubbs, Brendon; Solmi, Marco; Fornaro, Michele; Fernandes, Brisa S; Muller, Christoph; Thompson, Trevor; Carvalho, André F; Maggi, Stefania

2018-02-01

Aspirin exhibits anti-atherosclerotic and anti-inflammatory properties-two potential risk factors for depression. The relationship between aspirin use and depression, however, remains unclear. We investigated whether the aspirin use is associated with a decreased incidence of depressive symptoms in a large North American cohort. Data from the Osteoarthritis Initiative dataset, a multicenter, longitudinal study on community-dwelling adults was analyzed. Aspirin use was defined through self-report in the past 30 days and confirmed by a trained interviewer. Incident depressive symptoms were defined as a score of ≥16 in the 20-item Center for Epidemiologic Studies-Depression scale. A total of 137 participants (mean age 65 y, 55.5% female) were using aspirin at baseline. Compared with 4003 participants not taking aspirin, no differences in Center for Epidemiologic Studies-Depression at baseline were evident (P = .65). After a median follow-up time of 8 years, the incidence of depressive symptoms was similar in those taking aspirin at baseline (43; 95% CI, 3-60) and in aspirin nonusers (38; 95% CI, 36-41) per 1000 y; log-rank test = 0.63). Based on Cox's regression analysis adjusted for 11 potential confounders, aspirin use was not significantly associated with the development of depressive symptoms (hazard ratio = 1.12; 95% CI, 0.78-1.62; P = .54). Adjustment for propensity scores or the use of propensity score matching did not alter the results. Our study found that prescription of aspirin offered no significant protection against incident depressive symptoms. Whether aspirin is beneficial in a subgroup of depression with high levels of inflammation remains to be investigated in future studies. Copyright © 2017 John Wiley & Sons, Ltd.

Post-pregnancy aspirin resistance appears not to be related with recurrent hypertensive disorders of pregnancy.

PubMed

Abheiden, Carolien N H; Fuijkschot, Wessel W; Arduç, Arda; van Diemen, Jeske J K; Harmsze, Ankie M; de Boer, Marjon A; Thijs, Abel; de Vries, Johanna I P

2017-03-01

The FRUIT-RCT concluded that low-molecular-weight heparin added to aspirin compared to treatment with aspirin alone is beneficial in the prevention of early-onset hypertensive disorders of pregnancy (HD) in women with inheritable thrombophilia and prior HD and/or a small-for-gestational age (SGA) infant leading to delivery before 34 weeks gestation. The aim of this study is to answer the question whether aspirin resistance is associated with recurrent HD. Women with and without recurrent HD matched for age, study arm, and chronic hypertension were invited for this follow-up study 6-16 years after they participated in the FRUIT-RCT. Aspirin resistance was tested after 10days of aspirin intake using three complementary tests: PFA-200, VerifyNow ® and serum thromboxane B 2 (TXB 2 ). An independent t-test, Mann-Whitney U test, Fisher's Exact test and Chi 2 test were used for the statistical analyses. Thirteen of 24 women with recurrent HD and 16 of 24 women without recurrent HD participated. The prevalence of laboratory aspirin resistance was 34.5% according to the PFA-200, 3.4% according to the VerifyNow ® and 24.1% according to TXB 2 . The prevalence of aspirin resistance by any test was 51.7%. Aspirin resistance per individual test did not differ between women with and without recurrent HD. Aspirin resistance measured by any test occurred more frequently in women without recurrent HD (p<0.01), irrespective of low-molecular-weight heparin. No relation could be demonstrated between recurrent HD and aspirin resistance per test, measured up to 16 years after pregnancy. On the contrary, complementary aspirin resistance measurements were encountered more frequently in women without recurrent HD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Safety of continuing aspirin therapy during spinal surgery: A systematic review and meta-analysis.

PubMed

Zhang, Chenggui; Wang, Guodong; Liu, Xiaoyang; Li, Yang; Sun, Jianmin

2017-11-01

Questions whether to continue or discontinue aspirin administration in the perioperative period of spinal surgery has not been systematically evaluated. The present systematic review is carried out to assess the impact of continuing aspirin administration on the bleeding and cardiovascular events in perispinal surgery period. Studies were retrieved through MEDLINE, EMBASE, and Springer Link Databases (search terms, aspirin, continue or discontinue, and spinal fusion), bibliographies of the articles retrieved, and the authors' reference files. We included studies that enrolled patients who underwent spinal surgery who were anticoagulated with aspirin alone and that reported bleeding or cardiovascular events as an outcome. Study quality was assessed using a validated form. 95% confidence interval (95% CI) was pooled to give summary estimates of bleeding and cardiovascular risk. We identified 4 studies assessing bleeding risk associated with aspirin continuation or cardiovascular risk with aspirin discontinuation during spinal surgery. The continuation of aspirin will not increase the risk of blood loss during the spinal surgery (95% CI, -111.72 to -0.59; P = .05). Also, there was no observed increase in the operative time (95% CI, -33.29 to -3.89; P = .01) and postoperative blood transfusion (95% CI, 0.00-0.27; P = .05). But as for the cardiovascular risk without aspirin continuation and mean hospital length of stay with aspirin continuation, we did not get enough samples to make an accurate decision about their relations with aspirin. Patients undergoing spinal surgery with continued aspirin administration do not have an increased risk for bleeding. In addition, there is no observed increase in the operation time and postoperative blood transfusion.

The Role of Aspirin as Antitumoral Agent for Heavily Pretreated Patients With Metastatic Colorectal Cancer Receiving Capecitabine Monotherapy.

PubMed

Giampieri, Riccardo; Restivo, Angelo; Pusceddu, Valeria; Del Prete, Michela; Maccaroni, Elena; Bittoni, Alessandro; Faloppi, Luca; Andrikou, Kalliopi; Bianconi, Maristella; Cabras, Francesco; Berardi, Rossana; Zorcolo, Luigi; Scintu, Francesco; Cascinu, Stefano; Scartozzi, Mario

2017-03-01

The potential clinical impact of aspirin use beyond its canonical indications is a novel matter of scientific debate. In patients with metastatic colorectal cancer failing all available options, regorafenib and TAS 102 represent the only chance of treatment. Although effective, these therapeutic options bring along a not-negligible burden in terms of economic costs and toxicity. In this setting, the indication to use aspirin in combination with chemotherapy would potentially represent a medical revolution under the economic and toxicity profile. We assessed the role of aspirin in patients with metastatic colorectal cancer who failed all previous treatments and were receiving capecitabine as a salvage option before the introduction of regorafenib and TAS-102. Sixty-six patients were eligible. Twenty patients (30%) were on incidental treatment with aspirin for cardiovascular diseases. Twelve (60%) partial responses were seen in patients on treatment with aspirin, compared with 3 (6%) partial responses in the remaining patients (P = .00007). Sixteen patients on aspirin (80%) obtained disease control versus 14 (30%) patients who were not on aspirin (P = .000377). The median progression-free survival for patients receiving treatment with aspirin was 6.5 months versus 3.3 months for patients who were not on aspirin (hazard ratio, 0.48; 95% confidence interval, 0.30-0.79; P = .0042). A significantly improved overall survival was also evident in aspirin users (median overall survival, 14.7 vs. 8.7 months, respectively; hazard ratio, 0.43; 95% confidence interval, 0.26-0.72; P = .0023). Aspirin may improve the clinical outcome of heavily pre-treated patients with metastatic colorectal cancer receiving chemotherapy. Further studies are necessary before application in the clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Short-term exposure of platelets to glucose impairs inhibition of platelet aggregation by cyclooxygenase inhibitors.

PubMed

Kobzar, Gennadi; Mardla, Vilja; Samel, Nigulas

2011-01-01

Aspirin treatment reduces cardiovascular events and deaths in high-risk non-diabetic patients, but not in patients suffering from diabetes. In these patients, hyperglycemia has been found to cause reduced platelet sensitivity to aspirin. It is supposed that long-term exposure of platelets to glucose leads to non-enzymatic glycosylation and impairs aspirin inhibition of platelet aggregation. On the other hand, short-term exposure of platelets to glucose also attenuates the effect of aspirin on platelets. The aim of the present work was to analyse the effect of short-term exposure of glucose on the inhibition of platelet aggregation by aspirin and other cyclooxygenase (COX) inhibitors. Already a 15 min exposure of platelets to glucose impaired aspirin inhibition of the platelet aggregation induced by collagen, thrombin, adenosine diphosphate (ADP), and arachidonic acid (AA). Aspirin inhibition of platelet aggregation in platelet-rich plasma (PRP) was attenuated by 5.6, 11.2, 16.8, and 22.4 mM of glucose in a concentration-dependent way. The same effect was observed with indomethacin and acetaminophen used as cyclooxygenase inhibitors instead of aspirin. N-methyl-L-arginine, an inhibitor of nitric oxide synthase, prevented the effect of glucose on aspirin, indomethacin and acetaminophen inhibition of platelet aggregation. Other monosaccharides, for example fructose and galactose, impaired aspirin inhibition as did glucose. Lactic acid (0.1, 0.2, 0.4, 0.8 mM), the end product of anaerobic glycolysis in platelets, impaired the inhibition of platelet aggregation with aspirin in a concentration-dependent way but did not affect indomethacin. It is suggested that lactic acid might be a mediator of the effect of glucose on aspirin inhibition in platelets.

Inhibition of the biosynthesis of prostaglandin E2 by low dose aspirin: implications for adenocarcinoma metastasis

PubMed Central

Boutaud, Olivier; Sosa, I. Romina; Amin, Taneem; Oram, Denise; Adler, David; Hwang, Hyun S.; Crews, Brenda C.; Milne, Ginger; Harris, Bradford K.; Hoeksema, Megan; Knollmann, Bjorn C.; Lammers, Philip E.; Marnett, Lawrence J.; Massion, Pierre P.; Oates, John A.

2016-01-01

Meta-analyses have demonstrated that low dose aspirin reduces the risk of developing adenocarcinoma metastasis, and when colon cancer is detected during aspirin treatment, there is a remarkable 83% reduction in risk of metastasis. As platelets participate in the metastatic process, the anti-platelet action of low dose aspirin likely contributes to its anti-metastatic effect. Cycloxooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) also contributes to metastasis, and we addressed the hypothesis that low dose aspirin also inhibits PGE2 biosynthesis. We show that low dose aspirin inhibits systemic PGE2 biosynthesis by 45% in healthy volunteers (p <0.0001). Aspirin is found to be more potent in colon adenocarcinoma cells than in the platelet, and in lung adenocarcinoma cells its inhibition is equivalent to that in the platelet. Inhibition of COX by aspirin in colon cancer cells is in the context of the metastasis of colon cancer primarily to the liver, the organ exposed to the same high concentrations of aspirin as the platelet. We find that the interaction of activated platelets with lung adenocarcinoma cells up-regulates COX-2 expression and PGE2 biosynthesis, and inhibition of platelet COX-1 by aspirin inhibits PGE2 production by the platelet-tumor cell aggregates. In conclusion, low dose aspirin has a significant effect on extraplatelet cyclooxygenase, and potently inhibits COX-2 in lung and colon adenocarcinoma cells. This supports a hypothesis that the remarkable prevention of metastasis from adenocarcinomas, and particularly from colon adenocarcinomas, by low dose aspirin results from its effect on platelet COX-1 combined with inhibition of PGE2 biosynthesis in metastasizing tumor cells. PMID:27554763

The Development of an In Vitro Assay for the Prospective Determination of Aspirin Sensitivity.

PubMed

Westphal, Erica S; Wisniewski, Caitlin; Rainka, Michelle; Smith, Nicholas M; Bates, Vernice; Gengo, Fran M

2018-05-18

Aspirin remains the standard for stroke prophylaxis. However, as many as 20%-25% of patients may fail to show a full response to aspirin. Ideally, patients who are resistant to aspirin could be identified, then receive an increased dose of aspirin or be changed to an alternative therapy more efficiently. We have developed an in vitro assay that may make this possible. Healthy volunteers (n = 13) between 18 and 50 years of age were tested for both ex vivo and in vivo responses to aspirin. Dimethyl sulfoxide (DMSO) was selected as the solvent for aspirin in the assay. DMSO can exhibit antiplatelet effects, necessitating the use of a concentration low enough to avoid such antiplatelet effects. Blood samples were tested against DMSO 0%, 0.05%, 0.5%, and 1% w/v with and without aspirin 0, 50, and 100 μM. The effects of both agents were measured via whole-blood aggregometry. A 3-dimensional response model described the data well, quantifying the combinatorial effect of DMSO and aspirin on platelet aggregation. Across all participants, baseline aggregation stimulated with collagen 1 μM or arachidonate 0.5 mM was approximately 18 and 13 Ω, respectively. The response model showed that 0.05% DMSO with 100 μM aspirin would provide platelet aggregation of 3.4 Ω. A DMSO concentration of 0.05% in the absence of aspirin would result in no discernable effects on platelet aggregation (17.7 Ω). Overall, the use of 100 μM of aspirin in 0.05% DMSO provides a robust method to test for ex vivo inhibition of platelet aggregation. © 2018, The American College of Clinical Pharmacology.

How important is aspirin adherence when evaluating effectiveness of low-dose aspirin?

PubMed

Navaratnam, Kate; Alfirevic, Zarko; Pirmohamed, Munir; Alfirevic, Ana

2017-12-01

Low-dose aspirin (LDA) is advocated for women at high-risk of pre-eclampsia, providing a modest, 10%, reduction in risk. Cardiology meta-analyses demonstrate 18% reduction in serious vascular events with LDA. Non-responsiveness to aspirin (sometimes termed aspirin resistance) and variable clinical effectiveness are often attributed to suboptimal adherence. The aim of this review was to identify the scope of adherence assessments in RCTs evaluating aspirin effectiveness in cardiology and obstetrics and discuss the quality of information provided by current methods. We searched MEDLINE, EMBASE and the Cochrane Library, limited to humans and English language, for RCTs evaluating aspirin in cardiology; 14/03/13-13/03/16 and pregnancy 1957-13/03/16. Search terms; 'aspirin', 'acetylsalicylic acid' appearing adjacent to 'myocardial infarction' or 'pregnancy', 'pregnant', 'obstetric' were used. 38% (25/68) of obstetric and 32% (20/62) of cardiology RCTs assessed aspirin adherence and 24% (6/25) and 29% (6/21) of obstetric and cardiology RCTs, respectively, defined acceptable adherence. Semi-quantitative methods (pill counts, medication weighing) prevailed in obstetric RCTs (93%), qualitative methods (interviews, questionnaires) were more frequent in obstetrics (67%). Two obstetric RCTs quantified serum thromboxane B 2 and salicylic acid, but no quantitative methods were used in cardiology Aspirin has proven efficacy, but suboptimal adherence is widespread and difficult to accurately quantify. Little is currently known about aspirin adherence in pregnancy. RCTs evaluating aspirin effectiveness show over-reliance on qualitative adherence assessments vulnerable to inherent inaccuracies. Reliable adherence data is important to assess and optimise the clinical effectiveness of LDA. We propose that adherence should be formally assessed in future trials and that development of quantitative assessments may prove valuable for trial protocols. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence of colorectal cancer in new users and non-users of low-dose aspirin without existing cardiovascular disease: A cohort study using The Health Improvement Network.

PubMed

Cea Soriano, Lucía; Soriano-Gabarró, Montse; García Rodríguez, Luis A

2017-12-01

Evidence regarding the chemo-protective effects of aspirin has influenced expert opinion in favour of low-dose aspirin use in certain patient populations without cardiovascular disease (CVD). The effects of aspirin in reducing the incidence of colorectal cancer (CRC) may be a large contributor to this favourable risk-benefit profile of low-dose aspirin in primary CVD prevention. Using The Health Improvement Network, we estimated the incidence of CRC in individuals free of CVD and either prescribed or not prescribed prophylactic low-dose aspirin. Two cohorts - new-users of low-dose aspirin (N=109,426) and a comparator cohort of non-users (N=154,056) at start of follow-up - were followed (maximum 13years) to identify incident CRC cases. Individuals with a record of CVD, cancer or low-dose aspirin prescription before start of follow-up were excluded. 2330 incident cases of CRC occurred; 885 in the aspirin cohort and 1445 in the comparator cohort, after mean follow-ups of 5.43years and 5.17years, respectively. Incidence rates of CRC per 10,000 person-years (95% confidence interval) were 14.90 (13.95-15.92) in the aspirin cohort and 18.15 (17.24-19.12) in the comparator cohort; incidence rate ratio 0.82 (0.76-0.89) adjusted for age, sex and primary care practitioner (PCP) visits in the previous year. Lower incidence rates were seen in the aspirin cohort for all strata evaluated (gender, age group and number of PCP visits in the previous year) except those aged ≥80years. Among most individuals without established CVD, initiation of low-dose aspirin is associated with a reduced incidence of CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

Aspirin use and endometrial cancer risk and survival.

PubMed

Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

2018-01-01

The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

PubMed Central

Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

2013-01-01

Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low Dose Aspirin

PubMed Central

Dudley, Alicia; Thomason, John; Fritz, Sara; Grady, Jesse; Stokes, John; Wills, Robert; Pinchuk, Lesya; Mackin, Andrew; Lunsford, Kari

2014-01-01

Background Low dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are non-responsive to the anti-platelet effects of aspirin (‘aspirin resistance’). Hypothesis/Objectives That low dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression. Animals Twenty-four healthy dogs Methods A repeated measures study. Platelet function (PFA-100® closure time, collagen/epinephrine), platelet COX-1 and COX-2 expression, and urine 11-dehydro-thromboxane B2 (11-dTXB2) was evaluated prior to and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, non-responders, and inconsistent responders. Results Low dose aspirin increased closure times significantly (62% by Day 10, P<0.001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX-1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, −29.7%–136.1%) (P=0.047) and 72% on Day 10 (range, −0.37–210.36%) (P<0.001). Platelet COX-2 MFI increased significantly by 34% (range, −29.2–270.4%) on Day 3 (P = 0.003) and 74% (range, −19.7–226.2%) on Day 10 (P<0.001). Urinary 11-dTXB2 concentrations significantly (P=0.005, P<0.001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production. Conclusions and Clinical Importance Low dose aspirin consistently inhibits platelet function in approximately one third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. Pre-treatment COX isoform expression did not predict aspirin resistance. PMID:23278865

Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets.

PubMed

Massimi, Isabella; Guerriero, Raffaella; Lotti, Lavinia Vittoria; Lulli, Valentina; Borgognone, Alessandra; Romani, Federico; Barillà, Francesco; Gaudio, Carlo; Gabbianelli, Marco; Frati, Luigi; Pulcinelli, Fabio M

2014-12-01

The aim of the study was to investigate whether human megakaryocytic cells have an adaptive response to aspirin treatment, leading to an enhancement of multidrug resistance protein-4 (MRP4) expression in circulating platelets responsible for a reduced aspirin action. We recently found that platelet MRP4 overexpression has a role in reducing aspirin action in patients after by-pass surgery. Aspirin enhances MRP4-mRNA levels in rat liver and drug administration transcriptionally regulates MRP4 gene expression through peroxisome proliferator-activated receptor-α (PPARα). The effects induced by aspirin or PPARα agonist (WY14643) on MRP4 modulation were evaluated in vitro in a human megakaryoblastic DAMI cell line, in megakaryocytes (MKs) and in platelets obtained from human haematopoietic progenitor cell (HPC) cultures, and in vivo platelets obtained from aspirin treated healthy volunteers (HV). In DAMI cells, aspirin and WY14643 treatment induced a significant increase in MRP4 and PPARα expression. In human MKs grown in the presence of either aspirin or WY14643, MRP4 and PPARα-mRNA were higher than in control cultures and derived platelets showed an enhancement in MRP4 protein expression. The ability of aspirin to modulate MRP4 expression in MKs and to transfer it to platelets was also confirmed in vivo. In fact, we found the highest MRP4 mRNA and protein expression in platelets obtained from HV after 15 days' aspirin treatment. The present study provides evidence, for the first time, that aspirin treatment affects the platelet protein pattern through MK genomic modulation. This work represents an innovative and attractive approach, useful both to identify patients less sensitive to aspirin and to improve pharmacological treatment in cardiovascular high-risk patients. © 2014 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Clopidogrel with aspirin in acute minor stroke or transient ischemic attack.

PubMed

Wang, Yongjun; Wang, Yilong; Zhao, Xingquan; Liu, Liping; Wang, David; Wang, Chunxue; Wang, Chen; Li, Hao; Meng, Xia; Cui, Liying; Jia, Jianping; Dong, Qiang; Xu, Anding; Zeng, Jinsheng; Li, Yansheng; Wang, Zhimin; Xia, Haiqin; Johnston, S Claiborne

2013-07-04

Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone. In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect. Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group. Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.).

Risk of Hemorrhage Attributed to Underlying Chronic Diseases and Uninterrupted Aspirin Therapy of Patients Undergoing Minor Oral Surgical Procedures: A Retrospective Cohort Study.

PubMed

Rojanaworarit, Chanapong; Limsawan, Soontaree

2017-01-01

This study aimed to estimate the risk of bleeding following minor oral surgical procedures and uninterrupted aspirin therapy in high-risk patients or patients with existing chronic diseases compared to patients who did not use aspirin during minor oral surgery at a public hospital. This retrospective cohort study analyzed the data of 2912 patients, aged 20 years or older, who underwent 5251 minor oral surgical procedures at a district hospital in Thailand. The aspirin group was comprised of patients continuing aspirin therapy during oral surgery. The non-aspirin group (reference) included all those who did not use aspirin during surgery. Immediate and late-onset bleeding was evaluated in each procedure. The risk ratio of bleeding was estimated using a multilevel Poisson regression. The overall cumulative incidence of immediate bleeding was 1.3% of total procedures. No late-onset bleeding was found. A significantly greater incidence of bleeding was found in the aspirin group (5.8% of procedures, p<0.001). After adjusting for covariates, a multilevel Poisson regression model estimated that the bleeding risk in the aspirin group was 4.5 times higher than that of the non-aspirin group (95% confidence interval, 2.0 to 10.0; p<0.001). However, all bleeding events were controlled by simple hemostatic measures. High-risk patients or patients with existing chronic diseases who continued aspirin therapy following minor oral surgery were at a higher risk of hemorrhage than general patients who had not used aspirin. Nonetheless, bleeding complications were not life-threatening and could be promptly managed by simple hemostatic measures. The procedures could therefore be provided with an awareness of increased bleeding risk, prepared hemostatic measures, and postoperative monitoring, without the need for discontinuing aspirin, which could lead to more serious complications.

Phospho-Aspirin (MDC-22) Prevents Pancreatic Carcinogenesis in Mice.

PubMed

Mattheolabakis, George; Papayannis, Ioannis; Yang, Jennifer; Vaeth, Brandon M; Wang, Ruixue; Bandovic, Jela; Ouyang, Nengtai; Rigas, Basil; Mackenzie, Gerardo G

2016-07-01

Pancreatic cancer is a deadly disease with a dismal 5-year survival rate of <6%. The currently limited treatment options for pancreatic cancer underscore the need for novel chemopreventive and therapeutic agents. Accumulating evidence indicates that aspirin use is associated with a decreased risk of pancreatic cancer. However, the anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we developed phospho-aspirin (MDC-22), a novel derivative of aspirin, and evaluated its chemopreventive efficacy in preclinical models of pancreatic cancer. Phospho-aspirin inhibited the growth of human pancreatic cancer cell lines 8- to 12-fold more potently than aspirin; based on the 24-hour IC50 values. In a Panc-1 xenograft model, phospho-aspirin, at a dose of 100 mg/kg/d 5 times per week for 30 days, reduced tumor growth by 78% (P < 0.01 vs. vehicle control). Furthermore, phospho-aspirin prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. In p48-Cre;Kras(G12D) mice, cerulein treatment (6 hourly injections two times per week for 3 weeks) led to a significant increase in ductal metaplasia, replacing the majority of the exocrine compartment. Administration of phospho-aspirin 100 mg/kg/day five times per week for 21 days (starting on the first day of cerulein injection) inhibited the acinar-to-ductal metaplasia, reducing it by 87% (P < 0.01, vs. cerulein-treated control). Phospho-aspirin appeared to be safe, with the animals showing no signs of toxicity during treatment. Mechanistically, phospho-aspirin inhibited EGFR activation in pancreatic cancer, an effect consistently observed in pancreatic cancer cells, primary acinar explants and in vivo In conclusion, our findings indicate that phospho-aspirin has strong anticancer efficacy in preclinical models of pancreatic cancer, warranting its further evaluation. Cancer Prev Res; 9(7); 624-34. ©2016 AACR. ©2016 American Association for Cancer Research.

Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers.

PubMed

Teng, Renli; Maya, Juan; Butler, Kathleen

2013-01-01

The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1-5; 200 mg bid Days 6-9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1-10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2-9) with either ticagrelor (200 mg bid Days 4-8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5-9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (Cmax), median time to Cmax (tmax), or mean area under the plasma concentration-time curve for the dosing interval (AUC0-τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean Cmax and AUC0-τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300 mg qd) with ticagrelor (50 mg bid, or 200 mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor.

Association of aspirin use with major bleeding in patients with and without diabetes.

PubMed

De Berardis, Giorgia; Lucisano, Giuseppe; D'Ettorre, Antonio; Pellegrini, Fabio; Lepore, Vito; Tognoni, Gianni; Nicolucci, Antonio

2012-06-06

The benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage. To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin. A population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensity-matched on a 1-to-1 basis with individuals who did not take aspirin during this period. Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy. There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39-5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44). In a population-based cohort, aspirin use was significantly associated with an increased risk of major gastrointestinal or cerebral bleeding episodes. Patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.

Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies.

PubMed

Khalaf, Natalia; Yuan, Chen; Hamada, Tsuyoshi; Cao, Yin; Babic, Ana; Morales-Oyarvide, Vicente; Kraft, Peter; Ng, Kimmie; Giovannucci, Edward; Ogino, Shuji; Stampfer, Meir; Cochrane, Barbara B; Manson, JoAnn E; Clish, Clary B; Chan, Andrew T; Fuchs, Charles S; Wolpin, Brian M

2018-04-01

Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; P trend 0.81; comparing participants in the highest quintile with those in the lowest quintile of plasma salicylurate). Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

76 FR 53907 - Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...] Determination That TALWIN COMPOUND (Aspirin; Pentazocine Hydrochloride) Tablets, 325 Milligrams; Equivalent to... determined that TALWIN COMPOUND (aspirin; pentazocine hydrochloride (HCl)) tablets, 325 milligrams (mg... determination will allow FDA to approve abbreviated new drug applications (ANDAs) for aspirin; pentazocine HCl...

Aspirin enhances the induction of type I allergic symptoms when combined with food and exercise in patients with food-dependent exercise-induced anaphylaxis.

PubMed

Harada, S; Horikawa, T; Ashida, M; Kamo, T; Nishioka, E; Ichihashi, M

2001-08-01

We examined the effect of aspirin as a substitute for exercise in inducing urticaria/anaphylaxis in three patients with food-dependent exercise-induced anaphylaxis (FDEIA). Two of the patients had specific IgE antibodies to wheat and the other had antibodies to shrimp. Administration of aspirin before ingestion of food allergens induced urticaria in one patient and urticaria and hypotension in another, while aspirin alone or food alone elicited no response. The third patient developed urticaria only when he took all three items, i.e. aspirin, food and additional exercise, whereas provocation with any one or or two of these did not induce any symptoms. These findings suggest that aspirin upregulates type I allergic responses to food in patients with FDEIA, and further shows that aspirin synergizes with exercise to provoke symptoms of FDEIA. This is the first report of a synergistic effect of aspirin in inducing urticaria/anaphylaxis, which was confirmed using challenge tests in patients with FDEIA.

Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

PubMed

Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Coluccia, Roberta; De Caterina, Raffaele

2017-09-01

While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

Effects of aspirin on small-cell lung cancer mortality and metastatic presentation.

PubMed

Maddison, Paul

2017-04-01

Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse. We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis. Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin. The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Tobacco use among designated air pollution victims and its association with lung function and respiratory symptoms: a retrospective cross-sectional study.

PubMed

Kotaki, Kenji; Senjyu, Hideaki; Tanaka, Takako; Yano, Yudai; Miyamoto, Naomi; Nishinakagawa, Tsuyoshi; Yanagita, Yorihide; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Sawai, Terumitsu; Honda, Sumihisa

2014-07-31

We sought to elucidate the long-term association of tobacco use and respiratory health in designated pollution victims with and without obstructive pulmonary defects. A retrospective cross-sectional study. The register of pollution victims in Kurashiki, Japan. 730 individuals over 65 years of age previously diagnosed with pollution-related respiratory disease. Patients were classified into four groups according to their smoking status and whether they had obstructive pulmonary disease. We then compared the prevalence of respiratory symptoms and lung function over time between groups. Spirometry was performed and a respiratory health questionnaire completed in the same season each year for up to 30 years. Rates of smoking and respiratory disease were high in our sample. Although respiratory function in non-smoking patients did not completely recover, the annual rate of change in lung function was within the normal range (p<0.01). However, smokers had worse lung function and were more likely to report more severe pulmonary symptoms (p<0.01). Patients' respiratory function did not fully recover despite improved air quality. Our results suggest that, in the context of exposure to air pollution, tobacco use causes additional loss of lung function and exacerbates respiratory symptoms. 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.

A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults

PubMed Central

Mai, Nguyen TH; Dobbs, Nicholas; Phu, Nguyen Hoan; Colas, Romain A; Thao, Le TP; Thuong, Nguyen TT; Nghia, Ho DT; Hanh, Nguyen HH; Hang, Nguyen T; Heemskerk, A Dorothee; Day, Jeremy N; Ly, Lucy; Thu, Do DA; Merson, Laura; Kestelyn, Evelyne; Wolbers, Marcel; Geskus, Ronald; Summers, David; Chau, Nguyen VV; Dalli, Jesmond

2018-01-01

Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3 and 4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg/day, and 40 to aspirin 1000 mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120 (76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114 (35.1%) participants. The primary safety outcome occurred in 5/36 (13.9%) given placebo, and in 8/35 (22.9%) and 8/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11/38 (28.9%) given placebo, 8/36 (22.2%) given aspirin 81 mg, and 6/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (Pheterogeneity = 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32 (34.4%) events in placebo vs. 4/27 (14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000 mg; p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A2 and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial. PMID:29482717

Aspirin for Primary Prevention of Cardiovascular Events

PubMed Central

Augustovski, Federico A.; Cantor, Scott B.; Thach, Chau T.; Spann, Stephen J.

1998-01-01

OBJECTIVE The use of aspirin for primary prevention of cardiovascular events in the general population is controversial. The purpose of this study was to create a versatile model to evaluate the effects of aspirin in the primary prevention of cardiovascular events in patients with different risk profiles. DESIGN A Markov decision-analytic model evaluated the expected length and quality of life for the cohort's next 10 years as measured by quality-adjusted survival for the options of taking or not taking aspirin. SETTING Hypothetical model of patients in a primary care setting. PATIENTS Several cohorts of patients with a range of risk profiles typically seen in a primary care setting were considered. Risk factors considered included gender, age, cholesterol levels, systolic blood pressure, smoking status, diabetes, and presence of left ventricular hypertrophy. The cohorts were followed for 10 years. Outcomes were myocardial infarction, stroke, gastrointestinal bleed, ulcer, and death. MAIN RESULTS For the cases considered, the effects of aspirin varied according to the cohort's risk profile. By taking aspirin, the lowest-risk cohort would be the most harmed with a loss of 1.8 quality-adjusted life days by taking aspirin; the highest risk cohort would achieve the most benefit with a gain of 11.3 quality-adjusted life days. Results without quality adjustment favored taking aspirin in all the cohorts, with a gain of 0.73 to 8.04 days. The decision was extremely sensitive to variations in the utility of taking aspirin and to aspirin's effects on cardiovascular mortality. The model was robust to other probability and utility changes within reasonable parameters. CONCLUSIONS The decision of whether to take aspirin as primary prevention for cardiovascular events depends on patient risk. It is a harmful intervention for patients with no risk factors, and it is beneficial in moderate and high-risk patients. The benefits of aspirin in this population are comparable to those of other widely accepted preventive strategies. It is especially dependent on the patient's risk profile, patient preferences for the adverse effects of aspirin, and on the level of beneficial effects of aspirin on cardiovascular-related mortality. PMID:9844080

Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

PubMed Central

García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

2016-01-01

Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin in prevention of cardiovascular events. PMID:27490468

Aspirin induces apoptosis in vitro and inhibits tumor growth of human hepatocellular carcinoma cells in a nude mouse xenograft model

PubMed Central

HOSSAIN, MOHAMMAD AKBAR; KIM, DONG HWAN; JANG, JUNG YOON; KANG, YONG JUNG; YOON, JEONG-HYUN; MOON, JEON-OK; CHUNG, HAE YOUNG; KIM, GI-YOUNG; CHOI, YUNG HYUN; COPPLE, BRYAN L.; KIM, NAM DEUK

2012-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce apoptosis in a variety of cancer cells, including colon, prostate, breast and leukemia. Among them, aspirin, a classical NSAID, shows promise in cancer therapy in certain types of cancers. We hypothesized that aspirin might affect the growth of liver cancer cells since liver is the principal site for aspirin metabolism. Therefore, we investigated the effects of aspirin on the HepG2 human hepatocellular carcinoma cell line in vitro and the HepG2 cell xenograft model in BALB/c nude mice. We found that treatment with aspirin inhibited cell growth and induced apoptosis involving both extrinsic and intrinsic pathways as measured by DNA ladder formation, alteration in the Bax/Bcl-2 ratio, activation of the caspase activities and related protein expressions. In vivo antitumor activity assay also showed that aspirin resulted in significant tumor growth inhibition compared to the control. Oral administration of aspirin (100 mg/kg/day) caused a significant reduction in the growth of HepG2 tumors in nude mice. These findings suggest that aspirin may be used as a promising anticancer agent against liver cancer. PMID:22179060

Time related neutralization of two doses acetyl salicylic acid.

PubMed

Aguejouf, O; Malfatti, E; Belon, P; Doutremepuich, C

2000-11-15

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis has become an important issue. In fact, hemorrhage complications are often associated with its use. On the other hand, previous studies showed unexpected thrombotic potencies associated with the presence of this drug at ultra low doses (ULD) in the circulation. In this study, we aimed to evaluate the effect of aspirin at ULD, injected 1, 2, or 3 hours after the administration of aspirin at 100 mg/kg, on hemostasis and bleeding in rats. We used an experimental model of thrombosis induced by laser beams to evaluate these effects. Platelet aggregation was determined by Cardinal and Flower method. Results from this investigation demonstrate that the neutralizing effect of aspirin at ULD did not operate significantly 1 hour after the injection of aspirin at 100 mg/kg. This effect was observed 2 and 3 hours after. The use of aspirin at ULD to neutralize the side effects of aspirin at high doses will reduce the hemorrhagic risk during extra corporeal circulation. The therapeutic benefit and safety of aspirin therapy in the treatment of cardiovascular diseases can be obtained.

Activation of activator protein 2 alpha by aspirin alleviates atherosclerotic plaque growth and instability in vivo

PubMed Central

Yang, Jing-Jing; Li, Peng; Wang, Fu; Liang, Wen-Jing; Ma, Hui; Chen, Yuan; Ma, Zhi-Min; Li, Quan-Zhong; Peng, Qi-Sheng; Zhang, Yun; Wang, Shuang-Xi

2016-01-01

Aims Aspirin has been used for the secondary prevention and treatment of cardiovascular disease for several decades. We investigated the roles of transcriptional factor activator protein 2α (AP-2α) in the beneficial effects of aspirin in the growth and vulnerability of atherosclerotic plaque. Methods and Results In mice deficient of apolipoprotein E (Apoe-/-), aspirin (20, 50 mg/kg/day) suppressed the progression of atherosclerosis in aortic roots and increased the plaque stability in carotid atherosclerotic plaques induced by collar-placement. In vivo lentivirus-mediated RNA interference of AP-2α reversed the inhibitory effects of aspirin on atherosclerosis in Apoe-/- mice. Mechanically, aspirin increased AP-2α phosphorylation and its activity, upregulated IkBα mRNA and protein levels, and reduced oxidative stress in cultured vascular smooth muscle cells. Furthermore, deficiency of AP-2α completely abolished aspirin-induced upregulation of IkBα levels and inhibition of oxidative stress in Apoe-/- mice. Clinically, conventional doses of aspirin increased AP-2α phosphorylation and IkBα protein expression in humans subjects. Conclusion Aspirin activates AP-2α to upregulate IkBα gene expression, resulting in attenuations of plaque development and instability in atherosclerosis. PMID:27391154

A New Approach for Identifying Patients with Undiagnosed Chronic Obstructive Pulmonary Disease

PubMed Central

Mannino, David; Leidy, Nancy Kline; Malley, Karen G.; Bacci, Elizabeth D.; Barr, R. Graham; Bowler, Russ P.; Han, MeiLan K.; Houfek, Julia F.; Make, Barry; Meldrum, Catherine A.; Rennard, Stephen; Thomashow, Byron; Walsh, John; Yawn, Barbara P.

2017-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated. Objectives: To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1 <60% predicted and/or exacerbation risk). Methods: We conducted a multisite, cross-sectional, case-control study in U.S. pulmonary and primary care clinics that recruited subjects from primary care settings. Cases were patients with COPD and at least one exacerbation in the past year or FEV1 less than 60% of predicted without exacerbation in the past year. Control subjects were persons with no COPD or with mild COPD (FEV1 ≥60% predicted, no exacerbation in the past year). In random forests analyses, we identified the smallest set of questions plus peak expiratory flow (PEF) with optimal sensitivity (SN) and specificity (SP). Measurements and Main Results: PEF and spirometry were recorded in 186 cases and 160 control subjects. The mean (SD) age of the sample population was 62.7 (10.1) years; 55% were female; 86% were white; and 16% had never smoked. The mean FEV1 percent predicted for cases was 42.5% (14.2%); for control subjects, it was 82.5% (15.7%). A five-item questionnaire, CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk), was used to assess exposure, breathing problems, tiring easily, and acute respiratory illnesses. CAPTURE exhibited an SN of 95.7% and an SP of 44.4% for differentiating cases from all control subjects, and an SN of 95.7% and an SP of 67.8% for differentiating cases from no-COPD control subjects. The PEF (males, <350 L/min; females, <250 L/min) SN and SP were 88.0% and 77.5%, respectively, for differentiating cases from all control subjects, and they were 88.0% and 90.8%, respectively, for distinguishing cases from no-COPD control subjects. The CAPTURE plus PEF exhibited improved SN and SP for all cases versus all control subjects (89.7% and 78.1%, respectively) and for all cases versus no-COPD control subjects (89.7% and 93.1%, respectively). Conclusions: CAPTURE with PEF can identify patients with COPD who would benefit from currently available therapy and require further diagnostic evaluation. Clinical trial registered with clinicaltrials.gov (NCT01880177). PMID:27783539

A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus.

PubMed

Rey-Jurado, Emma; Soto, Jorge; Gálvez, Nicolás; Kalergis, Alexis M

2017-09-02

The human Respiratory Syncytial Virus (hRSV) causes lower respiratory tract infections including pneumonia and bronchiolitis. Such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. Symptoms associated with hRSV infection are due to an exacerbated immune response characterized by low levels of IFN-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. Although hRSV is a major health problem, no vaccines are currently available. Different immunization approaches have been developed to achieve a vaccine that activates the immune system, without triggering an unbalanced inflammation. These approaches include live attenuated vaccine, DNA or proteins technologies, and the use of vectors to express proteins of the virus. In this review, we discuss the host immune response to hRSV and the immunological mechanisms underlying an effective and safe BCG vectored vaccine against hRSV.

Effects of traffic-related outdoor air pollution on respiratory illness and mortality in children, taking into account indoor air pollution, in Indonesia.

PubMed

Kashima, Saori; Yorifuji, Takashi; Tsuda, Toshihide; Ibrahim, Juliani; Doi, Hiroyuki

2010-03-01

To evaluate the effects of outdoor air pollution, taking into account indoor air pollution, in Indonesia. The subjects were 15,242 children from 2002 to 2003 Indonesia Demographic and Health Survey. The odds ratios and their confidence intervals for adverse health effects were estimated. Proximity increased the prevalence of acute respiratory infection both in urban and rural areas after adjusting for indoor air pollution. In urban areas, the prevalence of acute upper respiratory infection increased by 1.012 (95% confidence intervals: 1.005 to 1.019) per 2 km proximity to a major road. Adjusted odds ratios tended to be higher in the high indoor air pollution group. Exposure to traffic-related outdoor air pollution would increase adverse health effects after adjusting for indoor air pollution. Furthermore, indoor air pollution could exacerbate the effects of outdoor air pollution.

Summary of the Chronic Obstructive Pulmonary Disease Clinical Practice Guideline Revised in 2014 by the Korean Academy of Tuberculosis and Respiratory Disease

PubMed Central

Yoon, Hyoung Kyu; Park, Yong-Bum; Rhee, Chin Kook; Lee, Jin Hwa

2017-01-01

Chronic obstructive pulmonary disease (COPD) results in high morbidity and mortality among patients both domestically and globally. The Korean clinical practice guideline for COPD was revised in 2014. It was drafted by the members of the Korean Academy of Tuberculosis and Respiratory Diseases, as well as participating members of the Health Insurance Review and Assessment Service, Korean Physicians' Association, and Korea Respiration Trouble Association. This revised guideline covers a wide range of topics, including the epidemiology, diagnosis, assessment, monitoring, management, exacerbation, and comorbidities of COPD in Korea. We drafted a guideline on COPD management by performing systematic reviews on the topic of management with the help of a meta-analysis expert. We expect this guideline will be helpful medical doctors treating patients with respiratory conditions, other health care professionals, and government personnel in South Korea. PMID:28747955

21 CFR 343.13 - Rheumatologic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.13 - Rheumatologic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.12 - Cardiovascular active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.13 - Rheumatologic active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.13 - Rheumatologic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.12 - Cardiovascular active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.12 - Cardiovascular active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.12 - Cardiovascular active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

75 FR 8081 - Patrick J. Lais: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

..., among other things, subpotent burn spray, aspirin that had failed dissolution testing, and antacid... as ``Uncoated Aspirin.'' This drug failed its final dissolution testing. Neither Mr. Lais nor the... coated the failed aspirin and renumbered the lot. Part of this lot then was packaged as ``Coated Aspirin...

21 CFR 343.13 - Rheumatologic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.13 Rheumatologic active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

21 CFR 343.12 - Cardiovascular active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

...-COUNTER HUMAN USE Active Ingredients § 343.12 Cardiovascular active ingredients. (a) Aspirin. (b) Buffered aspirin. Aspirin identified in paragraph (a) of this section may be buffered with any antacid ingredient(s... milliequivalents of acid-neutralizing capacity per 325 milligrams of aspirin as measured by the procedure provided...

Aspirin resistance in patients with hemodynamic cerebral ischemia undergoing extracranial-intracranial bypass surgery.

PubMed

Jussen, Daniel; Horn, Peter; Vajkoczy, Peter

2013-01-01

Aspirin (acetylsalicylic acid, ASA) is the treatment of choice for prevention of vascular events in symptomatic steno-occlusive cerebrovascular disease (CVD). Cerebral revascularization using standard extracranial-intracranial (EC-IC) bypass surgery may be used to revert hemodynamic compromise. Aspirin is prescribed as standard medication in order to avoid bypass failure. Accumulating evidence of an increased risk of major adverse clinical events led to this study, in which we aimed to assess the prevalence of aspirin resistance and prothrombotic disorders among patients scheduled for EC-IC bypass surgery, and the effectiveness of aspirin dose escalation. We prospectively screened patients with circumscribed high-grade stenosis or occlusion of brain-supplying vessels fulfilling the hemodynamic criteria for EC-IC bypass surgery for aspirin resistance using a platelet function analyzer (PFA-100®) test. We also determined their smoking habits and screened for prothrombotic disorders and comorbidities. The patients were divided into 2 major groups: group A had atherosclerotic steno-occlusive CVD and group B consisted of patients with nonatherosclerotic steno-occlusive CVD (moyamoya disease) and a subgroup of pediatric moyamoya patients (pediatric subgroup). Bypass patency was documented via digital subtraction angiography. Standard initial ASA dose applied was 100 mg/day. In cases of aspirin resistance, doses were increased and the PFA-100 test was repeated. A total of 56 patients were included over a time period of 6 months. In group A (n = 25), we found a ratio of 40% of patients with primary resistance to aspirin 100 mg/day. In contrast, in group B (n = 25), only 20% of the patients were resistant to aspirin 100 mg/day; in the pediatric population (n = 6), there was no primary aspirin resistance. After a dose escalation to 300 mg/day, the ratio of aspirin resistance was reduced to 20% in group A and to 0% in group B. Altogether 5 patients with atherosclerotic steno-occlusive CVD remained aspirin-resistant despite the dose escalation; 2 of them suffered an early bypass failure. Smoking habits and diabetes mellitus were positively correlated with aspirin resistance. Moreover, 25% of all patients had laboratory signs of a prothrombotic disorder, but this had no influence on aspirin response or bypass patency. Aspirin resistance is common in the population of patients with hemodynamic cerebral ischemia scheduled for cerebral revascularization. It may have an adverse impact on the outcome of surgery. Screening and treatment via dose escalation of aspirin is a straightforward and sensible routine for patients undergoing EC-IC bypass surgery. Copyright © 2013 S. Karger AG, Basel.

Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

PubMed

Zhao, Qiang; Zhu, Yunpeng; Xu, Zhiyun; Cheng, Zhaoyun; Mei, Ju; Chen, Xin; Wang, Xiaowei

2018-04-24

The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown. To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG. Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017. Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation. Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography. Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with ticagrelor + aspirin; 2 with ticagrelor alone). Among patients undergoing elective CABG with saphenous vein grafting, ticagrelor + aspirin significantly increased graft patency after 1 year vs aspirin alone; there was no significant difference between ticagrelor alone and aspirin alone. Further research with more patients is needed to assess comparative bleeding risks. clinicaltrials.gov Identifier: NCT02201771.

Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

PubMed

Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

2008-03-01

Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

Bioavailability of aspirin in rats comparing the drug's uptake into gastrointestinal tissue and vascular and lymphatic systems: implications on aspirin's chemopreventive action.

PubMed

Lichtenberger, L M; Phan, T; Fang, D; Edler, S; Philip, J; Li-Geng, T; Dial, E J

2016-10-01

Aspirin is an effective analgesic and antiplatelet drug that in addition to its ability to reduce pain, inflammation and fever, appears to have efficacy in the prevention/treatment of a range of diseases including heart disease, numerous cancers and Alzheimer's. It is important to understand the bioavailability of aspirin and its major metabolite, salicylic acid, since dosage and route of administration can vary for treating differing diseases, and the major side-effects of aspirin, upper gastrointestinal ulceration and bleeding, are dose-dependent. We examined the time course for gastroduodenal uptake of aspirin and the appearance of its major metabolite salicylic acid in blood and lymph after intragastric (to simulate oral) and intraduodenal (to simulate enteric-coating) dosing in rats. Results show that after intragastric dosing, intact aspirin is absorbed primarily by the gastric mucosa and to a lesser extent by the duodenal mucosa. When aspirin is dosed intragastrically or intraduodenally, a much greater concentration of aspirin enters the lymph than the blood. In contrast, the concentration of salicylic acid was higher in blood than in lymph. Lymph levels of both aspirin and salicylic acid were sufficiently high so as to perform a pharmacologic function there, possibly as a chemopreventive agent against colon cancer and potentially the metastatic spread of non-gastrointestinal cancers.

Aspirin is associated with low oral pH levels and antacid helps to increase oral pH.

PubMed

Ediriweera, Dileepa Senajith; Dilina, Nuwani; Saparamadu, Vipula; Fernando, Inoka; Kurukulasuriya, Buddhika; Fernando, Deepika; Kurera, Janakie

2018-02-20

Aspirin is a commonly used medicine for primary and secondary prevention of cardiovascular diseases. It is an acidic medicine associated with gastric irritation and acid reflux, which in turn can lead to low oral pH levels. Therefore, it is important to understand the association between aspirin and oral pH levels in order to achieve an optimum oral health condition among patients who take aspirin on prescription. Out of 373 patients, 162 (44%) were males and 245 (66%) were on aspirin. 71% of aspirin taking patients and 29% of non-aspirin taking patients had oral pH less than 6.5 (P < 0.01). Aspirin showed a significant association with low oral pH levels (odds ratio = 1.91, 95% CI 1.23-2.99, P < 0.01). 78 patients were given antacids and followed up for 4 weeks, 63 of them (81%) showed an improvement in oral pH and the improvement was marked in the group who had oral pH between 5.5-6.0 compared to the group who had oral pH between 6.0-6.5 (P = 0.03). The results show that aspirin therapy is associated with low oral pH and administration of an antacid with aspirin helps to increase the oral pH level.

Papillary Necrosis in Rats Caused by Aspirin and Aspirin-containing Mixtures

PubMed Central

Nanra, Ranjit S.; Kincaid-Smith, Priscilla

1970-01-01

Nearly half the rats gavage-fed with aspirin and aspirin-containing mixtures developed papillary necrosis in 20 weeks. This incidence is similar to that found in rats on A.P.C. mixtures with high and low concentrations of p-chloracetanilide, an impurity of phenacetin. Aspirin alone produced necrosis in 7 out of 19 rats (36·8%) whereas phenacetin in the same dose had failed to cause any renal damage over six to nine months. If these results also apply to man they suggest that aspirin and not phenacetin may be the major factor in analgesic nephropathy in patients taking A.P.C. mixtures. An augmented clearance of aspirin appeared to afford some protection to the medulla, and it is suggested that this observation may have important clinical and epidemiological applications. Imagesp560-a PMID:5454357

Aspirin and the Kidney

PubMed Central

1974-01-01

A survey of 763 patients with rheumatoid arthritis and 145 with osteoarthritis in six clinics in New Zealand showed no association between aspirin intake and a score designed to detect analgesic nephropathy. Analgesic nephropathy was diagnosed clinically in three patients taking APC (aspirin, phenacetin, and caffeine or codeine or both) and in one who took aspirin and phenylbutazone and was suspected in one who took aspirin and paracetamol. Isolated aspirin was not implicated. The study showed that most people can take large quantities of salicylates without renal injury. The findings are, however, consistent with the view that there is a risk from APC compounds taken in large quantity, but the numbers at risk in this study were small. Aspirin may have an additive effect with other analgesics in causing renal damage. An increased frequency of urinary tract symptoms in those taking analgesics requires further investigation. PMID:4821007

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

PubMed

Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

1985-02-01

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Aspirin in Postoperative Management of Adult Ischemic Moyamoya Disease.

PubMed

Zhao, Yahui; Zhang, Qian; Zhang, Dong; Zhao, Yuanli

2017-09-01

Aspirin has been implicated in the postoperative management of moyamoya disease (MMD) in order to avoid bypass failure and decrease the incidence of subsequent stroke. However, its effect has not been completely determined yet. In this study, we retrospectively reviewed data of 184 adult patients (197 hemispheres) presented with ischemic-onset MMD who had undergone direct or combined revascularization in our hospital, to clarify the effect of postoperative aspirin therapy in the management of moyamoya disease. Fifty-nine hemispheres that had been administered with aspirin (100 mg/day) after bypass surgery were defined as the "aspirin group," whereas 138 that hadn't been given aspirin postoperatively were defined as the "control group". Among 197 hemispheres, the mortality rate was 0. The incidence of postoperative newly developed infarction, transient ischemic attack, and hemorrhage were not significantly different between the aspirin and control groups. The patency rate of bypass graft was not significantly different between the groups, either. Notably, more patients experienced major stroke in the control group (9/138) than the aspirin group (1/59), but no statistical difference was found (P > 0.05). In the aspirin group, more patients had improved outcome than the control group (P = 0.04). Our findings showed that aspirin might not decrease the incidence of postoperative ischemic stroke or increase patency rate of bypass graft, but it does not increase the risk of hemorrhages, either. Also, postoperative aspirin therapy might improve outcome. More studies are needed to provide evidence for postoperative antiplatelet therapy in MMD management. Copyright © 2017 Elsevier Inc. All rights reserved.

Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension?

PubMed

Hans, Harvir; Lone, Asad; Aksenov, Vadim; Rollo, C David

2015-01-01

We examined the impacts of aspirin and metformin on the life history of the cricket Acheta domesticus (growth rate, maturation time, mature body size, survivorship, and maximal longevity). Both drugs significantly increased survivorship and maximal life span. Maximal longevity was 136 days for controls, 188 days (138 % of controls) for metformin, and 194 days (143 % of controls) for aspirin. Metformin and aspirin in combination extended longevity to a lesser degree (163 days, 120 % of controls). Increases in general survivorship were even more pronounced, with low-dose aspirin yielding mean longevity 234 % of controls (i.e., health span). Metformin strongly reduced growth rates of both genders (<60 % of controls), whereas aspirin only slightly reduced the growth rate of females and slightly increased that of males. Both drugs delayed maturation age relative to controls, but metformin had a much greater impact (>140 % of controls) than aspirin (~118 % of controls). Crickets maturing on low aspirin showed no evidence of a trade-off between maturation mass and life extension. Remarkably, by 100 days of age, aspirin-treated females were significantly larger than controls (largely reflecting egg complement). Unlike the reigning dietary restriction paradigm, low aspirin conformed to a paradigm of "eat more, live longer." In contrast, metformin-treated females were only ~67 % of the mass of controls. Our results suggest that hormetic agents like metformin may derive significant trade-offs with life extension, whereas health and longevity benefits may be obtained with less cost by agents like aspirin that regulate geroprotective pathways.

Cost‐Effectiveness of Clopidogrel‐Aspirin Versus Aspirin Alone for Acute Transient Ischemic Attack and Minor Stroke

PubMed Central

Pan, Yuesong; Wang, Anxin; Liu, Gaifen; Zhao, Xingquan; Meng, Xia; Zhao, Kun; Liu, Liping; Wang, Chunxue; Johnston, S. Claiborne; Wang, Yilong; Wang, Yongjun

2014-01-01

Background Treatment with the combination of clopidogrel and aspirin taken soon after a transient ischemic attack (TIA) or minor stroke was shown to reduce the 90‐day risk of stroke in a large trial in China, but the cost‐effectiveness is unknown. This study sought to estimate the cost‐effectiveness of the clopidogrel‐aspirin regimen for acute TIA or minor stroke. Methods and Results A Markov model was created to determine the cost‐effectiveness of treatment of acute TIA or minor stroke patients with clopidogrel‐aspirin compared with aspirin alone. Inputs for the model were obtained from clinical trial data, claims databases, and the published literature. The main outcome measure was cost per quality‐adjusted life‐years (QALYs) gained. One‐way and multivariable probabilistic sensitivity analyses were performed to test the robustness of the findings. Compared with aspirin alone, clopidogrel‐aspirin resulted in a lifetime gain of 0.037 QALYs at an additional cost of CNY 1250 (US$ 192), yielding an incremental cost‐effectiveness ratio of CNY 33 800 (US$ 5200) per QALY gained. Probabilistic sensitivity analysis showed that clopidogrel‐aspirin therapy was more cost‐effective in 95.7% of the simulations at a willingness‐to‐pay threshold recommended by the World Health Organization of CNY 105 000 (US$ 16 200) per QALY. Conclusions Early 90‐day clopidogrel‐aspirin regimen for acute TIA or minor stroke is highly cost‐effective in China. Although clopidogrel is generic, Plavix is brand in China. If Plavix were generic, treatment with clopidogrel‐aspirin would have been cost saving. PMID:24904018

Pharmacological action of choline and aspirin coadministration on acute inflammatory pain.

PubMed

Yong-Ping, Shi; Jin-Da, Wang; Ru-Huan, Wang; Xiang-Di, Zhao; Hai-Tao, Yu; Hai, Wang

2011-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain but undesirable side effects limit their clinical usefulness. Choline is a α7 nicotinic receptor agonist that has antinociceptive effects in a variety of pain models. Drug combination is a strategy in the management of pain to reduce side effects. The aim of the study was to evaluate the nature of the interaction between choline and aspirin in two distinct inflammatory pain models. The analgesic mechanism of choline was also investigated. In the writhing test, intravenous administration of choline or aspirin showed dose-dependent antinociceptive activity, and isobolographic analysis revealed a synergistic nature of the interaction between choline and aspirin. More importantly, coadministration choline with aspirin could significantly shorten the antinociceptive latency of aspirin and prolong the antinociceptive duration of aspirin in the writhing test. In the carrageenan test, single administration of choline or aspirin significantly attenuated carrageenan-induced thermal hyperalgesia in a dose-dependent relationship. Coadministration of non-analgesic doses of aspirin with choline significantly suppressed the thermal hyperalgesia, with a longer duration efficacy. Furthermore, we found that α7 nicotinic, muscarinic, and opioid-receptors are involved in the antinociceptive effect of choline in the writhing test and the antinociceptive effect produced by systemically administered choline may be via a peripheral mechanism. In conclusion, coadministration of choline and aspirin holds promise for development as a safe analgesic drug combination for inflammatory pain, with a higher potency and longer duration than either aspirin or choline alone. Copyright © 2011 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Randomized controlled trial comparing impact on platelet reactivity of twice-daily with once-daily aspirin in people with Type 2 diabetes.

PubMed

Bethel, M A; Harrison, P; Sourij, H; Sun, Y; Tucker, L; Kennedy, I; White, S; Hill, L; Oulhaj, A; Coleman, R L; Holman, R R

2016-02-01

Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. Participants with Type 2 diabetes (n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow(™) ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.

PubMed

Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

2017-05-06

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. Copyright © 2017. Published by Elsevier Inc.

Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

PubMed Central

Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

2011-01-01

Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

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

Experiments with Aspirin.

ERIC Educational Resources Information Center

Borer, Londa L.; Barry, Edward

2000-01-01

Presents a series of experiments that can be used to demonstrate how aspirin can be synthesized and characterized, how the hydrolysis of aspirin can be used as an introduction to kinetics, and how coordination chemistry (chelation) can be introduced by preparing and characterizing the copper complexes of aspirin and salicylic acid. (Contains over…

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

16 CFR § 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

16 CFR 1700.14 - Substances requiring special packaging.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Aspirin. Any aspirin-containing preparation for human use in a dosage form intended for oral... following: (i) Effervescent tablets containing aspirin, other than those intended for pediatric use, provided the dry tablet contains not more than 15 percent aspirin and has an oral LD-50 in rats of 5 grams...

21 CFR 520.1409 - Methylprednisolone, aspirin tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Methylprednisolone, aspirin tablets. 520.1409... Methylprednisolone, aspirin tablets. (a) Specifications. Each tablet contains 0.5 milligram of methylprednisolone and 300 milligrams of aspirin. (b) Sponsor. See No. 000009 in § 510.600(c) of this chapter. (c) NAS/NRC...

Variability in the organisation and management of hospital care for COPD exacerbations in the UK.

PubMed

Hosker, Harold; Anstey, Katharine; Lowe, Derek; Pearson, Michael; Roberts, C Michael

2007-04-01

Previous smaller UK audits have demonstrated wide variation in organisation, resources, and process of care for acute chronic obstructive pulmonary disease (COPD) admissions. Smallest units appeared to do less well. UK acute hospitals supplied information on (1) resources and organisation of care, (2) clinical data on process of care and outcomes for up to 40 consecutive COPD admissions. Comparisons were made against national recommendations. Eight thousand and thirteen admissions involved 7529 patients from 233 units (93% of UK acute Trusts). Twenty-six percent of units had at most one whole-time equivalent respiratory consultant while 12% had at least four. Thirty percent patients were admitted under a respiratory specialist and 48% discharged under their care whilst 28% had no specialist input at all. Variation in care provision was wide across all hospitals but patients in smaller hospitals had less access to specialist respiratory or admission wards, pulmonary rehabilitation programs, specialty triage or an early discharge scheme. Six percent of units did not have access to NIV and 18% to invasive ventilatory support. There remains wide variation in all aspects of acute hospital COPD care in the UK, with smaller hospitals offering fewest services. Those receiving specialist input are more likely to be offered interventions of proven effect. Management guidelines alone are insufficient to address inequalities of care and a clear statement of minimum national standards for resource provision and organisation of COPD care are required. This study provides a unique insight into the current state of care for patients admitted with COPD exacerbations in the UK.

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

PubMed

Marchioni, Alessandro; Tonelli, Roberto; Ball, Lorenzo; Fantini, Riccardo; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Malerba, Mario; Pelosi, Paolo; Clini, Enrico

2018-03-23

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Small-bowel mucosal injuries in low-dose aspirin users with obscure gastrointestinal bleeding

PubMed Central

Iwamoto, Junichi; Mizokami, Yuji; Saito, Yoshifumi; Shimokobe, Koichi; Honda, Akira; Ikegami, Tadashi; Matsuzaki, Yasushi

2014-01-01

AIM: To investigate the clinical differences between small intestinal injuries in low-dose aspirin (LDA) users and in non-steroidal anti-inflammatory drug (NSAID) users who were examined by capsule endoscopy (CE) for obscure gastrointestinal bleeding (OGIB). METHODS: A total of 181 patients who underwent CE for OGIB were included in this study. Based on clinical records, laboratory data such as hemoglobin levels, major symptoms, underlying diseases, the types and duration of LDA and NSAID use, and endoscopic characteristics of CE were reviewed. RESULTS: Out of a total of 45 cases of erosive lesions, 27 cases were taking LDA or NSAIDs (7 were on NSAIDs, 9 were on LDA alone, 9 were on LDA and thienopyridine, and 2 were on LDA and warfarin).The prevalence of ulcers or erosion during chronic use of LDA, LDA and the anti-platelet drug thienopyridine (clopidogrel or ticlopidine), and NSAIDs were 64.3%, 80.0%, and 75.0%, respectively. Erosive lesions were observed predominantly in chronic LDA users, while ulcerative lesions were detected mainly in NSAID users. However, concomitant use of thienopyridine such as clopidogrel with LDA increased the proportion of ulcers. The erosive lesions were located in the whole of the small intestine (jejunum and ileum), whereas ulcerative lesions were mainly observed in the ileum (P < 0.05). CONCLUSION: Our CE findings indicate that chronic LDA users and NSAID users show different types and locations of small-bowel mucosal injuries. The concomitant use of anti-platelet drugs with LDA tends to exacerbate the injuries from LDA-type to NSAID-type injuries. PMID:25278707

Effect of a rehabilitation-based chronic disease management program targeting severe COPD exacerbations on readmission patterns.

PubMed

Lalmolda, C; Coll-Fernández, R; Martínez, N; Baré, M; Teixidó Colet, M; Epelde, F; Monsó, E

2017-01-01

Pulmonary rehabilitation (PR) is recommended after a severe COPD exacerbation, but its short- and long-term effects on health care utilization have not been fully established. The aims of this study were to evaluate patient compliance with a chronic disease management (CDM) program incorporating home-based exercise training as the main component after a severe COPD exacerbation and to determine its effects on health care utilization in the following year. COPD patients with a severe exacerbation were included in a case-cohort study at admission. An intervention group participated in a nurse-supervised CDM program during the 2 months after discharge, comprising of home-based PR with exercise components directly supervised by a physiotherapist, while the remaining patients followed usual care. Nineteen of the twenty-one participants (90.5%) were compliant with the CDM program and were compared with 29 usual-care patients. Compliance with the program was associated with statistically significant reductions in admissions due to respiratory disease in the following year (median [interquartile range]: 0 [0-1] vs 1 [0-2.5]; P =0.022) and in days of admission (0 [0-7] vs 7 [0-12]; P =0.034), and multiple linear regression analysis confirmed the protective effect of the CDM program (β coefficient -0.785, P =0.014, and R 2 =0.219). A CDM program incorporating exercise training for COPD patients without limiting comorbidities after a severe exacerbation achieves high compliance and reduces admissions in the year following after the intervention.