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Sample records for background acute exacerbations

  1. Prevention of Acute Exacerbations of COPD

    PubMed Central

    Bourbeau, Jean; Diekemper, Rebecca L.; Ouellette, Daniel R.; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S.; Bhutani, Mohit; Camp, Pat G.; Celli, Bartolome R.; Dechman, Gail; Dransfield, Mark T.; Fiel, Stanley B.; Foreman, Marilyn G.; Hanania, Nicola A.; Ireland, Belinda K.; Marchetti, Nathaniel; Marciniuk, Darcy D.; Mularski, Richard A.; Ornelas, Joseph; Stickland, Michael K.

    2015-01-01

    BACKGROUND: COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. METHODS: In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. RESULTS: The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in

  2. Acute Exacerbation in Interstitial Lung Disease

    PubMed Central

    Leuschner, Gabriela; Behr, Jürgen

    2017-01-01

    Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field. PMID:29109947

  3. Beta Blockers for the Prevention of Acute Exacerbations of COPD

    DTIC Science & Technology

    2017-10-01

    beta blockers , cardiovascular disease , COPD, exacerbation , metoprolol succinate, placebo- controlled, randomized 16. SECURITY CLASSIFICATION OF...basis. KEYWORDS: beta blockers cardiovascular disease COPD exacerbation metoprolol succinate placebo-controlled randomized...pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a

  4. Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Cardiovascular Links

    PubMed Central

    Laratta, Cheryl R.; van Eeden, Stephan

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants. COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function. The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature. Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease. PMID:24724085

  5. Augmentin in acute exacerbations of chronic bronchitis.

    PubMed

    Aigner, K; Schindl, R; Mittermayer, H

    1984-01-01

    Forty-five patients with acute chronic bronchitis were treated with Augmentin, an amoxycillin combined with the beta-lactamase inhibitor clavulanic acid, initially by parenteral administration followed by oral treatment after 3 days lasting in the mean 7.1 days. The over-all clinical evaluation showed a cure rate of 93%. Side-effects were comparable to therapy with other amoxycillins. Bacteriological evaluation of the sputum samples demonstrated in 91% of cases an elimination of the initially isolated organism. Prior to therapy we found in 25% of the isolated strains beta-lactamase-producing and Augmentin-sensitive organisms. The parenteral formulation of Augmentin seems to be a valuable addition to the parenteral therapy of lower respiratory tract infections.

  6. Analysis of Surgical Success in Preventing Recurrent Acute Exacerbations in Chronic Pancreatitis

    PubMed Central

    Nealon, William H.; Matin, Sina

    2001-01-01

    Objective To determine whether surgical intervention prevents recurrent acute exacerbations in chronic pancreatitis (CP). Summary Background Data The primary goal of surgical intervention in the treatment of CP has been relief of chronic unrelenting abdominal pain. A subset of patients with CP have intermittent acute exacerbations, often with increasing frequency and often unrelated to ongoing ethanol abuse. Little data exist regarding the effectiveness of surgery to prevent acute attacks. Methods From 1985 to 1999, all patients identified with a diagnosis of CP were recruited to participate in an ongoing program of serial clinic visits and functional and clinical evaluations. Patients were offered surgery using standard criteria. Data were gathered regarding ethanol abuse, pain, narcotic use, and recurrent acute exacerbations requiring hospital admission before and after surgery. Patients were broadly categorized as having severe unrelenting pain alone (group 1), severe pain with intermittent acute exacerbations (group 2), and intermittent acute exacerbations only (group 3). Results Two hundred fifty-nine patients were recruited. One hundred eighty-five patients underwent 199 surgical procedures (124 modified Puestow procedure [LPJ], 29 distal pancreatectomies [DP], and 46 pancreatic head resections [PHR; 14 performed after failure of LPJ]). There were no deaths. The complication rate was 4% for LPJ, 15% for DP, and 27% for PHR. Ethanol abuse was causative in 238 patients (92%). Mean follow-up was 81 months. There were 104 patients in group 1 (86 who underwent surgery), 71 patients in group 2 (64 who underwent surgery), and 84 in group 3 (49 who underwent surgery). No patient without surgery had spontaneous resolution of symptoms. Postoperative pain relief (freedom from narcotic analgesics) was achieved in 153 of 185 patients (83%) overall: 106 of 124 (86%) for LPJ, 19 of 29 (67%) for DP, and 42 of 46 (91%) for PHR. The mean rate of acute exacerbations was 6.3

  7. Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection

    PubMed Central

    Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco

    2008-01-01

    Background Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. Methods We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4–8 weeks. Results Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 ± 104 L/min vs 276 ± 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 ± 24.54 vs FEV1% 92.91 ± 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38–13.32). Conclusion Our data suggest an association between acute atypical infection and a more severe AEBA. PMID:18513407

  8. Predicting Acute Exacerbations in Chronic Obstructive Pulmonary Disease.

    PubMed

    Samp, Jennifer C; Joo, Min J; Schumock, Glen T; Calip, Gregory S; Pickard, A Simon; Lee, Todd A

    2018-03-01

    With increasing health care costs that have outpaced those of other industries, payers of health care are moving from a fee-for-service payment model to one in which reimbursement is tied to outcomes. Chronic obstructive pulmonary disease (COPD) is a disease where this payment model has been implemented by some payers, and COPD exacerbations are a quality metric that is used. Under an outcomes-based payment model, it is important for health systems to be able to identify patients at risk for poor outcomes so that they can target interventions to improve outcomes. To develop and evaluate predictive models that could be used to identify patients at high risk for COPD exacerbations. This study was retrospective and observational and included COPD patients treated with a bronchodilator-based combination therapy. We used health insurance claims data to obtain demographics, enrollment information, comorbidities, medication use, and health care resource utilization for each patient over a 6-month baseline period. Exacerbations were examined over a 6-month outcome period and included inpatient (primary discharge diagnosis for COPD), outpatient, and emergency department (outpatient/emergency department visits with a COPD diagnosis plus an acute prescription for an antibiotic or corticosteroid within 5 days) exacerbations. The cohort was split into training (75%) and validation (25%) sets. Within the training cohort, stepwise logistic regression models were created to evaluate risk of exacerbations based on factors measured during the baseline period. Models were evaluated using sensitivity, specificity, and positive and negative predictive values. The base model included all confounding or effect modifier covariates. Several other models were explored using different sets of observations and variables to determine the best predictive model. There were 478,772 patients included in the analytic sample, of which 40.5% had exacerbations during the outcome period. Patients with

  9. 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.

  10. Exacerbation of Acute Traumatic Brain Injury by Circulating Extracellular Vesicles.

    PubMed

    Hazelton, Isla; Yates, Abi; Dale, Ashley; Roodselaar, Jay; Akbar, Naveed; Ruitenberg, Marc J; Anthony, Daniel C; Couch, Yvonne

    2018-02-15

    Inflammatory lesions in the brain activate a systemic acute-phase response (APR), which is dependent on the release of extracellular vesicles (EVs) into the circulation. The resulting APR is responsible for regulating leukocyte mobilization and subsequent recruitment to the brain. Factors that either exacerbate or inhibit the APR will also exacerbate or inhibit central nervous system (CNS) inflammation as a consequence and have the potential to influence ongoing secondary damage. Here, we were interested to discover how the circulating EV population changes after traumatic brain injury (TBI) and how manipulation of the circulating EV pool impacts on the outcome of TBI. We found the number of circulating EVs increased rapidly post-TBI, and this was accompanied by an increase in CNS and hepatic leukocyte recruitment. In an adoptive transfer study, we then evaluated the outcomes of TBI after administering EVs derived from either in vitro macrophage or endothelial cell lines stimulated with lipopolysaccharide (LPS), or from murine plasma from an LPS challenge using the air-pouch model. By manipulating the circulating EV population, we were able to demonstrate that each population of transferred EVs increased the APR. However, the characteristics of the response were dependent on the nature of the EVs; specifically, it was significantly increased when animals were challenged with macrophage-derived EVs, suggesting that the cellular origins of EVs may determine their function. Selectively targeting EVs from macrophage/monocyte populations is likely to be of value in reducing the impact of the systemic inflammatory response on the outcome of traumatic CNS injury.

  11. Right ventricular function during acute exacerbation of severe equine asthma.

    PubMed

    Decloedt, A; Borowicz, H; Slowikowska, M; Chiers, K; van Loon, G; Niedzwiedz, A

    2017-09-01

    Pulmonary hypertension has been described in horses with severe equine asthma, but its effect on the right ventricle has not been fully elucidated. To evaluate right ventricular structure and function after a 1-week period of pulmonary hypertension secondary to acute exacerbation of severe equine asthma. Prospective study. A clinical episode of severe equine asthma was induced experimentally in six susceptible horses. Examinations in remission and on day 7 of the clinical episode included a physical examination with clinical scoring, echocardiography, arterial blood gas measurements, venous blood sampling for cardiac biomarkers, intracardiac pressure measurements, right ventricular and right atrial myocardial biopsies, airway endoscopy and bronchoalveolar lavage. After 1 month of recovery, physical examination, echocardiography and cardiac biomarker analysis were repeated. Echocardiographic and pressure measurements were compared with those in 10 healthy control horses. All horses developed clinical signs of acute pulmonary obstruction. Right heart pressures increased significantly. Altered right ventricular function could be detected by tissue Doppler and speckle tracking echocardiography. Cardiac troponin concentrations did not increase significantly, but were highly elevated in one horse which exercised in the paddock prior to sampling. Focal neutrophil infiltration was present in two myocardial samples. Even in remission, asthmatic horses showed a thicker right ventricular wall, an increased left ventricular end-systolic eccentricity index at chordal level and decreased right ventricular longitudinal strain compared with controls. The induced clinical episode was rather mild and the number of horses was limited because of the invasive nature of the study. Pulmonary obstruction in asthmatic horses induces pulmonary hypertension with right ventricular structural and functional changes. © 2017 EVJ Ltd.

  12. Analysis of acutely exacerbated chronic tinnitus by the Tinnitus Handicap Inventory.

    PubMed

    Zeng, X; Li, P; Li, Z; Cen, J; Li, Y; Zhang, G

    2016-01-01

    To examine factors potentially contributing to acutely exacerbated chronic tinnitus initiation using the Tinnitus Handicap Inventory. Sixty acutely exacerbated chronic tinnitus out-patients were divided into two groups depending on whether hearing loss was aggravated or stable during tinnitus exacerbation. Total Tinnitus Handicap Inventory scores and scores for the three subscales (assessing functional limitations, emotional attitudes and catastrophic thoughts) were analysed. Total Tinnitus Handicap Inventory scores did not differ between groups. In patients with acutely exacerbated chronic tinnitus and aggravated hearing loss, functional subscale scores were significantly higher after acutely exacerbated chronic tinnitus than at baseline, but catastrophic and emotional subscale scores did not change. In patients with acutely exacerbated chronic tinnitus and stable hearing loss, emotional subscale scores were significantly higher after acutely exacerbated chronic tinnitus than at baseline, but catastrophic and functional subscale scores did not change. Elevated Tinnitus Handicap Inventory functional subscale scores might indicate further hearing loss, whereas elevated emotional subscale scores might be associated with negative life or work events.

  13. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

    PubMed

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

  14. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats

    PubMed Central

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects. PMID:28824301

  15. [Chronic obstructive pulmonary disease: 2. Short-term prognostic scores for acute exacerbations].

    PubMed

    Junod, Alain F

    2014-01-22

    The chronic obstructive pulmonary disease or COPD is a slowly progressive disease whose course is frequently the subject of acute episodes, of variable severity, although, in general, reversible, called acute exacerbations. In the past five years (between 2008 and 2013), seven prognostic scores have been published to try to assess the short-term risk of these acute exacerbations. Their components and characteristics are analysed and commented upon. An Internet program with a detailed compilation of the main features of these scores (www.medhyg.ch/scoredoc) supplements this review.

  16. 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

  17. Early investigational antibiotics for the treatment of acute exacerbations of chronic bronchitis.

    PubMed

    Falagas, Matthew E; Georgiou, Maria

    2017-03-01

    Acute exacerbations in patients with chronic bronchitis are a leading cause of hospitalizations and death. Bacteria contribute significantly to such exacerbations. The aim of this review was to explore the potential role of investigational antibiotics in the treatment of these episodes. Areas covered: The available literature in PubMed database, in websites related to investigational drugs and in websites of the producing companies has been searched. The in vitro activity against pathogens involved in acute exacerbations of chronic bronchitis and the pharmacokinetic profile of antibiotics currently under development were taken into consideration for inclusion in the review. Expert opinion: Several novel antimicrobial agents have completed preclinical and Phase I studies and were well-tolerated. Further investigation is mandatory in order to evaluate their future in treatment of chronic bronchitis exacerbations and discover potential advantages compared to already approved antimicrobials.

  18. 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.

  19. A novel study design for antibiotic trials in acute exacerbations of COPD: MAESTRAL methodology

    PubMed Central

    Wilson, Robert; Anzueto, Antonio; Miravitlles, Marc; Arvis, Pierre; Faragó, Geneviève; Haverstock, Daniel; Trajanovic, Mila; Sethi, Sanjay

    2011-01-01

    Antibiotics, along with oral corticosteroids, are standard treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The ultimate aims of treatment are to minimize the impact of the current exacerbation, and by ensuring complete resolution, reduce the risk of relapse. In the absence of superiority studies of antibiotics in AECOPD, evidence of the relative efficacy of different drugs is lacking, and so it is difficult for physicians to select the most effective antibiotic. This paper describes the protocol and rationale for MAESTRAL (moxifloxacin in AECBs [acute exacerbation of chronic bronchitis] trial; www.clinicaltrials.gov: NCT00656747), one of the first antibiotic comparator trials designed to show superiority of one antibiotic over another in AECOPD. It is a prospective, multinational, multicenter, randomized, double-blind controlled study of moxifloxacin (400 mg PO [ per os] once daily for 5 days) vs amoxicillin/clavulanic acid (875/125 mg PO twice daily for 7 days) in outpatients with COPD and chronic bronchitis suffering from an exacerbation. MAESTRAL uses an innovative primary endpoint of clinical failure: the requirement for additional or alternate treatment for the exacerbation at 8 weeks after the end of antibiotic therapy, powered for superiority. Patients enrolled are those at high-risk of treatment failure, and all are experiencing an Anthonisen type I exacerbation. Patients are stratified according to oral corticosteroid use to control their effect across antibiotic treatment arms. Secondary endpoints include quality of life, symptom assessments and health care resource use. PMID:21760724

  20. Analysis of surgical success in preventing recurrent acute exacerbations in chronic pancreatitis.

    PubMed

    Nealon, W H; Matin, S

    2001-06-01

    To determine whether surgical intervention prevents recurrent acute exacerbations in chronic pancreatitis (CP). The primary goal of surgical intervention in the treatment of CP has been relief of chronic unrelenting abdominal pain. A subset of patients with CP have intermittent acute exacerbations, often with increasing frequency and often unrelated to ongoing ethanol abuse. Little data exist regarding the effectiveness of surgery to prevent acute attacks. From 1985 to 1999, all patients identified with a diagnosis of CP were recruited to participate in an ongoing program of serial clinic visits and functional and clinical evaluations. Patients were offered surgery using standard criteria. Data were gathered regarding ethanol abuse, pain, narcotic use, and recurrent acute exacerbations requiring hospital admission before and after surgery. Patients were broadly categorized as having severe unrelenting pain alone (group 1), severe pain with intermittent acute exacerbations (group 2), and intermittent acute exacerbations only (group 3). Two hundred fifty-nine patients were recruited. One hundred eighty-five patients underwent 199 surgical procedures (124 modified Puestow procedure [LPJ], 29 distal pancreatectomies [DP], and 46 pancreatic head resections [PHR; 14 performed after failure of LPJ]). There were no deaths. The complication rate was 4% for LPJ, 15% for DP, and 27% for PHR. Ethanol abuse was causative in 238 patients (92%). Mean follow-up was 81 months. There were 104 patients in group 1 (86 who underwent surgery), 71 patients in group 2 (64 who underwent surgery), and 84 in group 3 (49 who underwent surgery). No patient without surgery had spontaneous resolution of symptoms. Postoperative pain relief (freedom from narcotic analgesics) was achieved in 153 of 185 patients (83%) overall: 106 of 124 (86%) for LPJ, 19 of 29 (67%) for DP, and 42 of 46 (91%) for PHR. The mean rate of acute exacerbations was 6.3 +/- 2.1 events per year before surgery in group 2 and

  1. CRHR1 Gene SNPs and Response to Systemic Corticosteroids in Indian Asthmatic Children During Acute Exacerbation.

    PubMed

    Awasthi, Shally; Gupta, Sarika; Agarwal, Sarita; Sharma, Neeraj

    2015-09-01

    To determine association of corticotrophin releasing hormone receptor 1 (CRHR1) gene single nucleotide polymorphisms (SNPs), rs242939 (A>G) and rs242941 (G>T) with response to systemic corticosteroids in North Indian asthmatic children during acute exacerbation. This was a hospital based cross-sectional study. Sixty-eight children aged 1 to 12 y with acute exacerbation of asthma were included in the study. The study was approved by the institutional ethics committee and written informed consent was obtained from parents/guardians of recruited children. GINA guidelines 2008, were used for classification and treatment of acute exacerbation of asthma. As per the GINA guidelines 2008, children who had good response to injectable corticosteroid were classified as "Corticosteroid Responders" (CR). Rest of the children with incomplete or poor response to injectable corticosteroid were classified as "Corticosteroid Non Responders" (CNR). Among 68 hospitalized children, 45 (66.17 %) children were CR whereas 23 (33.83 %) children were CNR. On analyzing as dominant model, children with one or two copies of mutant allele of SNP rs242941 had statistically significant better response to systemic corticosteroid (OR = 5.00; 95 %CI = 1.32-19.64; p 0.013) as compared to children with no mutant allele. Thus, CRHR1 gene SNP rs242941 polymorphism is associated with better response to systemic corticosteroid during acute exacerbation of asthma.

  2. Efficacy of amoxycillin versus amoxycillin/clavulanate in acute exacerbations of chronic pulmonary obstructive disease in primary care

    PubMed Central

    Llor, Carl; Hernández, Silvia; Ribas, Anna; Álvarez, Carmen; Cots, Josep Maria; Bayona, Carolina; González, Isabel; Miravitlles, Marc

    2009-01-01

    Background Amoxycillin/clavulanate is considered first-line treatment for ambulatory exacerbations of COPD. However, narrow-spectrum antibiotics may be as useful for mild to moderate patients. Objective To compare the clinical efficacy of amoxycillin versus amoxicyllin/clavulanate in exacerbations of COPD in primary care. Methods A randomized, double-blind, noninferiority clinical trial was carried out in eight primary care centers in Catalonia, Spain. Spirometrically-diagnosed patients older than 40 years with COPD, without criteria of hospitalization and Anthonisen’s types I or II exacerbations were included. The main outcome was clinical cure at the end of treatment (EOT) visit on day 10. Results A total of 137 patients were enrolled in the study (68 assigned to amoxycillin and 69 to amoxycillin/clavulanate). The mean forced expiratory flow in one second was 61.6% and the mean age was 71.4 years. At EOT, 92.8% of patients in the amoxycillin/clavulanate and 90.9% in the amoxycillin group were considered clinically cured, a statistically non-significant difference. Adverse effects were observed in 11 subjects, 3 in the amoxycillin group and 8 in the amoxycillin/clavulanate group, 2 of whom required a change in treatment. Conclusions Amoxycillin was at least as effective clinically and as safe as amoxycilin/ clavulanate in the treatment of acute exacerbations of COPD in mild to moderate patients in primary care. PMID:19436696

  3. Management of acute exacerbation of COPD in rural Alberta emergency departments.

    PubMed

    McKenna, Paul; MacLeod, Kelsey; Le, Christopher; Tok, Kevin; Ursenbach, Jessie; Sutherland, Lindsey; Gaudet, Lindsay; Couperthwaite, Stephanie; Villa-Roel, Cristina; Rowe, Brian H

    2015-01-01

    Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a common presentation to emergency departments (EDs); however, limited information exists about the management of this condition in nonurban locations. We sought to examine the diagnostic and treatment approaches for acute exacerbation of COPD in 3 rural EDs, and to determine levels of adherence to recommendations from the Canadian Thoracic Society (CTS) clinical practice guideline. We conducted retrospective chart reviews to explore the management of patients who presented to 3 rural EDs for acute exacerbation of COPD in 2011. Data are reported as medians and interquartile ranges (IQRs) and proportions. Over a 1-year period, 192 patients presented a total of 266 times with acute exacerbation of COPD. The median age was 68 (IQR 58-77) years, and 54.9% of the patients were women. Diagnostic testing included chest radiography in 65.0%, blood tests in 45.1%, electrocardiography in 33.5%, and arterial blood gas tests in 6.4%; only a few patients received pulmonary function testing. In the ED, 58.7% of patients were given a short-acting β-agonist, 48.9% a short-acting anticholinergic, 27.4% corticosteroids and 19.9% antibiotics. Overall, short-acting β-agonists (63.5%), anticholinergic agents (53.4%), corticosteroids (54.5%) and antibiotics (71.1%) were prescribed more commonly to discharged patients (p < 0.05 for all). We found a low to moderate level of adherence to the CTS clinical practice guideline for the management of acute exacerbation of COPD in these rural EDs. Moreover, we identified gaps in both diagnostic and therapeutic care.

  4. Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure

    DOE PAGES

    Tyler, Christina R.; Noor, Shahani; Young, Tamara; ...

    2018-01-27

    The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O 3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C 57BL/6 male mice, aged 8-10 weeks or 12–18 months were exposed to either filtered air (FA) or 1.0 ppm O 3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression wasmore » assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 hours post-O 3 exposure. Flow cytometry analysis of brains revealed increased microglia “activation” and presentation of CD11b, F4/80 and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O 3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O 3 insult. The aged cerebellum was particularly vulnerable to acute O 3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C + inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O 3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Furthermore, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O 3 exposure, leading to greater neuroinflammatory outcomes.« less

  5. Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure

    SciT

    Tyler, Christina R.; Noor, Shahani; Young, Tamara

    The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O 3) exposure in aged mice, where increased blood brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C 57BL/6 male mice, aged 8-10 weeks or 12–18 months were exposed to either filtered air (FA) or 1.0 ppm O 3 for 4 hours; animals received a single IP injection of sodium fluorescein (FSCN) 20 hours post-exposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression wasmore » assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 hours post-O 3 exposure. Flow cytometry analysis of brains revealed increased microglia “activation” and presentation of CD11b, F4/80 and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O 3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O 3 insult. The aged cerebellum was particularly vulnerable to acute O 3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C + inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O 3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Furthermore, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O 3 exposure, leading to greater neuroinflammatory outcomes.« less

  6. Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure.

    PubMed

    Tyler, Christina R; Noor, Shahani; Young, Tamara L; Rivero, Valeria; Sanchez, Bethany; Lucas, Selita; Caldwell, Kevin K; Milligan, Erin D; Campen, Matthew J

    2018-05-01

    The role of environmental stressors, particularly exposure to air pollution, in the development of neurodegenerative disease remains underappreciated. We examined the neurological effects of acute ozone (O3) exposure in aged mice, where increased blood-brain barrier (BBB) permeability may confer vulnerability to neuroinflammatory outcomes. C57BL/6 male mice, aged 8-10 weeks or 12-18 months were exposed to either filtered air or 1.0 ppm O3 for 4 h; animals received a single IP injection of sodium fluorescein (FSCN) 20 h postexposure. One-hour post-FSCN injection, animals were transcardially perfused for immunohistochemical analysis of BBB permeability. β-amyloid protein expression was assessed via ELISA. Flow cytometric characterization of infiltrating immune cells, including neutrophils, macrophages, and microglia populations was performed 20 h post-O3 exposure. Flow cytometry analysis of brains revealed increased microglia "activation" and presentation of CD11b, F4/80, and MHCII in aged animals relative to younger ones; these age-induced differences were potentiated by acute O3 exposure. Cortical and limbic regions in aged brains had increased reactive microgliosis and β-amyloid protein expression after O3 insult. The aged cerebellum was particularly vulnerable to acute O3 exposure with increased populations of infiltrating neutrophils, peripheral macrophages/monocytes, and Ly6C+ inflammatory monocytes after insult, which were not significantly increased in the young cerebellum. O3 exposure increased the penetration of FSCN beyond the BBB, the infiltration of peripheral immune cells, and reactive gliosis of microglia. Thus, the aged BBB is vulnerable to insult and becomes highly penetrable in response to O3 exposure, leading to greater neuroinflammatory outcomes.

  7. Toll-like receptor-2 exacerbates murine acute viral hepatitis.

    PubMed

    Bleau, Christian; Burnette, Mélanie; Filliol, Aveline; Piquet-Pellorce, Claire; Samson, Michel; Lamontagne, Lucie

    2016-10-01

    Viral replication in the liver is generally detected by cellular endosomal Toll-like receptors (TLRs) and cytosolic helicase sensors that trigger antiviral inflammatory responses. Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined in vivo the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV-A59 serotype. To address this, C57BL/6 (wild-type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV-A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV-A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3-induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon-β, interleukin-6, tumour necrosis factor-α, CXCL1, CCL2, CXCL10 and alarmin (interleukin-33) than in MHV-A59-infected WT mice and in MHV3-infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3-infected WT mice whereas they were sustained in MHV-A59-infected WT mice and MHV3-infected TLR2 KO. MHV3 in vitro infection of macrophagic cells induced rapid and higher viral replication and/or interleukin-6 induction in comparison to MHV-A59, and depended on viral activation of TLR2 and p38 mitogen-activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3-induced acute fulminant hepatitis. © 2016 John Wiley & Sons Ltd.

  8. Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection.

    PubMed

    Cosentini, Roberto; Tarsia, Paolo; Canetta, Ciro; Graziadei, Giovanna; Brambilla, Anna Maria; Aliberti, Stefano; Pappalettera, Maria; Tantardini, Francesca; Blasi, Francesco

    2008-05-30

    Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4-8 weeks. Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 +/- 104 L/min vs 276 +/- 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 +/- 24.54 vs FEV1% 92.91 +/- 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38-13.32). Our data suggest an association between acute atypical infection and a more severe AEBA.

  9. 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.

  10. Prevalence of Mycoplasma pneumoniae infection in pediatric patients with acute asthma exacerbation.

    PubMed

    Kassisse, Elías; García, Hecmary; Prada, Linair; Salazar, Ixora; Kassisse, Jorge

    2018-06-01

    Mycoplasma pneumoniae may be involved in refractory asthma exacerbation. To determine the prevalence of Mycoplasma pneumoniae infection in patients with acute asthma exacerbation. Material and method. A prospective, crosssectional, observational, case-control study was carried out in patients older than 2 years old and younger than 12. Immunoglobulin M (IgM) antibodies were serologically determined for M. pneumoniae, using the NovaLisa® NovaTec kit for enzyme-linked immunosorbent assay (ELISA). Test results ≥ 11 NTU (NovaTec units) were regarded as positive. The statistical analysis was performed by means of the analysis of variance (ANOVA) and the χ² test, with a significance level of p < 0.05. One hundred and eighty children were studied, of which 130 had asthma and 50 comprised the control group. Specific IgM was positive for 60 patients, that is 46.15% of the asthmatic children (p < 0.001). The severity of the exacerbation was directly related to IgM levels (p < 0.001). Hospitalization rate was 75%, and it was significantly associated to specific IgM levels (p < 0.001). Our data suggest that children with acute asthma show a high prevalence (46%) of Mycoplasma pneumoniae infection and that there is a close relation between severe acute asthma exacerbation and the presence of Mycoplasma pneumoniae infection. These findings might result in therapeutic implications centered in the use of specific antibiotics to fight this atypical organism. Key words: acute asthma, exacerbation, Mycoplasma pneumoniae. Sociedad Argentina de Pediatría.

  11. Impact of a COPD discharge care bundle on readmissions following admission with acute exacerbation: interrupted time series analysis.

    PubMed

    Laverty, Anthony A; Elkin, Sarah L; Watt, Hilary C; Millett, Christopher; Restrick, Louise J; Williams, Sian; Bell, Derek; Hopkinson, Nicholas S

    2015-01-01

    We evaluated the impact of a COPD discharge care bundle on readmission rates following hospitalisation with an acute exacerbation. Interrupted time series analysis, comparing readmission rates for COPD exacerbations at nine trusts that introduced the bundle, to two comparison groups; (1) other NHS trusts in London and (2) all other NHS trusts in England. Care bundles were implemented at different times for different NHS trusts, ranging from October 2009 to April 2011. Nine NHS acute trusts in the London, England. Patients aged 45 years and older admitted to an NHS acute hospital in England for acute exacerbation of COPD. Data come from Hospital Episode Statistics, April 2002 to March 2012. Annual trend readmission rates (and in total bed days) within 7, 28 and 90 days, before and after implementation. In hospitals introducing the bundle readmission rates were rising before implementation and falling afterwards (e.g. readmissions within 28 days +2.13% per annum (pa) pre and -5.32% pa post (p for difference in trends = 0.012)). Following implementation, readmission rates within 7 and 28 day were falling faster than among other trusts in London, although this was not statistically significant (e.g. readmissions within 28 days -4.6% pa vs. -3.2% pa, p = 0.44). Comparisons with a national control group were similar. The COPD discharge care bundle appeared to be associated with a reduction in readmission rate among hospitals using it. The significance of this is unclear because of changes to background trends in London and nationally.

  12. Noninvasive ventilation for acute exacerbations of asthma: A systematic review of the literature.

    PubMed

    Green, Elyce; Jain, Paras; Bernoth, Maree

    2017-11-01

    Asthma is a chronic disease characterised by reversible airway obstruction caused by bronchospasm, mucous and oedema. People with asthma commonly experience acute exacerbations of their disease requiring hospitalisation and subsequent utilisation of economic and healthcare resources. Noninvasive ventilation has been suggested as a treatment for acute exacerbations of asthma due to its ability to provide airway stenting, optimal oxygen delivery and decreased work of breathing. This paper is a systematic review of the available published research focused on the use of noninvasive ventilation for the treatment of acute exacerbations of asthma to determine if this treatment provides better outcomes for patients compared to standard medical therapy. Database searches were conducted using EBSCOhost, MEDLINE and PubMed. Search terms used were combinations of 'noninvasive ventilation', 'BiPAP', 'CPAP', 'wheez*' and 'asthma'. Articles were included if they were research papers focused on adult patients with asthma and a treatment of noninvasive ventilation, and were published in full text in English. Included articles were reviewed using the National Health and Medical Research Council (Australia) evidence hierarchy and quality appraisal tools. There were 492 articles identified from the database searches. After application of inclusion/exclusion criteria 13 articles were included in the systematic review. Studies varied significantly in design, endpoints and outcomes. There was a trend in better outcomes for patients with acute asthma who were treated with noninvasive ventilation compared to standard medical therapy, however, the variability of the studies meant that no conclusive recommendations could be made. More research is required before noninvasive ventilation can be conclusively recommended for the treatment of acute exacerbations of asthma. Copyright © 2017 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

  13. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline.

    PubMed

    Criner, Gerard J; Bourbeau, Jean; Diekemper, Rebecca L; Ouellette, Daniel R; Goodridge, Donna; Hernandez, Paul; Curren, Kristen; Balter, Meyer S; Bhutani, Mohit; Camp, Pat G; Celli, Bartolome R; Dechman, Gail; Dransfield, Mark T; Fiel, Stanley B; Foreman, Marilyn G; Hanania, Nicola A; Ireland, Belinda K; Marchetti, Nathaniel; Marciniuk, Darcy D; Mularski, Richard A; Ornelas, Joseph; Road, Jeremy D; Stickland, Michael K

    2015-04-01

    COPD is a major cause of morbidity and mortality in the United States as well as throughout the rest of the world. An exacerbation of COPD (periodic escalations of symptoms of cough, dyspnea, and sputum production) is a major contributor to worsening lung function, impairment in quality of life, need for urgent care or hospitalization, and cost of care in COPD. Research conducted over the past decade has contributed much to our current understanding of the pathogenesis and treatment of COPD. Additionally, an evolving literature has accumulated about the prevention of acute exacerbations. In recognition of the importance of preventing exacerbations in patients with COPD, the American College of Chest Physicians (CHEST) and Canadian Thoracic Society (CTS) joint evidence-based guideline (AECOPD Guideline) was developed to provide a practical, clinically useful document to describe the current state of knowledge regarding the prevention of acute exacerbations according to major categories of prevention therapies. Three key clinical questions developed using the PICO (population, intervention, comparator, and outcome) format addressed the prevention of acute exacerbations of COPD: nonpharmacologic therapies, inhaled therapies, and oral therapies. We used recognized document evaluation tools to assess and choose the most appropriate studies and to extract meaningful data and grade the level of evidence to support the recommendations in each PICO question in a balanced and unbiased fashion. The AECOPD Guideline is unique not only for its topic, the prevention of acute exacerbations of COPD, but also for the first-in-kind partnership between two of the largest thoracic societies in North America. The CHEST Guidelines Oversight Committee in partnership with the CTS COPD Clinical Assembly launched this project with the objective that a systematic review and critical evaluation of the published literature by clinical experts and researchers in the field of COPD would lead to

  14. Acute Exacerbation of Sleep Apnea by Hyperoxia Impairs Cognitive Flexibility in Brown-Norway Rats

    PubMed Central

    Topchiy, Irina; Amodeo, Dionisio A.; Ragozzino, Michael E.; Waxman, Jonathan; Radulovacki, Miodrag; Carley, David W.

    2014-01-01

    Study Objectives: To determine whether learning deficits occur during acute exacerbation of spontaneous sleep related breathing disorder (SRBD) in rats with high (Brown Norway; BN) and low (Zucker Lean; ZL) apnea propensity. Design: Spatial acquisition (3 days) and reversal learning (3 days) in the Morris water maze (MWM) with polysomnography (12:00–08:00): (1) with acute SRBD exacerbation (by 20-h hyperoxia immediately preceding reversal learning) or (2) without SRBD exacerbation (room air throughout). Setting: Randomized, placebo-controlled, repeated-measures design. Participants: 14 BN rats; 16 ZL rats. Interventions: 20-h hyperoxia. Measurements and Results: Apneas were detected as cessation of respiration ≥ 2 sec. Swim latency in MWM, apnea indices (AI; apneas/hour of sleep) and percentages of recording time for nonrapid eye movement (NREM), rapid eye movement (REM), and total sleep were assessed. Baseline AI in BN rats was more than double that of ZL rats (22.46 ± 2.27 versus 10.7 ± 0.9, P = 0.005). Hyperoxia increased AI in both BN (34.3 ± 7.4 versus 22.46 ± 2.27) and ZL rats (15.4 ± 2.7 versus 10.7 ± 0.9) without changes in sleep stage percentages. Control (room air) BN and ZL rats exhibited equivalent acquisition and reversal learning. Acute exacerbation of AI by hyperoxia produced a reversal learning performance deficit in BN but not ZL rats. In addition, the percentage of REM sleep and REM apnea index in BN rats during hyperoxia negatively correlated with reversal learning performance. Conclusions: Acute exacerbation of sleep related breathing disorder by hyperoxia impairs reversal learning in a rat strain with high apnea propensity, but not a strain with a low apnea propensity. This suggests a non-linear threshold effect may contribute to the relationships between sleep apnea and cognitive dysfunctions, but strain-specific differences also may be important. Citation: Topchiy I, Amodeo DA, Ragozzino ME, Waxman J, Radulovacki M, Carley DW. Acute

  15. 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.

  16. Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma.

    PubMed

    Kato, Masahiko; Suzuki, Kazuo; Yamada, Yoshiyuki; Maruyama, Kenichi; Hayashi, Yasuhide; Mochizuki, Hiroyuki

    2015-09-01

    Little information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma. We investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls. Viruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged <3 years and children aged ≥3 years. Serum concentrations of ECP, IL-5, and IP-10 were significantly elevated in virus-induced acute asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged <3 years. Among the 27 cytokines/chemokines, serum IP-10 was significantly higher in virus-induced asthma in patients <3 years than in those ≥3 years. Serum ECP and IL-5 production correlated significantly with age, whereas serum IP-10 showed an inverse correlation with age. Age-related differences in cytokine profiles and eosinophil activation may be related to virus-induced acute exacerbations of childhood asthma. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  17. Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD

    PubMed Central

    Echevarria, C; Steer, J; Heslop-Marshall, K; Stenton, SC; Hickey, PM; Hughes, R; Wijesinghe, M; Harrison, RN; Steen, N; Simpson, AJ; Gibson, GJ; Bourke, SC

    2016-01-01

    Background Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. Methods The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identified by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. Results In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. Conclusions DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0–1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3–6) for escalation planning or appropriate early palliation. Trial registration number UKCRN ID 14214. PMID:26769015

  18. The PEARL score predicts 90-day readmission or death after hospitalisation for acute exacerbation of COPD

    PubMed Central

    Echevarria, C; Steer, J; Heslop-Marshall, K; Stenton, S C; Hughes, R; Wijesinghe, M; Harrison, R N; Steen, N; Simpson, A J; Gibson, G J; Bourke, S C

    2017-01-01

    Background One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. Methods In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. Results Of 2417 patients, 936 were readmitted or died within 90 days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. Conclusions The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. Trial registration number UKCRN ID 14214. PMID:28235886

  19. High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy.

    PubMed

    Depositario-Cabacar, Dewi T; Peters, Jurriaan M; Pong, Amanda W; Roth, Julie; Rotenberg, Alexander; Riviello, James J; Takeoka, Masanori

    2010-07-01

    We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.

  20. Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation.

    PubMed

    Quan-Jun, Yang; Jian-Ping, Zhang; Jian-Hua, Zhang; Yong-Long, Han; Bo, Xin; Jing-Xian, Zhang; Bona, Dai; Yuan, Zhang; Cheng, Guo

    2017-03-01

    Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic

  1. Thyroid Echography-induced Thyroid Storm and Exacerbation of Acute Heart Failure.

    PubMed

    Nakabayashi, Keisuke; Nakazawa, Naomi; Suzuki, Toshiaki; Asano, Ryotaro; Saito, Hideki; Nomura, Hidekimi; Isomura, Daichi; Okada, Hisayuki; Sugiura, Ryo; Oka, Toshiaki

    2016-01-01

    Hyperthyroidism and thyroid storm affect cardiac circulation in some conditions. Several factors including trauma can induce thyroid storms. We herein describe the case of a 57-year-old woman who experienced a thyroid storm and exacerbation of acute heart failure on thyroid echography. She initially demonstrated a good clinical course after medical rate control for atrial fibrillation; however, thyroid echography for evaluating hyperthyroidism led to a thyroid storm and she collapsed. A multidisciplinary approach stabilized her thyroid hormone levels and hemodynamics. Thus, the medical staff should be prepared for a deterioration in the patient's condition during thyroid echography in heart failure patients with hyperthyroidism.

  2. Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    McCurdy, BR

    2012-01-01

    Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

  3. Can mean platelet volume and neutrophil-to-lymphocyte ratio be biomarkers of acute exacerbation of bronchiectasis in children?

    PubMed Central

    Erdem, Semiha Bahceci; Karaman, Sait; Yazici, Selcuk; Can, Demet

    2017-01-01

    Introduction Bronchiectasis (BE) is a parenchymal lung disease evolving as a result of recurrent lung infections and chronic inflammation. Although it has been shown in adult studies that mean platelet volume (MPV) and neutrophil-to-lymphocyte ratio (NLR) can be used as biomarkers of airway inflammation, knowledge is limited in the paediatric age group. The aim of our study is to investigate the potential of MPV and NLR as biomarkers that may indicate acute exacerbations of non-cystic fibrosis BE in children. Material and methods Children with non-cystic fibrosis BE (n = 50), who were followed in the division of Paediatric Pulmonology of our hospital between June 2010 and July 2015, were involved in the present retrospective cross-sectional study. Haemogram values during acute exacerbations and non-exacerbation periods, and a control group were compared. Results In children with bronchiectasis, the average leukocyte count (p < 0.001), platelet count (p = 0.018), absolute neutrophil count (p < 0.001), and NLR (p < 0.001) were higher, as expected, when compared with the control group. NLR values, in the period of acute exacerbation were significantly higher than the values of both the non-exacerbation periods (p = 0.02) and the control group (p < 0.001). In contrast, MPV values in the period of acute exacerbation did not exhibit a significant difference from those of non-exacerbation periods (p = 0.530) and the control group (p = 0.103). Conclusions It was concluded that leukocyte count, platelet count, absolute neutrophil count, and NLR can be used to show chronic inflammation in BE, but only NLR and absolute neutrophil count can be used as biomarkers to show acute exacerbations. PMID:29472813

  4. Burden of Obesity on Pediatric Inpatients with Acute Asthma Exacerbation in the United States.

    PubMed

    Okubo, Yusuke; Nochioka, Kotaro; Hataya, Hiroshi; Sakakibara, Hiroshi; Terakawa, Toshiro; Testa, Marcia

    Obesity and asthma are common health problems in the United States. The objective of this study was to evaluate the clinical and economic burdens of obesity on hospitalized children with acute asthma exacerbation in 2012. Hospital discharge records of patients aged 2 to 18 years with a diagnosis of asthma were obtained from the 2012 Kids' Inpatient Database, wherein the data were compiled by the Agency for Healthcare Research and Quality. The discharge records were weighted to estimate the number of hospitalizations because of asthma exacerbations in the United States. To classify whether the patient was obese or not, we used the International Classification of Diseases, Ninth Revision, Clinical Modification code 278.0x. We compared the odds of using noninvasive or invasive mechanical ventilation, mean total charges for inpatient service, and length of hospital stay between obese and nonobese patients. A total of 74,338 patient discharges were extracted. Of these, 3,494 discharges were excluded because of chronic medical conditions. Using discharge weight variables, we estimated a total of 100,157 hospitalizations with asthma exacerbations among children aged between 2 and 18 years in 2012. Obesity was significantly associated with higher odds of using mechanical ventilation (odds ratio 1.59, 95% CI 1.28-1.99), higher mean total hospital charges (adjusted difference: $1588, 95% CI $802-$2529), and longer mean length of hospital stay (0.24 days, 95% CI 0.17-0.32 days) compared with nonobesity. These findings suggest that obesity is a significant risk factor of severe asthma exacerbation that requires mechanical ventilation, and obesity is an economically complicating factor. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Impact of acute exacerbations on platelet reactivity in chronic obstructive pulmonary disease patients.

    PubMed

    Muñoz-Esquerre, Mariana; Ferreiro, José Luis; Huertas, Daniel; Marcano, Ana Lucrecia; López-Sánchez, Marta; Roura, Gerard; Gómez-Hospital, Joan Antoni; Dorca, Jordi; Cequier, Angel; Santos, Salud

    2018-01-01

    A higher risk of atherothrombotic cardiovascular events, which are platelet-driven processes, has been described during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the relevance of platelet reactivity during AECOPD and whether this is affected by antiplatelet agents are not fully elucidated to date. This study aimed to evaluate whether platelet reactivity is augmented during an exacerbation in COPD patients with and without antiplatelet therapy and its association with systemic inflammatory parameters. Prospective, observational, ex vivo investigation was conducted in consecutive patients suffering an exacerbation of COPD. Platelet reactivity was assessed during AECOPD and at stable state. Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay expressed as P2Y 12 reactivity index (PRI), 2) multiple electrode aggregometry and 3) optical aggregometry. Systemic inflammatory parameters such as leukocyte count, interleukin-6 and fibrinogen were also assessed. Higher platelet reactivity was observed during AECOPD compared to stability measured by vasodilator-stimulated phosphoprotein (PRI: 75.2%±1.9% vs 68.8%±2.4%, p =0.001). This augmented platelet aggregability was also observed in the subset of patients on antiplatelet therapy (PRI: 72.8%±3.1% vs 61.7%±7.5%, p =0.071). Consistent findings were observed with all other platelet function tests. Patients with greater enhancement of inflammatory markers during AECOPD were more likely to present a higher increase in platelet reactivity. Platelet reactivity is increased during AECOPD, which may contribute to the augmented cardiovascular risk of these patients. Additionally, the increase in platelet reactivity might be associated with an increment in inflammatory markers during exacerbations.

  6. Acute exacerbations of chronic bronchitis: a pharmacoeconomic review of antibacterial use.

    PubMed

    Morris, Stephen; Anderson, Pippa; Irwin, Debra E

    2002-01-01

    Chronic bronchitis is a common problem affecting a large proportion of the adult population. People with chronic bronchitis are subject to recurrent attacks of bronchial inflammation called acute exacerbations of chronic bronchitis (AECBs). In patients with AECBs, symptoms may worsen due to a bacterial infection; the exacerbation is then known as an acute bacterial exacerbation of chronic bronchitis (ABECB). ABECBs are thought to be controllable through the use of antibacterial agents. In this paper we review current evidence on the cost of chronic bronchitis and AECBs, the cost effectiveness of antibacterials in the management of ABECB, and the factors that may affect the cost-effectiveness of antibacterials in the management of ABECB. We find that the number of economic evaluations conducted in this area is small. Of the few economic evaluations that have been conducted there has been only one prospective economic evaluation based on a clinical trial. The remainder are simple decision analysis-based modelling studies or retrospective database studies. Our principle findings are as follows: a key factor affecting the cost-effective use of antibacterials in the management of ABECB is the definitive diagnosis of the condition. Unfortunately, diagnosing a bacterial cause of an AECB is difficult, which presents problems in ensuring that antibacterials are not prescribed unnecessarily;current evidence suggests but does not prove that use of more effective but more costly first-line antibacterials may be relatively cost effective and may minimise overall expenditure by reducing the high costs associated with treatment failure;chronic bronchitis and AECB have a significant and negative physical and psychological effect on health-related quality of life. In conclusion, the small number of economic evaluations conducted in this area, coupled with the nature of the design of these studies, precludes a definitive statement recommending which specific antibacterial should be

  7. Improving childcare staff management of acute asthma exacerbation - An Australian pilot study.

    PubMed

    Soo, Yien Yien; Luckie, Kate Helen; Saini, Bandana; Kritikos, Vicky; Brannan, John D; Moles, Rebekah Jane

    2017-09-01

    This study aimed to evaluate the effectiveness of an asthma first-aid training tool for childcare staff in Australia. The effects of training on both asthma knowledge and skills were assessed. A pre/post-study design was utilised to assess changes in asthma knowledge and asthma first-aid skills in childcare staff before and after an educational intervention. Asthma first-aid skills were assessed from the participant's response to two scenarios in which a child was having a severe exacerbation of asthma. Asthma knowledge and asthma skills scores were collected at base-line and 3 weeks post the education session, which involved feedback on each individual's skills and a brief lecture on asthma delivered via PowerPoint presentation. There was a significant improvement after intervention in asthma knowledge (Z = -3.638, p < 0.001) and asthma first-aid skills for both scenario 1 (Z = -6.012, p < 0.001) and scenario 2 (Z = -6.018, p < 0.001). In scenario 1 and 2, first-aid skills improved by 65% (p < 0.001) and 57% (p < 0.001), respectively. Asthma knowledge was high at baseline (79%) and increased by 7% (p < 0.001) after the educational intervention. These asthma knowledge results were not significant when adjusted for prior knowledge. Results suggest that knowledge assessment alone may not predict the practical skills needed for asthma first-aid. Skills assessment is a useful adjunct to knowledge assessment when gauging the ability of childcare staff to manage acute asthma exacerbation. Skills assessment could be considered for incorporation into future educational interventions to improve management of acute asthma exacerbation.

  8. Daily spirometry in an acute exacerbation of adult cystic fibrosis patients.

    PubMed

    Stephen, Michael J; Long, Alex; Bonsall, Chad; Hoag, Jeffrey B; Shah, Smita; Bisberg, Dorothy; Holsclaw, Douglas; Varlotta, Laurie; Fiel, Stan; Du, Doantrang; Zanni, Robert; Hadjiliadis, Denis

    2017-01-01

    To help answer the question of length of intravenous antibiotics during an acute exacerbation of cystic fibrosis (CF), we had subjects to follow daily home spirometry while on intravenous antibiotics. CF patients, 18 and older, with an acute exacerbation requiring intravenous antibiotics had a daily FEV1. The average time to a 10% increase over their initial sick FEV1 was calculated, as well as the time to a new baseline. A total of 25 subjects completed the study. Ten of the 25 subjects did not have a sustainable 10% increase in FEV1. Of the 15 subjects with a sustainable 10% increase in FEV1, it took 5.2 days (±4.5) after day 1, while a new baseline was achieved on average at 6.6 days (±4.8) after day 1. Given the wide range of time to a 10% improvement and new baseline, it is recommended there should be flexibility in length of intravenous antibiotics in CF, not by a preset number.

  9. A Serological Biomarker of Versican Degradation is Associated with Mortality Following Acute Exacerbations of Idiopathic Interstitial Pneumonia.

    PubMed

    Sand, Jannie M B; Tanino, Yoshinori; Karsdal, Morten A; Nikaido, Takefumi; Misa, Kenichi; Sato, Yuki; Togawa, Ryuichi; Wang, Xintao; Leeming, Diana J; Munakata, Mitsuru

    2018-05-04

    Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exacerbations and investigated this by serological neo-epitope biomarkers. Patients who were sequentially admitted to the hospital with acute exacerbations of IIP were retrospectively analyzed for ECM remodeling at time of exacerbation (AE-IIP) and at clinical stability (S-IIP). Biomarkers released by matrix metalloproteinase-mediated degradation of collagen type I (C1M), III (C3M), IV (C4M), and VI (C6M), elastin (ELM7), versican (VCANM), biglycan (BGM), and C-reactive protein (CRPM) were assessed in serum by competitive ELISAs utilizing neo-epitope specific monoclonal antibodies. Sixty-eight patients at AE-IIP and 29 at S-IIP were included in this retrospective analysis. Of these, 28 and 11 patients, respectively, had idiopathic pulmonary fibrosis. At AE-IIP, serum levels of C4M (p = 0.002) and C6M (p = 0.024) were increased as compared with S-IIP, while ELM7 (p = 0.024) and VCANM (p < 0.0001) were decreased. Lower VCANM levels at AE-IIP were associated with increased risk of mortality (HR 0.64 [95% CI 0.43-0.94], p = 0.022). The ECM remodeling profile was significantly altered during acute exacerbations of IIP, and a biomarker of versican degradation was related to mortality outcome. These results indicate that biomarkers of ECM remodeling may be useful in the non-invasive evaluation of acute exacerbations of IIP. Especially versican degradation, as measured serologically by VCANM, may have prognostic potential and help guide treatment for acute exacerbations.

  10. Can the six-minute walk distance predict the occurrence of acute exacerbations of COPD in patients in Brazil?

    PubMed Central

    Morakami, Fernanda Kazmierski; Morita, Andrea Akemi; Bisca, Gianna Waldrich; Felcar, Josiane Marques; Ribeiro, Marcos; Furlanetto, Karina Couto; Hernandes, Nidia Aparecida; Pitta, Fabio

    2017-01-01

    ABSTRACT Objective: To evaluate whether a six-minute walk distance (6MWD) of < 80% of the predicted value can predict the occurrence of acute exacerbations of COPD in patients in Brazil over a 2-year period. Methods: This was a retrospective cross-sectional study involving 50 COPD patients in Brazil. At enrollment, anthropometric data were collected and patients were assessed for pulmonary function (by spirometry) and functional exercise capacity (by the 6MWD). The patients were subsequently divided into two groups: 6MWD ≤ 80% of predicted and 6MWD > 80% of predicted. The occurrence of acute exacerbations of COPD over 2 years was identified by analyzing medical records and contacting patients by telephone. Results: In the sample as a whole, there was moderate-to-severe airflow obstruction (mean FEV1 = 41 ± 12% of predicted) and the mean 6MWD was 469 ± 60 m (86 ± 10% of predicted). Over the 2-year follow-up period, 25 patients (50%) experienced acute exacerbations of COPD. The Kaplan-Meier method showed that the patients in whom the 6MWD was ≤ 80% of predicted were more likely to have exacerbations than were those in whom the 6MWD was > 80% of predicted (p = 0.01), whereas the Cox regression model showed that the former were 2.6 times as likely to have an exacerbation over a 2-year period as were the latter (p = 0.02). Conclusions: In Brazil, the 6MWD can predict acute exacerbations of COPD over a 2-year period. The risk of experiencing an acute exacerbation of COPD within 2 years is more than twice as high in patients in whom the 6MWD is ≤ 80% of predicted. PMID:29365003

  11. Clinical efficacy of farcosolvin syrup (ambroxol–theophylline–guaiphenesin mixture) in the treatment of acute exacerbation of chronic bronchitis

    PubMed Central

    Yakoot, Mostafa; Salem, Amel; Omar, Abdel-Mohsen

    2010-01-01

    Background: Acute exacerbations of chronic bronchitis (AECB) are defined as recurrent attacks of worsening bronchial inflammation that are marked by an increase in the volume of daily sputum produced, a change in color of the expectorated sputum, and worsening dyspnea. Farcosolvin® (Pharco Pharmaceuticals, Alexandria, Egypt) is a mixture of ambroxol (15 mg); theophylline (50 mg); and guaiphenesin (30 mg), per 5 mL syrup. Objective: To test the clinical efficacy of Farcosolvin in the treatment of AECB in a randomized, single-blinded, controlled study design. Patients and methods: One hundred patients with AECB were randomized to either Farcosolvin or guaiphenesin treatment groups, in addition to the standard medical treatment for their cases. Baseline clinical symptomatolgy of breathlessness, cough, and sputum severity scoring were compared before and after 3 and 7 days of treatment in both groups and the differences compared between groups. Changes in perceived improvement were also compared between groups using the Clinical Global Impression of Improvement or Change Scale (CGIC). Results: There were statistically significant improvements in breathlessness and cough scores in both groups (pretreatment versus posttreatment at day 3 and at day 7; P < 0.05). There were highly statistically significant differences between groups in improvement in breathlessness and cough scores, after 3 and 7 days treatment, in favor of the Farcosolvin treatment group (P < 0.001). Out of 50 patients, 48 (96%) in the Farcosolvin-treated group rated their improvement on the CGIC scale as “much” and “very much” improved, while only 41 patients (82%) reported such a degree of improvement in the control group. The difference was statistically significant (P < 0.05). Conclusion: We concluded from our study that Farcosolvin syrup might be safe and effective in improving symptoms in cases of acute exacerbation of chronic bronchitis. PMID:20714379

  12. Influence of psychological factors on acute exacerbation of tension-type headache: Investigation by ecological momentary assessment.

    PubMed

    Kikuchi, Hiroe; Yoshiuchi, Kazuhiro; Ando, Tetsuya; Yamamoto, Yoshiharu

    2015-09-01

    In this study, we investigated whether psychological factors were associated with subsequent acute exacerbation of tension-type headache (TTH) in a prospective and ecologically valid manner with computerized ecological momentary assessment. Eighteen women and five men with TTH wore watch-type computers that acted as an electronic diary for 1week. The subjects recorded momentary headache intensity, psychological stress, anxiety, and depressive mood with a visual analog scale of 0-100 approximately every 6h as well as when waking up, when going to bed, and at acute headache exacerbations. Multilevel logistic regression analysis with acute headache exacerbation occurrence as the outcome was conducted. Person-mean centering was applied to psychological factors to disaggregate between- and within-individual association. Momentary psychological stress was associated with subsequent increase in headache exacerbation within 3h [Odds Ratio (95% CI)=1.32 (1.07, 1.64) for 10-point increments] while the individual mean of psychological stress was not. These results support the possibility that psychological stress could trigger acute exacerbations of TTH. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Clinical significance of the infection-free interval in the management of acute bacterial exacerbations of chronic bronchitis.

    PubMed

    Chodosh, Sanford

    2005-06-01

    Rational and appropriate antibiotic use for patients with acute exacerbation of chronic bronchitis (AECB) is a major concern, as approximately half of these patients do not have a bacterial infection. Typically, the result of antimicrobial therapy for patients with acute bacterial exacerbation of chronic bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute symptoms. However, the length of time before the next bacterial exacerbation can be another important variable, as the frequency of exacerbations will affect the overall health of the patient and the rate of lung deterioration over time. Clinical trials comparing antimicrobial therapies commonly measure resolution of symptoms in AECB patients as the primary end point, regardless of whether the exacerbation is documented as bacterial in nature. Ideally, the scientific approach to assessing the efficacy of antibiotic therapy for ABECB should include a measurement of acute bacterial eradication rates in patients with documented bronchial bacterial infection followed by measurement of the infection-free interval (IFI), ie, the time to the next ABECB. The use of these variables can provide a standard for comparing various antimicrobial therapies. As we learn more about how antibiotics can affect the IFI, treatment decisions should be adapted to ensure optimal management of ABECB for the long-term.

  14. Serum Procalcitonin for Differential Diagnosis of Acute Exacerbation and Bacterial Pneumonia in Patients With Interstitial Lung Disease.

    PubMed

    Sim, Jae Kyeom; Oh, Jee Youn; Lee, Eun Joo; Hur, Gyu Young; Lee, Seung Heon; Lee, Sung Yong; Lee, Sang Yeub; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Min, Kyung Hoon

    2016-05-01

    Acute exacerbation and bacterial pneumonia are major life-threatening conditions in patients with interstitial lung disease (ILD). The rapid recognition of these 2 different conditions is important for their proper treatment. An elevated procalcitonin (PCT) level is commonly detected in patients with bacterial infections. This study assessed the usefulness of the serum PCT level as a biomarker for the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD. In this prospective observational study, we enrolled patients with ILD who had experienced recently progressive dyspnea and exhibited new infiltrations on chest radiographs. We classified these patients into an acute exacerbation group and a bacterial pneumonia group and compared their baseline characteristics and laboratory parameters, including the PCT level. Of 21 patients with ILD, 9 patients had bacterial pneumonia. Both the groups showed similar baseline characteristics. The bacterial pneumonia group demonstrated a high PCT level. The PCT level in the acute exacerbation group was significantly lower than that in the bacterial pneumonia group (0.05 versus 0.91ng/mL, respectively; P < 0.001). Other parameters, such as the C-reactive protein level, leukocyte count and body temperature, were also lower in the acute exacerbation group. At a cutoff value of 0.1ng/mL, the sensitivity, specificity and negative predictive values of the serum PCT level were 88.9%, 100.0% and 92.3%, respectively. These findings suggest that the serum PCT level is useful in the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  15. Association Between Acute Medical Exacerbations and Consuming or Producing Web-Based Health Information: Analysis From Pew Survey Data.

    PubMed

    Gidwani, Risha; Zulman, Donna

    2015-06-23

    The Internet is an increasingly important resource for individuals who seek information from both health professionals and peers. While the demographic and health characteristics of persons who use health information technology has been well described, less is known about the relationship between these health characteristics and level of engagement with health information technology. Even less is known about whether persons who produce Web-based health information differ in health status from persons who consume such content. We explored the health characteristics of persons who engage with the Internet for the purposes of consuming or producing Web-based health information, and specifically, whether healthier versus sicker persons engage with health information technology in different ways. We analyzed data from the 2012 Pew Health survey, a landline and cell phone survey of 3104 adults in the United States. Using multiple logistic regression with sampling weights, we examined the association between sociodemographic and health characteristics and the consumption or production of Web-based health information. Sociodemographic variables included age, sex, race, and education. Health characteristics included self-reported health status, presence of chronic condition(s), and having an acute medical exacerbation. Acute medical exacerbations were defined as an emergency department visit, hospitalization, or other serious medical emergency in the last 12 months. The majority of the sample reported good or excellent health (79.7%), although 50.3% reported having at least one chronic condition. About a fifth (20.2%) of the sample experienced an acute medical exacerbation in the past year. Education was the sociodemographic characteristic most strongly associated with consuming Web-based health information. The strongest health-related predictors of consuming Web-based health information were an acute medical exacerbation (OR 2.39, P<.001) and having a chronic condition

  16. 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

  17. Optimizing nonpharmacological management following an acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Harrison, Samantha L; Goldstein, Roger; Desveaux, Laura; Tulloch, Verity; Brooks, Dina

    2014-01-01

    Though the guidelines for the optimal management of chronic obstructive pulmonary disease (COPD) following an acute exacerbation (AE) are well established, issues associated with poor adherence to nonpharmacological interventions such as self-management advice and pulmonary rehabilitation will impact on hospital readmission rates and health care costs. Systems developed for clinically stable patients with COPD may not be sufficient for those who are post-exacerbation. A redesign of the manner in which such interventions are delivered to patients following an AECOPD is necessary. Addressing two or more components of the chronic care model is effective in reducing health care utilization in patients with COPD, with self-management support contributing a key role. By refining self-management support to incorporate the identification and treatment of psychological symptoms and by providing health care professionals adequate time and training to deliver respiratory-specific advice and self-management strategies, adherence to nonpharmacological therapies following an AE may be enhanced. Furthermore, following up patients in their own homes allows for the tailoring of advice and for the delivery of consistent health care messages which may enable knowledge to be retained. By refining the delivery of nonpharmacological therapies following an AECOPD according to components of the chronic care model, adherence may be improved, resulting in better disease management and possibly reducing health care utilization.

  18. 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.

  19. Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case.

    PubMed

    Kanaya, Hiroaki; Konno, Wataru; Fukami, Satoru; Hirabayashi, Hideki; Haruna, Shin-ichi

    2014-12-01

    The fibrous variant of Hashimoto thyroiditis is uncommon, accounting for approximately 10% of all cases of Hashimoto thyroiditis. We report a case of this variant that behaved like a malignant neoplasm. The patient was a 69-year-old man who presented with a right-sided anterior neck mass that had been rapidly growing for 2 weeks. Fine-needle aspiration cytology revealed clusters of large multinucleated cells suggestive of an anaplastic carcinoma. A week after presentation, we ruled out that possibility when the mass had shrunk slightly. Instead, we diagnosed the patient with an acute exacerbation of Hashimoto thyroiditis on the basis of laboratory findings. We performed a right thyroid lobectomy, including removal of the isthmus, to clarify the pathology and alleviate pressure symptoms. The final diagnosis was the fibrous variant of Hashimoto thyroiditis, with no evidence of malignant changes. Physicians should keep in mind that on rare occasions, Hashimoto thyroiditis mimics a malignant neoplasm.

  20. 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.

  1. Effect of formoterol/budesonide combination on arterial blood gases in patients with acute exacerbation of COPD.

    PubMed

    Cazzola, M; Noschese, P; De Michele, F; D'Amato, G; Matera, M G

    2006-02-01

    Patients with severe chronic airway obstruction might suffer dangerous hypoxemia after administration of a beta-agonist despite bronchodilation. We first compared the acute effects on gas exchange of two doses of formoterol Turbuhaler (9 and 18 microg) in 10 patients with acute exacerbation of COPD. Afterwards, we compared the acute effects of formoterol Turbuhaler 9 microug with those of formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg in 10 other patients with acute exacerbation of COPD. Finally, we compared the changes in PaO(2) induced by formoterol Turbuhaler 9 microg or formoterol/budesonide combination in a single inhaler (Turbuhaler) 9/320 microg with those in FEV(1) in 10 other patients with acute exacerbation of COPD. Each agent was given on separate days, and the patients' arterial blood gases were measured at baseline and at intervals of 120 min. Small but statistically significant declines in PaO(2) were found after administration of both formoterol 9 and 18 microg. In the second group of patients, formoterol 9 microg alone again induced a significant decrease in PaO(2). However, the simultaneous administration of budesonide 320 microg significantly reduced the acute effect of formoterol on PaO(2). In a third group of 10 patients we confirmed a small but significant decrease in PaO(2) after formoterol alone and the reduction of this effect when budesonide was administered simultaneously. Moreover, we also documented that addition of budesonide amplified the fast onset of action of formoterol. These results suggest that when treating patients suffering from acute exacerbation of COPD with formoterol, it is prudent to check their arterial blood gases. In any case, combined administration of formoterol and budesonide reduces the potential for acute effects of formoterol on blood-gas tensions.

  2. [Acute exacerbation of tuberculous osteoarthritis of the knee caused by trauma: clinical management].

    PubMed

    Sauer, B; Hofmann, G O; Tiemann, A

    2009-01-01

    With this manuscript we want to show a means of the clinical management in an advanced stage of tuberculous destruction of the knee in elderly, polymorbid patients with a high risk of undergoing surgery. We describe the case of a patient who suffered from a Mycobacterium bovis infection of the left knee that led to spontaneous ankylosis in her childhood. At the age of 87 years an acute exacerbation of the tuberculous osteoarthritis occurred due to a drop attack with a fracture in the region of the previous knee ankylosis. Considering the patient's age and general poor condition, it was our paramount goal to preserve her walking ability and to avoid that she becomes bedridden. After radical surgical debridement and resection of the ankylosis, we achieved macroscopically clean bone and soft tissue conditions. We performed palliative arthrodesis with a long intramedullary nail and a cement spacer. Additionally, the patient underwent a tuberculostatic therapy for 8 months. The acute inflammatory process could be stopped and the ability of the patient to walk could be preserved. Because of the increased incidence of tuberculosis in the industrialised countries during the past 20 years, it should be considered as a differential diagnosis in cases of unclear septic arthritis. Georg Thieme Verlag KG Stuttgart, New York.

  3. Cost and clinical consequence of antibiotic non-adherence in acute exacerbations of chronic bronchitis.

    PubMed

    Sorensen, S V; Baker, T; Fleurence, R; Dixon, J; Roberts, C; Haider, S; Hughes, D

    2009-08-01

    To quantify the impact of non-adherence on the clinical effectiveness of antibiotics for acute exacerbations of chronic bronchitis (AECB) and to estimate the economic consequences for Spain, Italy and the United States. Standard systematic reviewing procedures were followed to identify randomised controlled clinical trials of antibiotic treatment for acute respiratory tract infection for which adherence was reported. A decision-analytic model was then constructed to evaluate the impact of non-adherence to antibiotic treatment on clinical effectiveness and costs per AECB episode. The model compared the total treatment costs, cure rates and incremental costs per cure for a poor compliance group (PCG) against a good compliance group (GCG). Clinical and resource use estimates were from the published literature and physician surveys. Twenty-five articles met the criteria of the systematic review, although only one reported treatment success by adherence status. The relative risk of clinical effectiveness if non-adherent was 0.75 (95%CI 0.73-0.78). Based on this single study, the model predicted that 16-29% more patients would be cured in the GCG vs. the PCG, and payers would save up to euro122, euro179 and US$141 per AECB episode in Spain, Italy and the United States, respectively. Non-adherence to antibiotics for AECB may have an impact on clinical effectiveness, which is associated with increased costs.

  4. Utility of serum Aspergillus-galactomannan antigen to evaluate the risk of severe acute exacerbation in chronic obstructive pulmonary disease

    PubMed Central

    Yoshimura, Katsuhiro; Inoue, Yusuke; Nishimoto, Koji; Karayama, Masato; Furuhashi, Kazuki; Enomoto, Noriyuki; Nakamura, Yutaro; Inui, Naoki; Yokomura, Koushi; Imokawa, Shiro; Suda, Takafumi

    2018-01-01

    Background Recent studies have shown that the microbiome, namely Aspergillus species, play a previously unrecognized role in both stable and exacerbated chronic obstructive pulmonary disease (COPD). Galactomannan is a major component of the Aspergillus cell wall that has been widely used as a diagnostic marker. Objectives To explore whether serum levels of Aspergillus-galactomannan antigen could be used to evaluate the risk of severe acute exacerbation of COPD (AE-COPD). Methods We measured the Aspergillus-galactomannan antigen levels of 191 patients with stable COPD, and examined its clinical relevance including AE-COPD. Results There were 77 (40.3%) patients who were positive for serum Aspergillus-galactomannan antigen (≥0.5). High Aspergillus-galactomannan antigen level (≥0.7) was associated with older age and presence of bronchiectasis and cysts on computed tomography images. Compared to patients with low Aspergillus-galactomannan antigen level (<0.7), patients with high Aspergillus-galactomannan antigen level had significantly higher incidence of severe AE-COPD (P = 0.0039, Gray’s test) and respiratory-related mortality (P = 0.0176, log-rank test). Multivariate analysis showed that high Aspergillus-galactomannan antigen level was independently associated with severe AE-COPD (hazard ratio, 2.162; 95% confidence interval, 1.267−3.692; P = 0.005). Conclusion Serum Aspergillus-galactomannan antigen was detected in patients with COPD, and elevated serum Aspergillus-galactomannan antigen was associated with severe AE-COPD. PMID:29870550

  5. [Correlation between arterial and venous blood gas analysis parameters in patients with acute exacerbation of chronic obstructive pulmonary disease].

    PubMed

    Novović, Miloš; Topić, Vesna

    2012-01-01

    Arterial blood gas (ABG) analyses have an important role in the assessment and monitoring of the metabolic and oxygen status of patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Arterial puncture could have a lot of adverse effects, while sampling of venous blood is simpler and is not so invasive. The aim of this study was to evaluate whether venous blood gas (VBG) values of pH, partial pressure of carbon dioxide (PCO2), partial oxygen pressure (PO2), bicarbonate (HCO3), and venous and arterial blood oxygen saturation (SO2) can reliably predict ABG levels in patients with acute exacerbation of COPD. Forty-seven patients with a prior diagnosis of COPD were included in this prospective study. The patients with acute exacerbation of this disease were examined at the General Hospital EMS Department in Prijepolje. ABG samples were taken immediately after venous sampling, and both were analyzed. The Pearson correlation coefficients between arterial and venous parameters were 0.828, 0.877, 0.599, 0.896 and 0.312 for pH, PCO2, PO2, HCO3 and SO2, respectively. The statistically significant correlation between arterial and venous pH, PCO2 and HCO3, values was found in patients with acute exacerbation of COPD (p<0.001). When we cannot provide arterial blood for analysis, venous values of the pH, Pv,CO2 and HCO3 parameters can be an alternative to their arterial equivalents in the interpretation of the metabolic status in patients with acute exacerbation of COPD, while the values of venous Pv,O, and Sv,O2 cannot be used as predictors in the assessment of oxygen status of such patients.

  6. Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations.

    PubMed

    Paniagua, Natalia; Lopez, Rebeca; Muñoz, Natalia; Tames, Miriam; Mojica, Elisa; Arana-Arri, Eunate; Mintegi, Santiago; Benito, Javier

    2017-12-01

    To determine whether 2 doses of dexamethasone is as effective as 5 days of prednisolone/prednisone therapy in improving symptoms and quality of life of children with asthma exacerbations admitted to the emergency department (ED). We conducted a randomized, noninferiority trial including patients aged 1-14 years who presented to the ED with acute asthma to compare the efficacy of 2 doses of dexamethasone (0.6 mg/kg/dose, experimental treatment) vs a 5-day course of prednisolone/prednisone (1.5 mg/kg/d, followed by 1 mg/kg/d on days 2-5, conventional treatment). Two follow-up telephone interviews were completed at 7 and 15 days. The primary outcome measures were the percentage of patients with asthma symptoms and quality of life at day 7. Secondary outcomes were unscheduled returns, admissions, adherence, and vomiting. During the study period, 710 children who met the inclusion criteria were invited to participate and 590 agreed. Primary outcome data were available in 557 patients. At day 7, experimental and conventional groups did not show differences related to persistence of symptoms (56.6%, 95% CI 50.6-62.6 vs 58.3%, 95% CI 52.3-64.2, respectively), quality of life score (80.0 vs 77.7, not significant [ns]), admission rate (23.9% vs 21.7%, ns), unscheduled ED return visits (4.6% vs 3.3%, ns), and vomiting (2.1% vs 4.4%, ns). Adherence was greater in the dexamethasone group (99.3% vs 96.0%, P < .05). Two doses of dexamethasone may be an effective alternative to a 5-day course of prednisone/prednisolone for asthma exacerbations, as measured by persistence of symptoms and quality of life at day 7. clinicaltrialsregister.eu: 2013-003145-42. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The cumulative effect of air pollutants on the acute exacerbation of COPD in Shanghai, China.

    PubMed

    Sun, Xian Wen; Chen, Pei Li; Ren, Lei; Lin, Ying Ni; Zhou, Jian Ping; Ni, Lei; Li, Qing Yun

    2018-05-01

    Epidemiologic studies have shown the effect of air pollutants on acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, little is known regarding the dose-response relationship. This study aimed to investigate the cumulative effect of air pollutants on AECOPD. We collected 101 patients with AECOPD from November 2010 through August 2011 in Shanghai. Multiple logistic regression was used to estimate associations between air pollutants and AECOPD. Poisson regression was then applied to determine the cumulative effect of air pollutants including particulate matter 10 (PM10), PM2.5, nitrogen dioxide (NO 2 ), sulphur dioxide (SO 2 ) and ozone (O 3 ) on AECOPD, of which the seasonal variation was further explored. The monthly episodes of AECOPD were associated with the concentrations of PM2.5 (r=0.884, p<0.05) and NO 2 (r=0.763, p<0.05). The cutoff value of PM2.5 and NO 2 for predicting AECOPD was 83.0μg/m 3 and 53.5μg/m 3 , respectively. It showed that per 10μg/m 3 increment in PM2.5 increased the relative risks (RR) for AECOPD was 1.09 with 3days cumulative effect in cold season, whereas 7days in warm season. The RR for AECOPD for per 10μg/m 3 increment in NO 2 was 1.07, with a 5-day cumulative effect without seasonal variation. High consecutive levels of PM2.5 and NO 2 increase the risk of developing AECOPD. Cumulative effect of PM2.5 and NO 2 appears before the exacerbation onset. These gradations were more evident in the PM2.5 during different seasons. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The Most Common Detected Bacteria in Sputum of Patients with the Acute Exacerbation of COPD

    PubMed Central

    Cukic, Vesna

    2013-01-01

    Introduction: Acute exacerbation of COPD (AECOPD) may be triggered by infection with bacteria or viruses or by environmental pollutants; the cause of about one-third of exacerbations cannot be identified. Objective: To determine the most common bacteria in sputum culture of patients with AECOPD hospitalized in Intensive care unit of Clinic for pulmonary disease and TB “Podhrastovi” in the 2012. Material and methods: This is a retrospective analysis of sputum bacterial cultures of patients with AECOPD treated in the Intensive care unit of Clinic for pulmonary disease and TB “Podhrastovi” during 2012 .year. Each patient was required to give two sputum for bacterial examination. Each patient was treated with antibiotics prior to admission in Clinic “Podhrastovi”. The results of sputum bacterial culture findings are expressed in absolute number and percentage of examined patients. Results: In 2012, 75 patients with AECOPD were treated in Intensive care unit of Clinic for pulmonary disease and TB“Podhrastovi”. 44 (58.66%) of patients had normal –nonpathogenic – usual bacterial flora isolated in sputum cultures, 31 (41.34%) had a pathogen bacteria in sputum culture as follows: 7 had Streptoccocus pneumoniae, 8 had Klebsiella pneumoniae (2 with Streptococcus pneumoniae, one with Acinetobacter baumani) ,4 Escherichia colli, others are one or two cases with other bacteria. Conclusion: Bacterial airway infections play a great role in many, but not in all, of cases of AECOPD. So there is the need to do a sputum bacterial culture examination in each patient with AECOPD and with appropriate antibiotics to contribute to curing of them. PMID:24511262

  9. Acute exacerbations of chronic obstructive pulmonary disease: diagnosis, management, and prevention in critically ill patients.

    PubMed

    Dixit, Deepali; Bridgeman, Mary Barna; Andrews, Liza Barbarello; Narayanan, Navaneeth; Radbel, Jared; Parikh, Amay; Sunderram, Jag

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is a substantial source of disability in the United States. Moderate-to-severe acute exacerbations of COPD (AECOPD) can progress to respiratory failure, necessitating ventilator assistance in patients in the intensive care unit (ICU). Patients in the ICU with AECOPD requiring ventilator support have higher morbidity and mortality rates as well as costs compared with hospitalized patients not in the ICU. The mainstay of management for patients with AECOPD in the ICU includes ventilator support (noninvasive or invasive), rapid-acting inhaled bronchodilators, systemic corticosteroids, and antibiotics. However, evidence supporting these interventions for the treatment of AECOPD in critically ill patients admitted to the ICU is scant. Corticosteroids have gained widespread acceptance in the management of patients with AECOPD necessitating ventilator assistance, despite their lack of evaluation in clinical trials as well as controversies surrounding optimal dosage regimens and duration of treatment. Recent studies evaluating the safety and efficacy of corticosteroids have found that higher doses are associated with increased adverse effects, which therefore support lower dosing strategies, particularly for patients admitted to the ICU for COPD exacerbations. This review highlights recent findings from the current body of evidence on nonpharmacologic and pharmacologic treatment and prevention of AECOPD in critically ill patients. In addition, the administration of bronchodilators using novel delivery devices in the ventilated patient and the conflicting evidence surrounding antibiotic use in AECOPD in the critically ill is explored. Further clinical trials, however, are warranted to clarify the optimal pharmacotherapy management for AECOPD, particularly in critically ill patients admitted to the ICU. © 2015 Pharmacotherapy Publications, Inc.

  10. Antibiotic management of methicillin-resistant Staphylococcus aureus--associated acute pulmonary exacerbations in cystic fibrosis.

    PubMed

    Fusco, Nicholas M; Toussaint, Kimberly A; Prescott, William Allan

    2015-04-01

    To review the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) in cystic fibrosis (CF). A search of PubMed, MEDLINE, Cochrane Library and Clinicaltrials.gov databases through November 2014 was conducted using the search terms Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, pulmonary exacerbations, and cystic fibrosis. All English-language research articles, case reports, and case series were evaluated. A total of 185 articles were identified related to MRSA and CF; 30 articles that studied treatments of MRSA APE in CF were included. The persistent presence of MRSA in the respiratory tract of patients with CF has been associated with higher morbidity and an increased risk of death. Limited clinical data exist supporting the efficacy of any specific antimicrobial currently available for the treatment of APE secondary to MRSA. Data extrapolated from other populations suggest that vancomycin and linezolid are appropriate first-line treatment options for the treatment of APE secondary to MRSA. Second-line options include doxycycline or minocycline and trimethoprim/sulfamethoxazole, each of which may be useful in patients coinfected with other respiratory pathogens, for which they may provide overlapping coverage. Ceftaroline and ceftobiprole are newer antibiotics that appear to have a potential role in the treatment of APE in CF, but the latter is not currently available to the US market. Although potentially useful, clindamycin is limited by high rates of resistance, telavancin is limited by its toxicity profile, and tigecycline is limited by a lack of demonstrated efficacy for infections that are similar to that seen in the CF population. Studies investigating the clinical utility of the above-cited antibiotics for APE in CF secondary to MRSA are desperately needed to broaden the treatment armamentarium for this medical condition. © The Author(s) 2015.

  11. 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

  12. 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.

  13. Impact of acute antibiotic therapy on the pulmonary exacerbation endpoint in cystic fibrosis clinical trials.

    PubMed

    Mayer-Hamblett, Nicole; Saiman, Lisa; Lands, Larry C; Anstead, Michael; Rosenfeld, Margaret; Kloster, Margaret; Fisher, Leigh; Ratjen, Felix

    2013-09-01

    In a chronic disease setting such as cystic fibrosis (CF), antibiotics are often prescribed for emergent symptoms and it is unclear whether this affects endpoints in a clinical trial. Pulmonary exacerbations (PEs) are defined episodes of acute worsening and a key clinical efficacy measure in CF. Our hypothesis was that acute antibiotics given for illnesses not meeting the PE definition may alter estimates of treatment effect that do not account for this antibiotic use. A randomized, placebo-controlled trial of azithromycin (AZ) including 260 participants with CF was utilized for this study. PEs were defined using a priori criteria. Physician initiated antibiotic therapy (PIT) not meeting the PE endpoint was characterized and its impact on treatment effect assessed. 40% (104/260) of participants were prescribed 188 courses of PIT in the absence of a PE; 19% (25/129) of placebo and 10% (13/131) of AZ participants received ≥2 courses of PIT and never fulfilled the PE definition (9% difference, 95% confidence interval: 1%, 18%, p = 0.04). Accounting for PIT through use of a composite endpoint including time to PE or need for repeated PIT altered treatment effect estimates (a 56% reduction in the event rate comparing AZ to placebo [p < 0.0001] as compared to a 50% reduction not accounting for PIT [p = 0.003]). PIT is common in CF and may impact treatment effect estimates. Optimization of the PE endpoint to include meaningful events necessitating treatment may improve our ability to conduct efficient trials by reducing the sample size 30-50%, ultimately enabling rapid evaluation of new therapies. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Effect of indacaterol on arterial blood gases in patients suffering from acute exacerbation of COPD.

    PubMed

    Rogliani, Paola; Ora, Josuel; Ciaprini, Chiara; Senis, Lucia; Stirpe, Emanuele; Cazzola, Mario

    2014-02-01

    The administration of β2-agonists to patients with airways obstruction often results in transient decrease in PaO2 despite concomitant bronchodilation. This effect is potentially dangerous for patients suffering from acute exacerbation of COPD (AECOPD). In this study, we investigated the effect of indacaterol 150 μg and 300 μg on the arterial blood gas tensions of hospitalised patients with AECOPD. We explored the acute effects on arterial blood gases and spirometry of two doses of indacaterol Breezhaler (150 and 300 μg) in 12 patients hospitalised because of an AECOPD in 2 non-consecutive days under open-label, randomized, crossover conditions, with blind evaluation. Blood specimens were taken just before the inhalation and at 15, 30, 60, 120, 240 and 360 min after inhalation of each treatment, and spirometry was performed at the same time points. Both doses of indacaterol did not cause significant changes in blood gases, although some patients with relatively well-preserved PaO2 presented transient episodes of oxygen desaturation that normalize spontaneously in a very short time. Moreover, they induced a significant mean increase in FEV1 and FVC, although the improvement caused by indacaterol 300 μg was larger. Indacaterol up to 300 μg is a potent bronchodilator that may induce small, transient decrease in PaO2 mainly in patients with relatively well-preserved PaO2. There appeared to be no clinical consequences of these PaO2 abnormalities in patients suffering from AECOPD. Copyright © 2013. Published by Elsevier Ltd.

  15. Role of Vitamin D in reducing number of acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) patients.

    PubMed

    Khan, Dur Muhammad; Ullah, Aziz; Randhawa, Fawad Ahmad; Iqtadar, Somia; Butt, Nasir Farooq; Waheed, Khadija

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic incompletely reversible poor airflow and air trapping and usually this debilitating disorder limits the outside activities of the patients depriving them of sunlight which is a rich source of Vitamin D. The objective of this study was to determine the effect of vitamin D supplementation in reducing number of acute exacerbation in COPD patients. This randomized control trial was conducted at East Medical Ward Mayo Hospital Lahore from January to December 2015 as exacerbations of COPD are season dependent. Diagnosis was confirmed by performing Pulmonary Function Tests (PFTs). Basic demographical information was obtained and baseline PFTs of the patient was done. Only Group A patients was treated with oral vitamin D intake of 2000 IU daily for 6 months. Vitamin D level was measured at 0, 2, 4, and 6 months and exacerbation of COPD, FEV1 and FVC was measured weekly. Both the groups were given standard treatment for exacerbation of COPD. Spirometry was repeated at each visit. Blood samples were collected every 2 months for vitamin D. Supplementation was stopped if vitamin D level exceeded 100ng/ml. The mean age of the patients was 46.28±8.83 years, the male to female ratio was 1.8:1. The mean 25(OH) level at baseline was 24.08±2.58 and at 6th month was 29.60±8.74. The mean FVC at baseline was 77.83±5.49 and at 6th month was 91.34±5.52. The exacerbation at baseline was present in all 120(100%) patients and at 6th month was reduced to 4(3.3%). Vitamin D supplementation has significant effect in reducing number of acute exacerbation in COPD patients when it is given for prolonged period.

  16. Daily step count predicts acute exacerbations in a US cohort with COPD.

    PubMed

    Moy, Marilyn L; Teylan, Merilee; Weston, Nicole A; Gagnon, David R; Garshick, Eric

    2013-01-01

    COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs). Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations. In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count. We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St. George's Respiratory Questionnaire Activity Score (SGRQ-AS). AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months. Mean daily step count was 5804±3141 steps. Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year). Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42). There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003). Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations. Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations. Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history. These results support the importance of

  17. 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

  18. Expert consensus on acute exacerbation of chronic obstructive pulmonary disease in the People’s Republic of China

    PubMed Central

    Cai, Bai-qiang; Cai, Shao-xi; Chen, Rong-chang; Cui, Li-ying; Feng, Yu-lin; Gu, Yu-tong; Huang, Shao-guang; Liu, Rong-yu; Liu, Guang-nan; Shi, Huan-zhong; Shi, Yi; Song, Yuan-lin; Sun, Tie-ying; Wang, Chang-zheng; Wang, Jing-lan; Wen, Fu-qiang; Xiao, Wei; Xu, Yong-jian; Yan, Xi-xin; Yao, Wan-zhen; Yu, Qin; Zhang, Jing; Zheng, Jin-ping; Liu, Jie; Bai, Chun-xue

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People’s Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD. PMID:24812503

  19. [Pharmacoeconomic analysis of patients with acute exacerbation of chronic bronchitis treated with telithromycin or cefuroxime-axetil].

    PubMed

    Rubio-Terrés, C; Cots, J M; Domínguez-Gil, A; Herreras, A; Sánchez Gascón, F; Chang, J; Trilla, A

    2004-11-01

    A pharmacoeconomic analysis was done to compare the efficiency of two treatments in the acute exacerbation of chronic bronchitis: telithromycin and cefuroxime-axetil. Restrospective analysis, modeled through a decision tree. The effectiveness of the treatments was estimated through a randomized and double-blind clinical trial in which 800 mg/day (5 days) of telithromycin were compared with 1,000 mg/day (10 days) of cefuroxime-axetil in patients with acute exacerbation of chronic bronchitis (140 and 142 patients, respectively). Resources use was estimated from clinical trial and from Spanish data, and the unit costs through a health costs dabatase. The model was validated by a panel of Spanish clinical experts. Since the clinical trial was designed to demonstrate equivalence, there were no significant differences of effectiveness among both treatments (with a rate of clinical cure of 86.4% and 83.1%, respectively) which means that an analysis of costs minimization was done. In the average case, the average cost of the disease by patient was 174.83 Euros with telithromycin and 194.68 Euros with cefuroxime-axetil (a difference of 19.85 Euros). The results were maintained in the analysis of sensitivity, with favorable differences for telithromycin that ranged between 18.04 Euros and 22.25 Euros. With telithromycin up to 22 Euros by patient with acute exacerbation of chronic bronchitis could be saved, in comparison with cefuroxime-axetil.

  20. Early rehabilitation exercise program for inpatients during an acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled trial.

    PubMed

    Tang, Clarice Y; Blackstock, Felicity C; Clarence, Michael; Taylor, Nicholas F

    2012-01-01

    To determine whether an early rehabilitation program was safe and feasible for patients during an acute exacerbation of chronic obstructive pulmonary disease (COPD). In this phase 1 randomized controlled trial, patients with an acute exacerbation of COPD admitted to the hospital were randomly allocated to a low-intensity exercise group, a moderate- to high-intensity exercise group, or a control group, who received routine physical therapy. In addition to routine physical therapy, patients in the exercise group had to participate in an exercise program. The program consisted of twice-daily aerobic and resistance exercise sessions. Primary outcomes were the number and classification of adverse events and program adherence. In 174 exercise sessions, there was 1 serious adverse event of arrhythmia in the low-intensity exercise group that resolved within 1 hour. There were 12 other minor adverse events involving 5 patients with no significant differences between groups. Patients completed an average of 80% of their scheduled sessions with no significant between-group differences. The exercise groups improved significantly in walking distance; however, no significant between-group differences were observed. There was preliminary evidence that it was safe and feasible to implement an exercise program for patients during an acute exacerbation of COPD. Additional studies with larger sample sizes are required to accurately evaluate program effectiveness.

  1. Acute Kidney Injury Facilitates Hypocalcemia by Exacerbating the Hyperphosphatemic Effect of Muscle Damage in Rhabdomyolysis.

    PubMed

    Higaki, Masato; Tanemoto, Masayuki; Shiraishi, Takeshi; Taniguchi, Kei; Fujigaki, Yoshihide; Uchida, Shunya

    2015-01-01

    Hypocalcemia is an important complication of rhabdomyolysis for which several pathogenic factors, including acute kidney injury (AKI), have been proposed. To gain insight regarding the hypocalcemic roles of AKI in rhabdomyolysis, we retrospectively examined patients with rhabdomyolysis. Of 28,387 patients admitted to the Department of Internal Medicine, 51 patients met the inclusion criteria for the study. Serum calcium was analyzed based on laboratory data including indicators of AKI, serum creatine kinase (CK) and serum inorganic phosphate (iP). Twenty-two patients (43%) had hypocalcemia. Compared with patients without hypocalcemia, they had a higher prevalence of AKI (82 vs. 55%; p = 0.046), higher levels of peak CK (39,100 ± 50,600 vs. 9,800 ± 11,900 IU/l; p = 0.003) and higher levels of peak iP (1.77 ± 1.10 vs. 1.10 ± 0.35 mmol/l; p = 0.007). Indicators of AKI were correlated with peak CK and peak iP and were not significant variables in the regression analysis for hypocalcemia. Peak CK and peak iP were not correlated with each other. Impaired phosphate use by muscle contributed to the increased iP. These findings indicate that muscle damage is the primary hypocalcemic factor in rhabdomyolysis. AKI facilitated hypocalcemia by exacerbating the hyperphosphatemic effects of muscle damage. Aggressive hydration, which could increase oxygen supply and subsequently repair phosphate use in muscle, might reduce the incidence of hypocalcemia in rhabdomyolysis. © 2015 S. Karger AG, Basel.

  2. Two 6-minute Walk Tests Are Required During Hospitalisation for Acute Exacerbation of COPD.

    PubMed

    Osadnik, Christian R; Borges, Rodrigo C; McDonald, Christine F; Carvalho, Celso R F; Holland, Anne E

    2016-06-01

    The 6-minute walk test (6MWT) is recommended to be performed twice to accurately assess exercise performance in stable chronic obstructive pulmonary disease (COPD) due to the presence of a learning effect. It is unknown whether a learning effect exists when the 6MWT is performed during hospitalisation for acute exacerbation of COPD (AECOPD). This study investigated whether repeat 6MWTs are necessary when conducted in inpatients with AECOPD. Pooled analysis was undertaken of data from two studies (Australia and Brazil) involving 46 participants (25 males, mean age 67.2 years, FEV1 43% predicted) admitted with AECOPD. Two 6MWTs, separated by ≥20 minutes, were performed on the day of discharge. Six-minute walk distance (6MWD; primary outcome), perceived dyspnoea (Borg scale), heart rate and oxyhaemoglobin saturation were recorded. 6MWD data from tests one (T1) and two (T2) were analysed via visual inspection of Bland-Altman plots. Factors associated with test improvement or decline were explored. Mean 6MWD difference between T1 and T2 was 6.2 m, however limits of agreement were wide (-92.2 m to 104.5 m). 32 (70%) participants improved (by any distance) from T1 to T2 by a mean (± standard deviation) of 32 m ± 28 m. Of these, 14 (30%) improved by a distance > 30 m. Fourteen (30%) participants recorded poorer 6MWD at T2 by a mean of 52 m ± 36 m. No factors were able to identify participants who improved or declined upon repeat testing. When performed in patients admitted to hospital with AECOPD, the 6MWT needs to be conducted twice in order to better estimate 6MWD.

  3. Bacterial flora in the sputum and comorbidity in patients with acute exacerbations of COPD.

    PubMed

    Boixeda, Ramon; Almagro, Pere; Díez-Manglano, Jesús; Cabrera, Francisco Javier; Recio, Jesús; Martin-Garrido, Isabel; Soriano, Joan B

    2015-01-01

    To determine in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the association between the isolation of potential pathogens in a conventional sputum culture and comorbidities. The ESMI study is a multicenter observational study. Patients with AE-COPD admitted to the Internal Medicine departments of 70 hospitals were included. The clinical characteristics, treatments, and comorbidities were gathered. The results of conventional sputum cultures were recorded. A total of 536 patients were included, of which 161 produced valid sputum and a potentially pathogenic microorganism was isolated from 88 subjects (16.4%). The isolation of Pseudomonas aeruginosa (30.7%) was associated with a greater severity of the lung disease (previous admissions [P= 0.026], dyspnea scale [P=0.047], post-broncodilator forced expiratory volume in 1 second (FEV1) [P=0.005], and the BODEx index [P=0.009]); also with higher prevalence of cor pulmonale (P=0.017), heart failure (P=0.048), and cerebrovascular disease (P=0.026). Streptococcus pneumoniae (26.1%) was associated with more comorbidity according to number of diseases (P=0.018); notably, peripheral artery disease (P=0.033), hypertension (P=0.029), dyslipidemia (P=0.039), osteoporosis (P=0.0001), and depression (P=0.005). Patients with AE-COPD and P. aeruginosa present higher severity of COPD, while those with S. pneumoniae present greater comorbidity. The potentially pathogenic microorganism obtained in the sputum culture depends on the associated comorbidities.

  4. Bacterial flora in the sputum and comorbidity in patients with acute exacerbations of COPD

    PubMed Central

    Boixeda, Ramon; Almagro, Pere; Díez-Manglano, Jesús; Cabrera, Francisco Javier; Recio, Jesús; Martin-Garrido, Isabel; Soriano, Joan B

    2015-01-01

    Objective To determine in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the association between the isolation of potential pathogens in a conventional sputum culture and comorbidities. Patients and methods The ESMI study is a multicenter observational study. Patients with AE-COPD admitted to the Internal Medicine departments of 70 hospitals were included. The clinical characteristics, treatments, and comorbidities were gathered. The results of conventional sputum cultures were recorded. Results A total of 536 patients were included, of which 161 produced valid sputum and a potentially pathogenic microorganism was isolated from 88 subjects (16.4%). The isolation of Pseudomonas aeruginosa (30.7%) was associated with a greater severity of the lung disease (previous admissions [P= 0.026], dyspnea scale [P=0.047], post-broncodilator forced expiratory volume in 1 second (FEV1) [P=0.005], and the BODEx index [P=0.009]); also with higher prevalence of cor pulmonale (P=0.017), heart failure (P=0.048), and cerebrovascular disease (P=0.026). Streptococcus pneumoniae (26.1%) was associated with more comorbidity according to number of diseases (P=0.018); notably, peripheral artery disease (P=0.033), hypertension (P=0.029), dyslipidemia (P=0.039), osteoporosis (P=0.0001), and depression (P=0.005). Conclusion Patients with AE-COPD and P. aeruginosa present higher severity of COPD, while those with S. pneumoniae present greater comorbidity. The potentially pathogenic microorganism obtained in the sputum culture depends on the associated comorbidities. PMID:26664106

  5. Airway clearance techniques in acute exacerbations of COPD: a survey of Australian physiotherapy practice.

    PubMed

    Osadnik, Christian R; McDonald, Christine F; Holland, Anne E

    2013-06-01

    To identify airway clearance techniques (ACTs) used to treat patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and identify factors underpinning their utilisation, including therapists' knowledge of the literature. Cross-sectional postal survey using Likert scales and multiple-choice responses. 112 'large' or 'principal referral' Australian public hospitals. 189 physiotherapists from 89 hospitals (response rate 81%). Purpose designed survey measuring self-reported rate of ACT prescription; perception of ACT indications, aims, importance and effectiveness; factors influencing ACT choice; and knowledge of the evidence. Most physiotherapists (123/189, 65%) prescribed ACTs for 60-100% of patients with AECOPDs. The most frequently prescribed ACTs were physical exercise (169/189, 89%), the forced expiratory technique (153/189, 81%) and the active cycle of breathing technique (149/189, 79%). Most were rated highly effective. Physiotherapists who perceived the role of ACTs to be important to patients' overall management (137/189, 73%) and those with less than 5 years cardiorespiratory experience (113/189, 60%) prescribed ACTs significantly more frequently than others. The main factors influencing ACT choice were precautions/contraindications to individual techniques (148/189, 78%) and degree of dyspnoea (136/189, 72%). The primary aim of ACT prescription was to clear sputum (178/189, 94%). Understanding of the evidence for ACTs in AECOPDs was mixed, with 43% citing it as supportive, 30% inconclusive and 19% unsure. Australian physiotherapists frequently prescribe ACTs for patients with AECOPDs and perceive their role to be important. Physical exercise is frequently prescribed for airway clearance and warrants further investigation. Copyright © 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  6. Interleukin 1 Receptor (IL-1R1) Activation Exacerbates Toxin-Induced Acute Kidney Injury.

    PubMed

    Privratsky, Jamie R; Zhang, Jiandong; Lu, Xiaohan; Rudemiller, Nathan; Wei, Qingqing; Yu, Yen-Rei; Gunn, Michael Dee; Crowley, Steven D

    2018-05-23

    Acute kidney injury (AKI) is a leading cause of morbidity and mortality. Cisplatin is an effective chemotherapeutic agent whose administration is limited by nephrotoxicity. Therapies to prevent cisplatin-induced AKI are lacking. While tumor necrosis factor-α (TNF) plays a key role in the pathogenesis of cisplatin nephrotoxicity, the immune signaling pathways that trigger TNF generation in this context require elucidation. Sterile injury triggers the release and activation of both isoforms of interleukin(IL)-1, IL-1α and IL-1β, and stimulation of the interleukin-1 receptor (IL-1R1) by these ligands engages a pro-inflammatory signaling cascade that induces TNF induction. We therefore hypothesized that IL-1R1 activation exacerbates cisplatin-induced AKI by inducing TNF production thereby augmenting inflammatory signals between kidney parenchymal cells and infiltrating myeloid cells. IL-1R1+/+ (WT) and IL-1R1-/- (KO) mice were subjected to cisplatin-induced AKI. Compared to WT mice, IL-1R1 KO mice had attenuated AKI as measured by serum creatinine and BUN; renal NGAL mRNA levels; and blinded histological analysis of kidney pathology. In the cisplatin-injured kidney, IL-1R1 KO mice had diminished levels of whole kidney TNF and fewer Ly6G-expressing neutrophils. In addition, an unbiased machine learning analysis of intra-renal immune cells revealed a diminished number of CD11bint/CD11cint myeloid cells in IL-1R1 KO injured kidneys compared to IL-1R1 WT kidneys. Following cisplatin, IL-1R1 KO kidneys, compared to WTs, had fewer TNF-producing macrophages, CD11bint/CD11cint cells, and neutrophils, consistent with an effect of IL-1R1 to polarize intra-renal myeloid cells toward a pro-inflammatory phenotype. Interruption of IL-1-dependent signaling pathways warrants further evaluation to decrease nephrotoxicity during cisplatin therapy.

  7. Effect of acetazolamide on post-NIV metabolic alkalosis in acute exacerbated COPD patients.

    PubMed

    Fontana, V; Santinelli, S; Internullo, M; Marinelli, P; Sardo, L; Alessandrini, G; Borgognoni, L; Ferrazza, A M; Bonini, M; Palange, P

    2016-01-01

    Non-invasive ventilation (NIV) is an effective treatment in patients with acute exacerbation of COPD (AECOPD). However, it may induce post-hypercapnic metabolic alkalosis (MA). This study aims to evaluate the effect of acetazolamide (ACET) in AECOPD patients treated with NIV. Eleven AECOPD patients, with hypercapnic respiratory failure and MA following NIV, were treated with ACET 500 mg for two consecutive days and compared to a matched control group. Patients and controls were non invasively ventilated in a bilevel positive airway pressure (BiPAP) mode to a standard maximal pressure target of 15-20 cmH2O. ACET intra-group analysis showed a significant improvement for PaCO2 (63.9 ± 9.8 vs. 54.9 ± 8.3 mmHg), HCO3- (43.5 ± 5.9 vs. 36.1 ± 5.4 mmol/L) and both arterial pH (7.46 ± 0.06 vs. 7.41 ± 0.06) and urinary pH (6.94 ± 0.77 vs 5.80 ± 0.82), already at day 1. No significant changes in endpoints considered were observed in the control group at any time-point. Inter-group analysis showed significant differences between changes in PaCO2 and HCO3- (delta), both at day 1 and 2. Furthermore, the length of NIV treatment was significantly reduced in the ACET group compared to controls (6 ± 8 vs. 19 ± 19 days). No adverse events were recorded in the ACET and control groups. ACET appears to be effective and safe in AECOPD patients with post-NIV MA.

  8. Electrical stimulation-based renal nerve mapping exacerbates ventricular arrhythmias during acute myocardial ischaemia.

    PubMed

    Huang, Bing; Zhou, Xiaoya; Wang, Menglong; Li, Xuefei; Zhou, Liping; Meng, Guannan; Wang, Yuhong; Wang, Zhuo; Wang, Songyun; Yu, Lilei; Jiang, Hong

    2018-06-01

    Blood pressure elevation in response to transient renal nerve stimulation (RNS) has been used to determine the ablation target and endpoint of renal denervation. This study aimed to evaluate the safety of transient RNS in canines with normal or ischaemic hearts. In ten normal (Group 1) and six healed myocardial infarction (HMI) (Group 2) canines, a large-tip catheter was inserted into the left or right renal artery to perform transient RNS. The left stellate ganglion neural activity (LSGNA) and ventricular electrophysiological parameters were measured at baseline and during transient RNS. In another 20 acute myocardial infarction (AMI) canines, RNS (Group 3, n = 10) or sham RNS (Group 4, n = 10) was intermittently (1 min ON and 4 min OFF) performed for 1 h following AMI induction. The LSGNA and AMI-induced ventricular arrhythmias were analysed. In normal and HMI canines, although transient RNS significantly increased the LSGNA and facilitated the action potential duration (APD) alternans, it did not induce any ventricular arrhythmias and did not change the ventricular effective refractory period, APD or maximum slope of the APD restitution curve. In AMI canines, transient RNS significantly exacerbated LSG activation and promoted the incidence of ventricular arrhythmias. Transient RNS did not increase the risk of ventricular arrhythmias in normal or HMI hearts, but it significantly promoted the occurrence of ventricular arrhythmias in AMI hearts. Therefore, electrical stimulation-based renal nerve mapping may be unsafe in AMI patients and in patients with a high risk for malignant ventricular arrhythmias.

  9. Pirfenidone for acute exacerbation of idiopathic pulmonary fibrosis: A retrospective study.

    PubMed

    Furuya, Kenta; Sakamoto, Susumu; Shimizu, Hiroshige; Sekiya, Muneyuki; Kinoshita, Arisa; Isshiki, Takuma; Sugino, Keishi; Matsumoto, Keiko; Homma, Sakae

    2017-05-01

    Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a rapid and ultimately fatal condition, and no effective treatment has been established. Pirfenidone has antifibrotic effects in IPF; however, its efficacy for AE-IPF is unclear. To evaluate the efficacy of pirfenidone for AE-IPF. We retrospectively reviewed the medical records of 135 IPF patients treated during the period from April 2008 to April 2015 and identified and extracted 47 AE-IPF patients (42 men, 5 women; mean age, 73.5 years). The clinical features and outcomes of the 20 patients treated with pirfenidone were compared with those of the 27 patients treated without pirfenidone. We then excluded the 25 patients who did not receive recombinant human soluble thrombomodulin (rhTM) and analyzed data from the remaining 22 patients (20 men, 2 women; mean age, 73.7 years). Clinical features and outcomes were compared between the 10 patients treated with pirfenidone and the 12 patients who did not receive pirfenidone. There were no significant differences between the two groups in baseline characteristics, except for pirfenidone use before onset. Three-month survival was significantly better in patients treated with pirfenidone than in the control group (55% vs 34%, p = 0.042). In univariate analysis, nonuse of pirfenidone was a potential risk factor for death at 3 months (hazard ratio, 6.993; p = 0.043) in patients treated with rhTM. A regimen of pirfenidone combined with corticosteroids and rhTM may improve survival in patients with AE-IPF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Efficacy of amoxycillin versus amoxycillin/clavulanate in acute exacerbations of chronic pulmonary obstructive disease in primary care.

    PubMed

    Llor, Carl; Hernández, Silvia; Ribas, Anna; Alvarez, Carmen; Cots, Josep Maria; Bayona, Carolina; González, Isabel; Miravitlles, Marc

    2009-01-01

    Amoxycillin/clavulanate is considered first-line treatment for ambulatory exacerbations of COPD. However, narrow-spectrum antibiotics may be as useful for mild to moderate patients. To compare the clinical efficacy of amoxycillin versus amoxicyllin/clavulanate in exacerbations of COPD in primary care. A randomized, double-blind, noninferiority clinical trial was carried out in eight primary care centers in Catalonia, Spain. Spirometrically-diagnosed patients older than 40 years with COPD, without criteria of hospitalization and Anthonisen's types I or II exacerbations were included. The main outcome was clinical cure at the end of treatment (EOT) visit on day 10. A total of 137 patients were enrolled in the study (68 assigned to amoxycillin and 69 to amoxycillin/clavulanate). The mean forced expiratory flow in one second was 61.6% and the mean age was 71.4 years. At EOT, 92.8% of patients in the amoxycillin/clavulanate and 90.9% in the amoxycillin group were considered clinically cured, a statistically non-significant difference. Adverse effects were observed in 11 subjects, 3 in the amoxycillin group and 8 in the amoxycillin/clavulanate group, 2 of whom required a change in treatment. Amoxycillin was at least as effective clinically and as safe as amoxycilin/ clavulanate in the treatment of acute exacerbations of COPD in mild to moderate patients in primary care.

  11. 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.

  12. Molecular profiling of mucosal tissue associated microbiota in patients manifesting acute exacerbations and remission stage of ulcerative colitis.

    PubMed

    Walujkar, Sandeep A; Kumbhare, Shreyas V; Marathe, Nachiket P; Patangia, Dhrati V; Lawate, Parimal S; Bharadwaj, Renu S; Shouche, Yogesh S

    2018-05-23

    Dysbiosis of intestinal microflora has been postulated in ulcerative colitis (UC), which is characterized by imbalance of mucosal tissue associated bacterial communities. However, the specific changes in mucosal microflora during different stages of UC are still unknown. The aim of the current study was to investigate the changes in mucosal tissue associated microbiota during acute exacerbations and remission stages of UC. The mucosal microbiota associated with colon biopsy of 12 patients suffering from UC (exacerbated stage) and the follow-up samples from the same patients (remission stage) as well as non-IBD subjects was studied using 16S rRNA gene-based sequencing and quantitative PCR. The total bacterial count in patients suffering from exacerbated phase of UC was observed to be two fold lower compared to that of the non-IBD subjects (p = 0.0049, Wilcox on matched-pairs signed rank tests). Bacterial genera including Stenotrophomonas, Parabacteroides, Elizabethkingia, Pseudomonas, Micrococcus, Ochrobactrum and Achromobacter were significantly higher in abundance during exacerbated phase of UC as compared to remission phase. The alterations in bacterial diversity with an increase in the abnormal microbial communities signify the extent of dysbiosis in mucosal microbiota in patients suffering from UC. Our study helps in identifying the specific genera dominating the microbiota during the disease and thus lays a basis for further investigation of the possible role of these bacteria in pathogenesis of UC.

  13. 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

  14. Acute stress exposure preceding transient global brain ischemia exacerbates the decrease in cortical remodeling potential in the rat retrosplenial cortex.

    PubMed

    Kutsuna, Nobuo; Yamashita, Akiko; Eriguchi, Takashi; Oshima, Hideki; Suma, Takeshi; Sakatani, Kaoru; Yamamoto, Takamitsu; Yoshino, Atsuo; Katayama, Yoichi

    2014-01-01

    Doublecortin (DCX)-immunoreactive (-ir) cells are candidates that play key roles in adult cortical remodeling. We have previously reported that DCX-ir cells decrease after stress exposure or global brain ischemia (GBI) in the cingulate cortex (Cg) of rats. Herein, we investigate whether the decrease in DCX-ir cells is exacerbated after GBI due to acute stress exposure preconditioning. Twenty rats were divided into 3 groups: acute stress exposure before GBI (Group P), non-stress exposure before GBI (Group G), and controls (Group C). Acute stress or GBI was induced by a forced swim paradigm or by transient bilateral common carotid artery occlusion, respectively. DCX-ir cells were investigated in the anterior cingulate cortex (ACC) and retrosplenial cortex (RS). The number of DCX-ir cells per unit area (mm(2)) decreased after GBI with or without stress preconditioning in the ACC and in the RS (ANOVA followed by a Tukey-type test, P<0.001). Moreover, compared to Group G, the number in Group P decreased significantly in RS (P<0.05), though not significantly in ACC. Many of the DCX-ir cells were co-localized with the GABAergic neuronal marker parvalbumin. The present study indicates that cortical remodeling potential of GABAergic neurons of Cg decreases after GBI, and moreover, the ratio of the decrease is exacerbated by acute stress preconditioning in the RS. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  15. Should patients with acute exacerbation of chronic bronchitis be treated with antibiotics? Advantages of the use of fluoroquinolones.

    PubMed

    Mensa, J; Trilla, A

    2006-05-01

    The pathological changes in chronic bronchitis (CB) produce airflow obstruction, reduce the effectiveness of the mucocilliary drainage system and lead to bacterial colonisation of bronchial secretion. The presence of bacteria induces an inflammatory response mediated by leukocytes. There is a direct relationship between the degree of impairment of the mucocilliary drainage system, the density of bacteria in mucus and the number of leukocytes in the sputum. Purulent sputum is a good marker of a high bacterial load. Eventually, if the number of leukocytes is high, their normal activity could decrease the effectiveness of the drainage system, increase the bronchial obstruction and probably damage the lung parenchyma. Whenever the density of bacteria in the bronchial lumen is >or=10(6) CFU/mL, there is a high probability that the degree of inflammatory response will lead to a vicious cycle which in turn tends to sustain the process. This situation can arise during the clinical course of any acute exacerbation of CB, independently of its aetiology, provided the episode is sufficiently severe and/or prolonged. Fluoroquinolones of the third and fourth generation are bactericidal against most microorganisms usually related to acute exacerbations of CB. Their diffusion to bronchial mucus is adequate. When used in short (5-day) treatment they reduce the bacterial load in a higher proportion than is achieved by beta-lactam or macrolide antibiotics given orally. Although the clinical cure rate is similar to that obtained with other antibiotics, the time between exacerbations could be increased.

  16. Kinematic Analysis of Gait Following Intra-articular Corticosteroid Injection into the Knee Joint with an Acute Exacerbation of Arthritis

    PubMed Central

    Mehta, Saurabh; Szturm, Tony; El-Gabalawy, Hani S.

    2011-01-01

    ABSTRACT Purpose: The objective of this study was to examine the effects of intra-articular corticosteroid injection (ICI) on ipsilateral knee flexion/extension, ankle dorsiflexion/plantarflexion (DF/PF), and hip abduction/adduction (abd/add) during stance phase in people with an acute exacerbation of rheumatoid arthritis (RA) of the knee joint. The study also assessed the effects of ICI on spatiotemporal parameters of gait and functional status in this group. Methods: Nine people with an exacerbation of RA of the knee were recruited. Kinematic and spatiotemporal gait parameters were obtained for each participant. Knee-related functional status was assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS). Spatiotemporal gait parameters and joint angles (knee flexion, ankle DF/PF, hip abd/add) of the affected side were compared pre- and post-ICI. Results: Data for eight people were available for analysis. Median values for knee flexion and ankle PF increased significantly following ICI. Gait parameters of cadence, velocity, bilateral stride length, bilateral step length, step width, double-support percentage, and step time on the affected side also showed improvement. Pain and knee-related functional status as measured by the KOOS showed improvement. Conclusions: This study demonstrated a beneficial short-term effect of ICI on knee-joint movements, gait parameters, and knee-related functional status in people with acute exacerbation of RA of the knee. PMID:22942516

  17. 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.

  18. Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

    PubMed

    Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

    2017-09-01

    Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  19. Doxycycline for outpatient-treated acute exacerbations of COPD: a randomised double-blind placebo-controlled trial.

    PubMed

    van Velzen, Patricia; Ter Riet, Gerben; Bresser, Paul; Baars, Jeroen J; van den Berg, Bob T J; van den Berg, Jan W K; Brinkman, Paul; Dagelet, Jennece W F; Daniels, Johannes M A; Groeneveld-Tjiong, Dewi R G L; Jonkers, René E; van Kan, Coen; Krouwels, Frans H; Pool, Karin; Rudolphus, Arjan; Sterk, Peter J; Prins, Jan M

    2017-06-01

    Antibiotics do not reduce mortality or short-term treatment non-response in patients receiving treatment for acute exacerbations of COPD in an outpatient setting. However, the long-term effects of antibiotics are unknown. The aim of this study was to investigate if the antibiotic doxycycline added to the oral corticosteroid prednisolone prolongs time to next exacerbation in patients with COPD receiving treatment for an exacerbation in the outpatient setting. In this randomised double-blind placebo-controlled trial, we recruited a cohort of patients with COPD from outpatient clinics of nine teaching hospitals and three primary care centres in the Netherlands. Inclusion criteria were an age of at least 45 years, a smoking history of at least 10 pack-years, mild-to-severe COPD (Global Initiative of Chronic Obstructive Lung Disease [GOLD] stage 1-3), and at least one exacerbation during the past 3 years. Exclusion criteria were poor mastery of the Dutch language, poor cognitive functioning, known allergy to doxycycline, pregnancy, and a life expectancy of shorter than 1 month. If a participant had an exacerbation, we randomly assigned them (1:1; with permuted blocks of variable sizes [ranging from two to ten]; stratified by GOLD stage 1-2 vs 3) to a 7 day course of oral doxycycline 100 mg daily (200 mg on the first day) or placebo. Exclusion criteria for randomisation were fever, admission to hospital, and current use of antibiotics or use within the previous 3 weeks. Patients in both groups received a 10 day course of 30 mg oral prednisolone daily. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary outcome was time to next exacerbation in all randomly allocated patients except for those incorrectly randomly allocated who did not meet the inclusion criteria or met the exclusion criteria. This trial is registered with the Netherlands Trial Register, number NTR2499. Between Dec 22, 2010, and Aug 6, 2013, we randomly

  20. Pulse Oximeter Plethysmograph Estimate of Pulsus Paradoxus as a Measure of Acute Asthma Exacerbation Severity and Response to Treatment.

    PubMed

    Arnold, Donald H; Wang, Li; Hartert, Tina V

    2016-03-01

    Pulsus paradoxus is one of the few objective bedside measures of acute asthma exacerbation severity but is difficult to measure in tachypneic and tachycardic patients and in noisy clinical environments. Our primary objective was to examine whether pulse oximeter plethysmograph estimate of pulsus paradoxus (PEP) is associated with physiologic and symptom measures of acute exacerbation severity (airway resistance by impulse oscillometry [%IOS] and the Acute Asthma Intensity Research Score [AAIRS]). Secondary objectives were to validate the previous association of PEP with percent predicted forced expiratory volume in 1 second (%FEV1 ) and to examine associations of change of PEP with change of these outcomes after 2 hours of treatment. This was a secondary analysis of data from a prospective observational study of patients aged 5-17 years with acute asthma exacerbations. The predictor variable, PEP, was measured using a dedicated pulse oximeter and waveform analysis program. Outcome measures included the AAIRS, %IOS, and %FEV1 at baseline and after 2 hours of treatment. We examined associations of PEP with %IOS and the AAIRS at baseline using multiple linear regression models adjusted for age, sex, and race. As secondary analyses we similarly examined the association of PEP with %FEV1 at baseline and change of PEP with change of %IOS, the AAIRS, and %FEV1 after 2 hours of treatment using multiple linear regression models adjusted for the baseline value of the outcome measure and the AAIRS. Among 684 participants (61% males; 61% African American) there were associations of baseline PEP with %IOS, the AAIRS, and %FEV1 (p < 0.001). Change of PEP after 2 hours of treatment was associated with change of %FEV1 (p < 0.001) and change of the AAIRS (p = 0.01) but not with change of %IOS (p = 0.60). PEP demonstrates criterion validity in predicting baseline %IOS, the AAIRS, and %FEV1 , and responsiveness to change of the AAIRS and %FEV1 . Data contained in the oximeter

  1. Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg.

    PubMed

    Martinez, F J; Grossman, R F; Zadeikis, N; Fisher, A C; Walker, K; Ambruzs, M E; Tennenberg, A M

    2005-06-01

    This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness. Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days. Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively). In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.

  2. Cognitive Dysfunction and Malnutrition Are Independent Predictor of Dysphagia in Patients with Acute Exacerbation of Congestive Heart Failure

    PubMed Central

    Yamanaka, Shinsuke; Takahashi, Yoshimi; Fujita, Hiroshi; Yamaguchi, Nobuhiro; Onoue, Noriko; Ishizuka, Takeshi; Shinozaki, Tsuyoshi; Kohzuki, Masahiro

    2016-01-01

    Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia. PMID:27898735

  3. Cognitive Dysfunction and Malnutrition Are Independent Predictor of Dysphagia in Patients with Acute Exacerbation of Congestive Heart Failure.

    PubMed

    Yokota, Junichi; Ogawa, Yoshiko; Yamanaka, Shinsuke; Takahashi, Yoshimi; Fujita, Hiroshi; Yamaguchi, Nobuhiro; Onoue, Noriko; Ishizuka, Takeshi; Shinozaki, Tsuyoshi; Kohzuki, Masahiro

    2016-01-01

    Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia.

  4. Tanreqing injection combined with conventional Western medicine for acute exacerbations of chronic obstructive pulmonary disease: a systematic review.

    PubMed

    Zhong, Yunqing; Mao, Bing; Wang, Gang; Fan, Tao; Liu, Xuemei; Diao, Xiang; Fu, Juanjuan

    2010-12-01

    In China, most patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) are usually treated with Tanreqing injection plus conventional Western medicine. However, the value of its use remains uncertain. The objective of this systematic review is to compare the efficacy of Tanreqing injection plus conventional Western medicine with that of conventional Western medicine alone (therapy A versus therapy B, respectively) in the management of acute exacerbations of COPD. Literature retrieval was conducted using the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,(®) EMBASE, Chinese Biomedical Database (CBM), and other electronically available databases from respective inception to August 2009. In addition, manual search of some traditional Chinese journals was performed to identify potential studies. Review authors independently extracted the trial data and assessed the quality of each trial. The following outcomes were evaluated: (1) forced expiratory volume in 1 second as a percentage of the predicted value; (2) arterial partial pressure of oxygen (Po(2)); (3) arterial partial pressure of carbon dioxide (Pco(2)); (4) length of hospital stay; (5) marked efficacy rate; (6) interleukin-8; and (7) adverse events. Based on the search strategy, 14 trials involving 954 patients were finally included. Our results showed that compared with therapy B, therapy A improved Po(2), clinical efficacy, and lung function, reduced Pco(2), shortened the length of hospital stay, and was thus more therapeutically beneficial. No serious adverse events were reported. Within the limitations of this systematic review, we can conclude that compared with therapy B, therapy A may provide more benefits for patients with acute exacerbations of COPD. Further large-scale high-quality trials are warranted.

  5. [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.

  6. Acute Exacerbations of COPD Are Associated With Increased Expression of Heparan Sulfate and Chondroitin Sulfate in BAL.

    PubMed

    Papakonstantinou, Eleni; Klagas, Ioannis; Roth, Michael; Tamm, Michael; Stolz, Daiana

    2016-03-01

    Acute exacerbations of COPD (AECOPDs) are associated with accelerated aggravation of clinical symptoms and deterioration of pulmonary function. The mechanisms by which exacerbations may contribute to airway remodeling and declined lung function are poorly understood. We investigated whether AECOPDs are associated with differential expression of glycosaminoglycans in BAL in a cohort of 97 patients with COPD. Patients with COPD with either stable disease (n = 53) or AECOPD (n = 44) and undergoing diagnostic bronchoscopy were matched for demographics and lung function parameters. Levels of heparan sulfate, chondroitin sulfate, dermatan sulfate, and matrix metalloproteinases (MMPs) in BAL were measured by enzyme-linked immunosorbent assay. Heparan sulfate and chondroitin sulfate were significantly increased in BAL of patients during exacerbations. Levels of heparan sulfate were higher in the BAL of patients with microbial infections. Chondroitin sulfate was negatively correlated with FEV1 % predicted but not with diffusing capacity of lung for carbon monoxide % predicted, indicating that chondroitin sulfate is associated with airway remodeling, leading to obstruction rather than to emphysema. Furthermore, heparan sulfate and chondroitin sulfate were significantly correlated with MMP-9, MMP-2, and MMP-12 in BAL, indicating that they were cleaved from their respective proteoglycans by MMPs and subsequently washed out in BAL. During AECOPD, there is increased expression of heparan sulfate and chondroitin sulfate in BAL. These molecules are significantly correlated with MMPs in BAL, indicating that they may be associated with airway remodeling and may lead to lung function decline during exacerbations of COPD. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  7. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus-related chronic liver disease.

    PubMed

    Kumar, Manoj; Sharma, Barjesh C; Sarin, Shiv K

    2008-06-01

    Hepatitis E virus (HEV) has recently been implicated in episodes of acute decompensation in patients having underlying chronic liver disease (CLD) of varying etiology. However, HEV as a cause of acute exacerbation of previously asymptomatic and unrecognized hepatitis B virus (HBV)-infected patients is less well described. The aim of the present study was to investigate the etiology of acute exacerbation of previously asymptomatic and unrecognized HBV-infected patients and to evaluate the relative role of HEV. We also investigated the effect of superinfection on the clinical spectrum of underlying HBV infection. Forty-three patients presented with the following were retrospectively analyzed: (i) clinical features suggestive of acute hepatitis; (ii) with hepatitis B surface antigen (HBsAg) (+); (iii) IgM hepatitis B core antibody (IgM anti-HBc) (-); (iv) no previous history of liver disease; (v) no features suggestive of CLD at presentation; (vi) HBsAg remaining (+) for at least 12 months on follow up; and (vii) having a follow-up biopsy during the convalescent phase showing evidence of chronic hepatitis B. Of the 43 patients, 21 were hepatitis e antigen (HBeAg) (+) (Gr.1) and 22 HBeAg (-) (Gr.2) at presentation. In Gr.1, only two (9.5%) had superinfection (both with hepatitis A virus), whereas in Gr.2, 11 (50%) had superinfection (27.3% hepatitis E, 13.6% hepatitis A and 9.1% both) (P = 0.007). In Gr.1, the remaining 19 (90.5%) patients had spontaneous exacerbation (immune clearance with spontaneous seroconversion) whereas in Gr.2, the remaining 11 (50%) had spontaneous exacerbation (due to reactivation). Overall, HEV superinfection contributed to 20% of acute exacerbation episodes and, in particular, 36% of episodes in initially HBeAg (-) patients. Time to alanine aminotransferase normalization was longer in patients with superinfection (n = 13) as compared to spontaneous exacerbation (n = 30) (median [range] 36 [8-48]vs 16 [6-36] weeks, P = 0.001). During

  8. 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.

  9. The Role of Regulatory T Cell in Nontypeable Haemophilus influenzae-Induced Acute Exacerbation of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Guan, Xuewa; Lu, Yanjiao; Wang, Guoqiang; Fang, Keyong; Wang, Ziyan; Pang, Zhiqiang; Guo, Yingqiao; Lu, Junying; Yuan, Yuze; Ran, Nan

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is associated with irreversible persistent airflow limitation and enhanced inflammation. The episodes of acute exacerbation (AECOPD) largely depend on the colonized pathogens such as nontypeable Haemophilus influenzae (NTHi), one of the most commonly isolated bacteria. Regulatory T cells (Tregs) are critical in controlling inflammatory immune responses and maintaining tolerance; however, their role in AECOPD is poorly understood. In this study, we hypothesized a regulatory role of Tregs, as NTHi participated in the progress of COPD. Immunological pathogenesis was investigated in a murine COPD model induced by cigarette smoke (CS). NTHi was administrated through intratracheal instillation for an acute exacerbation. Weight loss and lung function decline were observed in smoke-exposed mice. Mice in experimental groups exhibited serious inflammatory responses via histological and cytokine assessment. Expression levels of Tregs and Th17 cells with specific cytokines TGF-β1 and IL-17 were detected to assess the balance of pro-/anti-inflammatory influence partially. Our findings suggested an anti-inflammatory activity of Tregs in CS-induced model. But this activity was suppressed after NTHi administration. Collectively, these data suggested that NTHi might play a necessary role in downregulating Foxp3 to impair the function of Tregs, helping development into AECOPD. PMID:29725272

  10. Acute exacerbation of previously undiagnosed chronic focal myositis in an Aboriginal patient on maintenance haemodialysis

    PubMed Central

    Stewart, Benjamin James; Majoni, Sandawana William

    2014-01-01

    We describe a haemodialysis patient who presented with an exacerbation of previously undiagnosed chronic focal myositis during a hospital admission for missed dialysis and chronic foot osteomyelitis. The association of focal myositis with haemodialysis has been reported once previously, but we report the third case in our experience and argue that it is probably more common than previously appreciated. We consider a focused differential diagnosis for a diabetic dialysis patient with leg pain and discuss important features of this rare condition. PMID:25342033

  11. Self-reported alcohol intake and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study.

    PubMed

    Wetherbee, Erin E; Niewoehner, Dennis E; Sisson, Joseph H; Lindberg, Sarah M; Connett, John E; Kunisaki, Ken M

    2015-01-01

    To evaluate the relationship between alcohol consumption and the risk of acute exacerbation of COPD (AECOPD). We conducted a secondary analysis of data previously collected in a large, multicenter trial of daily azithromycin in COPD. To analyze the relationship between amount of baseline self-reported alcohol consumption in the past 12 months and subsequent AECOPD, we categorized the subjects as minimal (<1 drink/month), light-to-moderate (1-60 drinks/month), or heavy alcohol users (>60 drinks/month). The primary outcome was time to first AECOPD and the secondary outcome was AECOPD rate during the 1-year study period. Of the 1,142 enrolled participants, 1,082 completed baseline alcohol questionnaires and were included in this analysis. Six hundred and forty-five participants reported minimal alcohol intake, 363 reported light-to-moderate intake, and 74 reported heavy intake. There were no statistically significant differences in median time to first AECOPD among minimal (195 days), light-to-moderate (241 days), and heavy drinkers (288 days) (P=0.11). The mean crude rate of AECOPD did not significantly differ between minimal (1.62 events per year) and light-to-moderate (1.44 events per year) (P=0.095), or heavy drinkers (1.68 events per year) (P=0.796). There were no significant differences in hazard ratios for AECOPD after adjustment for multiple covariates. Among persons with COPD at high risk of exacerbation, we found no significant relationship between self-reported baseline alcohol intake and subsequent exacerbations. The number of patients reporting heavy alcohol intake was small and further study is needed to determine the effect of heavy alcohol intake on AECOPD risk.

  12. Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

    PubMed Central

    Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

    2012-01-01

    Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

  13. Supplementation of Low- and High-fat Diets with Fermentable Fiber Exacerbates Severity of DSS-induced Acute Colitis.

    PubMed

    Miles, Jennifer P; Zou, Jun; Kumar, Matam-Vijay; Pellizzon, Michael; Ulman, Edward; Ricci, Matthew; Gewirtz, Andrew T; Chassaing, Benoit

    2017-07-01

    Lack of dietary fiber has been suggested to increase the risk of developing various chronic inflammatory diseases, whereas supplementation of diets with fiber might offer an array of health-promoting benefits. Consistent with this theme, we recently reported that in mice, compositionally defined diets that are made with purified ingredients and lack fermentable fiber promote low-grade inflammation and metabolic syndrome, both of which could be ameliorated by supplementation of such diets with the fermentable fiber inulin. Herein, we examined if, relative to a grain-based mouse diet (chow), compositionally defined diet consumption would impact development of intestinal inflammation induced by dextran sulfate sodium (DSS) and moreover, whether DSS-induced colitis might also be attenuated by diets supplemented with inulin. Analogous to their promotion of low-grade inflammation, compositionally defined diet of high- and low-fat content with cellulose increased the severity of DSS-induced colitis relative to chow. However, in contrast to the case of low-grade inflammation, addition of inulin, but not the insoluble fiber cellulose, further exacerbated the severity of colitis and its associated clinical manifestations (weight loss and bleeding) in both low- and high-fat diets. While inulin, and perhaps other fermentable fibers, can ameliorate low-grade inflammation and associated metabolic disease, it also has the potential to exacerbate disease severity in response to inducers of acute colitis.

  14. Study of Pre-disposing Factors of Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Antibiotic Prescribing Pattern with Reference to Antibiotic Sensitivity Test.

    PubMed

    Shrestha, R; Shrestha, B; Shakya Shrestha, S; Pant, A; Prajapati, B; Karmacharya, B M

    2015-01-01

    Background Chronic Obstructive Pulmonary Disease (COPD) affects about 329 million people worldwide, which is nearly 5% of the entire global population. In the context of Nepal, COPD accounts for 43% of the non-communicable disease burden and 2.56% of hospitalizations. Various pre-disposing factors like bacterial, viral, fungal, smoking, occupational exposures and genetic factors have been proposed to precipitate COPD and its exacerbation though, the definitive pre-disposing factors and factors related to acute exacerbation have not been determined in the context of Nepal. Objective To find out the pre-disposing factors and the related causative agents for COPD. Method A cross sectional study was conducted in a tertiary care hospital. Patients of all age group who were diagnosed as COPD and admitted in the hospital were included in this study. Patients were interviewed using structured questionnaire. The sociodemographic data including personal and medical history were recorded from those participants. In addition, sputum from those patients was sent for culture to investigate the possible responsible pathogens as well as its antibiotic sensitivity pattern. Result A total of 150 patients having Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) who have admitted from either emergency or out-patient department of the hospital were included in this study. Among the total number of patients, more than half of them were female (n=82). In addition, analysis of occupations shows that most of them were either farmer (36.0%) or housewife (30.7%). In total studied patients (n=150), most of them were using traditional firewood (83%) for cooking purpose and majority of patients (91%) were smokers. Most of the sputum samples show growth of gram-positive cocci (26.7%) and gram negative bacilli (27.5%). Considering the overall sensitivity pattern, the higher sensitivity was recorded for Co-trimoxazole and Ciprofloxacin while higher rate of resistance was noted

  15. 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.

  16. Extremely elevated alpha-fetoprotein due to acute exacerbation of chronic hepatitis B without malignancy: a case report.

    PubMed

    Yoon, Young-Min; Kang, Da-Yeong; Kim, Da-Young; Seo, Jun-Won; Lim, Hyun-Jong; Lee, Hee-Jeong; Park, Sang-Gon

    2016-06-01

    Alpha-fetoprotein is produced by a variety of tumors such as hepatocellular carcinoma, hepatoblastoma, and germ cell tumors of the ovary and testes. However, we present a case of significantly elevated serum alpha-fetoprotein without evidence of malignant disease in a patient who is a carrier of chronic hepatitis B. A 60-year-old Korean man presented with markedly increased alpha-fetoprotein (2350 ng/mL; normal <5 ng/mL). Various diagnostic evaluations, including computed tomography of the abdomen and thorax and ultrasonography of the abdomen and testes, showed liver cirrhosis and mild splenomegaly; however, no mass was detected in the liver, testes, or other organs scanned. The laboratory findings showed elevated liver function, positivity for hepatitis B e antigen, and a marked increase in hepatitis B virus deoxyribonucleic acid copy number (>7 × 105 IU/mL). Our patient was diagnosed with acute exacerbation of chronic hepatitis B, and we presumed that this condition might be related to extremely elevated alpha-fetoprotein. When our patient was treated with entecavir, the serum alpha-fetoprotein level immediately decreased, in parallel with the hepatitis B virus deoxyribonucleic acid copy number. We report a rare case of extremely elevated alpha-fetoprotein due to acute exacerbation of chronic hepatitis B without any malignancy, and a decrease in this tumor marker simultaneous with a decrease in hepatitis B virus deoxyribonucleic acid copy number on entecavir treatment. This case report is important due to the rarity of the case; furthermore, it provides details of a diagnostic process for a variety of benign diseases and malignant tumors that should be considered in patients with elevated alpha-fetoprotein. Thus, we present a case report, along with a review, that will be helpful for diagnosis and treatment of patients with elevated alpha-fetoprotein.

  17. 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.

  18. Exacerbation of acute kidney injury by bone marrow stromal cells from rats with persistent renin-angiotensin system activation.

    PubMed

    Kankuri, Esko; Mervaala, Elina E; Storvik, Markus; Ahola, Aija M J; Levijoki, Jouko; Müller, Dominik N; Finckenberg, Piet; Mervaala, Eero M

    2015-06-01

    Hypertension and persistent activation of the renin-angiotensin system (RAS) are predisposing factors for the development of acute kidney injury (AKI). Although bone-marrow-derived stromal cells (BMSCs) have shown therapeutic promise in treatment of AKI, the impact of pathological RAS on BMSC functionality has remained unresolved. RAS and its local components in the bone marrow are involved in several key steps of cell maturation processes. This may also render the BMSC population vulnerable to alterations even in the early phases of RAS pathology. We isolated transgenic BMSCs (TG-BMSCs) from young end-organ-disease-free rats with increased RAS activation [human angiotensinogen/renin double transgenic rats (dTGRs)] that eventually develop hypertension and die of end-organ damage and kidney failure at 8 weeks of age. Control cells (SD-BMSCs) were isolated from wild-type Sprague-Dawley rats. Cell phenotype, mitochondrial reactive oxygen species (ROS) production and respiration were assessed, and gene expression profiling was carried out using microarrays. Cells' therapeutic efficacy was evaluated in a rat model of acute ischaemia/reperfusion-induced AKI. Serum urea and creatinine were measured at 24 h and 48 h. Acute tubular damage was scored and immunohistochemistry was used for evaluation for markers of inflammation [monocyte chemoattractant protein (MCP-1), ED-1], and kidney injury [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)]. TG-BMSCs showed distinct mitochondrial morphology, decreased cell respiration and increased production of ROS. Gene expression profiling revealed a pronounced pro-inflammatory phenotype. In contrast with the therapeutic effect of SD-BMSCs, administration of TG-BMSCs in the AKI model resulted in exacerbation of kidney injury and high mortality. Our results demonstrate that early persistent RAS activation can dramatically compromise therapeutic potential of BMSCs by causing a shift into a pro

  19. 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.

  20. Frailty is a predictive factor of readmission within 90 days of hospitalization for acute exacerbations of chronic obstructive pulmonary disease: a longitudinal study

    PubMed Central

    Bernabeu-Mora, Roberto; García-Guillamón, Gloria; Valera-Novella, Elisa; Giménez-Giménez, Luz M.; Escolar-Reina, Pilar; Medina-Mirapeix, Francesc

    2017-01-01

    Background: Readmission after hospital discharge is common in patients with acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD). Although frailty predicts hospital readmission in patients with chronic nonpulmonary diseases, no multidimensional frailty measures have been validated to stratify the risk for patients with COPD. Aim: The aim of this study was to explore multidimensional frailty as a potential risk factor for readmission due to a new exacerbation episode during the 90 days after hospitalization for AE-COPD and to test whether frailty could improve the identification of patients at high risk of readmission. We hypothesized that patients with moderate-to-severe frailty would be at greater risk for readmission within that period of follow up. A secondary aim was to test whether frailty could improve the accuracy with which to discriminate patients with a high risk of readmission. Our investigation was part of a wider study protocol with additional aims on the same study population. Methods: Frailty, demographics, and disease-related factors were measured prospectively in 102 patients during hospitalization for AE-COPD. Some of the baseline data reported were collected as part of a previously study. Readmission data were obtained on the basis of the discharge summary from patients’ electronic files by a researcher blinded to the measurements made in the previous hospitalization. The association between frailty and readmission was assessed using bivariate analyses and multivariate logistic regression models. Whether frailty better identifies patients at high risk for readmission was evaluated by area under the receiver operator curve (AUC). Results: Severely frail patients were much more likely to be readmitted than nonfrail patients (45% versus 18%). After adjusting for age and relevant disease-related factors in a final multivariate model, severe frailty remained an independent risk factor for 90-day readmission (odds ratio = 5.19; 95

  1. Shall We Focus on the Eosinophil to Guide Treatment with Systemic Corticosteroids during Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)? CON.

    PubMed

    Marcos, Pedro J; López-Campos, José Luis

    2018-06-08

    The employment of systemic corticosteroids in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) has been shown to improve airway limitation, decrease treatment failure and risk of relapse, and may improve symptoms in addition to decreasing the length of hospital stay. Nowadays, all clinical guidelines recommend systemic corticosteroids to treat moderate or severe COPD exacerbations. However, their use is associated with potential side effects, mainly hyperglycemia. In the era of precision medicine, the possibility of employing blood eosinophil count has emerged as a potential way of optimizing therapy. Issues regarding the intra-individual variability of blood eosinophil count determination, a lack of clear data regarding the real prevalence of eosinophilic acute exacerbations, the fact that previously published studies have demonstrated the benefit of systemic corticosteroids irrespective of eosinophil levels, and especially the fact that there is only one well-designed study justifying this approach have led us to think that we are not ready to use eosinophil count to guide treatment with systemic corticosteroids during acute exacerbations of COPD.

  2. Methionine sulfoxide reductase A deficiency exacerbates acute liver injury induced by acetaminophen.

    PubMed

    Singh, Mahendra Pratap; Kim, Ki Young; Kim, Hwa-Young

    2017-02-26

    Acetaminophen (APAP) overdose induces acute liver injury via enhanced oxidative stress and glutathione (GSH) depletion. Methionine sulfoxide reductase A (MsrA) acts as a reactive oxygen species scavenger by catalyzing the cyclic reduction of methionine-S-sulfoxide. Herein, we investigated the protective role of MsrA against APAP-induced liver damage using MsrA gene-deleted mice (MsrA -/- ). We found that MsrA -/- mice were more susceptible to APAP-induced acute liver injury than wild-type mice (MsrA +/+ ). The central lobule area of the MsrA -/- liver was more impaired with necrotic lesions. Serum alanine transaminase, aspartate transaminase, and lactate dehydrogenase levels were significantly higher in MsrA -/- than in MsrA +/+ mice after APAP challenge. Deletion of MsrA enhanced APAP-induced hepatic GSH depletion and oxidative stress, leading to increased susceptibility to APAP-induced liver injury in MsrA-deficient mice. APAP challenge increased Nrf2 activation more profoundly in MsrA -/- than in MsrA +/+ livers. Expression and nuclear accumulation of Nrf2 and its target gene expression were significantly elevated in MsrA -/- than in MsrA +/+ livers after APAP challenge. Taken together, our results demonstrate that MsrA protects the liver from APAP-induced toxicity. The data provided herein constitute the first in vivo evidence of the involvement of MsrA in hepatic function under APAP challenge. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Retrospective audit of antimicrobial prescribing practices for acute exacerbations of chronic obstructive pulmonary diseases in a large regional hospital.

    PubMed

    Brownridge, D J; Zaidi, S T R

    2017-06-01

    Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality, and frequent exacerbations are associated with an increased risk of death, deterioration in lung function and reduced quality of life. Current Australian guidelines developed by the Lung Foundation of Australia (the COPD-X Plan) recommends the use of a short course of corticosteroids and oral antibiotics (amoxycillin or doxycycline) as part of the treatment of an AECOPD; however, it was noted that clinical practice at the study hospital had deviated from these guidelines. To evaluate the antibiotic prescribing practices in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients, and to compare the differences in clinical outcomes (primarily mean length of stay and the rate of unplanned readmissions) between patients who received broad- vs. narrow-spectrum antibiotics in a large regional hospital. Retrospective audit of medical records for patients admitted with uncomplicated AECOPD during January-September, 2014 in a 224 acute bed regional hospital in Victoria, Australia. Fifty-nine per cent of patients received broad-spectrum antibiotics (ceftriaxone), whereas only 10% of prescriptions were concordant with current Australian guideline recommendations. Patients receiving a broad-spectrum regimen were more likely to be older (74·9 vs. 69·9 years; P = 0·009), have a higher COPD severity score (i.e. BAP-65 score, 1·55 vs. 1·06; P = 0·002) and a higher CRP (59·2 vs. 25·5 mg/L; P = 0·003) on admission. The mean LOS was not significantly different between those who received ceftriaxone and those who did not (5·09 vs. 4·55 days; P = 0·47). There was no significant difference between the groups in rates of readmissions. The antibiotic prescribing patterns for AECOPD in rural and regional Australian hospitals have not previously been examined in the current literature. In the study hospital, the majority of patients received broad

  4. Differential prognostic utility of NTproBNP and Cystatin C in patients with acute exacerbation of chronic pulmonary disease

    PubMed Central

    Pérez-Calvo, Juan I; Sánchez-Marteles, Marta; Ruiz-Ruiz, Francisco-José; Morales-Rull, José-Luis; Nieto-Rodríguez, José-Antonio

    2010-01-01

    Objectives To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease. Design Prospective, observational, non-interventional study. Setting CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease. Participants Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure. Main outcome measures NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded. Results During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44–4628.55) vs 502.70 pg/mL (95% CI 395.44–645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21–1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09–1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57–1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80–632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007). Conclusions In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can

  5. Methionine sulfoxide reductase A deficiency exacerbates acute liver injury induced by acetaminophen

    SciT

    Singh, Mahendra Pratap; School of Bioengineering and Biosciences, Department of Zoology, Lovely Professional University, Phagwara, 144411, Punjab; Kim, Ki Young

    Acetaminophen (APAP) overdose induces acute liver injury via enhanced oxidative stress and glutathione (GSH) depletion. Methionine sulfoxide reductase A (MsrA) acts as a reactive oxygen species scavenger by catalyzing the cyclic reduction of methionine-S-sulfoxide. Herein, we investigated the protective role of MsrA against APAP-induced liver damage using MsrA gene-deleted mice (MsrA{sup −/−}). We found that MsrA{sup −/−} mice were more susceptible to APAP-induced acute liver injury than wild-type mice (MsrA{sup +/+}). The central lobule area of the MsrA{sup −/−} liver was more impaired with necrotic lesions. Serum alanine transaminase, aspartate transaminase, and lactate dehydrogenase levels were significantly higher in MsrA{supmore » −/−} than in MsrA{sup +/+} mice after APAP challenge. Deletion of MsrA enhanced APAP-induced hepatic GSH depletion and oxidative stress, leading to increased susceptibility to APAP-induced liver injury in MsrA-deficient mice. APAP challenge increased Nrf2 activation more profoundly in MsrA{sup −/−} than in MsrA{sup +/+} livers. Expression and nuclear accumulation of Nrf2 and its target gene expression were significantly elevated in MsrA{sup −/−} than in MsrA{sup +/+} livers after APAP challenge. Taken together, our results demonstrate that MsrA protects the liver from APAP-induced toxicity. The data provided herein constitute the first in vivo evidence of the involvement of MsrA in hepatic function under APAP challenge. - Highlights: • MsrA deficiency increases APAP-induced liver damage. • MsrA deletion enhances APAP-induced hepatic GSH depletion and oxidative stress. • MsrA deficiency induces more profound activation of Nrf2 in response to APAP. • MsrA protects the liver from APAP-induced toxicity.« less

  6. 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

  7. Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia

    PubMed Central

    Cao, Muhua; Li, Tao; He, Zhangxiu; Wang, Lixiu; Yang, Xiaoyan; Kou, Yan; Zou, Lili; Dong, Xue; Novakovic, Valerie A.; Bi, Yayan; Kou, Junjie; Yu, Bo; Fang, Shaohong; Wang, Jinghua; Zhou, Jin

    2017-01-01

    Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death because of hemorrhage remains unacceptably common, and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs). Results from a series of coagulation assays have shown that promyelocytic extracellular chromatin increases thrombin and plasmin generation, causes a shortening of plasma clotting time of APL cells, and increases fibrin formation. DNase I but not anti-tissue factor antibody could inhibit these effects. Immunofluorescence staining showed that promyelocytic extracellular chromatin and phosphatidylserine on APL cells provide platforms for fibrin deposition and render clots more resistant to fibrinolysis. Additionally, coincubation assays revealed that promyelocytic extracellular chromatin is cytotoxic to ECs, converting them to a procoagulant phenotype. This cytotoxity was blocked by DNase I by 20% or activated protein C by 31%. Our current results thus delineate the pathogenic role of promyelocytic extracellular chromatin in APL coagulopathy. Furthermore, the remaining coagulation disturbance in high-risk APL patients after ATRA administration may be treatable by intrinsic pathway inhibition via accelerating extracellular chromatin degradation. PMID:28053193

  8. Cost analysis of an integrated care model in the management of acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Bakerly, Nawar Diar; Davies, C; Dyer, M; Dhillon, P

    2009-01-01

    Home treatment models for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) proved to be a safe alternative to hospitalization. These models have the potential to free up resources; however, in the United Kingdom, it remains unclear to whether they provide cost savings compared with hospital treatment. Over a 12-month period from August 2003, 130 patients were selected for the integrated care group (total admissions with AECOPD = 546). These patients were compared with 95 retrospective controls in the hospital treatment group. Controls were selected from admissions during the previous 12 months (total of 662 admissions) to match the integrated care group in age, sex, and postal code. Resource use data were collected for both groups and compared using National Health Service (NHS) perspective for cost minimization analysis. In the integrated care group (130 patients), 107 (82%) patients received home support with average length of stay 3.3 (SD 3.9) days compared with 10.4 (SD 7.7) in the hospital group (95 patients). Average number of visits per patients in the integrated care group was 3.08 (SD = 0.95; 95% CI = 2.9-3.2). Cost per patient in the integrated care group was pound1653 (95% CI, pound1521-1802) compared with pound2256 (95% CI, pound2126- 2407) in the hospital group. The integrated care group resulted in cost saving of approximately pound600 (P < 0.001) per patient. This integrated care model for the management of patients with AECOPD offered cost savings of pound600 per patient over the conventional hospital treatment model using the new NHS tariff from an acute trust provider perspective.

  9. Amoxicillin-clavulanate for patients with acute exacerbation of chronic rhinosinusitis: a prospective, double-blinded, placebo-controlled trial.

    PubMed

    Sabino, Henrique Augusto Cantareira; Valera, Fabiana Cardoso Pereira; Aragon, Davi Casale; Fantucci, Marina Zilio; Titoneli, Carolina Carneiro; Martinez, Roberto; Anselmo-Lima, Wilma T; Tamashiro, Edwin

    2017-02-01

    The management of acute exacerbation of chronic rhinosinusitis (AECRS) is still under debate, especially because there are no adequate studies to support a best-evidence treatment for this condition. Antibiotic use for AECRS has been recommended based on extrapolation of data from acute rhinosinusitis (ARS) or non-placebo-controlled studies. This study aimed to evaluate whether antibiotic therapy modifies the course of AECRS in a randomized, placebo-controlled study. Patients with AECRS were randomized in a double-blinded manner (2:1 ratio) to receive either amoxicillin-clavulanate 875 mg/125 mg twice daily (BID) (AMX-CLAV, n = 21) or placebo capsules (n = 11) during 14 days. All patients were also treated with mometasone furoate and nasal washes with saline. Global sinonasal symptoms (Severity Symptom Assessment [SSA]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), nasal endoscopic score (Lund-Kennedy), and microbiological evaluation were compared to evaluate the efficacy of antibiotic therapy in AECRS. Despite the majority of bacteria cultured from the middle meatus swab were sensitive for AMX-CLAV (84%), both AMX-CLAV and placebo-treated groups presented the same clinical course, with no difference between groups. Both groups exhibited overall improvement of symptoms on day 14 compared to day 0 (p < 0.01), especially the items "nasal secretion" and "nasal obstruction" (p < 0.05). We also observed the same evolution of nasal endoscopic and quality of life scores between placebo and AMX-CLAV. We concluded that AMX-CLAV for 14 days did not change the clinical course of AECRS compared with placebo. The addition of an oral antibiotic to ongoing topical intranasal steroid spray may not provide additional benefit during management of AECRS. © 2016 ARS-AAOA, LLC.

  10. Harmful impact of air pollution on severe acute exacerbation of chronic obstructive pulmonary disease: particulate matter is hazardous.

    PubMed

    Choi, Juwhan; Oh, Jee Youn; Lee, Young Seok; Min, Kyung Hoon; Hur, Gyu Young; Lee, Sung Yong; Kang, Kyung Ho; Shim, Jae Jeong

    2018-01-01

    Particulate matter and air pollution in Korea are becoming worse. There is a lack of research regarding the impact of particulate matter on patients with COPD. Therefore, the purpose of this study was to investigate the effects of various air pollution factors, including particulate matter, on the incidence rate of severe acute exacerbations of COPD (AECOPD) events. We analyzed the relationship between air pollutants and AECOPD events that required hospitalization at Guro Hospital in Korea from January 1, 2015 to May 31, 2017. We used general linear models with Poisson distribution and log-transformation to obtain adjusted relative risk (RR). We conducted further analysis through the Comprehensive Air-quality Index (CAI) that is used in Korea. Among various other air pollutants, particulate matter was identified as a major source of air pollution in Korea. When the CAI score was over 50, the incidence rate of severe AECOPD events was statistically significantly higher [RR 1.612, 95% CI, 1.065-2.440, P =0.024]. Additionally, the particulate matter levels 3 days before hospitalization were statistically significant [RR 1.003, 95% CI, 1.001-1.005, P =0.006]. Particulate matter and air pollution increase the incidence rate of severe AECOPD events. COPD patients should be cautioned against outdoor activities when particulate matter levels are high.

  11. Evaluation of platelet lymphocyte ratio and 90-day mortality in patients with acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Kumar, Praneel; Law, Stephanie; Sriram, Krishna B

    2017-06-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have high mortality and health care costs. The platelet to lymphocyte ratio (PLR) is a marker of inflammation and has been reported to be elevated in patients with AECOPD compared to stable state. In this study, we sought to evaluate the association of the PLR in patients with AECOPD with 90-day mortality. We conducted a retrospective cohort study of patients admitted to our institution with a primary diagnosis of AECOPD between January 2014 and July 2014. Blood test results on admission were recorded. The primary outcomes were 90-day mortality. One hundred and eighty-one AECOPD patients were considered for the study. Death had occurred in 16 (9%) patients within 90 days of hospital discharge. Univariable analysis identified age, haemoglobin, neutrophil count, and urea level, neutrophil lymphocyte ratio (NLR) and PLR as being associated with increased 90-day mortality. Multivariable logistic regression analysis variables demonstrated that only PLR (P=0.03) was significantly associated with death at 90 days. Receiver operator characteristic analysis identified PLR ≥235 had a sensitivity of 63% and specificity of 74% in predicting 90-day mortality. PLR was ≥235 was also associated with worse survival (days) [mean ± standard deviation (SD): PLR ≥235 vs. PLR <235: 512±358 vs. 626±346, P=0.004]. A PLR ≥235 was significantly associated with 90-day mortality, which may provide prognostic guidance to clinicians.

  12. Severe forms of fibromyalgia with acute exacerbation of pain: costs, comorbidities, and length of stay in inpatient care.

    PubMed

    Romeyke, Tobias; Noehammer, Elisabeth; Scheuer, Hans Christoph; Stummer, Harald

    2017-01-01

    As a disease of the musculoskeletal system, fibromyalgia is becoming increasingly important, because of the direct and indirect costs to health systems. The purpose of this study of health economics was to obtain information about staff costs differentiated by service provider, and staff and material costs of the nonmedical infrastructure in inpatient care. This study looked at 263 patients who received interdisciplinary inpatient treatment for severe forms of fibromyalgia with acute exacerbation of pain between 2011 and 2014. Standardized cost accounting and an analysis of additional diagnoses were performed. The average cost per patient was €3,725.84, with staff and material costs of the nonmedical infrastructure and staff costs of doctors and nurses accounting for the highest proportions of the costs. Each fibromyalgia patient had an average of 6.1 additional diagnoses. Severe forms of fibromyalgia are accompanied by many concomitant diseases and associated with both high clinical staff costs and high medical and nonmedical infrastructure costs. Indication-based cost calculations provide important information for health policy and hospital managers if they include all elements that incur costs in both a differentiated and standardized way.

  13. Modified GAP index for prediction of acute exacerbation of idiopathic pulmonary fibrosis in non-small cell lung cancer.

    PubMed

    Kobayashi, Haruki; Omori, Shota; Nakashima, Kazuhisa; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Murakami, Haruyasu; Endo, Masahiro; Takahashi, Toshiaki

    2017-10-01

    Predicting the incidence rate of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) and its prognosis in patients with non-small cell lung cancer (NSCLC) and IPF is difficult. The aim was to study the incidence of IPF-AE during the clinical course of the disease and its prognosis in patients with both NSCLC and IPF. In this retrospective study, we compared the incidence rate of AE during the clinical course of the disease as well as the 1-year survival rate and overall survival (OS) of patients with NSCLC and IPF using a modified gender, age and physiology (mGAP) staging system based on gender, age and percent predicted forced vital capacity. Of 43 patients with NSCLC and IPF included in the final analysis, 17 patients (40%; 95% CI: 26-54%) experienced AE during the clinical course of the disease. One-year survival and median OS were 41.9% (95% CI: 28-57%) and 9.4 months, respectively. Further analysis showed that the incidence of IPF-AE gradually increased and that the 1-year survival rate and median OS gradually decreased with increasing mGAP index score and stage. Our study suggested that mGAP index score and cancer stage may predict IPF-AE and its prognosis in patients with NSCLC and IPF. © 2017 Asian Pacific Society of Respirology.

  14. Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

    PubMed Central

    dos Santos, G.C.; Parra, E.R.; Stegun, F.W.; Cirqueira, C.S.; Capelozzi, V.L.

    2013-01-01

    Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures. PMID:24270907

  15. Multicentre investigation of pathogenic bacteria and antibiotic resistance genes in Chinese patients with acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Ma, Xiuqing; Cui, Junchang; Wang, Jing; Chang, Yan; Fang, Qiuhong; Bai, Changqing; Zhou, Xiumei; Zhou, Hong; Feng, Huasong; Wang, Ying; Zhao, Weiguo; Wen, Zhongguang; Wang, Ping; Liu, Yi; Yu, Ling; Li, Chunsun; Chen, Liangan

    2015-10-01

    A prospective observational study to investigate the distribution and antimicrobial resistance of pathogenic bacteria in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing, China. Patients with AECOPD were recruited from 11 general hospitals. Sputum specimens were cultured and bacteria identified. Antibiotic susceptibility was determined for each isolate, and presence of antibiotic resistance genes was evaluated using polymerase chain reaction. Pathogenic bacteria were isolated from 109/318 patients (34.28%); 124 isolates of 22 pathogenic bacterial species were identified, including Klebsiella pneumoniae (16.94%), Pseudomonas aeruginosa (16.94%), Acinetobacter baumannii (11.29%), Streptococcus pneumoniae (8.87%), and Staphylococcus aureus (7.26%). S. aureus was sensitive to tigecycline, teicoplanin, vancomycin and linezolid but resistant to penicillin and levofloxacin. K.pneumoniae, P. aeruginosa, A. baumannii and E. coli were susceptible to amikacin and cefoperazone. K. pneumoniae and P. aeruginosa are the most common pathogenic bacteria in AECOPD cases in Beijing, China. Our antibiotic resistance findings may be helpful in selecting antibiotic therapy. © The Author(s) 2015.

  16. Intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation: an interview study.

    PubMed

    Kvangarsnes, Marit; Torheim, Henny; Hole, Torstein; Öhlund, Lennart S

    2013-02-01

    To report a study conducted to explore intensive care unit nurses' perceptions of patient participation in the acute phase of chronic obstructive pulmonary disease exacerbation. An acute exacerbation is a life-threatening situation, which patients often consider to be extremely frightening. Healthcare personnel exercise considerable power in this situation, which challenges general professional notions of patient participation. Critical discourse analysis. In the autumn of 2009, three focus group interviews with experienced intensive care nurses were conducted at two hospitals in western Norway. Two groups had six participants each, and one group had five (N = 17). The transcribed interviews were analysed by means of critical discourse analysis. The intensive care nurses said that an exacerbation is often an extreme situation in which healthcare personnel are exercising a high degree of control and power over patients. Patient participation during exacerbation often takes the form of non-involvement. The participating nurses attached great importance to taking a sensitive approach when meeting patients. The nurses experienced challenging ethical dilemmas. This study shows that patient participation should not be understood in universal terms, but rather in relation to a specific setting and the interactions that occur in this setting. Healthcare personnel must develop skill, understanding, and competence to meet these challenging ethical dilemmas. A collaborative inter-professional approach between physicians and nurses is needed to meet the patients' demand for involvement. © 2012 Blackwell Publishing Ltd.

  17. Randomized, double-blind study of grepafloxacin versus amoxycillin in patients with acute bacterial exacerbations of chronic bronchitis.

    PubMed

    Langan, C E; Cranfield, R; Breisch, S; Pettit, R

    1997-12-01

    This randomized, multicentre, double-blind, double-dummy study compared the efficacy and safety of grepafloxacin and amoxycillin in acute bacterial exacerbations of chronic bronchitis (ABECB). Patients were randomized to receive grepafloxacin 400 mg or 600 mg od, or amoxycillin 500 mg tds, for 7 or 10 days. The trial recruited 656 patients, of whom 566 (86%) completed the study. Clinical success rates at the 2 week follow-up visit for the population evaluable for clinical efficacy were 82% (165/202 patients) in the grepafloxacin 400 mg group, 85% (175/206) in the grepafloxacin 600 mg group and 85% (172/203 patients) in the amoxycillin group. The 95% confidence interval confirmed the equivalence of the two grepafloxacin doses and amoxycillin, with no significant difference between the grepafloxacin groups. The microbiological success rates at follow-up showed equivalence between the grepafloxacin 400 mg and amoxycillin groups: 86% (144/168 isolates) and 83% (162/195), respectively. The grepafloxacin 600 mg group achieved a statistically significantly higher eradication rate (92%, 150/164; 95% CI 2.0%, 16.1%) than the amoxycillin group in the follow-up assessment for microbiological and clinical efficacy (evaluable population). There was no significant difference between the two grepafloxacin treatment groups (95% CI -13.3%, 0.9%; P= 0.087). All three treatment regimens successfully eradicated the pathogens most commonly isolated during the study, including Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae. Grepafloxacin had a good safety profile, comparable to that of amoxycillin, although grepafloxacin 600 mg was associated with a higher incidence of nausea, dyspepsia and taste perversion than amoxycillin. It can be concluded that grepafloxacin 400 mg or 600 mg od is as effective as amoxycillin 500 mg tds in the treatment of ABECB.

  18. High-dose methylprednisolone treatment of laser-induced retinal injury exacerbates acute inflammation and long-term scarring

    NASA Astrophysics Data System (ADS)

    Schuschereba, Steven T.; Cross, Michael E.; Scales, David K.; Pizarro, Jose M.; Edsall, Peter R.; Stuck, Bruce E.; Marshall, John

    1999-06-01

    Purpose. To evaluate therapeutics for attenuating retinal laser injury. Methods. New Zealand Red rabbits (n=76) were pretreated (IV) with either a single dose of hydroxyethyl starch conjugated deferoxamine (HES-DFO, n=29) (6.1 ml/kg, 16.4 mg/ml) or methylprednisolone sodium succinate (MP, n=22) (30 mg/kg, followed by taper of 30, 20, 20, and 10 mg/kg/day for a total of 5d). Controls were untreated (n=25). Fifteen min later, animals were irradiated with a multiline cw argon laser (285 mW, 10 msec pulse durations, 16 lesions/eye). Funduscopy, fluorescein angiography, histology, and morphometry were performed at 10 min, 1h, 3h, 24h, 1 mo, and 6 mo after irradiation. Leukocytes were counted at lesion centers for retinal and choroidal compartments at 1, 3, and 24h. Results. At 3h, percent area incrase for the lesions was highest for MP (44%) and lowest for HES-DFO (16%)(p<0.05). In hemorrhagic lesions, MP treatment resulted in the highest increase of retinal neotrophils by 24h (p<0.05), and by 1 and 6 mo extensive chorio-retinal scarring occurred in nonhemorrhagic and hemorrhagic lesions. Also, no benefit was demonstrated on sparing of photoreceptors with MP treatment. Conclusions. Treatment of laser-induced retinal injury with methylprednisolone (MP) exacerbates acute inflammation and long-term chorio-retinal scarring; however, hydroxyethyl starch conjugated deferoxamine therapy ameliorates these aspects of injury. Data suggest caution in the use of MP therapy for laser injuries.

  19. Low forced vital capacity predicts cytotoxic chemotherapy-associated acute exacerbation of interstitial lung disease in patients with lung cancer.

    PubMed

    Enomoto, Yasunori; Inui, Naoki; Kato, Terufumi; Baba, Tomohisa; Karayama, Masato; Nakamura, Yutaro; Ogura, Takashi; Suda, Takafumi

    2016-06-01

    Although acute exacerbation of pre-existing interstitial lung disease (AE-ILD) associated with cytotoxic chemotherapy has been recognized as a severe complication in lung cancer treatment, its risk factors have not been fully studied. Among lung cancer patients receiving cytotoxic chemotherapy, patients with pre-existing ILD were identified based on the pretreatment high-resolution computed tomography (HRCT) findings. Chemotherapy-associated AE-ILD was defined as deterioration or development of dyspnea and HRCT findings of new bilateral ground-glass attenuations with/without non-segmental consolidation superimposed on pre-existing interstitial shadows, without evidence of pulmonary infection, congestion, or pulmonary embolism, within four weeks after the last administration of chemotherapy. Baseline characteristics were reviewed and the risk factors for chemotherapy-associated AE-ILD were evaluated by logistic regression analyses. Among 85 patients identified as having pre-existing ILD, chemotherapy-associated AE-ILD occurred in 26 patients (30.6%); 8 patients died and 11 patients had a severely deteriorated general condition despite intensive treatment. Compared with those without AE-ILD, patients with AE-ILD had significantly lower forced vital capacity (FVC) (median: 91.1% versus 76.6%, P=0.01). Univariate and multivariate logistic regression analyses identified baseline lower FVC and non-small cell lung cancer (NSCLC) as the risk factors for this severe event (odds ratio of FVC: 0.97, 95% confidence interval: 0.94-0.99; odds ratio of NSCLC: 4.65, 95% confidence interval: 1.10-19.76). Chemotherapy-associated AE-ILD was a frequent and lethal complication in lung cancer treatment for patients with pre-existing ILD. Spirometric assessment of pulmonary function may be useful to predict the event. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Cystathionine γ-Lyase Deficiency Exacerbates CCl4-Induced Acute Hepatitis and Fibrosis in the Mouse Liver.

    PubMed

    Ci, Lei; Yang, Xingyu; Gu, Xiaowen; Li, Qing; Guo, Yang; Zhou, Ziping; Zhang, Mengjie; Shi, Jiahao; Yang, Hua; Wang, Zhugang; Fei, Jian

    2017-07-20

    The present study examined the role of cystathionine γ-lyase (CSE) in carbon tetrachloride (CCl 4 )-induced liver damage. A CSE gene knock-out and luciferase gene knock-in (KI) mouse model was constructed to study the function of CSE and to trace its expression in living status. CCl 4 or lipopolysaccharide markedly downregulated CSE expression in the liver of mice. CSE-deficient mice showed increased serum alanine aminotransferase and aspartate aminotransferase levels, and liver damage after CCl 4 challenge, whereas albumin and endogenous hydrogen sulfide (H 2 S) levels decreased significantly. CSE knockout mice showed increased serum homocysteine levels, upregulation of inflammatory cytokines, and increased autophagy and IκB-α degradation in the liver in response to CCl 4 treatment. The increase in pro-inflammatory cytokines, including tumor necrosis factor-alpha in CSE-deficient mice after CCl 4 challenge, was accompanied by a significant increase in liver tissue hydroxyproline and α-smooth muscle actin and histopathologic changes in the liver. However, H 2 S donor pretreatment effectively attenuated most of these imbalances. Here, a CSE knock-out and luciferase KI mouse model was established for the first time to study the transcriptional regulation of CSE expression in real time in a non-invasive manner, providing information on the effects and potential mechanisms of CSE on CCl 4 -induced liver injury. CSE deficiency increases pro-inflammatory cytokines in the liver and exacerbates acute hepatitis and liver fibrosis by reducing H 2 S production from L-cysteine in the liver. The present data suggest the potential of an H 2 S donor for the treatment of liver diseases such as toxic hepatitis and fibrosis. Antioxid. Redox Signal. 27, 133-149.

  1. Risk factors for acute exacerbations of COPD in a primary care population: a retrospective observational cohort study

    PubMed Central

    Müllerová, Hana; Shukla, Amit; Hawkins, Adam; Quint, Jennifer

    2014-01-01

    Objectives To evaluate risk factors associated with exacerbation frequency in primary care. Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts. Design Retrospective observational cohort study. Setting Electronic medical records database (England and Wales). Participants 58 589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink. Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted. Outcome measures Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics. Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models. Results During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none). Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer). Conclusions Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. PMID:25524545

  2. Risk factors for acute exacerbations of COPD in a primary care population: a retrospective observational cohort study.

    PubMed

    Müllerová, Hana; Shukla, Amit; Hawkins, Adam; Quint, Jennifer

    2014-12-18

    To evaluate risk factors associated with exacerbation frequency in primary care. Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts. Retrospective observational cohort study. Electronic medical records database (England and Wales). 58,589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink. Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted. Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics. Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models. During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none). Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer). Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions. 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.

  3. Trends in Outcomes, Financial Burden, and Mortality for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) in the United States from 2002 to 2010.

    PubMed

    Jinjuvadia, Chetna; Jinjuvadia, Raxitkumar; Mandapakala, Chaitanya; Durairajan, Navin; Liangpunsakul, Suthat; Soubani, Ayman O

    2017-02-01

    Chronic obstructive pulmonary disease (COPD) is the cause of substantial economic and social burden. We evaluated the temporal trends of hospitalizations from acute exacerbation of COPD and determined its outcome and financial impact using the National (Nationwide) Inpatient Sample (NIS) databases (2002-2010). Individuals aged ≥ 18 years were included. Subjects who were hospitalized with primary diagnosis of COPD exacerbation and those who were admitted for other causes but had underlying acute exacerbation of COPD (secondary diagnosis) were captured by International Classification of Diseases-Ninth Revision (ICD-9) codes. The hospital outcomes and length of stay were determined. Multivariate logistic regression was used to identify the independent predictors of inpatient mortality. Overall acute exacerbation of COPD-related hospitalizations accounted for nearly 3.31% of all hospitalizations in the year 2002. This did not change significantly to year 2010 (3.43%, p = 0.608). However, there was an increase in hospitalization with secondary diagnosis of COPD. Elderly white patients accounted for most of the hospitalizations. Medicare was the primary payer source for most of the hospitalizations (73-75%). There was a significant decrease in inpatient mortality from 4.8% in 2002 to 3.9% in 2010 (slope -0.096, p < 0.001). Similarly, there was a significant decrease in average length of stay from 6.4 days in 2002 to 6.0 days in 2010 (slope -0.042, p < 0.001). Despite this, the hospitalization cost was increased substantially from $22,187 in 2002 to $38,455 in 2010. However, financial burden has increased over the years.

  4. Importance of Aspergillus spp. isolation in Acute exacerbations of severe COPD: prevalence, factors and follow-up: the FUNGI-COPD study

    PubMed Central

    2014-01-01

    Background Acute exacerbations of COPD (AECOPD) are often associated with infectious agents, some of which may be non-usual, including Aspergillus spp. However, the importance of Aspergillus spp. in the clinical management of AECOPD still remains unclear. Objectives The aims of the study were to analyze the prevalence and risk factors associated with Aspergillus spp. isolation in AECOPD, and to investigate the associated clinical outcomes during a 1-year follow-up period. Methods Patients presenting with an AECOPD requiring hospitalization were prospectively included from four hospitals across Spain. Clinical, radiological and microbiological data were collected at admission and during the follow-up period (1, 6 and 12 months after discharge), and re-admissions and mortality data collected during the follow-up. Results A total of 240 patients with severe AECOPD were included. Valid sputum samples were obtained in 144 (58%) patients, and in this group, the prevalence of Aspergillus spp. isolation was 16.6% on admission and 14.1% at one-year follow-up. Multivariate logistic-regression showed that AECOPD in the previous year (OR 12.35; 95% CI, 1.9-29.1; p < 0.001), concurrent isolation of pathogenic bacteria (OR 3.64; 95% CI 1.65-9.45, p = 0.001) and concomitant isolation of Pseudomonas aeruginosa (OR 2.80; 95% IC, 1.81-11.42; p = 0.001) were the main risk factors for Aspergillus spp. isolation. Conclusions The main risk factors for Aspergillus spp. isolation were AECOPD in the previous year and concomitant isolation of Pseudomonas aeruginosa. However, although Aspergillus spp. is often isolated in sputum samples from patients with AECOPD, the pathogenic and clinical significance remains unclear. PMID:24517318

  5. The association between glucose levels and hospital outcomes in patients with acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Islam, Ebtesam A.; Limsuwat, Chok; Nantsupawat, Teerapat; Berdine, Gilbert G.; Nugent, Kenneth M.

    2015-01-01

    BACKGROUND: Corticosteroids used for chronic obstructive pulmonary disease (COPD) exacerbations can cause hyperglycemia in hospitalized patients, and hyperglycemia may be associated with increased mortality, length of stay (LOS), and re-admissions in these patients. MATERIALS AND METHODS: We did three retrospective studies using charts from July 2008 through June 2009, January 2006 through December 2010, and October 2010 through March 2011. We collected demographic and clinical information, laboratory results, radiographic results, and information on LOS, mortality, and re-admission. RESULTS: Glucose levels did not predict outcomes in any of the studied cohorts, after adjustment for covariates in multivariable analysis. The first database included 30 patients admitted to non-intensive care unit (ICU) hospital beds. Six of 20 non-diabetic patients had peak glucoses above 200 mg/dl. Nine of the ten diabetic patients had peak glucoses above 200 mg/dl. The maximum daily corticosteroid dose had no apparent effect on the glucose levels. The second database included 217 patients admitted to ICUs. The initial blood glucose was higher in patients who died than those who survived using bivariate analysis (P = 0.015; odds ratio, OR, 1.01) but not in multivariable analysis. Multivariable logistic regression analysis also demonstrated that glucose levels did not affect LOS. The third database analyzing COPD re-admission rates included 81 patients; the peak glucose levels were not associated with re-admission. CONCLUSIONS: Our data demonstrate that COPD patients treated with corticosteroids developed significant hyperglycemia, but the increase in blood glucose levels did not correlate with the maximum dose of corticosteroids. Blood glucose levels were not associated with mortality, LOS, or re-admission rates. PMID:25829959

  6. Acute Exacerbation of Hepatitis in Liver Cirrhosis with Very High Levels of alpha-Fetoprotein But No Occurrence of Hepatocellular Carcinoma

    PubMed Central

    Park, Sang Jong; Park, Kwang Bo; Paik, So Ya; Ryu, Jin Kyung; Choi, Chang Kyu; Hwang, Tae Joon

    2005-01-01

    Aminotransferase levels do not always increase during acute hepatitis or during an acute flare-up of chronic hepatitis. Persistently increased levels of serum alpha-Fetoprotein in an adult with liver disease suggest not only the presence or progression of hepatocellular carcinoma or its recurrence after hepatic resection or after other therapeutic approaches such as chemotherapy or chemoembolization, but also it suggests that there is an acute exacerbation of hepatitis or liver cirrhosis. We report here on two unusual cases of HBV- & HCV-related liver cirrhosis with acute exacerbation of hepatitis in which there was an insignificant elevation of the aminotransferase levels, but there were markedly increased alpha-Fetoprotein levels observed. The levels of alpha-Fetoprotein decreased gradually in both cases since the beginning of antiviral therapy, which implies that the increased levels were due to aggravation of the accompanying hepatitis. These cases also emphasize that using only the measurement of alpha-Fetoprotein is not sufficient for the diagnosis of hepatocellular carcinoma, and that this diagnosis also requires a more specific measurement such as AFP L3 along with the standard imaging studies. PMID:15906959

  7. Changes in plasma levels of B-type natriuretic peptide with acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Nishimura, Koichi; Nishimura, Takashi; Onishi, Katsuya; Oga, Toru; Hasegawa, Yoshinori; Jones, Paul W

    2014-01-01

    Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD). In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited. Plasma BNP levels were compared cross-sectionally and longitudinally. Transthoracic echocardiographic examinations were also performed in the hospitalized subjects. In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9-129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0-45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0-53.7) for grade II; 22.1 (9.1-52.6) for grade III; and 17.2 (9.6-22.9) pg/mL for grade I V, all P<0.001. In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8-32.2) pg/mL before AECOPD, 72.7 (27.7-146.3) pg/mL during AECOPD, and 14.6 (12.9-39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively). Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4-555.0) than in 48 successfully discharged subjects 48.5 (24.2-104.0) pg/mL (P=0.0066). Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms. BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman's rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman's rank correlation

  8. Significance of NT-pro-BNP in acute exacerbation of COPD patients without underlying left ventricular dysfunction.

    PubMed

    Adrish, Muhammad; Nannaka, Varalaxmi Bhavani; Cano, Edison J; Bajantri, Bharat; Diaz-Fuentes, Gilda

    2017-01-01

    B-type natriuretic peptide (BNP) and the N-terminal fragment of pro-BNP (NT-pro-BNP) are established biomarkers of heart failure. Increased levels of natriuretic peptide (NP) have been associated with poor outcomes in acute exacerbation of COPD (AECOPD); however, most studies did not address the conditions that can also increase NT-pro-BNP levels. We aimed to determine if NT-pro-BNP levels correlate with outcomes of AECOPD in patients without heart failure and other conditions that can affect NT-pro-BNP levels. We conducted a retrospective study in patients hospitalized for AECOPD with available NT-pro-BNP levels and normal left ventricular ejection fraction. We compared patients with normal and elevated NT-pro-BNP levels and analyzed the clinical and outcome data. A total of 167 of 1,420 (11.7%) patients met the study criteria. A total of 77% of male patients and 53% of female patients had elevated NT-pro-BNP levels ( P =0.0031). NT-pro-BNP levels were not associated with COPD severity and comorbid illnesses. Log-transformed NT-pro-BNP levels were positively associated with echocardiographically estimated right ventricular systolic pressure ( r =0.3658; 95% confidence interval [CI]: 0.2060-0.5067; P <0.0001). Patients with elevated NT-pro-BNP levels were more likely to require intensive care (63% vs 43%; P =0.0207) and had a longer hospital length of stay ( P =0.0052). There were no differences in the need for noninvasive positive pressure ventilation ( P =0.1245) or mechanical ventilation ( P =0.9824) or in regard to in-hospital mortality ( P =0.5273). Patients with AECOPD and elevated NT-pro-BNP levels had increased hospital length of stay and need for intensive care. Based on our study, serum NT-pro-BNP levels cannot be used as a biomarker for increased mortality or requirement for invasive or noninvasive ventilation in this group of patients.

  9. [Proportion and prevention of venous thromboembolism among hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease in Beijing].

    PubMed

    Liang, Li-rong; Zhang, Zhu; Wang, Hong; Xu, Zhen-yang; Qian, Xiao-sen; Zhang, Zuo-qing; Chen, Jin; Zhang, Feng-zhen; Yang, Yuan-hua

    2013-08-13

    To explore the proportion and prevention status of venous thromboembolism (VTE) among hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing. Based on a multi-center retrospective study, a total of 636 hospitalized AECOPD patients from 17 class 2/3 hospitals in Beijing were examined from September 1, 2011 to March 31, 2012. They fulfilled one of the following criteria: respiratory failure type II, on invasive or non-invasive mechanical ventilation, hospitalization for pulmonary infection, bedridden duration ≥ 3 days and congestive heart failure. All investigators received standardized training and used a standardized questionnaire to collect data on VTE risk factors, the diagnosis of VTE and the utilization of VTE prophylaxis. According to Caprini score, they were categorized into 3 groups of lower risk (Caprini score ≤ 3), moderate risk (Caprini score 4-6) and high risk ( ≥ 7) to compare the intergroup differences in the VTE proportion and the utilization of VTE prophylaxis. A total of 636 patients were assessed. There were 416 males and 220 females with a mean (SD) age of 74.9 ± 9.3 years. Among them, 133 patients received lower extremity venous ultrasonic examination and 92 were diagnosed with deep venous thrombosis (DVT) including 2 patients with pulmonary thromboembolism (PTE). Thus the overall incidence of VTE was 14.5% (92/636) and increased with age (Ptrend = 0.044). The proportion of VTE in asymptomatic patients was higher in those symptomatic ones (21.1% vs 8.0%, P = 0.000). And it was the highest in high risk group, followed by lower risk and moderate risk groups at 17.9% (14/78), 16.0% (26/163) and 13.2% (52/395) respectively, There was no statistical significance (P = 0.450 for group difference, Ptrend = 0.946). Among 544 patients without VTE, only 19.1% (104/544) employed the pharmacologic and/or mechanical methods for preventing VTE. The prevention proportion gradually increased with rising

  10. Self-treatment of acute exacerbations of chronic obstructive pulmonary disease requires more than symptom recognition - a qualitative study of COPD patients' perspectives on self-treatment.

    PubMed

    Laue, Johanna; Melbye, Hasse; Risør, Mette Bech

    2017-01-25

    Self-treatment of acute exacerbations of COPD with antibiotics and/or oral corticosteroids has emerged as a promising strategy to reduce hospitalization rates, mortality and health costs. However, for reasons little understood, the effect of self-treatment, particularly when not part of comprehensive self-management programs, remains unclear. Therefore, this study aims to get insight into the patients' perspective on self-treatment of acute exacerbations of COPD, focusing specifically on how patients decide for the right moment to start treatment with antibiotics and/or oral corticosteroids, what they consider important when making this decision and aspects which might interfere with successful implementation. We interviewed 19 patients with chronic obstructive pulmonary disease using qualitative semi-structured interviews, and applied thematic analysis for data analysis. Patients were well equipped with experiential knowledge to recognize and promptly respond to worsening COPD symptoms. Worries regarding potential adverse effects of antibiotics and oral corticosteroids played an important role in the decision to start treatment and could result in hesitation to start treatment. Although self-treatment represented a practical and appreciated option for some patients with predictable symptom patterns and treatment effect, all patients favoured assistance from a medical professional when their perceived competence reached its limits. However, a feeling of obligation to succeed with self-treatment or distrust in their doctors or the health care system could keep patients from timely help seeking. COPD patients regard self-treatment of exacerbations with antibiotics and/or oral corticosteroids as a valuable alternative. How they engage in self-treatment depends on their concerns regarding the medications' adverse effects as well as on their understanding of and preferences for self-treatment as a means of health care. Caregivers should address these perspectives in a

  11. 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

  12. β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol

    PubMed Central

    Bhatt, Surya P; Connett, John E; Voelker, Helen; Lindberg, Sarah M; Westfall, Elizabeth; Wells, J Michael; Lazarus, Stephen C; Criner, Gerard J; Dransfield, Mark T

    2016-01-01

    Introduction A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. Methods and analyses This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. Ethics and dissemination The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national

  13. β-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (βLOCK COPD): a randomised controlled study protocol.

    PubMed

    Bhatt, Surya P; Connett, John E; Voelker, Helen; Lindberg, Sarah M; Westfall, Elizabeth; Wells, J Michael; Lazarus, Stephen C; Criner, Gerard J; Dransfield, Mark T

    2016-06-07

    A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest β-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3-year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national and international conferences and publications in peer

  14. Acute Ozone (O3) Exposure Enhances Aortic Contraction in Healthy Rats while Exacerbating Pulmonary Injury in Diabetics

    EPA Science Inventory

    Air pollution exposure affects health adversely in individuals with type 2 diabetes (T2D) and diet induced obesity (DIO). We hypothesized that T2D and DIO would exacerbate O3 induced pulmonary responses and alter arterial reactivity. Male Wistar and Goto Kakizaki (GK) rats, a l...

  15. Is It Time to Change the Definition of Acute Exacerbation of Chronic Obstructive Pulmornary Disease? What Do We Need to Add?

    PubMed

    Montes de Oca, Maria; Laucho-Contreras, Maria Eugenia

    2018-06-14

    Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) are associated with increased mortality, rate of hospitalization, use of healthcare resources, and have a negative impact on disease progression, quality of life and lung function of patients with chronic obstructive pulmonary disease (COPD). There is an imperative need to homogenize the definition of AECOPD because the incidence of exacerbations has a significant influence or implication on treatment decision making, particularly in pharmacotherapy and could impact the outcome or change the statistical significance of a therapeutic intervention in clinical trials. In this review, using PubMed searches, we have analyzed the weaknesses and strengths of the different used AECOPD definitions (symptom-based, healthcare-based definition or the combinations of both), as well as the findings of the studies that have assessed the relationship of different biomarkers with the diagnosis, etiology and differential diagnosis of AECOPD and the progress towards the development of a more precise definition of COPD exacerbation. Finally, we have proposed a simple definition of AECOPD, which must be validated in future clinical trials to define its accuracy and usefulness in daily practice.

  16. Acute care costs of patients admitted for management of chronic obstructive pulmonary disease exacerbations: contribution of disease severity, infection and chronic heart failure.

    PubMed

    Hutchinson, A; Brand, C; Irving, L; Roberts, C; Thompson, P; Campbell, D

    2010-05-01

    In 2003, chronic obstructive pulmonary disease (COPD) accounted for 46% of the burden of chronic respiratory disease in the Australian community. In the 65-74-year-old age group, COPD was the sixth leading cause of disability for men and the seventh for women. To measure the influence of disease severity, COPD phenotype and comorbidities on acute health service utilization and direct acute care costs in patients admitted with COPD. Prospective cohort study of 80 patients admitted to the Royal Melbourne Hospital in 2001-2002 for an exacerbation of COPD. Patients were followed for 12 months and data were collected on acute care utilization. Direct hospital costs were derived using Transition II, an activity-based costing system. Individual patient costs were then modelled to ascertain which patient factors influenced total direct hospital costs. Direct costs were calculated for 225 episodes of care, the median cost per admission was AU$3124 (interquartile range $1393 to $5045). The median direct cost of acute care management per patient per year was AU$7273 (interquartile range $3957 to $14 448). In a multivariate analysis using linear regression modelling, factors predictive of higher annual costs were increasing age (P= 0.041), use of domiciliary oxygen (P= 0.008) and the presence of chronic heart failure (P= 0.006). This model has identified a number of patient factors that predict higher acute care costs and awareness of these can be used for service planning to meet the needs of patients admitted with COPD.

  17. Shuttle walking test and 6-minute walking test induce a similar cardiorespiratory performance in patients recovering from an acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Vagaggini, B; Taccola, M; Severino, S; Marcello, M; Antonelli, S; Brogi, S; De Simone, C; Giardina, A; Paggiaro, P L

    2003-01-01

    The incremental shuttle walking test (SWT) has recently been proposed as a more valid and reproducible alternative to the conventional 6-min walking test (6MWT) in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). To compare the cardiorespiratory performance obtained during two sessions of SWT with that obtained during two sessions of 6MWT. We examined 18 patients (forced expiratory volume in 1 s: 48 +/- 14%) recovering from an acute exacerbation of COPD that had required hospitalization. In the same afternoon, each patient performed two SWT and two 6MWT, with an interval of at least 30 min between each test; the sequence of the tests was randomized. Mean walking distance was greater in the second SWT test than in the first SWT. The changes from baseline in systolic blood pressure, heart rate, respiratory rate, oxygen saturation and dyspnea Borg index at the end of the test were similar between the two 6MWT and the two SWT. There was a highly significant correlation between walking distances measured during SWT and during 6MWT (rho: 0.85, p < 0.0005). Neither SWT nor 6MWT correlated with functional data of COPD. SWT, though being considered to be closer to a submaximal exercise test than 6MWT, does not induce a greater cardiorespiratory performance than 6MWT in patients recovering from acute exacerbation of COPD. Copyright 2003 S. Karger AG, Basel

  18. Beneficial effects of warmed humidified oxygen combined with nebulized albuterol and ipratropium in pediatric patients with acute exacerbation of asthma in winter months.

    PubMed

    Nibhanipudi, Kumara; Hassen, Getaw Worku; Smith, Arthur

    2009-11-01

    The objective of this study was to determine whether a combination of nebulized albuterol and ipratropium with warmed humidified oxygen would be more beneficial when compared to the same combination with humidified oxygen at room temperature. Albuterol alone was tested in the same settings. All patients between 6 and 17 years of age who presented to a pediatric emergency department in the winter months with acute exacerbation of bronchial asthma were given a combination of nebulized albuterol and ipratropium with warmed or room temperature humidified oxygen. Peak flow was measured before and after the treatment. Sixty patients were enrolled in the study, with 15 subjects in each group. The mean increase in peak flow in the albuterol-ipratropium with warm humidified oxygen group was 52.6, and in the albuterol-ipratropium with humidified oxygen at room temperature group, it was 26.2. The results of the albuterol with warmed humidified oxygen and with humidified oxygen at room temperature groups were 20.6 and 34.3, respectively. The differences between the groups were statistically significant. Our study shows that warmed humidified oxygen given along with the combination of nebulized albuterol and ipratropium is more beneficial for pediatric patients having an acute exacerbation of bronchial asthma in the winter months when compared to nebulized albuterol alone with warmed humidified oxygen, nebulized albuterol alone with room temperature humidified oxygen, or a combination of nebulized albuterol and ipratropium with room temperature humidified oxygen.

  19. Cost-effectiveness of FreeO2 in patients with chronic obstructive pulmonary disease hospitalised for acute exacerbations: analysis of a pilot study in Quebec.

    PubMed

    Poder, Thomas G; Kouakou, Christian R C; Bouchard, Pierre-Alexandre; Tremblay, Véronique; Blais, Sébastien; Maltais, François; Lellouche, François

    2018-01-23

    Conduct a cost-effectiveness analysis of FreeO 2 technology versus manual oxygen-titration technology for patients with chronic obstructive pulmonary disease (COPD) hospitalised for acute exacerbations. Tertiary acute care hospital in Quebec, Canada. 47 patients with COPD hospitalised for acute exacerbations. An automated oxygen-titration and oxygen-weaning technology. The costs for hospitalisation and follow-up for 180 days were calculated using a microcosting approach and included the cost of FreeO 2 technology. Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap resampling with 5000 replications. The main effect variable was the percentage of time spent at the target oxygen saturation (SpO 2 ). The other two effect variables were the time spent in hyperoxia (target SpO 2 +5%) and in severe hypoxaemia (SpO 2 <85%). The resamplings were based on data from a randomised controlled trial with 47 patients with COPD hospitalised for acute exacerbations. FreeO 2 generated savings of 20.7% of the per-patient costs at 180 days (ie, -$C2959.71). This decrease is nevertheless not significant at the 95% threshold (P=0.13), but the effect variables all improved (P<0.001). The improvement in the time spent at the target SpO 2 was 56.3%. The ICERs indicate that FreeO 2 technology is more cost-effective than manual oxygen titration with a savings of -$C96.91 per percentage point of time spent at the target SpO 2 (95% CI -301.26 to 116.96). FreeO 2 technology could significantly enhance the efficiency of the health system by reducing per-patient costs at 180 days. A study with a larger patient sample needs to be carried out to confirm these preliminary results. NCT01393015; Post-results. © 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.

  20. Cost-effectiveness of FreeO2 in patients with chronic obstructive pulmonary disease hospitalised for acute exacerbations: analysis of a pilot study in Quebec

    PubMed Central

    Poder, Thomas G; Kouakou, Christian R C; Bouchard, Pierre-Alexandre; Tremblay, Véronique; Blais, Sébastien; Maltais, François; Lellouche, François

    2018-01-01

    Objective Conduct a cost-effectiveness analysis of FreeO2 technology versus manual oxygen-titration technology for patients with chronic obstructive pulmonary disease (COPD) hospitalised for acute exacerbations. Setting Tertiary acute care hospital in Quebec, Canada. Participants 47 patients with COPD hospitalised for acute exacerbations. Intervention An automated oxygen-titration and oxygen-weaning technology. Methods and outcomes The costs for hospitalisation and follow-up for 180 days were calculated using a microcosting approach and included the cost of FreeO2 technology. Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap resampling with 5000 replications. The main effect variable was the percentage of time spent at the target oxygen saturation (SpO2). The other two effect variables were the time spent in hyperoxia (target SpO2+5%) and in severe hypoxaemia (SpO2 <85%). The resamplings were based on data from a randomised controlled trial with 47 patients with COPD hospitalised for acute exacerbations. Results FreeO2 generated savings of 20.7% of the per-patient costs at 180 days (ie, −$C2959.71). This decrease is nevertheless not significant at the 95% threshold (P=0.13), but the effect variables all improved (P<0.001). The improvement in the time spent at the target SpO2 was 56.3%. The ICERs indicate that FreeO2 technology is more cost-effective than manual oxygen titration with a savings of −$C96.91 per percentage point of time spent at the target SpO2 (95% CI −301.26 to 116.96). Conclusion FreeO2 technology could significantly enhance the efficiency of the health system by reducing per-patient costs at 180 days. A study with a larger patient sample needs to be carried out to confirm these preliminary results. Trial registration number NCT01393015; Post-results. PMID:29362258

  1. 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.

  2. 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

  3. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study

    PubMed Central

    Li, Huafang; Li, Yan; Feng, Yu; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson

    2018-01-01

    Purpose To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week), differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. Patients and methods PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18–65 years) diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score), secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire) and safety were assessed in this post hoc analysis. Results Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates (P≤0.01), PANSS subscales (positive and general psychopathology; all P≤0.01), PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P≤0.01), Personal and Social Performance scale scores (P≤0.05) and Clinical Global Impression-Severity categorical summary (P≤0.05) were significantly greater in the ≤1 week subgroup versus >1 week subgroup (P≤0.05). The readiness for hospital discharge questionnaire improved over time for the overall study population, but remained similar between subgroups at all-time points. Treatment-emergent adverse events were similar between the subgroups. Conclusion Early initiation of once-monthly paliperidone palmitate in hospitalized patients with acute exacerbation of schizophrenia led to greater improvements in psychotic symptoms with comparable safety than treatment initiation following 1 week of hospitalization. PMID:29731633

  4. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study.

    PubMed

    Li, Huafang; Li, Yan; Feng, Yu; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson

    2018-01-01

    To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week), differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18-65 years) diagnosed with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition). Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score), secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire) and safety were assessed in this post hoc analysis. Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates ( P ≤0.01), PANSS subscales (positive and general psychopathology; all P ≤0.01), PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P ≤0.01), Personal and Social Performance scale scores ( P ≤0.05) and Clinical Global Impression-Severity categorical summary ( P ≤0.05) were significantly greater in the ≤1 week subgroup versus >1 week subgroup ( P ≤0.05). The readiness for hospital discharge questionnaire improved over time for the overall study population, but remained similar between subgroups at all-time points. Treatment-emergent adverse events were similar between the subgroups. Early initiation of once-monthly paliperidone palmitate in hospitalized patients with acute exacerbation of schizophrenia led to greater improvements in psychotic symptoms with comparable safety than treatment initiation following 1 week of hospitalization.

  5. [EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

    PubMed

    Gerych, P; Yatsyshyn, R

    2015-01-01

    Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

  6. Prognostic and diagnostic significance of mid-regional pro-atrial natriuretic peptide in acute exacerbation of chronic obstructive pulmonary disease and acute heart failure: data from the ACE 2 Study.

    PubMed

    Pervez, Mohammad Osman; Winther, Jacob A; Brynildsen, Jon; Strand, Heidi; Christensen, Geir; Høiseth, Arne Didrik; Myhre, Peder L; Røysland, Ragnhild; Lyngbakken, Magnus Nakrem; Omland, Torbjørn; Røsjø, Helge

    2018-05-07

    To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea. MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n = 313), on day 2 (n = 234), and before discharge (n = 91) and compared for diagnosing acute heart failure (HF; n = 143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n = 84) separately. The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p < 0.001) and the receiver-operating area under the curve was 0.85 (95% CI 0.81-0.89) for MR-proANP and 0.86 (0.82-0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816 days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio ( ln MR-proANP) 1.98 (95% CI 1.17-3.34). MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.

  7. A pilot study: a combined therapy using polymyxin-B hemoperfusion and extracorporeal membrane oxygenation for acute exacerbation of interstitial pneumonia.

    PubMed

    Itai, Junji; Ohshimo, Shinichiro; Kida, Yoshiko; Ota, Kohei; Iwasaki, Yasumasa; Hirohashi, Nobuyuki; Bonella, Francesco; Guzman, Josune; Costabel, Ulrich; Kohno, Nobuoki; Tanigawa, Koichi

    2015-01-05

    Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) might be beneficial for treating acute exacerbation (AE) of interstitial pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an emerging tool to avoid ventilator-induced lung injury. This is a report presenting the first three patients with AE of IP treated with a combined therapy of PMX-DHP and VV-ECMO. Patient 1 was a 68-year-old male with acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen vascular disease-associated interstitial pneumonia. All patients were severely hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP and VV-ECMO was initiated with support of intravenous corticosteroids and antibiotics. Radiological findings, oxygenation and laboratory findings markedly improved and all patients survived without severe complications. A combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of IP.

  8. A randomized, controlled multicentric study of inhaled budesonide and intravenous methylprednisolone in the treatment on acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Ding, Zhen; Li, Xiu; Lu, Youjin; Rong, Guangsheng; Yang, Ruiqing; Zhang, Ruixia; Wang, Guiqin; Wei, Xiqiang; Ye, Yongqing; Qian, Zhaoxia; Liu, Hongyan; Zhu, Daifeng; Zhou, Ruiqing; Zhu, Kun; Ni, Rongping; Xia, Kui; Luo, Nan; Pei, Cong

    2016-12-01

    Almost all international guidelines recommend corticosteroids for management of exacerbations of chronic obstructive pulmonary disease (COPD), because it leads to improved outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Nevertheless, due to its side effects, there are still concerns regarding the use of systemic corticosteroid (SC). Inhaled corticosteroids (IC) can be used as an alternative to SC, while reducing the risk of occurrence of side effects. To measure the clinical efficacy and side effects of nebulized budesonide and systemic methylprednisolone in AECOPD. Valid data from 410 AECOPD patients in 10 hospitals was collected. Patients were randomly divided into 2 groups; budesonide group, treated with nebulized budesonide (2 mg 3 times/day); and methylprednisolone group, treated with intravenously injected methylprednisolone (40 mg/day). COPD assessment test (CAT), arterial blood gas analysis, hospitalization days, adverse effects, fasting blood glucose, serum creatinine, alanine aminotransferase levels, and blood drug were measured and analyzed in both groups. Symptoms, pulmonary function and arterial blood gas analysis were significantly improved after treatment in both groups (P < 0.05), with no significant differences between them (P > 0.05), while incidence of adverse events in the budesonide group was lower (P < 0.05). No significant differences in CAT score, days of admission, blood gas analysis results and physiological and biochemical indexes were found between the two groups. Patients treated with methylprednisolone showed a higher degree of PaO 2 level improvement. Results show that inhalation of budesonide (2 mg 3 times/day) and systemic methylprednisolone (40 mg/day) had similar clinical outcome in AECOPD. In conclusion, inhaled budesonide is an alternative to systemic corticosteroids in AECOPD treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. The use of a prospective audit proforma to improve door-to-mask times for acute exacerbations chronic obstructive pulmonary disease (COPD) requiring non-invasive ventilation (NIV).

    PubMed

    Mandal, S; Howes, T Q; Parker, M; Roberts, C M

    2014-12-01

    Non-invasive ventilation (NIV) is an evidence based management of acidotic, hypercapnic exacerbations of COPD. Previous national and international audits of clinical practice have shown variation against guideline standards with significant delays in initiating NIV. We aimed to map the clinical pathway to better understand delays and reduce the door-to-NIV time to less than 3 hours for all patients with acidotic, hypercapnic exacerbations of COPD requiring this intervention, by mandating the use of a guideline based educational management proforma.The proforma was introduced at 7 acute hospitals in North London and Essex and initiated at admission of the patient. It was used to record the clinical pathway and patient outcomes until the point of discharge or death. Data for 138 patients were collected. 48% of patients commenced NIV within 3 hours with no reduction in door-to-mask time during the study period. Delays in starting NIV were due to: time taken for review by the medical team (101 minutes) and time taken for NIV to be started once a decision had been made (49 minutes). There were significant differences in door-to-NIV decision and mask times between differing respiratory on-call systems, p < 0.05). The introduction of the proforma had no effect on door-to-mask times over the study period. Main reasons for delay were related to timely access to medical staff and to NIV equipment; however, a marked variation in practice within these hospitals was been noted, with a 9-5 respiratory on-call system associated with shorter NIV initiation times.

  10. Patients' and their family members' experiences of participation in care following an acute exacerbation in chronic obstructive pulmonary disease: A phenomenological-hermeneutic study.

    PubMed

    Andersen, Ingrid Charlotte; Thomsen, Thora Grothe; Bruun, Poul; Bødtger, Uffe; Hounsgaard, Lise

    2017-12-01

    To explore the experiences of patients with chronic obstructive pulmonary disease and their family members relating both to participation in care during hospitalisation for an acute exacerbation in chronic obstructive pulmonary disease, and to the subsequent day-to-day care at home. When recovering from an exacerbation, the challenges associated with an unpredictable health condition dominate everyday life for patients and can involve their family members. Proper patient and family participation in care during discharge and follow-up can help patients to improve self-management. However, knowledge of the significance of patient and family participation for recovery and subsequent everyday life is still limited. This study adopted a longitudinal design informed by ethnographic fieldwork principles. Participant observations and interviews with 15 patients and 12 family members were conducted on a Danish hospital ward and twice at the participants' homes. A phenomenological-hermeneutic approach inspired by Ricoeur's theory of interpretation guided the data analysis. Participation in care was perceived as valuable, but could be associated with tensions and increased uncertainty. While patients mostly demonstrated a reactive approach to care, family members strived to be more proactive. In hospital, preparing for discharge included an effort to find a balance between powerlessness and influence during interactions with healthcare professionals. At home, managing further recovery and self-management were characterised by navigating between mutual pressure and consideration within the family. Family members play an important role in ensuring that patients are seen, heard and understood, but want to be acknowledged more by healthcare professionals. Appropriate interactions with healthcare professionals are crucial in order to support discharge and daily self-management. Knowledge of the challenges that patients with chronic obstructive pulmonary disease and their family

  11. Early Supported Discharge/Hospital At Home For Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Review and Meta-Analysis.

    PubMed

    Echevarria, Carlos; Brewin, Karen; Horobin, Hazel; Bryant, Andrew; Corbett, Sally; Steer, John; Bourke, Stephen C

    2016-08-01

    A systematic review and meta-analysis was performed to assess the safety, efficacy and cost of Early Supported Discharge (ESD) and Hospital at Home (HAH) compared to Usual Care (UC) for patients with acute exacerbation of COPD (AECOPD). The structure of ESD/HAH schemes was reviewed, and analyses performed assuming return to hospital during the acute period (prior to discharge from home treatment) was, and was not, considered a readmission. The pre-defined search strategy completed in November 2014 included electronic databases (Medline, Embase, Amed, BNI, Cinahl and HMIC), libraries, current trials registers, national organisations, key respiratory journals, key author contact and grey literature. Randomised controlled trials (RCTs) comparing ESD/HAH to UC in patients admitted with AECOPD, or attending the emergency department and triaged for admission, were included. Outcome measures were mortality, all-cause readmissions to 6 months and cost. Eight RCTs were identified; seven reported mortality and readmissions. The structure of ESD/HAH schemes, particularly selection criteria applied and level of support provided, varied considerably. Compared to UC, ESD/HAH showed a trend towards lower mortality (RRMH = 0.66; 95% CI 0.40-1.09, p = 0.10). If return to hospital during the acute period was not considered a readmission, ESD/HAH was associated with fewer readmissions (RRMH = 0.74, 95% CI: 0.60-0.90, p = 0.003), but if considered a readmission, the benefit was lost (RRMH = 0.84; 95% CI 0.69-1.01, p = 0.07). Costs were lower for ESD/HAH than UC. ESD/HAH is safe in selected patients with an AECOPD. Further research is required to define optimal criteria to guide patient selection and models of care.

  12. Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation

    PubMed Central

    Rehal, Sunita; Arbane, Gill; Bourke, Stephen; Calverley, Peter M. A.; Crook, Angela M.; Dowson, Lee; Duffy, Nicholas; Gibson, G. John; Hughes, Philip D.; Hurst, John R.; Lewis, Keir E.; Mukherjee, Rahul; Nickol, Annabel; Oscroft, Nicholas; Patout, Maxime; Pepperell, Justin; Smith, Ian; Stradling, John R.; Wedzicha, Jadwiga A.; Polkey, Michael I.; Elliott, Mark W.; Hart, Nicholas

    2017-01-01

    Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0

  13. 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

  14. 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

  15. THE ACUTE TOXICITY OF MAJOR ION SALTS TO CERIODAPHNIA DUBIA: I. INFLUENCE OF BACKGROUND WATER CHEMISTRY

    PubMed Central

    Mount, David R.; Erickson, Russell J.; Highland, Terry L.; Hockett, J. Russell; Hoff, Dale J.; Jenson, Correne T.; Norberg-King, Teresa J.; Peterson, Kira N.; Polaske, Zach; Wisniewski, Stephanie

    2018-01-01

    The ions Na+, K+, Ca2+, Mg2+, Cl−, SO42−, and HCO3−/CO32− (referred to here as “major ions”) are present in all fresh waters and are physiologically required by aquatic organisms, but can increase to harmful levels from a variety of anthropogenic activities. It is also known that the toxicities of major ion salts can vary depending on the concentrations of other ions, and understanding these relationships is key to establishing appropriate environmental limits. In this paper we present a series of experiments with Ceriodaphnia dubia to evaluate the acute toxicity of twelve major ion salts and to determine how toxicity of these salts varies as a function of background water chemistry. All salts except CaSO4 and CaCO3 were acutely toxic below saturation, with the lowest LC50s found for K salts. All ten salts that showed toxicity also showed some degree of reduced toxicity as the ionic content of the background water increased. Experiments that independently varied Ca:Mg ratio, Na:K ratio, Cl:SO4 ratio, and alkalinity/pH demonstrated that Ca concentration was the primary factor influencing the toxicities of Na and Mg salts, while the toxicities of K salts were primarily influenced by the concentration of Na. These experiments also indicated multiple mechanisms of toxicity and suggested important aspects of dosimetry: the toxicities of K, Mg, and Ca salts were best related to the chemical activity of the cation, while the toxicities of Na salts also reflected an influence of the anions and were well correlated with osmolarity. Understanding these relationships between major ion toxicity and background water chemistry should aid in the development of sensible risk assessment and regulatory standards. PMID:27167636

  16. [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.

  17. C-reactive protein and N-terminal prohormone brain natriuretic peptide as biomarkers in acute exacerbations of COPD leading to hospitalizations.

    PubMed

    Chen, Yu-Wei Roy; Chen, Virginia; Hollander, Zsuzsanna; Leipsic, Jonathon A; Hague, Cameron J; DeMarco, Mari L; FitzGerald, J Mark; McManus, Bruce M; Ng, Raymond T; Sin, Don D

    2017-01-01

    There are currently no accepted and validated blood tests available for diagnosing acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In this study, we sought to determine the discriminatory power of blood C-reactive protein (CRP) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in the diagnosis of AECOPD requiring hospitalizations. The study cohort consisted of 468 patients recruited in the COPD Rapid Transition Program who were hospitalized with a primary diagnosis of AECOPD, and 110 stable COPD patients who served as controls. Logistic regression was used to build a classification model to separate AECOPD from convalescent or stable COPD patients. Performance was assessed using an independent validation set of patients who were not included in the discovery set. Serum CRP and whole blood NT-proBNP concentrations were highest at the time of hospitalization and progressively decreased over time. Of the 3 classification models, the one with both CRP and NT-proBNP had the highest AUC in discriminating AECOPD (cross-validated AUC of 0.80). These data were replicated in a validation cohort with an AUC of 0.88. A combination of CRP and NT-proBNP can reasonably discriminate AECOPD requiring hospitalization versus clinical stability and can be used to rapidly diagnose patients requiring hospitalization for AECOPD.

  18. Efficacy of Various Scoring Systems for Predicting the 28-Day Survival Rate among Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease Requiring Emergency Intensive Care.

    PubMed

    Feng, Zhihong; Wang, Tao; Liu, Ping; Chen, Sipeng; Xiao, Han; Xia, Ning; Luo, Zhiming; Wei, Bing; Nie, Xiuhong

    2017-01-01

    We aimed to investigate the efficacy of four severity-of-disease scoring systems in predicting the 28-day survival rate among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) requiring emergency care. Clinical data of patients with AECOPD who required emergency care were recorded over 2 years. APACHE II, SAPS II, SOFA, and MEDS scores were calculated from severity-of-disease indicators recorded at admission and compared between patients who died within 28 days of admission (death group; 46 patients) and those who did not (survival group; 336 patients). Compared to the survival group, the death group had a significantly higher GCS score, frequency of comorbidities including hypertension and heart failure, and age ( P < 0.05 for all). With all four systems, scores of age, gender, renal inadequacy, hypertension, coronary heart disease, heart failure, arrhythmia, anemia, fracture leading to bedridden status, tumor, and the GCS were significantly higher in the death group than the survival group. The prediction efficacy of the APACHE II and SAPS II scores was 88.4%. The survival rates did not differ significantly between APACHE II and SAPS II ( P = 1.519). Our results may guide triage for early identification of critically ill patients with AECOPD in the emergency department.

  19. 16S rDNA-based metagenomic analysis of dental plaque and lung bacteria in patients with severe acute exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Tan, L; Wang, H; Li, C; Pan, Y

    2014-12-01

    Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are leading causes of mortality in hospital intensive care units. We sought to determine whether dental plaque biofilms might harbor pathogenic bacteria that can eventually cause lung infections in patients with severe AE-COPD. Paired samples of subgingival plaque biofilm and tracheal aspirate were collected from 53 patients with severe AE-COPD. Total bacterial DNA was extracted from each sample individually for polymerase chain reaction amplification and/or generation of bacterial 16S rDNA sequences and cDNA libraries. We used a metagenomic approach, based on bacterial 16S rDNA sequences, to compare the distribution of species present in dental plaque and lung. Analysis of 1060 sequences (20 clones per patient) revealed a wide range of aerobic, anaerobic, pathogenic, opportunistic, novel and uncultivable bacterial species. Species indistinguishable between the paired subgingival plaque and tracheal aspirate samples (97-100% similarity in 16S rDNA sequence) were dental plaque pathogens (Aggregatibacter actinomycetemcomitans, Capnocytophaga sputigena, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) and lung pathogens (Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Streptococcus pneumoniae). Real-time polymerase chain reaction of 16S rDNA indicated lower levels of Pseudomonas aeruginosa and Porphyromonas gingivalis colonizing the dental plaques compared with the paired tracheal aspirate samples. These results support the hypothesis that dental bacteria may contribute to the pathology of severe AE-COPD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Utility of the combination of serum highly-sensitive C-reactive protein level at discharge and a risk index in predicting readmission for acute exacerbation of COPD*,**

    PubMed Central

    Chang, Chun; Zhu, Hong; Shen, Ning; Han, Xiang; Chen, Yahong; He, Bei

    2014-01-01

    OBJECTIVE: Frequent readmissions for acute exacerbations of COPD (AECOPD) are an independent risk factor for increased mortality and use of health-care resources. Disease severity and C-reactive protein (CRP) level are validated predictors of long-term prognosis in such patients. This study investigated the utility of combining serum CRP level with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) exacerbation risk classification for predicting readmission for AECOPD. METHODS: This was a prospective observational study of consecutive patients hospitalized for AECOPD at Peking University Third Hospital, in Beijing, China. We assessed patient age; gender; smoking status and history (pack-years); lung function; AECOPD frequency during the last year; quality of life; GOLD risk category (A-D; D indicating the greatest risk); and serum level of high-sensitivity CRP at discharge (hsCRP-D). RESULTS: The final sample comprised 135 patients. Of those, 71 (52.6%) were readmitted at least once during the 12-month follow-up period. The median (interquartile) time to readmission was 78 days (42-178 days). Multivariate analysis revealed that serum hsCRP-D ≥ 3 mg/L and GOLD category D were independent predictors of readmission (hazard ratio = 3.486; 95% CI: 1.968-6.175; p < 0.001 and hazard ratio = 2.201; 95% CI: 1.342-3.610; p = 0.002, respectively). The ordering of the factor combinations by cumulative readmission risk, from highest to lowest, was as follows: hsCRP-D ≥ 3 mg/L and GOLD category D; hsCRP-D ≥ 3 mg/L and GOLD categories A-C; hsCRP-D < 3 mg/L and GOLD category D; hsCRP-D < 3 mg/L and GOLD categories A-C. CONCLUSIONS: Serum hsCRP-D and GOLD classification are independent predictors of readmission for AECOPD, and their predictive value increases when they are used in combination. PMID:25410837

  1. Effectiveness and safety of noninvasive positive-pressure ventilation for severe hypercapnic encephalopathy due to acute exacerbation of chronic obstructive pulmonary disease: a prospective case-control study.

    PubMed

    Zhu, Guang-fa; Zhang, Wei; Zong, Hua; Xu, Qiu-fen; Liang, Ying

    2007-12-20

    Although severe encephalopathy has been proposed as a possible contraindication to the use of noninvasive positive-pressure ventilation (NPPV), increasing clinical reports showed it was effective in patients with impaired consciousness and even coma secondary to acute respiratory failure, especially hypercapnic acute respiratory failure (HARF). To further evaluate the effectiveness and safety of NPPV for severe hypercapnic encephalopathy, a prospective case-control study was conducted at a university respiratory intensive care unit (RICU) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) during the past 3 years. Forty-three of 68 consecutive AECOPD patients requiring ventilatory support for HARF were divided into 2 groups, which were carefully matched for age, sex, COPD course, tobacco use and previous hospitalization history, according to the severity of encephalopathy, 22 patients with Glasgow coma scale (GCS) < 10 served as group A and 21 with GCS = 10 as group B. Compared with group B, group A had a higher level of baseline arterial partial CO2 pressure ((102 +/- 27) mmHg vs (74 +/- 17) mmHg, P < 0.01), lower levels of GCS (7.5 +/- 1.9 vs 12.2 +/- 1.8, P < 0.01), arterial pH value (7.18 +/- 0.06 vs 7.28 +/- 0.07, P < 0.01) and partial O(2) pressure/fraction of inspired O(2) ratio (168 +/- 39 vs 189 +/- 33, P < 0.05). The NPPV success rate and hospital mortality were 73% (16/22) and 14% (3/22) respectively in group A, which were comparable to those in group B (68% (15/21) and 14% (3/21) respectively, all P > 0.05), but group A needed an average of 7 cm H2O higher of maximal pressure support during NPPV, and 4, 4 and 7 days longer of NPPV time, RICU stay and hospital stay respectively than group B (P < 0.05 or P < 0.01). NPPV therapy failed in 12 patients (6 in each group) because of excessive airway secretions (7 patients), hemodynamic instability (2), worsening of dyspnea and deterioration of gas exchange (2), and gastric

  2. Genetic Deletion of Neuronal PPARγ Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPARγ Function.

    PubMed

    Domi, Esi; Uhrig, Stefanie; Soverchia, Laura; Spanagel, Rainer; Hansson, Anita C; Barbier, Estelle; Heilig, Markus; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-12-14

    PPARγ is one of the three isoforms of the Peroxisome Proliferator-Activated Receptors (PPARs). PPARγ is activated by thiazolidinediones such as pioglitazone and is targeted to treat insulin resistance. PPARγ is densely expressed in brain areas involved in regulation of motivational and emotional processes. Here, we investigated the role of PPARγ in the brain and explored its role in anxiety and stress responses in mice. The results show that stimulation of PPARγ by pioglitazone did not affect basal anxiety, but fully prevented the anxiogenic effect of acute stress. Using mice with genetic ablation of neuronal PPARγ (PPARγ NestinCre ), we demonstrated that a lack of receptors, specifically in neurons, exacerbated basal anxiety and enhanced stress sensitivity. The administration of GW9662, a selective PPARγ antagonist, elicited a marked anxiogenic response in PPARγ wild-type (WT), but not in PPARγ NestinCre knock-out (KO) mice. Using c-Fos immunohistochemistry, we observed that acute stress exposure resulted in a different pattern of neuronal activation in the amygdala (AMY) and the hippocampus (HIPP) of PPARγ NestinCre KO mice compared with WT mice. No differences were found between WT and KO mice in hypothalamic regions responsible for hormonal response to stress or in blood corticosterone levels. Microinjection of pioglitazone into the AMY, but not into the HIPP, abolished the anxiogenic response elicited by acute stress. Results also showed that, in both regions, PPARγ colocalizes with GABAergic cells. These findings demonstrate that neuronal PPARγ is involved the regulation of the stress response and that the AMY is a key substrate for the anxiolytic effect of PPARγ. Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) is a classical target for antidiabetic therapies with thiazolidinedione compounds. PPARγ agonists such as rosiglitazone and pioglitazone are in clinical use for the treatment of insulin resistance. PPARγ has recently attracted

  3. Variability of antibiotic prescribing in patients with chronic obstructive pulmonary disease exacerbations: a cohort study

    PubMed Central

    2013-01-01

    Background The role of antibiotics in treating mild or moderate exacerbations in patients with acute chronic obstructive pulmonary disease (COPD) is unclear. The aims were to: (i) describe patient characteristics associated with acute exacerbations amongst a representative COPD population, (ii) explore the relationship between COPD severity and outcomes amongst patients with exacerbations, and (iii) quantify variability by general practice in prescribing of antibiotics for COPD exacerbations. Method A cohort of 62,747 patients with COPD was identified from primary care general practices (GP) in England, and linked to hospital admission and death certificate data. Exacerbation cases were matched to three controls and characteristics compared using conditional logistic regression. Outcomes were compared using incidence rates and Cox regression, stratified by disease severity. Variability of prescribing at the GP level was evaluated graphically and by using multilevel models. Results COPD severity was found to be associated with exacerbation and subsequent mortality (very severe vs. mild, odds ratio for exacerbation 2.12 [95%CI 19.5–2.32]), hazard ratio for mortality 2.14 [95%CI 1.59–2.88]). Whilst 61% of exacerbation cases were prescribed antibiotics, this proportion varied considerably between GP practices (interquartile range, 48–73%). This variation is greater than can be explained by patient characteristics alone. Conclusions There is significant variability between GP practices in the prescribing of antibiotics to COPD patients experiencing exacerbations. Combined with a lack of evidence on the effects of treatment, this supports the need and opportunity for a large scale pragmatic randomised trial of the prescribing of antibiotics for COPD patients with exacerbations, in order to clarify their effectiveness and long term outcomes whilst ensuring the representativeness of subjects. PMID:23724907

  4. Rapid onset of treatment effects on psychosis, depression, and mania in patients with acute exacerbation of schizoaffective disorder following treatment with oral extended-release paliperidone.

    PubMed

    Fu, Dong-Jing; Turkoz, Ibrahim; Bossie, Cynthia A; Patel, Hiren; Alphs, Larry

    2016-03-15

    Patients with schizoaffective disorder (SCA) experience complicated interplays of psychotic, depressive, and manic symptoms. Paliperidone extended-release (pali ER) tablets have been shown to be efficacious in these patients, but treatment response has not been studied relative to the onset of effects for these symptom domains. In a pooled analysis of data from two 6-week, randomized, placebo-controlled studies, the onset of treatment effects with oral pali ER was evaluated by symptom domain (psychosis, depression, mania) in patients with an acute SCA exacerbation. Subjects were categorized as having prominent psychotic (Positive and Negative Syndrome Scale score >70), depressive (Hamilton Rating Scale for Depression-21 score ≥16), or manic (Young Mania Rating Scale score ≥16) symptoms at baseline. Of the 614 patients in these analyses, 597 (97.2%), 411 (66.9%), and 488 (79.5%) had prominent psychotic, depressive, and manic symptoms at baseline, respectively. Pali ER treatment was associated with rapid and significant improvement of all three symptom domains versus placebo within 1 week of initiation, regardless of whether treatment was given as monotherapy or in combination with mood stabilizers and/or antidepressants. Adverse events were similar to those reported in the original published studies. This post hoc analysis of two phase 3 trials requires confirmation in prospective studies. This pooled analysis suggests that treatment with pali ER is associated with rapid control of psychotic, depressive, and manic symptoms in patients with SCA. Its findings support the benefit of pali ER as a primary treatment for the management of SCA. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Safe and effective prescription of exercise in acute exacerbations of chronic obstructive pulmonary disease: rationale and methods for an integrated knowledge translation study.

    PubMed

    Camp, Pat; Reid, W Darlene; Yamabayashi, Cristiane; Brooks, Dina; Goodridge, Donna; Chung, Frank; Marciniuk, Darcy D; Neufeld, Andrea; Hoens, Alsion

    2013-01-01

    Patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) engage in low levels of activity, putting them at risk for relapse and future readmissions. There is little direction for health care providers regarding the parameters for safe exercise during an AECOPD that is effective for increasing activity tolerance before discharge from hospital, especially for patients with associated comorbid conditions. To report the rationale for and methods of a study to develop evidence-informed care recommendations that guide health care providers in the assessment, prescription, monitoring and progression of exercise for patients hospitalized with AECOPD. The present study was a multicomponent knowledge translation project incorporating evidence from systematic reviews of exercise involving populations with chronic obstructive pulmonary disease and⁄or common comorbidities. A Delphi process was then used to obtain expert opinion from clinicians, academics and patients to identify the parameters of safe and effective exercise for patients with AECOPD. Clinical decision-making tool(s) for patients and practitioners supported by a detailed knowledge dissemination, implementation and evaluation framework. The present study addressed an important knowledge gap: the lack of availability of parameters to guide safe and effective exercise prescription for hospitalized patients with AECOPD, with or without comorbid conditions. In the absence of such parameters, health care professionals may adopt an 'activity as tolerated' approach, which may not improve physical activity levels in their patients. The present study synthesizes the best available evidence and expert opinion, and will generate decision-making tools for use by patients and their health care providers.

  6. Analysis of acute exacerbation of interstitial lung disease associated with chemotherapy in patients with lung cancer: A feasibility of S-1.

    PubMed

    Kakiuchi, Soji; Hanibuchi, Masaki; Tezuka, Toshifumi; Saijo, Atsuro; Otsuka, Kenji; Sakaguchi, Satoshi; Toyoda, Yuko; Goto, Hisatsugu; Kawano, Hiroshi; Azuma, Masahiko; Ogushi, Fumitaka; Nishioka, Yasuhiko

    2017-03-01

    Interstitial lung disease (ILD) is commonly concomitant with lung cancer, and its acute exacerbation (AE) is the most serious complication in patients receiving treatment for lung cancer. To investigate the incidence and characteristic features of AE of ILD, we conducted a retrospective study of 665 consecutive patients with lung cancer who were treated at our institute between 2008 and 2014. Among the 665 patients, 74 (11.1%) had preexisting ILD, and 64 of them received chemotherapy. Four of the 64 patients (6.3%) had experienced AE of ILD, and two (3.1%) died of respiratory failure during first-line chemotherapy. The use of a combination of carboplatin with tegafur-gimeracil-oteracil potassium (S-1) or paclitaxel as a first-line chemotherapy for non-small cell lung cancer led to a lower frequency of AE, at 8.3% (1/12) and 9.1% (1/11), respectively. The incidence of AE rose to 12.8% (5/39) during second-line treatment, and 14 (total: 15 times) of the 64 patients (21.9%) experienced AE from the time of diagnosis to the end of treatment. The incidence of AE was 17.7% (6/34), 15.8% (3/19), 5.0% (2/40), and 4.2% (1/24) in the paclitaxel-, vinorelbine-, etoposide-, and S-1-containing regimens, respectively. No difference in clinical features and laboratory data was detected between the AE and non-AE groups. Although this was a small retrospective study, its findings showed that S-1 and etoposide may be relatively safe options for the treatment of patients with lung cancer and concomitant ILD. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  7. An Audit of Change in Clinical Practice: From Oxygen-Driven to Air-Driven Nebulisers for Prehospital Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD).

    PubMed

    Heys, Deborah; Swain, Andrew; Knowles, Sarah; Waugh, Amy; Bailey, Mark

    2017-11-29

    In developed countries, ambulances normally carry oxygen cylinders but not compressed air. Treatment of acute exacerbations of COPD (AECOPD) with oxygen-driven nebulisers can result in hypercapnia and acidosis. Attempts to avoid this have involved interrupted administration of oxygen. 1 However, small battery-powered air nebulisers are now available. This study aims to compare the prehospital oxygen saturations and treatment of patients suffering from AECOPD before and after the introduction of air nebulisers. The oxygen saturations and treatment of 200 AECOPD patients before and 200 AECOPD patients after the introduction of air nebulisers were compared. Compliance with a target saturation of 88-92% was calculated. The median final oxygen saturation was lower for the post-intervention category (94%) than the pre-intervention category (96%). There was an increase in air nebuliser use from 0% to 56% (p < 0.001) and a decrease in oxygen use from 100% to 71.5% (p < 0.001). There was a numerical increase in the proportion of patients arriving at hospital with oxygen saturations of 88 - 92% following introduction of the air nebulisers (24% vs 16.5%) and a decrease in patients arriving with high saturations (67.5% vs 76.5%). The likelihood of achieving the target oxygen saturations following introduction of air nebulisers increased (odds ratio 1.598; 95% confidence interval 0.974, 2.621). The introduction of prehospital air nebulisers resulted in a reduction in oxygen therapy in patients with AECOPD and a lower median prehospital oxygen saturation. This study supports the use of air nebulisers in the prehospital setting. This article is protected by copyright. All rights reserved.

  8. 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

  9. 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.

  10. Bronchopulmonary pharmacokinetic and pharmacodynamic profiles of levofloxacin 750 mg once daily in adults undergoing treatment for acute exacerbation of chronic bronchitis.

    PubMed

    Nicolau, David P; Sutherland, Christina; Winget, Donna; Baughman, Robert P

    2012-02-01

    While previous reports have described the bronchopulmonary profile of the fluoroquinolones in healthy volunteers, limited data are available in infected patients. The purpose of this study was to determine the intrapulmonary profile of high-dose (750 mg) levofloxacin in patients during an acute exacerbation of chronic bronchitis (AECB). Twenty-four patients experiencing clinical signs and symptoms of AECB were enrolled. Once enrolled, patients received levofloxacin 750 mg once daily × 5 days. Bronchoalveolar lavage aspirates and simultaneous plasma samples were obtained at 4 h, 12 h or 24 h after the third dose. Concentrations in biologic matrixes were determined with a validated HPLC method. Epithelial lining fluid (ELF) concentrations were calculated using the urea dilution method. Five patients did not complete the trial, 19 patients underwent bronchoscopy, 18 (52 ± 13 yrs) had sufficient samples for analysis and confirmed medication compliance. Mean plasma concentrations at 4, 12, and 24 h were 8.0 ± 2.5, 5.8 ± 1.2, and 2.2 ± 1.2 μg/mL. Mean ELF values at 4, 12, and 24 h were 7.5 ± 3.0, 8.3 ± 6.0, and 1.2 ± 0.9 μg/mL. Mean alveolar macrophage (AM) concentrations at 4, 12, and 24 h were 38.5 ± 43.7, 13.4 ± 14.4, and 9.0 ± 7.5 μg/mL. The penetration (ELF/plasma ratio) into the infection site was 113%. In these subjects with AECB, levofloxacin 750 mg once daily reached adequate exposures in the plasma, ELF, and AMs for the most commonly associated pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Comparison of the efficacy of extended-release clarithromycin tablets and amoxicillin/clavulanate tablets in the treatment of acute exacerbation of chronic bronchitis.

    PubMed

    Anzueto, A; Fisher, C L; Busman, T; Olson, C A

    2001-01-01

    Clarithromycin has established efficacy and safety in the treatment of respiratory infections. This study examined the efficacy and safety of a new extended-release formulation of clarithromycin compared with amoxicillin/clavulanate in the treatment of acute exacerbation of chronic bronchitis (AECB). This phase IIIB, multicenter, randomized, parallel-group, investigator-blinded study in patients with AECB and productive cough with purulent sputum compared treatment with extended-release clarithromycin (two 500-mg tablets once daily for 7 days) and amoxicillin/clavulanate (one 875-mg tablet twice daily for 10 days). Assessments were performed before treatment, between study days 10 and 12 (or within 48 hours after premature discontinuation), and between study days 17 and 21 (test of cure). Of 287 patients randomized and treated, 270 were clinically evaluable (137 clarithromycin, 133 amoxicillin/clavulanate). Treatment groups were well matched in terms of demographic characteristics, medical condition, and history. Among clinically evaluable patients at test of cure, 85% and 87% of clarithromycin- and amoxicillin/clavulanate-treated patients, respectively, demonstrated clinical cure (as defined in 1998 draft US Food and Drug Administration guidelines); among clinically and bacteriologically evaluable patients, 92% versus 89%, respectively, demonstrated bacteriologic cure. Overall pathogen eradication rates were similar in the 2 groups (88% clarithromycin, 89% amoxicillin/clavulanate). Rates of premature discontinuation of study drug for any reason differed between treatments: 3% (4/142) of clarithromycin-treated patients versus 12% (17/145) of amoxicillin/clavulanate-treated patients (P = 0.005). One percent (2/142) and 6% (8/145) of the respective treatment groups discontinued study drug because of adverse events. Adverse events generally occurred with a similar frequency in the 2 groups; however, taste alteration was more common with clarithromycin (9/142 [6

  12. Speed of recovery from acute exacerbations of chronic obstructive pulmonary disease after treatment with antimicrobials : results of a two-year study.

    PubMed

    Miravitlles, Marc; Zalacain, Rafael; Murio, Cristina; Ferrer, Montserrat; Alvarez-Sala, José L; Masa, Juan F; Verea, Héctor; Ros, Fernando; Vidal, Rafael

    2003-01-01

    We performed a multicentre study under a 2-year observational protocol that included data on time to recovery from acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) in patients receiving moxifloxacin and comparator antimicrobials. Outpatients with moderate or severe COPD were recruited from respiratory clinics throughout Spain. Moxifloxacin was available in year 2, and was to be prescribed to 50% of patients in that period in a non-randomised allocation. Time to recovery was compared in successfully treated AE-COPD; cross-sectionally for all AE-COPD over 2 years, first AE-COPD and all AE-COPD in year 2, and longitudinally in patients receiving comparator antimicrobials for AE-COPD in year 1 and moxifloxacin in year 2. 614 AE-COPD were treated in 441 patients over 2 years (mean age 66.7 +/- 8.3 years, 98% males, mean forced expiratory volume in 1 second [FEV(1)] 35.9 +/- 8.8%). Mean time to recovery overall was 4.6 days (SD 3.3) with moxifloxacin 400 mg/day for 5 days, and 5.8 days (SD 4.6) with comparators (p < 0.01), which were most frequently amoxicillin/clavulanic acid 500/125mg/8h, clarithromycin 500mg/12h and cefuroxime axetil 500mg/12h for 7-10 days. Longitudinal analysis showed that 27 patients treated with moxifloxacin in the second year of the study recovered in a mean of 3.7 days (SD 3.1), and the same patients treated with comparator antimicrobials in year one recovered in a mean of 6.8 days (SD 4.6) [p = 0.02]. In contrast, in 66 patients treated with comparator antimicrobials in both years, mean time to recovery was 7.4 days (SD 7.3) in year one and 5.5 days (SD 3.5) in year two (p = 0.24). All subgroup analyses showed a statistically significant reduction of 18-25% in time to recovery with moxifloxacin compared with other antibiotics. Moxifloxacin significantly reduced time to recovery from AE-COPD in patients with moderate to severe disease by approximately 20% (>1 day) compared with other antimicrobials. Faster recovery should

  13. 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.

  14. [The value of coexisting pneumonia and British Thoracic Society CURB-65 score in predicting early mortality rate in patients with acute exacerbation of chronic obstructive pulmonary disease].

    PubMed

    Zhang, Mei; Zhao, Yun-feng; Luo, Yi-min; Wang, Xi-hua; Yang, Yuan; Lin, Yong

    2013-04-01

    To investigate the value of coexisting pneumonia and British Thoracic Society CURB-65 score in predicting early mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). In this prospective study, 483 consecutive in-patients with AECOPD were recruited between January 2010 and September 2012, including 295 males and 188 females. The patients were aged 45 to 92 years. They were divided into 2 groups: non-pneumonia (npAECOPD) and with pneumonia (pAECOPD). The start point of this study was the date when the patients were admitted into the respiratory ward, and the endpoint was the 30 day mortality. Clinical and demographic data were collected for all the patients, and the value of coexisting pneumonia and CURB-65 in predicting in-hospital mortality and 30 day mortality were assessed and compared. According to the inclusion/exclusion criteria, eventually 457 patients were included in this research, with 278 males and 179 females, and an average age of (75 ± 9) years. Of the 457 patients, 120 (26.3%) patients were in the pAECOPD group and 337 (73.7%) patients in the npAECOPD group. The in-hospital mortality, the 30 day mortality and the assisted ventilation rate were significantly higher in the pAECOPD group as compared to the npAECOPD group 18.3% (22/120) vs 4.7% (16/337), 21.7% (26/120) vs 7.4% (25/337); 49.2% (59/120) vs 27.0% (91/337), χ(2) = 18.1 - 21.4, all P < 0.05, respectively. Furthermore, the in-hospital mortality of the pAECOPD patients with CURB-65 score < 2, = 2 and > 2 was 4.4% (2/45), 15.2% (7/46) and 44.8% (13/29), respectively, while that of the npAECOPD patients was 0.9% (1/113), 3.4% (4/119) and 10.5% (11/105), respectively. The 30 day mortality of the pAECOPD patients with CURB-65 score < 2, = 2 and > 2 was 4.4% (2/45), 19.6% (9/46) and 51.7% (15/29), respectively, while that of the npAECOPD patients was 0.9% (1/113), 5.0% (6/119) and 17.1% (18/105), respectively. Stratified by CURB-65 Score, the in

  15. Clinical Decision-Making Tool for Safe and Effective Prescription of Exercise in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Results From an Interdisciplinary Delphi Survey and Focus Groups.

    PubMed

    Camp, Pat G; Reid, W Darlene; Chung, Frank; Kirkham, Ashley; Brooks, Dina; Goodridge, Donna; Marciniuk, Darcy D; Hoens, Alison M

    2015-10-01

    Exercise is recommended for people with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), yet there is little information to guide safe and effective mobilization and exercise for these patients. The purpose of this study was to develop a clinical decision-making tool to guide health care professionals in the assessment, prescription, monitoring, and progression of mobilization and therapeutic exercise for patients with AECOPD. A 3-round interdisciplinary Delphi panel identified and selected items based on a preselected consensus of 80%. These items were summarized in a paper-based tool titled Mobilization in Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD-Mob). Focus groups and questionnaires were subsequently used to conduct a sensibility evaluation of the tool. Nine researchers, 13 clinicians, and 7 individuals with COPD identified and approved 110 parameters for safe and effective exercise in AECOPD. These parameters were grouped into 5 categories: (1) "What to Assess Prior to Mobilization," (2) "When to Consider Not Mobilizing or to Discontinue Mobilization," (3) "What to Monitor During Mobilization for Patient Safety," (4) "How to Progress Mobilization to Enhance Effectiveness," and (5) "What to Confirm Prior to Discharge." The tool was evaluated in 4 focus groups of 18 health care professionals, 90% of whom reported the tool was easy to use, was concise, and would guide a health care professional who is new to the acute care setting and working with patients with AECOPD. The tool was developed based on published evidence and expert opinion, so the applicability of the items to patients in all settings cannot be guaranteed. The Delphi panel consisted of health care professionals from Canada, so items may not be generalizable to other jurisdictions. The AECOPD-Mob provides practical and concise information on safe and effective exercise for the AECOPD population for use by the new graduate or novice acute care

  16. 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

  17. Comorbidities and short-term prognosis in patients hospitalized for acute exacerbation of COPD: the EPOC en Servicios de medicina interna (ESMI) study.

    PubMed

    Almagro, Pedro; Cabrera, Francisco Javier; Diez, Jesus; Boixeda, Ramon; Alonso Ortiz, M Belen; Murio, Cristina; Soriano, Joan B

    2012-11-01

    Comorbidities are frequent in patients hospitalized for COPD exacerbation, but little is known about their relation with short-term mortality and hospital readmissions. Our hypothesis is that the frequency and type of comorbidities impair the prognosis within 12 weeks after discharge. A longitudinal, observational, multicenter study of patients hospitalized for a COPD exacerbation with spirometric confirmation was performed. Comorbidity information was collected using the Charlson index and a questionnaire that included other common conditions not included in this index. Dyspnea, functional status, and previous hospitalization for COPD or other reasons among other variables were investigated. Information on mortality and readmissions for COPD or other causes was collected up to 3 months after discharge. We studied 606 patients, 594 men (89.9%), with a mean (SD) age of 72.6 (9.9) years and a postbronchodilator FEV1 of 43.2% (21.2). The mean Charlson index score was 3.1 (2.0). On admission, 63.4% of patients had arterial hypertension, 35.8% diabetes mellitus, 32.8% chronic heart failure, 20.8% ischemic heart disease, 19.3% anemia, and 34% dyslipemia. Twenty-seven patients (4.5%) died within 3 months. The Charlson index was an independent predictor of mortality (P < .003; OR,1.23; 95% CI, 1.07-1.40), even after adjustment for age, FEV1, and functional status measured with the Katz index. Comorbidity was also related with the need for hospitalization from the ED, length of stay, and hospital readmissions for COPD or other causes. Comorbidities are common in patients hospitalized for a COPD exacerbation, and they are related to short-term prognosis.

  18. Systemic lupus erythematosus due to Epstein-Barr virus or Epstein-Barr virus infection provocating acute exacerbation of systemic lupus erythematosus?

    PubMed

    Kasapcopur, Ozgur; Ergul, Yakup; Kutlug, Seyhan; Candan, Cengiz; Camcioglu, Yildiz; Arisoy, Nil

    2006-06-01

    Systemic lupus erythematosus (SLE) is a rheumatologic disease characterized by an inflammatory destruction of the target organ systems of the body in an unknown way by autoantibodies formed against self-antigens. Infectious agents like Epstein-Barr virus (EBV), cytomegalovirus and parvovirus B19 may have a role in the occurrence or the exacerbation of the SLE. In this report, the clinical follow-up of a 14-year-old girl diagnosed with SLE following an EBV infection with bicytopenia, lymphadenomegaly and hepatomegaly is discussed. This case could support the role of viral infections in the etiology of SLE.

  19. 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

  20. 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.

  1. Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload.

    PubMed

    Fetterman, Jessica L; Zelickson, Blake R; Johnson, Larry W; Moellering, Douglas R; Westbrook, David G; Pompilius, Melissa; Sammy, Melissa J; Johnson, Michelle; Dunham-Snary, Kimberly J; Cao, Xuemei; Bradley, Wayne E; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G; Kesterson, Robert A; Dell'italia, Louis J; Darley-Usmar, Victor M; Welch, Danny R; Ballinger, Scott W

    2013-10-15

    Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial-nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress.

  2. Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

    PubMed Central

    Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

    2013-01-01

    Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

  3. Non-traumatic rhabdomyolysis: Background, laboratory features, and acute clinical management.

    PubMed

    Cervellin, Gianfranco; Comelli, Ivan; Benatti, Mario; Sanchis-Gomar, Fabian; Bassi, Antonella; Lippi, Giuseppe

    2017-08-01

    Rhabdomyolysis is a relatively rare condition, but its clinical consequences are frequently dramatic in terms of both morbidity and mortality. Although no consensus has been reached so far about the precise definition of this condition, the term rhabdomyolysis describes a rapid breakdown of striated, or skeletal, muscle. It is hence characterized by the rupture and necrosis of muscle fibers, resulting in release of cell degradation products and intracellular elements within the bloodstream and extracellular space. Notably, the percentage of patients with rhabdomyolysis who develop acute kidney injury, the most dramatic consequence, varies from 13% to over 50% according to both the cause and the clinical and organizational setting where they are diagnosed. Despite direct muscle injury (i.e., traumatic rhabdomyolysis) remains the most common cause, additional causes, frequently overlapping, include hypoxic, physical, chemical or biological factors. The conventional triad of symptoms includes muscle pain, weakness and dark urine. The laboratory diagnosis is essentially based on the measurement of biomarkers of muscle injury, being creatine kinase (CK) the biochemical "gold standard" for diagnosis, and myoglobin the "gold standard" for prognostication, especially in patients with non-traumatic rhabdomyolysis. The essential clinical management in the emergency department is based on a targeted intervention to manage the underlying cause, combined with infusion of fluids and eventually sodium bicarbonate. We will present and discuss in this article the pathophysiological and clinical features of non-traumatic rhabdomyolysis, focusing specifically on Emergency Department (ED) management. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Incidence of pulmonary embolism during COPD exacerbation*, **

    PubMed Central

    Akpinar, Evrim Eylem; Hoşgün, Derya; Akpýnar, Serdar; Ataç, Gökçe Kaan; Doğanay, Beyza; Gülhan, Meral

    2014-01-01

    OBJECTIVE: Because pulmonary embolism (PE) and COPD exacerbation have similar presentations and symptoms, PE can be overlooked in COPD patients. Our objective was to determine the prevalence of PE during COPD exacerbation and to describe the clinical aspects in COPD patients diagnosed with PE. METHODS: This was a prospective study conducted at a university hospital in the city of Ankara, Turkey. We included all COPD patients who were hospitalized due to acute exacerbation of COPD between May of 2011 and May of 2013. All patients underwent clinical risk assessment, arterial blood gas analysis, chest CT angiography, and Doppler ultrasonography of the lower extremities. In addition, we measured D-dimer levels and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. RESULTS: We included 172 patients with COPD. The prevalence of PE was 29.1%. The patients with pleuritic chest pain, lower limb asymmetry, and high NT-pro-BNP levels were more likely to develop PE, as were those who were obese or immobile. Obesity and lower limb asymmetry were independent predictors of PE during COPD exacerbation (OR = 4.97; 95% CI, 1.775-13.931 and OR = 2.329; 95% CI, 1.127-7.105, respectively). CONCLUSIONS: The prevalence of PE in patients with COPD exacerbation was higher than expected. The association between PE and COPD exacerbation should be considered, especially in patients who are immobile or obese. PMID:24626268

  5. 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.

  6. Past racial discrimination exacerbates the acute effects of racial discrimination on negative affect, perceived control, and alcohol-risk cognitions among Black young adults

    PubMed Central

    Stock, Michelle L.; Peterson, Laurel M.; Molloy, Brianne; Lambert, Sharon F.

    2017-01-01

    Racial discrimination is associated with alcohol use and risky sex cognitions and behaviors, which are risk factors for negative health outcomes, including human immunodeficiency virus (HIV) infection. The current study investigated the causal impact of racial discrimination on alcohol and sexual-risk cognitions while exploring potential mediators that might help explain this relation: negative affect, perceived control, and meaningful existence. We also examined if past discrimination impacts the strength of (moderates) these effects. Participants were 287 Black/African American young adults aged 18 to 25. They were randomly assigned to be excluded or included by White peers via the game Cyberball. Racial exclusion (vs. inclusion) predicted greater: perceived racial discrimination, negative affect, alcohol use willingness, and reduced perceived control and meaningful existence. Furthermore, excluded participants who experienced more past racial discrimination reported the lowest perceived control, and greatest negative affect and alcohol-risk cognitions. The findings suggest that past racial discrimination exacerbates the harmful health effects of immediate experiences of discrimination. PMID:27646550

  7. Validity of the Common Cold Questionnaire (CCQ) in Asthma Exacerbations

    PubMed Central

    Powell, Heather; Smart, Joanne; Wood, Lisa G.; Grissell, Terry; Shafren, Darren R.; Hensley, Michael J.; Gibson, Peter G.

    2008-01-01

    Background The common cold questionnaire (CCQ) is used to discriminate those with and without a viral infection. Its usefulness in people with acute asthma is unknown. Our aim was to assess the ability of the CCQ to detect viral infection and to monitor recovery during a viral induced asthma exacerbation and confirmed by virological testing. Methodology/Principal Findings We studied subjects (≥7 yrs) admitted to hospital with acute asthma and diagnosed as positive (n = 63), or negative to viral infection (n = 27) according to molecular and virological testing from respiratory samples. CCQ, asthma history and asthma control questionnaires were completed and repeated 4–6 weeks later. Sensitivity, specificity, and response to change of the CCQ were assessed by receiver operator curve (ROC) analysis and effect size calculation respectively. The CCQ did not discriminate between viral and non-viral infection for subjects with asthma (sensitivity = 76.2%; specificity = 29.6%). ROC analysis could not differentiate between positive or negative virus in subjects with asthma. The CCQ had a large response to change following recovery (effect size = 1.01). 39% of subjects recovering from viral exacerbation remained positive to virological testing at follow-up despite improvement in clinical symptoms. The CCQ reflected clinical improvement in these subjects, thus providing additional information to complement virological testing. Conclusions/Significance The CCQ is a useful instrument for monitoring response to viral infection in people with asthma. Reliable differentiation between viral and non-viral asthma exacerbations was not achieved with the CCQ and requires specific virological testing. When combined with virological testing, the CCQ should be a useful outcome measure for evaluating therapies in viral-induced asthma. PMID:18350141

  8. CD4 T Cell Depletion Exacerbates Acute Mycobacterium tuberculosis While Reactivation of Latent Infection Is Dependent on Severity of Tissue Depletion in Cynomolgus Macaques

    PubMed Central

    Lin, Philana Ling; Rutledge, Tara; Green, Angela M.; Bigbee, Matthew; Fuhrman, Carl; Klein, Edwin

    2012-01-01

    Abstract CD4 T cells are believed to be important in protection against Mycobacterium tuberculosis, but the relative contribution to control of initial or latent infection is not known. Antibody-mediated depletion of CD4 T cells in M. tuberculosis-infected cynomolgus macaques was used to study the role of CD4 T cells during acute and latent infection. Anti-CD4 antibody severely reduced levels of CD4 T cells in blood, airways, and lymph nodes. Increased pathology and bacterial burden were observed in CD4-depleted monkeys during the first 8 weeks of infection compared to controls. CD4-depleted monkeys had greater interferon (IFN)-γ expression and altered expression of CD8 T cell activation markers. During latent infection, CD4 depletion resulted in clinical reactivation in only three of six monkeys. Reactivation was associated with lower CD4 T cells in the hilar lymph nodes. During both acute and latent infection, CD4 depletion was associated with reduced percentages of CXCR3+ expressing CD8 T cells, reported to be involved in T cell recruitment, regulatory function, and effector and memory T cell maturation. CXCR3+ CD8 T cells from hilar lymph nodes had more mycobacteria-specific cytokine expression and greater coexpression of multiple cytokines compared to CXCR3− CD8 T cells. CD4 T cells are required for protection against acute infection but reactivation from latent infection is dependent on the severity of depletion in the draining lymph nodes. CD4 depletion influences CD8 T cell function. This study has important implications for human HIV–M. tuberculosis coinfection. PMID:22480184

  9. Acute Traumatic Brain Injury Does Not Exacerbate Amyotrophic Lateral Sclerosis in the SOD1G93A Rat Model1,2,3

    PubMed Central

    Thomsen, Gretchen M.

    2015-01-01

    Abstract Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease in which upper and lower motor neurons degenerate, leading to muscle atrophy, paralysis, and death within 3 to 5 years of onset. While a small percentage of ALS cases are genetically linked, the majority are sporadic with unknown origin. Currently, etiological links are associated with disease onset without mechanistic understanding. Of all the putative risk factors, however, head trauma has emerged as a consistent candidate for initiating the molecular cascades of ALS. Here, we test the hypothesis that traumatic brain injury (TBI) in the SOD1 G93A transgenic rat model of ALS leads to early disease onset and shortened lifespan. We demonstrate, however, that a one-time acute focal injury caused by controlled cortical impact does not affect disease onset or survival. Establishing the negligible involvement of a single acute focal brain injury in an ALS rat model increases the current understanding of the disease. Critically, untangling a single focal TBI from multiple mild injuries provides a rationale for scientists and physicians to increase focus on repeat injuries to hopefully pinpoint a contributing cause of ALS. PMID:26464984

  10. Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study

    PubMed Central

    Wells, J. Michael; Farris, Roopan F.; Gosdin, Taylor A.; Dransfield, Mark T.; Wood, Michelle E.; Bell, Scott C.; Rowe, Steven M.

    2017-01-01

    Background Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis (CF). The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We investigated the association between pulmonary artery enlargement (PA:A>1), a marker of pulmonary vascular disease, and exacerbations. Methods We analyzed clinical, computed tomography (CT), and prospective exacerbation data in a derivation cohort of 74 adult CF patients, measuring the PA:A at the level of the PA bifurcation. We then replicated our findings in a validation cohort of 190 adult CF patients. Patients were separated into groups based on the presence or absence of a PA:A>1 and were followed for 1-year in the derivation cohort and 2-years in the validation cohort. The primary endpoint was developing ≥1 acute pulmonary exacerbation during follow-up. Linear and logistic regression models were used to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine time to first exacerbation in the validation cohort. Findings We found that PA:A>1 was present in n=37/74 (50%) of the derivation and n=89/190 (47%) of the validation cohort. In the derivation cohort, n=50/74 (68%) had ≥1 exacerbation at 1 year and n=133/190 (70%) in the validation cohort had ≥1 exacerbation after 2 years. PA:A>1 was associated with younger age in both cohorts and with elevated sweat chloride (100.5±10.9 versus 90.4±19.9mmol/L, difference between groups 10.1mmol/L [95%CI 2.5–17.7], P=0.017) in the derivation group. PA:A>1 was associated with exacerbations in the derivation (OR 3.49, 95%CI 1.18–10.3, P=0.023) and validation (OR 2.41, 95%CI 1.06–5.52, P=0.037) cohorts when adjusted for confounders. Time to first exacerbation was shorter in PA:A>1 versus PA:A<1 [HR 1.66 (95%CI 1.18–2.34), P=0.004] in unadjusted analysis, but not when adjusted for sex, BMI, prior exacerbation

  11. Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990–2009

    PubMed Central

    Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

    2016-01-01

    Background: Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. Methods: AL cases diagnosed over 1990–2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002–2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. Results: AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Conclusions: Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland. Citation: Demoury C, Marquant F, Ielsch G, Goujon S, Debayle C, Faure L, Coste A, Laurent O, Guillevic J, Laurier D, Hémon D, Clavel J

  12. Impaired Hemorheology in Exacerbations of COPD

    PubMed Central

    Can, Ilknur; Kilic-Erkek, Ozgen; Altinisik, Goksel; Bor-Kucukatay, Melek

    2017-01-01

    Background Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation. Cardiovascular-related comorbidities are established to contribute to morbidity and mortality especially during exacerbations. The aim of the current study was to determine alterations in hemorheology (erythrocyte aggregation, deformability) in newly diagnosed COPD patients and their response to medical treatment and to compare with values of COPD patients with exacerbations. Materials and Methods The study comprised 13 COPD patients, 12 controls, and 16 COPD patients with exacerbations. The severity of COPD was determined according to Global Initiative for Chronic Obstructive Lung Disease guidelines. Red blood cell (RBC) deformability and aggregation were measured by an ektacytometer. Results RBC deformability of COPD patients with exacerbations was decreased compared to the other groups. Erythrocyte aggregation and plasma fibrinogen of COPD patients determined during exacerbations were higher than control. Conclusion Decreased RBC deformability and increased aggregation associated with exacerbations of COPD may serve as unfavorable mechanisms to worsen oxygenation and thus clinical symptoms of the patient. Treatment modalities that modify rheological parameters might be beneficial. PMID:29089816

  13. Assessment and prevention of acute health effects of weather conditions in Europe, the PHEWE project: background, objectives, design

    PubMed Central

    Michelozzi, Paola; Kirchmayer, Ursula; Katsouyanni, Klea; Biggeri, Annibale; McGregor, Glenn; Menne, Bettina; Kassomenos, Pavlos; Anderson, Hugh Ross; Baccini, Michela; Accetta, Gabriele; Analytis, Antonis; Kosatsky, Tom

    2007-01-01

    Background The project "Assessment and prevention of acute health effects of weather conditions in Europe" (PHEWE) had the aim of assessing the association between weather conditions and acute health effects, during both warm and cold seasons in 16 European cities with widely differing climatic conditions and to provide information for public health policies. Methods The PHEWE project was a three-year pan-European collaboration between epidemiologists, meteorologists and experts in public health. Meteorological, air pollution and mortality data from 16 cities and hospital admission data from 12 cities were available from 1990 to 2000. The short-term effect on mortality/morbidity was evaluated through city-specific and pooled time series analysis. The interaction between weather and air pollutants was evaluated and health impact assessments were performed to quantify the effect on the different populations. A heat/health watch warning system to predict oppressive weather conditions and alert the population was developed in a subgroup of cities and information on existing prevention policies and of adaptive strategies was gathered. Results Main results were presented in a symposium at the conference of the International Society of Environmental Epidemiology in Paris on September 6th 2006 and will be published as scientific articles. The present article introduces the project and includes a description of the database and the framework of the applied methodology. Conclusion The PHEWE project offers the opportunity to investigate the relationship between temperature and mortality in 16 European cities, representing a wide range of climatic, socio-demographic and cultural characteristics; the use of a standardized methodology allows for direct comparison between cities. PMID:17456236

  14. An observational study of PM10 and hospital admissions for acute exacerbations of chronic respiratory disease in Tasmania, Australia 1992-2002.

    PubMed

    Mészáros, D; Markos, J; FitzGerald, D G; Walters, E H; Wood-Baker, R

    2015-01-01

    Particulate matter with a diameter below 10 µ (PM10) has been a major concern in the Tamar Valley, Launceston, where wood heaters are extensively used. We examined the relationship between PM10 levels, meteorological variables, respiratory medications and hospital admissions for respiratory disease over the decade 1992-2002. PM10 levels were provided by the Department of Primary Industry Water, Parks and Environment, and meteorological variables from the Bureau of Meteorology. We obtained hospital discharge codes for the Launceston General Hospital. Poisson regression was used for statistical analyses. Mean daily PM10 levels declined from 50.7 to 16.5 μg/m(3). Hospitalisations for asthma decreased from 29 to 21 per month, whereas chronic obstructive pulmonary disease (COPD) increased and bronchitis/bronchiolitis remained unchanged. We found a 10 μg/m(3) increase in PM10 to be associated with a 4% increase in admissions for acute bronchitis/bronchiolitis (p0.05), but no association with asthma or COPD was found. All respiratory diseases showed seasonal patterns of hospitalisation. This is the first long-term study in Australia to demonstrate an association between PM10 levels and respiratory diseases. Reducing exposure to PM10 may decrease hospital admissions for respiratory diseases. Better preventive measures, including sustained public health initiatives to combat air pollution, are required to reduce respiratory morbidity.

  15. Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations

    PubMed Central

    Ducharme, F M; Zemek, R; Gravel, J; Chalut, D; Poonai, N; Laberge, S; Quach, C; Krajinovic, M; Guimont, C; Lemière, C; Guertin, M C

    2014-01-01

    Introduction Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. Methods and analysis The design is a prospective cohort study of 1008 children aged 1–17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. Ethics and dissemination Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host–environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide

  16. Dark chocolate exacerbates acne.

    PubMed

    Vongraviopap, Saivaree; Asawanonda, Pravit

    2016-05-01

    The effects of chocolate on acne exacerbations have recently been reevaluated. For so many years, it was thought that it had no role in worsening acne. To investigate whether 99% dark chocolate, when consumed in regular daily amounts, would cause acne to worsen in acne-prone male subjects, twenty-five acne prone male subjects were asked to consume 25 g of 99% dark chocolate daily for 4 weeks. Assessments which included Leeds revised acne scores as well as lesion counts took place weekly. Food frequency questionnaire was used, and daily activities were recorded. Statistically significant changes of acne scores and numbers of comedones and inflammatory papules were detected as early as 2 weeks into the study. At 4 weeks, the changes remained statistically significant compared to baseline. Dark chocolate when consumed in normal amounts for 4 weeks can exacerbate acne in male subjects with acne-prone skin. © 2015 The International Society of Dermatology.

  17. Poor concordance between different definitions of worsening renal function in patients with acute exacerbation of chronic heart failure: a retrospective study.

    PubMed

    De Vecchis, Renato; Baldi, Cesare; Di Biase, Giuseppina

    2016-04-01

    Approximately one-third of patients with acute decompensated heart failure (ADHF) treated with an intravenous (iv) loop diuretic at a relatively high dose (>80 mg/day of furosemide, or an equivalent dose of another loop diuretic), exhibit worsening renal function (WRF) after a single course of iv infusions or iv bolus injections maintained for several days. WRF is currently defined as an increase in serum creatinine >0.3 mg/dL (WRF-Cr) or a decrease in the estimated glomerular filtration rate of ≥20% (WRF-GFR) compared to baseline measurements. Furthermore, small increases in serum creatinine in the high-normal range of its values are indicative of significant reductions in estimated glomerular filtration rate (eGFR) due to the exponential relationship between serum creatinine and eGFR. Therefore, underestimating this relationship could lead to an erroneous quantitative estimate of new-onset renal dysfunction, diuretic-related. The relationship between baseline serum creatinine (exposure variable) and the risk of diuretic-related WRF (dichotomous outcome variable), expressed either as WRF-Cr or as WRF-GFR, was assessed by logistic regression analysis. For this purpose, medical records with a diagnosis of previous ADHF were collated, and retrospectively analyzed. The eGFR was calculated using the equation "Modification of Diet in Renal Disease" (MDRD). The WRF was inferred from measurements of serum creatinine that had been made daily during the scheduled courses of intravenous diuretic therapy. Thirty-eight patients with chronic heart failure (CHF) and history of a previous episode of ADHF were enrolled in the study. An increase higher than 0.3 mg/dL of serum creatinine (WRF-Cr) was detected in 14 of 38 patients (36.8%). In addition, a decrease of ≥20% in GFR (WRF-GFR) was detected in 14 of 38 patients (36.8%). However, a poor concordance between the two criteria was found (Cohen's Kappa =0.208, 95% CI: -0.110 to 0.526). WRF-Cr and WRF-GFR showed opposing

  18. Levofloxacin 750 mg QD for five days versus amoxicillin/clavulanate 875 mg/125 mg BID for ten days for treatment of acute bacterial exacerbation of chronic bronchitis: a post hoc analysis of data from severely ill patients.

    PubMed

    Grossman, Ronald F; Ambrusz, Mary E; Fisher, Alan C; Khashab, Mohammed M; Kahn, James B

    2006-08-01

    This post hoc analysis of data from a previous randomized, blinded, multicenter, parallel, noninferiority study assessed the bacterial etiology, symptom resolution, and tolerability of severe acute bacterial exacerbation of chronic bronchitis (ABECB) patients treated with either levofloxacin 750 mg QD for 5 days or amoxicillin/clavulanate 875 mg/125 mg BID for 10 days. Severe ABECB was defined as ABECB and forced expiratory volume in 1 second (FEV(1)) <50% of the predicted value, or (FEV(1)) of 50% to 65% of the predicted value plus comorbidities, or > or =4 exacerbations per year. A total of 369 patients were included in the intent-to-treat (ITT) population (187 treated with levofloxacin and 182 treated with amoxicillin/clavulanate), and 175 patients were microbiologically assessable (MA) (86 treated with levofloxacin and 89 treated with amoxicillin/clavulanate). In the ITT population, the mean age was 58.7 years, 49.1 % were male, and 48.2% were current smokers. At the on-treatment visit, a significantly higher proportion of MA patients in the levofloxacin group resolved purulent sputum production (57.5% vs 35.6%; P < 0.006), sputum production (65.4% vs 45.3%; P < 0.013), and cough (60.0% vs 44.0%; P < 0.045), compared with the amoxicillin/clavulanate group. However, no significant between-group differences were observed at posttreatment. A total of 341 pathogens were isolated, of which 143 (41.9%) were traditional ABECB flora, 181 (53.1%) were other gram-negative organisms, and 17 (5.0%) were gram-positive organisms. Overall susceptibility of the pathogens was 97.1% for levofloxacin and 90.6% for amoxicillin/clavulanate (P < 0.001). The prevalence of treatment-emergent adverse events was 42.1 % in patients who received levofloxacin and 48.6 % in those who received amoxicillin/clavulanate (95% CI,-4.0 to 17.0).

  19. 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.

  20. Residential Exposure to Natural Background Radiation and Risk of Childhood Acute Leukemia in France, 1990-2009.

    PubMed

    Demoury, Claire; Marquant, Fabienne; Ielsch, Géraldine; Goujon, Stéphanie; Debayle, Christophe; Faure, Laure; Coste, Astrid; Laurent, Olivier; Guillevic, Jérôme; Laurier, Dominique; Hémon, Denis; Clavel, Jacqueline

    2017-04-01

    Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland.

  1. Characterisation of a collection of Streptococcus pneumoniae isolates from patients suffering from acute exacerbations of chronic bronchitis: in vitro susceptibility to antibiotics and biofilm formation in relation to antibiotic efflux and serotypes/serogroups.

    PubMed

    Vandevelde, Nathalie M; Tulkens, Paul M; Diaz Iglesias, Yvan; Verhaegen, Jan; Rodriguez-Villalobos, Hector; Philippart, Ivan; Cadrobbi, Julie; Coppens, Nathalie; Boel, An; Van Vaerenbergh, Kristien; Francart, Hugo; Vanhoof, Raymond; Liistro, Giuseppe; Jordens, Paul; d'Odemont, Jean-Paul; Valcke, Yvan; Verschuren, Franck; Van Bambeke, Françoise

    2014-09-01

    The correlation between Streptococcus pneumoniae serotypes, biofilm production, antibiotic susceptibility and drug efflux in isolates from patients suffering from acute exacerbations of chronic bronchitis (AECB) remains largely unexplored. Using 101 isolates collected from AECB patients for whom partial (n=51) or full (n=50) medical details were available, we determined serotypes (ST)/serogroups (SG) (Quellung reaction), antibiotic susceptibility patterns [MIC (microdilution) using EUCAST and CLSI criteria] and ability to produce biofilm in vitro (10-day model; crystal violet staining). The majority of patients were 55-75 years old and <5% were vaccinated against S. pneumoniae. Moreover, 54% showed high severity scores (GOLD 3-4), and comorbidities were frequent including hypertension (60%), cancer (24%) and diabetes (20%). Alcohol and/or tobacco dependence was >30%. Isolates of SG6-11-15-23, known for large biofilm production and causing chronic infections, were the most prevalent (>15% each), but other isolates also produced biofilm (SG9-18-22-27 and ST8-20 being most productive), except SG7, SG29 and ST5 (<2% of isolates each). Resistance (EUCAST breakpoints) was 8-13% for amoxicillin and cefuroxime, 35-39% for macrolides, 2-8% for fluoroquinolones and 2% for telithromycin. ST19A isolates showed resistance to all antibiotics, ST14 to all except moxifloxacin, and SG9 and SG19 to all except telithromycin, moxifloxacin and ceftriaxone (SG19 only). Solithromycin and telithromycin MICs were similar. No correlation was observed between biofilm production and MIC or efflux (macrolides, fluoroquinolones). S. pneumoniae serotyping may improve AECB treatment by avoiding antibiotics with predictable low activity, but it is not predictive of biofilm production. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. A double-blind, randomized, placebo-controlled study with JNJ-37822681, a novel, highly selective, fast dissociating D₂ receptor antagonist in the treatment of acute exacerbation of schizophrenia.

    PubMed

    Schmidt, Mark E; Kent, Justine M; Daly, Ella; Janssens, Luc; Van Osselaer, Nancy; Hüsken, Gitta; Anghelescu, Ion-George; Van Nueten, Luc

    2012-10-01

    JNJ-37822681 is a novel, highly selective dopamine D₂ receptor antagonist characterized by a rapid dissociation rate from the dopamine D₂ receptor. This profile was hypothesized to confer antipsychotic efficacy and improved tolerability. In this 12-week study, the efficacy and safety of JNJ-37822681 were evaluated in patients with an acute exacerbation of schizophrenia, randomly assigned (1:1:1:1:1) to JNJ-37822681 (10-, 20- or 30-mg bid), olanzapine (15 mg once-daily), or placebo (for 6 weeks followed by olanzapine for 6 weeks). Of 498 randomized patients, 298 (60%) completed the study. All JNJ-37822681 dose groups and the olanzapine group showed significantly greater reduction in PANSS total score from baseline to week 6 versus placebo (all p-values < 0.001). Least-squares adjusted mean changes from baseline to week 6 in PANSS total score were: -6.4 (placebo); -18.4 (10 mg JNJ-37822681), -17.7 (20 mg JNJ-37822681), -20.0 (30 mg JNJ-37822681) and -22.9 (olanzapine). All JNJ-37822681 groups showed significant improvement versus placebo from baseline to week 6 in the PANSS subscales, Marder factors, Clinical Global Impression of Severity, and in the Subjective Well-Being on Neuroleptics scale (all p-values < 0.05). The most common treatment-emergent adverse events with JNJ-37822681 were insomnia (17%) and akathisia (13%). Incidences of extrapyramidal symptoms were dose-related and were comparable for JNJ-37822681 10 mg bid and olanzapine groups. All JNJ-37822681 dose groups showed lesser weight gain compared with olanzapine. The efficacy and tolerability profile of the JNJ-37822681 10 mg bid was consistent with the study hypothesis. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

  3. Asenapine for the treatment of adults with an acute exacerbation of schizophrenia: results from a randomized, double-blind, fixed-dose, placebo-controlled trial with olanzapine as an active control.

    PubMed

    Landbloom, Ronald; Mackle, Mary; Wu, Xiao; Kelly, Linda; Snow-Adami, Linda; McIntyre, Roger S; Mathews, Maju; Hundt, Carla

    2017-08-01

    Evaluate the efficacy and safety of asenapine 2.5 mg twice daily (bid; n=97) or 5 mg bid (n=113) versus placebo (n=101) in adults with acute exacerbation of schizophrenia. Adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) schizophrenia diagnosis were randomized to asenapine 2.5 mg bid, 5 mg bid, placebo, or olanzapine 15 mg once daily. The primary objective was to test superiority of asenapine versus placebo as measured by the change from baseline to day 42 in the Positive and Negative Syndrome Scale (PANSS) total score. The key safety objective was to evaluate weight change in asenapine versus olanzapine at day 42. The primary efficacy endpoint was met; the difference in least squares mean change from baseline to day 42 in PANSS total score between asenapine 5 mg bid and placebo was -5.5 points (unadjusted 95% CI: -10.1, -1.0; multiplicity adjusted P=0.0356). Neither asenapine 2.5 mg bid nor olanzapine 15mg were superior to placebo. Both asenapine groups demonstrated significantly less weight gain than olanzapine at day 42. Significantly higher incidences of oral hypoesthesia and dysgeusia (combined) for asenapine 2.5 mg bid (5.2% vs 0.0%; P=0.0217) and 5 mg bid (7.1% vs 0.0%; P=0.0033) were observed versus placebo. There were no significant differences between asenapine and placebo for insomnia, extrapyramidal symptoms, akathisia, dizziness, or combination of somnolence/sedation/hypersomnia. This study supports previous efficacy and safety findings of asenapine; asenapine 5 mg bid is the lowest effective dose in adults with schizophrenia. Asenapine was associated with significantly less weight gain than olanzapine at day 42.

  4. General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial.

    PubMed

    Bates, Janine; Francis, Nick A; White, Patrick; Gillespie, David; Thomas-Jones, Emma; Breen, Rachel; Kirby, Nigel; Hood, Kerry; Gal, Micaela; Phillips, Rhiannon; Naik, Gurudutt; Cals, Jochen; Llor, Carl; Melbye, Hasse; Wootton, Mandy; Riga, Evgenia; Cochrane, Ann; Howe, Robin; Fitzsimmons, Deborah; Sewell, Bernadette; Alam, Mohammed Fasihul; Butler, Christopher C

    2017-09-29

    Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status. This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be

  5. Early use of noninvasive techniques for clearing respiratory secretions during noninvasive positive-pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease and hypercapnic encephalopathy: A prospective cohort study.

    PubMed

    Wang, Jinrong; Cui, Zhaobo; Liu, Shuhong; Gao, Xiuling; Gao, Pan; Shi, Yi; Guo, Shufen; Li, Peipei

    2017-03-01

    Noninvasive positive-pressure ventilation (NPPV) might be superior to conventional mechanical ventilation (CMV) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). Inefficient clearance of respiratory secretions provokes NPPV failure in patients with hypercapnic encephalopathy (HE). This study compared CMV and NPPV combined with a noninvasive strategy for clearing secretions in HE and AECOPD patients.The present study is a prospective cohort study of AECOPD and HE patients enrolled between October 2013 and August 2015 in a critical care unit of a major university teaching hospital in China.A total of 74 patients received NPPV and 90 patients received CMV. Inclusion criteria included the following: physician-diagnosed AECOPD, spontaneous airway clearance of excessive secretions, arterial blood gas analysis requiring intensive care, moderate-to-severe dyspnea, and a Kelly-Matthay scale score of 3 to 5. Exclusion criteria included the following: preexisting psychiatric/neurological disorders unrelated to HE, upper gastrointestinal bleeding, upper airway obstruction, acute coronary syndromes, preadmission tracheostomy or endotracheal intubation, and urgent endotracheal intubation for cardiovascular, psychomotor agitation, or severe hemodynamic conditions.Intensive care unit participants were managed by NPPV. Participants received standard treatment consisting of controlled oxygen therapy during NPPV-free periods; antibiotics, intravenous doxofylline, corticosteroids (e.g., salbutamol and ambroxol), and subcutaneous low-molecular-weight heparin; and therapy for comorbidities if necessary. Nasogastric tubes were inserted only in participants who developed gastric distension. No pharmacological sedation was administered.The primary and secondary outcome measures included comparative complication rates, durations of ventilation and hospitalization, number of invasive devices/patient, and in-hospital and 1-year mortality rates

  6. Acute asthma during pregnancy.

    PubMed Central

    Stenius-Aarniala, B. S.; Hedman, J.; Teramo, K. A.

    1996-01-01

    BACKGROUND: Acute asthma during pregnancy is potentially dangerous to the fetus. The aim of this study was to investigate the effect of an acute attack of asthma during pregnancy on the course of pregnancy or delivery, or the health of the newborn infant, and to identify undertreatment as a possible cause of the exacerbations. METHODS: Five hundred and four pregnant asthmatic subjects were prospectively followed and treated. The data on 47 patients with an attack of asthma during pregnancy were compared with those of 457 asthmatics with no recorded acute exacerbation and with 237 healthy parturients. RESULTS: Of 504 asthmatics, 177 patients were not initially treated with inhaled corticosteroids. Of these, 17% had an acute attack compared with only 4% of the 257 patients who had been on inhaled anti-inflammatory treatment from the start of pregnancy. There were no differences between the groups as to length of gestation, length of the third stage of labour, or amount of haemorrhage after delivery. No differences were observed between pregnancies with and without an exacerbation with regard to relative birth weight, incidence of malformations, hypoglycaemia, or need for phototherapy for jaundice during the neonatal period. CONCLUSIONS: Patients with inadequate inhaled anti-inflammatory treatment during pregnancy run a higher risk of suffering an acute attack of asthma than those treated with an anti-inflammatory agent. However, if the acute attack of asthma is relatively mild and promptly treated, it does not have a serious effect on the pregnancy, delivery, or the health of the newborn infant. PMID:8733495

  7. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura.

    PubMed

    Peyvandi, F; Scully, M; Kremer Hovinga, J A; Knöbl, P; Cataland, S; De Beuf, K; Callewaert, F; De Winter, H; Zeldin, R K

    2017-07-01

    Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with significant morbidity/mortality. Caplacizumab's effect on major thromboembolic (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated patients had a major TE event, an exacerbation, or died versus placebo. Caplacizumab has the potential to reduce the acute morbidity and mortality associated with aTTP. Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations, and death. In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody ® was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. Objective The clinical benefit of caplacizumab was further investigated in a post hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and thrombotic thrombocytopenic purpura-related death during the study. Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) for 'embolic and thrombotic events' was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab and 37 received placebo. Results Four events (one pulmonary embolism and three aTTP exacerbations) were reported in four patients in the caplacizumab group, and 20 such events were reported in 14 patients in the placebo group (two acute myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. Conclusion In total, 11.4% of caplacizumab

  8. Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS

    PubMed Central

    Paul, Gabriel G.; Azar, Antoine; Wise, Robert A.; O’Neal, Wanda K.; Dransfield, Mark T.; Woodruff, Prescott G.; Curtis, Jeffrey L.; Comellas, Alejandro P.; Drummond, M. Bradley; Lambert, Allison A.; Paulin, Laura M.; Fawzy, Ashraf; Kanner, Richard E.; Paine, Robert; Han, MeiLan K.; Martinez, Fernando J.; Bowler, Russell P.; Barr, R. Graham; Hansel, Nadia N.

    2018-01-01

    Background Decreased but measurable serum IgA levels (≤70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD. This study tested the hypothesis that subnormal serum IgA levels would be associated with exacerbation risk in COPD. Methods Data were analyzed from 1,049 COPD participants from the observational cohort study SPIROMICS (535 (51%) women; mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA measured using the Myriad RBM biomarker discovery platform. Exacerbation data was collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear, logistic and zero-inflated negative binomial regressions were performed. Results Mean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum IgA (<7 mg/dL) and 25 (2.4%) had IgA level ≤70 mg/dL. Participants with IgA ≤70 mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those with higher IgA. In adjusted models, IgA ≤70 mg/dL was associated with higher exacerbation incidence rates (IRR 1.71, 95% CI 1.01–2.87, p = 0.044) and greater risk for any severe exacerbation (OR 2.99, 95% CI 1.30–6.94, p = 0.010). In adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL decrement in IgA (analyzed continuously) was associated with more exacerbations during follow-up (β 0.24, 95% CI 0.017–0.46, p = 0.035). Conclusions Subnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity. Additionally, a dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk. Future COPD studies should more comprehensively characterize immune status to define the clinical relevance of these findings and their potential for therapeutic correction

  9. A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan Oncology Group 6711 L (PEOPLE Study).

    PubMed

    Iwata, Takekazu; Yoshino, Ichiro; Yoshida, Shigetoshi; Ikeda, Norihiko; Tsuboi, Masahiro; Asato, Yuji; Katakami, Nobuyuki; Sakamoto, Kazuhiro; Yamashita, Yoshinori; Okami, Jiro; Mitsudomi, Tetsuya; Yamashita, Motohiro; Yokouchi, Hiroshi; Okubo, Kenichi; Okada, Morihito; Takenoyama, Mitsuhiro; Chida, Masayuki; Tomii, Keisuke; Matsuura, Motoki; Azuma, Arata; Iwasawa, Tae; Kuwano, Kazuyoshi; Sakai, Shuji; Hiroshima, Kenzo; Fukuoka, Junya; Yoshimura, Kenichi; Tada, Hirohito; Nakagawa, Kazuhiko; Nakanishi, Yoichi

    2016-07-22

    Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer. Pirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone was dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks of 1200-mg/day administration. The primary endpoint was non-AE-IPF rate during postoperative days 0-30, compared to the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF were confirmed by an independent review committee. From June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both pirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39 patients (94.9 % [95 % confidential interval: 82.7-99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 % confidential interval: 85.5-99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient, after AE-IPF; no other grade 3-5 adverse events were observed. Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (REGISTRATION NUMBER: UMIN000007774 ).

  10. Predicting asthma exacerbations in children.

    PubMed

    Forno, Erick; Celedón, Juan C

    2012-01-01

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

  11. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.

    PubMed

    Han, MeiLan K; Quibrera, Pedro M; Carretta, Elizabeth E; Barr, R Graham; Bleecker, Eugene R; Bowler, Russell P; Cooper, Christopher B; Comellas, Alejandro; Couper, David J; Curtis, Jeffrey L; Criner, Gerard; Dransfield, Mark T; Hansel, Nadia N; Hoffman, Eric A; Kanner, Richard E; Krishnan, Jerry A; Martinez, Carlos H; Pirozzi, Cheryl B; O'Neal, Wanda K; Rennard, Stephen; Tashkin, Donald P; Wedzicha, Jadwiga A; Woodruff, Prescott; Paine, Robert; Martinez, Fernando J

    2017-08-01

    Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time. In this longitudinal, prospective analysis of exacerbations in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort, we analysed patients aged 40-80 years with COPD for whom 3 years of prospective data were available, identified through various means including care at academic and non-academic medical centres, word of mouth, and existing patient registries. Participants were enrolled in the study between Nov 12, 2010, and July 31, 2015. We classified patients according to yearly exacerbation frequency: no exacerbations in any year; one exacerbation in every year during 3 years of follow-up; and those with inconsistent exacerbations (individuals who had both years with exacerbations and years without during the 3 years of follow-up). Participants were characterised by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric category (1-4) on the basis of post-bronchodilator FEV 1 . Stepwise logistic regression was used to compare factors associated with one or more acute exacerbations of COPD every year for 3 years versus no exacerbations in the same timeframe. Additionally, a stepwise zero-inflated negative binomial model was used to assess predictors of exacerbation count during follow-up in all patients with available data. Baseline symptom burden was assessed with the COPD assessment test. This trial is registered with ClinicalTrials.gov, number NCT01969344. 2981 patients were enrolled during the study. 1843 patients had COPD, of which 1105 patients had 3 years of complete, prospective follow-up data. 538 (49%) of 1105 patients had at least one acute exacerbation during the 3 years of follow-up, whereas

  12. Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A.; Lynch, Susan V.

    2014-01-01

    Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome. PMID:24850358

  13. Diagnosis of complications associated with acute cholecystitis using computed tomography and diffusion-weighted imaging with background body signal suppression/T2 image fusion.

    PubMed

    Tomizawa, Minoru; Shinozaki, Fuminobu; Tanaka, Satomi; Sunaoshi, Takafumi; Kano, Daisuke; Sugiyama, Eriko; Shite, Misaki; Haga, Ryouta; Fukamizu, Yoshiya; Fujita, Toshiyuki; Kagayama, Satoshi; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2017-07-01

    In a clinical setting, it is important to diagnose complications of acute cholecystitis accurately. Diffusion-weighted whole body imaging with background body signal suppression/T2-weighted image fusion (DWIBS/T2) provides high signal intensity with a strong contrast against surrounding tissues in anatomical settings. In the present study, patients who were being treated for acute cholecystitis and underwent DWIBS/T2 in the National Hospital Organization Shimoshizu Hospital between December 2012 and August 2015 were enrolled. A total of 10 men and 4 women underwent DWIBS/T2. Records, including DWIBS/T2 and computed tomography (CT) imaging, were retrospectively analyzed for patients with acute cholecystitis. CT images revealed thickened gallbladder walls in patients with acute cholecystitis, and high signal intensity was observed in DWIBS/T2 images for the thickened gallbladder wall. Inflammation of the pericholecystic space and the liver resulted in high intensity signals with DWIBS/T2 imaging, whereas CT imaging revealed a low-density area in the cholecystic space. Plain CT scanning identified a low-density area in the liver, which became more obvious with contrast-enhanced CT. DWIBS/T2 imaging showed the inflammation of the liver and pericholesyctic space as an area of high signal intensity. Detectability of inflammation of the pericholecystic space and the liver was the same for DWIBS/T2 and CT, which suggests that DWIBS/T2 has the same sensitivity as CT scanning for the diagnosis of complicated acute cholecystitis. However, the strong contrast shown by DWIBS/T2 allows for easier evaluation of acute cholecystitis than CT scanning.

  14. A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD

    PubMed Central

    Wilkinson, Tom M A; Aris, Emmanuel; Bourne, Simon; Clarke, Stuart C; Peeters, Mathieu; Pascal, Thierry G; Schoonbroodt, Sonia; Tuck, Andrew C; Kim, Viktoriya; Williams, Nicholas; Williams, Anthony; Wootton, Stephen; Devaster, Jeanne-Marie

    2017-01-01

    Background The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood. Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events. Methods In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40–85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Results are presented for subjects in the full cohort, followed for 1 year. Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses. Findings The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50). At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus. Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)). When NTHi was detected, the increased risk of exacerbation was greater in high season (October–March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)). Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%). A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031). Conclusions AECOPD aetiology varies with season. Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection. Trial registration number Results, NCT01360398. PMID:28432209

  15. An analysis of National Health Service Trust websites on the occupational backgrounds of 'Non-Executive Directors' on England's Acute Trusts.

    PubMed

    Pritchard, Colin; Harding, Andrew Je

    2014-05-01

    To explore the occupational backgrounds of English Non-Executive Directors (NED) on Acute National Health Service (NHS) Trusts. Data extrapolated from Trust websites of NED' occupational backgrounds by gender and occupations, and inter-rater reliability test undertaken. Data were available on all but 24 of the 166 Acute Trusts' from all regions. Trust Chairs and NED were categorised by their dominant occupation. Differentiating NED with and without health or social care leadership experience. The ratings of NED' occupations positively correlated (p < 0.001). Occupational categories were Commerce and Finance from private and public sectors or with Medical or Community leadership experience. Only 4% of Chairs were Medical, 2% from Community - the majority (61%) from Commerce and Finance. Of the 1001 NED, 8% and 6% respectively had Medical or Community leadership experience; most (86%) were Commerce, Finance and non-clinical Managerial backgrounds. Females made up 27% of NED. With a predominance of Chairs and NED without health or social care leadership experience, are current Boards equipped to avoid inadvertently 'doing the system's business' (Francis, 2013) rather than developing a more patient-centred, clinically led and integrated NHS? It is suggested that Boards need more NED with health and social care leadership experience and methods to identify the 'patient's agenda' to create 'a common culture' that places 'patients at the centre of everything we do' (Hunt, 2012). A key context for Trust Boards operations is funding, which Francis' terms of reference excluded, an issue that is briefly discussed.

  16. 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.

  17. 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

  18. 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.

  19. THE ROLE OF INHALATORY CORTI-COSTEROIDS AND LONG ACTING *β2 AGONISTS IN THE TREATMENT OF PATIENTS ADMITTED TO HOSPITAL DUE TO ACUTE EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (AECOPD)

    PubMed Central

    Mehić, Bakir

    2007-01-01

    There is the question about the role of fixed combination of inhalatory corticosteroids and long acting β2 agonists in the treatment of patients admitted in hospital due to AECOPD. The objective of this study is to determine the frequency of etiologic factors of AECOPD, to research the length of recovery time and the time free from exacerbation due to AECOPD at the patients treated with fixed combination inhalers containing F/S versus patients who were not treated with this combination. This is retrospective-prospective, randomized, clinical study with a sample size of 70 patients who admitted to hospital due to AECOPD type I or II. Patients are randomized in two groups. Prospective group from 36 patients have been treated with oral or parenteral corticosteroids 7 - 14 days, other medications and fixed combination inhalers containing a F/S. Second, retrospective group from 34 patients have been treated with oral or parenteral corticosteroids 7 - 14 days (in time when we didn’t have fixed combination inhalers containing a F/S) and other medications. In both groups (prospective and retrospective) the most frequent etiological factors of AECOPD was bacterial infection, after that viral infection, other factors as well as congestive heart failure. Average recovery time for symptoms of AECOPD was statistically significant shorter in group patients treated with fixed combination inhalers containing F/S (prospective group) than in group treated without this fixed combination. There are also significant differences in average number of days need for recovery in subgroups of patients by etiological factors of AECOPD, except in cases of AECOPD onset because of congestive heart failure. Average free time from exacerbation at the patients treated with fixed combination inhalers was statistically significant longer than in group of patients who were not treated with this combination. In this study has demonstrated the presence of pathogenic bacteria in 53% our patients

  20. Determination of exacerbation predictors in patients with COPD in physical therapy - a longitudinal study

    PubMed Central

    Marino, Diego M.; Marrara, Kamilla T.; Arcuri, Juliano F.; Candolo, Cecília; Jamami, Maurício; Lorenzo, Valéria A. Pires Di

    2014-01-01

    Background Chronic obstructive pulmonary disease (COPD) typically presents the characteristic clinical condition of exacerbation, with more intense symptoms associated with greater functional loss and consequently lower chances of patient survival. Objectives This study sought to determine the predictors of exacerbation, alone or in combination, in patients with chronic obstructive pulmonary disease (COPD) who received physical therapeutic treatment over 6 months. Method This was an observational, longitudinal and prospective study in which 63 COPD patients residing within the municipality of São Carlos, SP, Brazil were evaluated. These patients had COPD stages II and III and were entered into a physical therapy program, consisting of 3 periods of assessment over 6 months. We evaluated the occurrence of acute exacerbation as well as the patients' body mass index (BMI), fat-free mass (FFM), fat-free mass index, forced expiratory volume in 1 second (FEV1), dyspnea, distance walked (DW) in the 6-minute walk test (6MWT) and handgrip strength. Results When applying Cox settings with each covariate separately, the results revealed 5% significance only for the DW in the 6MWT, which demonstrated an interaction between BMI and FFM. Comparison of the 3 periods of assessment across the covariates measured showed a significant difference only for the DW between evaluations in the 3rd and 6th months. Conclusion Upon analyzing the predictors of risk over 6 months of follow-up in patients with COPD, we found that the DW in the 6MWT was associated with the risk of exacerbation, although this risk also depended on the covariates BMI and FFM. PMID:24845022

  1. Effects of Tiotropium on Exacerbations in Patients with COPD with Low or High Risk of Exacerbations: A Post-Hoc Analysis from the 4-Year UPLIFT® Trial

    PubMed Central

    Celli, Bartolome R.; Decramer, Marc; Asijee, Guus M.; Kupas, Katrin; Tashkin, Donald P.

    2015-01-01

    Background: A history of past exacerbations is a predictor of future events for patients with chronic obstructive pulmonary disease (COPD). Very little is known about the effect of pharmacologic therapies on patients with frequent or infrequent exacerbations. Methods: We conducted a post-hoc analysis of the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®)trial database. Patients were classified as having a low risk of exacerbations if they experienced ≤1 exacerbation and no COPD-related hospitalization(s) in the year preceding trial entry or as high risk of exacerbations if they had ≥2 exacerbations (courses of oral steroids/antibiotics) or ≥1 COPD-related hospitalization(s) in the year preceding the trial. Results: In patients at low risk or high risk for exacerbations, compared to placebo, tiotropium significantly reduced: 1) the time to first COPD exacerbation (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.74, 0.88; p <0.0001; HR: 0.89; 95% CI: 0.81, 0.97; p=0.0066, respectively); 2) the number of COPD exacerbations (rate ratio [RR]: 0.79; 95% CI: 0.72, 0.86; p<0.0001; RR: 0.88; 95% CI: 0.81; 0.95; p=0.0009). Furthermore, upon treatment with tiotropium, the proportion of patients transitioning from the low- to the high-risk exacerbations group was statistically lower compared to placebo (RR: 0.78; 95% CI: 0.67, 0.92; p=0.0030) Conclusions: This analysis shows that tiotropium reduces the risk of subsequent exacerbation and also prolongs time to first exacerbation, in both the high- and low-risk exacerbator subgroups. It also decreases the proportion of patients who shift from the low- to the high-risk exacerbations group compared to placebo. PMID:28848836

  2. Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications

    PubMed Central

    Chou, Timothy Y; Hong, Bennett Y

    2014-01-01

    Eye disease due to herpes simplex virus (HSV) is a leading cause of ocular morbidity and the number one infectious cause of unilateral corneal blindness in the developed parts of the globe. Recurrent keratitis can result in progressive corneal scarring, thinning, and vascularization. Antiviral agents employed against HSV have primarily been nucleoside analogs. Early generation drugs included idoxuridine, iododesoxycytidine, vidarabine, and trifluridine. While effective, they tended to have low bioavailability and measurable local cellular toxicity due to their nonselective mode of action. Acyclovir 0.3% ointment is a more selective agent, and had become a first-line topical drug for acute HSV keratitis in Europe and other places outside of the US. Ganciclovir 0.15% gel is the most recently approved topical treatment for herpes keratitis. Compared to acyclovir 0.3% ointment, ganciclovir 0.15% gel has been shown to be better tolerated and no less effective in several Phase II and III trials. Additionally, topical ganciclovir does not cause adverse systemic side effects and is therapeutic at lower concentrations. Based on safety, efficacy, and tolerability, ganciclovir 0.15% gel should now be considered a front-line topical drug in the treatment of dendritic herpes simplex epithelial keratitis. Topics of future investigation regarding other potential uses for ganciclovir gel may include the prophylaxis of recurrent HSV epithelial keratitis, treatment of other forms of ocular disease caused by herpesviruses and adenovirus, and ganciclovir gel as an adjunct to antitumor therapy. PMID:25187721

  3. An analysis of National Health Service Trust websites on the occupational backgrounds of ‘Non-Executive Directors’ on England’s Acute Trusts

    PubMed Central

    Harding, Andrew JE

    2014-01-01

    Summary Objectives To explore the occupational backgrounds of English Non-Executive Directors (NED) on Acute National Health Service (NHS) Trusts. Design Data extrapolated from Trust websites of NED’ occupational backgrounds by gender and occupations, and inter-rater reliability test undertaken. Setting Data were available on all but 24 of the 166 Acute Trusts’ from all regions. Participants Trust Chairs and NED were categorised by their dominant occupation. Main outcome measure Differentiating NED with and without health or social care leadership experience. Results The ratings of NED’ occupations positively correlated (p < 0.001). Occupational categories were Commerce and Finance from private and public sectors or with Medical or Community leadership experience. Only 4% of Chairs were Medical, 2% from Community – the majority (61%) from Commerce and Finance. Of the 1001 NED, 8% and 6% respectively had Medical or Community leadership experience; most (86%) were Commerce, Finance and non-clinical Managerial backgrounds. Females made up 27% of NED. Conclusions With a predominance of Chairs and NED without health or social care leadership experience, are current Boards equipped to avoid inadvertently ‘doing the system's business’ (Francis, 2013) rather than developing a more patient-centred, clinically led and integrated NHS? It is suggested that Boards need more NED with health and social care leadership experience and methods to identify the ‘patient’s agenda’ to create ‘a common culture’ that places ‘patients at the centre of everything we do’ (Hunt, 2012). A key context for Trust Boards operations is funding, which Francis’ terms of reference excluded, an issue that is briefly discussed. PMID:25057396

  4. Asthma exacerbations after the East Japan Disaster.

    PubMed

    Ishiura, Yoshihisa; Fujimura, Masaki; Yamamoto, Hiroki; Shiba, Yasutaka; Ohkura, Noriyuki; Kasahara, Kazuo; Ishida, Youichi

    2013-01-01

    On March 11, 2011, a 9.0-magnitude earthquake struck east Japan, following tsunami. Many people are forced to live in evacuation shelters without enough life-saving drugs. Asthma control for management of health crisis is required, because asthma exacerbation is a major cause of morbidity, can need acute care and results in death. However, it remains obscure what parameter should be used in primary clinic of evacuation shelters. The objective of this study is to elucidate the practical efficacy of asthma assessment tool in primary clinic for victims of this disaster. Asthma control test (ACT), a brief and patient-based tool to evaluate asthma control, was conducted for 17 patients with asthma in evacuation shelters at Tohoku district. Total sum of ACT scores were significantly decreased after this disaster. Significant decreases were observed for the items; "Asthma keeps you from getting much done at work", "Shortness of breath", "Asthma symptoms wake you up" and "Patient rating of control". ACT, an easy and practicable tool, clearly demonstrated the asthma exacerbation in evacuation shelters without the use of lung function testing. ACT may contribute to the management of health crisis not only for this East Japan disaster but also for the other forthcoming unavoidable disasters.

  5. The profile of psychiatric symptoms exacerbated by methamphetamine use.

    PubMed

    McKetin, Rebecca; Dawe, Sharon; Burns, Richard A; Hides, Leanne; Kavanagh, David J; Teesson, Maree; McD Young, Ross; Voce, Alexandra; Saunders, John B

    2016-04-01

    Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, χ(2)(df1)=3.66, p=0.056). Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. 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

  7. Neuronal Antibody Biomarkers for Sydenham’s Chorea Identify a New Group of Children with Chronic Recurrent Episodic Acute Exacerbations of Tic and Obsessive Compulsive Symptoms Following a Streptococcal Infection

    PubMed Central

    Singer, Harvey S.; Mascaro-Blanco, Adda; Alvarez, Kathy; Morris-Berry, Christina; Kawikova, Ivana; Ben-Pazi, Hilla; Thompson, Carol B.; Ali, Syed F.; Kaplan, Edward L.; Cunningham, Madeleine W.

    2015-01-01

    Several autoantibodies (anti-dopamine 1 (D1R) and 2 (D2R) receptors, anti-tubulin, anti-lysoganglioside-GM1) and antibody-mediated activation of calcium calmodulin dependent protein kinase II (CaMKII) signaling activity are elevated in children with Sydenham’s chorea (SC). Recognizing proposed clinical and autoimmune similarities between SC and PANDAS (pediatric autoimmune neuropsychiatric disorder associated with a streptococcal infection), we sought to identify serial biomarker changes in a slightly different population. Antineuronal antibodies were measured in eight children (mean 11.3 years) with chronic, dramatic, recurrent tics and obsessive-compulsive disorder (OCD) associated with a group A β-hemolytic streptococcal (GABHS) respiratory tract infection, but differing because they lacked choreiform movements. Longitudinal serum samples in most subjects included two pre-exacerbation samples, Exac), one midst Exac (abrupt recurrence of tic/OCD; temporally association with a GABHS infection in six of eight subjects), and two post-Exac. Controls included four groups of unaffected children (n = 70; mean 10.8 years) obtained at four different institutions and published controls. Clinical exacerbations were not associated with a significant rise in antineuronal antibody titers. CaMKII activation was increased at the GABHS exacerbation point in 5/6 subjects, exceeded combined and published control’s 95th percentile at least once in 7/8 subjects, and median values were elevated at each time point. Anti-tubulin and anti-D2R titers did not differ from published or combined control group’s 95th percentile or median values. Differences in anti-lysoganglioside-GM1 and anti-D1R titers were dependent on the selected control. Variances in antibody titers and CaMKII activation were identified among the institutional control groups. Based on comparisons to published studies, results identify two groups of PANDAS: 1) a cohort, represented by this study, which lacks

  8. What happens to COPD patients before an admission with exacerbation?

    PubMed

    Stone, Robert; Lowe, Derek; Buckingham, Rhona; Pursey, Nancy; Potter, Jonathan; Roberts, C Michael

    2012-10-01

    To obtain patient-generated data relating to the management of their chronic obstructive pulmonary disease (COPD) in Primary Care before hospitalisation with exacerbation. Previous audits of COPD have shown high rates of hospital admission and readmission. There is significant interest in understanding the reasons so that useful preventative strategies may be developed. As part of the 2008 UK COPD audit, which comprised 9716 cases of COPD admission across 97% of acute units, we obtained a sample of patient-generated data to assess understanding of COPD, use of healthcare resources, access to care and self-management in Primary Care prior to hospitalisation with exacerbation. We anticipated the data would provide useful insight for directing improvement strategies. A paper-based, anonymised survey was completed by patients identified as having exacerbation by participating hospital teams. Response rate was an estimated 46%. Understanding and awareness of COPD was very variable. Patients noticed symptoms of COPD exacerbation, particularly change in sputum, for some time prior to hospitalisation but tended not to react promptly to these changes. A minority had self-care plans, many bypassed Primary Care Services and there was variable access to a named health professional or advice. Patients using home oxygen and nebulisers were at particular risk of admission. We conclude these sick patients use a lot of resources and the data suggest a need to support and educate them in the proactive management of exacerbation. There needs to be better 'exacerbation planning' so patients know how to recognise and treat flare-up but also whom to contact in the event of decline. Targetted support should be considered for the most vulnerable, particularly those using home oxygen and nebulisers, who have very high rates of hospitalisation.

  9. 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.

  10. 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.

  11. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection.

    EPA Science Inventory

    Background: Viral infections and exposure to oxidant air pollutants are two ofthe most important inducers ofasthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial ce...

  12. Variability of antibiotic prescribing in patients with chronic obstructive pulmonary disease exacerbations: a cohort study.

    PubMed

    Boggon, Rachael; Hubbard, Richard; Smeeth, Liam; Gulliford, Martin; Cassell, Jackie; Eaton, Susan; Pirmohamed, Munir; van Staa, Tjeerd-Pieter

    2013-05-31

    The role of antibiotics in treating mild or moderate exacerbations in patients with acute chronic obstructive pulmonary disease (COPD) is unclear. The aims were to: (i) describe patient characteristics associated with acute exacerbations amongst a representative COPD population, (ii) explore the relationship between COPD severity and outcomes amongst patients with exacerbations, and (iii) quantify variability by general practice in prescribing of antibiotics for COPD exacerbations. A cohort of 62,747 patients with COPD was identified from primary care general practices (GP) in England, and linked to hospital admission and death certificate data. Exacerbation cases were matched to three controls and characteristics compared using conditional logistic regression. Outcomes were compared using incidence rates and Cox regression, stratified by disease severity. Variability of prescribing at the GP level was evaluated graphically and by using multilevel models. COPD severity was found to be associated with exacerbation and subsequent mortality (very severe vs. mild, odds ratio for exacerbation 2.12 [95%CI 19.5-2.32]), hazard ratio for mortality 2.14 [95%CI 1.59-2.88]). Whilst 61% of exacerbation cases were prescribed antibiotics, this proportion varied considerably between GP practices (interquartile range, 48-73%). This variation is greater than can be explained by patient characteristics alone. There is significant variability between GP practices in the prescribing of antibiotics to COPD patients experiencing exacerbations. Combined with a lack of evidence on the effects of treatment, this supports the need and opportunity for a large scale pragmatic randomised trial of the prescribing of antibiotics for COPD patients with exacerbations, in order to clarify their effectiveness and long term outcomes whilst ensuring the representativeness of subjects.

  13. 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.

  14. Antibiotics for exacerbations of asthma.

    PubMed

    Normansell, Rebecca; Sayer, Ben; Waterson, Samuel; Dennett, Emma J; Del Forno, Manuela; Dunleavy, Anne

    2018-06-25

    Asthma is a chronic respiratory condition that affects over 300 million adults and children worldwide. It is characterised by wheeze, cough, chest tightness, and shortness of breath. Symptoms typically are intermittent and may worsen over a short time, leading to an exacerbation. Asthma exacerbations can be serious, leading to hospitalisation or even death in rare cases. Exacerbations may be treated by increasing an individual's usual medication and providing additional medication, such as oral steroids. Although antibiotics are sometimes included in the treatment regimen, bacterial infections are thought to be responsible for only a minority of exacerbations, and current guidance states that antibiotics should be reserved for cases in which clear signs, symptoms, or laboratory test results are suggestive of bacterial infection. To determine the efficacy and safety of antibiotics in the treatment of asthma exacerbations. We searched the Cochrane Airways Trials Register, which contains records compiled from multiple electronic and handsearched resources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search in October 2017. We included studies comparing antibiotic therapy for asthma exacerbations in adults or children versus placebo or usual care not involving an antibiotic. We allowed studies including any type of antibiotic, any dose, and any duration, providing the aim was to treat the exacerbation. We included parallel studies of any duration conducted in any setting and planned to include cluster trials. We excluded cross-over trials. We included studies reported as full-text articles, those published as abstracts only, and unpublished data. At least two review authors screened the search results for eligible studies. We extracted outcome data, assessed risk of bias in duplicate, and resolved discrepancies by involving another review author. We analysed dichotomous data as odds ratios (ORs) or risk

  15. Acute movement disorders in the medical setting.

    PubMed

    Zawar, Ifrah; Caro, Mario A; Feldman, Lara; Jimenez, Xavier F

    2016-07-01

    Objective Psychosomatic medicine psychiatrists are often tasked with the evaluation and treatment of complex neuropsychiatric states which may be motoric in phenotype. Little energy has been dedicated to understanding acute movement disorders in the hospital environment. Method Recognizing the importance of frontal-subcortical (corticostriatothalamocortical) circuitry and basal ganglia structures, we present a case series of acute movement disorder phenotypes resulting from underlying medical conditions, commonly-administered medications, or the interaction of both. We organize these scenarios into neurodegenerative disorders, primary psychiatric disorders, neuroinflammation, and polypharmacy, demonstrating a clinical example of each followed by background references on a variety of clinical states and medications contributing to acute movement disorders. In addition, we offer visual illustration of implicated neurocircuitry as well as proposed neurotransmitter imbalances involving glutamate, gamma aminobutyric acid, and dopamine. Furthermore, we review the various clinical syndromes and medications involved in the development of acute movement disorders. Results Acute movement disorder's involve complex interactions between frontal-subcortical circuits and acute events. Given the complexity of interactions, psychopharmacological considerations become critical, as some treatments may alleviate acute movement disorders while others will exacerbate them. Conclusion Integrating underlying medical conditions and acutely administered (or discontinued) pharmacological agents offers an interactional, neuromedical approach to acute movement disorders that is critical to the work of psychosomatic medicine.

  16. Characterisation of exacerbation risk and exacerbator phenotypes in the POET-COPD trial.

    PubMed

    Beeh, Kai M; Glaab, Thomas; Stowasser, Susanne; Schmidt, Hendrik; Fabbri, Leonardo M; Rabe, Klaus F; Vogelmeier, Claus F

    2013-10-29

    Data examining the characteristics of patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD) and associated hospitalisations and mortality are scarce. Post-hoc analysis of the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial, targeting exacerbations as the primary endpoint. Patients were classified as non-, infrequent, and frequent exacerbators (0, 1, or ≥ 2 exacerbations during study treatment), irrespective of study treatment. A multivariate Cox regression model assessed the effect of covariates on time to first exacerbation. In total, 7376 patients were included in the analysis: 63.5% non-exacerbators, 22.9% infrequent, 13.6% frequent exacerbators. Factors significantly associated with exacerbation risk were age, sex, body mass index, COPD duration and severity, smoking history, baseline inhaled corticosteroid use, and preceding antibiotic or systemic corticosteroid courses. Frequent exacerbators had greater severity and duration of COPD, received more pulmonary medication, and ≥ 2 systemic corticosteroid or antibiotic courses in the preceding year, and were more likely to be female and ex-smokers. The small proportion of frequent exacerbators (13.6%) accounted for 56.6% of exacerbation-related hospitalisations, which, overall, were associated with a three-fold increase in mortality. The frequent exacerbator phenotype was closely associated with exacerbation-related hospitalisations, and exacerbation-related hospitalisations were associated with poorer survival. NCT00563381; Study identifier: BI 205.389.

  17. An international observational prospective study to determine the cost of asthma exacerbations (COAX).

    PubMed

    Lane, Stephen; Molina, Jesus; Plusa, Tadeusz

    2006-03-01

    Asthma is a common chronic condition that places substantial burden on patients and healthcare services. Despite the standards of asthma control that international guidelines recommend should be achieved, many patients continue to suffer sub-optimal control of symptoms and experience exacerbations (acute asthma attacks). In addition to being associated with reduced quality of life, asthma exacerbations are a key cost driver in asthma management. Routine clinical practice for the management of asthma exacerbations varies in different healthcare systems, so healthcare providers require local costs to be able to assess the value of therapies that reduce the frequency and severity of exacerbations. This prospective study, conducted in a total of 15 countries, assessed the local cost of asthma exacerbations managed in either primary or secondary care. Healthcare resources used were costed using actual values appropriate to each country in local currency and in Euros. Results are presented for exacerbations managed in primary care in Brazil, Bulgaria, Croatia, Czech Republic, Hungary, Poland, Russia, Slovakia, Slovenia, Spain and Ukraine, and in secondary care in Croatia, Denmark, Ireland, Latvia, Norway, Poland, Russia, Slovakia, Slovenia and Spain. Multiple regression analysis of the 2052 exacerbations included in the economic analysis showed that the cost of exacerbations was significantly affected by country (P<0.0001). Mean costs were significantly higher in secondary care (euro 1349) than primary care (euro 445, P=0.0003). Age was a significant variable (P=0.0002), though the effect showed an interaction with care type (P<0.0001). As severity of exacerbation increased, so did secondary care costs, though primary care costs remained essentially constant. In conclusion, the study showed that asthma exacerbations are costly to manage, suggesting that therapies able to increase asthma control and reduce the frequency or severity of exacerbations may bring economic

  18. Bringing stability to the COPD patient: clinical and pharmacological considerations for frequent exacerbators

    PubMed Central

    Gulati, Swati

    2017-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A “frequent exacerbator” is a sub-phenotype of COPD that is defined as an individual who experiences ≥2 moderate to severe exacerbations per year. This distinct subgroup has higher mortality and account for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for utilizing combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: 1) maximizing bronchodilation, 2) reducing inflammation, and 3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies include combination long acting muscarinic agents (LAMA) plus long acting beta agonists (LABA) show promising results compared to monotherapy or LABA inhaled corticosteroid (ICS) combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase (PDE4) inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on identification of various subtypes or “endotypes” and targeting therapies based on their pathophysiology. This review aims to describe the impact of AECOPD, challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these

  19. Severe exacerbation of rosacea induced by cinnamon supplements.

    PubMed

    Campbell, Tracy M; Neems, Rachel; Moore, Julie

    2008-06-01

    The authors report a case of a 68-year-old Caucasian female with type 2 diabetes mellitus who experienced an acute exacerbation of her rosacea 2 weeks after self-initiating cinnamon oil pills to lower her blood sugar levels. Historically, cinnamon oil has been used for a variety of medicinal purposes, but recently the use of cinnamon oil in lowering blood glucose and cholesterol levels in patients with type 2 diabetes is being investigated and gaining popularity amongst the general population. The use of cinnamon has commonly produced cutaneous side effects of irritant or allergic contact dermatitis and been reported to have vasodilatory effects. Yet, there are no reports of cinnamon use triggering a rosacea exacerbation in the literature.

  20. 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

  1. 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

  2. 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

  3. Migraine exacerbation during Ramadan fasting.

    PubMed

    Abu-Salameh, Ibrahim; Plakht, Ygal; Ifergane, Gal

    2010-12-01

    Fasting for approximately 1 month is an obligatory practice for Muslims during the month of Ramadan. We attempted to evaluate the effect of the Ramadan fasting on the frequency of migraine attacks among observant Muslim migraine sufferers using a cohort cross-over study. Thirty-two observant Muslim migraine sufferers filled a migraine diary during the Ramadan month and the following month (control). Two patients failed to complete the fast because of migraine suffering. During the Ramadan month, the patient expressed 9.4 ± 4.3 migraine days in average (range 3-20) when compared with 3.7 ± 2.1 migraine days in average (range 1-10) during the control month (p < 0.001). This phenomenon was associated with longer duration of migraine, lower frequency of migraine attacks, and migraine with aura. It seemed to be less pronounced in patients experiencing throbbing headaches and in married patients. Previous prophylactic therapy did not dampen this. Physicians treating Muslim migraine patients should discuss potential Ramadan month exacerbation with their patients and provide counseling regarding the prevention of dehydration and caffeine withdrawal. Pharmacological prophylactic treatment should be considered.

  4. Dietary Salt Exacerbates Experimental Colitis.

    PubMed

    Tubbs, Alan L; Liu, Bo; Rogers, Troy D; Sartor, R Balfour; Miao, Edward A

    2017-08-01

    The Western diet is characterized by high protein, sugar, fat, and low fiber intake, and is widely believed to contribute to the incidence and pathogenesis of inflammatory bowel disease (IBD). However, high sodium chloride salt content, a defining feature of processed foods, has not been considered as a possible environmental factor that might drive IBD. We set out to bridge this gap. We examined murine models of colitis on either a high salt diet (HSD) or a low salt diet. We demonstrate that an HSD exacerbates inflammatory pathology in the IL-10-deficient murine model of colitis relative to mice fed a low salt diet. This was correlated with enhanced expression of numerous proinflammatory cytokines. Surprisingly, sodium accumulated in the colons of mice on an HSD, suggesting a direct effect of salt within the colon. Similar to the IL-10-deficient model, an HSD also enhanced cytokine expression during infection by Salmonella typhimurium This occurred in the first 3 d of infection, suggesting that an HSD potentiates an innate immune response. Indeed, in cultured dendritic cells we found that high salt media potentiates cytokine expression downstream of TLR4 activation via p38 MAPK and SGK1. A third common colitis model, administration of dextran sodium sulfate, was hopelessly confounded by the high sodium content of the dextran sodium sulfate. Our results raise the possibility that high dietary salt is an environmental factor that drives increased inflammation in IBD. Copyright © 2017 by The American Association of Immunologists, Inc.

  5. 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

    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.

  6. Effects of varenicline therapy in combination with advanced behavioral support on smoking cessation and quality of life in inpatients with acute exacerbation of COPD, bronchial asthma, or community-acquired pneumonia: A prospective, open-label, preference-based, 52-week, follow-up trial.

    PubMed

    Politis, Alexios; Ioannidis, Vasileios; Gourgoulianis, Konstantinos I; Daniil, Zoe; Hatzoglou, Chrissi

    2018-05-01

    Quitting smoking is the most important element in the therapeutic management of chronic respiratory diseases. Combining pharmacotherapy with behavioral support increases smoking cessation success rates. In addition, hospitalized smokers have increased motivation to quit. We investigated the efficacy on smoking cessation, of varenicline in combination with behavioral support, in smokers hospitalized due to (a) acute exacerbation of chronic obstructive pulmonary disease (COPD), or (b) bronchial asthma attack, or (c) community-acquired pneumonia (CAP). The method used is prospective, open-label, preference-based, parallel group, 52-week trial. Patients chose the smoking cessation intervention they preferred: a standard regimen of varenicline combined with post-discharge advanced behavioral support (group A) or one private consultation session during hospitalization (group B). Follow-up phone calls were scheduled in weeks 1, 2, and 4 and months 3, 6, and 9. The final hospital visit was performed in week 52. Primary outcome was success rate defined as the percentage (%) of smoking abstinence at week 52 and secondary outcomes were (a) changes in quality of life (QoL) indicated by the scores on the Short Form 36 (SF36) questionnaire and (b) predictors of smoking abstinence investigated with multiple binary logistic regression. One hundred one patients were enrolled, 44 (43.6%) in group A and 57 (56.4%) in group B. Respective abstinence rates were 54.5% and 15.8% at week 12 and 52.3% and 14.0% at week 52. Scores on SF36 were statistically significantly increased in both groups. Predictors of smoking abstinence were varenicline (odds ratio (OR) 7.29; 95% confidence interval (CI) 2.15, 24.77; p = 0.001), age (OR 1.07; 95%CI 1.00, 1.15; p = 0.042), Fagerstrom score (OR 0.37; 95%CI 0.20, 0.68; p = 0.001), SF36 domains "vitality" (OR 1.12; 95%CI 1.04, 1.21; p = 0.003), and "social functioning" (OR 0.95; 95%CI 0.90, 1.00; p = 0.041). Varenicline in combination with behavioral

  7. Can Circadian Dysregulation Exacerbate Migraines?

    PubMed

    Ong, Jason C; Taylor, Hannah L; Park, Margaret; Burgess, Helen J; Fox, Rina S; Snyder, Sarah; Rains, Jeanetta C; Espie, Colin A; Wyatt, James K

    2018-05-04

    This observational pilot study examined objective circadian phase and sleep timing in chronic migraine (CM) and healthy controls (HC) and the impact of circadian factors on migraine frequency and severity. Sleep disturbance has been identified as a risk factor in the development and maintenance of CM but the biological mechanisms linking sleep and migraine remain largely theoretical. Twenty women with CM and 20 age-matched HC completed a protocol that included a 7 day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. We compared CM vs HC on sleep parameters and circadian factors. Subsequently, we examined associations between dim-light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). CM and HC did not differ on measures of sleep or circadian phase. Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49, P = .039) and later sleep episode (r = .47, P = .037). In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine-related disability (r = .48, P = .042). These relationships remained significant after adjusting for total sleep time. This pilot study revealed that circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity, which was not better accounted for by the amount of sleep. These findings support the plausibility and need for further investigation of a circadian pathway in the development and maintenance of chronic headaches. Specifically, circadian misalignment and delayed sleep timing could serve as an exacerbating factor in chronic migraines when combined with biological predispositions or environmental factors. © 2018 American Headache Society.

  8. Identification and assessment of COPD exacerbations.

    PubMed

    Oliveira, A S; Munhá, J; Bugalho, A; Guimarães, M; Reis, G; Marques, A

    2017-12-24

    Chronic Obstructive Pulmonary Disease (COPD) exacerbations play a central role in the disease natural history of the disease, affecting its overall severity, decreasing pulmonary function, worsening underlying co-morbidities, impairing quality of life (QoL) and leading to severe morbidity and mortality. Therefore, identification and correct assessment of COPD exacerbations is paramount, given it will strongly influence therapy success. For the identification of exacerbations, several questionnaires exist, with varying degrees of complexity. However, most questionnaires remain of limited clinical utility, and symptom scales seem to be more useful in clinical practice. In the assessment of exacerbations, the type and degree of severity should be ascertained in order to define the management setting and optimize treatment options. Still, a consensual and universal classification system to assess the severity and type of an exacerbation is lacking, and there are no established criteria for less severely ill patients not requiring hospital assessment. This might lead to under-reporting of minor to moderate exacerbations, which has an impact on patients' health status. There is a clear unmet need to develop clinically useful questionnaires and a comprehensive system to evaluate the severity of exacerbations that can be used in all settings, from primary health care to general hospitals. Copyright © 2017. Published by Elsevier España, S.L.U.

  9. The reliability and validity of patient-reported chronic obstructive pulmonary disease exacerbations.

    PubMed

    Mohan, Arjun; Sethi, Sanjay

    2014-03-01

    Despite the increasing awareness of their pathogenesis and clinical consequences, research on and clinical management of acute exacerbations of chronic obstructive lung disease (AECOPDs) have been hindered by the lack of a consistent and reliable definition. Symptom-based definitions of exacerbations are sensitive to events and account for unreported exacerbations. Event (healthcare utilization)-based definitions are somewhat more definitive but miss unreported events. Objective quantification of symptoms in AECOPD is now possible with the development of the Exacerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT-PRO), a patient-reported outcome (PRO) measure. Several studies have revealed that unreported AECOPDs are more frequent than reported events and are associated with long-term adverse consequences. New antibiotic development for AECOPD has been hampered by the lack of validated measures for resolution of exacerbations. As a result of these observations, a unique collaborative effort between academia, industry and regulatory agencies resulted in the development of the EXACT-PRO. It consists of 14 questions that generate a score between 0 and 100, and it has been shown to have excellent reliability and validity. In the absence of a reliable biomarker, the definition and measurement of exacerbations has been subjective and imprecise. PRO measures such as EXACT can provide much needed objectivity in assessing symptom-defined exacerbations, which may translate into a uniform outcome measure in clinical trials. With further development and validation, it may have a role in clinical practice in the earlier detection of exacerbations, stratification of an exacerbation severity and the assessment of clinical response to treatment.

  10. Blood Coagulation and Asthma Exacerbation in Children.

    PubMed

    Manuyakorn, Wiparat; Mairiang, Dara; Sirachainan, Nongnuch; Kadegasem, Praguywan; Kamchaisatian, Wasu; Benjaponpitak, Suwat; Chuansumrit, Ampaiwan

    2016-01-01

    Recent studies have demonstrated the activation of coagulation pathways in asthmatic airways. This study aimed to determine systemic blood coagulation during asthma exacerbation compared with the stable state in children. Pediatric patients (aged between 5 and 15 years) suffering from asthma exacerbation were enrolled. von Willebrand factor (vWF), plasminogen activator inhibitor type-1 (PAI-1), protein C, D-dimer, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), and C-reactive protein (CRP) levels were measured during asthma exacerbation and stable state. A total of 22 patients were enrolled. The median vWF, PAI-1, and CRP during asthma exacerbation were significantly higher than those of the stable state: 147.5% (interquartile range, IQR: 111.05-196.57) versus 94% (IQR: 69.72-109.62, p < 0.001), 41.9 ng/ml (IQR: 21.91-48.61) versus 26.17 ng/ml (IQR: 15.89-34.44, p < 0.03), and 4.46 mg/l (IQR: 2.15-16.23) versus 0.87 mg/l (IQR: 0.20-3.89, p < 0.015), respectively. However, the median protein C during asthma exacerbation was significantly lower than that of the stable state: 99.5% (IQR: 86.75-117) versus 113% (IQR: 94-115.25), p = 0.01. No significant difference was found between the levels of D-dimer, F1 + 2, and TAT during asthma exacerbation and stable state. Ultimately, D-dimer was positively correlated with asthma exacerbation score (R = 0.466, p = 0.027). A significant correlation was observed between vWF and CRP (R = 0.527, p = 0.012). Evidence was found of increased endothelial activation and increased PAI-1 during asthma exacerbation. This may emphasize the potential role of blood coagulation in asthma exacerbation. © 2016 S. Karger AG, Basel.

  11. Validity of the common cold questionnaire (CCQ) in asthma exacerbations.

    PubMed

    Powell, Heather; Smart, Joanne; Wood, Lisa G; Grissell, Terry; Shafren, Darren R; Hensley, Michael J; Gibson, Peter G

    2008-03-19

    The common cold questionnaire (CCQ) is used to discriminate those with and without a viral infection. Its usefulness in people with acute asthma is unknown. Our aim was to assess the ability of the CCQ to detect viral infection and to monitor recovery during a viral induced asthma exacerbation and confirmed by virological testing. We studied subjects (> or =7 yrs) admitted to hospital with acute asthma and diagnosed as positive (n = 63), or negative to viral infection (n = 27) according to molecular and virological testing from respiratory samples. CCQ, asthma history and asthma control questionnaires were completed and repeated 4-6 weeks later. Sensitivity, specificity, and response to change of the CCQ were assessed by receiver operator curve (ROC) analysis and effect size calculation respectively. The CCQ did not discriminate between viral and non-viral infection for subjects with asthma (sensitivity = 76.2%; specificity = 29.6%). ROC analysis could not differentiate between positive or negative virus in subjects with asthma. The CCQ had a large response to change following recovery (effect size = 1.01). 39% of subjects recovering from viral exacerbation remained positive to virological testing at follow-up despite improvement in clinical symptoms. The CCQ reflected clinical improvement in these subjects, thus providing additional information to complement virological testing. The CCQ is a useful instrument for monitoring response to viral infection in people with asthma. Reliable differentiation between viral and non-viral asthma exacerbations was not achieved with the CCQ and requires specific virological testing. When combined with virological testing, the CCQ should be a useful outcome measure for evaluating therapies in viral-induced asthma.

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

    PubMed

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

    2004-12-01

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

  13. 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

  14. The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

    PubMed

    Lambert, Katrina A; Prendergast, Luke A; Dharmage, Shyamali C; Tang, Mimi; O'Sullivan, Molly; Tran, Thomas; Druce, Julian; Bardin, Philip; Abramson, Michael J; Erbas, Bircan

    2017-10-11

    It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender. Virus strain was determined for 113 children with HRV detectable at the time of admission for asthma exacerbation. Patient characteristics were collected on admission and exacerbation severity was scored using several validated scales. HRV species by itself was not associated with moderate/severe vs. mild exacerbations. Boys with HRV-C infections were more likely (OR: 3.7, 95% CI: 1.2-13.4) to have a moderate/severe exacerbation than girls with HRV-C (p = 0.04 for interaction term). Higher odds were observed in younger boys (3 years old: OR: 9.1, 95% CI: 1.8-47.1 vs 5 years old: OR: 3.3, 95% CI: 0.9-11.8 vs 7 years old: OR: 1.2, 95% CI: 0.2-6.6). In contrast, children with HRV-C infection and sensitized to pollen during the pollen season were less likely to have moderate/severe exacerbations (p = 0.01 for the interaction term). Acute asthma exacerbations are more likely to be moderate/severe in boys under 5 years of age who had HRV-C infection on admission. The opposite was found in children with sensitization to pollen during pollen season.

  15. 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.

  16. Beta Blockers for the Prevention of Acute Exacerbations of COPD

    DTIC Science & Technology

    2016-10-01

    metoprolol in trials of patients with coronary artery disease , congestive heart failure and hypertension range from 12.5 to 200 mg, and doses in this...distinguish from usual, primary respiratory-related events. In add- ition to a higher frequency of ischaemic heart disease , COPD is associated with diastolic...for the diagnosis and management of patients with stable ischemic heart disease : a report of the American College of Cardiology Foundation/American

  17. 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.

  18. COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members

    PubMed Central

    Pasquale, Margaret K; Xu, Yihua; Baker, Christine L; Zou, Kelly H; Teeter, John G; Renda, Andrew M; Davis, Cralen C; Lee, Theodore C; Bobula, Joel

    2016-01-01

    Background The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs. Methods The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs. Results Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P<0.001 for all). The odds ratio for high vs low symptoms using CAT was 2.51 (P<0.001). Similarly, exacerbation-related costs were 73% higher with each incremental pre-index exacerbation, and over four fold higher for high-vs low-symptom patients using CAT (each P<0.001). The symptoms using mMRC were not

  19. 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

  20. Acute Ethanol Has Biphasic Effects on Short- and Long-Term Memory in Both Foreground and Background Contextual Fear Conditioning in C57BL/6 Mice

    PubMed Central

    Gulick, Danielle; Gould, Thomas J.

    2009-01-01

    Background Ethanol is a frequently abused, addictive drug that impairs cognitive function. Ethanol may disrupt cognitive processes by altering attention, short-term memory, and/ or long-term memory. Interestingly, some research suggests that ethanol may enhance cognitive processes at lower doses. The current research examined the dose-dependent effects of ethanol on contextual and cued fear conditioning. In addition, the present studies assessed the importance of stimulus salience in the effects of ethanol and directly compared the effects of ethanol on short-term and long-term memory. Methods This study employed both foreground and background fear conditioning, which differ in the salience of contextual stimuli, and tested conditioning at 4 hours, 24 hours, and 1 week in order to assess the effects of ethanol on short-term and long-term memory. Foreground conditioning consisted of 2 presentations of a foot shock unconditioned stimulus (US) (2 seconds, 0.57 mA). Background conditioning consisted of 2 auditory conditioned stimulus (30 seconds, 85 dB white noise)–foot shock (US; 2 seconds, 0.57 mA) pairings. Results For both foreground and background conditioning, ethanol enhanced short-term and long-term memory for contextual and cued conditioning at a low dose (0.25 g/kg) and impaired short-term and long-term memory for contextual and cued conditioning at a high dose (1.0 g/kg). Conclusions These results suggest that ethanol has long-lasting, biphasic effects on short-term and long-term memory for contextual and cued conditioning. Furthermore, the effects of ethanol on contextual fear conditioning are independent of the salience of the context. PMID:17760787

  1. Antibiotics for exacerbations of chronic obstructive pulmonary disease.

    PubMed

    Vollenweider, Daniela J; Jarrett, Harish; Steurer-Stey, Claudia A; Garcia-Aymerich, Judith; Puhan, Milo A

    2012-12-12

    Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment

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

    PubMed Central

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

    2016-01-01

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

  3. Risk Factors and Predictive Clinical Scores for Asthma Exacerbations in Childhood

    PubMed Central

    Forno, Erick; Fuhlbrigge, Anne; Soto-Quirós, Manuel E.; Avila, Lydiana; Raby, Benjamin A.; Brehm, John; Sylvia, Jody M.; Weiss, Scott T.

    2010-01-01

    Background: Asthma is a major public health problem that affects millions of children worldwide, and exacerbations account for most of its morbidity and costs. Primary-care providers lack efficient tools to identify children at high risk for exacerbations. We aimed to construct a clinical score to help providers to identify such children. Methods: Our main outcome was severe asthma exacerbation, which was defined as any hospitalization, urgent visit, or systemic steroid course for asthma in the previous year, in children. A clinical score, consisting of a checklist questionnaire made up of 17 yes-no questions regarding asthma symptoms, use of medications and health-care services, and history, was built and validated in a cross-sectional study of Costa Rican children with asthma. It was then evaluated using data from the Childhood Asthma Management Program (CAMP), a longitudinal trial cohort of North American children. Results: Compared with children at average risk for an exacerbation in the Costa Rican validation set, the odds of an exacerbation among children in the low-risk (OR, 0.2; 95% CI, 0.1-0.4) and high-risk (OR, 5.4; 95% CI, 1.5-19.2) score categories were significantly reduced and increased, respectively. In CAMP, the hazard ratios for an exacerbation after 1-year follow-up in the low-risk and high-risk groups were 0.6 (95% CI, 0.5-0.7) and 1.9 (95% CI, 1.4-2.4), respectively, with similar results at 2 years. Conclusions: The proposed Asthma Exacerbation Clinical Score is simple to use and effective at identifying children at high and low risk for asthma exacerbations. The tool can easily be used in primary-care settings. PMID:20472862

  4. Inverse relationship between nonadherence to original GOLD treatment guidelines and exacerbations of COPD

    PubMed Central

    Foda, Hussein D; Brehm, Anthony; Goldsteen, Karen; Edelman, Norman H

    2017-01-01

    Background Prescriber disagreement is among the reasons for poor adherence to COPD treatment guidelines; it is yet not clear whether this leads to adverse outcomes. We tested whether undertreatment according to the original Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines led to increased exacerbations. Methods Records of 878 patients with spirometrically confirmed COPD who were followed from 2005 to 2010 at one Veterans Administration (VA) Medical Center were analyzed. Analysis of variance was performed to assess differences in exacerbation rates between severity groups. Logistic regression analysis was performed to assess the relationship between noncompliance with guidelines and exacerbation rates. Findings About 19% were appropriately treated by guidelines; 14% overtreated, 44% under-treated, and in 23% treatment did not follow any guideline. Logistic regression revealed a strong inverse relationship between undertreatment and exacerbation rate when severity of obstruction was held constant. Exacerbations per year by GOLD stage were significantly different from each other: mild 0.15, moderate 0.27, severe 0.38, very severe 0.72, and substantially fewer than previously reported. Interpretation The guidelines were largely not followed. Undertreatment predominated but, contrary to expectations, was associated with fewer exacerbations. Thus, clinicians were likely advancing therapy primarily based upon exacerbation rates as was subsequently recommended in revised GOLD and other more recent guidelines. In retrospect, a substantial lack of prescriber adherence to treatment guidelines may have been a signal that they required re-evaluation. This is likely to be a general principle regarding therapeutic guidelines. The identification of fewer exacerbations in this cohort than has been generally reported probably reflects the comprehensive nature of the VA system, which is more likely to identify relatively asymptomatic (ie, nonexacerbating) COPD

  5. Efficacy and safety of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 milligrams twice daily for 5 days versus amoxicillin-clavulanate at 875/125 milligrams twice daily for 7 days in the treatment of acute exacerbations of chronic bronchitis.

    PubMed

    Sethi, Sanjay; Breton, John; Wynne, Brian

    2005-01-01

    This randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment of acute exacerbations of chronic bronchitis (AECB). Amoxicillin-clavulanate at 2,000/125 mg was designed to extend the therapeutic levels of amoxicillin in serum over the 12-h dosing interval, compared with conventional formulations, to eradicate bacterial strains for which amoxicillin MICs were < or =4 microg/ml while retaining efficacy against beta-lactamase-producing pathogens. A total of 893 patients were randomized and received study medication (amoxicillin-clavulanate at 2,000/125 mg for 443 patients and 875/125 mg for 450 patients). Overall, 141 patients receiving amoxicillin-clavulanate at 2,000/125 mg and 135 receiving the comparator formulation had at least one pathogen identified at screening. Amoxicillin-clavulanate at 2,000/125 mg was as effective clinically in the per-protocol (PP) population at the test of cure (days 14 to 21, primary efficacy endpoint) as amoxicillin-clavulanate at 875/125 mg (clinical success rates of 93.0 and 91.2%, respectively; treatment difference, 1.8; 95% confidence interval [CI], -2.2, 5.7). Bacteriological success in the bacteriology PP population was high for both formulations (amoxicillin-clavulanate at 2,000/125 mg, 76.7%; amoxicillin-clavulanate at 875/125 mg, 73.0%; treatment difference, 3.8; 95% CI, -7.5, 15.0). Both therapies were well tolerated, with a similar incidence of adverse events. Fewer than 5% of patients in each group withdrew from the study due to adverse events. The shorter, 5-day course of amoxicillin-clavulanate at 2,000/125 mg was shown to be as effective clinically as a longer, 7-day course of amoxicillin-clavulanate at 875/125 mg, with high bacteriological efficacy and no difference in

  6. Efficacy and Safety of Pharmacokinetically Enhanced Amoxicillin-Clavulanate at 2,000/125 Milligrams Twice Daily for 5 Days versus Amoxicillin-Clavulanate at 875/125 Milligrams Twice Daily for 7 Days in the Treatment of Acute Exacerbations of Chronic Bronchitis

    PubMed Central

    Sethi, Sanjay; Breton, John; Wynne, Brian

    2005-01-01

    This randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment of acute exacerbations of chronic bronchitis (AECB). Amoxicillin-clavulanate at 2,000/125 mg was designed to extend the therapeutic levels of amoxicillin in serum over the 12-h dosing interval, compared with conventional formulations, to eradicate bacterial strains for which amoxicillin MICs were ≤4 μg/ml while retaining efficacy against β-lactamase-producing pathogens. A total of 893 patients were randomized and received study medication (amoxicillin-clavulanate at 2,000/125 mg for 443 patients and 875/125 mg for 450 patients). Overall, 141 patients receiving amoxicillin-clavulanate at 2,000/125 mg and 135 receiving the comparator formulation had at least one pathogen identified at screening. Amoxicillin-clavulanate at 2,000/125 mg was as effective clinically in the per-protocol (PP) population at the test of cure (days 14 to 21, primary efficacy endpoint) as amoxicillin-clavulanate at 875/125 mg (clinical success rates of 93.0 and 91.2%, respectively; treatment difference, 1.8; 95% confidence interval [CI], −2.2, 5.7). Bacteriological success in the bacteriology PP population was high for both formulations (amoxicillin-clavulanate at 2,000/125 mg, 76.7%; amoxicillin-clavulanate at 875/125 mg, 73.0%; treatment difference, 3.8; 95% CI, −7.5, 15.0). Both therapies were well tolerated, with a similar incidence of adverse events. Fewer than 5% of patients in each group withdrew from the study due to adverse events. The shorter, 5-day course of amoxicillin-clavulanate at 2,000/125 mg was shown to be as effective clinically as a longer, 7-day course of amoxicillin-clavulanate at 875/125 mg, with high bacteriological efficacy and no difference in

  7. Determining the diagnostic value of endogenous carbon monoxide in chronic obstructive pulmonary disease exacerbations.

    PubMed

    Dogan, Nurettin Özgür; Corbacioglu, Seref Kerem; Bildik, Fikret; Kilicaslan, Isa; Günaydin, Gül Pamukcu; Cevik, Yunsur; Ülker, Volkan; Hakoglu, Onur; Gökcen, Emre

    2014-09-01

    To determine whether endogenous carbon monoxide levels in exacerbations of Chronic Obstructive Pulmonary Disease patients were higher compared to healthy individuals and to investigate alteration of carbon monoxide levels across the three different severity stages of Global Initiative for Chronic Obstructive Lung Disease criteria related to Chronic Obstructive Pulmonary Disease exacerbations. The prospective study was conducted from January to March 2011 at two medical institutions in Ankara, Turkey, and comprised patients of acute Chronic Obstructive Pulmonary Disease exacerbations. The severity of the exacerbations was based on the Global Initiative for Chronic Obstructive Lung Disease criteria. Patients with active tobacco smoking, suspicious carbon monoxide poisoning and uncertain diagnosis were excluded. healthy control subjects who did not have any comorbid diseases and smoking habitus were also enrolled to compare the differences between carboxyhaemoglobin levels A two-tailed Mann-Whitney U test with Bonferroni correction was done following a Kruskal-Wallis test for statistical purposes. There were 90 patients and 81 controls in the study. Carboxyhaemoglobin levels were higher in the patients than the controls (p < 0.001). As for the three severity stages, Group 1 had a median carboxyhaemoglobin of 1.6 (0.95- 2.00). The corresponding levels in Group 2 (1.8 [1.38-2.20]) and Group 3 (1.9 [1.5-3.0]) were higher than the controls (p < 0.001 and p < 0.005 respectively). No statistically significant difference between Group 1 and the controls (1.30 [1.10-1.55]) was observed (p < 0.434). Carboxyhaemoglobin levels were significantly higher in exacerbations compared with the normal population. Also, in more serious exacerbations, carboxyhaemoglobin levels were significantly increased compared with healthy individuals and mild exacerbations.

  8. MARGINAL IODINE DEFICIENCY EXACERBATES PERCHLORATE THYROID TOXICITY.

    EPA Science Inventory

    The environmental contaminant perchlorate disrupts thyroid homeostasis via inhibition of iodine uptake into the thyroid. This work tested whether iodine deficiency exacerbates the effects of perchlorate. Female 27 day-old LE rats were fed a custom iodine deficient diet with 0, 50...

  9. Pulmonary rehabilitation and severe exacerbations of COPD: solution or white elephant?

    PubMed Central

    Puhan, Milo A.; Harrison, Samantha L.; Jordan, Rachel E.; Quint, Jennifer K.; Singh, Sally J.

    2015-01-01

    Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the “comprehensive” nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision) but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact. PMID:27730157

  10. Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

    PubMed Central

    Rogers, Geraint B; Hoffman, Lucas R; Johnson, Matt W; Mayer-Hamblett, Nicole; Schwarze, Jürgen; Carroll, Mary P; Bruce, Kenneth D

    2011-01-01

    Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations. PMID:21405970

  11. 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.

  12. [Precipitating factors in patients with repetitive exacerbation of chronic left heart failure].

    PubMed

    Sasaki, T; Yanagitani, Y; Kubo, T; Matsuo, H; Miyatake, K

    1998-04-01

    The precipitating factors of repetitive exacerbation were investigated in 110 consecutive patients with chronic left heart failure admitted due to acute exacerbation more than twice to the medical emergency ward of National Cardiovascular Center from January, 1992 to December, 1996. The controls were 189 consecutive patients with chronic left heart failure admitted to the ward due to acute exacerbation only once during the same period. Excessive intake of water or sodium, overwork and infection were common precipitating factors in the first decompensation of left heart failure, but the former two factors became less common with repeated admission. Patient mistakes such as excessive intake of water or sodium, overwork and noncompliance with medications, and new onset arrhythmias were common precipitating factors in patients (n = 13) admitted to the ward more than four times. Infection was a common precipitating factor (63%) in patients with a time interval between readmission and the last discharge of longer than 2 years. Despite repeated admission, infection was a common precipitating factor in patients with valvular heart disease (n = 31), patient mistakes were common in heart disease with left ventricular hypertrophy (n = 20), and infection and new onset arrhythmias were common in dilated cardiomyopathy (n = 28) and old myocardial infarction (n = 31). Patient mistakes and new onset arrhythmias were the common factors that led to repetitive exacerbation of left heart failure, and precipitating factors were characterized by the etiology of left heart failure.

  13. Difference in serum magnesium level among patients with stable chronic obstructive pulmonary disease (COPD) and exacerbated COPD

    NASA Astrophysics Data System (ADS)

    Sanowara, R.; Keliat, E. N.; Abidin, A.

    2018-03-01

    Stable COPD is marked with various degrees of inflammation throughout large and small airways also in the alveoli which cause mucus hypersecretion, narrowing of the airway, and alveoli damage. Exacerbation is an episode of elevated inflammation. The relation between inflammation response and magnesium has been observed with the increase of proinflammation cytokines in magnesium deficiency. A cross-sectional study of 34 patients who came to RSUP H. Adam Malik (17 stable COPD patients and 17 acute exacerbated COPD patients) was conducted to examine serum magnesium level and spirometry in stable condition. Mean serum magnesium level for stable COPD patients group was 2.09 ± 0.11 mEq/L. It was higher than in the exacerbated COPD patients group 1.69 ± 0.27 mEq/L. Mann–Whitney statistical analysis showed a significant difference in magnesium level between stable COPD and exacerbated COPD groups (p<0.05).

  14. Free cholesterol accumulation in liver sinusoidal endothelial cells exacerbates acetaminophen hepatotoxicity via TLR9 signaling.

    PubMed

    Teratani, Toshiaki; Tomita, Kengo; Suzuki, Takahiro; Furuhashi, Hirotaka; Irie, Rie; Hida, Shigeaki; Okada, Yoshikiyo; Kurihara, Chie; Ebinuma, Hirotoshi; Nakamoto, Nobuhiro; Saito, Hidetsugu; Hibi, Toshifumi; Miura, Soichiro; Hokari, Ryota; Kanai, Takanori

    2017-10-01

    Although obesity is a risk factor for acute liver failure, the pathogenic mechanisms are not yet fully understood. High cholesterol (HC) intake, which often underlies obesity, is suggested to play a role in the mechanism. We aimed to elucidate the effect of a HC diet on acetaminophen-induced acute liver injury, the most frequent cause of acute liver failure in the USA. C57BL/6 Toll-like receptor 9 (TLR9) knockout (Tlr9 -/- ) mice and their Tlr9 +/+ littermates were fed an HC diet for fourweeks and then treated with acetaminophen. Liver sinusoidal endothelial cells (LSECs) were isolated from the mice for in vivo and in vitro analyses. The HC diet exacerbated acetaminophen-induced acute liver injury in a TLR9/inflammasome pathway-dependent manner. LSECs played a major role in the cholesterol loading-induced exacerbation. The accumulation of free cholesterol in the endolysosomes in LSECs enhanced TLR9-mediated signaling, thereby exacerbating the pathology of acetaminophen-induced liver injury through the activation of the TLR9/inflammasome pathway. The accumulation of free cholesterol in LSEC endolysosomes induced a dysfunction of the Rab7 membrane trafficking recycling mechanism, thus disrupting the transport of TLR9 from late endosomes to the lysosomes. Consequently, the level of active TLR9 in the late endosomes increased, thereby enhancing TLR9 signaling in LSECs. HC intake exaggerated acetaminophen-induced acute liver injury via free cholesterol accumulation in LSECs, demonstrating a novel role of free cholesterol as a metabolic factor in TLR9 signal regulation and pathologies of acetaminophen-induced liver injury. Therapeutic approaches may target this pathway. Lay summary: High cholesterol intake exacerbated acetaminophen-induced acute liver injury via the accumulation of free cholesterol in the endolysosomes of liver sinusoidal endothelial cells. This accumulation enhanced Toll-like receptor 9 signaling via impairment of its membrane trafficking mechanism

  15. The association between previous and future severe exacerbations of chronic obstructive pulmonary disease: Updating the literature using robust statistical methodology.

    PubMed

    Sadatsafavi, Mohsen; Xie, Hui; Etminan, Mahyar; Johnson, Kate; FitzGerald, J Mark

    2018-01-01

    There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course. Previous studies on this topic did not generate causally-interpretable estimates. Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients. Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes. We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events. Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics. 35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up. The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations. This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event. The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality. There was substantial heterogeneity in the individual-specific rate of severe exacerbations. Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile. Using robust statistical methodology that controlled

  16. Fine particulate pollution and asthma exacerbations.

    PubMed

    Bouazza, Naïm; Foissac, Frantz; Urien, Saik; Guedj, Romain; Carbajal, Ricardo; Tréluyer, Jean-Marc; Chappuy, Hélène

    2017-12-19

    As the results from epidemiological studies about the impact of outdoor air pollution on asthma in children are heterogeneous, our objective was to investigate the association between asthma exacerbation in children and exposure to air pollutants. A database of 1 264 585 paediatric visits during the 2010-2015 period to the emergency rooms from 20 emergency departments (EDs) of 'Assistance Publique Hôpitaux de Paris (APHP)', the largest hospital group in Europe, was used. A total of 47 107 visits were classified as asthma exacerbations. Concentration of air pollutants (nitrogen dioxide, ozone, fine particulate matter (PM) with an aerodynamic diameter smaller than 10  µm (PM 10 ) and 2.5 µm (PM 2.5 )), as well as meteorological data, evolution of respiratory syncytial virus infection and pollen exposition, were collected on an hourly or daily basis for the same period using institutional databases. To assess the association between air pollution and asthma, mixed-effects quasi-Poisson regression modelling was performed. The only compound independently associated with ED visits for asthma was PM 2.5 (P<10 -4 ). The association between asthma exacerbation and PM 2.5 was not linear, and a sigmoid function described the relationshipsatisfactorily. PM 2.5 concentration, which gives half the maximum effect, was estimated at 13.5 µg/m 3 . We found an association between daily asthma exacerbation in paediatric visits to the ED and fine particulate air pollutants. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Patients’ experience of identifying and managing exacerbations in COPD: a qualitative study

    PubMed Central

    Williams, Veronika; Hardinge, Maxine; Ryan, Sara; Farmer, Andrew

    2014-01-01

    Background: Effective self-management in chronic obstructive pulmonary disease (COPD) is crucial to reduce hospital admissions and improve outcomes for patients. This includes early detection and treatment of exacerbations by patients themselves. Aims: To explore patients’ current understanding and experience of managing and identifying COPD exacerbations at home. Methods: A qualitative, interview-based study was carried out in patients’ homes. Interviews were audio-recorded, transcribed and analysed using a grounded theory approach. Forty-four patients (17 women, 27 men; age range 55–85 years), with moderate-to-very-severe COPD, were recruited to the interview study from primary and secondary care settings in Oxford, UK, during 2012–2013. Results: Patients identified exacerbations on the basis of measurable, ‘visible’ symptoms, such as cough and sputum and ‘invisible’ symptoms, such as chest sensations and bodily knowledge. Most patients seemed to use a combination of these approaches when identifying exacerbations, according to the symptoms that had the most impact on their well-being. Patients used additional self-management strategies during an exacerbation, such as self-medication (antibiotics and steroids) and monitored their recovery. Contact with health-care professionals usually occurred when patients felt no longer able to manage themselves. Conclusions: Patients use both assessment of objective biomarkers, which are aligned with medical knowledge, and subjective symptoms based on their experience, to identify and manage exacerbations of COPD. Health-care professionals and clinicians should acknowledge this ‘expert patient’ knowledge and integrate this into patients’ care plans to facilitate early recognition and treatment of exacerbations. PMID:25372181

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. [Predictive factors associated with severity of asthma exacerbations].

    PubMed

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

    2008-01-01

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

  3. 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

  4. Asthma exacerbations: risk factors for hospital readmissions.

    PubMed

    Gonzalez-Barcala, F-J; Calvo-Alvarez, U; Garcia-Sanz, M-T; Garcia-Couceiro, N; Martin-Lancharro, P; Pose, A; Carreira, J-M; Moure-Gonzalez, J-D; Valdes-Cuadrado, L; Muñoz, X

    2018-02-01

    The aim of our study is to analyse hospital readmissions due to asthma, as well as the factors associated with their increase. We carried out a retrospective study including all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The data were gathered by two members of the research team, by reviewing the clinical records. The first hospital admission of each patient was included for this study. An early readmission (ER) was defined as that which occurred in the following 15 days after hospital discharge and late readmission (LR) to that occurring from 16 days after discharge. This study included 2166 hospital admissions and 1316 patients, with a mean age of 62.6 years. Of the 1316 patients analysed, 36 (2.7%) had one ER and 313 (23.8%) one LR. The only factor independently associated with a higher probability of an ER was poor lung function. A higher probability of LR was associated with a greater severity of the asthma (OR: 17.8, for severe asthma versus intermittent asthma), to have had any hospital admission in the previous year (OR: 3.5) and the use of a combination of ICS-LABA as maintenance treatment. About 25% of the patients in our area admitted to hospital due to asthma exacerbation had repeat episodes of hospitalisation.

  5. Domiciliary pulse-oximetry at exacerbation of chronic obstructive pulmonary disease: prospective pilot study

    PubMed Central

    2010-01-01

    Background The ability to objectively differentiate exacerbations of chronic obstructive pulmonary disease (COPD) from day-to-day symptom variations would be an important development in clinical practice and research. We assessed the ability of domiciliary pulse oximetry to achieve this. Methods 40 patients with moderate-severe COPD collected daily data on changes in symptoms, heart-rate (HR), oxygen saturation (SpO2) and peak-expiratory flow (PEF) over a total of 2705 days. 31 patients had data suitable for baseline analysis, and 13 patients experienced an exacerbation. Data were expressed as multiples of the standard deviation (SD) observed from each patient when stable. Results In stable COPD, the SD for HR, SpO2 and PEF were approximately 5 min-1, 1% and 10l min-1. There were detectable changes in all three variables just prior to exacerbation onset, greatest 2-3 days following symptom onset. A composite Oximetry Score (mean magnitude of SpO2 fall and HR rise) distinguished exacerbation onset from symptom variation (area under receiver-operating characteristic curve, AUC = 0.832, 95%CI 0.735-0.929, p = 0.003). In the presence of symptoms, a change in Score of ≥1 (average of ≥1SD change in both HR and SpO2) was 71% sensitive and 74% specific for exacerbation onset. Conclusion We have defined normal variation of pulse oximetry variables in a small sample of patients with COPD. A composite HR and SpO2 score distinguished exacerbation onset from symptom variation, potentially facilitating prompt therapy and providing validation of such events in clinical trials. PMID:20961450

  6. Effects of Puberty on Cystic Fibrosis Related Pulmonary Exacerbations in Women Versus Men

    PubMed Central

    Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

    2014-01-01

    Summary Background Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. Objective In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Methods Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Results Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre-and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P < 0.001) despite controlling for morphometrics, co-morbidities, and microbiologic variables. Conclusion After puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. PMID:23460461

  7. 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

  8. Parental Numeracy and Asthma Exacerbations in Puerto Rican Children

    PubMed Central

    Rosas-Salazar, Christian; Ramratnam, Sima K.; Brehm, John M.; Han, Yueh-Ying; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Apter, Andrea J.

    2013-01-01

    Background: Puerto Ricans share a disproportionate burden of childhood asthma in the United States. Little is known about the impact of low parental numeracy (a health literacy skill) on asthma morbidity in Puerto Rican children. Our objective was to examine whether low parental numeracy is associated with increased asthma morbidity in Puerto Rican children. Methods: This was a cross-sectional study of 351 children with asthma, aged 6 to 14 years, living in San Juan, Puerto Rico. Parents of study participants completed a modified version of the Asthma Numeracy Questionnaire. Multivariate linear or logistic regression was used to examine the relation between low parental numeracy (defined as no correct answers in the modified Asthma Numeracy Questionnaire) and indicators of asthma morbidity (severe asthma exacerbations, core measures of asthma exacerbations, and lung function measures). All multivariate models were adjusted for age, sex, household income, reported use of inhaled corticosteroids in the previous 6 months, and exposure to secondhand tobacco smoke. Results: Low parental numeracy was associated with increased odds of visits to the ED or urgent care for asthma (adjusted OR [aOR] = 1.7, 95% CI = 1.03-2.7, P = .04). The association between low parental numeracy and hospitalizations for asthma was significant only among children not using inhaled corticosteroids (aOR = 2.8, 95% CI = 1.4-5.6, P = .004). There was no association between low parental numeracy and use of systemic steroids or lung function measures. Conclusions: Low parental numeracy is associated with increased asthma morbidity in Puerto Rican children. PMID:23493983

  9. Action plans for COPD: strategies to manage exacerbations and improve outcomes.

    PubMed

    Jalota, Leena; Jain, Vipul V

    2016-01-01

    COPD is the third-largest killer in the world, and certainly takes a toll on the health care system. Recurrent COPD exacerbations accelerate lung-function decline, worsen mortality, and consume over US$50 billion in health care spending annually. This has led to a tide of payment reforms eliciting interest in strategies reducing preventable COPD exacerbations. In this review, we analyze and discuss the evidence for COPD action plan-based self-management strategies. Although action plans may provide stabilization of acute symptomatology, there are several limitations. These include patient-centered attributes, such as comprehension and adherence, and nonadherence of health care providers to established guidelines. While no single intervention can be expected independently to translate into improved outcomes, structured together within a comprehensive integrated disease-management program, they may provide a robust paradigm.

  10. [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.

  11. Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and asthma exacerbations.

    PubMed

    Kljaic-Bukvic, Blazenka; Blekic, Mario; Aberle, Neda; Curtin, John A; Hankinson, Jenny; Semic-Jusufagic, Aida; Belgrave, Danielle; Simpson, Angela; Custovic, Adnan

    2014-10-01

    We investigated the interaction between genetic variants in endotoxin signalling pathway and domestic endotoxin exposure in relation to asthma presence, and amongst children with asthma, we explored the association of these genetic variants and endotoxin exposure with hospital admissions due to asthma exacerbations. In a case-control study, we analysed data from 824 children (417 asthmatics, 407 controls; age 5-18 yr). Amongst asthmatics, we extracted data on hospitalization for asthma exacerbation from medical records. Endotoxin exposure was measured in dust samples collected from homes. We included 26 single-nucleotide polymorphisms (SNPs) in the final analysis (5 CD14, 7LY96 and 14 TLR4). Two variants remained significantly associated with hospital admissions with asthma exacerbations after correction for multiple testing: for CD14 SNP rs5744455, carriers of T allele had decreased risk of repeated hospital admissions compared with homozygotes for C allele [OR (95% CI), 0.42 (0.25-0.88), p = 0.01, False Discovery Rate (FDR) p = 0.02]; for LY96 SNP rs17226566, C-allele carriers were at a lower risk of hospital admissions compared with T-allele homozygotes [0.59 (0.38-0.90), p = 0.01, FDR p = 0.04]. We observed two interactions between SNPs in CD14 and LY96 with environmental endotoxin exposure in relation to hospital admissions due to asthma exacerbation which remained significant after correction for multiple testing (CD14 SNPs rs2915863 and LY96 SNP rs17226566). Amongst children with asthma, genetic variants in CD14 and LY96 may increase the risk of hospital admissions with acute exacerbations. Polymorphisms in endotoxin pathway interact with domestic endotoxin exposure in further modification of the risk of hospitalization. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice.

    PubMed

    Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Fernandes, Lynette B; Zosky, Graeme R; Sly, Peter D; Larcombe, Alexander N

    2014-01-01

    Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle) daily for 10 days. On day 9, mice were inoculated with human-rhinovirus-1B (or UV-inactivated human-rhinovirus-1B). Forty-eight hours after inoculation, we assessed bronchoalveolar cellular inflammation, levels of relevant cytokines/serum antibodies, lung function and responsiveness/sensitivity to methacholine. House-dust-mite exposure did not result in a classical TH2-driven response, but was more representative of noneosinophilic asthma. However, there were significant effects of house-dust-mite exposure on most of the parameters measured including increased cellular inflammation (primarily macrophages and neutrophils), increased total IgE and house-dust-mite-specific IgG1 and increased responsiveness/sensitivity to methacholine. There were limited effects of human-rhinovirus-1B infection alone, and the combination of the two insults resulted in additive increases in neutrophil levels and lung parenchymal responses to methacholine (tissue elastance). We conclude that acute rhinovirus infection exacerbates house-dust-mite-induced lung disease in adult mice. The similarity of our results using the naturally occurring allergen house-dust-mite, to previous studies using ovalbumin, suggests that the exacerbation of allergic airways disease by rhinovirus infection could act via multiple or conserved mechanisms.

  13. Exhaled nitric oxide levels in exacerbations of asthma, chronic obstructive pulmonary disease and pneumonia.

    PubMed

    Al-Ali, M K; Howarth, P H

    2001-03-01

    Nitric oxide is known to be present in the exhaled air of normal subjects and at higher concentrations in asthmatics. The aim of this study was to measure exhaled nitric oxide levels in patients admitted to hospital with acute exacerbations of asthma, or chronic obstructive pulmonary disease, or with pneumonia. Within 24 hours of admission exhaled nitric oxide levels were measured by a chemiluminescent analyzer in 11 patients with acute sever asthma, 19 patients with acute exacerbation of chronic obstructive pulmonary disease, and in 12 patients with pneumonia. In asthmatics measurements were made on 3 occasions, at day 1, 4, and 28 and were related to changes in peak expiratory flow rate. On admission median exhaled nitric oxide levels (range) were significantly higher in asthmatics 22 (9.3-74) parts per billion in comparison to patients with chronic obstructive pulmonary disease 10.3 (2.7-34) parts per billion; p < 0.01, pneumonia 7 (4-17) parts per billion; p<0.001, and normal subjects 8.7 (5-13.3) parts per billion; p < 0.001. Following treatment the asthmatics had a significant reduction in their exhaled nitric oxide levels from 22 (9.3-74) parts per billion on day 1 to 9.7 (5.7-18.3) parts per billion on day 28; p = 0.005. Peak expiratory flow rate measurements increased from 200 (120-280) l/min on day 1 to 280 (150-475) l/min on day 4; p < 0.05 and to 390 (150-530) l/min on day 28; p < 0.01. A strong negative correlation existed between peak expiratory flow rate measurements and exhaled nitric oxide levels in asthmatics on day 28 (r = -0.70; p = 0.017). Acute exacerbations of asthma are associated with increased levels of exhaled nitric oxide in contrast to exacerbations of chronic obstructive pulmonary disease and acute pneumonia. Exhaled nitric oxide may be a useful indirect marker of asthmatic airway inflammation. The differing time course of response of nitric oxide to peak flow measures suggests that these two measures are reflecting differing airway

  14. Lethal acute demyelinization with encephalo-myelitis as a complication of cured Cushing's disease.

    PubMed

    Chevalier, N; Hieronimus, S; Vandenbos, F; Delmont, E; Cua, E; Cherick, F; Paquis, P; Michiels, J-F; Fenichel, P; Brucker-Davis, F

    2010-12-01

    Cushing's disease is usually associated with higher mortality rate, especially from cardiovascular causes. Development or exacerbation of autoimmune or inflammatory diseases is known to occur in patients with hypercortisolism after cure. We report for the first time a 34-year old woman with a psychiatric background, who developed four months after the surgical cure of Cushing's disease an acute disseminated encephalomyelitis (ADEM) presenting initially as a psychiatric illness. We hypothesize that the recent correction of hypercortisolism triggered ADEM and that the atypical presentation, responsible for diagnosis delay, led to the death of this patient. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  15. [Treatment of multiple sclerosis symptoms and exacerbations].

    PubMed

    Prieto González, José María

    2014-12-01

    In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. 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

  17. COPD Exacerbation and Cholinesterase Therapy in Dementia Patients.

    PubMed

    Mahan, Rebecca J; Blaszczyk, Amie Taggart

    2016-04-01

    Chronic obstructive pulmonary disease (COPD) is a nonreversible inflammatory condition of the lungs. Acetylcholine is a neurotransmitter involved in autonomic regulation of the airways, resulting in bronchoconstriction and mucous production. Cholinesterase inhibitors (ChEIs), a cornerstone therapy of dementia treatment, increase acetylcholine. Theoretically, ChEI use in patients with COPD can place patients at increased risk of exacerbation secondary to increased acetylcholine activity. A retrospective chart review was performed comparing veterans with dementia and COPD who received ChEIs with those who did not at the Veterans Affairs North Texas Health Care System. Frequency of exacerbation in the first 90 days following ChEI initiation was compared. Secondary outcomes assessed exacerbation severity and a potential protective effect of inhaled anticholinergics. A total of 94 patients were eligible for the study; 52 received a ChEI and 42 did not. The risk of exacerbation over 90 days was higher in the ChEI users with 10 (19%) experiencing an exacerbation compared with 3 (7%) in the nonusers (P = 0.133), showing a clinically significant trend. Of the patients experiencing an exacerbation, 2 patients on ChEIs had multiple exacerbations over the 90 days. The use of inhaled anticholinergics was not found to decrease the risk of exacerbation. The use of ChEIs may increase the risk of COPD exacerbation in the first 90 days of therapy in patients with dementia and COPD. This finding is clinically significant as previous studies have indicated no risk.

  18. 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

  19. 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

  20. How do patients with exacerbated chronic obstructive pulmonary disease experience care in the intensive care unit?

    PubMed Central

    Torheim, Henny; Kvangarsnes, Marit

    2014-01-01

    The aim was to gain insight into how patients with advanced chronic obstructive pulmonary disease (COPD) experience care in the acute phase. The study has a qualitative design with a phenomenological approach. The empirics consist of qualitative in-depth interviews with ten patients admitted to the intensive care units in two Norwegian hospitals. The interviews were carried out from November 2009 to June 2011. The data have been analysed through meaning condensation, in accordance with Amadeo Giorgi's four-step method. Kari Martinsen's phenomenological philosophy of nursing has inspired the study. An essential structure of the patients' experiences of care in the intensive care unit by acute COPD-exacerbation may be described as: Feelings of being trapped in a life-threatening situation in which the care system assumes control over their lives. This experience is conditioned not only by the medical treatment, but also by the entire interaction with the caregivers. The essence of the phenomenon is presented through three themes which describe the patient's lived experience: preserving the breath of life, vulnerable interactions and opportunities for better health. Acute COPD-exacerbation is a traumatic experience and the patients become particularly vulnerable when they depend on others for breathing support. The phenomenological analysis shows that the patients experience good care during breath of life preservation when the care is performed in a way that gives patients more insight into their illness and gives new opportunities for the future. PMID:24313779

  1. A pilot study to monitor changes in spirometry and lung volume, following an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), as part of a supported discharge program.

    PubMed

    Cushen, Breda; McCormack, Niamh; Hennigan, Kerrie; Sulaiman, Imran; Costello, Richard W; Deering, Brenda

    2016-10-01

    One-third of patients with an exacerbation of Chronic Obstructive Pulmonary Disease(COPD) are re-hospitalised at 90 days. Exacerbation recovery is associated with reductions in lung hyperinflation and improvements in symptoms and physical activity. We assessed the feasibility of monitoring these clinical parameters in the home. We hypothesised that the degree of change in spirometry and lung volumes differs between those who had an uneventful recovery and those who experienced a further exacerbation. Hospitalised patients with an acute exacerbation of COPD referred for a supported discharge program participated in the study. Spirometry and Inspiratory Vital Capacity(IVC) were measured in the home at Days 1, 14 and 42 post-discharge. Patients also completed Medical Research Council(MRC), Borg and COPD Assessment Test(CAT) scores and were provided with a tri-axial accelerometer. Any new exacerbation events were recorded. Sixty-five patients with 72 exacerbation episodes were recruited. Fifty percent experienced a second exacerbation. Adequate IVC measurements were achieved by 90%, while only 70% completed spirometry. Uneventful recovery was accompanied by significant improvements in physiological measurements at day14, improved symptom scores and step count, p < 0.05. Failure of MRC to improve was predictive of re-exacerbation(Area Under Receiver Operating Curve(AUROC) 0.6713) with improvements in FEV 1 ≥100 ml(AUROC 0.6613) and mean daily step count ≥396 steps(AUROC 0.6381) predictive of recovery. Monitoring the pattern of improvement in spirometry, lung volumes, symptoms and step count following a COPD exacerbation may help to identify patients at risk of re-exacerbation. It is feasible to carry out these assessments in the home as part of a supported discharge programme. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Long-term Prognosis in COPD Exacerbation: Role of Biomarkers, Clinical Variables and Exacerbation Type.

    PubMed

    Grolimund, Eva; Kutz, Alexander; Marlowe, Robert J; Vögeli, Alaadin; Alan, Murat; Christ-Crain, Mirjam; Thomann, Robert; Falconnier, Claudine; Hoess, Claus; Henzen, Christoph; Zimmerli, Werner; Mueller, Beat; Schuetz, Philipp

    2015-06-01

    Long-term outcome prediction in COPD is challenging. We conducted a prospective 5-7-year follow-up study in patients with COPD to determine the association of exacerbation type, discharge levels of inflammatory biomarkers including procalctionin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and plasma proadrenomedullin (ProADM), alone or combined with demographic/clinical characteristics, with long-term all-cause mortality in the COPD setting. The analyzed cohort comprised 469 patients with index hospitalization for pneumonic (n = 252) or non-pneumonic (n = 217) COPD exacerbation. Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/primary care physicians. We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve (AUC). After a median [25th-75th percentile] 6.1 [5.6-6.5] years, mortality was 55% (95%CI 50%-59%). Discharge ProADM concentration was strongly associated with 5-7-year non-survival: adjusted hazard ratio (HR)/10-fold increase (95%CI) 10.4 (6.2-17.7). Weaker associations were found for PCT and no significant associations were found for CRP or WBC. Combining ProADM with demographic/clinical variables including age, smoking status, BMI, New York Heart Association dyspnea class, exacerbation type, and comorbidities significantly improved long-term predictive accuracy over that of the demographic/clinical model alone: AUC (95%CI) 0.745 (0.701-0.789) versus 0.727 (0.681-0.772), (p) = .043. In patients hospitalized for COPD exacerbation, discharge ProADM levels appeared to accurately predict 5-7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/clinical mortality risk assessment.

  3. Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: a pilot randomized study of high-dose vitamin D3 administration

    PubMed Central

    Alvarez, Jessica A.; Chong, Elizabeth Y.; Walker, Douglas I.; Chandler, Joshua D.; Michalski, Ellen S.; Grossmann, Ruth E.; Uppal, Karan; Li, Shuzhao; Frediani, Jennifer K.; Tirouvanziam, Rabindra; Tran, ViLinh T.; Tangpricha, Vin; Jones, Dean P.; Ziegler, Thomas R.

    2017-01-01

    Background Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. Objective We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. Design Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000 IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. Results Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways--predominantly representing amino acid pathways-- differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3

  4. Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

    PubMed Central

    Glabinski, Andrzej

    2015-01-01

    Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

  5. 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.

  6. Experiences of patients undergoing pulmonary rehabilitation during an exacerbation of chronic respiratory disease.

    PubMed

    Vincent, Emma E; Chaplin, Emma J; Williams, Johanna Ea; Harvey-Dunstan, Theresa; Greening, Neil J; Steiner, Michael C; Morgan, Mike D; Singh, Sally J

    2017-08-01

    Chronic obstructive pulmonary disease (COPD) is characterized in the later stages by acute exacerbations that often require hospitalization. Pulmonary rehabilitation is recommended for patients with COPD to aid symptom control, improve quality of life and increase physical activity. We have previously reported a large intervention trial commenced during a hospital admission. The aim of this sub-study was to evaluate the patients' experiences of discharge following the hospitalization for an acute exacerbation of COPD. During a programme of early rehabilitation (ER) patient perceptions, experiences and healthcare use were collated during the month that followed their discharge. ER (started during their admission) was comprised of exercise training techniques that were modified to suit the environment of acute illness, together with an education and self-management programme. Each patient was then supported on the programme by telephone contact, following their discharge home, at 48 hours, 2 weeks and 4 weeks. We collected information in relation to the walking and exercise progression; we monitored patient recall of healthcare use, compliance/understanding of medical therapy, as well as their wider perceptions that may have influenced the recovery process. Healthcare use was captured using GP records and data analysis. Of the 100 patients, 47 males, (mean (standard deviation)) 71 (9.3) years, FEV 1 1.14 L (0.6), BMI 26.6 (6.9), pack smoked years 45.8 (29.6), ethnicity White British 97%, were discharged home following an acute exacerbation of their respiratory symptoms, to an ER programme. At 48 hours following discharge, a minority (20%) of patients stated their symptoms were 'feeling better'; 15% highlighted that they found the prescribed 'exercise difficult'; 44% of patients felt at the end of the month that prescribed exercise programme had a 'positive effect' on their recovery from their exacerbation; 38% of patients felt their family had a positive effect on

  7. Aluminum exacerbates cyclosporin induced nephrotoxicity in rats.

    PubMed

    Tariq, M; Morais, C; Sujata, B; Sobki, S; al Sulaiman, M; al Khader, A

    1999-01-01

    Cyclosporin (CSA) has been universally used as an immunosuppressant for the management of allotransplantation and autoimmune diseases. However, nephrotoxicity of CSA limits its use to optimum level. Aluminum (Al) is an extensively distributed element in the environment and human exposure to this metal is unavoidable. Recent studies suggest that even a slight impairment of renal function may increase the Al body burden significantly, which may lead to neurotoxicity, nephrotoxicity, osteodystrophy or hypochromic anemia. In the present study, an attempt was made to study the effect of concomitant use of Al and CSA on structure and function of kidney in rats. This study was undertaken in two steps. In the first set of experiments, the effect of single dose of Al (1% Al2(SO4)3 18H2O) on the nephrotoxicity of multiple doses of CSA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) was studied, where as in the second set of experiments the effect of multiple doses of Al (0.25%, 0.5% and 1%) on single dose of CSA (50 mg/kg) was undertaken. Male Sprague-Dawley rats (weighing 230 +/- 20 g) were used in this study. CSA was given once a day by gavage for seven days, where as Al was given in drinking water for the same period. Twenty four hours after the last dose of CSA, animals were sacrificed and blood and kidney were collected for biochemical and histopathological studies. The bio-chemical parameters included blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Al levels. The kidney homogenates were assayed for malondialdehyde (MDA) and lipid hydroperoxides (LPH). Treatment of rats with CSA alone produced dose-dependent structural and functional changes in kidney. Although Al alone failed to produce any deleterious effect on renal function, it significantly increased the bioavailability and nephrotoxicity of CSA. Al also exacerbated CSA induced increase in oxidative stress (as evident by increased MDA and LPH). Thus, the exacerbation of CSA nephrotoxicity by Al may be attributed to

  8. 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.

  9. Donor Brain Death Exacerbates Complement-Dependent Ischemia Reperfusion Injury in Transplanted Hearts

    PubMed Central

    Atkinson, Carl; Floerchinger, Bernhard; Qiao, Fei; Casey, Sarah; Williamson, Tucker; Moseley, Ellen; Stoica, Serban; Goddard, Martin; Ge, Xupeng; Tullius, Stefan G.; Tomlinson, Stephen

    2013-01-01

    Background Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia reperfusion injury (IRI) post-transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on post transplant cardiac IRI. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of BD donor hearts, and addressed the clinical relevance of these studies by analysis of human heart biopsies from BD and domino (living) donors. Methods and Results Hearts from living or brain dead donor C57BL/6 mice were transplanted into C57BL/6 or BALB/c recipients. Recipient mice were treated with the complement inhibitor CR2-Crry or vehicle control (n=6). Isografts were analyzed 48 hours post-transplant for injury, inflammation and complement deposition, and allografts monitored for graft survival. Human cardiac biopsies were analyzed for complement deposition and inflammatory cell infiltration. In the murine model, donor BD exacerbated IRI and graft rejection as demonstrated by increased myocardial injury, serum cardiac troponin, cellular infiltration, inflammatory chemokine and cytokine levels, complement deposition, and decreased graft survival. CR2-Crry treatment of recipients significantly reduced all measured outcomes in grafts from both BD and living donors compared to controls. Analysis of human samples documented the relevance of our experimental findings and revealed exacerbated complement deposition and inflammation in grafts from BD donors compared to grafts from living donors. Conclusions BD exacerbates post-transplant cardiac IRI in mice and humans, and decreases survival of mouse allografts. Further, targeted complement inhibition in recipient mice ameliorates BD-exacerbated IRI. PMID:23443736

  10. Predicting asthma exacerbations using artificial intelligence.

    PubMed

    Finkelstein, Joseph; Wood, Jeffrey

    2013-01-01

    Modern telemonitoring systems identify a serious patient deterioration when it already occurred. It would be much more beneficial if the upcoming clinical deterioration were identified ahead of time even before a patient actually experiences it. The goal of this study was to assess artificial intelligence approaches which potentially can be used in telemonitoring systems for advance prediction of changes in disease severity before they actually occur. The study dataset was based on daily self-reports submitted by 26 adult asthma patients during home telemonitoring consisting of 7001 records. Two classification algorithms were employed for building predictive models: naïve Bayesian classifier and support vector machines. Using a 7-day window, a support vector machine was able to predict asthma exacerbation to occur on the day 8 with the accuracy of 0.80, sensitivity of 0.84 and specificity of 0.80. Our study showed that methods of artificial intelligence have significant potential in developing individualized decision support for chronic disease telemonitoring systems.

  11. Early life persistent vitamin D deficiency exacerbates ...

    EPA Pesticide Factsheets

    Epidemiological and animal data have conclusively linked adverse cardiovascular outcomes to air pollution exposure. As such, cardiovascular function is maintained by adequate levels of certain essential micronutrients like vitamin D. Unfortunately, vitamin D deficiency (VDD) has become highly prevalent in the United States, as well as in the world, even affecting otherwise healthy individuals. My initial studies showed that VDD alters cardiac function, increases cardiac arrhythmia and HRV (i.e. indirect measure of autonomic tone) in mice; this response is further exacerbated after smog exposure. VDD has been shown to alter the responsiveness of transient receptor potential A1 (TRPA1) channels, which we have previously shown to be involved in cardiopulmonary dysfunction to acrolein, which is a ubiquitous air pollutant and potent TRPA1 agonist. The effect of VDD on TRPA1-induced air pollution responses is not known and is the purpose of this study. 3-week old mice were placed on a VDD or normal diet (ND) for 19 weeks and then implanted with radiotelemeters for the measurement of heart rate, electrocardiogram and HRV. Mice were exposed to filtered air then acrolein for 3 hours each on separate days. During exposure, ventilatory function and ECG were simultaneously recorded. Acrolein increased parasympathetic tone in ND mice, but not VDD mice during exposure. However, acrolein caused cardiac arrhythmias only in VDD mice during exposure. Similar to previous studies,

  12. 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.

  13. Effects of written action plan adherence on COPD exacerbation recovery.

    PubMed

    Bischoff, Erik W M A; Hamd, Dina H; Sedeno, Maria; Benedetti, Andrea; Schermer, Tjard R J; Bernard, Sarah; Maltais, François; Bourbeau, Jean

    2011-01-01

    The effects of written action plans on recovery from exacerbations of chronic obstructive pulmonary disease (COPD) have not been well studied. The aims of this study were to assess the effects of adherence to a written action plan on exacerbation recovery time and unscheduled healthcare utilisation and to explore factors associated with action plan adherence. This was a 1-year prospective cohort study embedded in a randomised controlled trial. Exacerbation data were recorded for 252 patients with COPD who received a written action plan for prompt treatment of exacerbations with the instructions to initiate standing prescriptions for both antibiotics and prednisone within 3 days of exacerbation onset. Following the instructions was defined as adherence to the action plan. From the 288 exacerbations reported by 143 patients, start dates of antibiotics or prednisone were provided in 217 exacerbations reported by 119 patients (53.8% male, mean age 65.4 years, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 43.9% predicted). In 40.1% of exacerbations, patients adhered to their written action plan. Adherence reduced exacerbation recovery time with statistical (p=0.0001) and clinical (-5.8 days) significance, but did not affect unscheduled healthcare utilisation (OR 0.94, 95% CI 0.49 to 1.83). Factors associated with an increased likelihood of adherence were influenza vaccination, cardiac comorbidity, younger age and lower FEV(1) as percentage predicted. This study shows that adherence to a written action plan is associated with a reduction in exacerbation recovery time by prompt treatment. Knowing the factors that are associated with proper and prompt utilisation of an action plan permits healthcare professionals to better focus their self-management support on appropriate patients.

  14. [Exacerbations of asthma in Guadeloupe (French West Indies) and volcanic eruption in Montserrat (70 km from Guadeloupe)].

    PubMed

    Cadelis, G; Tourres, R; Molinie, J; Petit, R H

    2013-03-01

    This study evaluates the impact of the ash cloud emitted in February 2010 during the eruption of the Soufrière Hill volcano of the island of Montserrat (70 km from Guadeloupe), on asthma exacerbations registered by the emergency hospital services in the archipelago of Guadeloupe in February 2010. We first recorded the clinical features and outcome of each adult patient admitted as an emergency with an acute asthma exacerbation during this period, then compared the admission rates for asthma exacerbation, concentrations of particulates and chemical pollutants, and climatic parameters before, during, and after exposure to the ash cloud. Then, using a generalized linear model defined by a Poisson regression, we calculated the risks related to these factors. There was an increase in acute asthma admissions during and after exposure to the ash cloud (2.44/day versus 5.6/day, P<0.003). PM10 (particles<10 microns) were the major particulate pollution episodes (mean: 223 μg/m(3)). Asthmatics admitted acutely during the period of pollution were young adults (35 [18-49] years old), and the majority had asthma classified as intermittent (57%, n=27). In multivariate analysis, PM10 were a risk factor for acute asthma presentations during this period (aRR 2.89, 95% [from 1.69 to 4.93]). This study describes the clinical data and outcome of adult patients admitted to emergency asthma exacerbation during the eruption of the Soufrière Hills Volcano in Montserrat and indicates that there was a significant impact of the ash plume on respiratory health, mainly in patients with intermittent asthma. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  15. Acupuncture for acute hordeolum

    PubMed Central

    Cheng, Ke; Law, Andrew; Guo, Menghu; Wieland, L. Susan; Shen, Xueyong; Lao, Lixing

    2017-01-01

    Background Hordeolum is an acute, purulent inflammation of the eyelid margin usually caused by obstructed orifices of the sebaceous glands of the eyelid. The condition, which affects sebaceous glands internally or externally, is common. When the meibomian gland in the tarsal plate is affected, internal hordeolum occurs, while when the glands of Zeis or Moll associated with eyelash follicles are affected, external hordeolum, or stye occurs. The onset of hordeolum is usually self limited, and may resolve in about a week with spontaneous drainage of the abscess. When the condition is severe, it can spread to adjacent glands and tissues. Recurrences are very common. As long as an internal hordeolum remains unresolved, it can develop into a chalazion or generalized eyelid cellulitis. Acupuncture is a traditional Chinese medical therapy aimed to treat disease by using fine needles to stimulate specific points on the body. However, it is unclear if acupuncture is an effective and safe treatment for acute hordeolum. Objectives The objective of this review was to investigate the effectiveness and safety of acupuncture to treat acute hordeolum compared with no treatment, sham acupuncture, or other active treatment. We also compared the effectiveness and safety of acupuncture plus another treatment with that treatment alone. Search methods We searched CENTRAL, Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, Embase, PubMed, Latin American and Caribbean Health Sciences Literature Database (LILACS), three major Chinese databases, as well as clinical trial registers all through 7 June 2016. We reviewed the reference lists from potentially eligible studies to identify additional randomised clinical trials (RCTs). Selection criteria We included RCTs of people diagnosed with acute internal or external hordeola. We included RCTs comparing acupuncture with sham acupuncture or no treatment, other active treatments, or

  16. Relationship between airway colonization, inflammation and exacerbation frequency in COPD.

    PubMed

    Tumkaya, Munir; Atis, Sibel; Ozge, Cengiz; Delialioglu, Nuran; Polat, Gurbuz; Kanik, Arzu

    2007-04-01

    To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.

  17. Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

    PubMed Central

    Mansur, Adel H.; Pertseva, Tetyana; Kaiser, Kirsten; McIver, Tammy; Grothe, Birgit; Dissanayake, Sanjeeva

    2016-01-01

    Abstract Background: A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations. Methods: The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs. Results: The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively. Conclusions: The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be

  18. Claims-based risk model for first severe COPD exacerbation.

    PubMed

    Stanford, Richard H; Nag, Arpita; Mapel, Douglas W; Lee, Todd A; Rosiello, Richard; Schatz, Michael; Vekeman, Francis; Gauthier-Loiselle, Marjolaine; Merrigan, J F Philip; Duh, Mei Sheng

    2018-02-01

    To develop and validate a predictive model for first severe chronic obstructive pulmonary disease (COPD) exacerbation using health insurance claims data and to validate the risk measure of controller medication to total COPD treatment (controller and rescue) ratio (CTR). A predictive model was developed and validated in 2 managed care databases: Truven Health MarketScan database and Reliant Medical Group database. This secondary analysis assessed risk factors, including CTR, during the baseline period (Year 1) to predict risk of severe exacerbation in the at-risk period (Year 2). Patients with COPD who were 40 years or older and who had at least 1 COPD medication dispensed during the year following COPD diagnosis were included. Subjects with severe exacerbations in the baseline year were excluded. Risk factors in the baseline period were included as potential predictors in multivariate analysis. Performance was evaluated using C-statistics. The analysis included 223,824 patients. The greatest risk factors for first severe exacerbation were advanced age, chronic oxygen therapy usage, COPD diagnosis type, dispensing of 4 or more canisters of rescue medication, and having 2 or more moderate exacerbations. A CTR of 0.3 or greater was associated with a 14% lower risk of severe exacerbation. The model performed well with C-statistics, ranging from 0.711 to 0.714. This claims-based risk model can predict the likelihood of first severe COPD exacerbation. The CTR could also potentially be used to target populations at greatest risk for severe exacerbations. This could be relevant for providers and payers in approaches to prevent severe exacerbations and reduce costs.

  19. Impact of exacerbations on health care cost and resource utilization in chronic obstructive pulmonary disease patients with chronic bronchitis from a predominantly Medicare population

    PubMed Central

    Pasquale, Margaret K; Sun, Shawn X; Song, Frank; Hartnett, Heather J; Stemkowski, Stephen A

    2012-01-01

    Background Exacerbations of chronic obstructive pulmonary disease (COPD) lead to significant increases in resource utilization and cost to the health care system. COPD patients with chronic bronchitis and a history of exacerbations pose an additional burden to the system. This study examined health care utilization and cost among these patients. Methods For this retrospective analysis, data were extracted from a large national health plan with a predominantly Medicare population. This study involved patients who were aged 40–89 years, had been enrolled continuously for 24 months or more, had at least two separate insurance claims for COPD with chronic bronchitis (International Classification of Diseases, Ninth Revision, Clinical Modification code 491.xx), and had pharmacy claims for COPD maintenance medications between January 1, 2007, and March 31, 2009. Two years of data were examined for each patient; the index date was defined as the first occurrence of COPD. Baseline characteristics were obtained from the first year of data, with health outcomes tracked in the second year. Severe exacerbation was defined by COPD-related hospitalization or death; moderate exacerbation was defined by oral or parenteral corticosteroid use. Adjusted numbers of exacerbations and COPD-related costs per patient were estimated controlling for demographic and clinical characteristics. Results The final study sample involved 8554 patients; mean age was 70.1 ± 8.6 years and 49.8% of the overall population had exacerbation, 13.9% had a severe exacerbation only, 29.1% had a moderate exacerbation only, and 6.8% had both a severe and moderate exacerbation. COPD-related mean annual costs were $4069 (all figures given in US dollars) for the overall population and $6381 for patients with two or more exacerbations. All-cause health care costs were $18,976 for the overall population and $23,901 for patients with history of two or more exacerbations. Severity of exacerbations, presence of

  20. Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications

    PubMed Central

    Qureshi, Hammad; Sharafkhaneh, Amir

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations which have major short- and long-term implications on the patient and healthcare system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. Several factors can identify populations at risk of exacerbations. Implementing prevention measures in patients at risk is a major goal in the management of COPD. PMID:25177479

  1. 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

  2. High-dose nebulized budesonide is effective for mild asthma exacerbations in children under 3 years of age.

    PubMed

    Saito, M; Kikuchi, Y; Kawarai Lefor, A; Hoshina, M

    2017-01-01

    Background. High-dose inhaled steroid therapy has been shown to be effective in children and adults with asthma exacerbations. However, few reports are available regarding its efficacy for asthma exacerbations in younger children. Objective. In this study, we administered high-dose nebulized budesonide therapy for mild asthma exacerbations in children < 3 years of age and compared its efficacy and safety with systemic steroid therapy. Methods. This study included children < 3 years old with mild asthma exacerbations. Patients were randomly assigned to two groups: the BIS group was given 1 mg of nebulized budesonide twice daily, and the PSL group received prednisolone 0.5 mg/kg iv three times daily. Days to disappearance of wheezing, days of steroid use, days of oxygen use, serum cortisol level, and incidence of adverse events during treatment were compared between the groups. Result. Wheezing disappeared after an average of five days, and steroids were administered for an average of five days in both groups, with no significant difference in days of oxygen use. Serum cortisol levels at initiation and during the course of treatment remained unchanged in the BIS group, and were decreased in the PSL group; however, the decrease in the latter group was not pathologic. Conclusion. For children < 3 years old with mild asthma exacerbations, high-dose nebulized budesonide therapy is equally as effective as systemic steroid therapy.

  3. Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to Ambient Air Pollutants

    PubMed Central

    Tétreault, Louis-Francois; Doucet, Marieve; Gamache, Philippe; Fournier, Michel; Brand, Allan; Kosatsky, Tom; Smargiassi, Audrey

    2016-01-01

    Background: It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). Method: Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the child’s residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. Results: Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 μg/m3) of 1.095 (95% CI 1.058–1.131), 1.052 (95% CI 1.037–1.066) and 1.025 (95% CI 1.017–1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO2 or O3. Conclusions: Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth. PMID:27490556

  4. Occupational exposures associated with severe exacerbation of asthma.

    PubMed

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

    2015-02-01

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

  5. 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

  6. Fungal Exposure, Atopy, and Asthma Exacerbations in Puerto Rican Children

    PubMed Central

    Blatter, Joshua; Forno, Erick; Brehm, John; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Thorne, Peter S.; Metwali, Nervana; Canino, Glorisa

    2014-01-01

    Background: Glucan is a component of the fungal cell wall that is used as a marker of fungal exposure. Little is known about indoor glucan, atopy, and asthma exacerbations among children living in tropical environments such as Puerto Rico. Our objective was to examine whether glucan exposure is associated with degree of atopy or visits to the emergency department (ED)/urgent care for asthma in Puerto Rican children. Methods: This was a cross-sectional study of 317 children aged 6 to 14 years with (cases, n = 160) and without (control subjects, n = 157) asthma in San Juan, Puerto Rico. Our primary outcomes were the number of positive skin tests to allergens (range, 0–15) and (in cases only) having had at least one visit to the ED/urgent care for asthma in the prior year. Levels of glucan, endotoxin, peptidoglycan, and five allergens (Der p 1, Bla g 2, Fel d 1, Can f 1, and Mus m 1) were measured in samples of house dust. Linear or logistic regression was used for the multivariate analysis. Measurements and Main Results: In a multivariate analysis adjusting for case-control status, mouse allergen, and other covariates, children exposed to glucan levels in the second and third quartiles had approximately two more positive skin tests than those in the lowest quartile (P < 0.01 in both instances). Among children with asthma, exposure to the highest quartile of glucan was associated with nearly ninefold greater odds of one or more visits to the ED/urgent care for asthma (95% confidence interval for adjusted odds ratio, 2.7–28.4; P < 0.001). Conclusions: Our results suggest that indoor fungal exposure leads to an increased degree of atopy and visits to the ED/urgent care for asthma in Puerto Rican children. PMID:24915164

  7. Exacerbations in patients with chronic obstructive pulmonary disease receiving physical therapy: a cohort-nested randomised controlled trial

    PubMed Central

    2014-01-01

    Background Physical exercise training aims at reducing disease-specific impairments and improving quality of life in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations in particular negatively impact COPD progression. Physical therapy intervention seems indicated to influence exacerbations and their consequences. However, information on the effect of physical therapy on exacerbation occurrence is scarce. This study aims to investigate the potential of a protocol-directed physical therapy programme as a means to prevent or postpone exacerbations, to shorten the duration or to decrease the severity of exacerbations in patients with COPD who have recently experienced an exacerbation. Besides, this study focuses on the effect of protocol-directed physical therapy on health status and quality of life and on cost-effectiveness and cost-utility in patients with COPD who have recently experienced an exacerbation. Methods/Design A prospective cohort of 300 COPD patients in all GOLD stages will be constructed. Patients will receive usual multidisciplinary COPD care including guideline-directed physical therapy. Patients in this cohort who have GOLD stage 2 to 4 (post-bronchodilator FEV1/FVC < 0.7 and FEV1 < 80% of predicted), who receive reimbursement by health insurance companies for physical therapy (post-bronchodilator Tiffeneau-index < 0.6) and who experience a COPD exacerbation will be asked within 56 days to participate in a cohort-nested prospective randomised controlled trial (RCT). In this RCT, the intervention group will receive a strict physical therapy programme for patients with COPD. This protocol-directed physical therapy (pdPT) will be compared to a control group that will receive sham-treatment, meaning no or very low-intensity exercise training (ST). An economic evaluation will be embedded in the RCT. Anthropometric measurements, comorbidities, smoking, functional exercise capacity, peripheral muscle strength

  8. [The effect of fenspiride on the number of exacerbations and the time of first exacerbation in patients with chronic bronchitis].

    PubMed

    Pirozyński, Michał; Skucha, Wojciech; Słomiński, Marek; Chyczewska, Elzbieta; Malinowski, Janusz; Nowak, Dariusz; Bartmińiski, Wojciech; Pachocki, Robert

    2005-08-01

    The aim of the work was evaluation of efficacy of fenspiride b.i.d. on the number of exacerbations and the time to the first exacerbation in patients with chronic bronchitis. Randomized, multicentre study controlled versus placebo was carried out in 12 centers in Poland. All patients, 89 females and 68 males aged between 20 and 74, were treated with fenspiride at the dose of 160 mg/day for a period of 6 months. The following symptoms were recorded every month in order to evaluate the therapeutic efficacy: sputum quality and quantity, cough intensity, dyspnea and bronchospasm. Based on these symptoms diagnosis of exacerbation was performed according to American Thoracic Society criteria. Quality and quantity of sputum and cough significantly improved in the fenspiride group (comparing to the placebo group p= 0.027 and p = 0.049 adequately for sputum and cough). A significant difference between groups was observed in the number of exacerbation episodes and their duration. In the fenspiride group there were 0.53 episodes of exacerbation compared with 1.12 episodes in the placebo group (p = 0.038). Mean duration of exacerbation was 3.3 days in the fenspiride group and 7.3 days in the placebo treated patients (p = 0.034). Time to the first exacerbation differed between groups, but this difference was not statistically significant. Number of side effects observed did not differ between groups. Fenspiride treatment was assessed as relatively effective in terms of influence on exacerbations, and well tolerated during six month therapy.

  9. Choline Triggers Exacerbations of Chronic Obstructive Pulmonary Disease in Patients Infected with Pseudomonas aeruginosa

    PubMed Central

    Grumelli, Sandra

    2017-01-01

    Background Although exacerbations of chronic obstructive pulmonary disease produced by Pseudomonas aeruginosa infections are a major cause of death, the molecular mechanism that produces them is not well known. Here we focused on the energetic basis of dyspnoea, hypercapnia and acidosis symptoms. Methods and Findings We used an in vivo exacerbation model exposing mice to cigarette smoke and LPS, to mimic emphysema and infections, and choline challenges to trigger exacerbations, that showed 31% increased in the airway resistance for naïve mice and 250% for smoke/LPS treatment. Tissue resistance was increased 32%, in naïve mice, and 169% for smoke/LPS treatment. A decreased tissue elastance, was confirmed by decreased collagen content and increased alveoli chord length. Consequently, the O2 demanded was 260% greater for smoke/LPS treated mice, to provide the energy required to pump the same volume of air then for naïve mice. The extra CO2 produced per ml of air pumped caused hypercapnia and acidosis by 4% decrease in pH. In addition, the bacteria grown with choline had a decrease of 67% in phosphate, 23% ATP and 85% phospholipids with an increase of 57% in polyphosphates, 50% carbohydrates, 100% LPS, consuming 45% less energy relative to the bacteria grown with succinate. Conclusion choline, released by P. aeruginosa, triggers exacerbation symptoms by increasing lung resistance, O2 consumption and producing more pCO2 in blood with dyspnea, hypercapnia and acidosis. The energetic shift of decreased O2 bacterial demand and increased lung demand benefits the infection, thus restoring the energetic balance on the host will favor P. aeruginosa eradication. PMID:29386986

  10. Determinants of change in physical activity during moderate-to-severe COPD exacerbation

    PubMed Central

    Esteban, Cristóbal; Quintana, José M; Garcia-Gutierrez, Susana; Anton-Ladislao, Ane; Gonzalez, Nerea; Baré, Marisa; Fernández de Larrea, Nerea; Rivas-Ruiz, Francisco

    2016-01-01

    Background Data are scarce on patient physical activity (PA) level during exacerbations of chronic obstructive pulmonary disease (eCOPD). The objective of the study was to evaluate the level and determinants of change in PA during an eCOPD. Materials and methods We conducted a prospective cohort study with recruitment from emergency departments (EDs) of 16 participating hospitals from June 2008 to September 2010. Data were recorded on socioeconomic characteristics, dyspnea, forced expiratory volume in 1 second (FEV1%), comorbidities, health-related quality of life, factors related to exacerbation, and PA in a stable clinical condition and during the eCOPD episode. Results We evaluated 2,487 patients. Common factors related to the change in PA during hospital admission or 7 days after discharge to home from the ED were lower PA at baseline and during the first 24 hours after the index evaluation. Age, quality of life, living alone, length of hospital stay, and use of anticholinergic or systemic corticosteroids in treating the exacerbation were associated with the change in PA among hospitalized patients. Predictors of change among patients not admitted to hospital were baseline FEV1% and dyspnea at rest on ED arrival. Conclusion Among the patients evaluated in an ED for an eCOPD, the level and change in PA was markedly variable. Factors associated with exacerbation (PA 24 hours after admission, medication during admission, and length of hospital stay) and variables reflecting patients’ stable clinical condition (low level of PA, age, quality of life, FEV1%) are predictors of the change in PA during a moderate-to-severe eCOPD. PMID:26893555

  11. Tiotropium versus salmeterol for the prevention of exacerbations of COPD.

    PubMed

    Vogelmeier, Claus; Hederer, Bettina; Glaab, Thomas; Schmidt, Hendrik; Rutten-van Mölken, Maureen P M H; Beeh, Kai M; Rabe, Klaus F; Fabbri, Leonardo M

    2011-03-24

    Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-to-very-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β(2)-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β(2)-agonist salmeterol in preventing exacerbations of COPD. In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year. A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group. These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.).

  12. Natural History of COPD Exacerbations in a General Practice Based COPD Population.

    PubMed

    Rothnie, Kieran J; Müllerová, Hana; Smeeth, Liam; Quint, Jennifer K

    2018-02-23

    Rationale Acute exacerbations (AECOPD) are important adverse events in the natural history of COPD. Objectives To investigate the natural history of AECOPD over 10-years of follow-up. Methods and Results We identified 99,574 patients with COPD 01/Jan/04-31/March/15 from the UK Clinical Practice Research Datalink. We defined moderate AECOPD as those managed outside hospital and severe as those requiring hospitalisation. During the baseline period (first year of follow-up), patients were grouped according to the number and severity of AECOPD and then followed for a maximum of 10 years (mean 4.9 years). We investigated the effect of baseline AECOPD number and severity on risk of further events and death. Around one-quarter of the COPD patients did not exacerbate during follow-up. Compared to no AECOPD in the baseline period, AECOPD number predicted the future long-term rate of AECOPD in a graduated fashion, ranging from HR 1.71(1.66-1.77) for one to HR 3.41(3.27-3.56) for 5+ events. Two or more moderate AECOPD were also associated with an increased risk of death in a graduated fashion, ranging from HR 1.10(1.03-1.18) for 2 moderate AECOPD to HR 1.57(1.45-1.70) for 5+ moderate AECOPD, compared to those with no AECOPD at baseline. Severe AECOPD were associated with an even higher risk of death (HR 1.79,1.65-1.94). Conclusions A large proportion of COPD patients do not exacerbate over a maximum 10 years of follow-up. AECOPD frequency in a single year predicts long-term AECOPD rate. Increasing frequency and severity of AECOPD is associated with risk of death, and highlights the importance of preventing AECOPD.

  13. Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection.

    PubMed

    Zosky, Graeme R; Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D

    2009-11-01

    The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10(4.5) plaque-forming units of influenza A/Mem/1/71 in 50 microl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue damping and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue damping, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage sample was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-alpha, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

  14. Oklahoma City bombing: exacerbation of symptoms in veterans with PTSD.

    PubMed

    Moyers, F

    1996-02-01

    Posttraumatic stress disorder (PTSD) develops following exposure to an extremely traumatic stressor and consists of reexperiencing, avoidance, and hyperarousal symptoms. Exposure to stimuli reminiscent of the original trauma often causes an exacerbation of symptoms. Models attempting to explain this phenomenon include classical conditioning, emotional network imagery, and memory consolidation. The recent bombing in Oklahoma City caused an exacerbation of symptoms in veterans from World War II, the Korean War, and Vietnam, ranging from images of combat to memories of being called "baby-killer." These various responses to identical stimuli might help to explain the importance of attached meaning to traumatic events.

  15. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

    PubMed

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

    2018-03-08

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

  16. Background sources at PEP

    SciT

    Lynch, H.; Schwitters, R.F.; Toner, W.T.

    Important sources of background for PEP experiments are studied. Background particles originate from high-energy electrons and positrons which have been lost from stable orbits, ..gamma..-rays emitted by the primary beams through bremsstrahlung in the residual gas, and synchrotron radiation x-rays. The effect of these processes on the beam lifetime are calculated and estimates of background rates at the interaction region are given. Recommendations for the PEP design, aimed at minimizing background are presented. 7 figs., 4 tabs.

  17. Interventions for autumn exacerbations of asthma in children.

    PubMed

    Pike, Katharine C; Akhbari, Melika; Kneale, Dylan; Harris, Katherine M

    2018-03-08

    Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere. To assess the effects of pharmacotherapy and behavioural interventions enacted in anticipation of school return during autumn that are designed to reduce asthma exacerbations in children during this period. We searched the Cochrane Airways Group Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, reference lists of primary studies and existing reviews, and manufacturers' trial registries (Merck, Novartis and Ono Parmaceuticals). We searched databases from their inception to 1 December 2017, and imposed no restriction on language of publication. We included all randomised controlled trials comparing interventions aimed specifically at reducing autumn exacerbations with usual care, (no systematic change in management in preparation for school return). We included studies providing data on children aged 18 years or younger. We used standard methodological procedures expected by Cochrane. Two review authors independently screened records identified by the search and then extracted data and assessed bias for trials meeting the inclusion criteria. A third review author checked for accuracy and mediated consensus on disagreements. The primary outcome was proportion of children experiencing one or more asthma exacerbations requiring hospitalisation or oral corticosteroids during the autumn period. Our searches returned 546 trials, of which five met our inclusion criteria

  18. Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

    PubMed Central

    Kim, Victor; Regan, Elizabeth; Williams, André A. A.; Santorico, Stephanie A.; Make, Barry J.; Lynch, David A.; Hokanson, John E.; Washko, George R.; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J.; Ramsdell, Joe; Han, MeiLan K.; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D.; Dransfield, Mark; Wells, J. Michael; Hersh, Craig P.; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P.; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K.; van Beek, Edwin J. R.; Wilson, Carla; Wendt, Christine; Wise, Robert A.; Curtis, Jeffrey; Kazerooni, Ella; Hanania, Nicola; Alapat, Philip; Bandi, Venkata; Guntupalli, Kalpalatha; Guy, Elizabeth; Lunn, William; Mallampalli, Antara; Trinh, Charles; Atik, Mustafa; DeMeo, Dawn; Hersh, Craig; Jacobson, Francine; Graham Barr, R.; Thomashow, Byron; Austin, John; MacIntyre, Neil; Washington, Lacey; Page McAdams, H.; Rosiello, Richard; Bresnahan, Timothy; McEvoy, Charlene; Tashjian, Joseph; Wise, Robert; Hansel, Nadia; Brown, Robert; Casaburi, Richard; Porszasz, Janos; Fischer, Hans; Budoff, Matt; Sharafkhaneh, Amir; Niewoehner, Dennis; Allen, Tadashi; Rice, Kathryn; Foreman, Marilyn; Westney, Gloria; Berkowitz, Eugene; Bowler, Russell; Friedlander, Adam; Meoni, Eleonora; Criner, Gerard; Kim, Victor; Marchetti, Nathaniel; Satti, Aditi; James Mamary, A.; Steiner, Robert; Dass, Chandra; Bailey, William; Dransfield, Mark; Gerald, Lynn; Nath, Hrudaya; Ramsdell, Joe; Ferguson, Paul; Friedman, Paul; McLennan, Geoffrey; van Beek, Edwin JR; Martinez, Fernando; Han, MeiLan; Thompson, Deborah; Kazerooni, Ella; Wendt, Christine; Allen, Tadashi; Sciurba, Frank; Weissfeld, Joel; Fuhrman, Carl; Bon, Jessica; Anzueto, Antonio; Adams, Sandra; Orozco, Carlos; Santiago Restrepo, C.; Mumbower, Amy; Crapo, James; Silverman, Edwin; Make, Barry; Regan, Elizabeth; Samet, Jonathan; Willis, Amy; Stinson, Douglas; Beaty, Terri; Klanderman, Barbara; Laird, Nan; Lange, Christoph; Ionita, Iuliana; Santorico, Stephanie; Silverman, Edwin; Lynch, David; Schroeder, Joyce; Newell, John; Reilly, John; Coxson, Harvey; Judy, Philip; Hoffman, Eric; San Jose Estepar, Raul; Washko, George; Leek, Rebecca; Zach, Jordan; Kluiber, Alex; Rodionova, Anastasia; Mann, Tanya; Crapo, Robert; Jensen, Robert; Farzadegan, Homayoon; Murphy, James; Everett, Douglas; Wilson, Carla; Hokanson, John

    2014-01-01

    BACKGROUND: The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS: Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George’s Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS: Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD. PMID:24945159

  19. Clinical Characterization and Treatment Patterns for the Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease with Severe or Very Severe Airflow Limitation.

    PubMed

    Blasi, Francesco; Neri, Luca; Centanni, Stefano; Falcone, Franco; Di Maria, Giuseppe

    2017-02-01

    Chronic obstructive pulmonary disease (COPD) patients experiencing several episodes of acute clinical derangement suffer from increased morbidity, mortality, and accelerated decline in lung function. Nevertheless, the relationship between co-morbidity profile and exacerbation rates in the frequent exacerbator phenotype is poorly characterized, and evidence-based management guidelines are lacking. We sought to evaluate the co-morbidity profile and treatment patterns of "frequent exacerbators" with severe or very severe airflow limitation. We conducted a cross-sectional, multicenter study in 50 Italian hospitals. Pulmonologists abstracted clinical information from medical charts of 743 COPD frequent exacerbators. We evaluated the exacerbation risk and center-related variations in diagnostic testing. One-third of patients (n = 210) underwent a bronchodilator response test, and 163 (22%) received a computerized tomography (CT) scan; 35 had a partial response to bronchodilators, while 119 had a diagnosis of emphysema; 584 (79%) lacked sufficient diagnostic testing for classification. Only 17% of patients did not have any coexistent disease. Cardiovascular conditions were the most frequent co-morbidities. A history of heart failure [odds ratio (OR): 1.89; 95% confidence interval (CI) 1.48-2.3] and affective disorders (OR: 1.66; 95% CI 1.24-2.1) was associated with the frequency of exacerbations. Center membership was strongly associated with exacerbation risk, independent of casemix (variance partition coefficient = 29.6%). Examining the regional variation in health outcomes and health care behavior may help identify the best practices, especially when evidence-based recommendations are lacking and uncertainties surround clinical decision-making.

  20. How Clinical Diagnosis Might Exacerbate the Stigma of Mental Illness

    ERIC Educational Resources Information Center

    Corrigan, Patrick W.

    2007-01-01

    Stigma can greatly exacerbate the experience of mental illness. Diagnostic classification frequently used by clinical social workers may intensify this stigma by enhancing the public's sense of "groupness" and "differentness" when perceiving people with mental illness. The homogeneity assumed by stereotypes may lead mental health professionals and…

  1. Episodic Mood Changes Preceding an Exacerbation of Multiple Sclerosis

    PubMed Central

    Sharma, Priya; Morrow, Sarah A.; Owen, Richard J.

    2015-01-01

    Multiple sclerosis is a neurologic inflammatory disease that can manifest with psychiatric symptoms. Although depression is the most common psychiatric diagnosis in patients with multiple sclerosis, how depression develops is not fully understood. We present the case of an individual who displayed episodic mood changes preceding an exacerbation of multiple sclerosis symptoms. The clinical and research implications of this association are discussed. PMID:26835163

  2. Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

    PubMed

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

    2018-03-08

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

  3. 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

  4. Cysteinyl Leukotriene 1 Receptor Expression Associated With Bronchial Inflammation in Severe Exacerbations of COPD

    PubMed Central

    Zhu, Jie; Bandi, Venkata; Qiu, Shengyang; Figueroa, David J.; Evans, Jilly F.; Barnes, Neil; Guntupalli, Kay K.

    2012-01-01

    Background: Cysteinyl leukotriene 1 (CysLT1) receptor expression is known to be increased in the airway mucosa of patients with asthma, especially during exacerbations; however, nothing is known of its expression in COPD. Methods: We applied immunohistochemistry and in situ hybridization to endobronchial biopsies to determine inflammatory cell CysLT1 receptor protein and mRNA expression in the following: (1) 15 nonsmoker control subjects (NSC), (2) 16 smokers with moderate to severe COPD in its stable phase (S-COPD), and (3) 15 smokers with COPD hospitalized for a severe exacerbation (SE-COPD). Results: The total number of bronchial mucosal inflammatory cells (CD45+) and those expressing CysLT1 receptor protein were significantly greater in SE-COPD (CysLT1 receptor protein: median [range] = 139 [31-634]) as compared with S-COPD (32 [6-114]) or NSC (16 [4-66]) (P < .001 for both). CysLT1 receptor gene expression showed similar differences. A greater proportion of CD451 cells expressed CysLT1 receptor protein in SE-COPD (median [range] = 22% [8-81]) compared with S-COPD (10% [4-32]) (P < .03) or NSC (7% [1-19]) (P < .002). In SE-COPD, the relative frequencies of CysLT1 receptor-expressing cells were as follows: tryptase1 mast cells > CD681 monocytes/macrophage > neutrophils > CD201 B lymphocytes = EG21 eosinophils. Moreover, there were positive correlations between the numbers of cells expressing CysLT1 receptor protein and the numbers of CD451 cells (r = 0.78; P < .003) and tryptase1 mast cells (r = 0.62; P < .02). Conclusions: Bronchial mucosal CysLT1 receptor-positive inflammatory cells are present in the bronchial mucosa in COPD in greatest number in those experiencing a severe exacerbation. PMID:22871757

  5. Induction of Thymic Stromal Lymphopoietin Production by Nonanoic Acid and Exacerbation of Allergic Inflammation in Mice

    PubMed Central

    Yamashita, Saori; Segawa, Ryosuke; Satou, Nozomi; Hiratsuka, Masahiro; Leonard, Warren J.; Hirasawa, Noriyasu

    2013-01-01

    Background Thymic stromal lymphopoietin (TSLP) plays critical roles in the induction and exacerbation of allergic diseases. We tested various chemicals in the environment and found that xylene and 1,2,4-trimethylbenzene induced the production of TSLP in vivo. These findings prompted us to search for additional chemicals that induce TSLP production. In this study, we examined whether fatty acids could induce the production of TSLP in vivo and exacerbate allergic inflammation. Methods Various fatty acids and related compounds were painted on the ear lobes of mice and the amount of TSLP in the homogenate of ear lobe tissue was determined. The effects of nonanoic acid on allergic inflammation were also examined. Results Octanoic acid, nonanoic acid, and decanoic acid markedly induced TSLP production, while a medium-chain aldehyde and alcohol showed only weak activity. Nonanoic acid induced the production of TSLP with a maximum at 24 h. TSLP production was even observed in nonanoic acid-treated C3H/HeJ mice that lacked functional toll-like receptor 4. The aryl hydrocarbon receptor agonist β-naphthoflavone did not induce TSLP production. Nonanoic acid promoted sensitization to ovalbumin, resulting in an enhancement in the cutaneous anaphylactic response. In addition, painting of nonanoic acid after the sensitization augmented picryl chloride-induced thickening of the ear, which was reversed in TSLP receptor-deficient mice. Conclusion Nonanoic acid and certain fatty acids induced TSLP production, resulting in the exacerbation of allergic inflammation. We propose that TSLP-inducing chemical compounds such as nonanoic acid be recognized as chemical allergo-accelerators. PMID:24060765

  6. Exacerbation of allergic inflammation in mice exposed to diesel exhaust particles prior to viral infection

    PubMed Central

    Jaspers, Ilona; Sheridan, Patricia A; Zhang, Wenli; Brighton, Luisa E; Chason, Kelly D; Hua, Xiaoyang; Tilley, Stephen L

    2009-01-01

    Background Viral infections and exposure to oxidant air pollutants are two of the most important inducers of asthma exacerbation. Our previous studies have demonstrated that exposure to diesel exhaust increases the susceptibility to influenza virus infections both in epithelial cells in vitro and in mice in vivo. Therefore, we examined whether in the setting of allergic asthma, exposure to oxidant air pollutants enhances the susceptibility to respiratory virus infections, which in turn leads to increased virus-induced exacerbation of asthma. Ovalbumin-sensitized (OVA) male C57BL/6 mice were instilled with diesel exhaust particles (DEP) or saline and 24 hours later infected with influenza A/PR/8. Animals were sacrificed 24 hours post-infection and analyzed for markers of lung injury, allergic inflammation, and pro-inflammatory cytokine production. Results Exposure to DEP or infection with influenza alone had no significant effects on markers of injury or allergic inflammation. However, OVA-sensitized mice that were exposed to DEP and subsequently infected with influenza showed increased levels of eosinophils in lung lavage and tissue. In addition Th2-type cytokines, such as IL-4 and IL-13, and markers of eosinophil chemotaxis, such as CCL11 and CCR3, were increased in OVA-sensitized mice exposed to DEP prior to infection with influenza. These mice also showed increased levels of IL-1α, but not IL-10, RANTES, and MCP-1 in lung homogenates. Conclusion These data suggest that in the setting of allergic asthma, exposure to diesel exhaust could enhance virus-induced exacerbation of allergic inflammation. PMID:19682371

  7. The Cosmic Background Explorer.

    ERIC Educational Resources Information Center

    Gulkis, Samuel; And Others

    1990-01-01

    Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)

  8. The Clinical and Economic Impact of Exacerbations of Chronic Obstructive Pulmonary Disease: A Cohort of Hospitalized Patients

    PubMed Central

    Blasi, Francesco; Cesana, Giancarlo; Conti, Sara; Chiodini, Virginio; Aliberti, Stefano; Fornari, Carla; Mantovani, Lorenzo Giovanni

    2014-01-01

    Background Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences. This study assesses the burden of COPD in the general population, and the influence of exacerbations (E-COPD) on disease progression and costs. Methods This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy. The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006. Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period. Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status. Results 15857 patients were enrolled –9911 males, mean age: 76 years (SD 10). Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%. A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD. On average, the healthcare system spent 6725€ per year per person (95%CI 6590–6863). Occurrence and type of exacerbations drove the direct healthcare cost. Less than one quarter of patients presented claims for pulmonary function tests. Conclusions COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes. A more tailored approach to the management of COPD patients is required. PMID:24971791

  9. 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.

  10. Exacerbations and health care resource utilization in patients with airflow limitation diseases attending a primary care setting: the PUMA study

    PubMed Central

    Montes de Oca, Maria; Aguirre, Carlos; Lopez Varela, Maria Victorina; Laucho-Contreras, Maria E; Casas, Alejandro; Surmont, Filip

    2016-01-01

    Background COPD, asthma, and asthma–COPD overlap increase health care resource consumption, predominantly because of hospitalization for exacerbations and also increased visits to general practitioners (GPs) or specialists. Little information is available regarding this in the primary care setting. Objectives To describe the prevalence and number of GP and specialist visits for any cause or due to exacerbations in patients with COPD, asthma, and asthma–COPD overlap. Methods COPD was defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio <0.70; asthma was defined as prior medical diagnosis, wheezing in the last 12 months, or wheezing plus reversibility (post-bronchodilator FEV1 or FVC increase ≥200 mL and ≥12%); asthma–COPD overlap was defined as post-bronchodilator FEV1/FVC <0.70 plus prior asthma diagnosis. Health care utilization was evaluated as GP and/or specialist visits in the previous year. Results Among the 1,743 individuals who completed the questionnaire, 1,540 performed acceptable spirometry. COPD patients had a higher prevalence of any medical visits to any physician versus those without COPD (37.2% vs 21.8%, respectively) and exacerbations doubled the number of visits. The prevalence of any medical visits to any physician was also higher in asthma patients versus those without asthma (wheezing: 47.2% vs 22.7%; medical diagnosis: 54.6% vs 21.6%; wheezing plus reversibility: 46.2% vs 23.8%, respectively). Asthma patients with exacerbations had twice the number of visits versus those without an exacerbation. The number of visits was higher (2.8 times) in asthma–COPD overlap, asthma (1.9 times), or COPD (1.4 times) patients versus those without these respiratory diseases; the number of visits due to exacerbation was also higher (4.9 times) in asthma–COPD overlap, asthma (3.5 times), and COPD (3.8 times) patients. Conclusion COPD, asthma, and asthma–COPD overlap increase the prevalence of

  11. Backgrounds in Language.

    ERIC Educational Resources Information Center

    Maxwell, John C.; Long, Barbara K.

    "Backgrounds in Language," a field-tested inservice course designed for use by groups of 15 or 25 language arts teachers, provides the subject matter background teachers need to make informed decisions about what curriculum materials to use in what way, at what time, and with which students. The course is comprised of eight 2-hour sessions,…

  12. Optimal background matching camouflage.

    PubMed

    Michalis, Constantine; Scott-Samuel, Nicholas E; Gibson, David P; Cuthill, Innes C

    2017-07-12

    Background matching is the most familiar and widespread camouflage strategy: avoiding detection by having a similar colour and pattern to the background. Optimizing background matching is straightforward in a homogeneous environment, or when the habitat has very distinct sub-types and there is divergent selection leading to polymorphism. However, most backgrounds have continuous variation in colour and texture, so what is the best solution? Not all samples of the background are likely to be equally inconspicuous, and laboratory experiments on birds and humans support this view. Theory suggests that the most probable background sample (in the statistical sense), at the size of the prey, would, on average, be the most cryptic. We present an analysis, based on realistic assumptions about low-level vision, that estimates the distribution of background colours and visual textures, and predicts the best camouflage. We present data from a field experiment that tests and supports our predictions, using artificial moth-like targets under bird predation. Additionally, we present analogous data for humans, under tightly controlled viewing conditions, searching for targets on a computer screen. These data show that, in the absence of predator learning, the best single camouflage pattern for heterogeneous backgrounds is the most probable sample. © 2017 The Authors.

  13. Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection

    PubMed Central

    Shimizu, Koichi; Libby, Peter; Rocha, Viviane Z.; Folco, Eduardo J.; Shubiki, Rica; Grabie, Nir; Jang, Sunyoung; Lichtman, Andrew H.; Shimizu, Ayako; Hogg, Nancy; Simon, Daniel I.; Mitchell, Richard N.; Croce, Kevin

    2011-01-01

    Background The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses, and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a pro-inflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14-/-) that lack MRP-8/14 complexes. Methods and Results We examined parenchymal rejection (PR) after major histocompatibility complex (MHC) class II allomismatched cardiac transplantation (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP14-/- recipients. Allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14-/- recipients, compared to > 12 weeks (n = 15, p < 0.0001) in WT recipients. Two weeks after transplantation, allografts in MRP14-/- recipients had significantly higher PR scores (2.8 ± 0.8, n=8) than did WT recipients (0.8 ± 0.8, n=12, p<0.0001). Compared to WT recipients, allografts in MRP14-/- recipients had significantly increased T-cell and macrophage infiltration, as well as increased mRNA levels of IFN-γ and IFN-γ–associated chemokines (CXCL9, CXCL10, and CXCL11), IL-6, and IL-17, with significantly higher levels of Th17 cells. MRP14-/- recipients also had significantly more lymphocytes in the adjacent paraaortic lymph nodes than did WT recipients (cell number per lymph node: 23.7 ± 0.7 × 105 for MRP14-/- vs. 6.0 ± 0.2 × 105 for WT, p < 0.0001). The dendritic cells (DCs) of the MRP14-/- recipients of bm12 hearts expressed significantly higher levels of the co-stimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks after transplantation. Mixed leukocyte reactions using allo-EC-primed MRP14-/- DCs resulted in significantly higher antigen-presenting function than

  14. Study protocol for Chronic Obstructive Pulmonary Disease-Sitting and ExacerbAtions Trial (COPD-SEAT): a randomised controlled feasibility trial of a home-based self-monitoring sedentary behaviour intervention

    PubMed Central

    Orme, Mark; Weedon, Amie; Esliger, Dale; Saukko, Paula; Morgan, Mike; Steiner, Michael; Downey, John; Singh, Sally; Sherar, Lauren

    2016-01-01

    Introduction An acute exacerbation of chronic obstructive pulmonary disease (COPD) marks a critical life event, which can lower patient quality of life and ability to perform daily activities. Patients with COPD tend to lead inactive and highly sedentary lifestyles, which may contribute to reductions in functional capacity. Targeting sedentary behaviour (SB) may be more attainable than exercise (at a moderate-to-vigorous intensity) for behaviour change in patients following an exacerbation. This study aims to evaluate the feasibility and acceptability of a 2-week at-home intervention providing education and self-monitoring to reduce prolonged periods of SB in patients with COPD discharged following an acute exacerbation. Methods and analysis Patients will be randomised into 1 of 3 conditions: usual care (control), education or education+feedback. The education group will receive information and suggestions about reducing long periods of sitting. The education+feedback group will receive real-time feedback on their sitting time, stand-ups and step count at home through an inclinometer linked to a smart device app. The inclinometer will also provide vibration prompts to encourage movement when the wearer has been sedentary for too long. Data will be collected during hospital admission and 2 weeks after discharge. Qualitative interviews will be conducted with patients in the intervention groups to explore patient experiences. Interviews with healthcare staff will also be conducted. All data will be collected January to August 2016. The primary outcomes are feasibility and acceptability, which will be assessed by qualitative interviews, uptake and drop-out rates, reasons for refusing the intervention, compliance, app usage and response to vibration prompts. Ethics and dissemination The research ethics committee East Midlands Leicester-Central has provided ethical approval for the conduct of this study. The results of the study will be disseminated through appropriate

  15. 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

  16. Sinus opacification associated with exacerbation of thyroid eye disease.

    PubMed

    Abazari, Azin; Chak, Garrick; Feldon, Steven E

    2010-01-01

    To describe the association of sinus opacification with exacerbation of thyroid eye disease. Three cases followed orbital decompression performed when disease was quiescent and one case occurred without prior orbital or sinus surgery. Retrospective observational case series. Four patients' charts were retrospectively reviewed. Three patients with thyroid eye disease (TED), whose ophthalmopathy was stable after orbital decompression surgery, experienced recurrence of TED signs and symptoms after development of sinus inflammation. The fourth patient with TED did not have orbital surgery but presented with unilateral ophthalmopathy and ipsilateral sinus opacification. Paranasal sinus disease can exacerbate TED, possibly through a nonspecific inflammatory response. Minimizing inflammation proximal to the orbit may afford some protection against progression of the orbital process occurring in TED.

  17. Background Underground at WIPP

    NASA Astrophysics Data System (ADS)

    Esch, Ernst-Ingo; Hime, A.; Bowles, T. J.

    2001-04-01

    Recent interest to establish a dedicated underground laboratory in the United States prompted an experimental program at to quantify the enviromental backgrounds underground at the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. An outline of this program is provided along with recent experimental data on the cosmic ray muon flux at the 650 meter level of WIPP. The implications of the cosmic ray muon and fast neutron background at WIPP will be discussed in the context of new generation, low background experiments envisioned in the future.

  18. Hepatic flares in chronic hepatitis C: spontaneous exacerbation vs hepatotropic viruses superinfection.

    PubMed

    Sagnelli, Evangelista; Sagnelli, Caterina; Pisaturo, Mariantonietta; Coppola, Nicola

    2014-06-14

    The hepatitis C virus (HCV) causes an acute infection that is frequently asymptomatic, but a spontaneous eradication of HCV infection occurs only in one-third of patients. The remaining two-thirds develop a chronic infection that, in most cases, shows an indolent course and a slow progression to the more advanced stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC) develop liver cirrhosis with or without hepatocellular carcinoma. The indolent course of the illness may be troubled by the occurrence of a hepatic flare, i.e., a spontaneous acute exacerbation of CHC due to changes in the immune response, immunosuppression and subsequent restoration, and is characterized by an increase in serum aminotransferase values, a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment. A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses, namely hepatitis B virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus, particularly in geographical areas with high endemicity levels. The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

  19. Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

    PubMed

    Couturier-Maillard, A; Froux, N; Piotet-Morin, J; Michaudel, C; Brault, L; Le Bérichel, J; Sénéchal, A; Robinet, P; Chenuet, P; Jejou, S; Dumoutier, L; Renauld, J C; Iovanna, J; Huber, S; Quesniaux, Vfj; Sokol, H; Ryffel, B

    2018-05-04

    Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22 -/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

  20. Hyperglycaemia during exacerbations of asthma and chronic obstructive pulmonary disease.

    PubMed

    Koskela, Heikki O; Salonen, Päivi H; Niskanen, Leo

    2013-10-01

    Hyperglycaemia is a well-known phenomenon among patients with an exacerbation of asthma or chronic obstructive pulmonary disease (COPD). It may be associated with increased risks of death and complications. To define the prevalence and determinants of hyperglycaemia in patients with an exacerbation of asthma or COPD. This was a prospective, cross-sectional study including 153 hospitalised patients with an exacerbation of asthma or COPD. All received inhaled beta-2-adrenergic bronchodilators and oral glucocorticoids in internationally recommend doses. Plasma glucose was measured seven times during the first day. Hyperglycaemia was defined as fasting glucose >6.9 mmol/L or postprandial glucose >11.1 mmol/L. In addition, the family history for diabetes and the Karnofsky performance score were assessed. Height, weight, waist circumference, oxygen saturation, blood pressure, temperature and heart rate were measured. Glycosylated haemoglobin A1c (gHbA1c), C-reactive protein, leucocytes, urea and arterial blood gas values were analysed. Eighty-two per cent of the patients demonstrated hyperglycaemia, with similar prevalence between asthma and COPD. Of the 130 patients without a previous diagnosis of diabetes, 79% showed hyperglycaemia. In binary logistic regression analysis, high gHbA1c, high C-reactive protein and Karnofsky score less than 80% associated with the presence of fasting hyperglycaemia. High gHbA1c and current smoking associated with postprandial hyperglycaemia. Hyperglycaemia is very common among hospitalised patients with an exacerbation of asthma or COPD. It is probably triggered by the medication and the patient's metabolic predisposition mainly determines its presence. Current smoking is the main treatable contributor to hyperglycaemia. © 2013 John Wiley & Sons Ltd.

  1. Doxycycline improves clinical outcomes during cystic fibrosis exacerbations.

    PubMed

    Xu, Xin; Abdalla, Tarek; Bratcher, Preston E; Jackson, Patricia L; Sabbatini, Gina; Wells, J Michael; Lou, Xiang-Yang; Quinn, Rebecca; Blalock, J Edwin; Clancy, J P; Gaggar, Amit

    2017-04-01

    Matrix metalloprotease-9 (MMP-9) plays a role in progression of cystic fibrosis, and doxycycline can reduce MMP-9 in vitro Here, we explore the effect of doxycycline during cystic fibrosis exacerbation treatment on MMP-9 related readouts and clinical end-points.This randomised, double-blind, placebo-controlled study enrolled hospitalised patients with cystic fibrosis undergoing exacerbation. In total, 20 participants were given doxycycline and 19 participants were given placebo over an 8-day period during hospitalisation. Biospecimens were collected at the beginning and the end of the study period. Primary end-points were total MMP-9 levels in the sputum and safety/tolerability. Secondary end-points included change in lung function, time to next exacerbation, and markers of MMP-9-related protease activity (active MMP-9 and TIMP-1). Nonparametric testing was used for within-group and between-group analyses.Doxycycline was well tolerated, with no treatment discontinuations or serious adverse events. Doxycycline reduced total sputum MMP-9 levels by 63.2% (p<0.05), and was also associated with a 56.5% reduction in active MMP-9 levels (p<0.05), a 1.6-fold increase in sputum TIMP-1 (p<0.05), improvement in forced expiratory volume in 1 s (p<0.05), and an increase in time to next exacerbation (p<0.01).Adjunctive use of doxycycline improved dysregulated MMP-9 levels in sputum, along with biomarkers consistent with a reduced proteolytic pulmonary environment. Improvement in clinical outcome measures suggests an important therapeutic benefit of doxycycline for individuals with cystic fibrosis. Copyright ©ERS 2017.

  2. [Local immune and oxidative status in exacerbated chronic apical periodontitis].

    PubMed

    Konoplya, A I; Goldobin, D D; Loktionov, A L

    The aim of the study was to define local immune and oxidative changes in patients with exacerbated chronic apical periodontitis. These changes were assessed in saliva of 67 patients with the mean age of 31±2.5 before and after treatment. The study revealed disturbances in cytokines and complement system balance and activation of lipids peroxidation. Combination of Gepon or Vobenzim with Essentiale forte H and Kaskatol proved to be the most effective for correction of this imbalance.

  3. Glucocorticoid exposure alters the pathogenesis of Theiler’s murine encephalomyelitis virus during acute infection

    PubMed Central

    Young, Erin E.; Prentice, Thomas W.; Satterlee, Danielle; McCullough, Heath; Sieve, Amy N.; Johnson, Robin R.; Welsh, Thomas H.; Welsh, C. Jane R.; Meagher, Mary W.

    2008-01-01

    Previous research has shown that chronic restraint stress exacerbates Theiler’s virus infection, a murine model for CNS inflammation and multiple sclerosis. The current set of experiments was designed to evaluate the potential role of glucocorticoids in the deleterious effects of restraint stress on acute CNS inflammatory disease. Exposure to chronic restraint stress resulted in elevated levels of corticosterone as well as increased clinical scores and weight loss (Experiment 1). In addition, corticosterone administration alone exacerbated behavioral signs of TMEV-induced sickness (i.e. decreased body weight, increased symptoms of encephalitis, and increased mortality) and reduced inflammation in the CNS (Experiment 2). Infected subjects receiving exogenous corticosterone showed exacerbation of acute phase measures of sickness and severe mortality as well as decreased viral clearance from CNS (Experiment 3). These findings indicate that corticosterone exposure alone is sufficient to exacerbate acute CNS inflammatory disease. PMID:18538803

  4. High salt intake does not exacerbate murine autoimmune thyroiditis

    PubMed Central

    Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

    2014-01-01

    Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

  5. Web-Based Study of Risk Factors for Pain Exacerbation in Osteoarthritis of the Knee (SPARK-Web): Design and Rationale

    PubMed Central

    Metcalf, Ben; Zhang, Yuqing; Bennell, Kim; March, Lyn; Hunter, David J

    2015-01-01

    Background Knee osteoarthritis (OA) is the most frequent cause of limited mobility and diminished quality of life. Pain is the main symptom that drives individuals with knee OA to seek medical care and a recognized antecedent to disability and eventually joint replacement. Many persons with symptomatic knee OA experience recurrent pain exacerbations. Knowledge and clarification of risk factors for pain exacerbation may allow those affected to minimize reoccurrence of these episodes. Objective The aim of this study is to use a Web-based case-crossover design to identify risk factors for knee pain exacerbations in persons with symptomatic knee OA. Methods Web-based case-crossover design is used to study persons with symptomatic knee OA. Participants with knee pain and radiographic knee OA will be recruited and followed for 90 days. Participants will complete an online questionnaire at the baseline and every 10 days thereafter (totaling up to 10 control-period questionnaires); participants will also be asked to report online when they experience an episode of increased knee pain. Pain exacerbation will be defined as an increase in knee pain severity of two points from baseline on a numeric rating scale (NRS 0-10). Physical activity, footwear, knee injury, medication use, climate, psychological factors, and their possible interactions will be assessed as potential triggers for pain exacerbation using conditional logistic regression models. Results This project has been funded by the National Health and Medical Research Council (NHMRC). The enrollment for the study has started. So far, 343 participants have been enrolled. The study is expected to be finished in October 2015. Conclusions This study will identify risk factors for pain exacerbations in knee OA. The identification and possible modification/elimination of such risk factors will help to prevent the reoccurrence of pain exacerbation episodes and therefore improve knee OA management. PMID:26156210

  6. Physiological Background of Differences in Quantitative Diffusion-Weighted Magnetic Resonance Imaging Between Acute Malignant and Benign Vertebral Body Fractures: Correlation of Apparent Diffusion Coefficient With Quantitative Perfusion Magnetic Resonance Imaging Using the 2-Compartment Exchange Model.

    PubMed

    Geith, Tobias; Biffar, Andreas; Schmidt, Gerwin; Sourbron, Steven; Dietrich, Olaf; Reiser, Maximilian; Baur-Melnyk, Andrea

    2015-01-01

    To test the hypothesis that apparent diffusion coefficient (ADC) in vertebral bone marrow of benign and malignant fractures is related to the volume of the interstitial space, determined with dynamic contrast-enhanced (DCE) magnetic resonance imaging. Patients with acute benign (n = 24) and malignant (n = 19) vertebral body fractures were examined at 1.5 T. A diffusion-weighted single-shot turbo-spin-echo sequence (b = 100 to 600 s/mm) and DCE turbo-FLASH sequence were evaluated. Regions of interest were manually selected for each fracture. Apparent diffusion coefficient was determined with a monoexponential decay model. The DCE magnetic resonance imaging concentration-time curves were analyzed using a 2-compartment tracer-kinetic model. Apparent diffusion coefficient showed a significant positive correlation with interstitial volume in the whole study population (Pearson r = 0.66, P < 0.001), as well as in the malignant (Pearson r = 0.64, P = 0.004) and benign (Pearson r = 0.52, P = 0.01) subgroup. A significant correlation between ADC and the permeability-surface area product could be observed when analyzing the whole study population (Spearman rs = 0.40, P = 0.008), but not when separately examining the subgroups. Plasma flow showed a significant correlation with ADC in benign fractures (Pearson r = 0.23, P = 0.03). Plasma volume did not show significant correlations with ADC. The results support the hypothesis that the ADC of a lesion is inversely correlated to its cellularity. This explains previous observations that ADC is reduced in more malignant lesions.

  7. The value of signs, symptoms and plasma heart-type fatty acid-binding protein (H-FABP) in evaluating patients presenting with symptoms possibly matching acute coronary syndrome: background and methods of a diagnostic study in primary care.

    PubMed

    Willemsen, Robert T A; Buntinx, Frank; Winkens, Bjorn; Glatz, Jan F; Dinant, Geert Jan

    2014-12-12

    Chest complaints presented to a general practitioner (GP) are frequently caused by diseases which have advantageous outcomes. However, in some cases, acute coronary syndrome (ACS) is present (1.5-22% of cases). The patient's signs, symptoms and electrocardiography results are insufficient diagnostic tools to distinguish mild disease from ACS. Therefore, most patients presenting chest complaints are referred to secondary care facilities where ACS is then ruled out in a majority of patients (78%). Recently, a point of care test for heart-type fatty acid-binding protein (H-FABP) using a low cut-off value between positive and negative of 4 ng/ml has become available. We aim to study the role of this point of care device in triage of patients presenting chest complaints possibly due to ACS, in primary care. Our research protocol is presented in this article. Results are expected in 2015. Participating GPs will register signs and symptoms in all patients presenting chest complaints possibly due to ACS. Point of care H-FABP testing will also be performed. Our study will be a derivation study to identify signs and symptoms that, combined with point of care H-FABP testing, can be part of an algorithm to either confirm or rule out ACS. The diagnostic value for ACS of this algorithm in general practice will be determined. A safe diagnostic elimination of ACS by application of the algorithm can be of significant clinical relevance. Improved triage and thus reduction of the number of patients with chest complaints without underlying ACS, that are referred to secondary care facilities, could lead to a substantial cost reduction. ClinicalTrials.gov, NCT01826994, accepted April 8th 2013.

  8. Notification: Background Investigation Services

    EPA Pesticide Factsheets

    Project #OA-FY15-0029, February 26, 2015. The Office of Inspector General (OIG) for the U.S. Environmental Protection Agency (EPA) plans to begin field work for our audit of background investigation services.

  9. Urban Background Study Webinar

    EPA Pesticide Factsheets

    This webinar presented the methodology developed for collecting a city-wide or urban area background data set, general results of southeastern cities data collected to date, and a case study that used this sampling method.

  10. Diet, Lung Function, and Asthma Exacerbations in Puerto Rican Children.

    PubMed

    Han, Yueh-Ying; Forno, Erick; Alvarez, Maria; Colón-Semidey, Angel; Acosta-Perez, Edna; Canino, Glorisa; Celedón, Juan C

    2017-12-01

    Changes in dietary patterns may partly explain the epidemic of asthma in industrialized countries. The objective of this study was to examine the relationship between dietary patterns and lung function and asthma exacerbations in Puerto Rican children. This is a case-control study of 678 Puerto Rican children (ages 6-14 years) in San Juan (Puerto Rico). All participants completed a respiratory health questionnaire and a 75-item food frequency questionnaire. Food items were aggregated into 7 groups: fruits, vegetables, grains, protein, dairy, fats, and sweets. Logistic regression was used to evaluate consumption frequency of each group and asthma. Based on the results, a dietary score was created [range from -2 (unhealthy diet: high consumption of dairy and sweets, low consumption of vegetables and grains) to 2 (healthy diet: high consumption of vegetables and grains and low consumption of dairy and sweet)]. Multivariable linear or logistic regression was used to assess the relationship between dietary score and lung function or asthma exacerbations. After adjustment for covariates, a healthier diet (each 1-point increment in dietary score) was associated with significantly higher %predicted forced expiratory volume in the first second (FEV 1 ) and %predicted forced vital capacity (FVC) in control subjects. Dietary pattern alone was not associated with asthma exacerbations, but children with an unhealthy diet and vitamin D insufficiency (plasma 25(OH)D <30 ng/mL) had higher odds of ≥1 severe asthma exacerbation [odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.5-7.5] or ≥1 hospitalization due to asthma (OR = 3.9, 95% CI = 1.6-9.8, OR = 3.4, 95% CI = 1.5-7.5) than children who ate a healthy diet and were vitamin D sufficient. A healthy diet, with frequent consumption of vegetables and grains and low consumption of dairy products and sweets, was associated with higher lung function (as measured by FEV 1 and FVC). Vitamin D

  11. Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart failure in two mouse models of cardiac hypertrophy

    PubMed Central

    2013-01-01

    Background Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In particular, exposure to traffic related PM2.5 has been associated with increases in left ventricular hypertrophy, a strong risk factor for cardiovascular mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE), we investigated the effects of chronic DE exposure on cardiac hypertrophy and heart failure in the adult mouse by exposing mice to DE combined with either of two mouse models of cardiac hypertrophy: angiotensin II infusion or pressure overload induced by transverse aortic banding. Methods Wild type male C57BL/6 J mice were either infused with angiotensin II (800 ng/kg/min) via osmotic minipump implanted subcutaneously for 1 month, or underwent transverse aortic banding (27 gauge needle 1 week for observing acute reactions, 26 gauge needle 3 months or 6 months for observing chronic reactions). Vehicle (saline) infusion or sham surgery was used as a control. Shortly after surgery, mice were transferred to our exposure facility and randomly assigned to either diesel exhaust (300 or 400 μg/m3) or filtered air exposures. After reaching the end of designated time points, echocardiography was performed to measure heart structure and function. Gravimetric analysis was used to measure the ventricular weight to body weight ratio. We also measured heart rate by telemetry using implanted ambulatory ECG monitors. Results Both angiotensin II and transverse aortic banding promoted cardiac hypertrophy compared to vehicle or sham controls. Transverse aortic banding for six months also promoted heart failure in addition to cardiac hypertrophy. In all cases, DE failed to exacerbate the development of hypertrophy or heart failure when compared to filtered air controls. Prolonged DE exposure also led to a decrease in average heart rate. Conclusions Up to 6-months of DE exposure had no effect on

  12. Continuous Cough Monitoring Using Ambient Sound Recording During Convalescence from a COPD Exacerbation.

    PubMed

    Crooks, Michael G; den Brinker, Albertus; Hayman, Yvette; Williamson, James D; Innes, Andrew; Wright, Caroline E; Hill, Peter; Morice, Alyn H

    2017-06-01

    Cough is common in chronic obstructive pulmonary disease (COPD) and is associated with frequent exacerbations and increased mortality. Cough increases during acute exacerbations (AE-COPD), representing a possible metric of clinical deterioration. Conventional cough monitors accurately report cough counts over short time periods. We describe a novel monitoring system which we used to record cough continuously for up to 45 days during AE-COPD convalescence. This is a longitudinal, observational study of cough monitoring in AE-COPD patients discharged from a single teaching hospital. Ambient sound was recorded from two sites in the domestic environment and analysed using novel cough classifier software. For comparison, the validated hybrid HACC/LCM cough monitoring system was used on days 1, 5, 20 and 45. Patients were asked to record symptoms daily using diaries. Cough monitoring data were available for 16 subjects with a total of 568 monitored days. Daily cough count fell significantly from mean ± SEM 272.7 ± 54.5 on day 1 to 110.9 ± 26.3 on day 9 (p < 0.01) before plateauing. The absolute cough count detected by the continuous monitoring system was significantly lower than detected by the hybrid HACC/LCM system but normalised counts strongly correlated (r = 0.88, p < 0.01) demonstrating an ability to detect trends. Objective cough count and subjective cough scores modestly correlated (r = 0.46). Cough frequency declines significantly following AE-COPD and the reducing trend can be detected using continuous ambient sound recording and novel cough classifier software. Objective measurement of cough frequency has the potential to enhance our ability to monitor the clinical state in patients with COPD.

  13. Mast Cells Limit the Exacerbation of Chronic Allergic Contact Dermatitis in Response to Repeated Allergen Exposure.

    PubMed

    Gimenez-Rivera, Vladimir-Andrey; Siebenhaar, Frank; Zimmermann, Carolin; Siiskonen, Hanna; Metz, Martin; Maurer, Marcus

    2016-12-01

    Allergic contact dermatitis is a chronic T cell-driven inflammatory skin disease that is caused by repeated exposure to contact allergens. Based on murine studies of acute contact hypersensitivity, mast cells (MCs) are believed to play a role in its pathogenesis. The role of MCs in chronic allergic contact dermatitis has not been investigated, in part because of the lack of murine models for chronic contact hypersensitivity. We developed and used a chronic contact hypersensitivity model in wild-type and MC-deficient mice and assessed skin inflammatory responses to identify and characterize the role of MCs in chronic allergic contact dermatitis. Ear swelling chronic contact hypersensitivity responses increased markedly, up to 4-fold, in MC-deficient Kit W-sh/W-sh (Sash) and MCPT5-Cre + iDTR + mice compared with wild-type mice. Local engraftment with MCs protected Sash mice from exacerbated ear swelling after repeated oxazolone challenge. Chronic contact hypersensitivity skin of Sash mice exhibited elevated levels of IFN-γ, IL-17α, and IL-23, as well as increased accumulation of Ag-specific IFN-γ-producing CD8 + tissue-resident memory T (T RM ) cells. The CD8 + T cell mitogen IL-15, which was increased in oxazolone-challenged skin of Sash mice during the accumulation of cutaneous T RM cells, was efficiently degraded by MCs in vitro. MCs protect from the exacerbated allergic skin inflammation induced by repeated allergen challenge, at least in part, via effects on CD8 + T RM cells. MCs may notably influence the course of chronic allergic contact dermatitis. A better understanding of their role and the underlying mechanisms may lead to better approaches for the treatment of this common, disabling, and costly condition. Copyright © 2016 by The American Association of Immunologists, Inc.

  14. Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

    PubMed Central

    Lugade, Amit A.; Bogner, Paul N.; Thatcher, Thomas H.; Sime, Patricia J.; Phipps, Richard P.; Thanavala, Yasmin

    2014-01-01

    The detrimental impact of tobacco on human health is clearly recognized and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease (COPD) are susceptible to recurrent respiratory infections with pathogens, including non-typeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. As mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study to investigate chronic infection and the generation of adaptive immune responses to NTHI following chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of antibodies against outer membrane lipoprotein P6, with impaired IgG1, IgG2a and IgA class-switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke exposed mice exhibited a similar defect in the generation of adaptive immunity following immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes COPD patients to recurrent infections, leading to exacerbations and contributing to mortality. PMID:24752444

  15. Computerized respiratory sounds: a comparison between patients with stable and exacerbated COPD.

    PubMed

    Jácome, Cristina; Oliveira, Ana; Marques, Alda

    2017-09-01

    Diagnosis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is often challenging as it relies on patients' clinical presentation. Computerized respiratory sounds (CRS), namely crackles and wheezes, may have the potential to contribute for the objective diagnosis/monitoring of an AECOPD. This study explored if CRS differ during stable and exacerbation periods in patients with COPD. 13 patients with stable COPD and 14 with AECOPD were enrolled. CRS were recorded simultaneously at trachea, anterior, lateral and posterior chest locations using seven stethoscopes. Airflow (0.4-0.6l/s) was recorded with a pneumotachograph. Breathing phases were detected using airflow signals; crackles and wheezes with validated algorithms. At trachea, anterior and lateral chest, no significant differences were found between the two groups in the number of inspiratory/expiratory crackles or inspiratory wheeze occupation rate. At posterior chest, the number of crackles (median 2.97-3.17 vs. 0.83-1.2, P < 0.001) and wheeze occupation rate (median 3.28%-3.8% vs. 1.12%-1.77%, P = 0.014-0.016) during both inspiration and expiration were significantly higher in patients with AECOPD than in stable patients. During expiration, wheeze occupation rate was also significantly higher in patients with AECOPD at trachea (median 3.12% vs. 0.79%, P < 0.001) and anterior chest (median 3.55% vs. 1.28%, P < 0.001). Crackles and wheezes are more frequent in patients with AECOPD than in stable patients, particularly at posterior chest. These findings suggest that these CRS can contribute to the objective diagnosis/monitoring of AECOPD, which is especially valuable considering that they can be obtained by integrating computerized techniques with pulmonary auscultation, a noninvasive method that is a component of patients' physical examination. © 2015 John Wiley & Sons Ltd.

  16. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy.

    PubMed

    Black, Sarah Wurts; Morairty, Stephen R; Fisher, Simon P; Chen, Tsui-Ming; Warrier, Deepti R; Kilduff, Thomas S

    2013-03-01

    Humans with narcolepsy and orexin/ataxin-3 transgenic (TG) mice exhibit extensive, but incomplete, degeneration of hypo-cretin (Hcrt) neurons. Partial Hcrt cell loss also occurs in Parkinson disease and other neurologic conditions. Whether Hcrt antagonists such as almorexant (ALM) can exert an effect on the Hcrt that remains after Hcrt neurodegeneration has not yet been determined. The current study was designed to evaluate the hypnotic and cataplexy-inducing efficacy of a Hcrt antagonist in an animal model with low Hcrt tone and compare the ALM efficacy profile in the disease model to that produced in wild-type (WT) control animals. Counterbalanced crossover study. Home cage. Nine TG mice and 10 WT mice. ALM (30, 100, 300 mg/kg), vehicle and positive control injections, dark/active phase onset. During the 12-h dark period after dosing, ALM exacerbated cataplexy in TG mice and increased nonrapid eye movement sleep with heightened sleep/wake fragmentation in both genotypes. ALM showed greater hypnotic potency in WT mice than in TG mice. The 100 mg/kg dose conferred maximal promotion of cataplexy in TG mice and maximal promotion of REM sleep in WT mice. In TG mice, ALM (30 mg/ kg) paradoxically induced a transient increase in active wakefulness. Core body temperature (Tb) decreased after acute Hcrt receptor blockade, but the reduction in Tb that normally accompanies the wake-to-sleep transition was blunted in TG mice. These complex dose- and genotype-dependent interactions underscore the importance of effector mechanisms downstream from Hcrt receptors that regulate arousal state. Cataplexy promotion by ALM warrants cautious use of Hcrt antagonists in patient populations with Hcrt neurodegeneration, but may also facilitate the discovery of anticataplectic medications. Black SW; Morairty SR; Fisher SP; Chen TM; Warrier DR; Kilduff TS. Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. SLEEP 2013;36(3):325-336.

  17. Overexpression of Human S100B Exacerbates Brain Damage and Periinfarct Gliosis After Permanent Focal Ischemia

    PubMed Central

    Mori, Takashi; Tan, Jun; Arendash, Gary W.; Koyama, Naoki; Nojima, Yoshiko; Town, Terrence

    2009-01-01

    Background and Purpose We have previously demonstrated that augmented and prolonged activation of astrocytes detrimentally influences both the subacute and chronic phases of cerebral ischemia. Furthermore, we have suggested that the astrocyte-derived protein S100B may be important in these pathogenic events. However, the causal relationship between S100B and exacerbation of brain damage in vivo remains to be elucidated. Methods Using transgenic mice overexpressing human S100B (Tg huS100B mice), we examined whether S100B plays a cardinal role in aggravation of brain damage after permanent middle cerebral artery occlusion (pMCAO). Results Tg huS100B mice had significantly larger infarct volumes and worse neurological deficits at any time point examined after pMCAO as compared with CD-1 background strain-matched control mice. Infarct volumes in Tg huS100B mice were significantly increased from 1 to 3 and 5 days after pMCAO (delayed infarct expansion), whereas those in control mice were not significantly altered. S100, glial fibrillary acidic protein, and Iba1 burdens in the periinfarct area were significantly increased through to 7 days after pMCAO in Tg huS100B mice, whereas those in control mice reached a plateau at 3 days after pMCAO. Conclusions These results provide genetic evidence that overexpression of human S100B acts to exacerbate brain damage and periinfarct reactive gliosis (astrocytosis and microgliosis) during the subacute phase of pMCAO. PMID:18451356

  18. Incidence of utilization- and symptom-defined COPD exacerbations in hospital- and population-recruited patients.

    PubMed

    Erdal, Marta; Johannessen, Ane; Eagan, Tomas Mikal; Bakke, Per; Gulsvik, Amund; Grønseth, Rune

    2016-01-01

    The objectives of this study were to estimate the impact of recruitment source and outcome definition on the incidence of acute exacerbations of COPD (AECOPD) and explore possible predictors of AECOPD. During a 1-year follow-up, we performed a baseline visit and four telephone interviews of 81 COPD patients and 132 controls recruited from a population-based survey and 205 hospital-recruited COPD patients. Both a definition bas