Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A
The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.
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.
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
Flattet, Yves; Garin, Nicolas; Serratrice, Jacques; Perrier, Arnaud; Stirnemann, Jérome; Carballo, Sebastian
Background Acute exacerbations are the leading causes of hospitalization and mortality in patients with COPD. Prognostic tools for patients with chronic COPD exist, but there are scarce data regarding acute exacerbations. We aimed to identify the prognostic factors of death and readmission after exacerbation of COPD. Methods This was a retrospective study conducted in the Department of Internal Medicine of Geneva University Hospitals. All patients admitted to the hospital with a diagnosis of exacerbation of COPD between 2008 and 2011 were included. The studied variables included comorbidities, Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity classification, and biological and clinical parameters. The main outcome was death or readmission during a 5-year follow-up. The secondary outcome was death. Survival analysis was performed (log-rank and Cox). Results We identified a total of 359 patients (195 men and 164 women, average age 72 years). During 5-year follow-up, 242 patients died or were hospitalized for the exacerbation of COPD. In multivariate analysis, age (hazard ratio [HR] 1.03, 95% CI 1.02–1.05; P<0.0001), severity of airflow obstruction (forced expiratory volume in 1 s <30%; HR 4.65, 95% CI 1.42–15.1; P=0.01), diabetes (HR 1.47, 95% CI 1.003–2.16; P=0.048), cancer (HR 2.79, 95% CI 1.68–4.64; P<0.0001), creatinine (HR 1.003, 95% CI 1.0004–1.006; P=0.02), and respiratory rate (HR 1.03, 95% CI 1.003–1.05; P=0.028) on admission were significantly associated with the primary outcome. Age, cancer, and procalcitonin were significantly associated with the secondary outcome. Conclusion COPD remains of ominous prognosis, especially after exacerbation requiring hospitalization. Baseline pulmonary function remains the strongest predictor of mortality and new admission. Demographic factors, such as age and comorbidities and notably diabetes and cancer, are closely associated with the outcome of the patient. Respiratory rate at admission
Rabbat, A; Guetta, A; Lorut, C; Lefebvre, A; Roche, N; Huchon, G
Exacerbations of COPD are common and cause a considerable burden to the patient and the healthcare system. To optimize the hospital care of patients with exacerbations of COPD, clinicians should be aware of some key points: management of exacerbations is broadly based on clinical features and severity. Initial clinical evaluation is crucial to define those patients requiring hospital admission and those who could be managed as outpatients. In hospitalized patients, the appropriate level of care should be determined by the initial severity and response to initial medical treatment. Medical treatment should follow recent recommendations, including rest, titrated oxygen therapy, inhaled or nebulized short-acting bronchodilators (Beta2-agonists and anticholinergic agents), DVT prevention with LMWH, steroids in most severely ill patients, unless there are contraindications and antibiotics in the case of a clear bacterial infectious aetiology. Severe exacerbations may lead to acute hypercapnic respiratory failure. Unless contraindicated, non-invasive ventilation (NIV) should be the first line ventilatory support for these patients. NIV should be commenced early, before severe acidosis ensues, to avoid the need for endotracheal intubation and to reduce mortality and treatment failures. Several randomised controlled clinical trials support the use of NIV in the management of acute exacerbations of COPD, demonstrating a decreased need for mechanical ventilation and an improved survival. In most severe cases, NIV should be provided in ICU. Although it has been shown that for less severe patients (with pH values>7.30), NIV can be administered safely and effectively on general medical wards, a lead respiratory consultant and trained nurses are mandatory. Mechanical ventilation through an endotracheal tube should be considered when patients have contraindications to the use of NIV or fail to improve on NIV. The duration of mechanical ventilation should be shortened as much as
Zhou, Aiyuan; Zhou, Zijing; Zhao, Yiyang; Chen, Ping
Exacerbations of COPD are clinically relevant events with therapeutic and prognostic implications. Yet, significant heterogeneity of clinical presentation and disease progression exists within acute exacerbations of COPD (AECOPD). Currently, different phenotypes have been widely used to describe the characteristics among patients with AECOPD. This has proved to be significant in the treatment and prediction of the outcomes of the disease. In this review of published literature, the phenotypes of AECOPD were classified according to etiology, inflammatory biomarkers, clinical manifestation, comorbidity, the frequency of exacerbations, and so on. This review concentrates on advancements in the use of phenotypes of AECOPD. PMID:28392685
Leuppi, Jörg D; Ott, Sebastian R
Asthma and chronic obstructive airways disease are chronic pulmonary diseases which have a high prevalence world-wide. Both conditions can deteriorate acutely and potentially put patients into life-threatening situations. Management of an acute exacerbation starts in the emergency consultation-setting and ends only once the longterm management has been thoroughly assessed and optimised in order to prevent future exacerbations. Exacerbation frequency is strongly associated with long-term morbidity and mortality in both diseases. Recent data have shown that short-course systemic steroids (5 days) for the treatment of an acute exacerbation of COPD are as successful as long-course treatments (14 days) in preventing exacerbations during the subsequent 6 months. Similarly the targeted use of antibiotics is discussed in this review.
Ni, Lei; Chuang, Chia-Chen; Zuo, Li
Chronic obstructive pulmonary disease (COPD) is a common airway disorder. In particular, acute exacerbations of COPD (AECOPD) can significantly reduce pulmonary function. The majority of AECOPD episodes are attributed to infections, although environmental stress also plays a role. Increasing urbanization and associated air pollution, especially in developing countries, have been shown to contribute to COPD pathogenesis. Elevated levels of particulate matter (PM) in polluted air are strongly correlated with the onset and development of various respiratory diseases. In this review, we have conducted an extensive literature search of recent studies of the role of PM2.5 (fine PM) in AECOPD. PM2.5 leads to AECOPD via inflammation, oxidative stress (OS), immune dysfunction, and altered airway epithelial structure and microbiome. Reducing PM2.5 levels is a viable approach to lower AECOPD incidence, attenuate COPD progression and decrease the associated healthcare burden. PMID:26557095
The mucolytic drug erdosteine (Erdotin - Galen) is licensed in the UK as treatment for up to 10 days "for the symptomatic treatment of acute exacerbations of chronic bronchitis in adults". This indication differs from that for carbocisteine and mecysteine, two older mucolytic drugs that are licensed for adjunctive treatment in respiratory disorders characterised by viscous mucus, and typically used for longer to prevent exacerbations of chronic obstructive pulmonary disease (COPD). Does erdosteine have a role for people with COPD exacerbations?
Pavord, Ian D; Jones, Paul W; Burgel, Pierre-Régis; Rabe, Klaus F
Exacerbations of chronic obstructive pulmonary disease (COPD) are defined as sustained worsening of a patient’s condition beyond normal day-to-day variations that is acute in onset, and that may also require a change in medication and/or hospitalization. Exacerbations have a significant and prolonged impact on health status and outcomes, and negative effects on pulmonary function. A significant proportion of exacerbations are unreported and therefore left untreated, leading to a poorer prognosis than those treated. COPD exacerbations are heterogeneous, and various phenotypes have been proposed which differ in biologic basis, prognosis, and response to therapy. Identification of biomarkers could enable phenotype-driven approaches for the management and prevention of exacerbations. For example, several biomarkers of inflammation can help to identify exacerbations most likely to respond to oral corticosteroids and antibiotics, and patients with a frequent exacerbator phenotype, for whom preventative treatment is appropriate. Reducing the frequency of exacerbations would have a beneficial impact on patient outcomes and prognosis. Preventative strategies include modification of risk factors, treatment of comorbid conditions, the use of bronchodilator therapy with long-acting β2-agonists or long-acting muscarinic antagonists, and inhaled corticosteroids. A better understanding of the mechanisms underlying COPD exacerbations will help to optimize use of the currently available and new interventions for preventing and treating exacerbations. PMID:26937187
Faner, Rosa; Sobradillo, Patricia; Noguera, Aina; Gomez, Cristina; Cruz, Tamara; López-Giraldo, Alejandra; Ballester, Eugeni; Soler, Nestor; Arostegui, Juan I.; Pelegrín, Pablo; Rodriguez-Roisin, Roberto; Yagüe, Jordi; Cosio, Borja G.; Juan, Manel
Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD. PMID:27730204
Faner, Rosa; Sobradillo, Patricia; Noguera, Aina; Gomez, Cristina; Cruz, Tamara; López-Giraldo, Alejandra; Ballester, Eugeni; Soler, Nestor; Arostegui, Juan I; Pelegrín, Pablo; Rodriguez-Roisin, Roberto; Yagüe, Jordi; Cosio, Borja G; Juan, Manel; Agustí, Alvar
Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.
Makris, Demosthenes; Bouros, Demosthenes
The introduction and acceptance of a standard definition for exacerbations of COPD can be helpful in prompt diagnosis and management of these events. The latest GOLD executive committee recognised this necessity and it has now included a definition of exacerbation in the guidelines for COPD which is an important step forward in the management of the disease. This definition is pragmatic and compromises the different approaches for exacerbation. However, the inclusion of the "healthcare utilisation" approach (".. may warrant a change in regular medication") in the definition may introduce in the diagnosis of exacerbation factors related to the access to health care services which may not be related to the underlying pathophysiological process which characterizes exacerbations. It should be also noted that the aetiology of COPD exacerbations has not yet been included in the current definition. In this respect, the definition does not acknowledge the fact that many patients with COPD may suffer from additional conditions (i.e. congestive cardiac failure or pulmonary embolism) that can masquerade as exacerbations but they should not be considered as causes of them. The authors therefore suggest that an inclusion of the etiologic factors of COPD exacerbations in the definition. Moreover, COPD exacerbations are characterized by increased airway and systemic inflammation and significant deterioration in lung function. These fundamental aspects should be accounted in diagnosis/definition of exacerbations. This could be done by the introduction of a "laboratory" marker in the diagnosis of these acute events. The authors acknowledge that the use of a test or a biomarker in the diagnosis of exacerbations meets certain difficulties related to performing lung function tests or to sampling during exacerbations. However, the introduction of a test that reflects airway or systemic inflammation in the diagnosis of exacerbations might be another step forward in the management of
Hillas, Georgios; Perlikos, Fotis; Tzanakis, Nikolaos
Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide. Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality. This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease. A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD). Exacerbations and comorbidities contribute to the overall severity in individual patients. Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease. In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”. AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. PMID:27471380
Piquet, Jacques; Chavaillon, Jean-Michel; David, Philippe; Martin, Francis; Blanchon, François; Roche, Nicolas
The aim of this study was to assess long-term mortality and predictive factors of death after hospital admission for acute exacerbation of chronic obstructive pulmonary disease (COPD). 1824 patients (23.2% female; mean age 70.3±11.3 years) consecutively admitted for acute exacerbation of COPD in the respiratory medicine departments of 68 general hospitals between October 2006 and June 2007 were prospectively enrolled in a follow-up cohort. Their vital status was documented between October 2010 and April 2011. Vital status was available for 1750 patients (95.9%), among whom 787 (45%) died during follow-up. Multivariate analysis found that age (60-80 years and ≥80 years versus <60 years, relative risk 2.99, 95% CI 2.31-3.89), lower body mass index (25-30 kg·m(-2) versus ≤20 kg·m(-2), relative risk 0.80, 95% CI 0.66-0.97), lung cancer (relative risk 2.08, 95% CI 1.43-3.01), cardiovascular comorbidity (relative risk 1.35, 95% CI 1.16-1.58), previous hospital admissions for acute exacerbation of COPD (four or more versus none, relative risk 1.91, 95% CI 1.44-2.53), use of accessory respiratory muscles (relative risk 1.19, 95% CI 1.01-1.40) or lower-limb oedema (relative risk 1.74, 95% CI (1.44-2.12)) at admission and treatment by long-term oxygen therapy at discharge (relative risk 2.09, 95% CI 1.79-2.45) were independent risk factors of death. Mortality rate during the 4 years following hospital admission for acute exacerbation of COPD was high (45%). Simple clinical information relating to respiratory and general status can help in identifying high-risk patients and targeting more intensive follow-up and care. Interestingly, cardiovascular comorbidities and past hospitalisations for acute exacerbation of COPD, but not forced expiratory volume in 1 s, independently predicted the risk of death.
Pizarro, Carmen; Herweg-Steffens, Neele; Buchenroth, Martin; Schulte, Wolfgang; Schaefer, Christian; Hammerstingl, Christoph; Werner, Nikos; Nickenig, Georg; Skowasch, Dirk
Background In acute exacerbation of COPD, increased plasma levels of cardiac troponin are frequent and associated with increased mortality. Thus, we aimed at prospectively determining the diagnostic value of coronary angiography in patients with exacerbated COPD and concomitantly elevated cardiac troponin. Patients and methods A total of 88 patients (mean age 72.9±9.2 years, 56.8% male) hospitalized for acute exacerbation of COPD with elevated plasma troponin were included. All patients underwent coronary angiography within 72 hours after hospitalization. Complementary 12-lead electrocardiogram, transthoracic echocardiography, pulmonary function, and angiological testing were performed. Results Coronary angiography objectified the presence of ischemic heart disease (IHD) in 59 patients (67.0%), of whom 34 patients (38.6% of total study population) underwent percutaneous coronary intervention. Among these 34 intervened patients, the vast majority (n=26, 76.5%) had no previously known IHD, whereas only eight out of 34 patients (23.5%) presented an IHD history. Patients requiring coronary intervention showed significantly reduced left ventricular ejection fraction (45.8%±13.1% vs 55.1%±13.3%, P=0.01) and a significantly more frequent electrocardiographic ST-segment depression (20.6% vs 7.4%, P=0.01). Neither additional laboratory parameters for inflammation and myocardial injury nor lung functional measurements differed significantly between the groups. Conclusion Angiographically confirmed IHD that required revascularization occurred in 38.6% of exacerbated COPD patients with elevated cardiac troponin. In this considerable portion of patients, coronary angiography emerged to be of diagnostic and therapeutic value. PMID:27695304
Sapey, E; Stockley, R A
Exacerbations of COPD are thought to be caused by complex interactions between the host, bacteria, viruses, and environmental pollution. These factors increase the inflammatory burden in the lower airways, overwhelming the protective anti-inflammatory defences leading to tissue damage. Frequent exacerbations are associated with increased morbidity and mortality, a faster decline in lung function, and poorer health status, so prevention or optimal treatment of exacerbations is a global priority. In order to evolve new treatment strategies there has been great interest in the aetiology and pathophysiology of exacerbations, but progress has been hindered by the heterogeneous nature of these episodes, vague definitions of an exacerbation, and poor stratification of known confounding factors when interpreting results. We review how an exacerbation should be defined, its inflammatory basis, and the importance of exacerbations on disease progression. Important aetiologies, with their potential underlying mechanisms, are discussed and the significance of each aetiology is considered.
Fernandez-Granero, Miguel Angel; Sanchez-Morillo, Daniel; Leon-Jimenez, Antonio
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. PMID:26512667
Fernandez-Granero, Miguel Angel; Sanchez-Morillo, Daniel; Leon-Jimenez, Antonio
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.
Akpinar, Evrim Eylem; Hoşgün, Derya; Akpýnar, Serdar; Ataç, Gökçe Kaan; Doğanay, Beyza; Gülhan, Meral
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
Meloni, F; Paschetto, E; Mangiarotti, P; Crepaldi, M; Morosini, M; Bulgheroni, A; Fietta, A
Rates of acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections were determined in 115 adults hospitalized for community-acquired pneumonia (CAP), purulent exacerbations of COPD and acute exacerbations of bronchial asthma, by means of serology and molecular methods. Results were compared with those obtained in a matched control group. Common respiratory pathogens were isolated by cultures in 22.5% and 22.2% of CAP and exacerbated COPD patients, respectively. Cultures from exacerbated asthma patients were always negative. Serological and molecular evidence of current C. pneumoniae infection was obtained in 10.0%, 8.9% and 3.3% of CAP, COPD and asthma cases. The corresponding rates of acute M. pneumoniae infection were 17.5%, 6.7% and 3.3%, respectively. Finally, no difference was found between typical and atypical pathogen rates. These findings highlight the importance of taking into account C. pneumoniae and M. pneumoniae infections in guiding the choice of empirical antibacterial treatment for CAP and purulent exacerbations of COPD.
Jeong, Suk Hyeon; Lee, Hyun; Carriere, KC; Shin, Sun Hye; Moon, Seong Mi; Jeong, Byeong-Ho; Koh, Won-Jung; Park, Hye Yun
Background Comorbidities have a serious impact on the frequent severe acute exacerbations (AEs) in patients with COPD. Previous studies have used the Charlson comorbidity index to represent a conglomerate of comorbidities; however, the respective contribution of each coexisting disease to the frequent severe AEs remains unclear. Methods A retrospective, observational study was performed in 77 COPD patients who experienced severe AE between January 2012 and December 2014 and had at least 1-year follow-up period from the date of admission for severe AE. We explored the incidence of frequent severe AEs (≥2 severe AEs during 1-year period) in these patients and investigated COPD-related factors and comorbidities as potential risk factors of these exacerbations. Results Out of 77 patients, 61 patients (79.2%) had at least one comorbidity. During a 1-year follow-up period, 29 patients (37.7%) experienced frequent severe AEs, approximately two-thirds (n=19) of which occurred within the first 90 days after admission. Compared with patients not experiencing frequent severe AEs, these patients were more likely to have poor lung function and receive home oxygen therapy and long-term oral steroids. In multiple logistic regression analysis, coexisting asthma (adjusted odds ratio [OR] =4.02, 95% confidence interval [CI] =1.30–12.46, P=0.016), home oxygen therapy (adjusted OR =9.39, 95% CI =1.60–55.30, P=0.013), and C-reactive protein (adjusted OR =1.09, 95% CI =1.01–1.19, P=0.036) were associated with frequent severe AEs. In addition, poor lung function, as measured by forced expiratory volume in 1 second (adjusted OR =0.16, 95% CI =0.04–0.70, P=0.015), was inversely associated with early (ie, within 90 days of admission) frequent severe AEs. Conclusion Based on our study, among COPD-related comorbidities, coexisting asthma has a significant impact on the frequent severe AEs in COPD patients. PMID:27536097
Boixeda, Ramon; Almagro, Pere; Díez-Manglano, Jesús; Cabrera, Francisco Javier; Recio, Jesús; Martin-Garrido, Isabel; Soriano, Joan B
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
Clark, Tristan W; Medina, Marie-Jo; Batham, Sally; Curran, Martin D; Parmar, Surendra; Nicholson, Karl G
Both viruses and bacteria are thought to cause exacerbations of chronic obstructive pulmonary disease (COPD); however, the relative importance of each remains uncertain. C-reactive protein (CRP) levels increase during exacerbations but the relationship with aetiology is not established. We aimed to explore the relationship between serum CRP and the rate of detection of viruses and bacteria. This was a prospectively recruited, observational study of patients hospitalised with exacerbations of COPD. Nasopharyngeal swabs were tested for respiratory viruses by reverse transcriptase-PCR. Sputum and blood were collected for bacterial culture and urine tested for pneumococcal antigen. CRP levels were measured on sera. CRP and other factors associated with viral, bacterial or mixed detection were assessed using multiple logistic regression analysis. 264 patients with exacerbations of COPD were studied: 26% tested positive for respiratory viruses only, 13% had bacteria only, 12% had mixed viral/bacterial detection, and 49% had no pathogens detected. CRP level and temperature were strongly associated with viral detection rate (p<0.001 and p=0.004, respectively) and mixed viral/bacterial detection rate (p=0.02 and p=0.03, respectively) on multivariate analysis. Bacterial detection rate was not associated with CRP level or body temperature. This study supports the role of viruses as important aetiological agents causing exacerbations of COPD.
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
Rothnie, Kieran J; Müllerová, Hana; Thomas, Sara L; Chandan, Joht S; Smeeth, Liam; Hurst, John R; Davis, Kourtney; Quint, Jennifer K
Background Accurate identification of hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) within electronic health care records is important for research, public health, and to inform health care utilization and service provision. We aimed to develop a strategy to identify hospitalizations for AECOPD in secondary care data and to investigate the validity of strategies to identify hospitalizations for AECOPD in primary care data. Methods We identified patients with chronic obstructive pulmonary disease (COPD) in the Clinical Practice Research Datalink (CPRD) with linked Hospital Episodes Statistics (HES) data. We used discharge summaries for recent hospitalizations for AECOPD to develop a strategy to identify the recording of hospitalizations for AECOPD in HES. We then used the HES strategy as a reference standard to investigate the positive predictive value (PPV) and sensitivity of strategies for identifying AECOPD using general practice CPRD data. We tested two strategies: 1) codes for hospitalization for AECOPD and 2) a code for AECOPD other than hospitalization on the same day as a code for hospitalization due to unspecified reason. Results In total, 27,182 patients with COPD were included. Our strategy to identify hospitalizations for AECOPD in HES had a sensitivity of 87.5%. When compared with HES, using a code suggesting hospitalization for AECOPD in CPRD resulted in a PPV of 50.2% (95% confidence interval [CI] 48.5%–51.8%) and a sensitivity of 4.1% (95% CI 3.9%–4.3%). Using a code for AECOPD and a code for hospitalization due to unspecified reason resulted in a PPV of 43.3% (95% CI 42.3%–44.2%) and a sensitivity of 5.4% (95% CI 5.1%–5.7%). Conclusion Hospitalization for AECOPD can be identified with high sensitivity in the HES database. The PPV and sensitivity of strategies to identify hospitalizations for AECOPD in primary care data alone are very poor. Primary care data alone should not be used to identify
MacDonald, Martin; Beasley, Richard W; Irving, Louis; Bardin, Philip G
COPD exacerbations have traditionally been defined on the basis of symptoms or health-care utilization without specific reference to the suspected aetiology. Consequently, the term 'exacerbation' has been used to include all patients experiencing an acute deterioration of symptoms associated with COPD. However, exacerbations are known to result from a variety of causes and do not necessarily constitute an equivalent event in the same patient, between different patients or between individual research studies. We therefore hypothesize that phenotyping exacerbations by aetiology may identify exacerbation subgroups, clarify benefits of therapeutic intervention in the subgroups and overall improve clinical care. An acronym is proposed to facilitate phenotyping COPD exacerbations.
Bernabeu-Mora, Roberto; García-Guillamón, Gloria; Montilla-Herrador, Joaquina; Escolar-Reina, Pilar; García-Vidal, José Antonio; Medina-Mirapeix, Francesc
Background Hospitalization is common for acute exacerbation of COPD, but little is known about its impact on the mental health of caregivers. Objective The aim of this study was to determine the rates and predictors of depressive symptoms in caregivers at the time of hospitalization for acute exacerbation of COPD and to identify the probability and predictors of subsequent changes in depressive status 3 months after discharge. Materials and methods This was a prospective study. Depression symptoms were measured in 87 caregivers of patients hospitalized for exacerbation at hospitalization and 3 months after discharge. We measured factors from four domains: context of care, caregiving demands, caregiver resources, and patient characteristics. Univariate and multivariate multiple logistic regressions were used to determine the predictors of depression at hospitalization and subsequent changes at 3 months. Results A total of 45 caregivers reported depression at the time of hospitalization. After multiple adjustments, spousal relationship, dyspnea, and severe airflow limitation were the strongest independent predictors of depression at hospitalization. Of these 45 caregivers, 40% had a remission of their depression 3 months after discharge. In contrast, 16.7% of caregivers who were not depressive at hospitalization became depressive at 3 months. Caregivers caring >20 hours per week for patients with dependencies had decreased odds of remission, and patients having dependencies after discharge increased the odds of caregivers becoming depressed. Conclusion Depressive symptoms are common among caregivers when patients are hospitalized for exacerbation of COPD. Although illness factors are determinants of depression at hospitalization, patient dependence determines fluctuations in the depressive status of caregivers. PMID:28008245
Bathoorn, Erik; Groenhof, Feikje; Hendrix, Ron; van der Molen, Thys; Sinha, Bhanu; Kerstjens, Huib AM; Friedrich, Alex W; Kocks, Janwillem WH
Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are generally treated with optimization of bronchodilation therapy and a course of oral corticosteroids, mostly without antibiotics. The Dutch guidelines recommend prudent use of antibiotics, with amoxicillin or doxycycline as first choice. Here we evaluate adherence to these guidelines with regard to antibiotic prescription in AECOPD in primary care and the use of sputum cultures. Methods We retrospectively analyzed a longitudinal cohort of patients in three primary care practices in the north-eastern region of the Netherlands from 2009 to 2013 (n=36,172 subjects) participating in the Registration Network Groningen. Antibiotics prescribed for AECOPD −10/+28 days from the start date of corticosteroid courses were evaluated. In addition, we assessed regional data on the susceptibility of respiratory pathogens from COPD patients. Results We identified 1,297 patients with COPD. Of these, 616 experienced one or more exacerbations, resulting in a total of 1,558 exacerbations, for which 1,594 antibiotic courses were prescribed. The recommended antibiotics doxycycline and amoxicillin accounted for 56% of the prescribed antibiotics overall and for 35% in subsequent antibiotic courses. The alternative choices were not based on culture results because only in 67 AECOPD events (2.9%) sputum samples were taken. Regional data including 3,638 sputum samples showed that pathogens relevant in AECOPD were detected in 19% of cultures. Conclusion Our study shows that guidelines regarding the prescription of antibiotics are poorly followed, particularly in recurrent exacerbations. Sputum cultures were performed in a small minority of cases. Performing sputum diagnostics in patients with early treatment failure or a repeated exacerbation when antibiotic treatment is started may further rationalize antibiotic treatment. PMID:28144133
Ceriana, Piero; Vitacca, Michele; Carlucci, Annalisa; Paneroni, Mara; Pisani, Lara; Nava, Stefano
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.
Aaron, Shawn D
Patients with chronic obstructive pulmonary disease (COPD) are prone to acute respiratory exacerbations, which can develop suddenly or subacutely over the course of several days. Exacerbations have a detrimental effect on patients' health status and increase the burden on the healthcare system. Initial treatment is unsuccessful in 24-27% of patients, who have a relapse or a second exacerbation within 30 days of the initial event. No obvious benefit has been seen in recent clinical trials of anti-tumour necrosis factor therapy, anti-leukotriene therapy, intensive chest physiotherapy, or early inpatient pulmonary rehabilitation for treatment of exacerbations. By contrast, clinical trials of prevention rather than acute treatment have shown promising results. Long acting β agonist (LABA) or long acting anti-muscarinic (LAMA) bronchodilators and inhaled corticosteroid-LABA combinations prevent exacerbations in patients at risk, with relative risk reductions averaging 14-27% for each of these drugs relative to placebo. Triple therapy with inhaled corticosteroid-LABA plus LAMA may provide additional benefit, although study results to date are heterogeneous and more studies are needed. Pneumonia is an important complication of treatment with inhaled corticosteroid-LABA products, and the risk of pneumonia seems to be doubled in patients with COPD who use fluticasone. The addition of azithromycin to usual COPD therapy prevents exacerbations, although it may prolong the Q-T interval and increase the risk of death from cardiovascular disease in patients prone to arrhythmia. New potential drugs--including mitogen activated protein kinase inhibitors, phosphodiesterase 3 inhibitors, and monoclonal antibodies to the interleukin 1 receptor--offer additional hope for treatments that may prevent exacerbations in the future.
Gallego, Miguel; Pomares, Xavier; Capilla, Silvia; Marcos, Maria Angeles; Suárez, David; Monsó, Eduard; Montón, Concepción
Background C-reactive protein (CRP) measurement has proven valuable for detecting exacerbations, but its usefulness in predicting etiology remains controversial. Likewise, its potential value as a marker of severity, which is well established in patients with pneumonia, remains unproven in chronic obstructive pulmonary disease (COPD) exacerbations. Methods A cohort study of 118 patients with severe COPD and acute infectious exacerbations were included and followed up over 1 year. Episodes of exacerbations meeting Anthonisen’s criteria type I–II were evaluated, analyzing the etiology and inflammatory response as measured by CRP in blood. Results A total of 380 episodes were recorded. Full microbiological analysis was available in 265 samples. Haemophilus influenzae was the most commonly isolated bacteria and rhinovirus the most common virus. Median CRP levels from the 265 episodes were higher in the cases with positive cultures for bacteria (58.30 mg/L, interquartile range [IQR] 21.0–28.2) than in episodes only positive for viruses (37.3 mg/L, IQR 18.6–79.1) and cases negative for any microorganism (36.4 mg/L, IQR 10.8–93.7) (P<0.014). H. influenzae and Streptococcus pneumoniae reached the highest CRP levels of 74.5 mg/L (IQR 23.9–167.9) and 74.1 mg/L (IQR 42.0–220.7), respectively. In the 380 exacerbations studied, 227 (~60%) were community-managed, while 153 (~40%) required hospital admission. In the multivariate analysis to assess the influence of inflammatory response on exacerbation severity, baseline hypercapnia (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.46–4.9) and CRP levels >100 mg/L (OR: 4.23, 95% CI: 2.12–8.44) were independent predictors after adjustment for baseline characteristics. Conclusion CRP level was higher in bacterial infections, especially when H. influenzae and S. pneumoniae were isolated. CRP values >100 mg/L were associated with a fourfold increased risk of hospital admission. Therefore, CRP blood levels may
Braido, F; Tarantini, F; Ghiglione, V; Melioli, G; Canonica, G W
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
Jinjuvadia, Chetna; Jinjuvadia, Raxitkumar; Mandapakala, Chaitanya; Durairajan, Navin; Liangpunsakul, Suthat; Soubani, Ayman O
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.
Ott, S R; Rohde, G; Lepper, P M; Hauptmeier, B; Bals, R; Pletz, M W R; Schumann, C; Steininger, C; Kleines, M; Geerdes-Fenge, H
In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2 (nd) part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options.
Bauer, T T; Nilius, G; Grüning, W; Rasche, K
The acute exacerbation of COPD (AECOPD) is a life-threatening clinical situation. This review summarizes the definition of AECOPD, the severity assessment, typical clinical signs and symptoms, and refers to clinical pitfalls of diagnosis and therapy. Important aspects of clinical history and physical examination in severe exacerbations are reported. The necessary accompanying examinations like chest X-ray, blood gas analysis, ECG and echocardiography and their differential diagnosis as well as therapeutic significance are described. The most important lab examinations are summarized and controversial parameters, e.g., procalcitonin, are commented upon. The differentiated need for a microbiological sputum screening is emphasized. The authors place special weight on the essential components of the therapeutic management of severe AECOPD. Practical aspects of uncontrolled oxygen therapy, drug selection, and application form of inhalative acute therapy, dose, and duration of glucocorticoids, the indication for antibiotics, mechanical ventilation, and also opiates are summarized.
The Belgian trial with azithromycin for acute COPD exacerbations requiring hospitalization: an investigator-initiated study protocol for a multicenter, randomized, double-blind, placebo-controlled trial
Vermeersch, Kristina; Gabrovska, Maria; Deslypere, Griet; Demedts, Ingel K; Slabbynck, Hans; Aumann, Joseph; Ninane, Vincent; Verleden, Geert M; Troosters, Thierry; Bogaerts, Kris; Brusselle, Guy G; Janssens, Wim
Background Long-term use of macrolide antibiotics is effective to prevent exacerbations in chronic obstructive pulmonary disease (COPD). As risks and side effects of long-term intervention outweigh the benefits in the general COPD population, the optimal dose, duration of treatment, and target population are yet to be defined. Hospitalization for an acute exacerbation (AE) of COPD may offer a targeted risk group and an obvious risk period for studying macrolide interventions. Methods/design Patients with COPD, hospitalized for an AE, who have a smoking history of ≥10 pack-years and had ≥1 exacerbation in the previous year will be enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (NCT02135354). On top of a standardized treatment of systemic corticosteroids and antibiotics, subjects will be randomized to receive either azithromycin or placebo during 3 months, at an uploading dose of 500 mg once a day for 3 days, followed by a maintenance dose of 250 mg once every 2 days. The primary endpoint is the time-to-treatment failure during the treatment phase (ie, from the moment of randomization until the end of intervention). Treatment failure is a novel composite endpoint defined as either death, the admission to intensive care or the requirement of additional systemic steroids or new antibiotics for respiratory reasons, or the diagnosis of a new AE after discharge. Discussion We investigate whether azithromycin initiated at the onset of a severe exacerbation, with a limited duration and at a low dose, might be effective and safe in the highest risk period during and immediately after the acute event. If proven effective and safe, this targeted approach may improve the treatment of severe AEs and redirect the preventive use of azithromycin in COPD to a temporary intervention in the subgroup with the highest unmet needs. PMID:27099485
Ogawa, Kazumasa; Kishi, Kazuma
Recently, it has been found that the number of patients with chronic obstructive pulmonary disease (COPD) who do not have a history of smoking is higher than expected, and a number of factors affect the development of COPD. Although adequate evidence for the relation of ambient air pollution, including the presence of particulate matter (PM2.5), with the development of COPD is lacking, higher mortality from respiratory and cardiovascular diseases has been reported among patients exposed to air pollution for a long time. In addition, several reports have pointed out the possibility that acute exacerbation of COPD can be caused by short-term exposure to air pollution. Tobacco smoke is the main cause of highly concentrated PM2.5 indoors, and second hand smoke is related with the development of COPD and the high mortality from COPD. In developing countries, biomass fuel combustion contributes to COPD, especially among housewives who do not smoke.
Tsiligianni, Ioanna; Goodridge, Donna; Marciniuk, Darcy; Hull, Sally; Bourbeau, Jean
The American College of Chest Physicians and Canadian Thoracic Society have jointly produced evidence-based guidelines for the prevention of exacerbations in chronic obstructive pulmonary disease (COPD). This educational article gives four perspectives on how these guidelines apply to the practical management of people with COPD. A current smoker with frequent exacerbations will benefit from support to quit, and from optimisation of his inhaled treatment. For a man with very severe COPD and multiple co-morbidities living in a remote community, tele-health care may enable provision of multidisciplinary care. A woman who is admitted for the third time in a year needs a structured assessment of her care with a view to stepping up pharmacological and non-pharmacological treatment as required. The overlap between asthma and COPD challenges both diagnostic and management strategies for a lady smoker with a history of asthma since childhood. Common threads in all these cases are the importance of advising on smoking cessation, offering (and encouraging people to attend) pulmonary rehabilitation, and the importance of self-management, including an action plan supported by multidisciplinary teams. PMID:25950092
Spruit, M; Gosselink, R; Troosters, T; Kasran, A; Gayan-Ramirez, G; Bogaerts, P; Bouillon, R; Decramer, M
Background: Chronic obstructive pulmonary disease (COPD) is often associated with peripheral muscle weakness, which is caused by several factors. Acute exacerbations may contribute, but their impact on muscle force remains unclear. Correlations between peripheral muscle force and inflammatory and anabolic markers have never been studied in COPD. The effect of an acute exacerbation on quadriceps peak torque (QPT) was therefore studied in hospitalised patients, and the aforementioned correlations were examined in hospitalised and in stable patients. Methods: Lung function, respiratory and peripheral muscle force, and inflammatory and anabolic markers were assessed in hospitalised patients on days 3 and 8 of the hospital admission and 90 days later. The results on day 3 (n=34) were compared with those in clinically stable outpatients (n=13) and sedentary healthy elderly subjects (n=10). Results: Hospitalised patients had lowest mean (SD) QPT (66 (22)% predicted) and highest median (IQR) levels of systemic interleukin-8 (CXCL8, 6.1 (4.5 to 8.3) pg/ml). Insulin-like growth factor I (IGF-I) tended to be higher in healthy elderly subjects (p=0.09). QPT declined between days 3 and 8 in hospital (mean -5% predicted (95% CI -22 to 8)) and partially recovered 90 days after admission to hospital (mean 6% predicted (95% CI -1 to 23)). QPT was negatively correlated with CXCL8 and positively correlated with IGF-I and lung transfer factor in hospitalised and in stable patients. Conclusions: Peripheral muscle weakness is enhanced during an acute exacerbation of COPD. CXCL8 and IGF-I may be involved in the development of peripheral muscle weakness in hospitalised and in stable patients with COPD. PMID:12947130
Hartl, Sylvia; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Castro-Acosta, Ady; Studnicka, Michael; Kaiser, Bernhard; Roberts, C Michael
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.
Ding, Hang; Karunanithi, Mohan; Kanagasingam, Yogi; Vignarajan, Janardhan; Moodley, Yuben
We conducted a six-month feasibility study of a mobile-phone-based home monitoring system, called M-COPD. Patients with a history of moderate Acute Exacerbation of COPD (AECOPD) were given a mobile phone to record major symptoms (dyspnoea, sputum colour and volume), minor symptoms (cough and wheezing) and vital signs. A care team remotely monitored the recorded data and provided clinical interventions. Eight patients (mean age 65 years) completed the trial. Ten acute exacerbations occurred during the trial and were successfully treated at home. Prior to the AECOPD episode, the combined score of the major symptoms increased significantly (P < 0.05). Following the intervention, it decreased significantly (P < 0.05) within two weeks and returned to the baseline. The score of the minor symptoms also increased significantly (P < 0.05), but the decrease following the intervention was not significant. There were significantly fewer hospital admissions during the trial, fewer ED presentations and fewer GP visits than in a six-month matched period in the preceding year. The results demonstrate the potential of home monitoring for analysing respiratory symptoms for early intervention of AECOPD.
Wang, Zhang; Bafadhel, Mona; Haldar, Koirobi; Spivak, Aaron; Mayhew, David; Miller, Bruce E; Tal-Singer, Ruth; Johnston, Sebastian L; Ramsheh, Mohammadali Yavari; Barer, Michael R; Brightling, Christopher E; Brown, James R
Increasing evidence suggests that the lung microbiome plays an important role in chronic obstructive pulmonary disease (COPD) severity. However, the dynamics of the lung microbiome during COPD exacerbations and its potential role in disease aetiology remain poorly understood.We completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on 476 sputum samples collected from 87 subjects with COPD at four visits defined as stable state, exacerbation, 2 weeks post-therapy and 6 weeks recovery.Our analysis revealed a dynamic lung microbiota where changes appeared to be associated with exacerbation events and indicative of specific exacerbation phenotypes. Antibiotic and steroid treatments appear to have differential effects on the lung microbiome. We depict a microbial interaction network for the lung microbiome and suggest that perturbation of a few bacterial operational taxonomic units, in particular Haemophilus spp., could greatly impact the overall microbial community structure. Furthermore, several serum and sputum biomarkers, in particular sputum interleukin-8, appear to be highly correlated with the structure and diversity of the microbiome.Our study furthers the understanding of lung microbiome dynamics in COPD patients and highlights its potential as a biomarker, and possibly a target, for future respiratory therapeutics.
Introduction The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven. Methods The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled. Results Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization. Conclusions The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged. Trial registration ClinicalTrials.gov NCT01291303. PMID:22115190
Liao, Lin-Yu; Chen, Kuei-Min; Chung, Wei-Sheng; Chien, Jung-Yien
Clinical trials identifier NCT02329873 Background Acute exacerbation (AE) of COPD is characterized by a sudden worsening of COPD symptoms. Previous studies have explored the effectiveness of respiratory rehabilitation for patients with COPD; however, no training program specific to acute exacerbation in elderly patients or unstable periods during hospitalization has been developed. Objective To evaluate the effects of a respiratory rehabilitation exercise training package on dyspnea, cough, exercise tolerance, and sputum expectoration among hospitalized elderly patients with AECOPD. Methods A randomized control trial was conducted. Pretest and posttest evaluations of 61 elderly inpatients with AECOPD (experimental group n=30; control group n=31) were performed. The experimental group received respiratory rehabilitation exercise training twice a day, 10–30 minutes per session for 4 days. The clinical parameters (dyspnea, cough, exercise tolerance, and sputum expectoration) were assessed at the baseline and at the end of the fourth day. Results All participants (median age =70 years, male =60.70%, and peak expiratory flow 140 L) completed the study. In the patients of the experimental group, dyspnea and cough decreased and exercise tolerance and sputum expectoration increased significantly compared with those of the patients in the control group (all P<0.05). Within-group comparisons revealed that the dyspnea, cough, and exercise tolerance significantly improved in the experimental group by the end of the fourth day (all P<0.05). Conclusion Results of this study suggest that the respiratory rehabilitation exercise training package reduced symptoms and enhanced the effectiveness of the care of elderly inpatients with AECOPD. PMID:26345529
Chang, Suchi; Shi, Jindong; Fu, Cuiping; Wu, Xu; Li, Shanqun
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
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.
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. PMID:28328968
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
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.
Kerkhof, Marjan; Freeman, Daryl; Jones, Rupert; Chisholm, Alison; Price, David B
Purpose Acute COPD exacerbations account for much of the rising disability and costs associated with COPD, but data on predictive risk factors are limited. The goal of the current study was to develop a robust, clinically based model to predict frequent exacerbation risk. Patients and methods Patients identified from the Optimum Patient Care Research Database (OPCRD) with a diagnostic code for COPD and a forced expiratory volume in 1 second/forced vital capacity ratio <0.7 were included in this historical follow-up study if they were ≥40 years old and had data encompassing the year before (predictor year) and year after (outcome year) study index date. The data set contained potential risk factors including demographic, clinical, and comorbid variables. Following univariable analysis, predictors of two or more exacerbations were fed into a stepwise multivariable logistic regression. Sensitivity analyses were conducted for subpopulations of patients without any asthma diagnosis ever and those with questionnaire data on symptoms and smoking pack-years. The full predictive model was validated against 1 year of prospective OPCRD data. Results The full data set contained 16,565 patients (53% male, median age 70 years), including 9,393 patients without any recorded asthma and 3,713 patients with questionnaire data. The full model retained eleven variables that significantly predicted two or more exacerbations, of which the number of exacerbations in the preceding year had the strongest association; others included height, age, forced expiratory volume in 1 second, and several comorbid conditions. Significant predictors not previously identified included eosinophilia and COPD Assessment Test score. The predictive ability of the full model (C statistic 0.751) changed little when applied to the validation data set (n=2,713; C statistic 0.735). Results of the sensitivity analyses supported the main findings. Conclusion Patients at risk of exacerbation can be identified
Tsoumakidou, Maria; Siafakas, Nikolaos M
Airway inflammation increases during acute exacerbations of COPD. Extrinsic factors, such as airway infections, increased air pollution, and intrinsic factors, such as increased oxidative stress and altered immunity may contribute to this increase. The evidence for this and the potential mechanisms by which various aetiological agents increase inflammation during COPD exacerbations is reviewed. The pathophysiologic consequences of increased airway inflammation during COPD exacerbations are also discussed. This review aims to establish a cause and effect relationship between etiological factors of increased airway inflammation and COPD exacerbations based on recently published data. Although it can be speculated that reducing inflammation may prevent and/or treat COPD exacerbations, the existing anti-inflammatory treatments are modestly effective.
Guerrero, Mónica; Crisafulli, Ernesto; Liapikou, Adamantia; Huerta, Arturo; Gabarrús, Albert; Chetta, Alfredo; Soler, Nestor; Torres, Antoni
Background and Objective Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge. The prognostic significance of early readmission is not fully understood. The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients. Methods The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge. Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years. Results Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity. Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51–4.05) was the only variable independently associated with 30-day readmission. The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10–5.59). In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5). Conclusion In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death. PMID:26943928
Mandal, S; Howes, T Q; Parker, M; Roberts, C M
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.
FitzGerald, J Mark; Haddon, Jennifer M; Bradley-Kennedy, Carole; Kuramoto, Lisa; Ford, Gordon T
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
Pauwels, R; Calverley, P; Buist, A S; Rennard, S; Fukuchi, Y; Stahl, E; Löfdahl, C G
Efforts to assess the efficacy of new therapies in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) have been hampered by the lack of a widely agreed and consistently used definition. A variety of definitions have been used in clinical studies, based on changes in patient symptoms or the requirement for antibiotic therapy, oral steroids or hospitalisation. To date, none of these definitions have been assessed in detail for their reliability, responsiveness and validity determined. Considerable heterogeneity in the aetiology and manifestation of COPD exacerbations makes identification and quantification of defining symptoms extremely difficult. New approaches are therefore being sought with a view to identifying a serum or tissue marker that can be used as a valuable diagnostic tool. Improvements in data recording will also contribute to the accuracy of data retrieval and assessment. If we are to progress to a level of sophistication seen in the diagnosis and management of other diseases, it is evident that considerable research efforts will be required to improve our understanding of COPD exacerbations and develop a standard definition for these events, thereby facilitating the assessment of therapeutic approaches.
Djamin, Remco S; Uzun, Sevim; Snelders, Eveline; Kluytmans, Jan J W; Hoogsteden, Henk C; Aerts, Joachim G J V; Van Der Eerden, Menno M
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.
Kurai, Daisuke; Saraya, Takeshi; Ishii, Haruyuki; Takizawa, Hajime
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and/or airflow limitation due to pulmonary emphysema. Chronic bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with airflow limitation; therefore, exacerbation of asthma may be associated with the pathophysiology of COPD. Furthermore, recent studies have suggested that the exacerbation of asthma, namely virus-induced asthma, may be associated with a wide variety of respiratory viruses. COPD and asthma have different underlying pathophysiological processes and thus require individual therapies. Exacerbation of both COPD and asthma, which are basically defined and diagnosed by clinical symptoms, is associated with a rapid decline in lung function and increased mortality. Similar pathogens, including human rhinovirus, respiratory syncytial virus, influenza virus, parainfluenza virus, and coronavirus, are also frequently detected during exacerbation of asthma and/or COPD. Immune response to respiratory viral infections, which may be related to the severity of exacerbation in each disease, varies in patients with both COPD and asthma. In this regard, it is crucial to recognize and understand both the similarities and differences of clinical features in patients with COPD and/or asthma associated with respiratory viral infections, especially in the exacerbative stage. In relation to definition, epidemiology, and pathophysiology, this review aims to summarize current knowledge concerning exacerbation of both COPD and asthma by focusing on the clinical significance of associated respiratory virus infections. PMID:24098299
Crooks, Michael G; Hayman, Yvette; Innes, Andrew; Williamson, James; Wright, Caroline E; Morice, Alyn H
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Cough and sputum production are associated with adverse outcomes in COPD and are common during COPD exacerbation (AE-COPD). This study of objective cough monitoring using the Hull Automated Cough Counter and Leicester Cough Monitor software confirms that this system has the ability to detect a significant decrease in cough frequency during AE-COPD convalescence. The ability to detect clinically meaningful change indicates a potential role in home monitoring of COPD patients.
Seemungal, Terence AR; Hurst, John R; Wedzicha, Jadwiga A
COPD is prevalent in Western society and its incidence is rising in the developing world. Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden. Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease. COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality. Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use. Erythromycin has been shown to decrease the rate of COPD exacerbations. Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life. Noninvasive ventilation is associated with improved quality of life. Long-term oxygen therapy improves mortality but only in hypoxic COPD patients. The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of. Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates. Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles. PMID:19554195
Seemungal, Terence A R; Hurst, John R; Wedzicha, Jadwiga A
COPD is prevalent in Western society and its incidence is rising in the developing world. Acute exacerbations of COPD, about 50% of which are unreported, lead to deterioration in quality of life and contribute significantly to disease burden. Quality of life deteriorates with time; thus, most of the health burden occurs in more severe disease. COPD severity and frequent and more severe exacerbations are all related to an increased risk of mortality. Inhaled corticosteroids (ICS) have similar effects on quality of life but ICS/long-acting bronchodilator combinations and the long-acting antimuscarinic tiotropium all improve health status and exacerbation rates and are likely to have an effect on mortality but perhaps only with prolonged use. Erythromycin has been shown to decrease the rate of COPD exacerbations. Pulmonary rehabilitation and regular physical activity are indicated in all severities of COPD and improve quality of life. Noninvasive ventilation is associated with improved quality of life. Long-term oxygen therapy improves mortality but only in hypoxic COPD patients. The choice of an inhaler device is a key component of COPD therapy and this requires more attention from physicians than perhaps we are aware of. Disease management programs, characterized as they are by patient centeredness, improve quality of life and decrease hospitalization rates. Most outcomes in COPD can be modified by interventions and these are well tolerated and have acceptable safety profiles.
Søgaard, Mette; Madsen, Morten; Løkke, Anders; Hilberg, Ole; Sørensen, Henrik Toft; Thomsen, Reimar W
Background Pneumonia may be a major contributor to hospitalizations for chronic obstructive pulmonary disease (COPD) exacerbation and influence their outcomes. Methods We examined hospitalization rates, health resource utilization, 30-day mortality, and risk of subsequent hospitalizations for COPD exacerbations with and without pneumonia in Denmark during 2006–2012. Results We identified 179,759 hospitalizations for COPD exacerbations, including 52,520 first-time hospitalizations (29.2%). Pneumonia was frequent in first-time exacerbations (36.1%), but declined in successive exacerbations to 25.6% by the seventh or greater exacerbation. Pneumonic COPD exacerbations increased 20% from 0.92 per 1,000 population in 2006 to 1.10 per 1,000 population in 2012. Nonpneumonic exacerbations decreased by 6% from 1.74 per 1,000 population to 1.63 per 1,000 population during the same period. A number of markers of health resource utilization were more prevalent in pneumonic exacerbations than in nonpneumonic exacerbations: length of stay (median 7 vs 4 days), intensive care unit admission (7.7% vs 12.5%), and several acute procedures. Thirty-day mortality was 12.1% in first-time pneumonic COPD exacerbations versus 8.3% in first-time nonpneumonic cases (adjusted HR [aHR] 1.20, 95% confidence interval [CI] 1.17–1.24). Pneumonia also predicted increased mortality associated with a second exacerbation (aHR 1.14, 95% CI 1.11–1.18), and up to a seventh or greater exacerbation (aHR 1.10, 95% CI 1.07–1.13). In contrast, the aHR of a subsequent exacerbation was 8%–13% lower for patients with pneumonic exacerbations. Conclusions Pneumonia is frequent among patients hospitalized for COPD exacerbations and is associated with increased health care utilization and higher mortality. Nonpneumonic COPD exacerbations predict increased risk of subsequent exacerbations. PMID:27042038
Borrell, Eulàlia; Rodríguez, Mar; Torán, Pere; Muñoz, Laura; Pera, Guillem; Montellà, Núria; Monteagudo, Mònica; Urrea, Magalí; Puigfel, Yolanda; Negrete, Antonio; Mezquiriz, Xavier; Domènech, Cristina; Lacasta, Anna; García, Ma Llum; Maneus, Sandra; Tintoré, Glòria
Background Worldwide, chronic obstructive pulmonary disease (COPD) is the fourth cause of death. Exacerbations have a negative impact on the prognosis of COPD and the frequency and severity of these episodes are associated with a higher patient mortality. Exacerbations are the first cause of decompensation, hospital admission and death in COPD. The incidence of exacerbations has mainly been estimated in populations of patients with moderate-severe COPD requiring hospital care. However, little is known regarding the epidemiology of exacerbations in patients with less severe COPD forms. It is therefore possible that a high number of these less severe forms of exacerbations are underdiagnosed and may, in the long-term, have certain prognostic importance for the COPD evolution. The aim of this study was to know the incidence and risk factors associated with exacerbations in patients with COPD in primary care. Methods and design A prospective, observational, 3-phase, multicentre study will be performed involving: baseline evaluation, follow up and final evaluation. A total of 685 smokers or ex-smokers from 40 to 80 years of age with COPD, without acute respiratory disease or any other long-term respiratory disease will be randomly selected among the population assigned to 21 primary care centres. The diagnosis of COPD and its severity will be confirmed by spirometry. Information regarding the baseline situation, quality of life and exposure to contaminants or other factors potentially related to exacerbations will be collected. A group of 354 patients with confirmed COPD of varying severity will be followed for one year through monthly telephone calls and daily reporting of symptoms with the aim of detecting all the exacerbations which occur. These patients will be evaluated again at the end of the study and the incidence of exacerbations and associated relative risks will be estimated by negative binomial regression. Discussion The results will be relevant to provide
Johnston, Neil W; Olsson, Marita; Edsbäcker, Staffan; Gerhardsson de Verdier, Maria; Gustafson, Per; McCrae, Christopher; Coyle, Peter V; McIvor, R Andrew
Rationale Common colds are associated with acute respiratory symptom exacerbations in COPD patients. Objective To determine exacerbation risk and severity in COPD patients with/without coincident self-reported colds. Methods Global initiative for chronic Obstructive Lung Disease stage I–IV COPD patients electronically transmitted respiratory symptom diaries to research staff daily between December 2006 and April 2009. Respiratory symptom worsening prompted contact by a study nurse and patient assessment to determine if a cold was present or an exacerbation underway. A composite daily symptom score was derived for each subject from diarized symptom data. The exacerbation/cold/virus relation was examined using a Poisson regression model, the relation of colds to respiratory symptom severity using generalized estimating equation models. Results Daily diary transmission compliance of >97% enabled detection of all possible exacerbations. Among 262 exacerbations meeting Anthonisen criteria, 218 (83%) had cold-like symptoms present at their inception, but respiratory viruses were detected in only 106 (40%). Within-subject exacerbation risk was 30 times (95% confidence interval [CI]: 20, 47; P<0.001) greater with colds present. Compared to cold- and virus-negative exacerbations (n=57), the mean increase in composite symptom score in those cold and virus positive (n=79) was 0.93 (95% CI: 0.61, 1.25; P<0.001), cold-positive and virus-negative exacerbations (n=100) 0.51 (95% CI: 0.21, 0.81; P<0.001), cold-negative and virus-positive exacerbations (n=26) 0.58 (95% CI: 0.23, 0.94; P<0.001). Conclusion This study emphasizes the importance of colds in COPD exacerbation risk and severity, even in the absence of virus detection. COPD patients should act promptly when cold symptoms appear to facilitate early intervention for exacerbation prevention or management. PMID:28331305
Chang, Chun; Zhu, Hong; Shen, Ning; Han, Xiang; Chen, Yahong; He, Bei
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
Lee, Hyun; Rhee, Chin Kook; Lee, Byung-Jae; Choi, Dong-Chull; Kim, Jee-Ae; Kim, Sang Hyun; Jeong, Yoolwon; Kim, Tae-Hyung; Chon, Gyu Rak; Jung, Ki-Suck; Lee, Sang Haak; Price, David; Yoo, Kwang Ha; Park, Hye Yun
Background Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD. Methods Patients with mild-to-moderate COPD (≥40 years) were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012) and were linked to the national health insurance reimbursement database to obtain medical service utilization records. Results Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6%) had severe exacerbations over the 6 years (0.012/person-year). Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P<0.001). A multiple logistic regression presented that asthma was an independent risk factor of severe exacerbations in patients with mild-to-moderate COPD regardless of adjustment for all possible confounding factors (adjusted odds ratio, 1.67; 95% confidence interval, 1.002–2.77, P=0.049). In addition, age, female, poor lung function, use of inhalers, and low EuroQoL five dimensions questionnaire index values were independently associated with severe exacerbation in patients with mild-to-moderate COPD. Conclusion In this population-based study, the prevalence of severe exacerbations in patients with mild-to-moderate COPD was relatively low, compared with previous clinical interventional studies. Coexisting asthma significantly impacted the frequency of severe exacerbations in patients with mild-to-moderate COPD, suggesting application of an exacerbation preventive strategy in these patients. PMID:27143869
Feng, Enzhi; Wan, Ronghua; Yang, Shengyue; Yan, Ziqiang; Wang, Shaolin; He, Wei; Zhang, Ying; Yin, He; Chen, Zongru; Liu, Ruinian
The aim of this study was to assess the expression levels of induced sputum interleukin (IL)-8 and IL-10 levels in patients with acute exacerbated chronic obstructive pulmonary disease (AECOPD) complicated with chronic cor pulmonale (CCP) at high altitude, and to evaluate the intervention effects of an inhaled corticosteroid (ICS) and a β2-adrenoceptor agonist in this disease. A total of 186 patients with AECOPD complicated with CCP were randomly divided into three groups, with 62 cases in each. With regard to the two treatment groups, group A was treated with salmeterol/fluticasone (50 μg/250 μg, respectively) by airway inhalation twice daily, while group B received budesonide (1 mg) as a spray inhalation, twice daily. The routine treatment group (group C) received only routine treatment. The levels of IL-8 and IL-10 in the induced sputum and the predicted percentage of forced expiratory volume in one second (FEV1%pred), partial pressure of oxygen in arterial blood (PaO2) and partial pressure of carbon dioxide in arterial blood (PaCO2) were examined on admission and at a stable stage two weeks following treatment. Forty healthy volunteers served as a control group (group D). Compared with group D values, the IL-8 induced sputum level and the PaCO2 were significantly increased, while the level of IL-10, FEV1%pred and the PaO2 were markedly decreased in the three COPD groups prior to treatment. Following treatment, the induced sputum IL-8 level and the PaCO2 were significantly decreased, while the induced sputum IL-10 level, FEV1%pred and the PaO2 were markedly increased in the three treatment groups compared with the values pre-therapy (all P<0.01). The post-treatment parameters were significantly different among the three groups (P<0.01). The results indicate that IL-8 and IL-10 are involved in the airway inflammation of AECOPD complicated by CCP. Treatment with an ICS was demonstrated to be a successful method of reducing the local expression of IL-8 and
Lykkegaard, Jesper; dePont Christensen, René; Davidsen, Jesper Rømhild; Støvring, Henrik; Andersen, Morten; Søndergaard, Jens
This study aimed to estimate time trends in the lifetime risk of hospitalisation with exacerbation of chronic obstructive pulmonary disease (COPD) in Denmark. During the period from 1994 to 2008, a register-based cohort study was conducted covering each subject in the entire population of Denmark (5.18 million in 2008). Based on previously validated diagnosis codes, all COPD hospitalisations were identified. Individual retrospective review periods of 8 years were used to determine first-time hospitalisations. From year 2002 to 2008, all first-time COPD hospitalised subjects aged ≥30 years were identified. The calculation of lifetime risk was based on age- and sex-specific first-time COPD hospitalisation rates and rates of COPD hospitalisation-free survival, assuming them to be calendar time stationary. The study included 23.9 million person-years of risk time and identified 48 959 first-time COPD hospitalisations. For 30-year-olds in Denmark, the lifetime risk of COPD hospitalisation was 12.0% (95% CI 11.9-12.2) for females and 10.9% (95% CI 10.8-11.1) for males. Trends were generally equal in both sexes. During the period from 2002 to 2008, the rate of first-time COPD hospitalisations decreased, while the survival of never COPD hospitalised subjects increased. In consequence, the lifetime risk of COPD hospitalisation remained constant.
Soler-Cataluna, J; Martinez-Garcia, M; Roman, S; Salcedo, E; Navarro, M; Ochando, R
Background: Patients with chronic obstructive pulmonary disease (COPD) often present with severe acute exacerbations requiring hospital treatment. However, little is known about the prognostic consequences of these exacerbations. A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality. Methods: Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital (visits to the emergency service and admissions), patient age, smoking, body mass index, co-morbidity, long term oxygen therapy, forced spirometric parameters, and arterial blood gas tensions in a prospective cohort of 304 men with COPD followed up for 5 years. The mean (SD) age of the patients was 71 (9) years and forced expiratory volume in 1 second was 46 (17)%. Results: Only older age (hazard ratio (HR) 5.28, 95% CI 1.75 to 15.93), arterial carbon dioxide tension (HR 1.07, 95% CI 1.02 to 1.12), and acute exacerbations of COPD were found to be independent indicators of a poor prognosis. The patients with the greatest mortality risk were those with three or more acute COPD exacerbations (HR 4.13, 95% CI 1.80 to 9.41). Conclusions: This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis. Mortality increases with the frequency of severe exacerbations, particularly if these require admission to hospital. PMID:16055622
Vassilakopoulos, Theodoros; Toumpanakis, Dimitrios
In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus) in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction). The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence. PMID:27713628
Mesquita, Carolina Bonfanti; Caram, Laura M. O.; Dourado, Victor Zuniga; de Godoy, Irma; Tanni, Suzana Erico
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
Reddy, Raghu M; Guntupalli, Kalpalatha K
Chronic obstructive pulmonary disease (COPD) is a major global healthcare problem. Studies vary widely in the reported frequency of mechanical ventilation in acute exacerbations of COPD. Invasive intubation and mechanical ventilation may be associated with significant morbidity and mortality. A good understanding of the airway pathophysiology and lung mechanics in COPD is necessary to appropriately manage acute exacerbations and respiratory failure. The basic pathophysiology in COPD exacerbation is the critical expiratory airflow limitation with consequent dynamic hyperinflation. These changes lead to further derangement in ventilatory mechanics, muscle function and gas exchange which may result in respiratory failure. This review discusses the altered respiratory mechanics in COPD, ways to detect these changes in a ventilated patient and formulating ventilatory techniques to optimize management of respiratory failure due to exacerbation of COPD.
Reddy, Raghu M; Guntupalli, Kalpalatha K
Chronic obstructive pulmonary disease (COPD) is a major global healthcare problem. Studies vary widely in the reported frequency of mechanical ventilation in acute exacerbations of COPD. Invasive intubation and mechanical ventilation may be associated with significant morbidity and mortality. A good understanding of the airway pathophysiology and lung mechanics in COPD is necessary to appropriately manage acute exacerbations and respiratory failure. The basic pathophysiology in COPD exacerbation is the critical expiratory airflow limitation with consequent dynamic hyperinflation. These changes lead to further derangement in ventilatory mechanics, muscle function and gas exchange which may result in respiratory failure. This review discusses the altered respiratory mechanics in COPD, ways to detect these changes in a ventilated patient and formulating ventilatory techniques to optimize management of respiratory failure due to exacerbation of COPD. PMID:18268918
Leung, Janice M.; Chen, Virginia; Hollander, Zsuzsanna; Dai, Darlene; Tebbutt, Scott J.; Aaron, Shawn D.; Vandemheen, Kathy L.; Rennard, Stephen I.; FitzGerald, J. Mark; Woodruff, Prescott G.; Lazarus, Stephen C.; Connett, John E.; Coxson, Harvey O.; Miller, Bruce; Borchers, Christoph; McManus, Bruce M.; Ng, Raymond T.; Sin, Don D.
Background Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in considerable morbidity and mortality. However, there are no objective biomarkers to diagnose AECOPD. Methods We used multiple reaction monitoring mass spectrometry to quantify 129 distinct proteins in plasma samples from patients with COPD. This analytical approach was first performed in a biomarker cohort of patients hospitalized with AECOPD (Cohort A, n = 72). Proteins differentially expressed between AECOPD and convalescent states were chosen using a false discovery rate <0.01 and fold change >1.2. Protein selection and classifier building were performed using an elastic net logistic regression model. The performance of the biomarker panel was then tested in two independent AECOPD cohorts (Cohort B, n = 37, and Cohort C, n = 109) using leave-pair-out cross-validation methods. Results Five proteins were identified distinguishing AECOPD and convalescent states in Cohort A. Biomarker scores derived from this model were significantly higher during AECOPD than in the convalescent state in the discovery cohort (p<0.001). The receiver operating characteristic cross-validation area under the curve (CV-AUC) statistic was 0.73 in Cohort A, while in the replication cohorts the CV-AUC was 0.77 for Cohort B and 0.79 for Cohort C. Conclusions A panel of five biomarkers shows promise in distinguishing AECOPD from convalescence and may provide the basis for a clinical blood test to diagnose AECOPD. Further validation in larger cohorts is necessary for future clinical translation. PMID:27525416
Lode, H; Eller, J; Linnhoff, A; Ioanas, M
Antibiotic treatment of bacterial exacerbation of chronic obstructive pulmonary disease (COPD) shows some immediate clinical benefits and may also minimise the frequency of further recurrences. Patients (n=511) were enrolled into a randomised double-blind multicentric study comparing the exacerbation-free interval (EFI), efficacy and safety of 7-day levofloxacin versus 10-day clarithromycin in patients with COPD exacerbation. Patients were monitored over a 1-yr period. A total of 434 patients (per protocol population) received the medication for > or =5 days. The median EFI in the per protocol population was 300 days for levofloxacin and 350 days for clarithromycin. For patients with a new documented exacerbation during follow-up (n=223), the median EFI was 100.5 days in the levofloxacin group and 95 days for clarithromycin. No significant differences in EFI between groups could be observed when stratifying the study population according to microbial aetiology and severity of bronchial obstruction. Levofloxacin and clarithromycin showed similar clinical success rates. The bacteriological success rate was significantly higher in the levofloxacin group. Both antibiotics were well tolerated. In summary, levofloxacin was associated with a significantly higher bacteriological eradication rate but similar exacerbation-free interval in patients with chronic obstructive pulmonary disease exacerbation compared to clarithromycin.
Monsó, E.; Garcia-Aymerich, J.; Soler, N.; Farrero, E.; Felez, M. A.; Antó, J. M.; Torres, A.
We examined the risk factors for bacterial exacerbation, defined as the presence of pathogenic bacteria in sputum, in 90 chronic obstructive pulmonary disease (COPD) patients with an exacerbation and changes in sputum characteristics. Smoking, alcohol, lung function, body mass index, medical visits and treatments were the independent variables assessed using multivariable logistic regression modelling (OR, 95% CI). A bacterial exacerbation was diagnosed in 39 (43.3%) of 90 patients. Bacterial exacerbations were more prevalent among current smokers (OR 3.77, 95% CI 1.17-12.12), in patients with poor compliance with inhalation therapy (OR 3.25, 95% CI 1.18-8.93) and with severe lung function impairment (FEV1 OR 0.96, 95% CI 0.93-1.00). Prior use of antibiotics was a risk factor for Pseudomonas aeruginosa infection (OR 6.06, 95% CI 1.29-28.44) and influenza vaccination appeared to have a protective effect against this infection (OR 0.15, 95% CI 0.03-0.67). We conclude that severe impairment of lung function, smoking and poor compliance with therapy are risk factors for bacterial infection in COPD, and P. aeruginosa should be suspected in patients who have been treated with antibiotics and in those not vaccinated against influenza. PMID:12948381
Santos, Salud; Marin, Alicia; Serra-Batlles, Joan; de la Rosa, David; Solanes, Ingrid; Pomares, Xavier; López-Sánchez, Marta; Muñoz-Esquerre, Mariana; Miravitlles, Marc
Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations. PMID:27042040
Abdellaoui, A; Préfaut, C; Gouzi, F; Couillard, A; Coisy-Quivy, M; Hugon, G; Molinari, N; Lafontaine, T; Jonquet, O; Laoudj-Chenivesse, D; Hayot, M
Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.
Farah, Raymond; Makhoul, Nicola
Background Chronic obstructive pulmonary disease (COPD) is a condition in which there is limited airflow during expiration (exhaling, or breathing out) that is not fully reversible and usually worsens over time. The disease is estimated to kill more than 100,000 Americans each year, and costs related to care of patients with COPD are significant. Physiologically, COPD represents a disruption in ventilation and in the exchange of gases in the lungs. Laboratory tests indicate elevated CO2 levels, gradual reduction of the levels of oxygen and pH in arterial blood, and a consequent rise in the dead space fraction (DSF) of the lungs. Objective Patients with COPD exacerbation represent a large portion of those artificially ventilated. In an attempt to develop a prognostic tool for length of treatment, we compared the proportion of DSF to the length of mechanical ventilation (MV). Methods This study included 73 patients admitted to the intensive care unit (ICU) where they received MV due to exacerbation of COPD. Each patient’s arterial blood gases (ABG) were measured upon admission. PeCO2 was tested using a Datex S/5 instrument. Subsequently, DSF was calculated using the Bohr equation. Statistical data was analyzed using SPSS software. Results Patients included in the study were ventilated from 6 to 160 hours (average 40 ± 47). In addition to ABG measurements, PeCO2 (expired CO2) levels were measured and DSF calculated for each patient. DSF values varied from 0.21 to 0.76 (average 0.119 ± 0.489). No correlation was found between DSF and length of artificial ventilation. Conclusion Evaluation of DSF does not provide a factor in estimating the length of treatment for patients with acute respiratory failure due to COPD exacerbation. PMID:20037683
Marino, Diego M.; Marrara, Kamilla T.; Arcuri, Juliano F.; Candolo, Cecília; Jamami, Maurício; Lorenzo, Valéria A. Pires Di
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
Calverley, Peter M A
Exacerbations of COPD are now recognised as being important events in the natural history of the condition and become more frequent as the disease worsens. Defining a minimum clinically important difference in exacerbation rate is fraught with difficulty. There is substantial between and within subject differences in the occurrence of these events that makes an individual evaluation of their importance problematic. At present, the most widely used definition of an exacerbation identifies an episode where the patient seeks medical help rather than a predefined change in one or more symptoms. Despite these problems, intervention studies with bronchodilator drugs, inhaled corticosteroids, and pulmonary rehabilitation appear to reduce the frequency of exacerbation events. In patients with an FEV1 below 50% predicted there is reasonable consistency about the magnitude of change and a 4-unit improvement in the St George's Respiratory Questionnaire is commonly associated with a 20-25% reduction in the reported number of exacerbations. Individual studies vary depending upon the recruitment protocol. Patients who experience symptomatic benefit may be those in whom a clinically important change in exacerbations occurs but this concept requires testing prospectively. Existing methodologies for estimating clinically important differences are hard to apply with a binary outcome like this, and more work will be needed to develop a robust approach for dealing with this important clinical variable.
McCullagh, Brian N.; Comellas, Alejandro P.; Ballas, Zuhair K.; Newell, John D.; Zimmerman, M. Bridget
Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a
Dimopoulos, G; Tsiodras, S; Lerikou, M; Chranioti, Aik; Perros, E; Anagnostopoulou, U; Karakitsos, P; Armaganidis, A
Background : To compare the differences between elderly and non-elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to viral infections. Methods : Patients with chronic obstructive pulmonary disease (COPD) exacerbation were recruited and classified as elderly (>65 years) and non-elderly (≤ 65 years). Sputum and oropharyngeal samples were assessed, PCR for respiratory viruses and cultures for common pathogens were performed. Results : 247 patients (median age: 69.3±9.5 years) were recruited and categorized into group A: non-elderly patients [n=81 (32.8%), median age 58±5.99] and group B: elderly patients [n=166 (67.2%), median age 74.8±4.8] years. In 133 (53.8%) patients a viral infection was identified and in 34 (13.8%) a bacterial pathogen was isolated from cultures. In 18 (7.3%) patients a double infection (bacterial+viral) was identified. In group B, the presence of cardiac failure (46.6% vs 28.3%, p<0.001), renal failure (10.5% vs 4%, p=0.03), bacterial co-infection (13.8% vs 7.4%, p=0.04), influenza vaccination rates (45.5% vs 215, p<0.001), and longer hospital stay (8.4±4.4 vs 7.5±3.2 days, p=0.02) were higher than group A. The overall rate of viral infections did not differ according to age. A trend to higher rates of infection with parainfluenza 3 [19 (20%) patients in group B vs3 (7.5%) patients in group A, p=0.04] was observed in older patients. Conclusion : No differences on the rate and type of viral infections were noted for elderly vs non elderly patients. However, they tended to have more bacterial co-infections that led to AECOPD and longer hospitalization stays compared to non-elderly patients. PMID:25741393
Sato, Minako; Chubachi, Shotaro; Sasaki, Mamoru; Haraguchi, Mizuha; Kameyama, Naofumi; Tsutsumi, Akihiro; Takahashi, Saeko; Nakamura, Hidetoshi; Asano, Koichiro; Betsuyaku, Tomoko
Background Patients with COPD might not report mild exacerbation. The frequency, risk factors, and impact of mild exacerbation on COPD status are unknown. Objectives The present study was performed to compare features between mild exacerbation and moderate or severe exacerbation in Japanese patients with COPD. Patients and methods An observational COPD cohort was designed at Keio University and affiliated hospitals to prospectively investigate the management of COPD comorbidities. This study analyzes data only from patients with COPD who had completed annual examinations and questionnaires over a period of 2 years (n=311). Results Among 59 patients with mild exacerbations during the first year, 32.2% also experienced only mild exacerbations in the second year. Among 60 patients with moderate or severe exacerbations during the first year, 40% also had the same severity of exacerbation during the second year. Findings of the COPD assessment test and the symptom component of the St George’s Respiratory Questionnaire at steady state were worse in patients with mild exacerbations than in those who were exacerbation free during the 2-year study period, although the severity of the ratio of predicted forced expiratory volume in 1 second did not differ between them. Severe airflow limitation (the ratio of predicted forced expiratory volume in 1 second <50%) and experience of mild exacerbations independently advanced the likelihood of an elevated COPD assessment test score to ≥2 per year. Conclusion The severity of COPD exacerbation seemed to be temporally stable over 2 years, and even mild exacerbations adversely impacted the health-related quality of life of patients with COPD. PMID:27354785
Wedzicha, Jadwiga A; Miravitlles, Marc; Hurst, John R; Calverley, Peter M A; Albert, Richard K; Anzueto, Antonio; Criner, Gerard J; Papi, Alberto; Rabe, Klaus F; Rigau, David; Sliwinski, Pawel; Tonia, Thomy; Vestbo, Jørgen; Wilson, Kevin C; Krishnan, Jerry A
This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations.Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation.The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.
Aasbø, Gunvor; Rugkåsa, Jorun; Solbraekke, Kari N; Werner, Anne
Healthcare policies often state that complex conditions are to be treated outside hospital in various forms of public-private partnership. Chronic obstructive pulmonary disease (COPD) is a progressive illness that includes episodes of serious acute exacerbations characterised by extreme breathlessness. There is limited knowledge about COPD exacerbations from the perspective of family caregivers and implications of the changing boundary between hospital care and care at home. In this paper, we explore how caregivers negotiate their role as caregivers with patients and healthcare professionals during acute exacerbations. We conducted 10 qualitative interviews with family caregivers of COPD patients in 2011, all were spouses over the age of 60. The participants were recruited through the patient pool of ambulatory pulmonary services of two hospitals in Oslo, Norway. Data were interpreted using thematic analysis. The caregivers described a lack of understanding and support from health professionals in some situations. They shouldered considerable responsibility, but were not always acknowledged as competent carers by professionals. Caregivers had to balance their involvement. They noted that they could lose the professionals' co-operation if their involvement was perceived as interfering or preventing the professionals from exercising their expertise. However, by not sharing their personalised knowledge about the patients, they risked that the professionals would not understand the severity of the exacerbation, which could undermine their own ability to maintain a sense of safety and control. The negotiations caregivers participated in and the uncertainty they experienced shed new light on the complexity of their role, and the discrepancy between practice and ideals in healthcare policy regarding collaboration of care. It is crucial to develop further knowledge about structural, interactional and communicational facilitators and barriers for reaching shared
Khalid, S; Elliott, A C; Pilling, A; Wolstenholme, R J
The current British Thoracic Society guidelines on COPD recommend that patients with COPD exacerbations should be admitted to hospital if they either have partial pressure of arterial oxygen of <7.0 kilopascals (kPa) or if they are living alone. This study was carried out to see if either of these factors have any effect on the outcome in patients presenting with COPD exacerbation in the setting of well established COPD services. This study was to see if patients with PaO2 < 7.0 kPa or those living alone were readmitted more frequently or had higher mortality than other patients discharged through the same scheme. A retrospective analysis was carried out on 1078 patients with acute exacerbation of COPD who were discharged home through Wigan "hospital at home" scheme in the period between November 1999 and February 2004 prior to the introduction of the new guidelines. This study found that there was no statistically significant difference in the rates of readmissions in patients with low PaO2 or those living in adverse social circumstances compared to other groups of patients. The number of patients dying in this period was too small to analyse with adequate power. This study indicates that such patients can be safely managed at home in the context of well established COPD services.
Li, Jinhui; Sun, Shengzhi; Tang, Robert; Qiu, Hong; Huang, Qingyuan; Mason, Tonya G; Tian, Linwei
Background Short-term exposure to major air pollutants (O3, CO, NO2, SO2, PM10, and PM2.5) has been associated with respiratory risk. However, evidence on the risk of chronic obstructive pulmonary disease (COPD) exacerbations is still limited. The present study aimed at evaluating the associations between short-term exposure to major air pollutants and the risk of COPD exacerbations. Methods After a systematic search up until March 30, 2016, in both English and Chinese electronic databases such as PubMed, EMBASE, and CNKI, the pooled relative risks and 95% confidence intervals were estimated by using the random-effects model. In addition, the population-attributable fractions (PAFs) were also calculated, and a subgroup analysis was conducted. Heterogeneity was assessed by I2. Results In total, 59 studies were included. In the single-pollutant model, the risks of COPD were calculated by each 10 μg/m3 increase in pollutant concentrations, with the exception of CO (100 μg/m3). There was a significant association between short-term exposure and COPD exacerbation risk for all the gaseous and particulate pollutants. The associations were strongest at lag0 and lag3 for gaseous and particulate air pollutants, respectively. The subgroup analysis not only further confirmed the overall adverse effects but also reduced the heterogeneities obviously. When 100% exposure was assumed, PAFs ranged from 0.60% to 4.31%, depending on the pollutants. The adverse health effects of SO2 and NO2 exposure were more significant in low-/middle-income countries than in high-income countries: SO2, relative risk: 1.012 (95% confidence interval: 1.001, 1.023); and NO2, relative risk: 1.019 (95% confidence interval: 1.014, 1.024). Conclusion Short-term exposure to air pollutants increases the burden of risk of COPD acute exacerbations significantly. Controlling ambient air pollution would provide benefits to COPD patients. PMID:28003742
Gupta, Barkha; Kant, Surya; Mishra, Rachna; Verma, Sanjay
Background Patients with Chronic Obstructive Pulmonary Disease (COPD) are frequently hospitalized with an acute exacerbation. Patients with COPD often lose weight. Consequently, deterioration in nutritional status (loss of lean body mass) is a likely repercussion of acute exacerbation in hospitalized COPD patients. The study was carried out to assess the nutritional status of COPD patients with acute exacerbation, during the period of hospital admission, and to evaluate the relationships between the nutritional indices and the pulmonary function parameters. Methods A cross sectional observation study constituting 83 COPD patients consecutively hospitalized with acute exacerbation on accrual during a period of one year. Lung function was measured by routine spirometry. Nutritional status was assessed by the measurement of anthropometric parameters. Hospital outcome was also assessed. Statistical analysis was performed using SPSS version 16.0 Independent t-tests and Pearsons correlation coefficient was used. Results Mean body weight was 50.03 ± 9.23 kg. Subjects had approximately 5 kg weight loss in previous six months. All the subjects had low BMI (19.38 ± 3.10) and MUAC (21.18 ± 2.31) that was significantly below the predicted levels. The correlation between body weight and FEV1/FVC% was good (r = 0.648, p = 0.003). BMI was negatively correlated (r = - 0.0103, p= 0.03) with duration of hospital stay. Conclusions The high prevalence of malnutrition among hospitalized COPD patients with acute exacerbation is related to their lung function and hospital outcome such as duration of hospital stay. Keywords Nutritional status; COPD; Acute exacerbation; Hospitalization PMID:21811522
Chen, Yu-Wei Roy; Leung, Janice M.; Sin, Don D.
The aims of this systematic review were to determine which blood-based molecules have been evaluated as possible biomarkers to diagnose chronic obstructive pulmonary disease (COPD) exacerbations (AECOPD) and to ascertain the quality of these biomarker publications. Patients of interest were those that have been diagnosed with COPD. MEDLINE, EMBASE, and CINAHL databases were searched systematically through February 2015 for publications relating to AECOPD diagnostic biomarkers. We used a modified guideline for the REporting of tumor MARKer Studies (mREMARK) to assess study quality. Additional components of quality included the reporting of findings in a replication cohort and the use of receiver-operating characteristics area-under-the curve statistics in evaluating performance. 59 studies were included, in which the most studied biomarkers were C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). CRP showed consistent elevations in AECOPD compared to control subjects, while IL-6 and TNF-α had variable statistical significance and results. mREMARK scores ranged from 6 to 18 (median score of 13). 12 articles reported ROC analyses and only one study employed a replication cohort to confirm biomarker performance. Studies of AECOPD diagnostic biomarkers remain inconsistent in their reporting, with few studies employing ROC analyses and even fewer demonstrating replication in independent cohorts. PMID:27434033
Tamayo-Uria, Ibon; Altzibar, Jone M; Mughini-Gras, Lapo; Dorronsoro, Miren
Chronic obstructive pulmonary disease (COPD) is a prevalent condition in adults aged ≥40 years characterized by progressive airflow limitation associated with chronic inflammatory response to noxious particles in the airways and lungs. Smoking, genetics, air pollution, nutrition and other factors may influence COPD development. Most hospitalizations and deaths for COPD are caused by its acute exacerbations, which greatly affect the health and quality of life of COPD patients and pose a high burden on health services. The aims of this project were to identify trends, geographic patterns and risk factors for COPD exacerbations, as revealed by hospitalizations and deaths, in the Basque Country, Spain, over a period of 12 years (2000-2011). Hospitalization and mortality rates for COPD were 262 and 18 per 100,000 population, respectively, with clusters around the biggest cities. Hospital mortality was 7.4%. Most hospitalized patients were male (77.4%) and accounted for 72.1% of hospital mortality. Hospitalizations decreased during the study period, except for 50-64 year-old women, peaking significantly. Using a multivariate modeling approach it was shown that hospitalizations were positively correlated with increased atmospheric concentrations of NO2, CO, PM10, and SO2, and increased influenza incidence, but were negatively associated with increased temperatures and atmospheric O3 concentration. COPD exacerbations decreased in the Basque Country during 2000-2011, but not among 50-64-year-old women, reflecting the high smoking prevalence among Spanish women during the 1970-1990s. The main metropolitan areas were those with the highest risk for COPD exacerbations, calling attention to the role of heavy car traffic. Influenza virus, cold temperatures, and increased atmospheric NO2, CO, PM10, and SO2 (but decreased O3) concentrations were identified as potential contributors to the burden of COPD exacerbations in the community. These findings are important for both the
Doll, Helen; Miravitlles, Marc
There is a lack of emphasis on health-related QOL (HR-QOL) changes associated with acute exacerbation of chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD). The aim of this review is to examine the use of HR-QOL instruments to evaluate acute exacerbation of CB or COPD, so as to form recommendations for future research.A literature search of papers published between 1966 and July 2003 identified more than 300 articles that used acute exacerbation of CB or COPD as the search term. However, only 21 of these studies employed HR-QOL measures as predictors of outcome or in the assessment of the impact, evolution or treatment of acute exacerbations of COPD or CB. A variety of HR-QOL measures were used, both generic and disease specific. The disease-specific St George's Respiratory Questionnaire (SGRQ), devised for patients with stable CB and with a recall period of 1-12 months, was the most widely used measure, with the Chronic Respiratory disease Questionnaire (CRQ) and the Baseline and Transitional Dyspnoea Index (BDI, TDI) being the only other disease-specific measures used. Most measures, both generic and disease specific, performed adequately when used during acute exacerbation of CB or COPD and indicated poor HR-QOL during acute exacerbation, which improved on resolution of the exacerbation. Relationships were evident between HR-QOL during an acute exacerbation and various outcomes, including post-exacerbation functional status, hospital re- admission for acute exacerbation or COPD, and mortality. There is a need for studies of treatments for acute exacerbation of CB or COPD to include an appropriate HR-QOL instrument to aid in the stratification of patients so as to target the right treatment to the right patient group. While a new instrument could be developed to measure HR-QOL during acute exacerbation of CB or COPD, currently available disease-specific measures such as the CRQ and the SGRQ appear to be acceptable to patients during acute
Fukuchi, Yoshinosuke; Tatsumi, Koichiro; Inoue, Hiromasa; Sakata, Yukinori; Shibata, Kai; Miyagishi, Hideaki; Marukawa, Yasuhiro; Ichinose, Masakazu
Background/aim Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. Methods In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg) or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication. The primary endpoint was exacerbation rate. Results A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression). However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6). Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group. The levels of improvement in forced expiratory volume in 1 second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52 weeks of the study. Conclusion The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation. PMID:27143873
Taylor, Stephanie Parks; Sellers, Eric; Taylor, Brice T
Long-term azithromycin therapy has been shown to reduce exacerbations of chronic obstructive pulmonary disease (COPD), and is recommended by recent society guidelines for use in COPD patients who are at risk for recurrent exacerbations. However, concerns about adverse effects have limited its widespread adoption. Physicians deciding whether to use long-term azithromycin therapy must weigh each patient's individual risk of cardiovascular complications and both the individual and population impact of macrolide resistance against the expected benefit. This review will summarize evidence on the effectiveness and safety of chronic azithromycin for the prevention of COPD exacerbations.
Pomares, Xavier; Montón, Concepción; Espasa, Mateu; Casabon, Jordi; Monsó, Eduard; Gallego, Miguel
Background The aim of this study was to determine whether long-term intermittent azithromycin therapy reduces the frequency of exacerbation in severe chronic obstructive pulmonary disease (COPD). Methods We retrospectively investigated the clinical benefits of long-term azithromycin (500 mg orally three times per week) over 12 months in patients with severe COPD and a minimum of four acute exacerbations (AECOPD) per year or chronic bronchial colonization by Pseudomonas aeruginosa, comparing the number of AECOPD, hospitalizations due to respiratory disease, days of hospital stay, and bacterial infections during azithromycin treatment and in the year prior to this therapy. Results Twenty patients who completed the 12-month treatment period were analyzed. No clinically significant adverse events were observed during azithromycin treatment. Compared with baseline data, azithromycin therapy significantly reduced the number of AECOPD (2.8 ± 2.5 versus 6.8 ± 2.8, P < 0.001), hospitalizations (1.4 ± 1.5 versus 3.6 ± 1.4, P < 0.001), and cumulative annual days of hospital stay (25 ± 32.2 versus 43.7 ± 21.4, P = 0.01). The improvement was particularly significant in patients with exacerbations caused by common potentially pathogenic microorganisms, who had 70% fewer AECOPD and hospitalizations. Patients colonized by P. aeruginosa had reductions of 43% in AECOPD and 47% in hospitalizations. Conclusion Long-term azithromycin is well tolerated and associated with significant reductions in AECOPD, hospitalizations, and length of hospital stay in patients with severe COPD. PMID:22003290
Collard, Harold R.; Moore, Bethany B.; Flaherty, Kevin R.; Brown, Kevin K.; Kaner, Robert J.; King, Talmadge E.; Lasky, Joseph A.; Loyd, James E.; Noth, Imre; Olman, Mitchell A.; Raghu, Ganesh; Roman, Jesse; Ryu, Jay H.; Zisman, David A.; Hunninghake, Gary W.; Colby, Thomas V.; Egan, Jim J.; Hansell, David M.; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kondoh, Yasuhiro; Lynch, David A.; Müller-Quernheim, Joachim; Myers, Jeffrey L.; Nicholson, Andrew G.; Selman, Moisés; Toews, Galen B.; Wells, Athol U.; Martinez, Fernando J.
The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed. PMID:17585107
Dilektasli, Asli Gorek; Demirdogen Cetinoglu, Ezgi; Uzaslan, Esra; Budak, Ferah; Coskun, Funda; Ursavas, Ahmet; Ercan, Ilker; Ege, Ercument
Introduction Chemokine (C-C motif) ligand 18 (CCL-18) has been shown to be elevated in chronic obstructive pulmonary disease (COPD) patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. Materials and methods Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp) were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. Results Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, P<0.0001). CCL-18 level was significantly correlated with the number of exacerbations (r=0.30, P=0.026), although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL) subgroups did not achieve statistical significance (P=0.09). Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92). Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, P<0.0001) and was found to be an independent risk factor for hospitalized exacerbations in the multivariable analysis. Conclusion CCL-18 is a promising biomarker in COPD, as it is associated with frequency of exacerbations, particularly with severe COPD exacerbations requiring hospitalization, as well as
Roche, N; Zureik, M; Soussan, D; Neukirch, F; Perrotin, D
The aim of the present prospective multicentric study was to develop a simple rule for the prediction of poor outcome in patients presenting to emergency departments with initially non-life threatening-chronic obstructive pulmonary disease (COPD) exacerbations in a real-life setting. All patients with an acute exacerbation of COPD visiting the emergency departments of 103 hospitals during a 3-month period were included, except those who immediately required intensive care unit admission and/or ventilatory support. The data collected included patient characteristics, in-hospital outcomes (mortality and length of stay) and mode of discharge (unsupported or need for post-hospital assistance). The in-hospital mortality rate was 7.4% (59 out of 794). Independent prognostic factors were age, number of clinical signs of severity (among cyanosis, impaired neurological status, lower limb oedema, asterixis and use of accessory inspiratory or expiratory muscles) and dyspnoea grade in the stable state. The need for post-hospital support was also predicted by female sex. In order to construct and validate a prediction score for mortality based on these items, patients were randomly allocated to a derivation and a validation cohort. The prediction score showed good discrimination, with a c-statistic of 0.79 in the derivation cohort and 0.83 in the validation cohort. Thus simple purely clinical factors can reliably predict the risk of death and requirement for post-hospital support in an initially non-life threatening-acute exacerbation of chronic obstructive pulmonary disease. Their use needs to be prospectively validated.
Zendedel, Abolfazl; Gholami, Mohammadreza; Anbari, Khatereh; Ghanadi, Kourosh; Bachari, Elham Ceneicel; Azargon, Alireza
Aim: This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD. Methods: This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012. Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital. They were randomly allocated to case and placebo group. The patients received routine treatment for COPD. Along with the routine treatment, placebo group received 100,000 IU of oral vitamin D per month, for 6 months. Data was analyzed using SPSS computer software, paired t-test, independent t-test, non parametric t-test and Pearson correlation coefficients. Results: In each group, there were 44 patients. After the intervention, there were significant differences in FEV1 and the number of COPD exacerbation between the case and control group patients. Also, after the study, in the case group, FEV1 was increased and the number of COPD exacerbation was decreased significantly. Conclusion: Vitamin D intake decreased COPD exacerbation and improved FEV1 in the patients with severe and very severe COPD. It is suggested that baseline serum vitamin D levels will recorded in similar studies and the effect of vitamin D intake will evaluated regarding the baseline serum vitamin D levels. PMID:25946929
DeVries, Rebecca; Kriebel, David; Sama, Susan
The breathlessness, cough and sputum scale (BCSS) is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms). Researchers have explored the utility of this tool to quantify efficacy of treatment following a chronic obstructive pulmonary disease (COPD) exacerbation; however, little work has been done to investigate the ability of the BCSS to predict COPD exacerbation. As part of a prospective case-crossover study among a cohort of 168 COPD patients residing in central Massachusetts, patients were asked standard BCSS questions during exacerbation and randomly identified non-exacerbation (or healthy) weeks. We found that the BCSS was strongly associated with COPD exacerbation (OR=2.80, 95% CI=2.27–3.45) and that a BCSS sum score of 5.0 identified COPD exacerbation with 83% sensitivity and 68% specificity. These results may be useful in the clinical setting to expedite interventions of exacerbation. PMID:27906157
Erdal, Marta; Johannessen, Ane; Eagan, Tomas Mikal; Bakke, Per; Gulsvik, Amund; Grønseth, Rune
Objectives 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. Patients and methods 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 based on health care utilization and a symptom-based definition of AECOPD were applied. For multivariate analyses, we chose a negative binomial regression model. Results COPD patients from the population- and hospital-based samples experienced on average 0.4 utilization-defined and 2.9 symptom-defined versus 1.0 and 5.9 annual exacerbations, respectively. The incidence rate ratios for utilization-defined AECOPD were 2.45 (95% CI 1.22–4.95), 3.43 (95% CI 1.59–7.38), and 5.67 (95% CI 2.58–12.48) with Global Initiative on Obstructive Lung Disease spirometric stages II, III, and IV, respectively. The corresponding incidence rate ratios for the symptom-based definition were 3.08 (95% CI 1.96–4.84), 3.45 (95% CI 1.92–6.18), and 4.00 (95% CI 2.09–7.66). Maintenance therapy (regular long-acting muscarinic antagonists, long-acting beta-2 agonists, inhaled corticosteroids, or theophylline) also increased the risk of AECOPD with both exacerbation definitions (incidence rate ratios 1.65 and 1.73, respectively). The risk of AECOPD was 59%–78% higher in the hospital sample than in the population sample. Conclusion If externally valid conclusions are to be made regarding incidence and predictors of AECOPD, studies should be based on general population samples or adjustments should be made on account of a likely higher incidence in other samples. Likewise, the effect of different AECOPD definitions should be taken into consideration. PMID:27621614
López-Campos, Jose Luis; Hartl, Sylvia; Pozo-Rodriguez, Francisco; Roberts, C. Michael
Chronic obstructive pulmonary disease (COPD) care across Europe has high heterogeneity with respect to cost and the services available. Variations in length of stay (LOS) may be attributed to patient characteristics, resource and organisational characteristics, and/or the so-called hospital cluster effect. The European COPD Audit in 13 countries included data from 16 018 hospitalised patients. The recorded variables included information on patient and disease characteristics, and resources available. Variables associated with LOS were evaluated by a multivariate, multilevel analysis. Mean±sd LOS was 8.7±8.3 days (median 7 days, interquartile range 4–11 days). Crude variability between countries was reduced after accounting for clinical factors and the clustering effect. The main factors associated with LOS being longer than the median were related to disease or exacerbation severity, including GOLD class IV (OR 1.77) and use of mechanical ventilation (OR 2.15). Few individual resource variables were associated with LOS after accounting for the hospital cluster effect. This study emphasises the importance of the patients' clinical severity at presentation in predicting LOS. Identifying patients at risk of a long hospital stay at admission and providing targeted interventions offers the potential to reduce LOS for these individuals. The complex interactions between factors and systems were more important that any single resource or organisational factor in determining differences in LOS between hospitals or countries. PMID:27730166
Tuggey, J; Plant, P; Elliott, M
Methods: A cost and consequences analysis of domiciliary NIV based on a before and after case note audit was performed in patients with recurrent acidotic exacerbations of COPD who tolerated and responded well to NIV. The primary outcome measure was the total cost incurred per patient per year from the perspective of the acute hospital. Effectiveness outcomes were total days in hospital and in intensive care. Results: Thirteen patients were identified. Provision of a home NIV service resulted in a mean (95% CI) saving of £8254 (£4013 to £12 495) (€11 720; €5698 to €17 743) per patient per year. Total days in hospital fell from a mean (SD) of 78 (51) to 25 (25) (p=0.004), number of admissions from 5 (3) to 2 (2) (p=0.007), and ICU days fell from a total of 25 to 4 (p=0.24). Outpatient visits fell from a mean of 5 (3) to 4 (2) (p=0.14). Conclusions: This study suggests that domiciliary NIV for a highly selected group of COPD patients with recurrent admissions requiring NIV is effective at reducing admissions and minimises costs from the perspective of the acute hospital. Such evidence is important in obtaining financial support for providing such a service. PMID:14514940
Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems. Innovative sampling techniques have led to the identification of several pulmonary biomarkers. Although some molecules are promising, their usefulness in clinical practice is not yet established. Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD. We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method. Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further. Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease’s clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment. According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels. Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis. Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited. In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes. However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use. Clinical trials that incorporate biomarkers in decisional algorithms are required. PMID:24143945
Bacteria are isolated in more than 50% of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). The most prevalent respiratory pathogens include Gram-positive (Streptococcus pneumoniae) and Gram-negative (Haemophilus influenzae, Moraxella catarrhalis) microorganims. Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including atypicals and those resistant to most common antibiotics. The bioavailability and half-life of moxifloxacin provides potent bactericidal effects at a dose of 400 mg once daily. Among the fluoroquinolones, the ratio of the area under the concentration-time curve (AUC) to minimal inhibitory concentration of moxifloxacin is the highest against S. pneumoniae. Moxifloxacin has demonstrated better eradication in exacerbations of CB and COPD compared with standard therapy, in particular, with macrolides. Patients treated with moxifloxacin showed a prolonged time to the next exacerbation and observational studies suggest that moxifloxacin induces a faster release of symptoms of exacerbation. Some guidelines recommend the use of moxifloxacin as first-line therapy in bacterial exacerbations in patients with moderate to severe COPD and in patients with mild COPD with risk factors. The current article reviews the use of moxifloxacin in bacterial exacerbations of CB and COPD. PMID:18229559
Al Rajeh, Ahmed M.; Hurst, John R.
Introduction: The value of monitoring physiological parameters to predict chronic obstructive pulmonary disease (COPD) exacerbations is controversial. A few studies have suggested benefit from domiciliary monitoring of vital signs, and/or lung function but there is no existing systematic review. Objectives: To conduct a systematic review of the effectiveness of monitoring physiological parameters to predict COPD exacerbation. Methods: An electronic systematic search compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. The search was updated to April 6, 2016. Five databases were examined: Medical Literature Analysis and Retrieval System Online, or MEDLARS Online (Medline), Excerpta Medica dataBASE (Embase), Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and the Cochrane clinical trials database. Results: Sixteen articles met the pre-specified inclusion criteria. Fifteen of these articules reported positive results in predicting COPD exacerbation via monitoring of physiological parameters. Nine studies showed a reduction in peripheral oxygen saturation (SpO2%) prior to exacerbation onset. Three studies for peak flow, and two studies for respiratory rate reported a significant variation prior to or at exacerbation onset. A particular challenge is accounting for baseline heterogeneity in parameters between patients. Conclusion: There is currently insufficient information on how physiological parameters vary prior to exacerbation to support routine domiciliary monitoring for the prediction of exacerbations in COPD. However, the method remains promising. PMID:27897995
Margüello, Miguel Santibañez; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; Miravitlles, Marc; García-Rivero, Juan Luis
Few studies have researched the independent effect of COPD severity on the risk of future exacerbations adjusted by previous exacerbation frequency. We aimed to analyse the independent effect of COPD severity on the risk of exacerbations in the following year, and whether this effect was stronger or not than the effect of a previous history of exacerbations. We conducted a retrospective population-based cohort study including 900 patients with confirmed COPD. Exacerbation frequency was observed for the previous year and for the following year. Patients were defined as ‘Frequent Exacerbator’ (FE) phenotype if they suffered ⩾2 exacerbations in a year, and were categorised according to the severity of COPD (GOLD Grades 1–4). Odds ratios (ORs) were estimated by logistic regression adjusting for age, gender, smoking status, severity of COPD and being FE in the previous year. The main predictor of being FE among all grades of COPD severity was a history of frequent exacerbations in the previous year: adjusted OR 4.97; 95% confidence interval (CI) (3.54–6.97). COPD severity was associated with a higher risk of being FE: Crude OR GOLD Grade 4 3.86; 95% CI (1.50–9.93). However, this association diminished after adjusting for being FE in the previous year: adjusted OR 2.08; 95% CI (0.75–5.82). Our results support that a history of frequent exacerbations in the previous year is the most important independent predictor of exacerbations in the following year, also among the most severe COPD patients. Severity of COPD would be associated with a higher risk of exacerbations, but this effect would be partly determined by the exacerbations suffered in the previous year. PMID:27604472
Korpershoek, YJG; Vervoort, SCJM; Nijssen, LIT; Trappenburg, JCA; Schuurmans, MJ
Background In patients with COPD, self-management skills are important to reduce the impact of exacerbations. However, both detection and adequate response to exacerbations appear to be difficult for some patients. Little is known about the underlying process of exacerbation-related self-management. Therefore, the objective of this study was to identify and explain the underlying process of exacerbation-related self-management behavior. Methods A qualitative study using semi-structured in-depth interviews was performed according to the grounded theory approach, following a cyclic process in which data collection and data analysis alternated. Fifteen patients (male n=8; age range 59–88 years) with mild to very severe COPD were recruited from primary and secondary care settings in the Netherlands, in 2015. Results Several patterns in exacerbation-related self-management behavior were identified, and a conceptual model describing factors influencing exacerbation-related self-management was developed. Acceptance, knowledge, experiences with exacerbations, perceived severity of symptoms and social support were important factors influencing exacerbation-related self-management. Specific factors influencing recognition of exacerbations were heterogeneity of exacerbations and habituation to symptoms. Feelings of fear, perceived influence on exacerbation course, patient beliefs, ambivalence toward treatment, trust in health care providers and self-empowerment were identified as specific factors influencing self-management actions. Conclusion This study provided insight into factors influencing exacerbation-related self-management behavior in COPD patients. The conceptual model can be used as a framework for health care professionals providing self-management support. In the development of future self-management interventions, factors influencing the process of exacerbation-related self-management should be taken into account. PMID:27932877
Yawn, Barbara P; Raphiou, Ibrahim; Hurley, Judith S; Dalal, Anand A
Exacerbations contribute significantly to the morbidity of COPD, leading to an accelerated decline in lung function, reduced functional status, reduced health status and quality of life, poorer prognosis and increased mortality. Prevention of exacerbations is thus an important goal of COPD management. In patients with COPD, treatment with a combination of the inhaled corticosteroid fluticasone propionate (250 μg) and the long-acting β2-agonist salmeterol (50 μg) in a single inhaler (250/50 μg) is an effective therapy option that has been shown to reduce the frequency of exacerbations, to improve lung function, dyspnea and health status, and to be relatively cost-effective as a COPD maintenance therapy. Importantly, results of various studies suggest that fluticasone propionate and salmeterol have synergistic effects when administered together that improve their efficacy in controlling symptoms and reducing exacerbations. The present non-systematic review summarizes the role of fluticasone propionate/salmeterol combination therapy in the prevention of exacerbations of COPD and its related effects on lung function, survival, health status, and healthcare costs. PMID:20631816
Gulcev, Makedonka; Reilly, Cavan; Griffin, Timothy J; Broeckling, Corey D; Sandri, Brian J; Witthuhn, Bruce A; Hodgson, Shane W; Woodruff, Prescott G; Wendt, Chris H
Introduction Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD). Methods We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls. Individual metabolites were measured via selective reaction monitoring with mass spectrometry. We used a mixed-effect model to compare metabolite levels in cases compared to controls and a paired t-test to test for differences between days 0 and 30 in the AECOPD group. Results We identified 377 analytes at a false discovery rate of 5% that differed between cases (day 0) and controls, and 31 analytes that differed in the AECOPD cases between day 0 and day 30 (false discovery rate: 5%). Tryptophan was decreased at day 0 of AECOPD compared to controls corresponding to an increase in indoleamine 2,3-dioxygenase activity. Conclusion Patients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consistent with an increase in indoleamine 2,3-dioxygenase activity. PMID:27729784
Lee, Qing; Mocarski, Michelle; Sun, Shawn X.
Background Chronic lower respiratory disease, which includes chronic obstructive pulmonary disease (COPD), is the third leading cause of death in the United States. Roflumilast is an oral, once-daily, selective phosphodiesterase-4 inhibitor approved for reducing the risk for COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Objectives To evaluate the effects of roflumilast treatment timing on COPD exacerbation rates (primary objective) and on resource utilization and healthcare costs (secondary objective) after hospital or emergency department discharge associated with a COPD exacerbation. Methods In this retrospective cohort study, claims data from March 2011 to March 2013 were extracted from Truven Health MarketScan combined commercial healthcare claims and Medicare supplemental claims databases and were analyzed to compare the exacerbation rates and the healthcare resource utilization and costs between the early roflumilast treatment (treatment initiation ≤30 days after hospital or emergency department discharge) and the delayed roflumilast treatment (treatment initiation 31–180 days after discharge) cohorts. Multivariate logistic regression and generalized linear models with log-link function and gamma distribution were adjusted for age, sex, insurance plan type, COPD disease complexity, and comorbidities. Results A total of 995 patients (N = 280 early roflumilast treatment, N = 715 delayed roflumilast treatment) were included. Compared with the delayed roflumilast treatment group, patients in the early roflumilast treatment group were 39% less likely to have an exacerbation after hospital discharge (P = .004). The patients receiving early roflumilast treatment also had 42% (P = .003) and 37% (P = .005) lower risks for COPD-related and all-cause rehospitalizations, respectively, than patients in the delayed roflumilast treatment group. Significantly fewer patients receiving early roflumilast
Singh, Dave; Kampschulte, Jorg; Wedzicha, Jadwiga A; Jones, Paul W; Cohuet, Géraldine; Corradi, Massimo; Higenbottam, Tim; Petruzzelli, Stefano; Vestbo, Jørgen
Combination inhalers containing corticosteroids and long-acting β-agonists are used to reduce exacerbation rates in patients with severe chronic obstructive pulmonary disease (COPD). The FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The traditional physician diagnosis of exacerbations is a co-primary outcome, and the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting patient-reported outcome data are also being used to enhance the detection of exacerbation events. EXACT data are being collected using a novel application of a digital platform technology. FORWARD is therefore expected to provide information on the ability of EXACT to detect and measure exacerbations in a large clinical trial setting. The study design of FORWARD is described in this article.
Kang, Hye Seon; Rhee, Chin Kook; Kim, Sung Kyoung; Kim, Jin Woo; Lee, Sang Haak; Yoon, Hyung Kyu; Ahn, Joong Hyun; Kim, Yong Hyun
Purpose We compared the clinical characteristics and treatment outcomes of patients with eosinophilic and neutrophilic COPD exacerbations requiring hospital admission. Patients and methods This was a retrospective multicenter study performed between January 2010 and December 2014. In all, 1,688 COPD patients admitted via the outpatient clinics or emergency departments of six university hospitals were enrolled. The patients were grouped by complete blood counts: eosinophilic group, >2% peripheral blood eosinophils, and neutrophilic group, >65% peripheral blood neutrophils or >11,000 leukocytes/mL. The patients with radiographic evidence of pneumonia at the time of admission, those with lung cancer, those admitted for treatment of other medical problems, and those who chronically used steroids were excluded. Results A total of 605 patients hospitalized with COPD exacerbations (177 eosinophilic and 380 neutrophilic) were included. Pulmonary functions, including the forced expiratory volume in 1 second and forced vital capacity, were better in patients with eosinophilic exacerbations. Treatment outcomes, including the rate of admission to the intensive care unit and mortality, were poorer in patients with neutrophilic exacerbations (4.5% vs 12.4%, P=0.004; 1.1% vs 4.5%, P=0.043, respectively). Congestive heart failure (odds ratio [OR] =3.40, 95% confidence interval [CI]: 1.28–9.01) and neutrophilic exacerbation (OR = 2.81, 95% CI: 1.21–6.52) were independent risk factors for intensive care unit admission. Conclusion COPD patients with neutrophilic exacerbations experienced worse clinical outcomes than did those with eosinophilic exacerbations. The peripheral blood eosinophil count may be a useful predictor of clinical progress during hospitalization of COPD patients with acute exacerbations. PMID:27757029
Sánchez-Nieto, Juan Miguel; Andújar-Espinosa, Rubén; Bernabeu-Mora, Roberto; Hu, Chunshao; Gálvez-Martínez, Beatriz; Carrillo-Alcaraz, Andrés; Álvarez-Miranda, Carlos Federico; Meca-Birlanga, Olga; Abad-Corpa, Eva
Background Self-management interventions improve different outcome variables in various chronic diseases. Their role in COPD has not been clearly established. We assessed the efficacy of an intervention called the self-management program on the need for hospital care due to disease exacerbation in patients with advanced COPD. Methods Multicenter, randomized study in two hospitals with follow-up of 1 year. All the patients had severe or very severe COPD, and had gone to either an accident and emergency (A&E) department or had been admitted to a hospital at least once in the previous year due to exacerbation of COPD. The intervention consisted of a group education session on the main characteristics of the disease, an individual training session on inhalation techniques, at the start and during the 3rd month, and a written action plan containing instructions for physical activity and treatment for stable phases and exacerbations. We determined the combined number of COPD-related hospitalizations and emergency visits per patient per year. Secondary endpoints were number of patients with visits to A&E and the number of patients hospitalized because of exacerbations, use of antibiotics and corticosteroids, length of hospital stay, and all-cause mortality. Results After 1 year, the rate of COPD exacerbations with visits to A&E or hospitalization had decreased from 1.37 to 0.89 (P=0.04) and the number of exacerbations dropped from 52 to 42 in the group of patients who received the intervention. The numbers of patients hospitalized, at 19 (40.4%) versus 20 (52.6%) (P=0.26), and those who went to A&E, at 9 (19.1%) versus 14 (36.8%) (P=0.06), due to exacerbation of COPD were also lower in this group. Intake of antibiotics was higher in the intervention group, whereas use of glucocorticoids was slightly lower, though there were no significant differences (P=0.30). There were also no differences between groups in the length of hospital stay (P=0.154) or overall mortality (P=0
Vestbo, Jørgen; Lange, Peter
Exacerbations have significant impact on the morbidity and mortality of patients with chronic obstructive pulmonary disease. Most guidelines emphasise prevention of exacerbations by treatment with long-acting bronchodilators and/or anti-inflammatory drugs. Whereas most of this treatment is evidence-based, it is clear that patients differ regarding the nature of exacerbations and are likely to benefit differently from different types of treatment. In this short review, we wish to highlight this, suggest a first step in differentiating pharmacological exacerbation prevention and call for more studies in this area. Finally, we wish to highlight that there are perhaps easier ways of achieving similar success in exacerbation prevention using nonpharmacological tools.
Hoogendoorn, M; Hoogenveen, R T; Rutten-van Mölken, M P; Vestbo, J; Feenstra, T L
The aim of our study was to estimate the case fatality of a severe exacerbation from long-term survival data presented in the literature. A literature search identified studies reporting ≥1.5 yr survival after a severe chronic obstructive pulmonary disease (COPD) exacerbation resulting in hospitalisation. The survival curve of each study was divided into a critical and a stable period. Mortality during the stable period was then estimated by extrapolating the survival curve during the stable period back to the time of exacerbation onset. Case fatality was defined as the excess mortality that results from an exacerbation and was calculated as 1 minus the (backwardly) extrapolated survival during the stable period at the time of exacerbation onset. The 95% confidence intervals (CI) of the estimated case fatalities were obtained by bootstrapping. A random effect model was used to combine all estimates into a weighted average with 95% CI. The meta-analysis based on six studies that fulfilled the inclusion criteria resulted in a weighted average case-fatality rate of 15.6% (95% CI 10.9-20.3), ranging from 11.4% to 19.0% for the individual studies. A severe COPD exacerbation requiring hospitalisation not only results in higher mortality risks during hospitalisation, but also in the time-period after discharge and contributes substantially to total COPD mortality.
Arostegui, Inmaculada; Esteban, Cristobal; García-Gutierrez, Susana; Bare, Marisa; Fernández-de-Larrea, Nerea; Briones, Eduardo; Quintana, José M
Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations. Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis. The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes. We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain. Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD. Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis. Results were validated using key outcomes of ECOPD evolution. Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit. Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C. Subtypes A and B were primarily related to other serious complications. Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B. These results could help identify characteristics
Arostegui, Inmaculada; Esteban, Cristobal; García-Gutierrez, Susana; Bare, Marisa; Fernández-de-Larrea, Nerea; Briones, Eduardo; Quintana, José M.
Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition characterized by occasional exacerbations. Identifying clinical subtypes among patients experiencing COPD exacerbations (ECOPD) could help better understand the pathophysiologic mechanisms involved in exacerbations, establish different strategies of treatment, and improve the process of care and patient prognosis. The objective of this study was to identify subtypes of ECOPD patients attending emergency departments using clinical variables and to validate the results using several outcomes. We evaluated data collected as part of the IRYSS-COPD prospective cohort study conducted in 16 hospitals in Spain. Variables collected from ECOPD patients attending one of the emergency departments included arterial blood gases, presence of comorbidities, previous COPD treatment, baseline severity of COPD, and previous hospitalizations for ECOPD. Patient subtypes were identified by combining results from multiple correspondence analysis and cluster analysis. Results were validated using key outcomes of ECOPD evolution. Four ECOPD subtypes were identified based on the severity of the current exacerbation and general health status (largely a function of comorbidities): subtype A (n = 934), neither high comorbidity nor severe exacerbation; subtype B (n = 682), moderate comorbidities; subtype C (n = 562), severe comorbidities related to mortality; and subtype D (n = 309), very severe process of exacerbation, significantly related to mortality and admission to an intensive care unit. Subtype D experienced the highest rate of mortality, admission to an intensive care unit and need for noninvasive mechanical ventilation, followed by subtype C. Subtypes A and B were primarily related to other serious complications. Hospitalization rate was more than 50% for all the subtypes, although significantly higher for subtypes C and D than for subtypes A and B. These results could help identify
Singh, Dave; Fox, Steven M; Tal-Singer, Ruth; Bates, Stewart; Riley, John H; Celli, Bartolome
Patients with chronic obstructive pulmonary disease (COPD) who are defined as frequent exacerbators suffer with 2 or more exacerbations every year. The molecular mechanisms responsible for this phenotype are poorly understood. We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort. Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR) testing. Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01) between frequent compared to non-exacerbators. In sputum cells, only 6 genes were differentially expressed. The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes. Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10. The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively. There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations.
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
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
Foda, Hussein D; Brehm, Anthony; Goldsteen, Karen; Edelman, Norman H
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
Hoogendoorn, Martine; Feenstra, Talitha L; Hoogenveen, Rudolf T; Al, Maiwenn; Mölken, Maureen Rutten-van
Purpose: To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD. Methods: We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo. Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization. The association between the mean forced expiratory volume in one second (FEV1)% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects. The regression equations were applied to the mean FEV1% predicted for each GOLD stage to estimate the frequency per stage. Results: Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations. Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46–1.49) for mild, 1.17 (0.93–1.50) for moderate, 1.61 (1.51–1.74) for severe, and 2.10 (1.51–2.94) for very severe COPD. Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67–2.07), 1.44 (1.14–1.87), 1.76 (1.70–1.88), and 2.09 (1.57–2.82), respectively. For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02–0.56), 0.16 (0.07–0.33), 0.22 (0.20–0.23), and 0.28 (0.14–0.63), respectively. Study duration or type of study (cohort versus trial) did not significantly affect the outcomes. Conclusion: This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health
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
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
Caramori, G; Romagnoli, M; Casolari, P; Bellettato, C; Casoni, G; Boschetto, P; Fan, C; Barnes, P; Adcock, I; Ciaccia, A; Fabbri, L; Papi, A
Methods: Total and nuclear p65 immunoreactivity was measured by immunocytochemistry in the sputum cells of 11 smokers with moderate COPD during an exacerbation and after 6–8 weeks of clinical stability. Results: Total sputum cell count was significantly increased during exacerbations from a median (IQR) of 880 (510–1865) to 1914.5 (1065–3205) x 103/ml (p<0.05). The main inflammatory cells in the sputum were neutrophils (83.2 (75.4–92.3)%) and macrophages (14.7 (2.6–21.6)%) and their relative proportion did not change during exacerbations. Nuclear staining for p65 was absent in sputum neutrophils, both during exacerbations and in the stable phase. In contrast, the percentage of macrophages expressing nuclear p65 increased significantly during exacerbations from a median (IQR) of 16 (7–24)% to 41.4 (6–69)% (p<0.05). Conclusions: NF-κB appears to be activated in sputum macrophages but not in sputum neutrophils during exacerbations of COPD PMID:12668802
Esteban, Cristóbal; Quintana, José M; Garcia-Gutierrez, Susana; Anton-Ladislao, Ane; Gonzalez, Nerea; Baré, Marisa; Fernández de Larrea, Nerea; Rivas-Ruiz, Francisco
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
Melbye, Hasse; Al-ani, Salwan; Spigt, Mark
Background When assessing patients with exacerbation of asthma or COPD, it may be useful to know the drop in forced expiratory volume in 1 second (FEV1) compared with stable state, in particular when considering treatment with oral corticosteroids. The objective of the study was to identify indicators of drop in FEV1 during exacerbations. Methods In this prospective multicenter study from primary care, patients diagnosed with asthma or COPD were examined at stable state and during exacerbations the following year. Symptoms, chest findings, and pulse oximetry were recorded, and spirometry was performed. A fixed drop in FEV1 (10% and ≥200 mL) and percentage change in FEV1 were outcomes when possible indicators were evaluated. Results Three hundred and eighty patients attended baseline examination, and 88 with a subsequent exacerbation were included in the analysis. Thirty (34%) had a significant drop in FEV1 (10% and 200 mL). Increased wheezing was the only symptom associated with this drop with a likelihood ratio of 6.4 (95% confidence interval, 1.9–21.7). Crackles and any new auscultation finding were also associated with a significant drop in FEV1, as was a ≥2% drop in oxygen saturation (SpO2) to ≤92% in the subgroup diagnosed with COPD. Very bothersome wheezing and severe decrease in SpO2 were also very strong predictors of change in FEV1 in linear regression adjusted for age, gender, and baseline FEV1% predicted. Conclusion Increased wheezing, as experienced by the patient, and a decreased SpO2 value strongly indicated a drop in lung function during asthma and COPD exacerbations and should probably be taken into account when treatment with oral corticosteroids is considered. PMID:27994453
Cavassini, M; Calandra, T; Bridevaux, P O
Two thirds of the exacerbations of chronic obstructive pulmonary disease (COPD) are caused by infections of the respiratory tract. The causative microorganisms differ according to the degree of COPD severity, previous antibiotic therapy and prior bacterial infections. Antibiotics and intensification of bronchodilator therapy are the cornerstones of the management of moderate and severe exacerbations of COPD. Prompt therapy of COPD exacerbations has been shown to reduce the likelihood of hospitalisation and improve the quality of life. In this article, we have reviewed current recommendations regarding the use of antibiotics in the treatment of COPD exacerbations.
Miller, Craig; Cushley, Claire; Redler, Kasey; Mitchell, Claire; Aynsley Day, Elizabeth; Mansfield, Helen; Nye, Abigail
Admissions for exacerbations of chronic obstructive pulmonary disease (COPD) present a significant proportion of patients in the acute medical take. The British Thoracic Society (BTS) provides guidelines for time specific interventions, that should be delivered to those with an acute exacerbation of COPD through the admission care bundle. These include correct diagnosis, correct assessment of oxygenation, early administration of treatment, recognition of respiratory failure, and specialist review. Gloucestershire Hospitals NHS Foundation Trust (GHNHSFT) chose improvement in acute COPD care to be a local Commissioning for Quality and Innovation (CQUIN) scheme, which enables commissioners to reward excellence by linking a proportion of English healthcare providers' income to the achievement of local quality improvement goals. The effects of initiatives put in place by senior clinicians had waned, and further improvements were required to meet the CQUIN target. The aim of the scheme was to improve compliance with the BTS guidelines and CQUIN scheme for patients admitted with an exacerbation of COPD. Specific bundle paperwork to be used for all patients admitted to the Trust with an exacerbation of COPD was introduced to the Trust in June 2014, with training and education of medical staff at that time. This had improved compliance rates from 10% to 63% by September 2014. Compliance with each intervention was audited through the examination of notes of patients admitted with an exacerbation of COPD. Compliance rates had plateaued over the last three months, and so a focus group involving junior medical staff met in September 2014 to try to increase awareness further, in order to drive greater improvements in care, and meet the CQUIN requirements. Their strategies were implemented, and then compliance with the CQUIN requirements was reaudited as described above. The December 2014 audit results showed a further improvement in overall COPD care, with 73% of patients
Miller, Craig; Cushley, Claire; Redler, Kasey; Mitchell, Claire; Aynsley Day, Elizabeth; Mansfield, Helen; Nye, Abigail
Admissions for exacerbations of chronic obstructive pulmonary disease (COPD) present a significant proportion of patients in the acute medical take. The British Thoracic Society (BTS) provides guidelines for time specific interventions, that should be delivered to those with an acute exacerbation of COPD through the admission care bundle. These include correct diagnosis, correct assessment of oxygenation, early administration of treatment, recognition of respiratory failure, and specialist review. Gloucestershire Hospitals NHS Foundation Trust (GHNHSFT) chose improvement in acute COPD care to be a local Commissioning for Quality and Innovation (CQUIN) scheme, which enables commissioners to reward excellence by linking a proportion of English healthcare providers’ income to the achievement of local quality improvement goals. The effects of initiatives put in place by senior clinicians had waned, and further improvements were required to meet the CQUIN target. The aim of the scheme was to improve compliance with the BTS guidelines and CQUIN scheme for patients admitted with an exacerbation of COPD. Specific bundle paperwork to be used for all patients admitted to the Trust with an exacerbation of COPD was introduced to the Trust in June 2014, with training and education of medical staff at that time. This had improved compliance rates from 10% to 63% by September 2014. Compliance with each intervention was audited through the examination of notes of patients admitted with an exacerbation of COPD. Compliance rates had plateaued over the last three months, and so a focus group involving junior medical staff met in September 2014 to try to increase awareness further, in order to drive greater improvements in care, and meet the CQUIN requirements. Their strategies were implemented, and then compliance with the CQUIN requirements was reaudited as described above. The December 2014 audit results showed a further improvement in overall COPD care, with 73% of patients
Kamada, Takahiro; Kaneko, Masahiro; Tomioka, Hiromi
Background Forced oscillation technique (FOT) has been reported to be useful in the evaluation and management of obstructive lung disease, including COPD. To date, no data are available concerning long-term changes in respiratory system impedance measured by FOT. Additionally, although exacerbations have been reported to be associated with excessive lung function decline in COPD, the impact of exacerbations on the results of FOT has not been demonstrated. The aim of this study was to investigate the longitudinal changes in respiratory system impedance and the influence of exacerbations thereon. Methods Between March 2011 and March 2012, outpatients who attended Kobe City Medical Center West Hospital with a diagnosis of COPD were assessed for eligibility. Baseline patient characteristics (age, sex, body mass index, smoking history, current smoking status, COPD stage), lung function (post-bronchodilator forced expiratory volume in 1 second [FEV1]), blood tests (neutrophils and eosinophils), FOT, and COPD assessment test results were collected at enrollment. Lung function and FOT were examined every 6 months until March 2016. Annual changes in FEV1 and FOT parameters were obtained from the slope of the linear regression curve. The patients were divided into 2 groups based on exacerbation history. Results Fifty-one of 58 patients with COPD were enrolled in this study. The median follow-up period was 57 (52–59) months. Twenty-five (49%) patients experienced exacerbations. A significant annual decline in FEV1 and respiratory system impedance were shown. Additionally, annual changes in FEV1, respiratory system resistance at 5 Hz, respiratory system reactance at 5 Hz, and resonant frequency were greater in patients with exacerbations than in those without exacerbations. Conclusion Exacerbations of COPD lead not only to a decline in lung function but also to an increase in respiratory system impedance. PMID:28223791
Wedzicha, J A; Singh, D; Vestbo, J; Paggiaro, P L; Jones, P W; Bonnet-Gonod, F; Cohuet, G; Corradi, M; Vezzoli, S; Petruzzelli, S; Agusti, A
The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 μg pMDI, 2 inhalations BID, vs. FOR 12 μg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV(1) at 12 weeks. The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV(1) 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed. Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62-0.84], p < 0.001); (2) improved pre-dose morning FEV(1) (mean difference: 0.069 L [0.043-0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs. Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone.
Zhu, Min; Wang, Ting; Wang, Chengdi; Ji, Yulin
Background In recent years, the pleiotropic roles of vitamin D have been highlighted in various diseases. However, the association between serum vitamin D and COPD is not well studied. This updated systematic review and meta-analysis aimed to assess the relationship between vitamin D and the risk, severity, and exacerbation of COPD. Methods A systematic literature search was conducted in PubMed, Medline, EMBASE, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases. The pooled risk estimates were standardized mean difference (SMD) with 95% confidence interval (CI) for vitamin D levels and odds ratio (OR) with 95% CI for vitamin D deficiency. Meta-regression and subgroup analyses were performed on latitude, body mass index, and assay method. Results A total of 21 studies, including 4,818 COPD patients and 7,175 controls, were included. Meta-analysis showed that lower serum vitamin D levels were found in COPD patients than in controls (SMD: −0.69, 95% CI: −1.00, −0.38, P<0.001), especially in severe COPD (SMD: −0.87, 95% CI: −1.51, −0.22, P=0.001) and COPD exacerbation (SMD: −0.43, 95% CI: −0.70, −0.15, P=0.002). Vitamin D deficiency was associated with increased risk of COPD (OR: 1.77, 95% CI: 1.18, 2.64, P=0.006) and with COPD severity (OR: 2.83, 95% CI: 2.00, 4.00, P<0.001) but not with COPD exacerbation (OR: 1.17, 95% CI: 0.86, 1.59, P=0.326). Assay methods had significant influence on the heterogeneity of vitamin D deficiency and COPD risk. Conclusion Serum vitamin D levels were inversely associated with COPD risk, severity, and exacerbation. Vitamin D deficiency is associated with increased risk of COPD and severe COPD but not with COPD exacerbation. It is worth considering assay methods in the heterogeneity sources analysis of association between vitamin D deficiency and COPD. PMID:27799758
Papi, Alberto; Jones, Paul W; Dalvi, Prashant S; McAulay, Kirsten; McIver, Tammy; Dissanayake, Sanjeeva
Inhaled corticosteroid/long-acting β2-agonist combination therapy is recommended in chronic obstructive pulmonary disease (COPD) patients at high risk of exacerbations. The EFFECT (Efficacy of Fluticasone propionate/FormotErol in COPD Treatment) trial is a Phase III, 52-week, randomized, double-blind study to evaluate the efficacy and safety of two doses of fluticasone propionate/formoterol compared to formoterol monotherapy in COPD patients with FEV1 ≥50% predicted and a history of exacerbations. The primary endpoint is the annualized rate of moderate and severe exacerbations. Secondary endpoints include pre-dose FEV1, EXACT-PRO (EXAcerbations of Chronic pulmonary disease Tool – Patient-Reported Outcome)-defined exacerbations, St George’s Respiratory Questionnaire for COPD, COPD Assessment Test, and EXACT-Respiratory Symptoms total score. Lung-specific biomarkers (surfactant protein D and CC chemokine ligand-18) will be measured in a subset of patients to explore their relationship to other clinical indices in COPD and their predictive utility. Pneumonia will be diagnosed per criteria defined by the British Thoracic Society community acquired pneumonia guideline, primarily by radiological confirmation and, additionally, using clinical criteria when a chest radiograph cannot be obtained. Serial measurements of serum potassium, vital signs and electrocardiograms, 24-hour Holter monitoring, and 24-hour urinary cortisol measurement will be performed in a subset of patients in addition to conventional safety assessments. PMID:26648706
Pela, R; Marchesani, F; Agostinelli, C; Staccioli, D; Cecarini, L; Bassotti, C; Sanguinetti, C M
Patients affected with chronic obstructive pulmonary disease (COPD) undergo frequent exacerbations of their illness characterized by increased cough and expectoration. The precise aetiology of these episodes often remains unknown. In the absence of clinical or radiographic signs of pneumonia, bacterial or viral cultures of sputum usually provide little useful information. Thus, we performed fibreoptic bronchoscopy using a protected specimen brush (PSB) to obtain uncontaminated secretions for culture from 56 patients with COPD, 16 with stable clinical conditions and 40 affected with exacerbations of the disease. The aim of our study was to evaluate bronchial microbial flora by quantitative aerobic and anaerobic culture of each specimen. Twenty five subjects (45%), 4 (16%) in stable state and 21 (84%) with COPD exacerbations, had specimens which gave rise to significant bacterial growth (> 10(3) colony forming units.mL-1). The predominant bacteria were Streptococcus pneumoniae (in 10 cases) and alpha-haemolytic streptococci (in 6 cases); other bacteria found were coagulase-negative staphylococci and Branhamella catarralis in (2 cases each), and Proteus mirabilis, Haemophilus influenzae, Pseudomonas aeruginosa, Aerococcus viridans and Chromobacterium violaceum (each in a single case only). Although significant bacterial growth was more frequently found in patients with chronic obstructive pulmonary disease exacerbations and in those with a higher degree of bronchial inflammation, the differences between the two groups of patients were not statistically significant. Nevertheless, the results obtained in our study confirm the validity of and the need for reliable sampling methods (like the protected specimen brush) to demonstrate significant bacterial colonization of the airways in chronic obstructive pulmonary disease patients.
Gaude, Gajanan S; Rajesh, BP; Chaudhury, Alisha; Hattiholi, Jyothi
Background: Acute exacerbations of chronic obstructive pulmonary disorder (AECOPD) are known to be associated with increased morbidity and mortality and have a significant socioeconomic impact. The factors that determine frequent hospital readmissions for AECOPD are poorly understood. The present study was done to ascertain failures rates following AECOPD and to evaluate factors associated with frequent readmissions. Materials and Methods: We conducted a prospective study among 186 patients with COPD with one or more admissions for acute exacerbations in a tertiary care hospital. Frequency of previous re-admissions for AECOPD in the past year, and clinical characteristics, including spirometry were ascertained in the stable state both before discharge and at 6-month post-discharge. Failure rates following treatment were ascertained during the follow-up period. All the patients were followed up for a period of 2 years after discharge to evaluate re-admissions for the AECOPD. Results: Of 186 COPD patients admitted for AECOPD, 54% had one or more readmission, and another 45% had two or more readmissions over a period of 2 years. There was a high prevalence of current or ex-heavy smokers, associated co-morbidity, underweight patients, low vaccination prevalence and use of domiciliary oxygen therapy among COPD patients. A total of 12% mortality was observed in the present study. Immediate failure rates after first exacerbation was observed to be 34.8%. Multivariate analysis showed that duration >20 years (OR = 0.37; 95% CI: 0.10-0.86), use of Tiotropium (OR = 2.29; 95% CI: 1.12-4.69) and use of co-amoxiclav during first admission (OR = 2.41; 95% CI: 1.21-4.79) were significantly associated with higher immediate failure rates. The multivariate analysis for repeated admissions revealed that disease duration >10 years (OR = 0.50; 95% CI: 0.27-0.93), low usage of inhaled ICS + LABA (OR = 2.21; 95% CI: 1.08-4.54), and MRC dyspnea grade >3 (OR = 2.51; 95% CI: 1.08-5.82) were
Eisner, Mark D; Iribarren, Carlos; Yelin, Edward H; Sidney, Stephen; Katz, Patricia P; Sanchez, Gabriela; Blanc, Paul D
Secondhand smoke (SHS) is a major contributor to indoor air pollution. Because it contains respiratory irritants, it may adversely influence the clinical course of persons with chronic obstructive pulmonary disease (COPD). We used data from nonsmoking members of the FLOW cohort of COPD (n = 809) to elucidate the impact of SHS exposure on health status and exacerbations (requiring emergency department visits or hospitalization). SHS exposure was measured by a validated survey instrument (hours of exposure during the past week). Physical health status was measured by the SF-12 Physical Component Summary Score and disease-specific health-related quality of life (HRQL) by the Airways Questionnaire 20-R. Health care utilization for COPD was determined from Kaiser Permanente Northern California computerized databases. Compared to no SHS exposure, higher level SHS exposure was associated with poorer physical health status (mean score decrement −1.78 points; 95% confidence interval [CI] −3.48 to −0.074 points) after controlling for potential confounders. Higher level SHS exposure was also related to poorer disease-specific HRQL (mean score increment 0.63; 95% CI 0.016 to 1.25) and less distance walked during the Six-Minute Walk test (mean decrement −50 feet; 95% CI −102 to 1.9). Both lower level and higher level SHS exposure was related to increased risk of emergency department (ED) visits (hazard ratio [HR] 1.40; 95% CI 0.96 to 2.05 and HR 1.41; 95% CI 0.94 to 2.13). Lower level and higher level SHS exposure were associated with a greater risk of hospital-based care for COPD, which was a composite endpoint of either ED visits or hospitalizations for COPD (HR 1.52; 95% CI 1.06 to 2.18 and HR 1.40; 95% CI 0.94 to 2.10, respectively). In conclusion, SHS was associated with poorer health status and a greater risk of COPD exacerbation. COPD patients may comprise a vulnerable population for the health effects of SHS. PMID:19516915
Miravitlles, Marc; Llor, Carles; Molina, Jesús; Naberan, Karlos; Cots, Josep M; Ros, Fernando
Objective: To investigate the impact of exacerbations in health-related quality of life (HRQL) of patients with COPD and to compare the effect of treatment of COPD exacerbations with moxifloxacin (400 mg/day for 5 days) and amoxicillin/clavulanate (500/125 mg 3 times a day for 10 days) on HRQL. Methods: 229 outpatients with stable COPD (mean age 68.2 years; mean FEV1 % predicted 49.3%) participated in a prospective, observational study of 2 years’ duration. The St George’s Respiratory Questionnaire (SGRQ) was completed at baseline and every 6 months thereafter. Results: COPD exacerbations (mean 2.7 episodes/patient) occurred in 136 patients (124 patients received the study medications [amoxicillin/clavulanate 54, moxifloxacin 70]). Differences between baseline and the final visit were higher for moxifloxacin compared with amoxicillin/clavulanate for total SGRQ score (−2.60 [13.1] vs 4.21 [16.2], P = 0.05) and “Symptoms” subscale (−5.64 [16.7] vs 8.27 , P = 0.02). The same findings were observed in patients with two or more exacerbations. Conclusions: In COPD outpatients, treatment of exacerbations with moxifloxacin had a more favorable long-term effect on quality of life than amoxicillin/clavulanate. PMID:20368907
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
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.
Beeh, Kai-Michael; Beier, Jutta; Candler, Henning; Wittig, Thomas
Background Treating symptoms and preventing exacerbations are key components of chronic obstructive pulmonary disease (COPD) long-term management. Recently, a more tailored treatment approach has been proposed, in particular for two well-established clinical phenotypes, frequent exacerbators and chronic bronchitis-dominant COPD. ELOM-080 has demonstrated clinical efficacy in treating symptoms and preventing exacerbations in subjects with chronic bronchitis. However, little is known about the potential effects of ELOM-080 in COPD patients. Aim To evaluate the effect on exacerbation, cough sputum, and general state of health of long-term treatment with ELOM-080 in COPD patients with an exacerbation history and chronic bronchitis. Methods We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled parallel-group clinical trial of a 6-month treatment with ELOM-080 (3×300 mg) in patients with chronic bronchitis and concomitant COPD. The primary outcome was the proportion of subjects with at least one exacerbation over the 6-month study period. Secondary outcomes included the total number of exacerbations (ie, cumulative occurrence of exacerbations during the study period) and the proportion of acute exacerbations necessitating an antibiotic treatment, monthly evaluations of sputum and cough symptoms, and the general state of health and a safety analysis. Results Of 260 randomized subjects, 64 patients fulfilled the inclusion criteria for COPD (ELOM-080: 35, placebo: 29). Compared to placebo, ELOM-080 reduced the percentage of subjects with at least one exacerbation (29% versus 55%, P=0.031) and a reduction in the overall occurrence of exacerbations (ELOM-080: 10, placebo: 21, P=0.012) during the winter season. The percentage of asymptomatic or mildly symptomatic patients (sputum/expectoration and cough) was consistently higher in the ELOM-080 group compared to placebo, with statistical significant differences after 2 and 3 months of treatment
Wilson, Robert; Anzueto, Antonio; Miravitlles, Marc; Arvis, Pierre; Haverstock, Daniel; Trajanovic, Mila; Sethi, Sanjay
Background Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (≥60 years old) outpatients with acute Anthonisen type 1 exacerbations. Trial registration NCT00656747. Methods Based on the moxifloxacin in AECOPDs (acute exacerbations of chronic obstructive pulmonary disease) trial (MAESTRAL) database, this study evaluated pretherapy demographic, clinical, sputum bacteriological factors using multivariate logistic regression analysis, with internal validation by bootstrap replicates, to investigate their possible association with clinical failure at end of therapy (EOT) and 8 weeks posttherapy. Results The analyses found that the independent factors predicting clinical failure at EOT were more frequent exacerbations, increased respiratory rate and lower body temperature at exacerbation, treatment with long-acting anticholinergic drugs, and in vitro bacterial resistance to study drug. The independent factors predicting poor outcome at 8 weeks posttherapy included wheezing at preexacerbation, mild or moderate (vs extreme) sleep disturbances, lower body temperature at exacerbation, forced expiratory volume in 1 second <30%, lower body mass index, concomitant systemic corticosteroids for the current exacerbation, maintenance long-acting β2-agonist and long-acting anticholinergic treatments, and positive sputum culture at EOT. Conclusion Several bacteriological, historical, treatment-related factors were identified as predictors of early (EOT) and later (8 weeks posttherapy) clinical failure in this older outpatient population with moderate-to-severe chronic
He, Mei; Yu, Sue; Wang, Lemin; Lv, Hanjing; Qiu, Zhongmin
Background Pulmonary rehabilitation (PR) is able to improve dyspnea, endurance capacity, and health-related quality of life in chronic obstructive pulmonary disease (COPD) patients, but it is rarely used in China. This study aimed to assess the effectiveness and safety of PR after exacerbation of COPD. Material/Methods Patients admitted to hospital due to an exacerbation of COPD were randomized to receive either PR or routine care (control group). The PR program was performed from the second day of admission until discharge. The pre-post changes in 6-minute walk distance (6MWD), self-reported quality of life (QOL) assessed by CAT score and CRQ-SAS score, and activity of daily life assessed by ADL-D score were determined. The perceived end-effort dyspnea (Borg scale) was measured throughout the study. Results A total of 101 patients were enrolled, of whom 7 withdrew after randomization, and 94 completed this study. There were 66 patients in the PR group and 28 in the control group. The 6MWD, resting SpO2, and exercise Borg dyspnea score were significantly improved in the PR group. In addition, the PR group had greater improvement in the total CRQ-SAS score and had a lower CAT score. Significant improvements were also found in the ADL-D and BODE index in the PR group. No adverse events were recorded during exercise. Conclusions Our study provides evidence that it is safe and feasible to apply an early PR in patients with acute exacerbation of COPD. PMID:25783889
Zheng, Jin-Ping; Wen, Fu-Qiang; Bai, Chun-Xue; Wan, Huan-Ying; Kang, Jian; Chen, Ping; Yao, Wan-Zhen; Ma, Li-Jun; Xia, Qi-Kui; Gao, Yi; Zhong, Nan-Shan
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.
Emami Ardestani, Mohammad; Kalantary, Elham; Samaiy, Vajihe; Taherian, Keramat
Introduction: Corticosteroids are routinely used in management of chronic obstructive pulmonary disease (COPD) exacerbation. The main purpose of present study was to compare the efficacy of methyl prednisolone (MP) and dexamethasone (DXM) for this purpose. Methods: Adult COPD patients entered the present clinical trial. All patients received standard treatment on admission and were then divided into 2 groups of intravenous MP and DXM. Patients were asked to rate their shortness of breath; sputum volume and viscosity; dyspnea; cough; and general wellbeing on a 0-5 scale. Baseline parameters such as O2 saturation, arterial blood gas parameters, and white blood cell (WBC) count were compared on admission and day 7 and 14 of therapy using SPSS 22. Results: 68 patients were randomly allocated to 2 groups of 34 (82.4% male). The baseline characteristics of the two groups were similar (p < 0.05). Comparison of treatment outcomes for the 7th day showed a significant difference between the 2 groups only regarding cough (p = 0.047), HCO3 (p < 0.001), and O2 saturation (p = 0.042). On day 14 the 2 groups were different only regarding cough (p = 0.048) and sputum viscosity (p = 0.011). There was a significant difference between the two groups regarding trend of changes in dyspnea (p = 0.02; DXM >> MP) and cough (p = 0.035; MP >> DXM). There were no significant differences between the two medications regarding side effects on 7th and 14th day after treatment. Conclusion: It seems that MP and DXM have similar efficacy and side effects in treatment of COPD exacerbation and selecting drug of choice would better be based on the most prominent symptoms of patients on admission. PMID:28286842
Harrison, Samantha L; Goldstein, Roger; Desveaux, Laura; Tulloch, Verity; Brooks, Dina
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.
Pradan, Liana; Ferreira, Ivone; Postolache, Paraschiva
Chronic obstructive pulmonary disease (COPD) is a significant cause of global morbidity and mortality, with a substantial economic impact. Acute exacerbations of COPD (AECOPD) represent a dramatic event in the course of the disease; is an important cause of morbidity and the fourth cause of mortality worldwide. During the hospitalization for AECOPD mortality is 10%. AECOPD are also associated with a significant reduction of functional capacity and health-related quality of life. Despite these alarming evidence-based data the response of the healthcare system globally is not adequate to the gravity of the situation. A recently published study done in a Canadian hospital reveals that the treatment of the AECOPD is sub-optimal. The management of the COPD exacerbations prior, during and after the hospitalization showed inadequate adherence of the physicians (respirologists, internists and hospitalists) to the current guidelines. This review outlines the worrisome findings of this study and the proposed measures suggested by the authors in order to optimize the management of AECOPD.
Introduction COPD exacerbations have a negative impact on lung function, decrease quality of life (QoL) and increase the risk of death. The objective of this study was to assess the course of health status after an outpatient or inpatient exacerbation in patients with COPD. Methods This is an epidemiological, prospective, multicentre study that was conducted in 79 hospitals and primary care centres in Spain. Four hundred seventy-six COPD patients completed COPD assessment test (CAT) and Clinical COPD Questionnaire (CCQ) questionnaires during the 24 hours after presenting at hospital or primary care centres with symptoms of an exacerbation, and also at weeks 4–6. The scores from the CAT and CCQ were evaluated and compared at baseline and after recovery from the exacerbation. Results A total of 164 outpatients (33.7%) and 322 inpatients (66.3%) were included in the study. The majority were men (88.2%), the mean age was 69.4 years (SD = 9.5) and the mean FEV1 (%) was 47.7% (17.4%). During the exacerbation, patients presented high scores in the CAT: [mean: 22.0 (SD = 7.0)] and the CCQ: [mean: 4.4 (SD = 1.2)]. After recovery there was a significant reduction in the scores of both questionnaires [CAT: mean: -9.9 (SD = 5.1) and CCQ: mean: -3.1 (SD = 1.1)]. Both questionnaires showed a strong correlation during and after the exacerbation and the best predictor of the magnitude of improvement in the scores was the severity of each score at onset. Conclusions Due to their good correlation, CAT and CCQ can be useful tools to measure health status during an exacerbation and to evaluate recovery. However, new studies are necessary in order to identify which factors are influencing the course of the recovery of health status after a COPD exacerbation. PMID:23987232
Sala, E; Alegre, L; Carrera, M; Ibars, M; Orriols, F J; Blanco, M L; Cárceles, F; Bertran, S; Mata, F; Font, I; Agustí, A G
This prospective, controlled, but not formally randomized study investigates the feasibility and efficiency of an alternative to standard hospitalization for patients with exacerbated chronic obstructive pulmonary disease (COPD), based upon supported discharge with nurse supervision at home. Over a 12-month period, emergency physicians, not directly involved in the study, admitted 205 patients with exacerbated COPD to the authors' respiratory unit. Patients were included in the supported discharge group (n=105) if they voluntarily chose to participate in the programme and lived in the city of Palma de Mallorca (where adequate home support could be provided). Patients not fulfilling these criteria (mainly residents outside the city) served as controls (n=100). Inpatient treatment was standardized in all patients and included oxygen therapy, bronchodilators, antibiotics and steroids. Both groups were comparable in terms of age (mean +/- SD: 70 +/- 10 versus 65 +/- 11 yr for supported discharge and control group, respectively), severity of airflow obstruction (forced expiratory volume in one second 45 +/- 18% reference versus 46 +/- 19% ref.), comorbidity and socioeconomic status. Length of hospital stay (LOS) in the supported discharge group was shorter (5.9 +/- 2.8 versus 8.0 +/- 5.1 days, p < 0.001). After discharge, a respiratory nurse visited supported discharge patients at home during 7.3 +/- 3.8 days. Only one patient (1%) required hospital readmission during this period of time. The reduced LOS resulted in a lower utilization of hospital beds at any given point in time throughout the study period. Within the framework and potential limitations of this study, the results indicate that the supported discharge programme in Spain: 1) allows a significant reduction in the length of hospital stay of patients hospitalized because of an exacerbation of chronic obstructive pulmonary disease; 2) does not result in an inappropriately increased rate of hospital
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
Orme, Mark; Weedon, Amie; Esliger, Dale; Saukko, Paula; Morgan, Mike; Steiner, Michael; Downey, John; Singh, Sally; Sherar, Lauren
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
History of pneumonia is a strong risk factor for chronic obstructive pulmonary disease (COPD) exacerbation in South Korea: the Epidemiologic review and Prospective Observation of COPD and Health in Korea (EPOCH) study
Hwang, Yong Il; Lee, Sang Haak; Yoo, Jee Hong; Jung, Bock Hyun; Yoo, Kwang Ha; Na, Moon Jun; Lee, Jong Deog; Park, Myung Jae; Jung, Chi Young; Shim, Jae Jeong; Kim, Kyung Chan; Kim, Yeon Jae; Choi, Hye Sook; Choi, Ik Su; Lee, Choon-Taek; Lee, Sang Do; Kim, Do Jin; Uh, Soo-Taek; Lee, Ho Sung; Kim, Young Sam; Lee, Kwan Ho; Ra, Seung Won; Kim, Hak Ryul; Choi, Soo Jeon; Park, In Won; Park, Yong Bum; Park, So Young; Lee, Jaehee
Background In South Korea, chronic obstructive pulmonary disease (COPD) is one of the ten leading causes of death. COPD exacerbations are significantly associated with mortality in COPD patients. This study was conducted to investigate the epidemiology of COPD in South Korea, specifically the clinical characteristics of South Korean COPD patients, the COPD exacerbation rate and the risk factors associated with COPD exacerbations. Methods This study covers a 2-year interval. One year was data collected retrospectively and the second year was prospectively obtained data. Results A total of 1,114 subjects were enrolled in the study. These subjects were observed for a period of 1 year from the enrollment, and a total of 920 subjects completed the study. A total of 1,357 COPD exacerbations occurred in 711 subjects (63.8%) out of the total of 1,114 subjects during the study period of 2 years. Multivariate logistic regression results showed that if patients had had a pneumonia before the retrospective year of analysis, they had a 18 times greater chance of having an exacerbation during the prospective year when other variables were controlled. Also, the subjects who had a history of two or more exacerbations during the retrospective year were approximately 6 times more likely to experience the COPD exacerbation compared to those who did not. Conclusions This study examined the demographic and clinical characteristics of South Korean COPD patients and found that a history of pneumonia and two or more occurrences of exacerbation within 1 year was significantly associated with a higher rate of COPD exacerbation. PMID:26793342
Background Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED). Such information could help stratify these patients and guide medical decision-making. The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit. Methods This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals. Recruitment started in June 2008 and ended in September 2010. Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up. Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit. Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample. The score was compared with other published prediction rules for patients with stable COPD. Results In total, 2,487 patients were included in the study. Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85). Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model. The same variables were predictors of death at 1 month (AUC = 0.85). Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better
Background There is some evidence that quality of life measured by long disease-specific questionnaires may predict exacerbations in asthma and COPD, however brief quality of life tools, such as the Airways Questionnaire 20 (AQ20) or the Clinical COPD Questionnaire (CCQ), have not yet been evaluated as predictors of hospital exacerbations. Objectives To determine the ability of brief specific health-related quality of life (HRQoL) questionnaires (AQ20 and CCQ) to predict emergency department visits (ED) and hospitalizations in patients with asthma and COPD, and to compare them to longer disease-specific questionnaires, such as the St George´s Respiratory Questionnaire (SGRQ), the Chronic Respiratory Disease Questionnaire (CRQ) and the Asthma Quality of Life Questionnaire (AQLQ). Methods We conducted a two-year prospective cohort study of 208 adult patients (108 asthma, 100 COPD). Baseline sociodemographic, clinical, functional and psychological variables were assessed. All patients completed the AQ20 and the SGRQ. COPD patients also completed the CCQ and the CRQ, while asthmatic patients completed the AQLQ. We registered all exacerbations that required ED or hospitalizations in the follow-up period. Differences between groups (zero ED visits or hospitalizations versus ≥ 1 ED visits or hospitalizations) were tested with Pearson´s X2 or Fisher´s exact test for categorical variables, ANOVA for normally distributed continuous variables, and Mann–Whitney U test for non-normally distributed variables. Logistic regression analyses were performed to estimate the predictive ability of each HRQoL questionnaire. Results In the first year of follow-up, the AQ20 scores predicted both ED visits (OR: 1.19; p = .004; AUC 0.723) and hospitalizations (OR: 1.21; p = .04; AUC 0.759) for asthma patients, and the CCQ emerged as independent predictor of ED visits in COPD patients (OR: 1.06; p = .036; AUC 0.651), after adjusting for sociodemographic, clinical, and
Ostojić, Jelena; Mose, Jakov
Asthma is a chronic inflammatory disease of the airways. The global prevalence of asthma ranges from 1% to 18% of the population, so it remains a common problem with enormous medical and economic impacts. In majority of patients, asthma can be well controlled with simple regimens of inhaled anti-inflammatory and bronchodilating medications. However, some patients tend to suffer from poorly controlled disease in terms of chronic symptoms with episodic severe exacerbations. Major factors that may be related to the emergency department visits and hospitalisation include prior severe attacks, nonadherence to therapeutic regimens, inadequate use of inhaled corticosteroids, poor self-management skills, frequent use of inhaled short-acting beta-agonists, cigarette smoking, poor socioeconomic status and age over 40 years. Severe exacerbations of asthma are life-threatening medical emergencies and require careful brief assesment, treatment according to current GINA (Global Initiative for Asthma) guidelines with periodic reassesment of patient's response to therapy usually in an emergency department.
Black, Peter N; Morgan-Day, Althea; McMillan, Tracey E; Poole, Phillippa J; Young, Robert P
Background Prophylactic treatment with N-acetylcysteine (NAC) for 3 months or more is associated with a reduction in the frequency of exacerbations of chronic obstructive pulmonary disease (COPD). This raises the question of whether treatment with NAC during an acute exacerbation will hasten recovery from the exacerbation. Methods We have examined this in a randomised, double-blind, placebo controlled trial. Subjects, admitted to hospital with an acute exacerbation of COPD, were randomised within 24 h of admission to treatment with NAC 600 mg b.d. (n = 25) or matching placebo (n = 25). Treatment continued for 7 days or until discharge (whichever occurred first). To be eligible subjects had to be ≥ 50 years, have an FEV1 ≤ 60% predicted, FEV1/VC ≤ 70% and ≥ 10 pack year smoking history. Subjects with asthma, heart failure, pneumonia and other respiratory diseases were excluded. All subjects received concurrent treatment with prednisone 40 mg/day, nebulised salbutamol 5 mg q.i.d and where appropriate antibiotics. FEV1, VC, SaO2 and breathlessness were measured 2 hours after a dose of nebulised salbutamol, at the same time each day. Breathlessness was measured on a seven point Likert scale. Results At baseline FEV1 (% predicted) was 22% in the NAC group and 24% in the control group. There was no difference between the groups in the rate of change of FEV1, VC, SaO2 or breathlessness. Nor did the groups differ in the median length of stay in hospital (6 days for both groups). Conclusions Addition of NAC to treatment with corticosteroids and bronchodilators does not modify the outcome in acute exacerbations of COPD. PMID:15581425
Mammen, Manoj J; Sethi, Sanjay
Traditional culture techniques confirm that bacteria have an important role in Chronic Obstructive Pulmonary Disease (COPD). In individuals with COPD, acquisition of novel bacterial strains is associated with onset of acute exacerbation of COPD, which leads to further lung dysfunction and enormous health-care costs. Recent study of the human microbiome, the total composite of the bacteria on the human body, posited the microbiome as the last human organ studied, as the microbiome performs a multitude of metabolic functions absent in the human genome. The largest project to study the human microbiome was the National Institutes of Health (NIH) human microbiome project (HMP) started in 2007 to understand the 'normal' microbiome. However due to the presumption that the healthy human lung was sterile, the respiratory tract was not included in that study. The advent of next-generation sequencing technologies has allowed the investigation of the human respiratory microbiome, which revealed that the healthy lung does have a robust microbiome. Subsequent studies in individuals with COPD revealed that the microbiome composition fluctuates with severity of COPD, composition of the individual aero-digestive tract microbiomes, age, during an acute exacerbation of COPD and with the use of steroids and/or antibiotics. Understanding the impact of the microbiome on COPD progression and risk of exacerbation will lead to directed therapies for prevention of COPD progression and exacerbation.
Pradhan, Gourahari; Behera, Priyadarshini; Bhuniya, Sourin; Mohapatra, Prasanta Raghab; Turuk, Jyotirmayee; Mohanty, Srujana
Pulmonary strongyloidiasis is an uncommon presentation of Strongyloides infection, usually seen in immunocompromised hosts. The manifestations are similar to that of acute exacerbation of chronic obstructive pulmonary disease (COPD). Therefore, the diagnosis of pulmonary strongyloidiasis could be challenging in a COPD patient, unless a high index of suspicion is maintained. Here, we present a case of Strongyloides hyperinfection in a COPD patient mimicking acute exacerbation, who was on chronic steroid therapy. PMID:27790284
Worth, Heinrich; Schacher, Christian; Dethlefsen, Uwe
Background The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesised that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. Methods In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Results Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Conclusion Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane. Trial registration ISRCTN07600011 PMID:19624838
Kumar, Rakesh K; Herbert, Cristan; Foster, Paul S
Most of the healthcare costs associated with asthma relate to emergency department visits and hospitalizations because of acute exacerbations of underlying chronic disease. Development of appropriate animal models of acute exacerbations of asthma is a necessary prerequisite for understanding pathophysiological mechanisms and assessing potential novel therapeutic approaches. Most such models have been developed using mice. Relatively few mouse models attempt to simulate the acute-on-chronic disease that characterizes human asthma exacerbations. Instead, many reported models involve relatively short-term challenge with an antigen to which animals are sensitized, followed closely by an unrelated triggering agent, so are better described as models of potentiation of acute allergic inflammation. Triggers for experimental models of asthma exacerbations include (i) challenge with high levels of the sensitizing allergen (ii) infection by viruses or fungi, or challenge with components of these microorganisms (iii) exposure to environmental pollutants. In this review, we examine the strengths and weaknesses of published mouse models, their application for investigation of novel treatments and potential future developments.
Background It has been suggested that withdrawal of inhaled corticosteroids (ICS) in COPD patients on maintenance treatment results in deterioration of symptoms, lung function and exacerbations. The aim of this real-life, prospective, multicentric study was to investigate whether withdrawal of ICS in COPD patients at low risk of exacerbation is linked to a deterioration in lung function and symptoms and to a higher frequency of exacerbations. Methods 914 COPD patients, on maintenance therapy with bronchodilators and ICS, FEV1>50% predicted, and <2 exacerbations/year were recruited. Upon decision of the primary physicians, 59% of patients continued their ICS treatment whereas in 41% of patients ICS were withdrawn and regular therapy was continued with long-acting bronchodilators mostly (91% of patients). FEV1, CAT (COPD Assessment Test), and occurrence of exacerbations were measured at the beginning (T0) and at the end (T6) of the 6 months observational period. Results 816 patients (89.3%) concluded the study. FEV1, CAT and exacerbations history were similar in the two groups (ICS and no ICS) at T0 and at T6. We did not observe any deterioration of lung function symptoms, and exacerbation rate between the two groups at T0 and T6. Conclusions We conclude that the withdrawal of ICS, in COPD patients at low risk of exacerbation, can be safe provided that patients are left on maintenance treatment with long-acting bronchodilators. PMID:25005873
Background Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. Methods Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria. Results Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality. Conclusions In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures. PMID:23848435
Esteban, Cristóbal; Garcia-Gutierrez, Susana; Legarreta, Maria J; Anton-Ladislao, Ane; Gonzalez, Nerea; Lafuente, Iratxe; Fernandez de Larrea, Nerea; Vidal, Silvia; Bare, Marisa; Quintana, José M; -Copd Group, Iryss
Mortality is one of the most important outcomes in patients with chronic obstructive pulmonary disease (COPD). Different predictors have been associated with mortality, including the patient's level of physical activity (PA). The objective of this work was to establish the relationship between changes in PA during a moderate-to-severe COPD exacerbation (eCOPD) and 1-year mortality after the index event. This was a prospective observational cohort study with recruitment of 2,484 patients with an eCOPD attending the emergency department (ED) of 16 participating hospitals. Variables recorded included clinical and sociodemographic data from medical records, dyspnea, health-related quality of life, and PA before the index eCOPD and 2 months after the hospital or ED discharge, as reported by the patient. In the multivariate analysis worsening changes in PA from baseline to 2 months after the ED index visit [odds ratio (ORs) from 2.78 to 6.31] was related to 1-year mortality, using the age-adjusted Charlson comorbidity index (OR: 1.22), and previous use of long-term domiciliary oxygen therapy or non-invasive mechanical ventilation at home (OR: 1.68). The same variables were also predictive in the validation sample. Areas under the receiver operating characteristic curve in the derivation and validation sample were 0.79 and 0.78, respectively. In conclusion, PA is the strongest predictor of dying in the following year, i.e., those with worsened PA from baseline to 2 months after an eCOPD or with very low PA levels have a higher risk.
Background A home based tele-monitoring system was developed to assess the effects of heat stress (days > 25°C) on clinical and functional status in patients with chronic obstructive pulmonary disease (COPD). Methods Sixty-two COPD patients (GOLD II–IV) were randomized into a tele-monitoring Group (TG, N = 32) or Control Group (CG, N = 30). Tele-monitoring included 1) daily clinical status (COPD Assessment Test-CAT), 2) daily lung function and 3) weekly 6-minute walk test (6MWT). Duration of monitoring lasted a total of nine months (9 M). Results From June 1st–August 31st 2012, 32 days with heat stress (29.0 ± 2.5°C) were recorded and matched with 32 thermal comfort days (21.0 ± 2.9°C). During heat stress, the TG showed a significant reduction in lung function and exercise capacity (FEV1% predicted: 51.1 ± 7.2 vs. 57.7 ± 5.0%; P <0.001 and 6MWT performance: 452 ± 85 vs. 600 ± 76 steps; P <0.001) and increase in CAT scores (19.2 ± 7.9 vs. 16.2 ± 7.2; P <0.001). Over summer, significantly fewer TG patients suffered exacerbation of COPD compared to CG patients (3 vs. 14; P = 0.006). Over entire 9 M follow-up, the TG group had fewer exacerbations compared to CG (7 vs. 22; P = 0.012), shorter cumulative hospital stay (34 vs. 97 days) and 43% fewer specialist consultations (24. vs. 42; P = 0.04). Conclusion Heat stress affects clinical and functional status in COPD. Tele-monitoring reduces exacerbation frequency and health care utilization during heat stress and other periods of the year. Trial registration DRKS-ID: DRK00000705. PMID:24261700
de Matthaeis, Angela; Greco, Antonio; Dagostino, Mariangela Pia; Paroni, Giulia; Fontana, Andrea; Vinciguerra, Manlio; Mazzoccoli, Gianluigi; Seripa, Davide; Vendemiale, Gianluigi
Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium. PMID:24904207
Mathioudakis, Alexander G; Chatzimavridou-Grigoriadou, Victoria; Corlateanu, Alexandru; Vestbo, Jørgen
Challenges in the differentiation of the aetiology of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have led to significant overuse of antibiotics. Serum procalcitonin, released in response to bacterial infections, but not viral infections, could possibly identify AECOPD requiring antibiotics. In this meta-analysis we assessed the clinical effectiveness of procalcitonin-based protocols to initiate or discontinue antibiotics in patients presenting with AECOPD.Based on a prospectively registered protocol, we reviewed the literature and selected randomised or quasi-randomised trials comparing procalcitonin-based protocols to initiate or discontinue antibiotics versus standard care in AECOPD. We followed Cochrane and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidance to assess risk of bias, quality of evidence and to perform meta-analyses.We included eight trials evaluating 1062 patients with AECOPD. Procalcitonin-based protocols decreased antibiotic prescription (relative risk (RR) 0.56, 95% CI 0.43-0.73) and total antibiotic exposure (mean difference (MD) -3.83, 95% CI (-4.32--3.35)), without affecting clinical outcomes such as rate of treatment failure (RR 0.81, 0.62-1.06), length of hospitalisation (MD -0.76, -1.95-0.43), exacerbation recurrence rate (RR 0.96, 0.69-1.35) or mortality (RR 0.99, 0.58-1.69). However, the quality of the available evidence is low to moderate, because of methodological limitations and small overall study population.Procalcitonin-based protocols appear to be clinically effective; however, confirmatory trials with rigorous methodology are required.
Malerba, Mario; Ponticiello, Antonio; Radaeli, Alessandro; Bensi, Giuliano; Grassi, Vittorio
The objective of this prospective, randomized, double-blind, placebo-controlled, multicenter parallel-group study was to evaluate the effect of long-term ambroxol treatment in preventing exacerbations of chronic obstructive pulmonary disease (COPD). Two hundred and forty-two outpatients with COPD defined by ATS criteria with value of FEV1 between > or =60 and 80% of predicted and history of one or more exacerbations in the previous year were recruited by 26 Respiratory Medicine Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg twice daily or placebo. The percentage of patients free from exacerbation at 6 months was 63% with ambroxol and 60% with placebo (p=0.366) and at 12 months 56% with ambroxol and 53% with placebo (p=0.363). In a subset of 45 patients with more severe baseline symptoms, ambroxol therapy was associated with a significant higher percentage of patients free from exacerbation compared to placebo: 63 vs. 38% (p=0.038). In conclusion, we did not find a significant difference between long-term ambroxol therapy and placebo, in preventing exacerbations in patients with COPD. In patients with more severe respiratory symptoms at baseline, however, we observed a significant difference in the cumulative exacerbation-free persistence between ambroxol and placebo, suggesting that long-term muco-regulatory therapy with ambroxol could be useful in highly symptomatic patients with COPD.
COPD (chronic obstructive pulmonary disease) makes it hard for you to breathe. The two main types are chronic bronchitis and emphysema. The main cause of COPD is long-term exposure to substances that irritate ...
Silver, Jonathan S; Kearley, Jennifer; Copenhaver, Alan M; Sanden, Caroline; Mori, Michiko; Yu, Li; Pritchard, Gretchen Harms; Berlin, Aaron A; Hunter, Christopher A; Bowler, Russell; Erjefalt, Jonas S; Kolbeck, Roland; Humbles, Alison A
Innate lymphoid cells (ILCs) are critical mediators of mucosal immunity, and group 1 ILCs (ILC1 cells) and group 3 ILCs (ILC3 cells) have been shown to be functionally plastic. Here we found that group 2 ILCs (ILC2 cells) also exhibited phenotypic plasticity in response to infectious or noxious agents, characterized by substantially lower expression of the transcription factor GATA-3 and a concomitant switch to being ILC1 cells that produced interferon-γ (IFN-γ). Interleukin 12 (IL-12) and IL-18 regulated this conversion, and during viral infection, ILC2 cells clustered within inflamed areas and acquired an ILC1-like phenotype. Mechanistically, these ILC1 cells augmented virus-induced inflammation in a manner dependent on the transcription factor T-bet. Notably, IL-12 converted human ILC2 cells into ILC1 cells, and the frequency of ILC1 cells in patients with chronic obstructive pulmonary disease (COPD) correlated with disease severity and susceptibility to exacerbations. Thus, functional plasticity of ILC2 cells exacerbates anti-viral immunity, which may have adverse consequences in respiratory diseases such as COPD. PMID:27111143
Sanjuán, Pilar; Huerta, Arturo; Nieto-Codesido, Irene; Ferreira-Gonzalez, Lucía; Sibila, Oriol; Restrepo, Marcos I
Background Limited data are available regarding the impact of the potential validation of the Canadian Thoracic Society (CTS) guidelines recommendations in classifying patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in simple and complex. The aim of the present study was to assess the CTS recommendations regarding risk stratification on clinical outcomes among patients hospitalized with an AECOPD. Methods We developed a retrospective cohort study of patients admitted to one tertiary hospital with a diagnosis of AECOPD. The main clinical outcome was the percentage of treatment failure. Secondary outcomes were 30-day, 90-day, and 1-year readmission and mortality rate, length of stay in hospital, intensive care unit (ICU) admission rate, time to readmission, and time to death. Multivariate analyses were performed using 1-year mortality rate as the dependent measures. Results One hundred forty-three patients composed the final study population, most of them (106 [74.1%)] classified as complex acute exacerbation (C-AE) of COPD. C-AE patients had similar rate of treatment failure compared with simple acute exacerbation (S-AE) of COPD (31.1% vs. 27%; p = 0.63). There were no differences regarding the length of stay in hospital, ICU admission rate, and 30-day, 90-day, and 1-year readmission rate. C-AE patients had faster declined measures on time to death (691.6 ± 430 days vs. 998.1 ± 355 days; p = 0.02). In the multivariate analysis, after adjusting for comorbidity, lung function and previous treatment, C-AE patients had a significant higher mortality at one year (Odds Ratio [OR] = 4.9 (Confidence Interval [CI] 95%: 1.16-21); p = 0.031). Conclusions In hospitalized patients with an AECOPD, CTS classification, according to the presence of risk factors, was not associated with worse short-term clinical outcomes although it is related with long-term mortality. PMID:28265524
Newport, Sharon; Amin, Nikhil; Dozor, Allen J
Exhaled breath condensate (EBC) pH reflects the acid-base homeostasis of the airway lining fluid and is up to 3 log order lower in various inflammatory lung diseases including asthma, COPD, bronchiectasis, and cystic fibrosis (CF) than in normal controls. The aim of this study was to confirm this finding in CF and determine if there was a significant change in EBC pH after treatment of an acute pulmonary exacerbation. Ten subjects with CF and a pulmonary exacerbation, and 10 healthy age-matched control subjects were studied. EBC was collected at the onset of an acute pulmonary exacerbation and after treatment with intravenous antibiotics (median duration: 14 days (interquartile range, IQR): 12-14) when the exacerbation was considered resolved. The median age for CF patients was 15.9 years (IQR: 13-18.8), compared to 18 years (IQR: 15-24.8) for the control group, P = 0.242. All CF subjects had severe lung disease, median FEV(1) = 41.5% of predicted (IQR: 30.8-46.5%). Median EBC pH in CF subjects at the onset of a pulmonary exacerbation was 6.61 (IQR: 6.17-7.91) compared to median EBC pH of 8.14 (IQR: 7.45-9.08) in the control group, P < 0.02. Median EBC pH after resolution of an exacerbation was 7.02 (IQR: 5.8-8.64), not significantly different (P = 0.667) than during the acute exacerbation. EBC pH decreased in five subjects, increased in three subjects and there was no change in two subjects. There was no correlation between EBC pH and FEV(1) either before or after intravenous antibiotics. EBC ammonia, an important buffer of ASL, was also measured and similarly found to be lower than in normal controls. EBC pH is lower in CF than age-matched controls, and did not change consistently in response to treatment of an acute pulmonary exacerbation.
Laue, Johanna; Melbye, Hasse; Halvorsen, Peder A; Andreeva, Elena A; Godycki-Cwirko, Maciek; Wollny, Anja; Francis, Nick A; Spigt, Mark; Kung, Kenny; Risør, Mette Bech
Purpose To explore the decision-making of general practitioners (GPs) concerning treatment with antibiotics and/or oral corticosteroids and hospitalization for COPD patients with exacerbations. Methods Thematic analysis of seven focus groups with 53 GPs from urban and rural areas in Norway, Germany, Wales, Poland, Russia, the Netherlands, and Hong Kong. Results Four main themes were identified. 1) Dealing with medical uncertainty: the GPs aimed to make clear medical decisions and avoid unnecessary prescriptions and hospitalizations, yet this was challenged by uncertainty regarding the severity of the exacerbations and concerns about overlooking comorbidities. 2) Knowing the patient: contextual knowledge about the individual patient provided a supplementary framework to biomedical knowledge, allowing for more differentiated decision-making. 3) Balancing the patients’ perspective: the GPs considered patients’ experiential knowledge about their own body and illness as valuable in assisting their decision-making, yet felt that dealing with disagreements between their own and their patients’ perceptions concerning the need for treatment or hospitalization could be difficult. 4) Outpatient support and collaboration: both formal and informal caregivers and organizational aspects of the health systems influenced the decision-making, particularly in terms of mitigating potentially severe consequences of “wrong decisions” and concerning the negotiation of responsibilities. Conclusion Fear of overlooking severe comorbidity and of further deteriorating symptoms emerged as a main driver of GPs’ management decisions. GPs consider a holistic understanding of illness and the patients’ own judgment crucial to making reasonable decisions under medical uncertainty. Moreover, GPs’ decisions depend on the availability and reliability of other formal and informal carers, and the health care systems’ organizational and cultural code of conduct. Strengthening the
Ejiofor, Stanley I; Stolk, Jan; Fernandez, Pablo; Stockley, Robert A
Introduction Patients with chronic obstructive pulmonary disease often experience exacerbations. These events are important as they are a major cause of morbidity and mortality. Recently, it has been increasingly recognized that patients may experience symptoms suggestive of an exacerbation but do not seek treatment, which are referred to as unreported or untreated exacerbations. Symptom diaries used in clinical trials have the benefit of identifying both treated and untreated exacerbation events. Methods The Kamada study was a multicenter, double-blind randomized controlled trial of inhaled augmentation therapy in alpha-1 antitrypsin deficiency (AATD). A retrospective review of daily electronic symptom diary cards was undertaken from the two leading centers to identify symptomatic episodes consistent with a definition of an exacerbation. The aims were to explore the relationship between exacerbation events and classical “Anthonisen” symptoms and to characterize treated and untreated episodes. Results Forty-six AATD patients with airflow obstruction and history of exacerbations were included in the analysis. Two hundred thirty-three exacerbation episodes were identified: 103 untreated and 130 treated. Untreated episodes were significantly shorter (median 6 days; interquartile range [IQR] 3–10 days) than the treated episodes (median 10 days; IQR 5–18.25 days: P<0.001). Using logistic regression analysis, Anthonisen type and length of dyspnea were significant predictors of the treatment of an exacerbation event. Conclusion Real-time electronic diary cards provide valuable information about the characterization of exacerbations. Untreated episodes are common and are significantly shorter in duration than the treated episodes. Dyspnea is the most important single Anthonisen symptom in the prediction and/or driver of treatment. PMID:28182151
Bhatia, Ankit; Prakash, Ved; Kant, Surya; Verma, Ajay Kumar
Introduction: Acute exacerbations are a significant source of morbidity and mortality associated with chronic obstructive pulmonary disease (COPD). Some patients suffer an inordinate number of exacerbations while others remain relatively protected. The aim of this study was to evaluate the potentially modifiable precipitating parameters of frequent severe exacerbations requiring hospital admission in COPD. Materials and Methods: Consecutive patients admitted with acute exacerbation of COPD for a period of one year in a tertiary care hospital were evaluated prospectively. Data regarding the number of exacerbations in the previous year, current comorbidities, medications, and clinical and functional status of COPD patients were evaluated. Results: We included 98 COPD patients (81.63% men) admitted consecutively with exacerbations in our department. The mean number of severe exacerbations was (2.42 per patient/per year), and 65% of the patients had frequent severe exacerbations. Multivariate analysis indicated that serum uric acid, serum total IgE, depression and anxiety, gastroesophageal reflux disease symptoms, air pollution, poor adherence to inhaled therapy, and irregular outpatient followup visits were independent predictors of frequent severe exacerbations. Conclusion: COPD patients with frequent exacerbations should be carefully assessed for modifiable confounding risk factors regardless of poor lung function to decrease exacerbation frequency and related poor prognosis. Raised serum total IgE levels may point towards atopy as an additional comorbidity in COPD while uric acid can have a clinically useful role in risk stratification in a primary care setting. PMID:27890987
Diederen, B M W; van der Valk, P D L P M; Kluytmans, J A W J; Peeters, M F; Hendrix, R
The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Serological studies have suggested that Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila may play a role in acute exacerbations of COPD. The presence of these atypical pathogens in sputum samples was investigated in patients with stable COPD and with acute exacerbations of COPD using real-time PCR. The present study was part of a randomised, double-blind, single-centre study and a total of 248 sputum samples from 104 COPD patients were included. In total, 122 samples obtained during stable disease (stable-state sputa) and 126 samples obtained during acute exacerbations of COPD (exacerbation sputa) were tested. Of the 122 stable-state sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. Of the 126 exacerbation sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. The possible relationship between the presence of atypical pathogens and the aetiology of acute exacerbations in chronic obstructive pulmonary disease was investigated in patients with stable disease and in those with acute exacerbations using real-time PCR. No indication was found of a role for Legionella spp., Chlamydia pneumoniae or Mycoplasma pneumoniae in stable, moderately severe chronic obstructive pulmonary disease and in its exacerbations.
Kaul, Sundeep; Pearson, Michael; Coutts, Ian; Lowe, Derek; Roberts, Michael
Non-invasive ventilation (NIV) is a clinically proven, cost-effective intervention for acidotic exacerbations of COPD that is recommended by UK national guidelines. This study examines the extent to which these recommendations are being followed in the UK. Between August and October 2003 a national audit of COPD exacerbations was conducted by the Royal College of Physicians and the British Thoracic Society. 233 (94%) UK hospitals submitted data for 7,529 prospectively recruited acute COPD admissions, documenting process of care and outcomes from a retrospective case note audit. They also completed a resources and organisation of care proforma. Nineteen hospitals (8%) reported they did not offer NIV. There was no access to NIV in 92 (39%) intensive care units in 88 (36%), high-dependency units or on general wards of 85 (34%) hospitals. In 74 (30%) NIV was available on all 3 sites. A low pH (<7.35) was noted at some time during admission for 26% (1714/6544) of patients and NIV was administered to 31%. Patients receiving NIV were more often admitted under a respiratory physician, or seen at some stage by a respiratory specialist and had more severe disease (higher PaCO2 (median 9.8 v 7.8 kPa), lower oxygen tension (median 8.8 v 9.8 kPa), higher incidence of peripheral oedema (48% v 39%), of pneumonia (27% v 16%), higher in-hospital mortality (26% v 14%) and at 90 days (37% v 24%) and longer hospital stays (median 9 v 7 days) than those not receiving NIV. Hospitals with least usage of NIV had similar mortality rates to those using NIV more often. A comprehensive NIV service is not available in many hospitals admitting patients with acute respiratory failure secondary to COPD. Access to acute NIV is inadequate and does not conform with NICE and BTS guidelines. These observational audit data do not demonstrate benefits of NIV on survival when compared to conventional management, contrary to results from randomised trials. Reasons for this are unclear but unmeasured
Background Acute exacerbations of chronic bronchitis (AECB), including chronic obstructive pulmonary disease (AECOPD), represent a substantial patient burden. Few data exist on outpatient antibiotic management for AECB/AECOPD in Eastern/South Eastern Europe, in particular on the use of moxifloxacin (Avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies. Methods AVANTI (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, observational study conducted in eight Eastern European countries in patients > 35 years with AECB/AECOPD to whom moxifloxacin was prescribed. In addition to safety and efficacy outcomes, data on risk factors and the impact of exacerbation on daily life were collected. Results In the efficacy population (N = 2536), chronic bronchitis had been prevalent for > 10 years in 31.4% of patients and 66.0% of patients had concomitant COPD. Almost half the patients had never smoked, in contrast to data from Western Europe and the USA, where only one-quarter of COPD patients are non-smokers. The mean number of exacerbations in the last 12 months was 2.7 and 26.3% of patients had been hospitalized at least once for exacerbation. Physician compliance with the recommended moxifloxacin dose (400 mg once daily) was 99.6%. The mean duration of moxifloxacin therapy for the current exacerbation (Anthonisen type I or II in 83.1%; predominantly type I) was 6.4 ± 1.9 days. Symptom improvement was reported after a mean of 3.4 ± 1.4 days. After 5 days, 93.2% of patients reported improvement and, in total, 93.5% of patients were symptom-free after 10 days. In the safety population (N = 2672), 57 (2.3%) patients had treatment-emergent adverse events (TEAEs) and 4 (0.15%) had serious TEAEs; no deaths occurred. These results are in line with the known safety profile of moxifloxacin. Conclusions A significant number of patients in this observational study had risk
Lee, Hwa Young; Kim, Jin Woo; Lee, Sang Haak; Yoon, Hyoung Kyu; Shim, Jae Jeong; Park, Jeong-Woong; Lee, Jae-Hyung; Yoo, Kwang Ha; Jung, Ki-Suck
Background This study was designed to evaluate the effect of chronic bronchitis (CB) symptoms and degree of emphysema in a multicenter Korean cohort. Methods From April 2012 to May 2015, patients diagnosed with chronic obstructive lung disease (COPD) who were aged above 40 years at 46 hospitals throughout Korea were enrolled. All of the patients were classified according to CB symptoms and the diffusing capacity of the lung for carbon monoxide (DLCO); demographic data, symptom scores, and the result of lung function tests and exacerbations were then analyzed. Results A total of 812 patients were enrolled. Among these patients, 285 (35.1%) had CB symptoms. A total of 51% of patients had high DLCO without CB symptoms [CB (−) high DLCO], 24.9% had CB symptoms only [CB (+) high DLCO], 14.2% had low DLCO only [CB (−) low DLCO], and 10.2% had both low DLCO and CB [CB (+) low DLCO]. Patients with CB (+) low DLCO showed a significantly lower post-bronchodilator (BD) forced expiratory volume for 1 second (FEV1) and more severe dyspnea than patients with CB (−) high DLCO. On multivariate analysis, the risk of acute exacerbation was two times higher [odds ratio (OR) 2.06; 95% confidence interval (CI): 1.18–3.62; P=0.01] in the CB (+) low DLCO group than in the CB (−) high DLCO group. Conclusions In this COPD cohort, patients showed distinct clinical characteristics and outcomes according to the presence of CB and degree of DLCO. CB and low DLCO were associated with the risk of acute exacerbation. PMID:27293847
Oba, Yuji; Lone, Nazir A
Background A combination therapy with inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is recommended in severe chronic obstructive pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently, there are five ICS/LABA combination products available on the market. The purpose of this study was to systematically review the efficacy of various ICS/LABA combinations with a network meta-analysis. Methods Several databases and manufacturer’s websites were searched for relevant clinical trials. Randomized control trials, at least 12 weeks duration, comparing an ICS/LABA combination with active control or placebo were included. Moderate and severe exacerbations were chosen as the outcome assessment criteria. The primary analyses were conducted with a Bayesian Markov chain Monte Carlo method. Results Most of the ICS/LABA combinations reduced moderate-to-severe exacerbations as compared with placebo and LABA, but none of them reduced severe exacerbations. However, many studies excluded patients receiving long-term oxygen therapy. Moderate-dose ICS was as effective as high-dose ICS in reducing exacerbations when combined with LABA. Conclusion ICS/LABA combinations had a class effect with regard to the prevention of COPD exacerbations. Moderate-dose ICS/LABA combination therapy would be sufficient for COPD patients when indicated. The efficacy of ICS/LABA combination therapy appeared modest and had no impact in reducing severe exacerbations. Further studies are needed to evaluate the efficacy of ICS/LABA combination therapy in severely affected COPD patients requiring long-term oxygen therapy. PMID:24872685
Gunawardana, Natasha; Finney, Lydia; Johnston, Sebastian L; Mallia, Patrick
Chronic obstructive pulmonary disease (COPD) is a major public health problem and will be one of the leading global causes of mortality over the coming decades. Much of the morbidity, mortality and health care costs of COPD are attributable to acute exacerbations, the commonest causes of which are respiratory infections. Respiratory viruses are frequently detected in COPD exacerbations but direct proof of a causative relationship has been lacking. We have developed a model of COPD exacerbation using experimental rhinovirus infection in COPD patients and this has established a causative relationship between virus infection and exacerbations. In addition it has determined some of the molecular mechanisms linking virus infections to COPD exacerbations and identified potential new therapeutic targets. This new data should stimulate research into the role of antiviral agents as potential treatments for COPD exacerbations. Testing of antiviral agents has been hampered by the lack of a small animal model for rhinovirus infection and experimental rhinovirus infection in healthy volunteers has been used to test treatments for the common cold. Experimental rhinovirus infection in COPD subjects offers the prospect of a model that can be used to evaluate the effects of new treatments for virus-induced COPD exacerbations, and provide essential data that can be used in making decisions regarding large scale clinical trials.
Cordova, Francis C.; Ciccolella, David; Grabianowski, Carla; Gaughan, John; Brennan, Kathleen; Goldstein, Frederick; Criner, Gerard J.
Abstract Background: Patients with chronic obstructive pulmonary disease (COPD) may not recognize worsening symptoms that require intensification of therapy. They may also be reluctant to contact a healthcare provider for minor worsening of symptoms. A telemedicine application for daily symptom reporting may reduce these barriers and improve patient outcomes. Materials and Methods: Patients hospitalized for a COPD exacerbation within the past year or using supplemental O2 were approached for participation. Patients received optimal COPD care and were given a telecommunication device for symptom reporting. Initial symptom scores were obtained while patients were in their usual state of health. Patients were randomly assigned to an intervention group or a control group (usual medical care). The control group patients were instructed to seek medical care if their condition worsened. The intervention group symptom scores were assessed by a computer algorithm and compared with initial values. Scores 1 or more points above the initial score generated an “alert,” and patients were reviewed by a nurse and referred to a physician who prescribed treatment. Results: Eighty-six patients were screened; 79 met entry criteria and were randomized (intervention group, n=39; control group, n=40). Twelve patients submitted five or fewer symptom reports (5 intervention; 7 control) and were excluded from the analysis. Daily peak flow and dyspnea scores improved only in the intervention group. There were no differences in hospitalization and mortality rates between groups. No serious adverse events were reported. Conclusions: A telemedicine-based symptom reporting program facilitated early treatment of symptoms and improved lung function and functional status. PMID:26259074
Roberts, C Michael; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Hartl, Sylvia
Understanding how European care of chronic obstructive pulmonary disease (COPD) admissions vary against guideline standards provides an opportunity to target appropriate quality improvement interventions. In 2010-2011 an audit of care against the 2010 'Global initiative for chronic Obstructive Lung Disease' (GOLD) standards was performed in 16 018 patients from 384 hospitals in 13 countries. Clinicians prospectively identified consecutive COPD admissions over a period of 8 weeks, recording clinical care measures on a web-based data tool. Data were analysed comparing adherence to 10 key management recommendations. Adherence varied between hospitals and across countries. The lack of available spirometry results and variable use of oxygen and non-invasive ventilation (NIV) are high impact areas identified for improvement.
Koul, Parvaiz A; Mir, Hyder; Akram, Shabir; Potdar, Varsha; Chadha, Mandeep S
Objective: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) cause significant morbidity, mortality, and an inexorable decline of lung function. Data from developed countries have shown viruses to be important causes of AECOPD, but data from developing countries like India are scant. We set out to determine the contribution of viruses in the causation of hospitalized patients with AECOPD. Methods: Twin nasopharyngeal/oropharyngeal swabs collected from 233 patients admitted with an acute AECOPD and tested for respiratory viruses including respiratory syncytial virus A and B, parainfluenza were (PIV) 1, 2, 3, and 4, human metapneumovirus (hMPV) A and B, influenza A and B, enterovirus, corona NL65, OC43, and 229E viruses, adenovirus 2 and 4, rhinovirus, and bocavirus, by duplex real time reverse-transcription polymerase chain reaction (qRT-PCR) using CDC approved primers and probes. Samples positive for influenza A were subtyped for A/H1N1pdm09 and A/H3N2 whereas influenza B samples were subtyped into B/Yamagata and B/Victoria subtypes, using primers and probes recommended by CDC, USA. Results: Respiratory viruses were detected in 46 (19.7%) cases, influenza A/H3N2 and rhinoviruses being the most common viruses detected. More than one virus was isolated in four cases consisting of hMPV-B + adeno-2 + Inf-B; rhino + H3N2, PIV-1 + rhino; and PIV-1+ hMPV-B in one case each. Ancillary supportive therapeutic measures included bronchodilators, antibiotics, steroids, and ventilation (noninvasive in 42 and invasive in 4). Antiviral therapy was instituted in influenza-positive patients. Three patients with A/H3N2 infection died during hospitalization. Conclusions: We conclude that respiratory viruses are important contributors to AECOPD in India. Our data calls for prompt investigation during an exacerbation for viruses to obviate inappropriate antibiotic use and institute antiviral therapy in viral disease amenable to antiviral therapy. Appropriate
Collard, Harold R; Ryerson, Christopher J; Corte, Tamera J; Jenkins, Gisli; Kondoh, Yasuhiro; Lederer, David J; Lee, Joyce S; Maher, Toby M; Wells, Athol U; Antoniou, Katerina M; Behr, Juergen; Brown, Kevin K; Cottin, Vincent; Flaherty, Kevin R; Fukuoka, Junya; Hansell, David M; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kolb, Martin; Lynch, David A; Myers, Jeffrey L; Raghu, Ganesh; Richeldi, Luca; Taniguchi, Hiroyuki; Martinez, Fernando J
Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.
Wedzicha, Jadwiga A; Zhong, Nanshan; Ichinose, Masakazu; Humphries, Michael; Fogel, Robert; Thach, Chau; Patalano, Francesco; Banerji, Donald
Background The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting β2-agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study. Patients and methods Patients from Asian centers with moderate-to-very severe COPD and ≥1 exacerbation in the previous year from the 52-week, randomized FLAME study were included. IND/GLY was compared versus SFC for effects on exacerbations, lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), health status (St George’s Respiratory Questionnaire [SGRQ]), rescue medication use, and safety. Results A total of 510 Asian patients (IND/GLY, n=250 or SFC, n=260) were included. Compared to the overall FLAME population, the Asian cohort had more males, a shorter duration of COPD, fewer patients using inhaled corticosteroid (ICS) at screening, fewer current smokers, and more patients with very severe COPD. IND/GLY significantly reduced the rate of moderate/severe exacerbations (rate ratio: 0.75; 95% confidence interval: 0.58–0.97; P=0.027) and prolonged time to first moderate/severe exacerbation versus SFC (hazard ratio: 0.77; 95% confidence interval: 0.59–1.01; P=0.055). Predose trough FEV1 and FVC significantly improved in Asian patients (P<0.001). IND/GLY improved SGRQ for COPD (SGRQ-C score; P=0.006) and reduced rescue medication use (P=0.058) at week 52. Pneumonia incidence was 3.6% with IND/GLY and 7.7% with SFC (P=0.046). Conclusion In exacerbating Asian COPD patients, IND/GLY was more effective than SFC. PMID:28176893
Yu, Xuhua; Guo, Xinfeng; Xue, Charlie Changli
Objective. To evaluate the efficacy and safety of Weijing decoction combined with routine pharmacotherapy (RP) for the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods. Randomized controlled trials (RCT) evaluating Weijing decoction for AECOPD were included. English, Chinese, and Japanese databases were searched from their respective inceptions to June 2013. The methodological quality was assessed according to the Cochrane Collaboration's risk of bias tool. All data were analyzed and synthesized using RevMan 5.2 software. Results. Fifteen (15) studies involving 986 participants were included. Participants were diagnosed with COPD in the acute exacerbation stage. In addition, most of studies reported that they included participants with the Chinese medicine syndrome, phlegm-heat obstructing the Lung. Weijing decoction combined with RP improved lung function (forced expiratory volume in one second; FEV1), arterial blood gases (PaO2 and PaCO2), clinical effective rate, and reduced inflammatory biomarkers (TNF-α and IL-8) when compared with RP alone. No severe adverse events were reported in these studies. Conclusions. Weijing decoction appeared to be beneficial for AECOPD and well-tolerated when taken concurrently with RP, such as antibiotics, bronchodilators (oral and inhaled), and mucolytics. PMID:25165477
Lin, Su; Ye, Qiaoxia; Wang, Mingfang; Wu, Yinlian; Weng, Zhiyuan; Zhu, Yueyong
Background The aim of this study was to assess the efficacy and safety of peginterferon α-2a (pegIFN) and nucleos(t)ide analogues (NA) treatments in patients with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B (CHB) with mild acute exacerbation (AE). Methods Treatment-naive HBeAg-positive CHB patients with AE who received pegIFN or NA (entecavir (ETV) or telbivudine (LDT)) therapies were retrospectively selected. The HBeAg seroconversion rate, hepatitis B surface antigen (HBsAg) loss rate and the cost-effectiveness of different treatments were compared. Results A total of 63 patients with pegIFN therapy and 78 with NA (38 with ETV and 40 with LDT) therapy were included. The HBsAg loss rate was significantly higher in the pegIFN group when compared with the NA group (on week 96: 9/63 (14.29%) vs. 1/78 (1.28%), P = 0.005). No significant difference in hepatitis B virus (HBV) DNA negativity or the HBeAg/HBsAg seroconversion rate was found between ETV and LDT group. One year of pegIFN therapy resulted in 18.56 quality-adjusted life years (QALYs) per patient, and the incremental cost per additional QALY gained was $3,709. Conclusions PegIFN therapy is safe in HBeAg-positive CHB patients with mild AE, as it results in a higher HBsAg loss rate and longer QALYs than NA therapy. PMID:28270871
Background Acute respiratory illness is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular events characterizing acute respiratory illness-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of acute respiratory illness amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. Methods Transcriptional profiling experiments were performed using the Agilent Whole Human Genome 4X44K array platform. Time point-based microarray and principal component analyses were conducted to identify and distinguish acute respiratory illness-associated transcriptional profiles over the course of our study. Gene enrichment analysis was conducted to identify biological processes over-represented within each acute respiratory illness-associated profile, and gene expression was subsequently confirmed by quantitative polymerase chain reaction. Results We found that acute respiratory illness is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during acute respiratory illness. Most strikingly, we report that people with asthma who experience acute respiratory illness-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair, and the expression of a newly described exacerbation-specific transcriptional signature. Conclusion Findings from our study represent a significant contribution towards clarifying the complex molecular interactions that typify acute respiratory illness-induced asthma exacerbations. PMID:24433494
Kim, Hyo-Jung; Lee, Jaemoon; Kim, Jung-Hyun; Park, So-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom
Purpose Prolonged recovery time of pulmonary function after an asthma exacerbation is a significant burden on asthmatics, and management of these patients needs to be improved. The aim of this study was to evaluate factors associated with a longer recovery time of pulmonary function among asthmatic patients hospitalized due to a severe asthma exacerbation. Methods We retrospectively reviewed the medical records of 89 patients who were admitted for the management of acute asthma exacerbations. The recovery time of pulmonary function was defined as the time from the date each patient initially received treatment for asthma exacerbations to the date the patient reached his or her previous best FEV1% value. We investigated the influence of various clinical and laboratory factors on the recovery time. Results The median recovery time of the patients was 1.7 weeks. Multiple linear regression analysis revealed that using regular inhaled corticosteroids (ICS) before an acute exacerbation of asthma and concurrent with viral infection at admission were associated with the prolonged recovery time of pulmonary function. Conclusions The prolonged recovery time of pulmonary function after a severe asthma exacerbation was not shown to be directly associated with poor adherence to ICS. Therefore the results indicate that an unknown subtype of asthma may be associated with the prolonged recovery of pulmonary function time after an acute exacerbation of asthma despite regular ICS use. Further prospective studies to investigate factors affecting the recovery time of pulmonary function after an asthma exacerbation are warranted. PMID:27582400
Khan, Javed H.; Lababidi, Hani M. S.; Al-Moamary, Mohamed S.; Zeitouni, Mohammed O.; AL-Jahdali, Hamdan H.; Al-Amoudi, Omar S.; Wali, Siraj O.; Idrees, Majdy M.; Al-Shimemri, Abdullah A.; Al Ghobain, Mohammed O.; Alorainy, Hassan S.; Al-Hajjaj, Mohamed S.
The Saudi Thoracic Society (STS) launched the Saudi Initiative for Chronic Airway Diseases (SICAD) to develop a guideline for the diagnosis and management of chronic obstructive pulmonary disease (COPD). This guideline is primarily aimed for internists and general practitioners. Though there is scanty epidemiological data related to COPD, the SICAD panel believes that COPD prevalence is increasing in Saudi Arabia due to increasing prevalence of tobacco smoking among men and women. To overcome the issue of underutilization of spirometry for diagnosing COPD, handheld spirometry is recommended to screen individuals at risk for COPD. A unique feature about this guideline is the simplified practical approach to classify COPD into three classes based on the symptoms as per COPD Assessment Test (CAT) and the risk of exacerbations and hospitalization. Those patients with low risk of exacerbation (<2 in the past year) can be classified as either Class I when they have less symptoms (CAT < 10) or Class II when they have more symptoms (CAT ≥ 10). High-risk COPD patients, as manifested with ≥2 exacerbation or hospitalization in the past year irrespective of the baseline symptoms, are classified as Class III. Class I and II patients require bronchodilators for symptom relief, while Class III patients are recommended to use medications that reduce the risks of exacerbations. The guideline recommends screening for co-morbidities and suggests a comprehensive management approach including pulmonary rehabilitation for those with a CAT score ≥10. The article also discusses the diagnosis and management of acute exacerbations in COPD. PMID:24791168
Moore, Elizabeth; Chatzidiakou, Lia; Jones, Roderic L; Smeeth, Liam; Beevers, Sean; Kelly, Frank J; Barratt, Benjamin
Introduction Relationships between exacerbations of chronic obstructive pulmonary disease (COPD) and environmental factors such as temperature, humidity and air pollution are not well characterised, due in part to oversimplification in the assignment of exposure estimates to individuals and populations. New developments in miniature environmental sensors mean that patients can now carry a personal air quality monitor for long periods of time as they go about their daily lives. This creates the potential for capturing a direct link between individual activities, environmental exposures and the health of patients with COPD. Direct associations then have the potential to be scaled up to population levels and tested using advanced human exposure models linked to electronic health records. Methods and analysis This study has 5 stages: (1) development and deployment of personal air monitors; (2) recruitment and monitoring of a cohort of 160 patients with COPD for up to 6 months with recruitment of participants through the Clinical Practice Research Datalink (CPRD); (3) statistical associations between personal exposure with COPD-related health outcomes; (4) validation of a time-activity exposure model and (5) development of a COPD prediction model for London. Ethics and dissemination The Research Ethics Committee for Camden and Islington has provided ethical approval for the conduct of the study. Approval has also been granted by National Health Service (NHS) Research and Development and the Independent Scientific Advisory Committee. The results of the study will be disseminated through appropriate conference presentations and peer-reviewed journals. PMID:27412104
Hu, Guoping; Zhong, Nanshan; Ran, Pixin
Recently, many researchers paid more attentions to the association between air pollution and chronic obstructive pulmonary disease (COPD). Haze, a severe form of outdoor air pollution, affected most parts of northern and eastern China in the past winter. In China, studies have been performed to evaluate the impact of outdoor air pollution and biomass smoke exposure on COPD; and most studies have focused on the role of air pollution in acutely triggering symptoms and exacerbations. Few studies have examined the role of air pollution in inducing pathophysiological changes that characterise COPD. Evidence showed that outdoor air pollution affects lung function in both children and adults and triggers exacerbations of COPD symptoms. Hence outdoor air pollution may be considered a risk factor for COPD mortality. However, evidence to date has been suggestive (not conclusive) that chronic exposure to outdoor air pollution increases the prevalence and incidence of COPD. Cross-sectional studies showed biomass smoke exposure is a risk factor for COPD. A long-term retrospective study and a long-term prospective cohort study showed that biomass smoke exposure reductions were associated with a reduced decline in forced expiratory volume in 1 second (FEV1) and with a decreased risk of COPD. To fully understand the effect of air pollution on COPD, we recommend future studies with longer follow-up periods, more standardized definitions of COPD and more refined and source-specific exposure assessments.
Tabak, Monique; Brusse-Keizer, Marjolein; van der Valk, Paul; Hermens, Hermie; Vollenbroek-Hutten, Miriam
The objective of this pilot study was to investigate the use of and satisfaction with a chronic obstructive pulmonary disease (COPD) telehealth program applied in both primary and secondary care. The program consisted of four modules: 1) activity coach for ambulant activity monitoring and real-time coaching of daily activity behavior, 2) web-based exercise program for home exercising, 3) self-management of COPD exacerbations via a triage diary on the web portal, including self-treatment of exacerbations, and 4) teleconsultation. Twenty-nine COPD patients were randomly assigned to either the intervention group (telehealth program for 9 months) or the control group (usual care). Page hits on the web portal showed the use of the program, and the Client Satisfaction Questionnaire showed satisfaction with received care. The telehealth program with decision support showed good satisfaction (mean 26.4, maximum score 32). The program was accessed on 86% of the treatment days, especially the diary. Patient adherence with the exercise scheme was low (21%). Health care providers seem to play an important role in patients' adherence to telehealth in usual care. Future research should focus on full-scale implementation in daily care and investigating technological advances, like gaming, to increase adherence.
Vijayasaratha, Kesavaperumal; Stockley, Robert A
Background Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD), although factors influencing the length and frequency of each episode are poorly understood. This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT) deficiency (PiZ phenotype) and COPD. Methods Daily diary cards were collected over 2 years. Patients had emphysema visualized and quantified by computed tomography scan, and had at least one documented exacerbation in the previous year. Results The patients (n = 23) had a mean age of 52.5 years, forced expiratory volume in one second (FEV1) of 1.2 L (38.4% predicted), corrected gas transfer (KCO) of 0.90 mmol/min/kPa/L (59.7% predicted), and 15th percentile lung density of 44.55 g/L. Two hundred and sixty-three exacerbations (164 treated) were identified. The frequency of treated exacerbations correlated negatively with KCO% predicted (r = −0.432; P = 0.022). Exacerbation length (determined for 17 of the patients for whom diary card data through the episode were available) correlated negatively with baseline 15th percentile lung density (r = −0.361; P = 0.003), and increased the longer treatment was delayed (r = 0.503; P < 0.001). Treatment delay was shorter with higher day 1 symptom score, lower baseline FEV1, FEV1/forced vital capacity, and lower 15th percentile lung density (r = −0.368, 0.272, 0.461, and 0.786; P = 0.004, 0.036, <0.001, and <0.001, respectively). Time to resolution of exacerbation after treatment initiation was not affected by treatment delay, but correlated negatively with KCO% predicted (r = −0.647; P = 0.007). Conclusion In alpha-1 antitrypsin deficiency, the frequency and length of resolution of exacerbation were related to baseline gas transfer. Treatment delay adversely affected exacerbation length, and lung density was the best independent predictor of delay in starting treatment. PMID:23226015
Ides, Kris; Vos, Wim; De Backer, Lieve; Vissers, Dirk; Claes, Rita; Leemans, Glenn; Ongena, Kevin; Peters, Oswald; De Backer, Wilfried
Objective: Chest physiotherapy enhances sputum evacuation in COPD patients. It can be applied as a single technique or as a combination of techniques including intrapulmonary percussive ventilation (IPV). Recently developed assessment techniques may provide new insights into the effect of airway clearance techniques. Participants: Five moderate to severe COPD patients (three females and two males; mean forced expiratory volume in 1 second of 39.49% predicted) who were admitted in the hospital for an acute exacerbation were included in this study. Methods: A novel imaging technique was used, together with other conventional techniques, to visualize the short-term effects of a single IPV treatment in COPD patients. Results: No significant changes were noted in the lung function parameters or arterial blood gases measured within 1 hour after the end of the IPV session. Computed tomography images detected changes in the airway patency after the IPV treatment compared with before treatment. Local resistances, calculated for the three-dimensional models, showed local changes in airway resistance. Conclusion: The effects of a single IPV session can be visualized by functional imaging. This functional imaging allows a calculation of changes in local airway resistance and local changes in airway volume in COPD patients without affecting conventional lung function parameters. PMID:23055715
Pérez-Trallero, Emilio; Marimón, José M; Larruskain, Julián; Alonso, Marta; Ercibengoa, María
In the elderly, Streptococcus pneumoniae is the most common cause of pneumonia and one of the most frequently isolated pathogens in cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study was conducted to compare the pneumococcal isolates obtained during episodes of AECOPD and pneumonia in patients of ≥65 years old and to analyze whether in patients with AECOPD and pneumonia within a short interval, the same isolate caused both episodes. This laboratory-based study was performed between 2005 and 2008. Pneumococcal isolates from episodes of pneumonia (n = 401) and AECOPD (n = 398), matched one-to-one by date of isolation, were characterized. The serotypes and genotypes of other pneumococcal isolates causing pneumonia and AECOPD in the same patient were compared. In patients with pneumonia, COPD as an underlying disease was not associated with more-drug-resistant pneumococci. In contrast, isolates causing AECOPD showed higher rates of resistance than those causing pneumonia. Serotypes 1, 3, and 7F were more frequent in pneumonia. The same pneumococcus was involved in 25.7% (9/35 patients) of patients with two consecutive AECOPD episodes but in only 6.3% (2/32 patients) of COPD patients with pneumonia and exacerbation (Fisher's exact test; P = 0.047). Less invasive serotypes were isolated more often in AECOPD and were more resistant to antimicrobials. The presence of a specific pneumococcal serotype in AECOPD does not predict the etiology of subsequent pneumonia.
Lu, Xiaofan; Li, Ya; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang
Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14–18 days. All biomarkers were improved in treated groups with shorter recovery times of 4–10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333
Hewitt, Richard; Farne, Hugo; Ritchie, Andrew; Luke, Emma; Johnston, Sebastian L; Mallia, Patrick
Asthma and chronic obstructive pulmonary disease (COPD) are major causes of global morbidity and mortality worldwide. The clinical course of both asthma and COPD are punctuated by the occurrence of exacerbations, acute events characterized by increased symptoms and airflow obstruction. Exacerbations contribute most of the morbidity, mortality and excess healthcare costs associated with both asthma and COPD. COPD and asthma exacerbations are frequently associated with respiratory virus infections and this has led to an intense research focus into the mechanisms of virus-induced exacerbations over the past decade. Current therapies are effective in reducing chronic symptoms but are less effective in preventing exacerbations, particularly in COPD. Understanding the mechanisms of virus-induced exacerbation will lead to the development of new targeted therapies that can reduce the burden of virus-induced exacerbations. In this review we discuss current knowledge of virus-induced exacerbations of asthma and COPD with a particular focus on mechanisms, human studies, virus-bacteria interactions and therapeutic advances.
Huang, Yvonne J; Boushey, Homer A
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with--and perhaps to mediate--accelerated loss of lung function in COPD. Although the application of culture-independent methods for detection of bacteria have shown COPD to be associated with marked differences in the burden, diversity, and composition of the bronchial bacterial microbiome, few studies have examined the changes associated with community-acquired exacerbations of the disease. In a longitudinal cohort study of COPD, the availability of sputum samples from subjects obtained at the onset of an exacerbation and during periods of clinical stability before and after the event enabled us to recently address this gap in knowledge, using culture-independent, 16S rRNA-based analysis methods combined with in silico inference of metagenomic functions. We observed sputum bacterial composition to be generally stable over the preexacerbation period of clinical stability, but to change at the time of exacerbation, with specific enrichment in not only typical COPD-associated bacterial species (e.g., Haemophilus influenzae) but also other phylogenetically related species with pathogenic potential. Concurrently, we observed depleted abundance of other bacteria whose predicted metagenomes suggest functional capacities to produce a variety of antiinflammatory compounds. Most strikingly, we found that resolution of these exacerbation-related changes in sputum microbiota composition differed significantly, depending on the exacerbation treatments prescribed. Treatment with corticosteroids resulted in microbiome enrichment for a number of bacterial communities, mostly members of the Proteobacteria phylum, whereas prolonged suppression of microbiota was seen in those treated with antibiotics alone. Taken together, our findings suggest that exacerbations of COPD are associated with heterogeneous changes in the bronchial microbiome, with increases in the abundance of species
Eisner, Mark D.; Blanc, Paul D.; Omachi, Theodore A.; Yelin, Edward H.; Sidney, Stephen; Katz, Patricia P.; Ackerson, Lynn M.; Sanchez, Gabriela; Tolstykh, Irina; Iribarren, Carlos
Background Although COPD is a common cause of death and disability, little is known about the effects of socioeconomic status (SES) and race-ethnicity on health outcomes. Methods We aimed to determine the independent impacts of SES and race-ethnicity on COPD severity status, functional limitations, and acute exacerbations of COPD among patients with access to health care. Data were used from the FLOW cohort study of 1,202 Kaiser Permanente Northern California Medical Care Plan members with COPD. Results Lower educational attainment and household income were consistently related to greater disease severity, poorer lung function, and greater physical functional limitations in cross-sectional analysis. Black race was associated with greater COPD severity, but these differences were no longer apparent after controlling for SES variables and other covariates (comorbidities, smoking, body mass index, and occupational exposures). Both lower education and income were independently related to a greater prospective risk of acute COPD exacerbation (HR 1.5; 95% CI 1.01 to 2.1; and HR 2.1; 95% CI 1.4 to 3.4, respectively). Conclusion Low SES is a risk factor for a broad array of adverse COPD health outcomes. Clinicians and disease management programs should consider SES as a key patient-level marker of risk for poor outcomes. PMID:19854747
Long, Yanjun; Zhen, Xin; Zhu, Fengxin; Hu, Zheng; Lei, Wenjing; Li, Shuang; Zha, Yan; Nie, Jing
Hyperhomocysteinemia (HHcy) has been linked to several clinical manifestations including chronic kidney disease. However, it is not known whether HHcy has a role in the development of acute kidney injury (AKI). In the present study, we reported that HHcy mice developed more severe renal injury after cisplatin injection and ischemia-reperfusion injury shown as more severe renal tubular damage and higher serum creatinine. In response to cisplatin, HHcy mice showed more prevalent tubular cell apoptosis and decreased tubular cell proliferation. Mechanistically, a heightened ER stress and a reduced Akt activity were observed in kidney tissues of HHcy mice after cisplatin injection. Stimulating cultured NRK-52E cells with Hcy significantly increased the fraction of cells in G2/M phase and cell apoptosis together with decreased Akt kinase activity. Akt agonist IGF-1 rescued HHcy-induced cell cycle arrest and cell apoptosis. In conclusion, the present study provides evidence that HHcy increases the sensitivity and severity of AKI. PMID:28255274
Wen, Zongmei; Liu, Yan; Li, Feng; Ren, Feng; Chen, Dexi; Li, Xiuhui; Wen, Tao
Circulating histones are a newly recognized mediator implicated in various inflammatory diseases. It is likely that the release of histones, from dying hepatocytes or inflammatory leukocytes, into the circulation initiates and amplifies inflammation during the course of acute liver failure (ALF). In this study, we investigated a putative pathogenic role of circulating histones in a murine model of ALF induced by D-galactosamine (GalN) plus lipopolysaccharide (LPS). Hepatic function and histological indexes, myeloperoxidase (MPO) activity, hepatocyte apoptosis and the levels of circulating histone were measured in GalN/LPS-treated mice. GalN/LPS caused severe liver damage and a notable increase in plasma concentration of circulating histones. To further assess the role of circulating histones in our model, we administered exogenous histones and anti-histone H4 antibody. Notably, exogenous histones aggravated GalN/LPS-induced hepatotoxicity, whereas anti-histone antibody significantly protected mice. Circulating histones may serve as both a functional marker of ALF activity and as an inflammatory mediator contributing to the progression of ALF. Blockade of circulating histones shows potent protective effects, suggesting a potential therapeutic strategy for ALF.
Lee, Sang-Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Li, Jin; Latoche, Joseph D.; Peck Palmer, Octavia M.; Stolz, Donna Beer; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.
Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury. PMID:23275622
Muirhead, Corinne A.; Sanford, Jillian N.; McCullar, Benjamin G.; Nolt, Dawn; MacDonald, Kelvin D.
Cystic fibrosis (CF) is a chronic disorder characterized by acute pulmonary exacerbations that comprise increased cough, chest congestion, increased mucus production, shortness of breath, weight loss, and fatigue. Typically, severe episodes are treated in the inpatient setting and include intravenous antimicrobials, airway clearance therapy, and nutritional support. Children with less-severe findings can often be managed as outpatients with oral antimicrobials and increased airway clearance therapy at home without visiting the specialty CF center to begin treatment. Selection of specific antimicrobial agents is dependent on pathogens found in surveillance culture, activity of an agent in patients with CF, and the unique physiology of these patients. In this pediatric review, we present our practice for defining acute pulmonary exacerbation, deciding treatment location, initiating treatment either in-person or remotely, determining the frequency of airway clearance, selecting antimicrobial therapy, recommending timing for follow-up visit, and recognizing and managing treatment failures. PMID:27429564
Seo, Yu Bin; Choi, Won Suk; Baek, Ji Hyeon; Lee, Jacob; Song, Joon Young; Lee, Jin Soo; Cheong, Hee Jin; Kim, Woo Joo
There is a lack of targeted studies to validate the effectiveness of influenza vaccination on the reduction in influenza-related hospitalizations among patients with co-morbidities. In this study, we estimate the effectiveness of influenza vaccination on preventing hospitalizations in persons with cardiopulmonary disease and establish an evidence base for recommendations on influenza vaccination in this population. During the influenza epidemic in 2011-2012, we performed a multicenter, retrospective case-control study. Cases were patients hospitalized due to acute exacerbation of asthma, COPD, ischemic heart disease (IHD), and congestive heart failure (CHF). Controls were selected from outpatients who visited study hospitals but who were not hospitalized. Cases and controls were matched 1:1 based on age, gender, and date of hospital visit. Conditional logistic regression analyses were used to determine the effectiveness of vaccination. Between 25 December 2011 and 5 May 2012, 828 of each hospitalized and control subjects were identified. The influenza vaccination rate of the hospitalized and non-hospitalized patients was 54.2% and 60.4%, respectively (P = 0.006). The overall vaccine effectiveness for preventing hospitalization was 33.7% (95% confidence interval [CI] 14.0-49.0%; P = 0.002). Conditional logistic regression analysis showed that influenza vaccination significantly reduced the risk of hospitalization, especially due to acute exacerbation of IHD and CHF, in patients aged 65 y and older. The estimated vaccine effectiveness in these patients was 56.0% (95% CI 32.1-71.4%, P = 0.002). Influenza vaccination was associated with a reduction in the risk of hospitalization due to acute exacerbation of cardiopulmonary disease. We recommend the vaccine be given primarily to patients with underlying cardiovascular disease, particularly those 65 y of age and older.
Aydemir, Yusuf; Aydemir, Özlem; Kalem, Fatma
Background Acute exacerbations, which are a significant cause of mortality and morbidity, adversely affect chronic obstructive pulmonary disease (COPD) prognosis by accelerating loss of lung function. It is important to know the microorganisms that commonly cause exacerbations in the patient groups classified according to clinical and functional characteristics for fast and accurate treatment of acute exacerbations. Objectives The last Global Initiative for Chronic Obstructive Lung Disease (GOLD) publication recommended a new staging system containing obstruction degree, frequency of exacerbations, and quality of life questionnaires. This study is designed to analyze the relationship between the bacteria isolated in acute exacerbations and new GOLD stages. Methods Potentially pathogenic bacteria (PPB) isolation with culture and polymerase chain reaction methods were obtained from 114 acute exacerbation COPD patients, classified into A, B, C, and D groups by analyzing the forced expiratory volume in 1 second (FEV1) value, COPD Assessment Test (CAT) score, and exacerbation frequency according to the new GOLD staging system. Results There was a significant correlation between exacerbation frequency and PPB isolation (P=0.002). There was no relationship between GOLD stage, FEV1, and CAT score with PPB isolation. The isolated bacteria diversity and mixed infection frequency were higher in the GOLD stage D group. Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii were isolated only from D group patients. Conclusion Bacterial infection may cause an acute exacerbation equally in each stage for COPD. The difference in bacterial etiology is more related to exacerbation frequency than FEV1 and CAT scores for an acute exacerbation. Determining exacerbation frequency is significant for treatment success in empirical antibiotic selection. PMID:25298733
López-Campos, Jose Luis; Hartl, Sylvia; Pozo-Rodriguez, Francisco; Roberts, C Michael
Studies have suggested that larger hospitals have better resources and provide better care than smaller ones. This study aimed to explore the relationship between hospital size, resources, organisation of care and adherence to guidelines. The European COPD Audit was designed as a pilot study of clinical care and a survey of resources and organisation of care. Data were entered by clinicians to a multilingual web tool and analysed centrally. Participating hospitals were divided into tertiles on the basis of bed numbers and comparisons made of the resources, organisation of care and adherence to guidelines across the three size groups. 13 national societies provided data on 425 hospitals. The mean number of beds per tertile was 220 (lower), 479 (middle), and 989 (upper). Large hospitals were more likely to have resources and increased numbers of staff; hospital performance measures were related in a minority of indicators only. Adherence to guidelines also varied with hospital size, but the differences were small and inconsistent. There is a wide variation in the size, resources and organisation of care across Europe for hospitals providing chronic obstructive pulmonary disease care. While larger hospitals have more resources, this does not always equate to better accessibility or quality of care for patients.
Guerin, Coralie L; Blandinières, Adeline; Planquette, Benjamin; Silvestre, Jean-Sébastien; Israel-Biet, Dominique; Sanchez, Olivier; Smadja, David M
Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells involved in vascular and tissue regeneration and constitute a recruitable pool of stem/progenitor cells with putative instrumental role in organ repair. Here, we hypothesized that VSELs might be mobilized from the bone marrow (BM) to peripheral blood (PB) in patients with hypoxic lung disease or pulmonary hypertension (PH). The objective of the present study was then to investigate the changes in VSELs number in peripheral blood of patients with hypoxic lung disease and PH. We enrolled 26 patients with Chronic Obstructive Pulmonary Disease (COPD) with or without hypoxemia, 13 patients with PH and 20 controls without any respiratory or cardiovascular diseases. In PH patients, VSELs levels have been determined during right heart catheterization in pulmonary blood and PB. For this purpose, mononuclear cells were separated by density gradient and VSELs have been quantified by using a multiparametric flow cytometry approach. The number of PB-VSELs in hypoxic COPD patients was significantly increased compared with non-hypoxic COPD patients or controls (p = 0.0055). In patients with PH, we did not find any difference in VSELs numbers between arterial pulmonary blood and venous PB (p = 0.93). However, we found an increase in VSELs in the peripheral blood of patients with PH (p = 0.03). In conclusion, we unraveled that circulating VSELs were increased in peripheral blood of patients with hypoxic COPD or with PH. Thus, VSELs may serve as a reservoir of pluripotent stem cells that can be recruited into PB and may play an important role in promoting lung repair.
Lee, Byunghyuk; Ko, Eunhee; Lee, Jiyeon; Jo, Yuna; Hwang, Hyunju; Goh, Tae Sik; Joo, Myungsoo; Hong, Changwan
Cigarette smoking (CS) is a major cause of considerable morbidity and mortality by inducing lung cancer and COPD. COPD, a smoking-related disorder, is closely related to the alteration of immune system and inflammatory processes that are specifically mediated by T cells. Soluble common gamma chain (sγc) has recently been identified as a critical regulator of the development and differentiation of T cells. We examined the effects of sγc in a cigarette smoke extract (CSE) mouse model. The sγc level in CSE mice serum is significantly downregulated, and the cellularity of lymph node (LN) is systemically reduced in the CSE group. Overexpression of sγc enhances the cellularity and IFNγ production of CD8 T cells in LN and also enhances Th1 and Th17 differentiation of CD4 T cells in the respiratory tract. Mechanistically, the downregulation of sγc expression mediated by CSE is required to prevent excessive inflammatory T cell responses. Therefore, our data suggest that sγc may be one of the target molecules for the control of immunopathogenic progresses in COPD. PMID:28331303
COPD is not a homogenous disease but consists of at least four different phenotypes: Emphysema, COPD with chronic bronchitis, asthma-COPD overlap syndrome (ACOS), and COPD with recurrent exacerbations. With differentiation, treatment can be designed phenotype-specific. Some modern drugs are not indicated in all phenotypes.
Lee, Jung Su; Rhee, Chin Kook; Yoo, Kwang Ha; Lee, Ji-Hyun; Yoon, Ho Il; Kim, Tae-Hyung; Kim, Woo Jin; Lee, JinHwa; Lim, Seong Yong; Park, Tai Sun; Lee, Jae Seung; Lee, Sei Won; Lee, Sang-Do; Oh, Yeon-Mok
The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.
Hu, Guoping; Wu, Yankui; Zhou, Yumin; Wu, Zelong; Wei, Liping; Li, Yuqun; Peng, GongYong; Liang, Weiqiang; Ran, Pixin
Background and objective Serum D-dimer is elevated in respiratory disease. The objective of our study was to investigate the effect of D-dimer on in-hospital and 1-year mortality after acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods Upon admission, we measured 343 AECOPD patients’ serum D-dimer levels and arterial blood gas analysis, and recorded their clinical characteristics. The level of D-dimer that discriminated survivors and non-survivors was determined using a receiver operator curve (ROC). The risk factors for in-hospital mortality were identified through univariate analysis and multiple logistic regression analyses. To evaluate the predictive role of D-dimer for 1-year mortality, univariate and multivariate Cox regression analyses were performed. Results In all, 28 patients died, and 315 patients survived in the in-hospital period. The group of dead patients had lower pH levels (7.35±0.11 vs 7.39±0.05, P<0.0001), higher D-dimer, arterial carbon dioxide tension (PaCO2), C-reactive protein (CRP), and blood urea nitrogen (BUN) levels (D-dimer 2,244.9±2,310.7 vs 768.2±1,078.4 µg/L, P<0.0001; PaCO2: 58.8±29.7 vs 46.1±27.0 mmHg, P=0.018; CRP: 81.5±66, P=0.001; BUN: 10.20±6.87 vs 6.15±3.15 mmol/L, P<0.0001), and lower hemoglobin levels (118.6±29.4 vs 128.3±18.2 g/L, P=0.001). The areas under the ROC curves of D-dimer for in-hospital death were 0.748 (95% confidence interval (CI): 0.641–0.854). D-dimer ≥985 ng/L was a risk factor for in-hospital mortality (relative risk =6.51; 95% CI 3.06–13.83). Multivariate logistic regression analysis also showed that D-dimer ≥985 ng/L and heart failure were independent risk factors for in-hospital mortality. Both univariate and multivariate Cox regression analyses showed that D-dimer ≥985 ng/L was an independent risk factor for 1-year death (hazard ratio (HR) 3.48, 95% CI 2.07–5.85 for the univariate analysis; and HR 1.96, 95% CI 1.05–3.65 for the multivariate analysis
Bettoncelli, G; Blasi, F; Brusasco, V; Centanni, S; Corrado, A; De Benedetto, F; De Michele, F; Di Maria, G U; Donner, C F; Falcone, F; Mereu, C; Nardini, S; Pasqua, F; Polverino, M; Rossi, A; Sanguinetti, C M
COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60%predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2<88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal
Mohan, Anant; Arora, Sneh; Uniyal, Arvind; Poulose, Rosemary; Luthra, Kalpana; Pandey, RM; Guleria, Randeep
Background: Inflammatory and nutritional biomarkers have an important bearing on outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but the temporal profile of these compounds during an acute episode is unclear. Patients and Methods: Plasma leptin, prealbumin, and tumor necrosis factor-alpha (TNF-α) were estimated at baseline and before hospital discharge in patients with AECOPD. Results: A total of 82 patients were evaluated (66 males; mean (standard deviation) age, 61.6 (10.1) years. Of these, 74 subjects (90.2%) were current or former smokers, with median (range) pack-years of 15 (0–96), duration of COPD of 8 years (range, 2–25 years) and duration of current symptoms being 5 days (range, 1–30 days). Majority (41.5%) had type I (severe) exacerbation. During the current episode, 46 patients (58.9%) required mechanical ventilation for a median of 6 days (range, 1–34). The median duration of hospital stay was 13 days, (range, 1–110). At discharge, significant reduction was observed in dyspnea, total leukocyte count, erythrocyte sedimentation rate (ESR), partial pressure of carbon dioxide, hemoglobin, urea, creatinine, potassium, aspartate transferase, and TNF-α levels compared to baseline, whereas arterial pH, PO2, serum albumin, prealbumin, and leptin significantly improved. No difference was seen in leptin, prealbumin, and TNF-α between patients with mild/moderate and severe exacerbation, or between patients who required or did not require mechanical ventilation. Change in leptin correlated with body mass index and change in ESR; no associations were observed between leptin, prealbumin, and TNF-α with other clinico-laboratory variables. Conclusion: Plasma levels of novel inflammatory and nutritional biomarkers, i.e., leptin, TNF-α, and prealbumin are altered in AECOPD episodes and lag behind other parameters during recovery. These biomarkers are not reliable predictors of clinical outcomes in these patients. PMID
Medina-Mirapeix, Francesc; Bernabeu-Mora, Roberto; García-Guillamón, Gloria; Valera Novella, Elisa; Gacto-Sánchez, Mariano; García-Vidal, José Antonio
Background Hospitalization for acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) is common, but little is known about the impact of hospitalization on the development of disability. The purpose of this study was to determine the rate and time course of functional changes 3 months after hospital discharge for AE-COPD compared with baseline levels 2 weeks before admission, and to identify predictors of functional decline. Methods This was a prospective study including 103 patients (age mean, 71 years; standard deviation, 9.1 years) who were hospitalized with AE-COPD. Number of dependencies in Activities of Daily Living (ADLs) was measured at the preadmission baseline and at weeks 6 and 12 after discharge. Patterns of improvement, no change, and decline were defined over 3 consecutive intervals (baseline and weeks 6 and 12). Trajectories grouped patients with similar time courses of disability. Recovery was defined as returning to baseline function after functional decline. Univariate and multivariate multiple logistic regression was used to determine predictors of functional decline after week 12. Results Six trajectories of functional changes were found. From baseline to 12 weeks, 50% of patients continued to have the same function whereas 31% experienced functional decline after 6 weeks; 16.7% recovered over subsequent weeks. At week 12, as a consequence of all trajectories, 38% of patients showed functional declines compared with baseline function, 57% had not declined, and 6 improved. Length of stay (odds ratio [OR] = 1.12;95% [confidence interval] CI 1.03–1.22), dyspnea (OR = 1.85; 95% CI 1.05–3.26), and frailty (OR = 3.97; 95% CI 1.13–13.92) were independent predictors of functional decline after 12 weeks. Conclusions Hospitalization for AE-COPD is a risk factor for the progression of disability. More than one third of patients hospitalized for AE-COPD declined during the 12 weeks following discharge, with most of this decline
α1,6-Fucosyltransferase (Fut8) is implicated in vulnerability to elastase-induced emphysema in mice and a possible non-invasive predictive marker for disease progression and exacerbations in chronic obstructive pulmonary disease (COPD).
Kamio, Koichiro; Yoshida, Takayuki; Gao, Congxiao; Ishii, Takeo; Ota, Fumi; Motegi, Takashi; Kobayashi, Satoshi; Fujinawa, Reiko; Ohtsubo, Kazuaki; Kitazume, Shinobu; Angata, Takashi; Azuma, Arata; Gemma, Akihiko; Nishimura, Masaharu; Betsuyaku, Tomoko; Kida, Kozui; Taniguchi, Naoyuki
Fut8 (α1,6-Fucosyltransferase) heterozygous knock-out (Fut8(+/-)) mice had an increased influx of inflammatory cells into the lungs, and this was associated with an up-regulation of matrix metalloproteinases, MMP-2 and MMP-9, after treatment with porcine pancreatic elastase (PPE), exhibiting an emphysema-prone phenotype as compared with wild type mice (Fut8(+/+)). The present data as well as our previous data on cigarette-smoke-induced emphysema  led us to hypothesize that reduced Fut8 levels leads to COPD with increased inflammatory response in humans and is associated with disease progression. To test this hypothesis, symptomatic current or ex-smokers with stable COPD or at risk outpatients were recruited. We investigated the association between serum Fut8 activity and disease severity, including the extent of emphysema (percentage of low-attenuation area; LAA%), airflow limitation, and the annual rate of decline in forced expiratory volume in 1 s (FEV(1)). Association with the exacerbation of COPD was also evaluated over a 3-year period. Serum Fut8 and MMP-9 activity were measured. Fut8 activity significantly increased with age among the at risk patients. In the case of COPD patients, however, the association was not clearly observed. A faster annual decline of FEV(1) was significantly associated with lower Fut8 activity. Patients with lower Fut8 activity experienced exacerbations more frequently. These data suggest that reduced Fut8 activity is associated with the progression of COPD and serum Fut8 activity is a non-invasive predictive biomarker candidate for progression and exacerbation of COPD.
Huang, Yvonne J.; Kim, Eugenia; Cox, Michael J.; Brodie, Eoin L.; Brown, Ron; Wiener-Kronish, Jeanine P.
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
Huang, Yvonne J; Kim, Eugenia; Cox, Michael J; Brodie, Eoin L; Brown, Ron; Wiener-Kronish, Jeanine P; Lynch, Susan V
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.
Quan-Jun, Yang; Jian-Ping, Zhang; Jian-Hua, Zhang; Yong-Long, Han; Bo, Xin; Jing-Xian, Zhang; Bona, Dai; Yuan, Zhang; Cheng, Guo
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
Yalcinsoy, Murat; Salturk, Cuneyt; Oztas, Selahattin; Gungor, Sinem; Ozmen, Ipek; Kabadayi, Feyyaz; Oztim, Aysem Askim; Aksoy, Emine; Adıguzel, Nalan; Oruc, Ozlem; Karakurt, Zuhal
Purpose Noninvasive mechanical ventilation (NIMV) usage outside of intensive care unit is not recommended in patients with COPD for severe acute respiratory failure (ARF). We assessed the factors associated with failure of NIMV in patients with ARF and severe acidosis admitted to the emergency department and followed on respiratory ward. Patients and methods This is a retrospective observational cohort study conducted in a tertiary teaching hospital specialized in chest diseases and thoracic surgery between June 1, 2013 and May 31, 2014. COPD patients who were admitted to our emergency department due to ARF were included. Patients were grouped according to the severity of acidosis into two groups: group 1 (pH=7.20–7.25) and group 2 (pH=7.26–7.30). Results Group 1 included 59 patients (mean age: 70±10 years, 30.5% female) and group 2 included 171 patients (mean age: 67±11 years, 28.7% female). On multivariable analysis, partial arterial oxygen pressure to the inspired fractionated oxygen (PaO2/FiO2) ratio <200, delta pH value <0.30, and pH value <7.31 on control arterial blood gas after NIMV in the emergency room and peak C-reactive protein were found to be the risk factors for NIMV failure in COPD patients with ARF in the ward. Conclusion NIMV is effective not only in mild respiratory failure but also with severe forms of COPD patients presenting with severe exacerbation. The determination of the failure criteria of NIMV and the expertise of the team is critical for treatment success. PMID:27330283
Schikowski, Tamara; Mills, Inga C; Anderson, H Ross; Cohen, Aaron; Hansell, Anna; Kauffmann, Francine; Krämer, Ursula; Marcon, Alessandro; Perez, Laura; Sunyer, Jordi; Probst-Hensch, Nicole; Künzli, Nino
The role of ambient air pollution in the development of chronic obstructive pulmonary disease (COPD) is considered to be uncertain. We review the evidence in the light of recent studies. Eight morbidity and six mortality studies were identified. These were heterogeneous in design, characterisation of exposure to air pollution and methods of outcome definition. Six morbidity studies with objectively defined COPD (forced expiratory volume in 1 s/forced vital capacity ratio) were cross-sectional analyses. One longitudinal study defined incidence of COPD as the first hospitalisation due to COPD. However, neither mortality nor hospitalisation studies can unambiguously distinguish acute from long-term effects on the development of the underlying pathophysiological changes. Most studies were based on within-community exposure contrasts, which mainly assess traffic-related air pollution. Overall, evidence of chronic effects of air pollution on the prevalence and incidence of COPD among adults was suggestive but not conclusive, despite plausible biological mechanisms and good evidence that air pollution affects lung development in childhood and triggers exacerbations in COPD patients. To fully integrate this evidence in the assessment, the life-time course of COPD should be better defined. Larger studies with longer follow-up periods, specific definitions of COPD phenotypes, and more refined and source-specific exposure assessments are needed.
Huang, Yvonne J; Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A; Lynch, Susan V
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.
Soo, Yien Yien; FitzGerald, Kate Helen; Saini, Bandana; Kritikos, Vicky; Brannan, John D; Moles, Rebekah Jane
OBJECTIVE 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. METHODS 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 three weeks post the education session which involved feedback on each individual's skills and a brief lecture on asthma delivered via PowerPoint presentation. RESULTS 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. CONCLUSIONS 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.
Hou, Peng; Deng, Huaifu; Wu, Zhida; Liu, Haiping; Liu, Ni
Background The aim of this prospective study was to assess the utility of radionuclide salivagram for detecting salivary aspiration in AECOPD patients and to evaluate the adding value of SPECT/CT to planar imaging. Methods 52 consecutive AECOPD patients underwent radionuclide salivagram SPECT/CT and water swallow test between April 2012 and March 2014. All images were interpreted independently by two experienced nuclear medicine physicians. Final diagnosis was made by consensus of two readers. The radionuclide salivagram and water swallow test results were compared using kappa values. The relationship between radionuclide salivagram results and exacerbation frequency was evaluated with the Person χ2 test. Results Salivary aspiration was diagnosed by radionuclide salivagram in 17 of 52 patients. Aspiration into the right main bronchus and branch was seen in 8 patients, bilateral main bronchi in 6 patients, and left lung field in 3 patients. SPECT/CT provided more accurate information on the extent and location of salivary aspiration, in 11 cases, SPECT/CT demonstrated aspiration of pulmonary segment bronchus and the following areas. Moreover, SPECT/CT revealed salivary aspiration corresponding to aspiration pneumonia in 8 cases. There was general agreement between the radionuclide salivagram and water swallow test results (Kappa =0.712; 95% CI, 0.504–0.920; P<0.001). The incidence of frequent exacerbations was greater among subjects with positive salivagram than among those with negative salivagram results (RR =3.43; 95% CI, 1.90–6.19; P<0.001). Conclusions Radionuclide salivagram is an objective method for detecting salivary aspiration in AECOPD patients. Moreover, SPECT/CT can identify more precise location of salivary aspiration and suggest a possible role for saliva in the pathophysiology of aspiration pneumonia. PMID:27867548
Pothirat, Chaicharn; Liwsrisakun, Chalerm; Bumroongkit, Chaiwat; Deesomchok, Athavudh; Theerakittikul, Theerakorn; Limsukon, Atikun
Background Care for many chronic health conditions is delivered by both specialists and generalists. Differences in patients’ quality of care and management between generalists and specialists have been well documented for asthma, whereas a few studies for COPD reported no differences. Objective The objective of this study is to compare consistency with Global initiative for chronic Obstructive Lung Disease guidelines, as well as rate, health care utilization, and hospital outcomes of severe acute exacerbation (AE) of COPD patients managed by pulmonologists and internists. Materials and methods This is a 12-month prospective, comparative observational study among 208 COPD patients who were regularly managed by pulmonologists (Group A) and internists (Group B). Clinical data, health care utilization, and hospital outcomes of the two groups were statistically compared. Results Out of 208 enrolled patients, 137 (Group A) and 71 (Group B) were managed by pulmonologists and internists, respectively. Pharmacological treatment corresponding to disease severity stages between the two groups was not statistically different. Group A received care consistent with guidelines in terms of annual influenza vaccination (31.4% vs 9.9%, P<0.001) and pulmonary rehabilitation (24.1% vs 0%, P<0.001) greater than Group B. Group A had reduced rates (12.4% vs 23.9%, P=0.033) and numbers of severe AE (0.20±0.63 person-years vs 0.41±0.80 person-years, P=0.029). Among patients with severe AE requiring mechanical ventilation, Group A had reduced mechanical ventilator duration (1.5 [1–7] days vs 5 [3–29] days, P=0.005), hospital length of stay (3.5 [1–20] days vs 16 [6–29] days, P=0.012), and total hospital cost ($863 [247–2,496] vs $2,095 [763–6,792], P=0.049) as compared with Group B. Conclusion This study demonstrated that pulmonologists followed national COPD guidelines more closely than internists. The rates and frequencies of severe AE were significantly lower in patients
Toy, Edmond L; Gallagher, Kevin F; Stanley, Elizabeth L; Swensen, Andrine R; Duh, Mei Sheng
Chronic obstructive pulmonary disease (COPD) poses a significant economic burden on society, and a substantial portion is related to exacerbations of COPD. A literature review of the direct and indirect costs of COPD exacerbations was performed. A systematic search of the MEDLINE database from 1998-2008 was conducted and supplemented with searches of conference abstracts and article bibliographies. Articles that contained cost data related to COPD exacerbations were selected for in-depth review. Eleven studies examining healthcare costs associated with COPD exacerbations were identified. The estimated costs of exacerbations vary widely across studies: $88 to $7,757 per exacerbation (2007 US dollars). The largest component of the total costs of COPD exacerbations was typically hospitalization. Costs were highly correlated with exacerbation severity. Indirect costs have rarely been measured. The wide variability in the cost estimates reflected cross-study differences in geographic locations, treatment patterns, and patient populations. Important methodological differences also existed across studies. Researchers have used different definitions of exacerbation (e.g., symptom- versus event-based definitions), different tools to identify and measure exacerbations, and different classification systems to define exacerbation severity. Unreported exacerbations are common and may influence the long-term costs of exacerbations. Measurement of indirect costs will provide a more comprehensive picture of the burden of exacerbations. Evaluation of pharmacoeconomic analyses would be aided by the use of more consistent and comprehensive approaches to defining and measuring COPD exacerbations.
Tunsäter, Alf; Moutakis, Mikael; Borg, Sixten; Persson, Ulf; Strömberg, Leif; Nielsen, Anders Lassen
This paper reports on a retrospective analysis of hospital-based healthcare costs associated with the management of chronic obstructive pulmonary disease (COPD). During the second half of 2001, Simrishamn Hospital, Sweden, implemented a structured Disease Management Programme (DMP) for COPD and a total of 784 patients with COPD, enrolled in the DMP, were included in the analysis. The goal was to reduce the number of clinical events, such as severe exacerbations by early intervention, aggressive drug treatment, specialists easy available for advice, improved support for smoking cessation, increased number of scheduled follow-ups and closer tracking of high-risk COPD patients. The hospital administrative system provided data on resource consumption, such as outpatient care, inpatient care and drugs and unit cost, used in the economic analysis. The total cost of COPD drugs doubled (from euro 14,133 to euro 30,855 per year) as did the total number of outpatient visits (from 580 to 996 visits per year). The number of hospitalizations for acute COPD exacerbations and COPD with acute lower respiratory infection decreased from 67 to 25 per year. Total COPD-related healthcare costs decreased. The results presented here support the hypothesis that a COPD DMP can offer substantial overall direct cost savings.
Current primary care patterns for chronic obstructive pulmonary disease (COPD) focus on reactive care for acute exacerbations, often neglecting ongoing COPD management to the detriment of patient experience and outcomes. Proactive diagnosis and ongoing multifactorial COPD management, comprising smoking cessation, influenza and pneumonia vaccinations, pulmonary rehabilitation, and symptomatic and maintenance pharmacotherapy according to severity, can significantly improve a patient's health-related quality of life, reduce exacerbations and their consequences, and alleviate the functional, utilization, and financial burden of COPD. Redesign of primary care according to principles of the chronic care model, which is implemented in the patient-centered medical home, can shift COPD management from acute rescue to proactive maintenance. The chronic care model and patient-centered medical home combine delivery system redesign, clinical information systems, decision support, and self-management support within a practice, linked with health care organization and community resources beyond the practice. COPD care programs implementing two or more chronic care model components effectively reduce emergency room and inpatient utilization. This review guides primary care practices in improving COPD care workflows, highlighting the contributions of multidisciplinary collaborative team care, care coordination, and patient engagement. Each primary care practice can devise a COPD care workflow addressing risk awareness, spirometric diagnosis, guideline-based treatment and rehabilitation, and self-management support, to improve patient outcomes in COPD.
Katz, Patricia P.; Yelin, Edward H.; Iribarren, Carlos; Knight, Sara J.; Blanc, Paul D.; Eisner, Mark D.
Background: Psychologic factors affect how patients with COPD respond to attempts to improve their self-management skills. Learned helplessness may be one such factor, but there is no validated measure of helplessness in COPD. Methods: We administered a new COPD Helplessness Index (CHI) to 1,202 patients with COPD. Concurrent validity was assessed through association of the CHI with established psychosocial measures and COPD severity. The association of helplessness with incident COPD exacerbations was then examined by following subjects over a median 2.1 years, defining COPD exacerbations as COPD-related hospitalizations or ED visits. Results: The CHI demonstrated internal consistency (Cronbach α = 0.75); factor analysis was consistent with the CHI representing a single construct. Greater CHI-measured helplessness correlated with greater COPD severity assessed by the BODE (Body-mass, Obstruction, Dyspnea, Exercise) Index (r = 0.34; P < .001). Higher CHI scores were associated with worse generic (Short Form-12, Physical Component Summary Score) and respiratory-specific (Airways Questionnaire 20) health-related quality of life, greater depressive symptoms, and higher anxiety (all P < .001). Controlling for sociodemographics and smoking status, helplessness was prospectively associated with incident COPD exacerbations (hazard ratio = 1.31; P < .001). After also controlling for the BODE Index, helplessness remained predictive of COPD exacerbations among subjects with BODE Index ≤ median (hazard ratio = 1.35; P = .01), but not among subjects with higher BODE Index values (hazard ratio = 0.93; P = .34). Conclusions: The CHI is an internally consistent and valid measure, concurrently associated with health status and predictively associated with COPD exacerbations. The CHI may prove a useful tool in analyzing differential clinical responses mediated by patient-centered attributes. PMID:19837823
Dotson, Kurtis; Dallman, Michael; Bowman, C Michael; Titus, M Olivia
Since the 1970s, when inhaled anticholinergic agents were first introduced as adjunct therapies for the immediate treatment of pediatric asthma exacerbations, several trials have shown varying degrees of benefit from their use as bronchodilators in combination with inhaled short-acting beta-adrenergic agonists and systemic corticosteroids. Although other anticholinergics exist, ipratropium bromide (IB) specifically has emerged as the overwhelming choice of pulmonologists and emergency physicians because of its limited systemic absorption from the lungs when given as an inhaled preparation. However, although the varying trials, predominantly in the emergency department setting, have typically shown a trend toward improved outcomes, none has set forth clear dosing protocol recommendations for use by practicing physicians. It is our goal in this review of the available literature on the use of IB, as an adjunct to inhaled short-acting beta-adrenergic agonists, to summarize practical, evidence-based recommendations for use in the pediatric emergency department setting for acute asthma exacerbations. We also hope to better delineate the most effective dosing regimen in those patients who might benefit most from the addition of IB and to explore proposed additional benefits it may have as a modulator of cholinergic-induced effects from high-dose beta-agonist therapy and viral triggers.
Duan, Yanhong; Zhou, Min; Xiao, Jian; Wu, Chaomin; Zhou, Lei; Zhou, Feng; Du, Chunling; Song, Yuanlin
The present study aimed to identify genes and microRNAs (miRNAs or miRs) that were abnormally expressed in the vastus lateralis muscle of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The gene expression profile of GSE10828 was downloaded from the Gene Expression Omnibus database, and this dataset was comprised of 4 samples from patients with AECOPD and 5 samples from patients with stable COPD. Differentially expressed genes (DEGs) were screened using the Limma package in R. A protein-protein interaction (PPI) network of DEGs was built based on the STRING database. Module analysis of the PPI network was performed using the ClusterONE plugin and functional analysis of DEGs was conducted using DAVID. Additionally, key miRNAs were enriched using gene set enrichment analysis (GSEA) software and a miR-gene regulatory network was constructed using Cytoscape software. In total, 166 up- and 129 downregulated DEGs associated with muscle weakness in AECOPD were screened. Among them, NCL, GOT1, TMOD1, TSPO, SOD2, NCL and PA2G4 were observed in the modules consisting of upregulated or downregulated genes. The upregulated DEGs in modules (including KLF6 and XRCC5) were enriched in GO terms associated with immune system development, whereas the downregulated DEGs were enriched in GO terms associated with cell death and muscle contraction. Additionally, 39 key AECOPD-related miRNAs were also predicted, including miR-1, miR-9 and miR-23a, miR-16 and miR-15a. In conclusion, DEGs (NCL, GOT1, SOD2, KLF6, XRCC5, TSPO and TMOD1) and miRNAs (such as miR-1, miR-9 and miR-23a) may be associated with the loss of muscle force in patients during an acute exacerbation of COPD which also may act as therapeutic targets in the treatment of AECOPD. PMID:28025995
Li, Xiang-Nan; Pan, Xue; Qiu, Dong
The typical balance between Th17 and Treg T cell subsets is altered in various autoimmune diseases. Here, inflammatory markers in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) (n=32) and stable COPD (n=36) were compared with smokers with normal lung function (n=40, control group). Flow cytometry was used to detect proportions of Th17 and Treg cells in the peripheral blood. ELISA of induced sputum samples was used to detect IL-17 (secreted by Th17 cells) and TGF-β1 (secreted by Treg cells) concentrations. The proportion of Th17 cells in peripheral blood and secreted IL-17 and TGF-β1 levels in sputum were significantly higher in acute exacerbation of COPD patients than in stable COPD and control groups (P < 0.05). Additionally, the proportion of Treg cells was lower than in stable COPD but higher than in controls. Th17 proportions were negatively correlated with Treg proportions in both acute exacerbation and stable COPD patients, and positively correlated with IL-17 levels (P < 0.05). Further, there was a positive correlation between Treg proportion and TGF-β1 levels (P < 0.05). Thus, COPD patients have shifts in the balance of Th17/Treg cells. Acute exacerbation of COPD is shifted toward a pro-inflammatory response, while stable COPD is shifted toward an anti-inflammatory response. This finding may provide a new direction for future clinical treatment of COPD by seeking to repair the disrupted balance in T cells.
Li, Xiang-Nan; Pan, Xue; Qiu, Dong
The typical balance between Th17 and Treg T cell subsets is altered in various autoimmune diseases. Here, inflammatory markers in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) (n=32) and stable COPD (n=36) were compared with smokers with normal lung function (n=40, control group). Flow cytometry was used to detect proportions of Th17 and Treg cells in the peripheral blood. ELISA of induced sputum samples was used to detect IL-17 (secreted by Th17 cells) and TGF-β1 (secreted by Treg cells) concentrations. The proportion of Th17 cells in peripheral blood and secreted IL-17 and TGF-β1 levels in sputum were significantly higher in acute exacerbation of COPD patients than in stable COPD and control groups (P < 0.05). Additionally, the proportion of Treg cells was lower than in stable COPD but higher than in controls. Th17 proportions were negatively correlated with Treg proportions in both acute exacerbation and stable COPD patients, and positively correlated with IL-17 levels (P < 0.05). Further, there was a positive correlation between Treg proportion and TGF-β1 levels (P < 0.05). Thus, COPD patients have shifts in the balance of Th17/Treg cells. Acute exacerbation of COPD is shifted toward a pro-inflammatory response, while stable COPD is shifted toward an anti-inflammatory response. This finding may provide a new direction for future clinical treatment of COPD by seeking to repair the disrupted balance in T cells. PMID:25664038
Moya Sánchez, Elena; Medina Benítez, Antonio
We report the case of a patient with acute exacerbation of chronic pancreatitis and he suffered an atraumatic splenic rupture. Splenic rupture not associated with trauma is a rare entity that can occurs in normal spleen (spontaneous) or damaged spleen (pathological). This entity may be associated with local inflammatory processes, such as pancreatitis. Ultrasound is a non-invasive technique which is used in unstable patients. CT is useful for making a diagnosis of extension in patients with hemodynamic stability. Atraumatic splenic rupture as a complication of chronic pancreatitis is an unusual disease that requires a high index of suspicion which allows us an early diagnosis because it is a treatable entity that compromises the patient's life.
Gulati, Swati; Wells, J Michael
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with an 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 chronic obstructive pulmonary disease (COPD) and is defined as an individual who experiences two or more moderate-to-severe exacerbations per year. This distinct subgroup has higher mortality and accounts 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 using 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 including combination long-acting muscarinic agents plus long-acting beta agonists show promising results compared with monotherapy or a long-acting beta agonist inhaled corticosteroid combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase-4 inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on the identification of various subtypes or 'endotypes' and targeting therapies based on their pathophysiology. This review describes the impact of AECOPD and the challenges posed by frequent exacerbators, and explores the rationale for different
Chen, Shan-Shan; Yin, Zhao-Fang; Chen, Tao; Qiu, Hui; Wei, Ya-Ru; Du, Shan-Shan; Jin, Yue-Ping; Zhao, Meng-Meng; Wu, Qin
Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with severe pulmonary fibrosis. The main cause of IPF-associated death is acute exacerbation of IPF (AE-IPF). This study aims to develop a rat model of AE-IPF by two intratracheal perfusions with bleomycin (BLM). Methods Ninety male Sprague Dawley (SD) rats were randomized into three groups: an AE-IPF model group (BLM + BLM group), an IPF model group (BLM group), and a normal control group. Rats in the BLM + BLM group underwent a second perfusion with BLM on day 28 after the first perfusion with BLM. Rats in the other two groups received saline as the second perfusion. Six rats in each group were sacrificed on day 31, day 35, and day 42 after the first perfusion, respectively. Additional 18 rats in each group were observed for survival. Results Rats in the BLM + BLM group had significantly worse pulmonary alveolar inflammation and fibrosis than rats in the BLM group. Rats in the BLM + BLM group also developed large amounts of hyaline membrane, showed high levels of albumin (ALB) and various inflammatory factors in the bronchoalveolar lavage fluid (BALF), and had markedly increased lung water content. Furthermore, rat survival was reduced in the BLM + BLM group. The pathophysiological characteristics of rats in the BLM + BLM group resemble those of patients with AE-IPF. Conclusions A second perfusion with BLM appears to induce acute exacerbation of pulmonary fibrosis and may be used to model AE-IPF in rats. PMID:28203411
Zarepoor, Leila; Lu, Jenifer T; Zhang, Claire; Wu, Wenqing; Lepp, Dion; Robinson, Lindsay; Wanasundara, Janitha; Cui, Steve; Villeneuve, Sébastien; Fofana, Bourlaye; Tsao, Rong; Wood, Geoffrey A; Power, Krista A
Flaxseed (FS), a dietary oilseed, contains a variety of anti-inflammatory bioactives, including fermentable fiber, phenolic compounds (lignans), and the n-3 polyunsaturated fatty acid (PUFA) α-linolenic acid. The objective of this study was to determine the effects of FS and its n-3 PUFA-rich kernel or lignan- and soluble fiber-rich hull on colitis severity in a mouse model of acute colonic inflammation. C57BL/6 male mice were fed a basal diet (negative control) or a basal diet supplemented with 10% FS, 6% kernel, or 4% hull for 3 wk prior to and during colitis induction via 5 days of 2% (wt/vol) dextran sodium sulfate (DSS) in their drinking water (n = 12/group). An increase in anti-inflammatory metabolites (hepatic n-3 PUFAs, serum mammalian lignans, and cecal short-chain fatty acids) was associated with consumption of all FS-based diets, but not with anti-inflammatory effects in DSS-exposed mice. Dietary FS exacerbated DSS-induced acute colitis, as indicated by a heightened disease activity index and an increase in colonic injury and inflammatory biomarkers [histological damage, apoptosis, myeloperoxidase, inflammatory cytokines (IL-6 and IL-1β), and NF-κB signaling-related genes (Nfkb1, Ccl5, Bcl2a1a, Egfr, Relb, Birc3, and Atf1)]. Additionally, the adverse effect of the FS diet was extended systemically, as serum cytokines (IL-6, IFNγ, and IL-1β) and hepatic cholesterol levels were increased. The adverse effects of FS were not associated with alterations in fecal microbial load or systemic bacterial translocation (endotoxemia). Collectively, this study demonstrates that although consumption of a 10% FS diet enhanced the levels of n-3 PUFAs, short-chain polyunsaturated fatty acids, and lignans in mice, it exacerbated DSS-induced colonic injury and inflammation.
Cohen, Joshua S; Miles, Matthew C; Donohue, James F; Ohar, Jill A
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and health care expenditure worldwide. Relaxation of airway smooth muscle with inhaled bronchodilators is the cornerstone of treatment for stable COPD, with inhaled corticosteroids reserved for those with a history of exacerbations. Tiotropium has occupied center stage in COPD treatment for over 10 years and improves lung function, quality of life, exercise endurance, and reduces the risk of COPD exacerbation. Long-acting β2-agonists (LABAs) improve lung function, reduce dynamic hyperinflation, increase exercise tolerance, health-related quality of life, and reduce acute exacerbation of COPD. The combination of long-acting muscarinic antagonists (LAMAs) and LABAs is thought to leverage different pathways to induce bronchodilation using submaximal drug doses, increasing the benefits and minimizing receptor-specific side effects. Umeclidinium/vilanterol is the first combination of LAMA/LABA to be approved for use in stable COPD in USA and Europe. Additionally, indacaterol/glycopyrronium and aclidinium/formoterol have been approved in Europe and in numerous locations outside USA. Several other agents are in the late stages of development, most of which offer once-daily dosing. The benefits of new LAMA/LABA combinations include improved pulmonary function, dyspnea, and health-related quality of life, and in some cases, reduced exacerbations. These evolving treatments will provide new opportunities and challenges in the management of COPD. PMID:27143870
Rahimi-Rad, Mohammad Hossein; Sadighi, Tannaz; Rabieepour, Masomeh; Dinparast, Reza; RahimiRad, Shagayegh
Chronic Obstructive Pulmonary Disease (COPD) is going to be the third most common cause of death worldwide. The natural course of COPD is interrupted by acute exacerbations (AECOPD) with an overall mortality rate of 10%. Anemia is a well-known independent predictor of mortality in several chronic diseases. Little is known about the impact of anemia on mortality in AECOPD. The aims of this study were to determine the prevalence of anemia in AECOPD patients and its impact on mortality in a developing country setting. We retrospectively studied 200 hospitalized patients with AECOPD (100 died in hospital and 100 survived) in Imam Khomeini teaching hospital, Urmia, Iran. Prevalence of anemia between deceased and surviving patients compared by using x-square test. Mean admission day Hb and Hct level were compared between the two groups by using Student t-test. Anemia was defined according to WHO criteria: Hb<13 g/dl in males; Hb<12 g/dl in females. The prevalence of anemia was significantly higher in patients who died in hospital compared to those who survived (72% vs. 49%, p=0.001 and OR=2.68). The mean ±SD Hb level was 11.5±2.7 g/dl among deceased patients vs. 13.0±2.0 g/dl among survivors (p value<0.001). The duration of hospitalization was significantly higher (p<0,001) in anemic patients (mean 13.28 days in anemic vs. 7.0 days in non-anemic patients). In bivariate correlation analysis, Hb was positively correlated with FEV1 (r=+0.210, p=0.011) and negatively with duration of hospitalization (r=-0.389, p=0.000). Anemia was common in AECOPD patients in this developing country setting and was significantly associated with in hospital mortality.
Bunting, Melissa M; Shadie, Alexander M; Flesher, Rylie P; Nikiforova, Valentina; Garthwaite, Linda; Tedla, Nicodemus; Herbert, Cristan; Kumar, Rakesh K
We investigated the role of interleukin-33 (IL-33) in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM) were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.
Xu, Yang; Ito, Toshihiro; Fushimi, Soichiro; Takahashi, Sakuma; Itakura, Junya; Kimura, Ryojiro; Sato, Miwa; Mino, Megumi; Yoshimura, Akihiko; Matsukawa, Akihiro
Background Acute respiratory distress syndrome (ARDS) is a severe and life-threatening acute lung injury (ALI) that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK) pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred)-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK)-MAPK pathway, in lipopolysaccharide (LPS)-induced acute lung inflammation. Methods Wild-type (WT) mice and Spred-2−/− mice were exposed to intratracheal LPS (50 µg in 50 µL PBS) to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2−/− mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. Results LPS-induced acute lung inflammation was significantly exacerbated in Spred-2−/− mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-α, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2−/− mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. Conclusions The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls the
Hiroshima, Yuka; Garthwaite, Linda; Hsu, Kenneth; Yoo, Hyouna; Park, Sang-Ho; Geczy, Carolyn L; Kumar, Rakesh K; Herbert, Cristan
Glucocorticoids are commonly used for treating asthma and its exacerbations but have well-recognised adverse effects and are not always effective. Few alternative treatments exist. Using a murine model of an acute exacerbation of asthma, we assessed the ability of ISU201, a novel protein drug, to suppress the inflammatory response when administered after induction of an exacerbation. Sensitised mice were chronically challenged with a low mass concentration of aerosolised ovalbumin, and then received a single moderate-level challenge to simulate an allergen-induced exacerbation. ISU201 was administered to mice 2 and 8 hours later, while pulmonary inflammation and expression of mRNA for chemokines and proinflammatory cytokines were assessed after 4, 12, and 24 hours. Relative to vehicle-treated controls, ISU201 suppressed accumulation of pulmonary neutrophils and eosinophils, while accelerating the decline in CXCL1, TNF-α, and IL-6 in lavage fluid and lung tissue. ISU201 significantly reduced peak expression of mRNA for the chemokines Cxcl9 and Cxcl10, the adhesion molecules Icam1 and Vcam1, and the proinflammatory cytokines Il1b, Il12p40, and Csf1. The ability of ISU201 to promote resolution of inflammation suggests that it may have potential as an alternative to glucocorticoids in the management of asthma, including when administered after the onset of an acute exacerbation.
Pejkovska, Sava; Kaeva, Biserka Jovkovska; Goseva, Zlatica; Arsovski, Zoran; Janeva, Jelena Jovanovska; Zeynel, Sead
BACKGROUND: Noninvasive mechanical ventilation (NIV) applies ventilator support through the patient’s upper airway using a mask. AIM: The aim of the study is to define factors that will point out an increased risk of NIV failure in patients with exacerbation of Chronic Obstructive Pulmonary Disease (COPD). PATIENTS AND METHODS: Patients over the age of 40, treated with NIV, were prospectively recruited. After data processing, the patients were divided into two groups: 1) successful NIV treatment group; 2) failed NIV treatment group. RESULTS: On admission arterial pH and Glasgow coma scale (GCS) levels were lower (pH: p < 0.05, GCS: p < 0.05), and Acute Physiology and Chronic Health Evaluation II (APACHE) score and PaCO2 were higher (p < 0.05) in the NIV failure group. Arterial pH was lower (p < 0.05) and PaCO2 and respiratory rate were higher (p < 0.05) after 1h, and arterial pH was lower (p < 0.05) and PaCO2 (p < 0.05), respiratory and heart rate were higher (p < 0.05) after 4h in the NIV failure group. CONCLUSION: Measurement and monitoring of certain parameters may be of value in terms of predicting the effectiveness of NIV treatment. PMID:27275303
Chen, Jung-Yueh; Liu, Jui-Ming; Chang, Fung-Wei; Chang, Hung; Cheng, Kuan-Chen; Yeh, Chia-Lun; Wei, Yu-Feng; Hsu, Ren-Jun
Background Scabies is a common parasitic infectious disease, and COPD is a major pulmonary disease. However, there have been no previous studies that have investigated the relationship between scabies and COPD. Materials and methods This nationwide population-based study included a total of 3,568 patients with scabies as the study group and 14,255 patients as a control group. We followed up patients in both groups for a 5-year period to identify any new diagnoses of COPD. We then followed them up for an additional 2-year period to determine the severity of any newly diagnosed cases of COPD as indicated by acute respiratory events. Cox proportional hazard regression analyses were performed to calculate the hazard ratio (HR) of COPD during the 5-year follow-up period and COPD complication during the additional 2-year follow-up period. Results Of the 17,823 patients in the study, 2,765 (15.5%) were newly diagnosed with COPD during the 5-year follow-up period; 904 (32.7%) were from the scabies group; and 1,861 (67.3%) were from the control group. Compared to the patients without scabies, the adjusted HR (aHR) for COPD for the subjects with scabies was 1.72 (95% CI: 1.59–1.87) during the 5-year follow-up period. For those newly diagnosed with COPD, the aHR for COPD with acute exacerbation was 1.85 (95% CI: 1.67–2.06), the aHR for COPD with pneumonia was 3.29 (95% CI: 2.77–3.92), the aHR for COPD with acute respiratory failure was 4.00 (95% CI: 3.08–5.19), and the aHR for COPD with cardiopulmonary arrest was 3.95 (95% CI: 2.25–6.95) during the additional 2-year follow-up period. Conclusion The results of this study indicate a 72% increased risk for COPD among patients with scabies. The results also reveal an increased risk of severe COPD complications such as acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation among patients with scabies. This useful information may help physicians in treating scabies and remaining alert to the
Gray, Matthew P.; Morrison, Andrea K.; Levas, Michael N.; Kessler, Elizabeth A.; Hill, Garick D.; Gorelick, Marc H.; Jackson, Jeffrey L.
BACKGROUND AND OBJECTIVE: Dexamethasone has been proposed as an equivalent therapy to prednisone/prednisolone for acute asthma exacerbations in pediatric patients. Although multiple small trials exist, clear consensus data are lacking. This systematic review and meta-analysis aimed to determine whether intramuscular or oral dexamethasone is equivalent or superior to a 5-day course of oral prednisone or prednisolone. The primary outcome of interest was return visits or hospital readmissions. METHODS: A search of PubMed (Medline) through October 19, 2013, by using the keywords dexamethasone or decadron and asthma or status asthmaticus identified potential studies. Six randomized controlled trials in the emergency department of children ≤18 years of age comparing dexamethasone with prednisone/prednisolone for the treatment of acute asthma exacerbations were included. Data were abstracted by 4 authors and verified by a second author. Two reviewers evaluated study quality independently and interrater agreement was assessed. RESULTS: There was no difference in relative risk (RR) of relapse between the 2 groups at any time point (5 days RR 0.90, 95% confidence interval [CI] 0.46–1.78, Q = 1.86, df = 3, I2 = 0.0%, 10–14 days RR 1.14, 95% CI 0.77–1.67, Q = 0.84, df = 2, I2 = 0.0%, or 30 days RR 1.20, 95% CI 0.03–56.93). Patients who received dexamethasone were less likely to experience vomiting in either the emergency department (RR 0.29, 95% CI 0.12–0.69, Q = 3.78, df = 3, I2 = 20.7%) or at home (RR 0.32, 95% CI 0.14–0.74, Q = 2.09, df = 2, I2 = 4.2%). CONCLUSIONS: Practitioners should consider single or 2-dose regimens of dexamethasone as a viable alternative to a 5-day course of prednisone/prednisolone. PMID:24515516
Bourbeau, Jean; Casan, Pere; Tognella, Silvia; Haidl, Peter; Texereau, Joëlle B; Kessler, Romain
Introduction Most hospitalizations and costs related to COPD are due to exacerbations and insufficient disease management. The COPD patient Management European Trial (COMET) is investigating a home-based multicomponent COPD self-management program designed to reduce exacerbations and hospital admissions. Design Multicenter parallel randomized controlled, open-label superiority trial. Setting Thirty-three hospitals in four European countries. Participants A total of 345 patients with Global initiative for chronic Obstructive Lung Disease III/IV COPD. Intervention The program includes extensive patient coaching by health care professionals to improve self-management (eg, develop skills to better manage their disease), an e-health platform for reporting frequent health status updates, rapid intervention when necessary, and oxygen therapy monitoring. Comparator is the usual management as per the center’s routine practice. Main outcome measures Yearly number of hospital days for acute care, exacerbation number, quality of life, deaths, and costs. PMID:27418817
Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air p...
Baba, Mika; Gomwo, Ikuo
Cancer pain consists of continuous pain lasting almost all day and transient exacerbation of pain called breakthrough pain. Breakthrough pain is classified as somatic pain and visceral pain, neuropathic pain according to the character of pain. Although the immediate release opioid is used as the first treatment of choice to breakthrough pain, the effect is not enough when it shows the character of neuropathic pain. Pregabalin has become the first medicine for the treatment of neuropathic pain, and it sometimes reveals prompt analgesic effect based on its pharmacological profile. It has also been reported that pregabalin used with oxycodine reveals analgesic effect with smaller dosage than pregabalin alone. We experienced a young patient with lung cancer suffering from sudden exacerbation of symptomatic sciatica, whose pain was markedly reduced within 30 minutes by taking immediate release oxycodone 5 mg and pregabalin 75 mg simultaneously. Conclusions : Pregabalin with immediate release oxycodone simultaneously may be able to improve acute exacerbation of neuropathic cancer pain rapidly.
Leidy, Nancy K.; Malley, Karen G.; Steenrod, Anna W.; Mannino, David M.; Make, Barry J.; Bowler, Russ P.; Thomashow, Byron M.; Barr, R. G.; Rennard, Stephen I.; Houfek, Julia F.; Yawn, Barbara P.; Han, Meilan K.; Meldrum, Catherine A.; Bacci, Elizabeth D.; Walsh, John W.; Martinez, Fernando
Rationale This study is part of a larger, multi-method project to develop a questionnaire for identifying undiagnosed cases of chronic obstructive pulmonary disease (COPD) in primary care settings, with specific interest in the detection of patients with moderate to severe airway obstruction or risk of exacerbation. Objectives To examine 3 existing datasets for insight into key features of COPD that could be useful in the identification of undiagnosed COPD. Methods Random forests analyses were applied to the following databases: COPD Foundation Peak Flow Study Cohort (N=5761), Burden of Obstructive Lung Disease (BOLD) Kentucky site (N=508), and COPDGene® (N=10,214). Four scenarios were examined to find the best, smallest sets of variables that distinguished cases and controls:(1) moderate to severe COPD (forced expiratory volume in 1 second [FEV1] <50% predicted) versus no COPD; (2) undiagnosed versus diagnosed COPD; (3) COPD with and without exacerbation history; and (4) clinically significant COPD (FEV1<60% predicted or history of acute exacerbation) versus all others. Results From 4 to 8 variables were able to differentiate cases from controls, with sensitivity ≥73 (range: 73–90) and specificity >68 (range: 68–93). Across scenarios, the best models included age, smoking status or history, symptoms (cough, wheeze, phlegm), general or breathing-related activity limitation, episodes of acute bronchitis, and/or missed work days and non-work activities due to breathing or health. Conclusions Results provide insight into variables that should be considered during the development of candidate items for a new questionnaire to identify undiagnosed cases of clinically significant COPD. PMID:26835508
LI, CONGCONG; BO, LIYAN; LIU, QINGQING; LIU, WEI; CHEN, XIANGJUN; XU, DUNQUAN; JIN, FAGUANG
Calcium is an important second messenger and it is widely recognized that acute lung injury (ALI) is often caused by oscillations of cytosolic free Ca2+. Previous studies have indicated that the activation of transient receptor potential-vanilloid (TRPV) channels and subsequent Ca2+ entry initiates an acute calcium-dependent permeability increase during ALI. However, whether seawater exposure induces such an effect through the activation of TRPV channels remains unknown. In the current study, the effect of calcium, a component of seawater, on the inflammatory reactions that occur during seawater drowning-induced ALI, was examined. The results demonstrated that a high concentration of calcium ions in seawater increased lung tissue myeloperoxidase activity and the secretion of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β and IL-6. Further study demonstrated that the seawater challenge elevated cytosolic Ca2+ concentration, indicated by [Ca2+]c, by inducing calcium influx from the extracellular medium via TRPV1 channels. The elevated [Ca2+c] may have resulted in the increased release of TNF-α and IL-1β via increased phosphorylation of nuclear factor-κB (NF-κB). It was concluded that a high concentration of calcium in seawater exacerbated lung injury, and TRPV1 channels were notable mediators of the calcium increase initiated by the seawater challenge. Calcium influx through TRPV1 may have led to greater phosphorylation of NF-κB and increased release of TNF-α and IL-1β. PMID:26796050
Yasui, S; Fujiwara, K; Nakamura, M; Miyamura, T; Yonemitsu, Y; Mikata, R; Arai, M; Kanda, T; Imazeki, F; Oda, S; Yokosuka, O
The short-term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.
Kobayashi, Koji; Horikami, Daiki; Omori, Keisuke; Nakamura, Tatsuro; Yamazaki, Arisa; Maeda, Shingo; Murata, Takahisa
Thromboxane A2 (TXA2) is produced in the lungs of patients suffering from acute lung injury (ALI). We assessed its contribution in disease progression using three different ALI mouse models. The administration of hydrochloric acid (HCl) or oleic acid (OA)+ lipopolysaccharide (LPS) caused tissue edema and neutrophil infiltration with TXA2 production in the lungs of the experimental mice. The administration of LPS induced only neutrophil accumulation without TXA2 production. Pretreatment with T prostanoid receptor (TP) antagonist attenuated the tissue edema but not neutrophil infiltration in these models. Intravital imaging and immunostaining demonstrated that administration of TP agonist caused vascular hyper-permeability by disrupting the endothelial barrier formation in the mouse ear. In vitro experiments showed that TP-stimulation disrupted the endothelial adherens junction, and it was inhibited by Ca2+ channel blockade or Rho kinase inhibition. Thus endogenous TXA2 exacerbates ALI, and its blockade attenuates it by modulating the extent of lung edema. This can be explained by the endothelial hyper-permeability caused by the activation of TXA2-TP axis, via Ca2+- and Rho kinase-dependent signaling. PMID:27562142
Dres, Martin; Hausfater, Pierre; Foissac, Frantz; Bernard, Maguy; Joly, Luc-Marie; Sebbane, Mustapha; Philippon, Anne-Laure; Gil-Jardiné, Cédric; Schmidt, Jeannot; Maignan, Maxime; Treluyer, Jean-Marc; Roche, Nicolas
Background Exacerbations of COPD (ECOPD) are a frequent cause of emergency room (ER) visits. Predictors of early outcome could help clinicians in orientation decisions. In the current study, we investigated whether mid-regional pro-adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation, could predict short-term outcomes. Patients and methods This prospective blinded observational study was conducted in 20 French centers. Patients admitted to the ER for an ECOPD were considered for inclusion. A clinical risk score was calculated, and MR-proADM and copeptin levels were determined from a venous blood sample. The composite primary end point comprised 30-day death or transfer to the intensive care unit or a new ER visit. Results A total of 379 patients were enrolled in the study, of whom 277 were eventually investigated for the primary end point that occurred in 66 (24%) patients. In those patients, the median (interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77–1.48) versus 0.83 nmol/L (0.63–1.07) in patients who did not meet the primary end point (P=0.0009). In contrast, copeptin levels were similar in patients who met or did not meet the primary end point (P=0.23). MR-proADM levels increased with increasing clinical risk score category: 0.74 nmol/L (0.57–0.89), 0.83 nmol/L (0.62–1.12) and 0.95 nmol/L (0.75–1.29) for the low-, intermediate- and high-risk categories, respectively (P<0.001). MR-proADM was independently associated with the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10–2.48; P=0.015). MR-proADM predicted the occurrence of primary end point with a sensitivity of 46% (95% CI, 33%–58%) and a specificity of 79% (95% CI, 74–84). Conclusion MR-proADM but not copeptin was significantly associated with outcomes at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM, alone or combined with the clinical risk score, was a moderate strong predictor of short
Sub-lingual administration of a polyvalent mechanical bacterial lysate (PMBL) in patients with moderate, severe, or very severe chronic obstructive pulmonary disease (COPD) according to the GOLD spirometric classification: A multicentre, double-blind, randomised, controlled, phase IV study (AIACE study: Advanced Immunological Approach in COPD Exacerbation).
Braido, Fulvio; Melioli, Giovanni; Cazzola, Mario; Fabbri, Leonardo; Blasi, Francesco; Moretta, Lorenzo; Canonica, Giorgio Walter
Polyvalent mechanical bacterial lysates (PMBLs) have been shown to reduce the number of infectious episodes in patients with recurrent infections of the respiratory tract. Some previous investigations have also shown the effectiveness of PMBLs in reducing exacerbations of chronic obstructive pulmonary disease (COPD). The AIACE study, which was developed according to criteria of evidence-based medicine, evaluated whether the administration of PMBLs to COPD patients, in addition to the recommended treatment, was able to reduce the number of exacerbations by 25%. Two hundred eighty-eight patients with moderate to very severe COPD were recruited and randomly assigned to either placebo or PMBLs. The placebo or PMBLs were administered according to the standard scheme. The primary outcome of the study was not achieved. However, the number of days with fever (21 days per year versus 40.15; p < 0.001), the days of hospitalisation (65 days vs 162 days; p < 0.001), the interval between the first and second exacerbations (123.89 days vs 70.36; p = 0.03) and the number of days in poor health (109 days/year vs 171 days/year; p < 0.001) were significantly better in the PMBL group than in the placebo group. In conclusion, the results of this trials showed that Ismigen, in addition to guideline-suggested treatment, could not significantly reduce the number of exacerbations in the considered population; nevertheless, the secondary outcome results demonstrated potential benefits of this compound for relevant clinical outcomes.
Finney, Lydia J; Ritchie, Andrew; Pollard, Elizabeth; Johnston, Sebastian L; Mallia, Patrick
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. PMID:25342897
Finney, Lydia J; Ritchie, Andrew; Pollard, Elizabeth; Johnston, Sebastian L; Mallia, Patrick
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans.
Harvey, Christopher J; Thimmulappa, Rajesh K; Sethi, Sanjay; Kong, Xiaoni; Yarmus, Lonny; Brown, Robert H; Feller-Kopman, David; Wise, Robert; Biswal, Shyam
Patients with chronic obstructive pulmonary disease (COPD) have innate immune dysfunction in the lung largely due to defective macrophage phagocytosis. This deficiency results in periodic bacterial infections that cause acute exacerbations of COPD, a major source of morbidity and mortality. Recent studies indicate that a decrease in Nrf2 (nuclear erythroid-related factor 2) signaling in patients with COPD may hamper their ability to defend against oxidative stress, although the role of Nrf2 in COPD exacerbations has not been determined. Here, we test whether activation of Nrf2 by the phytochemical sulforaphane restores phagocytosis of clinical isolates of nontypeable Haemophilus influenza (NTHI) and Pseudomonas aeruginosa (PA) by alveolar macrophages from patients with COPD. Sulforaphane treatment restored bacteria recognition and phagocytosis in alveolar macrophages from COPD patients. Furthermore, sulforaphane treatment enhanced pulmonary bacterial clearance by alveolar macrophages and reduced inflammation in wild-type mice but not in Nrf2-deficient mice exposed to cigarette smoke for 6 months. Gene expression and promoter analysis revealed that Nrf2 increased phagocytic ability of macrophages by direct transcriptional up-regulation of the scavenger receptor MARCO. Disruption of Nrf2 or MARCO abrogated sulforaphane-mediated bacterial phagocytosis by COPD alveolar macrophages. Our findings demonstrate the importance of Nrf2 and its downstream target MARCO in improving antibacterial defenses and provide a rationale for targeting this pathway, via pharmacological agents such as sulforaphane, to prevent exacerbations of COPD caused by bacterial infection.
Eftekhari, Parivash; Hajizadeh, Sohrab; Raoufy, Mohammad Reza; Masjedi, Mohammad Reza; Yang, Ming; Hansbro, Nicole; Li, Jing Jing; Foster, Paul S
Oxidative stress appears to have an important role in glucocorticoid insensitivity, as a crucial problem in asthma therapy. We studied the preventive effect of antioxidant N-acetylcysteine (NAC) on the airway hyper-responsiveness (AHR) and the accumulation of inflammatory cells in the airways in an animal model of steroid resistant acute exacerbation of asthma. Systemically sensitized Balb/C mice were exposed to Ovalbumin aerosol on days 13, 14, 15 and 16, followed by intratracheal lipopolysaccharide (LPS) to induce acute exacerbation. NAC (intraperitoneal, 320 mg/kg 30 min before and 12 hours after each challenge) reduced hyper-responsiveness with/out dexamethasone. LPS application caused neutrophilia in bronchoalveolar lavage fluid (BALF) and eosinophil count was higher than respective control in BALF as well as neutrophils after dexamethasone treatment. NAC significantly decreased neutrophil and eosinophil count in BALF as well as inflammatory cytokines (IL-13 and IL-5).We concluded that addition of NAC to asthma therapy has beneficial preventive effects in an animal model of steroid resistant acute exacerbation of asthma. PMID:26417226
Hansel, Trevor T; Barnes, Peter J
Tobacco smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD), but viral and bacterial infections are the major causes of exacerbations in later stages of disease. Reactive oxygen species (ROS), pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs) activate families of pattern recognition receptors (PRRs) that include the toll-like receptors (TLRs). This understanding has led to the hypothesis that COPD is an archetypal disease of innate immunity. COPD is characterised by abnormal response to injury, with altered barrier function of the respiratory tract, an acute phase reaction, and excessive activation of macrophages, neutrophils, and fibroblasts in the lung. The activated non-specific immune system then mediates the processes of inflammation and repair, fibrosis, and proteolysis. COPD is also associated with corticosteroid resistance, abnormal macrophage and T-cell populations in the airway, autoinflammation and autoimmunity, aberrant fibrosis, accelerated ageing, systemic and concomitant disease, and defective regeneration. Such concepts have been used to generate a range of molecular targets, and clinical trials are taking place to identify effective drugs for the prevention and treatment of COPD exacerbations.
Hillas, Georgios; Perlikos, Fotis; Tsiligianni, Ioanna; Tzanakis, Nikolaos
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.
Korbila, Ioanna P.; Manta, Katerina G.; Siempos, Ilias I.; Dimopoulos, George; Falagas, Matthew E.
ABSTRACT OBJECTIVE To compare the effectiveness and toxicity of semisynthetic penicillins (SSPs) (amoxicillin, ampicillin, pivampicillin) and trimethoprim-based regimens (trimethoprim, trimethoprim-sulfamethoxazole, trimethoprim-sulfadiazine) in treating acute bacterial exacerbations of chronic bronchitis (ABECB). DATA SOURCES We searched MEDLINE, EMBASE, Current Contents, and the Cochrane Central Register of Controlled Trials to identify and extract data from relevant randomized controlled trials (RCTs). STUDY SELECTION Only RCTs comparing penicillins with trimethoprim-based regimens for the treatment of patients with ABECB that reported data on effectiveness, toxicity, or mortality were considered eligible for this meta-analysis. SYNTHESIS Out of 134 RCTs identified in the search, 5 RCTs involving 287 patients were included in the analysis. There were no differences between patients with ABECB treated with SSPs and those treated with trimethoprim, alone or in combination with a sulfonamide, in treatment success (intention-to-treat patients: n = 262, odds ratio [OR] 1.68, 95% confidence interval [CI] 0.91–3.09; clinically evaluable patients: n = 246, OR 1.59, 95% CI 0.79–3.20) or number of drug-related adverse events in general (n = 186 patients, OR 0.37, 95% CI 0.11–1.24), frequency of diarrhea or skin rashes, or number of withdrawals due to adverse events (n = 179 patients, OR 0.27, 95% CI 0.07–1.03). CONCLUSION Based on limited evidence leading to wide CIs of the estimated treatment effects, SSPs and trimethoprim-based regimens seem to be equivalent in terms of effectiveness and toxicity for ABECB. PMID:19155372
Forrest, A; Chodosh, S; Amantea, M A; Collins, D A; Schentag, J J
This analysis was designed to characterize the population pharmacokinetics and pharmacodynamics of oral grepafloxacin (OPC-17,116) in patients with acute bacterial exacerbations of chronic bronchitis (ABECB). The study group included 76 patients (43 male, 33 female) between 23 and 81 years of age, who were part of a multicentre, randomized, double-blind, dose-response study. Patients were randomly assigned to receive oral regimens of grepafloxacin, 200, 400 or 600 mg, each administered once daily for 14 days. Plasma samples for drug assay (typically eight per subject; four samples on either day 3, 4 or 5, plus troughs on other clinic visit days), were obtained during treatment. Population pharmacokinetic analysis was accomplished using iterative two-stage analysis. Cultures and quantitative Gram stains from serial 24 h collections of sputum were used to determine the time (in days) taken to eradicate each bacterial strain. Population pharmacodynamic analysis was performed for three measures of antibacterial response: probability of bacteriological cure, probability of clinical cure, and time to eradication. Grepafloxacin plasma concentration profiles were best fitted by a pharmacokinetic model with first-order absorption following a lag time between administration of the dose and onset of systemic absorption. All three measures of response were strongly related to the 24 h AUIC (AUC/MIC). At an AUIC of <75, the percent probability of clinical cure was 71%; at an AUIC of 75-175, it was 80% (P < 0.05) and at an AUIC of >175, it was 98% (P < 0.01). In conclusion, antibacterial response for grepafloxacin in ABECB patients was highly related to AUIC; values of <75 appear inadequate and values of >175 were optimal.
Varma-Basil, Mandira; Dwivedi, Shailendra K D; Kumar, Krishna; Pathak, Rakesh; Rastogi, Ritika; Thukral, S S; Shariff, Malini; Vijayan, V K; Chhabra, Sunil K; Chaudhary, Rama
Eighty per cent of the cases of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have an infective aetiology, atypical bacteria including Mycoplasma pneumoniae accounting for 5-10 % of these. However, the importance of association of M. pneumoniae with episodes of AECOPD still remains doubtful. The present study was therefore undertaken to delineate the extent of involvement of M. pneumoniae in patients with AECOPD at a referral hospital in Delhi, India. Sputum samples and throat swabs from a total of 100 AECOPD patients attending the Clinical Research Center of Vallabhbhai Patel Chest Institute, Delhi, were collected during a 2-year period (January 2004-June 2006). The samples were investigated for the presence of aerobic bacterial pathogens and M. pneumoniae. Diagnosis of infection with M. pneumoniae was based on culture, serology, direct detection of M. pneumoniae specific antigen and PCR. Bacterial aetiology could be established in 16 of the 100 samples studied. Pseudomonas spp. were recovered from eight cases, Streptococcus pneumoniae from four and Klebsiella spp. from two cases. Acinetobacter sp. and Moraxella catarrhalis were isolated from one case each. Serological evidence of M. pneumoniae infection and/or detection of M. pneumoniae specific antigen were seen in 16 % of the cases. One case with definite evidence of M. pneumoniae infection also had coinfection with Pseudomonas spp. However, no direct evidence of M. pneumoniae infection was found in our study population as defined by culture isolation or PCR. In conclusion, although the serological prevalence of M. pneumoniae infection in our study population was significantly higher than in the control group, there was no direct evidence of it playing a role in AECOPD.
Cazzola, M; Matera, M G; Tufano, M A; Polverino, M; Catalanotti, P; Varanese, L; Rossi, F
The aim of this study was to evaluate the concentrations of dirithromycin, a new macrolide antibiotic, in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF) and serum in 25 patients with acute exacerbation of chronic bronchitis after a 5-day, once-daily, dirithromycin regimen. All patients received dirithromycin, 500 mg (two 250 mg tablets) given orally once daily at 08.00 fasted, for 5 consecutive days. They were divided into five groups (n = 5 in each group) according to sampling time (24, 48, 72, 96 and 120 h, after the last dose). Mean serum concentrations remained low throughout the study (0.44 microgram/ml at 24 h, 0.31 microgram/ml at 48 h, 0.33 microgram/ml at 72 h, 0.12 microgram/ml at 96 h and 0.11 microgram/ml at 120 h, respectively), although they were higher than the MICs for Moraxella catarrhalis for up to 72 h and than that for Streptococcus pneumoniae for up to 120 h after the last dose. By contrast, in all other samples, mean concentrations were higher than the MICs for many relevant respiratory pathogens for at least 3 days, and higher than that for S. pneumonia and M. catarrhalis for up to 120 h (mean concentrations measured 2.67, 2.15, 1.74, 0.27 and 0.17 micrograms/ml, respectively, in BS; 2.59, 2.59, 1.96, 0.41 and 0.27 micrograms/g, respectively, in BM; 2.21, 2.25, 1.57, 0.22 and 0.15 micrograms/ml, respectively, in ELF). These findings demonstrate that dirithromycin is concentrated in each of these potential sites of infection for up to 3 days after a 5-day course of therapy. Therefore, short-term therapy with dirithromycin may be useful for many respiratory infections.
Teng, Sophie X.
Abstract Traumatic brain injury (TBI) represents a leading cause of death and disability among young persons with ∼1.7 million reported cases in the United States annually. Although acute alcohol intoxication (AAI) is frequently present at the time of TBI, conflicting animal and clinical reports have failed to establish whether AAI significantly impacts short-term outcomes after TBI. The objective of this study was to determine whether AAI at the time of TBI aggravates neurobehavioral outcomes and neuroinflammatory sequelae post-TBI. Adult male Sprague-Dawley rats were surgically instrumented with gastric and vascular catheters before a left lateral craniotomy. After recovery, rats received either a primed constant intragastric alcohol infusion (2.5 g/kg+0.3 g/kg/h for 15 h) or isocaloric/isovolumic dextrose infusion followed by a lateral fluid percussion TBI (∼1.4 J, ∼30 ms). TBI induced apnea and a delay in righting reflex. AAI at the time of injury increased the TBI induced delay in righting reflex without altering apnea duration. Neurological and behavioral dysfunction was observed at 6 h and 24 h post-TBI, and this was not exacerbated by AAI. TBI induced a transient upregulation of cortical interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1 mRNA expression at 6 h, which was resolved at 24 h. AAI did not modulate the inflammatory response at 6 h but prevented resolution of inflammation (IL-1, IL-6, tumor necrosis factor-α, and MCP-1 expression) at 24 h post-TBI. AAI at the time of TBI did not delay the recovery of neurological and neurobehavioral function but prevented the resolution of neuroinflammation post-TBI. PMID:24050411
Spohn, S; Wittmann, M; Petro, W
An education program for patients with COPD is presented. This program was created for inpatient pulmonary rehabilitation at the Klinik Bad Reichenhall. We intend to improve the patients' acceptance of disease and their understanding of therapy. Furthermore we want to impart basic knowledge about COPD and its treatment. The patients should be motivated to manage the disease in an active and more independent way: They should control the natural course of their disease by learning preventive and restorative health care behaviours and self-help activities in case of acute exacerbations. The aim is to attain the acceptance of changing life-style.
Cline, Douglas C
Both the National Asthma Education Prevention Program (NAEPP) guidelines for asthma and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) stress the importance of treating acute bronchospasm. Important steps for each disease are making a differential diagnosis, assessing the possibility of future exacerbations, applying disease management principles to prevent and/or treat bronchospasm exacerbations, identifying acutely ill patients, and determining when hospitalization or specialist referrals are appropriate.
Giacomini, M; DeJean, D; Simeonov, D; Smith, A
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
Mehta, Saurabh; Szturm, Tony; El-Gabalawy, Hani S.
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
Gaebel, Kathryn; McIvor, R Andrew; Xie, Feng; Blackhouse, Gord; Robertson, Diana; Assasi, Nazila; Hernandez, Paul; Goeree, Ron
Triple therapy for COPD consists of a long-acting anti-cholinergic bronchodilator, a long-acting beta-agonist bronchodilator, and an inhaled corticosteroid. Guidelines from the Canadian Thoracic Society advocate triple therapy for some patients with moderate-to-severe COPD. The objective of this review was to evaluate the evidence based clinical efficacy of triple therapy compared to dual bronchodilator therapy (long-acting anti-cholinergic bronchodilator + beta-agonist bronchodilator) or long-acting anti-cholinergic bronchodilator monotherapy for managing COPD. A systematic literature search was conducted to identify relevant clinical evaluations of triple therapy in the management of moderate to severe COPD. Databases searched included: Medline; EMBASE; CINAHL and PubMed (non-Medline records only). Of 2,314 publications, 4 articles evaluated triple therapy for the management of COPD. Hospitalization rates for COPD exacerbations, reported in 2 trials, were significantly reduced with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy, with reported relative risks of 0.53 (95% CI: 0.33, 0.86, p = 0.01) and 0.35 (95% CI: 0.16-0.78, p = 0.011). Exacerbation data is inconsistent between the two trials reporting this outcome. Lung function, dyspnea and quality of life data show statistical significant changes with triple therapy compared to long-acting anti-cholinergic bronchodilator monotherapy but the changes do not reach clinical importance. Triple therapy does decrease the number of hospitalizations for severe/acute COPD exacerbations compared with long-acting anti-cholinergic bronchodilator monotherapy. There is insufficient evidence to determine if triple therapy is superior to dual bronchodilator therapy.
Donahoe, Michael; Valentine, Vincent G.; Chien, Nydia; Gibson, Kevin F.; Raval, Jay S.; Saul, Melissa; Xue, Jianmin; Zhang, Yingze; Duncan, Steven R.
Background Severe acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are medically untreatable and often fatal within days. Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. We conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit AE-IPF patients. Methods Eleven (11) critically-ill AE-IPF patients with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Plasma anti-epithelial (HEp-2) autoantibodies and matrix metalloproteinase-7 (MMP7) were evaluated by indirect immunofluorescence and ELISA, respectively. Outcomes among the trial subjects were compared to those of 20 historical control AE-IPF patients treated with conventional glucocorticoid therapy prior to this experimental trial. Results Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one (5%) historical control. Two of the three trial subjects who relapsed after only five TPE responded again with additional TPE. The three latest subjects who responded to an augmented regimen of nine TPE plus rituximab plus IVIG have had sustained responses without relapses after 96-to-237 days. Anti-HEp-2 autoantibodies were present in trial subjects prior to therapy, and were reduced by TPE among those who responded to treatment. Conversely, plasma MMP7 levels were not systematically affected by therapy nor correlated with clinical responses. One-year survival of trial subjects was 46+15% vs. 0% among historical controls. No serious adverse events were attributable to the experimental medications. Conclusion This pilot trial indicates specific treatments that reduce autoantibodies
Nguyen, Michael H.K.; Isaac, Krista M.; Dougherty, Rebecca
Gastrointestinal perforations are a complication of 2–10% of duodenal ulcers. There are a variety of etiologies associated with duodenal ulcer formation and its complications. Corticosteroid use is associated with an increased risk of duodenal ulcer perforation, with the first documented case in 1950. Other important medications associated with perforation include NSAIDS and opioids. Beyond medication, one of the most common disease processes, chronic obstructive pulmonary disease (COPD), has been found to be associated with peptic ulcer disease. Up to 30% of COPD patients have been found to have peptic ulcers, and COPD frequency in peptic ulcer disease is 2–3 times the general population. We herein present a case of an acute duodenal ulcer perforation in a patient receiving corticosteroid treatment for an acute COPD exacerbation. PMID:27609727
Chi, Miao-Ching; Guo, Su-Er; Hwang, Su-Lun; Chou, Chiang-Ting; Lin, Chieh-Mo; Lin, Yu-Ching
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
Yamanaka, Shinsuke; Takahashi, Yoshimi; Fujita, Hiroshi; Yamaguchi, Nobuhiro; Onoue, Noriko; Ishizuka, Takeshi; Shinozaki, Tsuyoshi; Kohzuki, Masahiro
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
Yoshihara, S; Yamada, Y; Abe, T; Lindén, A; Arisaka, O
We examined whether epithelial damage is associated with mobilization of neutrophils or eosinophils in the airway lumen during acute exacerbations of paediatric asthma. Aspirated sputum samples were harvested from 65 paediatric patients (mean age 3·4 ± 0·4 years) during acute exacerbations of asthma. Patients with signs of infection were excluded. The presence of conglomerates of epithelial cells (i.e. ‘Creola bodies) in the aspirated sputum was utilized as a marker of epithelial damage. Among the paediatric asthma patients, 60% displayed Creola bodies (CrB+: n = 39) in their sputum samples whereas the remaining patients did not (CrB–: n = 26). CrB+ patients displayed more than a 20-fold increase in the concentration of the neutrophil-mobilizing cytokine interleukin (IL)-8 (pg/ml) and of the neutrophil product neutrophil elastase (NE, g/l), respectively, compared with CrB– patients (IL-8: 7468·2 ± 1953·6 versus 347·9 ± 72·6, P < 0·01; NE: 2072·4 ± 419·0 versus 438·5 ± 125·7, P < 0·01). Even though not statistically significant, a corresponding trend was observed for the relative number of sputum neutrophils. In contrast, the concentration of the eosinophil-mobilizing cytokine IL-5 and the esoinophil product ECP tended to be lower in CrB+ than in CrB– patients (P > 0·05). In conclusion, as indicated by the analysis of aspirated sputum, epithelial damage is associated with a locally enhanced chemotactic signal for and activity of neutrophils, but not eosinophils, during acute exacerbations of paediatric asthma. It remains to be determined whether these indirect signs of neutrophil mobilization in the airway lumen mirror an increased number of neutrophils in the surrounding airway tissue. PMID:16634793
Xiaomei, Wang; Hang, Xiao; Lingling, Liu; Xuejun, Li
The prevalence of osteoporosis in older patients with chronic obstructive pulmonary disease (COPD) is higher than in the age-matched elderly patients, but the exact cause in relation to COPD is not clear. We hypothesized that the underlying causes for this difference are related to bone metabolism with the possible risk factors that include the duration of COPD, GOLD grade, cor pulmonale, the frequencies of acute exacerbations within the past year, smoking and inhaled corticosteroid therapy. We conducted a matched-pair study of 100 patients aged older than 65 years at the Southwest Hospital from May to November 2012. The enrolled patients with COPD were matched to controls for age and gender. Clinical characteristics of cohorts were recorded. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and osteoporosis was diagnosed according to the definition of WHO. All cohorts accepted bone metabolism marker measurement, including Procollagen type 1 aminoterminal propeptide (P1NP), β-C-telopeptides of type I collagen (βCTX), and N-terminal midmolecule fragment osteocalcin (N-MID OC). Statistical analysis was calculated using the student's t test, ANOVA and multiple regression analysis at a significance level set at a p < 0.05. Circulating biochemical markers of bone formation (P1NP), resorption (βCTX) and turnover (N-MID OC) were significantly lower in the COPD group than control group, while mean 25-OH Vitamin D was similar in two groups. The P1NP, βCTX, and N-MID OC were still lower in men with COPD, but only P1NP was lower in women with COPD compared to that of controls. Multiple regression analysis in COPD group suggests that age, the frequency of acute exacerbation, and BMD are independent risk factors for P1NP. The frequency of acute exacerbation within the past one year and 25-OH D level are independent risk factors for βCTX; the frequency of acute exacerbation is the only independent risk factor for N-MID OC. These were significant
Bauman, Richard A; Widholm, John; Long, Joseph B
The purpose of these experiments was to determine whether secondary hypoxia exacerbates the metabolic consequences of fluid percussion injury (FPI). In Experiment I, rats were trained to press a lever for their entire daily ration of food at any time during a 12-h light/dark cycle and run in an activity wheel. After food intake and body weight stabilized, rats were surgically prepared, assigned to one of four groups [FPI+Hypoxia (IH), FPI+Normoxia (IN), Sham Injury+Hypoxia (SH), Sham Injury+Normoxia (SN)] and, after recovery from surgery, anesthetized with halothane delivered by a 21% O2 source. Immediately after injury or sham injury, the O2 source was switched to 13% for rats in Groups IH and SH for 30 min. Post-traumatic hypoxemia exacerbated the ensuing FPI-induced reductions of food intake and body weight, but did not change FPI-induced reduction in wheel running. In Experiment II, rats were assigned to one of three groups (SH, IN, or IH) and subjected to sham injury and 13% O2 or FPI and either 13 or 21% O2. Immediately after 30 min of hypoxia or normoxia, rats were confined to metabolism cages that were used to quantify rates of oxygen consumption (VO2), carbon dioxide production (VCO2), and heat production (H). Post-traumatic hypoxia exacerbated the FPI-induced increases in VO2, VCO2, and H. The results of Experiments I and II provide convergent confirmation that secondary hypoxemia exacerbates the FPI-induced hypermetabolic state in rats and therefore might significantly exacerbate the brain injury-induced disruptions of energy metabolism in humans.
Akiyama, Mitsuhiro; Kaneko, Yuko; Yamaoka, Kunihiro; Kondo, Harumi; Takeuchi, Tsutomu
The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60 years or older (OR 4.5, 95 % CI 2.2-9.4, P < 0.0001), smoking habit (OR 2.9, 95 % CI 1.5-5.5, P = 0.002), and high rheumatoid factor levels (OR 2.8, 95 % CI 1.4-5.5, P = 0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48 weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24 weeks (20.8 vs. 6.2, P = 0.019). Univariate analysis showed that CDAI > 10 at 24 weeks was a risk factor for acute exacerbation (OR 4.7, 95 % CI 2.1-10.4, P = 0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD.
Ren, F; Shi, H; Zhang, L; Zhang, X; Wen, T; Xie, B; Zheng, S; Chen, Y; Li, L; Chen, D; Duan, Z
Although endoplasmic reticulum (ER) stress is critical in various liver diseases, its role in acute-on-chronic liver failure (AoCLF) caused by acute exacerbation of chronic hepatitis B (CHB) is still elusive. This study aimed to analyse ER stress responses in the progression of HBV-related AoCLF. Normal liver tissues (n = 10), liver tissues of CHB (n = 12) and HBV-related patients with AoCLF (n = 19) were used. Electron microscopy of the ultrastructure of the ER was carried out on liver specimens. The gene and protein expression levels of ER stress-related genes were measured. We further analysed the correlation between the expression levels of ER stress-related molecules and liver injury. Electron microscopy identified typical features of the ER microstructure in AoCLF subjects. Among the three pathways of unfolded protein responses, the PKR-like ER kinase and inositol-requiring enzyme 1 signalling pathway were activated in CHB subjects and inactivated in AoCLF subjects, while the activating transcription factor 6 signalling pathway was sustained in the activated form during the progression of AoCLF; the expression of glucose-regulated protein (Grp)78 and Grp94 was gradually decreased in AoCLF subjects compared to healthy individuals and CHB subjects, showing a negative correlation with serum ALT, AST and TBIL; moreover, the ER stress-related apoptosis molecules were activated in the progression of acute exacerbation of CHB. The dysregulated ER stress response may play a complicated role in the pathogenesis of AoCLF, and a severe ER stress response may predict the occurrence of AoCLF caused by acute exacerbation of CHB.
Background Mechanical ventilation (MV) is imperative in many forms of acute respiratory failure (ARF) in COPD patients. Previous studies have shown the difficulty to identify parameters predicting the outcome of COPD patients treated by invasive MV. Our hypothesis was that a non specialized score as the activities daily living (ADL) score may help to predict the outcome of these patients. Methods We studied the outcome of 25 COPD patients admitted to the intensive care unit for ARF requiring invasive MV. The patients were divided into those weaning success (group A n = 17, 68%) or failure (group B n = 8, 32%). We investigated the correlation between the ADL score and the outcome and mortality. Results The ADL score was higher in group A (5.1 ±1.1 vs 3.7 ± 0.7 in group B, p < 0.01). Weaning was achieved in 76.5% of the cases with an ADL score ≥ 4 and in 23.5% of the cases with an ADL score < 4 (p < 0.05). Pulmonary function test, arterial blood gases collected during period of clinical stability and at admission and nutritional status were similar in both groups. The mortality, at six months, was 36%. The ADL score was a significant predictor of 6-month mortality (80 with an ADL score <4, 20 with an ADL score ≥4, p < 0.01). Conclusion Our pilot study demonstrates that the ADL score is predictive of weaning success and mortality at 6 months, suggesting that the assessment of daily activities should be an important component of ARF management in COPD patients. PMID:23078114
Cho, Hui-Ling; Tung, Heng-Hsin; Lin, Ming-Shian; Hsu, Wan-Chun; Lee, Chi-Pin
The purpose of this study was to evaluate the self-determined motivation predictors of exercise behavior following pulmonary rehabilitation in COPD recipients. This cross-sectional study was conducted with 135 COPD patients. A demographic questionnaire, clinical factors, behavioral regulations in exercise questionnaire, and leisure time exercise questionnaire were used to collect data. A logistic regression model was used to identify the predictors associated with demographics and self-determined motivation types regarding physical activity. Education level, episodes of acute exacerbation within 2 years, and identified regulation were significant predictors of executing physical activities with high metabolic equivalents. The results of this study imply that healthcare providers need to be aware of the importance of exercise motivation among COPD patients.
Ozyemisci-Taskiran, Ozden; Bozkurt, Sinem Ozcan; Kokturk, Nurdan; Karatas, Gulcin Kaymak
The aim of this study is to screen the cognitive function during exacerbation of chronic obstructive pulmonary disease (COPD) and investigate whether there is any association between cognitive function and functional impairment, disease severity, or other clinical parameters. Age and sex-matched 133 subjects with COPD exacerbation, 34 stable COPD subjects, and 34 non-COPD subjects were enrolled in this study. For the purpose of this study, mini-mental state examination (MMSE) and Hospital Anxiety and Depression scale were performed. Six-minute walk distance (6MWD) was recorded, and BODE index was calculated. COPD subjects with exacerbation had the lowest MMSE scores (p = 0.022). Frequency of subjects with MMSE score lower than 24 is 22.6, 8.8, and 8.8% in the COPD subjects with exacerbation, stable COPD, and non-COPD control subjects, respectively. The COPD subjects with exacerbation who had MMSE scores lower than 24 were older and less educated. Subjects with COPD exacerbation had shorter 6MWD than that of stable COPD and non-COPD subjects. After controlling for the impact of age and educational level on MMSE, there was no association between 6MWD and MMSE scores in subjects with COPD exacerbation. Cognitive impairment is an important comorbidity during COPD exacerbation. Functional capacity is also lower in exacerbation. However, no association was found between cognitive impairment and functional capacity during exacerbation.
Dreyse, Jorge; Díaz, Orlando; Repetto, Paula B; Morales, Arturo; Saldías, Fernando; Lisboa, Carmen
Background In addition to smoking, acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease (COPD). However, these findings come from studies including active smokers, while results in ex-smokers are scarce and contradictory. The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second (FEV1) and impairment of functional and clinical outcomes in ex-smoking COPD patients. Methods A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition. Evaluation included anthropometry, spirometry, inspiratory capacity, peripheral capillary oxygen saturation, severity of dyspnea, a 6-minute walking test, BODE (Body mass index, airflow Obstruction, Dyspnea, Exercise performance) index, and quality of life (St George’s Respiratory Questionnaire and Chronic Respiratory Disease Questionnaire). Severity of exacerbation was graded as moderate or severe according to health care utilization. Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year. Random effects modeling, within hierarchical linear modeling, was used for analysis. Results During follow-up, 419 (96% moderate) acute exacerbations were registered. At baseline, frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index, and also showed greater impairment in inspiratory capacity, forced vital capacity, peripheral capillary oxygen saturation, 6-minute walking test, and quality of life. However, no significant difference in FEV1 decline over time was found between the two groups (54.7±13 mL/year versus 85.4±15.9 mL/year in frequent exacerbators and infrequent exacerbators, respectively
Hurst, J; Wedzicha, J
Exacerbations of chronic obstructive pulmonary disease impose a considerable burden of morbidity, mortality, and health care cost. Management guidelines outlining best practice, based largely on consensus expert opinion, were produced by a number of organisations during the last decade. Current interest in the field is high. This has resulted in the publication of many further studies which have extended our understanding of the pathology involved and provided, for the first time, an evidence base for many of the therapeutic options. In this review we aim to bring the non-specialist reader up to date with current management principles and the evidence underlying such interventions. PMID:15356350
Brusse-Keizer, Marjolein; VanderValk, Paul; van der Zanden, Rogier W; Nijdam, Lars; van der Palen, Job; Hendrix, Ron; Movig, Kris
Background Acute exacerbations of chronic obstructive pulmonary disease (COPD) are often treated with antibiotics. Theoretically, to be maximally effective, the antibiotic concentration at sites of infection should exceed the minimum inhibitory concentration at which 90% of the growth of potential pathogens is inhibited (MIC90). A previous study showed that most hospitalized COPD patients had sputum amoxicillin concentrations
Yakoot, Mostafa; Salem, Amel; Omar, Abdel-Mohsen
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
Chatterjee, S.; Biswas, T.; Dutta, A.; Sengupta, G.; Mitra, A.; Kundu, S.
Objective: Acute exacerbation of chronic bronchitis (AECB) is a commonly encountered problem and those suspected to be due to bacterial infections require antibiotic therapy. This randomized, controlled trial was designed to evaluate the effectiveness and safety of gemifloxacin, a new fluoroquinolone, versus cefpodoxime, an oral third-generation cephalosporin, for the treatment of mild to moderately severe cases of AECB. Materials and Methods: Adult subjects diagnosed with chronic bronchitis with clinical symptoms suggestive of an Anthonisen type II acute exacerbation (any two of the following criteria – increased dyspnea, cough, sputum purulence) were eligible and those fulfilling the subject selection criteria were randomized to receive either gemifloxacin 320 mg once daily or cefpodoxime 200 mg twice daily orally for 7 days. The primary outcome measure was clinical success rate at day 14 visit and the secondary outcome measures were changes in Clinical Global impression (CGI) scales and incidence of adverse events (AEs). Fifty-two subjects were enrolled: 26 in gemifloxacin group and 24 in the other and 2 were lost to follow-up. Results: The clinical success rates were comparable (84.6% in gemifloxacin group versus 83.3% in cefpodoxime group) and no statistically significant difference was observed between the groups. AEs were mild, self-limiting and few (two in gemifloxacin and three in cefpodoxime arm) and tolerability was also good. Conclusion: The results of this randomized, single-blind trial demonstrated that a 7-day course of gemifloxacin is therapeutically comparable to cefpodoxime in terms of both clinical effectiveness and safety for the treatment of type II Anthonisen category AECB patients. PMID:21455420
Nyberg, André; Saey, Didier; Martin, Mickaël; Maltais, François
Exercising small muscle groups at a time allows higher muscle specific workloads compared with whole body aerobic exercises in people with chronic obstructive pulmonary disease (COPD). Whether similar effects also occur with partitioning exercise during low load/high-repetition resistance exercises is uncertain.
Qureshi, Hammad; Sharafkhaneh, Amir
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
Nurulain, Syed M; Shafiullah, Mohamed; Yasin, Javed; Adem, Abdu; Kaabi, Juma Al; Tariq, Saeed; Adeghate, Ernest; Ojha, Shreesh
Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under non-diabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD50) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBC-AChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition.
Faculty at Indiana University School of Medicine are set to launch a community paramedicine program aimed at preventing repeat hospital and ED visits for acute exacerbations of asthma in children. Under the program, all children who are treated in the hospital or ED for asthma will receive home visits by specially trained paramedics within a few days of discharge. Paramedics will conduct a comprehensive assessment and make referrals as necessary for followup care. Nearly 30% of children who have been hospitalized for asthma require readmission to the hospital not long after discharge, and as many as 25% of children who have been treated in the ED for asthma will return to the ED within 30 days for another asthma-related visit. The one-time home visits will be comprehensive, enabling EMS providers to initiate stop-gap measures so that if a child is starting to get sick, paramedics can make sure the appropriate medicines are started and that acute care needs are met. Developers will monitor 30-day, 90-day, and one-year readmission metrics among patients who have received home visits.They hope that resulting cost-savings will sustain the program beyond the initial period, which is being funded through a grant from the Department of Health and Human Services.
Omachi, Theodore A.; Katz, Patricia P.; Yelin, Edward H.; Iribarren, Carlos; Blanc, Paul D.
Background: A comprehensive survey-based COPD severity score has usefulness for epidemiologic and health outcomes research. We previously developed and validated the survey-based COPD Severity Score without using lung function or other physiologic measurements. In this study, we aimed to further validate the severity score in a different COPD cohort and using a combination of patient-reported and objective physiologic measurements. Methods: Using data from the Function, Living, Outcomes, and Work cohort study of COPD, we evaluated the concurrent and predictive validity of the COPD Severity Score among 1,202 subjects. The survey instrument is a 35-point score based on symptoms, medication and oxygen use, and prior hospitalization or intubation for COPD. Subjects were systemically assessed using structured telephone survey, spirometry, and 6-min walk testing. Results: We found evidence to support concurrent validity of the score. Higher COPD Severity Score values were associated with poorer FEV1 (r = −0.38), FEV1% predicted (r = −0.40), Body mass, Obstruction, Dyspnea, Exercise Index (r = 0.57), and distance walked in 6 min (r = −0.43) (P < .0001 in all cases). Greater COPD severity was also related to poorer generic physical health status (r = −0.49) and disease-specific health-related quality of life (r = 0.57) (P < .0001). The score also demonstrated predictive validity. It was also associated with a greater prospective risk of acute exacerbation of COPD defined as ED visits (hazard ratio [HR], 1.31; 95% CI, 1.24-1.39), hospitalizations (HR, 1.59; 95% CI, 1.44-1.75), and either measure of hospital-based care for COPD (HR, 1.34; 95% CI, 1.26-1.41) (P < .0001 in all cases). Conclusion: The COPD Severity Score is a valid survey-based measure of disease-specific severity, both in terms of concurrent and predictive validity. The score is a psychometrically sound instrument for use in epidemiologic and outcomes research in COPD. PMID:20040611
Kieszko, Robert; Szmygin-Milanowska, Katarzyna; Chudnicka, Alina; Gołebiowska, Izabela; Łagozna, Jolanta; Milanowski, Janusz
The objective of the study was determination of the most frequent bacterial factors, including Haemophilus parainfluenzae, suspected of causing COPD exacerbation, of the relation between bacterial strains and respiratory system functional status as well as of antibiotic sensitivity of sputum isolated bacteria. The examined group comprised 28 patients treated in the Pulmonary Department of Medical University of Lublin. The subjects fulfilled the criteria of type I COPD bacterial exacerbation. Patient's chest x-ray and spirometry tests were performed. Forty-nine bacterial strains were isolated. In the case of nine patients, more than one strain was isolated. Subjects having H. parainfluenzae in sputum had significantly higher (p<0.05) FVC and FEV1 values comparing to patients with H. influenzae or other Gram-negative bacteria. H. parainfluenzae may be an important etiologic factor of COPD exacerbation. Aetiology of bacterial COPD exacerbation depends on the level of respiratory parameter limitation.
Citgez, Emanuel; van der Palen, Job; Koehorst-ter Huurne, Kirsten; Movig, Kris; van der Valk, Paul; Brusse-Keizer, Marjolein
Background Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort. Methods 795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias. Results Statin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47). Conclusions In the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD. PMID:27403321
Isono, Yoshiaki; Matsusaki, Shimpei; Tanaka, Hiroki; Tochio, Tomomasa; Kumazawa, Hiroaki; Sase, Tomohiro; Saito, Tomonori; Okano, Hiroshi; Baba, Youichirou; Mukai, Katsumi
A 75-year-old woman with epigastric pain was admitted to our emergency department. She was diagnosed with an acute exacerbation of chronic pancreatitis based on the results of blood tests and abdominal computed tomography (CT). The abdominal CT and magnetic resonance cholangiopancreatography revealed pancreas divisum. Abdominal CT also showed a stone in the minor papilla, with impaction of the stone being the most likely cause of the acute episode. Therefore, endoscopic sphincterotomy of the minor papilla and endoscopic naso-pancreatic duct drainage were performed to remove the stone and decrease the internal pressure of the pancreatic duct. These procedures improved the patient's clinical status. The naso-pancreatic drainage tube was removed, and her pancreatitis has not recurred. Herein, we report a rare case of an impacted minor papilla stone in a patient with pancreas divisum that caused an acute exacerbation of chronic pancreatitis.
Brusse-Keizer, Marjolein; ten Bokum, Leonore; Movig, Kris; van der Valk, Paul; Kerstjens, Huib; van der Palen, Job; Hendrix, Ron
Amoxicillin is a widely used antibiotic in COPD. Little is known about the transfer of amoxicillin into sputum of COPD patients. The objective was to investigate the relationship between the concentration of amoxicillin in sputum in hospitalized COPD patients and length of hospitalization. To be effective against bacterial pathogens, the amoxicillin concentration in target tissues should be higher than the Minimal Inhibiting Concentration (MIC) of 2 mg/l. Therefore, this was also used as the cut-off value for the amoxicillin concentration in sputum, as a marker for lung tissue concentration. Fifty-two COPD in-patients with an exacerbation, treated with amoxicillin clavulanic acid, were included in this cohort study. Of these patients 7 also had pneumonia. Patients were divided in patients with an amoxicillin sputum concentration ≥ 2 mg/l and < 2 mg/l. Furthermore, inflammation markers in sputum and serum and clinical parameters were obtained. Of the 33 patients with usable sputum, 11 had a concentration in sputum ≥ 2 mg/l. The mean length of hospitalization for patients with concentrations below the MIC90 to common respiratory pathogens was 11.0 days, while for patients with concentrations at or above the MIC90 this was 7.0 days (p = 0.005). COPD patients admitted for an acute exacerbation of COPD, with a sputum concentration of amoxicillin ≥ 2 mg/l had a markedly reduced length of hospitalization compared to patients with a concentration < 2 mg/l. It is worthwhile testing whether individualized treatment based on sputum amoxicillin concentrations of patients during hospitalization for acute exacerbations can effectively reduce hospital stay.
Alvarez-Sala, Jose-Luis; Kardos, Peter; Martínez-Beltrán, Jesús; Coronel, Pilar; Aguilar, Lorenzo
A randomized, double-blind, double-dummy trial was performed comparing 200 mg of cefditoren-pivoxil twice daily for 5 days versus standard cefuroxime-axetil treatment (250 mg twice daily for 10 days) of Anthonisen type I or II acute exacerbations of chronic bronchitis. The modified intention-to-treat population included 541 patients. Patients were assessed during therapy, at the end of therapy (visit 3; primary evaluation time point), and at follow-up. Clinical success was obtained in 79.9% of the 264 patients included in the cefditoren-pivoxil group and in 82.7% of the 277 patients in the cefuroxime-axetil group (treatment difference, 95% confidence interval [CI]: −2.8, −9.7 to 3.6%). Treatment clinical effects were more clearly seen in sputum signs (decreasing volume and purulence from approximately 80% to approximately 10% of the patients). At the end of treatment, exploratory analysis of the per-pathogen bacteriological response showed 72.8% (of 103 isolates) in the cefditoren-pivoxil arm versus 67.0% (of 94 isolates) in the cefuroxime-axetil group (treatment difference; 95% CI: 5.8, −7.0 to 18.6%). Globally, the per-pathogen bacteriological response correlated well with clinical success: 83.5% of 164 baseline isolates from patients with a clinical success were eradicated or presumably eradicated, in contrast to only 3% of 33 isolates from patients with a clinical failure. Clinical success in patients infected with Haemophilus influenzae, the most frequent isolate, was 84% (of 50) and 82.5% (of 40) (treatment difference; 95% CI: 1.5, −14 to 17%) in the cefditoren-pivoxil versus the cefuroxime-axetil group. Although this study does not prove that either drug is better than a placebo, cefditoren-pivoxil and the standard 10-day cefuroxime-axetil course had similar point estimates of success in acute exacerbations of chronic bronchitis. PMID:16641447
Pérez-Calvo, Juan I; Sánchez-Marteles, Marta; Ruiz-Ruiz, Francisco-José; Morales-Rull, José-Luis; Nieto-Rodríguez, José-Antonio
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
Moreno, Dolores; Barroso, Judith; Garcia, Alexis
Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by chronic obstruction of lung airflow limitation. This disease is currently the fourth higher cause of death in the world, and it is predicted to be the third by the year 2020. Patients with COPD are frequently exposed to Human Rhinovirus, Respiratory Syncytial and Influenza Virus, as well as to Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. These infectious agents are responsible for exacerbations increasing morbidity and mortality in COPD patients. Prevention of infectious exacerbations by vaccination would improve quality of life and patient survival. A literature search: "vaccination of COPD patients" was performed using Medline, the Cochrane Library and other Non-Indexed Citations for this review. This article presents a brief overview of the different studies found, on the new patents, and the future strategies on the field.
Vizcaíno-Castillo, Andrea; Jiménez-Marín, Andrea; Espinoza, Bertha
A murine model was used to study the histopathological aspects and cytokine expression levels in skeletal muscle provoked by the infection with Mexican TcI strains. BALB/c mice were inoculated with the virulent Querétaro strain and the nonvirulent Ninoa strain. Parasite numbers were counted in blood and skeletal muscle at different times post-infection, and real time-PCR expression levels of the cytokines IL-12, IL-4, IL-10, IFN- γ , and TNF- α were evaluated. In the acute phase of infection, a high parasitic load, both in blood and skeletal muscle, was detected. The histopathological analyses showed an exacerbated inflammation and granulomatous-like infiltrate with the Querétaro strain. Interestingly, extensive calcification areas were observed in the skeletal muscle surrounded by inflammatory infiltrates. TNF- α and IL-10 expression exhibited a significant increase at the peak of infection. In summary, Querétaro strain, a Mexican TcI strain, is virulent enough to induce high inflammation and calcification in skeletal muscle of the hind limbs, which could be related to high expression levels of TNF- α .
Wang, Ye; Shen, Yongchun; Zuo, Qiunan; Zhao, Li; Wan, Chun; Tian, Panwen; Chen, Lei; Wen, Fuqiang
Background Appetite reduction is a major cause of cachexia in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study tested the correlation of appetite and circulating levels of acylated ghrelin in patients with AECOPD. Methods Thirty-six patients with AECOPD and 23 healthy adults were enrolled in this study. Circulating total ghrelin, acylated ghrelin, and obestatin levels, Simplified Nutritional Appetite Questionnaire (SNAQ) score, and caloric intake were compared in patients and healthy controls. Additionally, the above parameters were compared between admission and discharge in the patients with AECOPD. Results Compared with healthy controls, SNAQ scores and caloric intake were significantly lower in patients with AECOPD, but there were no significant differences in total ghrelin, acyl ghrelin, or obestatin levels. In patients with AECOPD, the total ghrelin level was significantly higher at admission than on discharge, the SNAQ score and caloric intake were significantly increased at discharge when compared with admission, and there was no significant difference in acylated ghrelin level between admission and discharge. Conclusion We demonstrated lower appetite scores and caloric intake in patients with AECOPD, but could not confirm that these effects were caused by insufficient levels of the orexigenic peptide, acyl ghrelin. Further studies are needed to confirm our findings and to determine the mechanism regulating appetite in patients with AECOPD. PMID:25152618
Deng, Long; Hong, Tao; Lin, Jinyi; Ding, Suling; Huang, Zheyong; Chen, Jinmiao; Jia, Jianguo; Zou, Yunzeng; Wang, Timothy C; Yang, Xiangdong; Ge, Junbo
Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b(+)Gr-1(+) immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC(-/-)) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b(+)Gr-1(+) IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration.
Zhornitsky, Simon; Potvin, Stéphane; Stip, Emmanuel; Rompré, Pierre-Paul
Recent clinical studies show that the atypical antipsychotic medication, quetiapine, may be beneficial in the treatment of substance abuse by alleviating the withdrawal-negative affect stage of addiction. Since the effect of quetiapine on central reward function is largely unknown we studied its effects on brain stimulation reward in animals under withdrawal from escalating doses of d-amphetamine. Male Sprague-Dawley rats were trained to produce an operant response to receive a short train of electrical stimulation to the lateral hypothalamus. Measures of reward threshold were determined with the curve-shift method in different groups of rats before, and during four days after treatment with escalating doses (1 to 10mg/kg, i.p.) of d-amphetamine or its vehicle. At 24h of withdrawal, the effects of two doses of quetiapine (2 and 10mg/kg i.p.) were tested. Animals treated with d-amphetamine showed a 25% reward deficit at 24h of withdrawal, an effect that decreased progressively over the next three days. Quetiapine attenuated reward in the vehicle-control animals, and amplified the anhedonia at the moderate, but not the low, dose in the animals under withdrawal. These results show that acute treatment with clinically relevant doses of quetiapine for the treatment of schizophrenia may exacerbate anhedonia induced by amphetamine withdrawal. Further research should investigate whether repeated treatment with quetiapine has the ability to reverse amphetamine withdrawal-induced anhedonia.
Huang, Fang; Zhao, Ang; Chen, Ren Jie; Kan, Hai Dong; Kuang, Xing Ya
The association between ambient temperature and acute exacerbation of chronic bronchitis (AECB) was still unknown. Therefore, we performed an epidemiological study in a large hospital of Shanghai to explore the relationship about temperature and outpatient visit for AECB. We adopted a quasi-Poisson generalized additive models and distributed lag nonlinear models to estimate the accumulative effects of temperature on AECB across multiple days. We found significant non-linear effects of cold temperature on hospital visits for AECB, and the potential effect of cold temperature might last more than 2 weeks. The relative risks of extreme cold (first percentiles of temperature throughout the study period) and cold (10th percentile of temperature) temperature over lags 0-14 d were 2.98 [95% confidence intervals (CI): 1.77, 5.04] and 1.63 (95% CI: 1.21, 2.19), compared with the 25th percentile of temperature. However, we found no positive association between hospital visits and hot weather. This study showed that exposure to both extreme cold and cold temperatures were associated with increased outpatient visits for AECB in a large hospital of Shanghai.
Fullen, Daniel J.; Murray, Bryan; Mori, Julie; Catchpole, Andrew; Borley, Daryl W.; Murray, Edward J.; Balaratnam, Ganesh; Gilbert, Anthony; Mann, Alex; Hughes, Fiona; Lambkin-Williams, Rob
Background Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. Methods and Stock Development A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children’s Hospital, USA) was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London. Human Challenge and Conclusions In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics. Trial Registration ClinicalTrials.gov NCT02522832 PMID:27936016
Hammond, Matthew D.; Taylor, Roslyn A.; Mullen, Michael T.; Ai, Youxi; Aguila, Hector L.; Mack, Matthias; Kasner, Scott E.; McCullough, Louise D.
Intracerebral hemorrhage (ICH) is a devastating type of stroke that lacks a specific treatment. An intense immune response develops after ICH, which contributes to neuronal injury, disability, and death. However, the specific mediators of inflammation-induced injury remain unclear. The objective of the present study was to determine whether blood-derived CCR2+Ly6Chi inflammatory monocytes contribute to disability. ICH was induced in mice and the resulting inflammatory response was quantified using flow cytometry, confocal microscopy, and neurobehavioral testing. Importantly, blood-derived monocytes were distinguished from resident microglia by differential CD45 staining and by using bone marrow chimeras with fluorescent leukocytes. After ICH, blood-derived CCR2+Ly6Chi inflammatory monocytes trafficked into the brain, outnumbered other leukocytes, and produced tumor necrosis factor. Ccr2−/− mice, which have few circulating inflammatory monocytes, exhibited better motor function following ICH than control mice. Chimeric mice with wild-type CNS cells and Ccr2−/− hematopoietic cells also exhibited early improvement in motor function, as did wild-type mice after inflammatory monocyte depletion. These findings suggest that blood-derived inflammatory monocytes contribute to acute neurological disability. To determine the translational relevance of our experimental findings, we examined CCL2, the principle ligand for the CCR2 receptor, in ICH patients. Serum samples from 85 patients were collected prospectively at two hospitals. In patients, higher CCL2 levels at 24 h were independently associated with poor functional outcome at day 7 after adjusting for potential confounding variables. Together, these findings suggest that inflammatory monocytes worsen early disability after murine ICH and may represent a therapeutic target for patients. PMID:24623768
Ross, Clare L; Hansel, Trevor T
Clinical trials with new drugs for chronic obstructive pulmonary disease (COPD) have been performed. Viruses exacerbate COPD and bacteria may play a part in severe COPD; therefore, antibiotic and antiviral approaches have a sound rationale. Antiinflammatory approaches have been studied. Advances in understanding the molecular basis of other processes have resulted in novel drugs to target reactive oxidant species, mucus, proteases, fibrosis, cachexia, and muscle wasting, and accelerated aging. Studies with monoclonal antibodies have been disappointing, highlighting the tendency for infections and malignancies during treatment. Promising future directions are lung regeneration with retinoids and stem cells.
Nardini, Stefano; Camiciottoli, Gianna; Locicero, Salvatore; Maselli, Rosario; Pasqua, Franco; Passalacqua, Giovanni; Pela, Riccardo; Pesci, Alberto; Sebastiani, Alfredo; Vatrella, Alessandro
The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient's functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.
Torheim, Henny; Kvangarsnes, Marit
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
This paper uses the emergent theories of chaos and complexity to explore the self-management supportive care of chronic obstructive pulmonary disease (COPD) patients within the evolving primary care setting. It discusses the concept of self-management support, the complexity of the primary care context and consultations, smoking cessation, and the impact of acute exacerbations and action planning. The author hopes that this paper will enable the acquisition of new insight and better understanding in this clinical area, as well as support meaningful learning and facilitate more thoughtful, effective and high quality patient-centred care within the context of primary care.
Curtis, Katrina J.; O’Brien, Katie A.; Tanner, Rebecca J.; Polkey, Juliet I.; Minnion, Magdalena; Feelisch, Martin; Polkey, Michael I.; Edwards, Lindsay M.; Hopkinson, Nicholas S.
Background Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD. Methods We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage. Results 21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m2; FEV1 percentage predicted 50.1±21.6%; peak VO2 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO2) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO2-percentage isotime curve. Conclusions Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype. Trial Registration ISRCTN Registry ISRCTN66099139 PMID:26698120
Novelli, Luca; Ruggiero, Roberto; De Giacomi, Federica; Biffi, Alice; Faverio, Paola; Bilucaglia, Luca; Gamberini, Silvia; Messinesi, Grazia; Pesci, Alberto
Acute Exacerbation (AEx) is a frequent and severe complication of Idiopathic Pulmonary Fibrosis (IPF). In the absence of consensus regarding treatment, studies evaluating the efficacy of specific therapies, such as corticosteroids and immunosuppresant agents, are needed. In this case series we evaluated the outcome in terms of survival of intravenous pulse doses of high-dose corticosteroid (methylprednisolone 1000 mg per day for 3 consecutive days) followed by montlhy cyclophosphamide administration (maximum 6 doses) in a cohort of patients with AEx-IPF referred to the Respiratory Unit, San Gerardo University Hospital, Monza, Italy, from 2009 to 2013. A total of 11 patients (7 males, median age 65 years) were enrolled. A median of five monthly pulse doses of cyclophosphamide were administered, with four patients receiving all 6 doses. Four patients died before completion. Three patients developed adverse events. Overall survival at 3 months was 73%, at 6 months 63%, at 12 months 55%, at 18 months 45% and at 2 years 27%. In-hospital mortality was 9%. Causes of death were: six respiratory failures from disease progression, one lung cancer and one breast cancer. Two patients received lung transplantation and were excluded from the Kaplan-Meier analysis. In conclusion, combined intravenous pulse doses of high-dose corticosteroid and cyclophosphamide could be a reasonable add-on therapy for AEx-IPF, considering the few side effects and safe profile. A complete and rapid diagnostic work-up associated to the proper management (e.g. support of respiratory failure with non-invasive ventilation) in the right setting, may also have a positive effect on patients' outcome.
Langan, C E; Cranfield, R; Breisch, S; Pettit, R
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.
... COPD is: A. allergies B. cigarette smoke C. air pollution Question 4. Common signs and symptoms of COPD ... smoke B. avoid other lung irritants, such as air pollution, chemical fumes, and dust C. follow your treatment ...
Toft-Petersen, Anne Pernille; Torp-Pedersen, Christian; Weinreich, Ulla Møller; Rasmussen, Bodil Steen
Background In general, previous studies have shown an association between prior exacerbations and mortality in COPD, but this association has not been demonstrated in the subpopulation of patients in need of assisted ventilation. We examined whether previous hospitalizations were independently associated with mortality among patients with COPD ventilated for the first time. Patients and methods In the Danish National Patient Registry, we established a cohort of patients with COPD ventilated for the first time from 2003 to 2011 and previously medicated for obstructive airway diseases. We assessed the number of hospitalizations for COPD in the preceding year, age, sex, comorbidity, mode of ventilation, survival to discharge, and days to death beyond discharge. Results The cohort consisted of 6,656 patients of whom 66% had not been hospitalized for COPD in the previous year, 18% once, 8% twice, and 9% thrice or more. In-hospital mortality was 45%, and of the patients alive at discharge, 11% died within a month and 39% within a year. In multivariate models, adjusted for age, sex, mode of ventilation, and comorbidity, odds ratios for in-hospital death were 1.26 (95% confidence interval [CI]: 1.11–1.44), 1.43 (95% CI: 1.19–1.72), and 1.56 (95% CI: 1.30–1.87) with one, two, and three or more hospitalizations, respectively. Hazard ratios for death after discharge from hospital were 1.32 (95% CI: 1.19–1.46), 1.76 (95% CI: 1.52–2.02), and 2.07 (95% CI: 1.80–2.38) with one, two, and three or more hospitalizations, respectively. Conclusion Preceding hospitalizations for COPD are associated with in-hospital mortality and after discharge in the subpopulation of patients with COPD with acute exacerbation treated with assisted ventilation for the first time. PMID:27217743
Bos, A C; Beemsterboer, P; Wolfs, T F W; Versteegh, F G A; Arets, H G M
Despite vaccination, pertussis is still endemic in the Netherlands. A literature search was performed to verify what is known about the role of Bordetella species in children with cystic fibrosis, with regard to the incidence of Bordetella infections, the involvement in pulmonary exacerbations and the influence on chronic course. Little is known about the frequency of Bordetella infections and the involvement of Bordetella species both in relation to the chronic course of cystic fibrosis and to pulmonary exacerbations. Since it is difficult to detect Bordetella species in cultures and few sputum cultures investigated have been obtained during an exacerbation, it is likely that the frequency of Bordetella species in CF patients is underestimated. Identification of Bordetella species in these patients may have serious consequences for the treatment of exacerbations in CF. Future research investigating the role of Bordetella species in cystic fibrosis should use specific techniques to detect Bordetella in cultures.
Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...
Toraldo, Domenico Maurizio; De Nuccio, Francesco; Gaballo, Annarita; Nicolardi, Giuseppe
Background Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although forced expiratory volume in 1 second (FEV1) inadequately describes this heterogeneity, a clear alternative has not emerged. This article discusses and refines the concept of phenotyping desaturators in COPD and shows a possible pattern which could be used as a framework for future research. Recent findings COPD is a complex condition with pulmonary and extrapulmonary manifestations. We suggest that COPD phenotypes should be associated with clinically meaningful outcomes. The innovation of COPD phenotyping is defined as COPD desaturators. Sleep-related hypoxemia and hypercapnia are well recognized in COPD and the development of systemic inflammation during sleep. These sleep-related changes predispose to nocturnal cardiac arrhythmias, pulmonary hypertension, and possibly death, particularly during acute exacerbations. Conclusion A more focused definition makes possible a classification of patients into two distinct subgroups for both clinical and research purposes. Establishing a common language for future research will facilitate our understanding and management of such diseases. Even if different treatment strategies have different outcomes for these groups, we will have confirmation, or otherwise, of the clinical value of cluster analysis. This knowledge could lead to pharmacological treatment and other interventions directed to specific phenotypic groups. PMID:22135488
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
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
Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial—the VITamin D and OmegA-3 TriaL (VITAL)—to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2×2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA] +docosahexaenoic acid [DHA], 1 g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. PMID:26784651
Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults.
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
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.
Deniz, Sami; Şengül, Aysun; Aydemir, Yusuf; Çeldir Emre, Jülide; Özhan, Mustafa Hikmet
Purpose We aimed to assess the effects of comorbidities on COPD costs and to investigate the relationship between comorbidities and clinical variables. Patients and methods All patients hospitalized with a diagnosis of COPD exacerbation between January 1, 2014, and December 31, 2014, at all state hospitals of Aydın province, a city located in the western part of Turkey, were included in this study. The costs examined in the study pertained to medications, laboratory tests, hospital stays, and other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees. Results A total of 3,095 patients with 5,237 exacerbations (mean age, 71.9±10.5 years; 2,434 males and 661 females) were evaluated. For 880 of the patients (28.9%), or 3,852 of the exacerbations (73.1%), at least one comorbid disease was recorded. The mean cost of each exacerbation was $808.5±1,586, including $325.1±879.9 (40.7%) for hospital stays, $223.1±1,300.9 (27.6%) for medications, $46.3±49.6 (0.9%) for laboratory expenditures, and $214±1,068 (26.5%) for other treatment-related factors, such as consumption of materials, doctor visits, and consultation fees. The cost of each exacerbation was $1,014.9 in patients with at least one comorbidity, whereas it was $233.6 in patients without comorbidity (P<0.001). Age >65 years, female gender, hospitalization in an intensive care unit, invasive or noninvasive mechanical ventilation, and a long duration of hospitalization were all found to be significant factors in increasing total costs during the exacerbations requiring hospitalization (P<0.05 for all). Conclusion Comorbidities have an important role in the total costs of acute exacerbations of COPD. Strategies for the prevention, diagnosis, and effective management of comorbidities would decrease the overall financial burden associated with acute exacerbations of COPD. PMID:27980399
Decramer, M; Janssens, W
It has been shown that mucus hypersecretion is associated with greater susceptibility for chronic obstructive pulmonary disease (COPD), excess forced expiratory volume in 1 s decline, hospitalisations and excess mortality. The effects of mucoactive drugs on outcomes have been reviewed in several meta-analyses, the largest one including 26 studies. 21 studies were performed in patients with chronic bronchitis and five in patients with COPD. The majority of these trials were performed with N-acetylcysteine (n = 13) and carbocysteine (n = 3). Overall, there was a significant reduction in exacerbations (0.05 per patient per month) and the number of days with disability (0.56 days per patient per month). Mucolytics were well tolerated and the number of adverse events was lower than with placebo (odds ratio 0.78). In the largest and best designed study with N-acetylcysteine in 523 patients with COPD, the reduction in exacerbations was only observed in patients not taking inhaled corticosteroids. In addition, a 374 mL reduction in functional residual capacity was found. A recent large study (n = 709) with high-dose carbocysteine (1,500 mg·day⁻¹) demonstrated a significant effect on exacerbations (25% reduction) and also reported an improvement in health-related quality of life (-4.06 units in St George's Respiratory Questionnaire). It is unclear what the mechanisms underlying these effects may be and which phenotypes benefit from this treatment. On the basis of this evidence mucoactive drugs may deserve consideration in the long-term treatment of COPD.
DeAbate, C A; Bettis, R; Munk, Z M; Fleming, H; Munn, N J; Riffer, E; Bagby, B; Giguere, G; Collins, J J
Three hundred eighty-nine patients were enrolled in a double-masked, multicenter, randomized clinical trial comparing the clinical and bacteriologic efficacies and safety of a 5-day course (n = 195) versus a 10-day course (n = 194) of grepafloxacin 400 mg once daily in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). Patients in the 5-day treatment group received placebo on days 6 through 10. Bacteriologic assessments were based on cultures of sputum specimens obtained before and, when possible, during and after treatment. Organisms were isolated from the pretreatment sputum specimens of 332 of 388 (86%) patients, the primary pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (29%, 19%, 4%, 5%, and 5% of isolates, respectively). Among isolates tested for beta-lactamase production, results were positive in 25% of H influenzae isolates and 90% of M catarrhalis isolates. Forty-two percent of S pneumoniae isolates demonstrated reduced susceptibility (intermediate or high-level resistance) to penicillin. A satisfactory clinical outcome (cure or improvement) was achieved in 83% (128 of 155) and 81% (122 of 150) of clinically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. Pathogens were eradicated or presumed eradicated in 77% (106 of 138) and 80% (98 of 123) of bacteriologically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. The 2 treatment groups were equivalent with respect to both clinical and bacteriologic efficacy, and no statistically significant differences in the incidence of drug-related adverse events were seen between the 2 groups. Substantial symptom relief was evident with both treatment regimens by the first during-treatment measurement, which occurred between days 3 through 5. These results indicate that treatment with 400 mg grepafloxacin once daily for 5 days is as well
Altınkanat Gelmez, Gülşen; Soysal, Ahmet; Kuzdan, Canan; Karadağ, Bülent; Hasdemir, Ufuk; Bakır, Mustafa; Söyletir, Güner
This study aimed to investigate serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates obtained from children with chronic respiratory diseases admitted to hospital with a diagnosis of acute exacerbations between 2008-2010 at Marmara University Hospital, Istanbul, Turkey. Sixty one S.pneumoniae strains isolated from the respiratory samples of patients were studied for erythromycin, clindamycin, tetracyline, trimethoprim-sulphametoxazole (TMP-SMX), vancomycin, levofloxacin susceptibilities by disk diffusion method; MIC values of penicillin and ceftriaxone were determined by E-test (AB Biodisk, Sweden). Results were evaluated according to the CLSI standards. The erythromycin-clindamycin double disc method was applied for the detection of macrolide resistance phenotypes. The presence of macrolide resistance genes, ermB, mef(A)/(E), ermTR were determined by PCR using specific primers for each gene. The serotypes were determined by multiplex PCR using specific primers for 40 different serotypes. According to CLSI criteria, penicillin resistance in S.pneumoniae isolates were found to be 8.2% (5/61) and intermediate resistance rate was 54% (33/61) for oral penicillin. Penicillin resistance were found to be only 1.6% (1/61) for parenteral penicillin. Resistance rates of erythromycin, clindamycin, tetracyline, TMP-SMX were detected as 55.8%, 46%, 47.5% and 67.2%; respectively. No resistance was detected to vancomycin and levofloxacin. Constitutive macrolide-lincosamide-streptogramin B (cMLSB) phenotype and M phenotype were observed in 82.4% (n= 28) and 17.6% (n= 6) of the macrolide resistant isolates, respectively. Inducible macrolide-lincosamide-streptogramin B (iMLSB) phenotype was not detected. The macrolid resistance genotypes, ermB, mef(A)/(E), were positive 50% and 14.7%; respectively. Both ermB and mef(A)/(E) genes were detected 35.3% of the macrolid resistant isolates. None of the isolates were positive for ermTR gene. The most
Matthews, Healther; Tooley, Cathy; Nicholls, Carol; Lindsey-Halls, Anna
In 2011, the respiratory nursing team at the James Paget University Hospital Foundation Trust were considering introducing a discharge care bundle for patients admitted with an acute exacerbation of chronic obstructive pulmonary disease. At the same time, the trust was asking for applications for Commissioning for Quality and Innovation schemes (CQUINs). These are locally agreed packages of quality improvement goals and indicators, which, if achieved in total, enable the provider to earn its full CQUIN payment. A CQUIN scheme should address the three domains of quality, safety and effectiveness, patient experience and also show innovation. This article discusses how the care bundle was introduced and how, over a 12-month period, it showed tangible results in improving the care pathway for COPD patients as well as reducing readmissions and saving a significant amount of money.
In the treatment of chronic obstructive pulmonary disease (COPD), bronchodilators such as long acting muscarinic antagonist (LAMA) and long acting β agonist(LABA) play key roles for improving respiratory function and symptoms, and reducing risk of exacerbation. However, inhaled corticosteroid (ICS), a key medicine for bronchial asthma, is limitedly used in COPD treatment. Japanese Respiratory Society recommends to use ICS for severe COPD patients who have been frequently exacerbated, because previous clinical studies indicated that ICS reduces exacerbation in moderate to severe COPD patients. Asthma sometimes overlaps with COPD, and symptoms of those patients are not well controlled by the bronchodilation therapy alone. Therefore, ICS/LABA or ICS/LAMA should be prescribed to those overlapped patients. Concentration of exhaled nitrogen oxide and percentage of peripheral eosinophil may be good biomarkers for discriminating the COPD patients who have good response to ICS treatment.
Allegra, L; Cordaro, C I; Grassi, C
The efficacy and safety of carbocysteine lysine salt monohydrate (SCMC-Lys) in the prevention of acute exacerbations associated with chronic obstructive bronchitis were evaluated in a multicenter double-blind, placebo-controlled, parallel group trial in 662 outpatients. After a 1-month run-in period, patients were randomized to three groups and assigned to receive one of the following oral treatments: continuous SCMC-Lys 2.7 g once daily, intermittent SCMC-Lys at the same dosage (1-week courses alternating with 1-week intervals on placebo) or placebo. Each treatment lasted for 6 months and spanned the cooler months of the year. Evaluation was based on a daily recording of relevant clinical symptoms and signs and subsequent evaluation of the collected data by three blinded independent physicians. A total of 146 patients (23%) failed to complete the 6-month treatment (mostly due to difficulties in complying with protocol requirements), without clear-cut differences in the dropout rate in the three groups. An intention-to-treat analysis revealed that the incidence of patients without exacerbations in the group assigned to continuous SCMC-Lys treatment was significantly higher than in the placebo-treated group (p < 0.001). The total number of patients with at least one exacerbation was 66 (29.6%) in the group treated with continuous SCMC-Lys compared with 100 (45.9%) with placebo. In the former group the time between initiation of treatment and first exacerbation was significantly prolonged. The average number of days with acute respiratory illness was significantly decreased in the group receiving continuous SCMC-Lys compared with the group receiving placebo, and this was associated with a significant reduction in the antibiotic consumption during the trial period. In patients assigned to intermittent treatment, results of the assessed endpoints did not differ significantly from those observed in the placebo group. No serious adverse effects were reported. It is
Eaton, T; Fergusson, W; Kolbe, J; Lewis, C A; West, T
Short-burst oxygen therapy (SBOT) remains widely advocated for patients with chronic obstructive pulmonary disease (COPD), despite a lack of supporting evidence. The aim of this randomised, double-blind, placebo-controlled, parallel group study was to determine whether SBOT improves health-related quality of life (HRQL) or reduces acute healthcare utilisation in patients discharged following an acute exacerbation of COPD. Consecutive patients were screened; 78 of 331 were eligible for randomisation to cylinder oxygen, cylinder air or usual care following discharge. Patients were elderly with high acute healthcare utilisation, forced expiratory volume in one second of <1 L and had dyspnoea limiting daily activity but were not hypoxaemic at rest. Over the 6-month study period, there were no significant differences between patient groups in HRQL (Chronic Respiratory Questionnaire (CRQ), 36-item Short-Form Health Survey, Hospital Anxiety and Depression Scale) except for CRQ emotion domain. There were no significant differences in acute healthcare utilisation. Time to readmission was greatest in the usual care group. Cylinder use was high initially, but rapidly fell to very low levels within weeks in both cylinder oxygen and air groups. In conclusion, the availability of short-burst oxygen therapy for chronic obstructive pulmonary disease patients discharged from hospital following an acute exacerbation did not improve health-related quality of life or reduce acute healthcare utilisation. These results provide no support for the widespread use of short-burst oxygen therapy.
Grus, Tomáš; Lambert, Lukáš; Rohn, Vilém; Klika, Tomáš; Grusová, Gabriela; Michálek, Pavel
We present a case of a female patient with infectious (mycotic) juxtarenal abdominal aneurysm with atypical symptoms beginning as acute exacerbation of chronic cholecystitis. Apart from common antibiotic treatment, the patient successfully underwent resection of the diseased segment and replacement by a fresh allograft in order to reduce the risk of infection of the graft, but with the need of subsequent life-long immunosuppressive therapy. Perioperative monitoring of the spinal cord by near infrared spectroscopy was used to identify possible spinal ischemia. The choice of the fresh allograft was based on our experience supported by review of the literature.
Kerolus, Ghaly; Ikladios, Ossama
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of disability and death worldwide. COPD exacerbation is usually treated with antibiotics, systemic corticosteroids, and inhaled bronchodilators. We present a case of recurrent COPD exacerbation that was treated repeatedly with standard therapy. Dynamic expiratory computed tomography of the chest was done, which revealed concomitant tracheomalacia. COPD and tracheomalacia may coexist during recurrent exacerbations of COPD, and delayed diagnosis can be associated with severe comorbidities. Ordering the appropriate imaging may aid in the correct diagnosis and facilitate appropriate management. PMID:27987292
Baker, Jillian G; Wilcox, Robert G
Treating people with cardiovascular disease and COPD causes significant clinician anxiety. β-Blockers save lives in people with heart disease, specifically postinfarction and heart failure. COPD and heart disease frequently coexist and people with both disorders have particularly high cardiovascular mortality. There are concerns about giving β-blockers to people with concomitant COPD that include reduced basal lung function, diminished effectiveness of emergency β-agonist treatments, reduced benefit of long-acting β-agonist treatment and difficulty in discriminating between asthma and COPD. β-Blockers appear to reduce lung function in both the general population and those with COPD because they are poorly selective for cardiac β1-adrenoceptors over respiratory β2-adrenoceptors, and studies have shown that higher β-agonist doses are required to overcome the β-blockade. COPD and cardiovascular disease share similar environmental risks and both disease states have high adrenergic and inflammatory activation. β-Blockers may therefore be particularly helpful in reducing cardiovascular events in this high-risk group. They may reduce the background inflammatory state, and inhibit the tachycardia and hypertension associated with both the endogenous adrenaline and high-dose β-agonist treatment associated with acute exacerbations of COPD. Some studies have suggested no increased and, at times, reduced mortality in patients with COPD taking β-blockers for heart disease. However, these are all observational studies and there are no randomised controlled trials. Potential ways to improve this dilemma include the development of highly β1-selective β-blockers or the use of non-β-blocking heart rate reducing agents, such as ivabridine, if these are proven to be beneficial in randomised controlled trials.
Azevedo, Pedro; Costa, João; Vaz-Carneiro, António
Acute exacerbations of chronic obstructive pulmonary disease are a major cause of hospital admissions and mortality, contributing to the decline in lung function, exercise capacity and quality of life. Infections are the major cause of exacerbations and treatment includes antibiotics, bronchodilators and systemic corticosteroids as anti- inflammatory agents. This Cochrane review compared: 1. use of oral and parenteral corticosteroids with placebo use; 2. routes of administration among themselves. The results indicate that there is evidence for the use of corticosteroids in the treatment of chronic obstructive pulmonary disease exacerbations since early improvement in lung function [assessed by forced expiratory volume in one second (FEV1)] has been noted, the likelihood of treatment failure and relapse in the first month has been reduced and it shortens the hospital stay in patients who do not require intensive care regimen. However, corticosteroid therapy causes an increase in adverse effects associated with drug, namely hyperglycaemia, especially if the route of administration is parenteral. Parenteral route has not shown to be superior to oral route in treatment failure, relapse, or death. Mortality up to 30 days does not seem to be affected by the use of corticosteroids.
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...
Brynildsen, Jon; Høiseth, Arne Didrik; Følling, Ivar; Brekke, Pål H.; Christensen, Geir; Hagve, Tor-Arne; Verbalis, Joseph G.; Omland, Torbjørn; Røsjø, Helge
Background Hyponatremia is prevalent and associated with mortality in patients with heart failure (HF). The prevalence and prognostic implications of hyponatremia in acute exacerbation of chronic obstructive pulmonary (AECOPD) have not been established. Method We included 313 unselected patients with acute dyspnea who were categorized by etiology of dyspnea according to established guidelines (derivation cohort). Serum Na+ was determined on hospital admission and corrected for hyperglycemia, and hyponatremia was defined as [Na+]<137 mmol/L. Survival was ascertained after a median follow-up of 816 days and outcome was analyzed in acute HF (n = 143) and AECOPD (n = 83) separately. Results were confirmed in an independent AECOPD validation cohort (n = 99). Results In the derivation cohort, median serum Na+ was lower in AECOPD vs. acute HF (138.5 [135.9–140.5] vs. 139.2 [136.7–141.3] mmol/L, p = 0.02), while prevalence of hyponatremia (27% [22/83] vs. 20% [29/143], p = 0.28) and mortality rate (42% [35/83] vs. 46% [66/143], p = 0.56) were similar. By univariate Cox regression analysis, hyponatremia was associated with increased mortality in acute HF (HR 1.85 [95% CI 1.08, 3.16], p = 0.02), but not in AECOPD (HR 1.00 [0.47, 2.15], p = 1.00). Analogous to the results of the derivation cohort, hyponatremia was prevalent also in the AECOPD validation cohort (25% [25/99]), but not associated with mortality. The diverging effect of hyponatremia on outcome between AECOPD and acute HF was statistically significant (p = 0.04). Conclusion Hyponatremia is prevalent in patients with acute HF and AECOPD, but is associated with mortality in patients with acute HF only. PMID:27529844
Chassany, Olivier; Bonaz, B.; Bruley Des Varannes, S.; Bueno, L.; Cargill, Guillaume; Coffin, Benoit; Ducrotte, Philippe; Grange, V.
Background Abdominal pain is the predominant symptom in IBS patients. Phloroglucinol (P) and its methylated derivative (TMP) are antispasmodic agents acting on smooth muscle. Aim To evaluate the efficacy of P/TMP on pain intensity during an acute exacerbation of pain of IBS over a one-week period treatment. Methods IBS Rome II patients seeking medical advice for an acute exacerbation of abdominal pain were randomised to P/TMP (62.2mg P + 80mg TMP) 2 pills tid or placebo for 7 days. Patients were included if they had a pain with a minimal intensity of 40 on a 100 mm visual analog scale, and if pain occurred at least 2 days during the week previous inclusion. Results 307 patients were included by 78 GPs. The intent to treat population included 300 patients, aged of 46.9±14.8 years (73% female). The relative decrease of pain intensity at day 7 was 57.8±31.7% vs. 46.3±34.7% (Δ=11.5±3.8%, [CI95%: 4.0; 19.1], p=0.0029) and the percentage of patients with at least a 50% decrease of pain intensity was 62.3% vs. 47.0% (Δ=15.3±5.7%, [CI95%: 4.1; 26.5], p=0.0078) in P/TMP and placebo groups respectively. Conclusions A one-week P/TMP treatment significantly reduces pain intensity in IBS patients consulting their GPs for pain exacerbation. PMID:17439513
Santibáñez, Miguel; Garrastazu, Roberto; Ruiz-Nuñez, Mario; Helguera, Jose Manuel; Arenal, Sandra; Bonnardeux, Cristina; León, Carlos; García-Rivero, Juan Luis
Background and Aim Exacerbations of chronic obstructive pulmonary disease (COPD) carry significant consequences for patients and are responsible for considerable health-care costs—particularly if hospitalization is required. Despite the importance of hospitalized exacerbations, relatively little is known about their determinants. This study aimed to analyze predictors of hospitalized exacerbations and mortality in COPD patients. Methods This was a retrospective population-based cohort study. We selected 900 patients with confirmed COPD aged ≥35 years by simple random sampling among all COPD patients in Cantabria (northern Spain) on December 31, 2011. We defined moderate exacerbations as events that led a care provider to prescribe antibiotics or corticosteroids and severe exacerbations as exacerbations requiring hospital admission. We observed exacerbation frequency over the previous year (2011) and following year (2012). We categorized patients according to COPD severity based on forced expiratory volume in 1 second (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 1–4). We estimated the odds ratios (ORs) by logistic regression, adjusting for age, sex, smoking status, COPD severity, and frequent exacerbator phenotype the previous year. Results Of the patients, 16.4% had ≥1 severe exacerbations, varying from 9.3% in mild GOLD grade 1 to 44% in very severe COPD patients. A history of at least two prior severe exacerbations was positively associated with new severe exacerbations (adjusted OR, 6.73; 95% confidence interval [CI], 3.53–12.83) and mortality (adjusted OR, 7.63; 95%CI, 3.41–17.05). Older age and several comorbidities, such as heart failure and diabetes, were similarly associated. Conclusions Hospitalized exacerbations occurred with all grades of airflow limitation. A history of severe exacerbations was associated with new hospitalized exacerbations and mortality. PMID:27362765
MacDonald, Martin; Korman, Tony; King, Paul; Hamza, Kais; Bardin, Philip
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are crucial events but causes remain poorly defined. A method to clinically 'phenotype' AECOPD have been proposed, and 52 hospitalized chronic obstructive pulmonary disease exacerbations according to underlying aetiology have now been prospectively phenotyped. Multiple exacerbation phenotypes were identified. A subpopulation coinfected with virus and bacteria had a significantly longer length of hospital stay, and this pilot study indicates that exacerbation phenotyping may be advantageous.
Song, Yuanlin; Chen, Rongchang; Zhan, Qingyuan; Chen, Shujing; Luo, Zujin; Ou, Jiaxian; Wang, Chen
COPD is characterized by a progressive decline in lung function and mental and physical comorbidities. It is a significant burden worldwide due to its growing prevalence, comorbidities, and mortality. Complication by bronchial-pulmonary infection causes 50%–90% of acute exacerbations of COPD (AECOPD), which may lead to the aggregation of COPD symptoms and the development of acute respiratory failure. Non-invasive or invasive ventilation (IV) is usually implemented to treat acute respiratory failure. However, ventilatory support (mainly IV) should be discarded as soon as possible to prevent the onset of time-dependent complications. To withdraw IV, an optimum timing has to be selected based on weaning assessment and spontaneous breathing trial or replacement of IV by non-IV at pulmonary infection control window. The former method is more suitable for patients with AECOPD without significant bronchial-pulmonary infection while the latter method is more suitable for patients with AECOPD with acute significant bronchial-pulmonary infection. PMID:27042042
Zhang, Jing; Song, Yuan-Lin; Bai, Chun-Xue
Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the 'MIOTIC study' to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management.
Zhang, Jing; Song, Yuan-lin; Bai, Chun-xue
Chronic obstructive pulmonary disease (COPD) is a common disease that leads to huge economic and social burden. Efficient and effective management of stable COPD is essential to improve quality of life and reduce medical expenditure. The Internet of Things (IoT), a recent breakthrough in communication technology, seems promising in improving health care delivery, but its potential strengths in COPD management remain poorly understood. We have developed a mobile phone-based IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial entitled the ‘MIOTIC study’ to investigate the influence of mIoT among stable COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group C or D COPD and with a history of at least two moderate-to-severe exacerbations within the previous year will be randomly allocated to the control group, which receives routine follow-up, or the intervention group, which receives mIoT management. Endpoints of the study include (1) frequency and severity of acute exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) measurement; (4) exercise capacity; and (5) direct medical cost per year. Results from this study should provide direct evidence for the suitability of mIoT in stable COPD patient management. PMID:24082784
Moretti, Maurizio; Fagnani, Stefano
Purpose Mucolytics can improve disease outcome in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The objectives of this study were to investigate the effects of erdosteine (ER), a mucolytic agent with antioxidant activity, on systemic inflammation, symptoms, recurrence of exacerbation, and time to first exacerbation postdischarge in hospitalized patients with AECOPD. Patients and methods Patients admitted to hospital with AECOPD were randomized to receive either ER 900 mg daily (n=20) or a matching control (n=20). Treatment was continued for 10 days until discharge. Patients also received standard treatment with steroids, nebulized bronchodilators, and antibiotics as appropriate. Serum C-reactive protein levels, lung function, and breathlessness–cough–sputum scale were measured on hospital admission and thereafter at days 10 and 30 posttreatment. Recurrence of AECOPD-requiring antibiotics and/or oral steroids and time to first exacerbation in the 2 months (days 30 and 60) postdischarge were also assessed. Results Mean serum C-reactive protein levels were lower in both groups at days 10 and 30, compared with those on admission, with significantly lower levels in the ER group at day 10. Improvements in symptom score and forced expiratory volume in 1 second were greater in the ER than the control group, which reached statistical significance on day 10. ER was associated with a 39% lower risk of exacerbations and a significant delay in time to first exacerbation (log-rank test P=0.009 and 0.075 at days 30 and 60, respectively) compared with controls. Conclusion Results confirm that the addition of ER (900 mg/d) to standard treatment improves outcomes in patients with AECOPD. ER significantly reduced airway inflammation, improved the symptoms of AECOPD, and prolonged time to first exacerbation. The authors suggest ER could be most beneficial in patients with recurring, prolonged, and/or severe exacerbations of COPD. PMID
Tang, Clarice Y; Taylor, Nicholas F; Blackstock, Felicity C
The aim of the study is to explore the experiences of inpatients with an acute exacerbation of chronic obstructive pulmonary disease, who participated in a very early exercise programme while acutely unwell. This qualitative study analysed responses from participant interviews as part of a mixed method trial whereby participants were randomly allocated into three groups: low intensity, moderate to high intensity aerobic and resistance exercises or a control group who received routine physiotherapy. Everyone allocated to the exercise groups were invited to participate in the qualitative study. Interviews were within a week post discharge and the results were analysed thematically. A total of 19 participants were interviewed and described their experience as positive and beneficial and reported an increased motivation towards exercising. These findings converged with the high levels of exercise adherence (83%) and within-group improvements in walking capacity observed in both exercise groups. Participants also reported commencement of a home exercise programme after discharge but intention to participate in community pulmonary rehabilitation remained low. Participation in a very early exercise programme while acutely unwell can lead to positive attitude towards exercise. The results converge with the quantitative results that provided preliminary evidence of programme feasibility and within-group improvement in exercise tolerance.
Toft-Petersen, Anne Pernille; Torp-Pedersen, Christian; Weinreich, Ulla Møller; Rasmussen, Bodil Steen
Low concentrations of hemoglobin have previously been demonstrated in many patients with COPD. There is evidence of anemia as a prognostic factor in acute exacerbations, but the detailed relationship between concentrations of hemoglobin and mortality is not known. A register-based cohort of patients admitted for the first time to Danish hospitals for acute exacerbations of COPD from 2007 through 2012 was established. Age, sex, comorbidities, medication, renal function, and concentrations of hemoglobin were retrieved. Sex-specific survival analyses were fitted for different rounded concentrations of hemoglobin. The cohort encompassed 6,969 patients. Hemoglobin below 130 g/L was present in 39% of males and below 120 g/L in 24% of females. The in-hospital mortality rates for patients with hemoglobin below or above these limits were 11.6% and 5.4%, respectively. After discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22–1.73), adjusted HR 1.37 (95% CI 1.15–1.64). Compared to hemoglobin 120 g/L, the HR for females with hemoglobin 110 g/L was 1.4 (95% CI 1.17–1.68), adjusted HR 1.28 (95% CI 1.06–1.53). In conclusion, low concentrations of hemoglobin are frequent in COPD patients with acute exacerbations, and predict long-term mortality. PMID:27877035
Poole, Phillippa J
There is, to date, no medical therapy that modifies the decline in lung function that occurs in COPD. As the disease becomes more severe, exacerbations of COPD become increasingly common, affecting patient quality of life and increasing health care costs. Mucolytic agents, through their actions on inflammatory and oxidative pathways, have potential benefits in COPD. This paper reviews the randomized controlled trial (RCT) evidence for the effectiveness of at least 2 months of daily therapy with oral mucolytics in COPD. Based on evidence from 26 RCTs, mucolytics reduce exacerbations by up to 0.8 exacerbations per year, with a greater effect in patients with more severe COPD. This effect appears to be of a similar magnitude to the reduction in exacerbations seen with tiotropium and inhaled corticosteroids (ICS), but RCTs that compared the agents would be required to confirm this. Mucolytics do not affect the rate of lung function decline, but they do not have any significant adverse effects. Mucolytic treatment should be considered in: patients with more severe COPD who have frequent or prolonged exacerbations; those who are repeatedly admitted to hospital; or in those patients with frequent exacerbations who are unable to take tiotropium or ICS. PMID:18046889
Xiang, Yu-Tao; Wong, Tak-Shun; Tsoh, Joshua; Ungvari, Gabor S; Correll, Christoph U; Ko, Fanny W S; Hui, David S C; Chiu, Helen F K
This study aimed to determine the frequency and sociodemographic/clinical correlates of insomnia in Chinese patients aged ≥60 years suffering from chronic obstructive pulmonary disease (COPD). In this case-control study of 142 outpatients with COPD and 218 sex- and age-matched control subjects, COPD patients were recruited from a prospective study sample hospitalized in Hong Kong for acute COPD exacerbation (≥2 major COPD symptoms or >1 major+minor COPD symptoms for ≥2 consecutive days). Controls were recruited from social centres in Hong Kong. Activity of daily living was assessed with the Instrumental Activities of Daily Living Scale, life events were evaluated using the Life Event Scale, depressive symptoms were ascertained with the Geriatric Depression Scale, and quality of life was measured using the Medical Outcomes Study Short Form-12. Early, middle and late insomnia were measured using items 4, 5 and 6 of the Hamilton Rating Scale for Depression. The frequency of ≥1 type of insomnia was 47.2% in patients and 25.7% in controls; frequencies of early, middle and late insomnia in patients were 24.6%, 31.0%, and 26.1%, respectively, compared to 14.7%, 14.7% and 11.9% in controls. Group differences were non-significant after controlling for relevant covariates. However, in multiple logistic regression analysis, more physical illnesses (p = 0.02, OR = 1.3, 95% CI = 1.1-1.7) and more severe depressive symptoms (p = 0.009, OR = 1.1, 95% CI = 1.03-1.3) were independently associated with any type of insomnia in COPD patients, accounting for 21.3% of the variance. A significant proportion of older adult Chinese COPD patients suffer from insomnia that warrants more attention in clinical practice.
Background The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. Methods We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study. Results 119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness. Conclusion Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history. Trial registration ClinicalTrials.gov: NCT00608764 PMID:21951550
Cazzola, Mario; Rogliani, Paola; Matera, Maria Gabriella
Chronic obstructive pulmonary disease (COPD) guidelines and strategies suggest escalating treatment, mainly depending on the severity of airflow obstruction. However, some de-escalation of therapy in COPD would be appropriate, although we still do not know when we should switch, step-up or step-down treatments in our patients. Unfortunately, trials comparing different strategies of step-up and step-down treatment (e.g. treatment initiation with one single agent and then further step-up if symptoms are not controlled versus initial use of double or triple therapy, possibly with lower doses of the individual components, or the role of N-acetylcysteine in combination therapy for a step-down approach) are still lacking. In general, there is a large and often inappropriate use of the inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination. However, the withdrawal of the ICS in COPD patients at low risk of exacerbation can be safe, provided that patients are under regular treatment with long-acting bronchodilators. Maximising the treatment in patients with a degree of clinical instability by including an ICS in the therapeutic regimen is useful to control the disease, but may not be needed during periods of clinical stability. In patients with severe but stable COPD, the withdrawal of the ICS from triple therapy [LABA + long-acting muscarinic antagonist (LAMA) + ICS] is possible, but not when the patient has been hospitalised for an acute exacerbation of COPD. We must still establish how long we should wait before withdrawing the ICS. It is still unclear whether the same is true when only the LABA or the LAMA is withdrawn while continuing treatment with the other bronchodilator and the ICS. In any case, we strongly believe that it is always better to avoid a therapeutic step-up progression when it is not needed rather than being forced subsequently into a step-down approach in which the outcome is always unpredictable.
Holm, Claire Præst; Holm, Jakob; Nørgaard, Annette; Godtfredsen, Nina
ABSTRACT Some COPD patients suffer from frequent exacerbations despite triple inhalation treatment. These frequent exacerbators should be identified, as exacerbations often lead to decreasing lung function and increasing mortality. Roflumilast reduces exacerbations in patients with a previous history of exacerbations. Our aim was to describe COPD patient characteristics and compare roflumilast treatment eligible to non-eligible patients. An observational cross-section study was conducted. Patients were included from a large COPD outpatient clinic. Information regarding COPD patient characteristics was registered on a standardized form and lung function was measured. Patients were categorized according to the GOLD classification. Eligibility for roflumilast treatment was assessed and patient characteristics compared between groups. 547 patients were included. Most patients (54%) were in GOLD group D. 62 patients (11.3%) met the criteria for treatment with roflumilast. Among the patients eligible for roflumilast treatment, only 14 patients (22.6%) were receiving treatment. There were no significant differences in FEV1, number of exacerbations, hospitalization due to exacerbation, MRC grade, age, smoking status and medication use between patients receiving roflumilast and not treated eligible patients. Our study documents low use of roflumilast treatment. In view of the established effect of roflumilast we think that this treatment should be considered more consistently as an option among COPD patients fulfilling the criteria for this therapy. PMID:28326174
Figueroa Casas, Juan Carlos; Schiavi, Eduardo; Mazzei, Juan Antonio; López, Ana María; Rhodius, Edgardo; Ciruzzi, Julián; Sívori, Martín
Since morbidity, mortality and socioeconomic costs from Chronic Obstructive Pulmonary Disease (COPD) are widely increasing, a group of respiratory medicine specialists was summoned by the AAMR to update basic knowledge on COPD and to issue recommendations for its prevention, diagnosis and treatment. The authors review the definition of COPD together with current knowledge on pathophysiology. Clinical presentation, functional evaluation and imaging are summarized. Early diagnosis through pulmonary function tests -mainly spirometry- and the role of smoking cessation are stressed. Smoking cessation strategies are described as well as pharmacological and non-pharmacological treatment. Long acting bronchodilators are considered the first pharmacological option for treatment due to its effectiveness and patient compliance. Inhaled corticosteroids are indicated in combination with long-acting bronchodilators in patients who present persistent airway obstruction associated with frequent exacerbations since they reduce their number although further studies are needed to confirm their cost/benefit. Annual influenza vaccination is recommended in all patients. In the non-pharmacological section, surgery for emphysema is suggested in very specific cases. Respiratory rehabilitation is a useful tool for patients with daily activities limitation. Long-term oxygen therapy at home improves survival in patients with severe chronic hypoxemia. Non-invasive home ventilation in chronic patients has limited indications in specific subgroups. Acute exacerbations should be aggressively treated with bronchodilators, oxygen, antibiotics, corticosteroids and eventually mechanical ventilation, as invasive as not invasive respiratory support. The importance of public education as well as of individual patients and their families is deemed essential in the prevention and treatment of the disease.
Andenaes, Randi; Moum, Torbjørn; Kalfoss, Mary H; Wahl, Astrid K
The purpose of this paper was to describe quality of life (QoL) following an acute exacerbation of chronic obstructive pulmonary disease (COPD), and to examine possible relationships between QoL, health status, psychological distress and QoL. This prospective longitudinal study examined data from hospitalization and two subsequent phases, collected over a 9-month period. The sample consisted of 51 COPD patients aged 48-87 years. Health status was assessed with the St George's Respiratory Questionnaire (SGRQ); psychological distress with the Hopkins Symptom Checklist (HSCL); and quality of life using the World Health Organization Quality of Life - Bref (WHOQOL - Bref). Health status improved significantly over the 9 months; from 65.95 to 59.40 (p = 0.001) in the SGRQ total score. Psychological distress improved significantly from hospitalization to the 1-month assessment (T2) (p = 0.001). QoL remained stable except for a significant increase in the physical domain from hospitalization to T2, and in the environmental domain from hospitalization to T2 and T3. Test-retest correlations of the WHOQOL - Bref were high. The results suggest an improvement in the health status over a 9-month period from being discharged after an exacerbation of COPD in spite of high levels of psychological distress and reduced QoL.
José, Anderson; Dal Corso, Simone
Background: The 6-minute walk test (6MWT) and the Glittre ADL-test (GT) are used to assess functional capacity and exercise tolerance; however, the reproducibility of these tests needs further study in patients with acute lung diseases. Objectives: The aim of this study was to investigate the reproducibility of the 6MWT and GT performed in patients hospitalized for acute and exacerbated chronic lung diseases. Method: 48 h after hospitalization, 81 patients (50 males, age: 52±18 years, FEV1: 58±20% of the predicted value) performed two 6MWTs and two GTs in random order on different days. Results: There was no difference between the first and second 6MWT (median 349 m [284-419] and 363 m [288-432], respectively) (ICC: 0.97; P<0.0001). A difference between the first and second tests was found in GT (median 286 s [220-378] and 244 s [197-323] respectively; P<0.001) (ICC: 0.91; P<0.0001). Conclusion: Although both the 6MWT and GT were reproducible, the best results occurred in the second test, demonstrating a learning effect. These results indicate that at least two tests are necessary to obtain reliable assessments. PMID:26039036
Chouinard, G; Safadi, G; Beauclair, L
We carried out a 9-day double-blind clinical trial comparing intramuscular zuclopenthixol acetate with liquid oral haloperidol in the treatment of 40 newly admitted schizophrenic patients with acute exacerbation. A parallel-group design was used with stratification by sex. Zuclopenthixol acetate (50 to 150 mg) was given intramuscularly every 3 days, whereas liquid haloperidol (10 to 30 mg daily) was given orally three times a day, with supplementary doses of each medication given under double-blind conditions when needed for agitation. No other sedative drugs, including benzodiazepines, were administered. The mean daily dose was 18.9 mg for haloperidol as compared with a mean dose per 3 days of 117.6 mg for zuclopenthixol. The two treatments were found to be equally efficacious on the Brief Psychiatric Rating Scale and Clinical Global Impression Scale. Both drugs induced similar extrapyramidal side effects. However, more tremors were associated with zuclopenthixol as was a tendency for tardive dyskinesia to be unmasked at the end of the injection interval. Sedation was higher with zuclopenthixol acetate than with haloperidol. Serum creatinine phosphokinase levels were not significantly increased after zuclopenthixol injections. The results of this trial suggest that zuclopenthixol acetate given intramuscularly every second to third day offers an alternative to conventional liquid oral haloperidol in the management of acute schizophrenia.
Poulaki, Vassiliki; Qin, Wenying; Joussen, Antonia M.; Hurlbut, Peter; Wiegand, Stanley J.; Rudge, John; Yancopoulos, George D.; Adamis, Anthony P.
Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy. Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats. Retinal nuclear extracts from insulin-treated rats contain higher hypoxia-inducible factor-1α (HIF-1α) levels and demonstrate increased HIF-1α–dependent binding to hypoxia-responsive elements in the VEGF promoter. Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect. The insulin-induced retinal HIF-1α and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1α–mediated increase in retinal VEGF expression. Insulin-induced VEGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1α–independent and requires PKC and p42/p44 MAPK. To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy. PMID:11901189
Nouira, Semir; Bouida, Wahid; Grissa, Mohamed H; Beltaief, Kaouther; Trimech, Mohamed N; Boubaker, Hamdi; Marghli, Soudani; Letaief, Mondher; Boukef, Riadh
Treatment with short-acting β2-agonists for exacerbations of chronic obstructive pulmonary disease (COPD) results in clinical improvement. It has not been established whether combining short-acting β2-agonists to other bronchodilators is more effective than β2-agonists alone. We conducted a study in patients presenting to the emergency department with exacerbation of COPD. They were randomized to receive nebulized ipratropium bromide (IB group; n = 62) or combined nebulized and intravenous bolus of magnesium sulfate (MgSO4 group; n = 62). All nebulized drugs were administered at 30-minute intervals for 2 hours. Primary outcome included hospital admission, endotracheal intubation, and hospital death rates. Secondary outcome measures were improvement in peak expiratory flow, dyspnea score, and arterial blood gas changes within the first 3 hours. There were no significant differences in primary outcome between MgSO4 and IB groups. Patients given IB average 32 L greater improvement in peak expiratory flow rate compared with magnesium sulfate (95% confidence interval, 19-43 L) at 180 minutes. Simultaneously, there was a significant reduction in PaCO2 compared with baseline values in IB group but not in MgSO4 group. There was a statistically nonsignificant trend toward a decrease in dyspnea score in both groups although adverse events were similar. Although the improvement in peak expiratory flow rate and arterial blood gas favored nebulized IB over magnesium sulfate, there was a nonsignificant difference between both drugs with regard to hospital admission, intubation, and hospital death rates in patients with COPD treated in the emergency department for acute exacerbation.
Soltaninejad, Forogh; Kheiri, Soleiman; Habibian, Roya; Amra, Arshia; Asgari-Savadjani, Shahin
Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. Exacerbation of COPD has negative effect on quality of life. Therapeutic effect of nebulized antibiotics in pulmonary infections has been reported previously. Hence, we evaluated the effect of nebulized gentamicin in acute exacerbation of COPD (AECOPD). Materials and Methods: In this clinical trial study, 86 hospitalized patients with AECOPD were divided into two groups for using nebulized gentamicin twice daily (case group) and placebo (control group) for 5 days in addition to standard treatment. On admission and on the 6th day, respiratory rate (RR), white blood cell (WBC), spirometry, and SPO2 (arterial O2 saturation by pulse oxymetry) were measured in groups. The severity of dyspnea was evaluated by the Medical Research Council scale. Results: In both groups, changes of SpO2, RR, forced an expiratory volume of first second (FEV1), and forced vital capacity (FVC) were significant during the times of intervention (P < 0.05). However, changes of FEV1 and FVC were significantly different between two groups (P < 0.05). So that increments of FEV1 and FVC were higher in the case group than control group. WBC decreased significantly in the case group (P < 0.05) compared to control group. There was no significant difference between groups in severity of dyspnea after intervention (P > 0.05). Conclusion: Treatment with Nebulized Gentamicin in AECOPD exacerbation resulted in further improvement of FVC and FEV1 on the 6th day. PMID:27904601
Chronic obstructive pulmonary disease (COPD) is associated with high incidence of morbidity and mortality. Oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, and carbocysteine; Nrf2 activators, and dietary polyphenols (curcumin, resveratrol, green tea, and catechins/quercetin) have been reported to increase intracellular thiol status alongwith induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD; it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD. PMID:19124382
Oishi, Keiji; Aoe, Keisuke; Mimura, Yusuke; Murata, Yoriyuki; Sakamoto, Kenji; Koutoku, Wataru; Matsumoto, Tsuneo; Ueoka, Hiroshi; Yano, Masafumi
Objective Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are fatal episodes of acute respiratory worsening of unknown etiology. Previous studies on acute respiratory distress syndrome have shown that direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) can have a beneficial effect on the respiratory status. This retrospective study investigated the prognosis and survival outcome of patients with AE-IPF who underwent PMX-DHP. Methods We examined the records of 50 patients with AE-IPF treated in our hospital. All patients received corticosteroid pulse therapy. We compared the disease outcome between 27 patients who underwent PMX-DHP (PMX group) and 23 patients who did not (non-PMX group). The independent predictors of survival were determined using Cox proportional hazards analyses. Results A multivariate analysis of all patients revealed that PMX-DHP therapy was a significant predictor of survival (HR=0.442, 95% CI 0.223-0.873; p=0.019). The 12-month survival rate was significantly higher in the PMX group than in the non-PMX group (41.7% vs. 9.8%; p=0.040). According to a subanalysis of the PMX group, the time from AE-IPF onset to PMX-DHP was a significant predictor of survival (HR=1.080, 95% CI 1.001-1.166; p=0.049). Conclusion PMX-DHP improved the prognosis of AE-IPF. The time from AE-IPF onset to PMX-DHP may therefore be informative for predicting the patient outcome. PMID:27980253
Tantucci, Claudio; Pini, Laura
COPD is a common cause of disability, morbidity and mortality worldwide and a major global health problem with enormous direct and indirect health care costs. Different reasons can be advanced to explain it, but among them the possibility that the recommended diagnostic and therapeutic approaches to COPD were less effective than they could be, should be also considered. The pharmacological baseline treatment of stable COPD has been widely based on the severity of airflow obstruction and recently, of chronic symptoms and on the annual number of previous exacerbations. These recommendations do not take into account the underlying prevalent disease that should be treated and the future risk. Our suggestion is that the therapy must be firstly tailored on the prevalent disease leading to COPD, independently from the degree of FEV1 reduction and chronic dyspnea and only after that, according to the severity of the disorder (and age of patient), to establish the level of the treatment in order to freeze, when possible, and not to follow the underlying pathological process, running after it. Moreover, given the relevance of exacerbations in the natural history of COPD, greater effort should be placed on recognition of their prevalent type in frequent exacerbators and to prevent them using more tailored and specific treatment. PMID:26648707
Lacoma, A; Prat, C; Andreo, F; Domínguez, J
Chronic obstructive pulmonary disease (COPD) is still a leading cause of morbidity and mortality worldwide, with a huge socioeconomic impact. New strategies for the management of COPD are required, not only for identifying the origin of the exacerbation episodes, but also to assess an individual risk for each patient. A promising approach is to measure systemic biomarkers and correlate their levels with exacerbation characteristics and clinical prognosis of the disease. Several biomarkers have clearly correlated with the aetiology of lower respiratory tract infections and the response to antibiotic treatment, indicating a potential utility in COPD exacerbation. Nevertheless, the results available at the moment, together with the absence of a gold standard for identifying the aetiological origin of an exacerbation, impedes establishing the real utility of these biomarkers for this concrete task. Regarding the clinical evolution and prognosis, several clinical characteristics have been correlated to biomarker levels. The potential influence of many factors (severity of the disease, presence of comorbidities and treatment) leads to the conclusion that, in the future, the best option would be to monitor levels individually, rather than establishing cut-off points for the general COPD population.
Krishnan, Jerry A.; Gussin, Hélène A.; Prieto-Centurion, Valentin; Sullivan, Jamie L.; Zaidi, Farhan; Thomashow, Byron M.
About 1 in 5 patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD) in the United States are readmitted within 30 days. The U.S. Centers for Medicare and Medicaid Services has recently expanded its Hospital Readmissions Reduction Program to financially penalize hospitals with higher than expected all-cause 30-day readmission rates following a hospitalization for COPD exacerbation. In October 2013, the COPD Foundation convened a multi-stakeholder National COPD Readmissions Summit to summarize our understanding of how to reduce hospital readmissions in patients hospitalized for COPD exacerbations. Over 225 individuals participated in the Summit, including patients, clinicians, health service researchers, policy makers and representatives of academic health care centers, industry, and payers. Summit participants recommend that programs to reduce hospital readmissions: 1) Include specific recommendations about how to promote COPD self-management skills training for patients and their caregivers; 2) Adequately address co-existing disorders common to COPD in care plans during and after hospitalizations; 3) Include an evaluation of adverse events when implementing strategies to reduce hospital readmissions; and 4) Develop a strategy (e.g., a learning collaboratory) to connect groups who are engaged in developing, testing, and implementing programs to reduce hospital readmissions for COPD and other conditions. PMID:25927076
Oki, Yutaro; Kaneko, Masahiro; Fujimoto, Yukari; Sakai, Hideki; Misu, Shogo; Mitani, Yuji; Yamaguchi, Takumi; Yasuda, Hisafumi; Ishikawa, Akira
Purpose Pulmonary hypertension and exercise-induced oxygen desaturation (EID) influence acute exacerbation of COPD. Computed tomography (CT)-detected pulmonary artery (PA) enlargement is independently associated with acute COPD exacerbations. Associations between PA to aorta (PA:A) ratio and EID in patients with COPD have not been reported. We hypothesized that the PA:A ratio correlated with EID and that results of the 6-minute walk test (6MWT) would be useful for predicting the risk associated with PA:A >1. Patients and methods We retrospectively measured lung function, 6MWT, emphysema area, and PA enlargement on CT in 64 patients with COPD. The patients were classified into groups with PA:A ≤1 and >1. Receiver-operating characteristic curves were used to determine the threshold values with the best cutoff points to predict patients with PA:A >1. Results The PA:A >1 group had lower forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1:FVC ratio, diffusion capacity of lung carbon monoxide, 6MW distance, and baseline peripheral oxygen saturation (SpO2), lowest SpO2, highest modified Borg scale results, percentage low-attenuation area, and history of acute COPD exacerbations ≤1 year, and worse BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index results (P<0.05). Predicted PA:A >1 was determined for SpO2 during 6MWT (best cutoff point 89%, area under the curve 0.94, 95% confidence interval 0.88–1). SpO2 <90% during 6MWT showed a sensitivity of 93.1, specificity of 94.3, positive predictive value of 93.1, negative predictive value of 94.3, positive likelihood ratio of 16.2, and negative likelihood ratio of 0.07. Conclusion Lowest SpO2 during 6MWT may predict CT-measured PA:A, and lowest SpO2 <89% during 6MWT is excellent for detecting pulmonary hypertension in COPD. PMID:27920514
Zhang, Wei; Chen, Chuanhui; Cui, Jian; Bai, Wei; Zhou, Jing
The present study explores the application of LAMP for rapid diagnosis of pathogenic bacteria in clinical sputum specimens of AECOPD as compared with conventional sputum culturing method. 120 sputum specimens of AECOPD patients, 46 sputum specimens of healthy controls, as well as 166 serum specimens as negative controls, were evaluated by LAMP assay using primers of eight typical respiratory pathogens. No cross-reactivity was observed in these negative control species using LAMP assay. The lower detection limit of LAMP assay was approximately 10(3) copies. 25 cases (20.8%) were detected at least one positive bacteria species by conventional sputum culturing method, while 73 cases (60.8%) were tested positive in LAMP assay. Moreover, compared with sputum culture, bacterial titers results of LAMP assay were more consistent with FEV1/FVC value of AECOPD patients. These results indicated that the sensitivity of LAMP assay was significantly higher than that of sputum culturing method.
Barnes, Peter J
Inhaled corticosteroids (ICS) are now very widely used in high doses in the management of COPD patients. In sharp contrast to the situation in asthma, ICS provide little or no benefit in COPD patients and may have long-term detrimental effects. High doses of ICS fail to reduce disease progression or mortality, even when combined with a long-acting beta(2)-agonist (LABA). Several trials have demonstrated that ICS reduce exacerbations by 20-25%, particularly in patients with more severe disease, but these studies are confounded by poor trial design and more appropriate analysis shows no benefit. Indeed, the benefit of combination inhalers seems to be largely due to the effect of the LABA, and long-acting bronchodilators--including tiotropium--provide similar benefits in reducing exacerbations. However, there may be some COPD patients, for example those with concomitant asthma, who benefit from ICS. Yet it has not been possible to identify any clinical factors that predict corticosteroid responsiveness in COPD patients in the large clinical trials. There is increasing evidence that high doses of ICS may have detrimental effects on bones and may increase the risk of pneumonia. ICS fail to suppress inflammation in COPD patients because there is a marked reduction in histone deacetylase-2, the nuclear enzyme that corticosteroids require to switch off activated inflammatory genes. In the future, alternative anti-inflammatory treatments will be needed for COPD or therapeutic strategies which reverse the molecular pathways that causes corticosteroid resistance.
Cheng, Shih-Lung; Lin, Ching-Hsiung
Background Blood eosinophil counts have been documented as a good biomarker for patients with chronic obstructive pulmonary disease (COPD) using inhaled corticosteroid (ICS) therapy. However, the effectiveness and safety of prescribing high or medium dose of ICS for patients with different eosinophil counts are unknown. Methods A post hoc analysis of a previous prospective randomized study was performed for COPD patients using higher dose (HD: Fluticasone 1,000 μg/day) or medium dose (MD: Fluticasone 500 μg/day) of ICS combined with Salmeterol (100 μg/day). Patients were classified into two groups: those with high eosinophil counts (HE ≥3%) and those with low eosinophil counts (LE <3%). Lung function was evaluated with forced expiratory volume in 1 second, forced vital capacity, and COPD assessment test. Frequencies of acute exacerbation and pneumonia were also measured. Results Two hundred and forty-eight patients were studied and classified into higher eosinophil (HE) (n=85, 34.3%) and lower eosinophil (LE) groups (n=163, 65.7%). The levels of forced expiratory volume in 1 second were significantly increased in patients of HE group treated with HD therapy, compared with the other groups (HE/HD: 125.9±27.2 mL vs HE/MD: 94.3±23.7 mL, vs LE/HD: 70.4±20.5 mL, vs LE/MD: 49.8±16.7 mL; P<0.05) at the end of the study. Quality of life (COPD assessment test) markedly improved in HE/HD group than in MD/LE group (HE/HD: 9±5 vs LE/MD: 16±7, P=0.02). The frequency of acute exacerbation was more decreased in HE/HD group patients, compared with that in LE/MD group (HE/HD: 13.5% vs LE/MD: 28.7%, P<0.01). Pneumonia incidence was similar in the treatment groups (HE/HD: 3.2%, HE/MD: 2.6%, LE/HD: 3.5%, LE/MD 2.8%; P=0.38). Conclusion The study results support using blood eosinophil counts as a biomarker of ICS response and show the benefits of greater improvement of lung function, quality of life, and decreased exacerbation frequency in COPD patients with blood eosinophil
Ramos, Frederick L; Krahnke, Jason S; Kim, Victor
Airway mucus is part of the lung’s native immune function that traps particulates and microorganisms, enabling their clearance from the lung by ciliary transport and cough. Mucus hypersecretion and chronic productive cough are the features of the chronic bronchitis and chronic obstructive pulmonary disease (COPD). Overproduction and hypersecretion by goblet cells and the decreased elimination of mucus are the primary mechanisms responsible for excessive mucus in chronic bronchitis. Mucus accumulation in COPD patients affects several important outcomes such as lung function, health-related quality of life, COPD exacerbations, hospitalizations, and mortality. Nonpharmacologic options for the treatment of mucus accumulation in COPD are smoking cessation and physical measures used to promote mucus clearance. Pharmacologic therapies include expectorants, mucolytics, methylxanthines, beta-adrenergic receptor agonists, anticholinergics, glucocorticoids, phosphodiesterase-4 inhibitors, antioxidants, and antibiotics. PMID:24493923
Zheng, Jingtong; Shi, Yue; Zhang, Weijie; Li, Ying; Gibson, Peter G.; Zhang, Chao; Lu, Junying; Sai, Jingying; Wang, Guoqiang
Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF-α, and MCP-1 were elevated in VP and coinfection subjects (p < 0.05), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls (p > 0.05). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF-α, and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD. PMID:28352642
Chirico, V; Lacquaniti, A; Leonardi, S; Grasso, L; Rotolo, N; Romano, C; Di Dio, G; Lionetti, E; David, A; Arrigo, T; Salpietro, C; La Rosa, M
Airway inflammation plays a central role in cystic fibrosis (CF) lung disease, and biomarkers of inflammation, such as high-mobility group box 1 (HMGB1) could be used to monitor disease activity. The main aim of this study was to confirm the role of HMGB1 in CF patients, correlating its serum and sputum levels with pulmonary function and inflammation. Serum and sputum HMGB1 were evaluated in a cohort of 31 CF patients and 30 non-smoking healthy subjects (HS group). Acute pulmonary exacerbation events and lung function decline have been also evaluated during a 3-year follow-up period. Serum HMGB1 levels were significantly higher than those measured in HS, such as sputum HMGB1. Kaplan-Meier survival curves revealed that patients with high HMGB1 values experienced a significantly faster evolution to decline of lung function. A multiple Cox regression analysis assessed that an increase of serum HMGB1 was associated with 5% increased risk of pulmonary disease progression, whereas elevated sputum HMGB1 was related to a 10% increased risk of lung function decline. In CF patients, HMGB1 closely reflects the entity of pulmonary impairment and represents a strong and independent risk marker for progression of lung function decline.
Crisafulli, Ernesto; Torres, Antoni; Huerta, Arturo; Méndez, Raúl; Guerrero, Mónica; Martinez, Raquel; Liapikou, Adamantia; Soler, Néstor; Sethi, Sanjay; Menéndez, Rosario
Recurrent hospitalizations in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients have clinical and economic consequences; particularly those readmitted soon after discharge. The aim of our observational study was to determine predictors of early readmission to hospital (30 days from discharge). Prospective data on 125 hospitalized AECOPD patients were collected over a 30-month period at two Spanish university hospitals. Based on readmission after discharge, patients were divided into non-readmitted (n = 96) and readmitted (n = 29). Measures of serum inflammatory biomarkers were recorded on admission to hospital, at day 3 and at discharge; data on clinical, laboratory, microbiological and severity features were also recorded. In a multivariate model, C-reactive protein (CRP) at discharge ≥ 7.6 mg/L, presence of diabetes and ≥ 1 hospitalization for AECOPD during previous year were significant risk factors for predicting readmission. Presence of all 3 risk factors perfectly identified the readmitted patients (positive and negative predictive values of 1.000; 95% CI, 1.00-1.00). A combination of 3 readily available clinical and biochemical parameters is accurate in identifying hospitalized AECOPD patients at risk for early readmission.
Laurin, Catherine; Moullec, Grégory; Bacon, Simon L; Lavoie, Kim L
Chronic obstructive pulmonary disease (COPD) exacerbations contribute significantly to morbidity and mortality. COPD is also associated with high levels of psychological distress, which has been linked with higher exacerbation rates. At a recent American Thoracic Society conference symposium titled "Depression and Obstructive Lung Disease: State of the Science and Future Directions" held in 2010 in New Orleans, clinicians and researchers identified a number of important research priorities related to psychiatric comorbidities, including the need to better understand their impact on COPD outcomes, such as exacerbations. This article reviews the current literature and quantifies the prospective impact of anxiety and depression on exacerbation risk in patients with COPD. The limitations of the existing literature and the perspectives for future research are addressed.
Torp-Pedersen, Christian; Weinreich, Ulla Møller; Rasmussen, Bodil Steen
Background Non-invasive ventilation (NIV) has been used for decades in treatment of exacerbations of chronic obstructive pulmonary disease (COPD). The impact of the changing use of assisted ventilation in acute exacerbations on outcomes has not been fully elucidated and we aimed to describe these changes in the Danish population and describe their consequences for mortality. Methods A register-based study was conducted of a cohort of 12,847 patients admitted for acute exacerbation of COPD (AECOPD) from 2004 through 2011, treated with invasive mechanical ventilation (IMV) or NIV for the first time. Age, sex, in-hospital mortality rates, time to death or readmission for AECOPD were established and changes over time tracked. Results The number of admissions for AECOPD where assisted ventilation was used was 1,130 in 2004 and had increased by 145% in 2011. First time ventilations increased by 88%. This was mainly due to an increase in use of NIV accounting for 36% of the total number of assisted ventilations in 2004 and 67% in 2011. The number of IMV with or without NIV treatments remained constant. The mean age of NIV patients increased from 71.5 to 73.6 years, but remained constant at 70.0 years in IMV patients. Mortality rates both in hospital and after discharge for patients receiving NIV remained constant throughout the period. In-hospital mortality following IMV increased from 30% to 38%, but mortality after discharge remained stable. Conclusion Assisted ventilation has been increasingly used in a broader spectrum of AECOPD patients since the introduction of NIV. The changes in treatment strategies have been followed by shifts in in-hospital mortality rates following IMV. PMID:28158267
Roche, Nicolas; Huchon, Gérard
COPD treatment begins with smoking cessation and influenza and pneumococcal vaccines. Bronchodilators are indicated when dyspnea on exertion is reported (usually, FEV1 < 80% predicted). On-demand short-acting agents are chosen when dyspnea is intermittent, daily long-acting agents are administered once dyspnea occurs in daily life activities. In all cases, anticholinergics and beta2 agonists can be associated when one class is not sufficiently effective. In patients with FEV1 < 50% predicted (budesonide-formoterol) or 60% predicted (fluticasone-salmeterol), repeated exacerbations and symptoms despite maintenance bronchodilators, fixed associations are indicated. When a handicap persists on pharmacological treatment, respiratory rehabilitation centered on education and exercise training has to be proposed. Care for COPD has to integrate treatment of comorbidities such as cardio-vascular diseases, anxiety-depression, malnutrition, muscle dysfunction, osteoporosis, anemia ... Ongoing research aims at identifying new therapeutic targets, focusing on inflammation, remodeling, protease-antiprotease balance, oxidative stress, lung regeneration/repair and mucus production.
Barrecheguren, Miriam; Román-Rodríguez, Miguel; Miravitlles, Marc
Background Some patients share characteristics of both COPD and asthma. As yet, there is no gold standard to identify patients with the so-called asthma–COPD overlap syndrome (ACOS). Objective To describe the differences between ACOS patients and the remaining COPD patients, and to compare the clinical characteristics of patients diagnosed with ACOS by two different criteria: previous diagnosis of asthma before the age of 40 years; and the diagnostic criteria of the Spanish guidelines of COPD. Methods Multicenter, observational, cross-sectional study performed in 3,125 COPD patients recruited in primary care and specialized outpatient clinics. Patients with COPD and a history of asthma before the age of 40 years were diagnosed with ACOS and compared to the remaining COPD patients. Subsequently, ACOS patients were subdivided based on whether they fulfilled the Spanish guidelines of the COPD diagnostic criteria or not, and they were compared. Results ACOS was diagnosed in 15.9% of the patients. These patients had different basal characteristics compared to the remaining COPD patients, including a higher frequency of women and more exacerbations despite lower tobacco exposure and better lung function. They were more likely to have features of asthma, such as a positive bronchodilator test, higher peripheral eosinophilia, and higher total immunoglobulin E. Within the ACOS group, only one-third fulfilled the diagnostic criteria of the Spanish guidelines of COPD; these individuals were not significantly different from the remaining ACOS patients, except for having more exacerbations and poorer lung function. Conclusion ACOS patients diagnosed on the basis of a previous diagnosis of asthma differed from the remaining COPD patients, but they were similar to ACOS patients diagnosed according to more restrictive criteria, suggesting that a history of asthma before the age of 40 years could be a useful criterion to suspect ACOS in a patient with COPD. PMID:26366067
Baines, Katherine J; Fu, Juan-juan; McDonald, Vanessa M; Gibson, Peter G
Background Exacerbations of asthma and COPD are a major cause of morbidity and mortality and are responsible for significant health care costs. This study further investigates interleukin (IL)-1 pathway activation and its relationship with exacerbations of asthma and COPD. Methods In this prospective cohort study, 95 participants with stable asthma (n=35) or COPD (n=60) were recruited and exacerbations recorded over the following 12 months. Gene expressions of IL-1 pathway biomarkers, including the IL-1 receptors (IL1R1, IL1R2, and IL1RN), and signaling molecules (IRAK2, IRAK3, and PELI1), were measured in sputum using real-time quantitative polymerase chain reaction. Mediators were compared between the frequent (≥2 exacerbations in the 12 months) and infrequent exacerbators, and the predictive relationships investigated using receiver operating characteristic curves and area under the curve (AUC) values. Results Of the 95 participants, 89 completed the exacerbation follow-up, where 30 participants (n=22 COPD, n=8 asthma) had two or more exacerbations. At the baseline visit, expressions of IRAK2, IRAK3, PELI1, and IL1R1 were elevated in participants with frequent exacerbations of both asthma and COPD combined and separately. In the combined population, sputum gene expression of IRAK3 (AUC=75.4%; P<0.001) was the best predictor of future frequent exacerbations, followed by IL1R1 (AUC=72.8%; P<0.001), PELI1 (AUC=71.2%; P<0.001), and IRAK2 (AUC=68.6; P=0.004). High IL-1 pathway gene expression was associated with frequent prior year exacerbations and correlated with the number and severity of exacerbations. Conclusion The upregulation of IL-1 pathway mediators is associated with frequent exacerbations of obstructive airway disease. Further studies should investigate these mediators as both potential diagnostic biomarkers predicting at-risk patients and novel treatment targets. PMID:28223794
Langan, C E; Zuck, P; Vogel, F; McIvor, A; Peirzchala, W; Smakal, M; Staley, H; Marr, C
The efficacy and safety of grepafloxacin were compared with clarithromycin in a randomized, double-blind, multicentre clinical trial of 805 patients with acute bacterial exacerbations of chronic bronchitis (ABECB). Patients were randomized to receive grepafloxacin 400 mg od for either 5 (n = 273) or 10 days (n = 268) or clarithromycin 250 mg bd for 10 days (n = 261). Patients were assessed pre-treatment, 3-5 days during treatment, 1-3 days post-treatment and at follow-up (21-28 days post-treatment). The clinical success rates for the evaluable patients were 91% in the 5 day grepafloxacin group, 95% in the 10 day grepafloxacin group and 86% in the clarithromycin group. At follow-up, respective rates were 72%, 81% and 73%. A total of 513 pathogens were isolated from the pre-treatment sputum specimens of 400 (49%) patients. The primary pathogens were Haemophilus influenzae (36% of isolates), Haemophilus parainfluenzae (27%), Moraxella catarrhalis (12%), Streptococcus pneumoniae (11%) and Staphylococcus aureus (3%). Pathogens were eradicated or presumed eradicated at post-treatment in 85%, 91% and 58% of evaluable patients treated with grepafloxacin for 5 days, grepafloxacin 10 days and clarithromycin 10 days, respectively. The eradication rates in both grepafloxacin groups were significantly greater than the clarithromycin group (P<0.001). All treatments were well tolerated and incidence of drug-related adverse events in each group was comparable. This study demonstrates that both a 5 and a 10 day regimen of grepafloxacin 400 mg od are as clinically and bacteriologically effective as in the treatment of ABECB clarithromycin 250 mg bd. for 10 days.
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
Wang, Jinrong; Cui, Zhaobo; Liu, Shuhong; Gao, Xiuling; Gao, Pan; Shi, Yi; Guo, Shufen; Li, Peipei
Abstract 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
Uribe Echevarría, Loli; Leimgruber, Carolina; García González, Jorge; Nevado, Alberto; Álvarez, Ruth; García, Luciana N; Quintar, Amado A; Maldonado, Cristina A
In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease’s development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about eosinophil extracellular trap cell death (EETosis) and its role in the pathogenesis of COPD. The aim of this study was to evaluate EETosis in stable COPD. Induced sputum obtained from healthy smokers and low exacerbation risk COPD A or B group patients or high exacerbation risk COPD C or D group patients were included. Samples were examined using electron microscopy and immunofluorescence. Healthy smokers (n=10) and COPD A (n=19) group exhibited neutrophilic or paucigranulocytic phenotypes, with NETosis being absent in these patients. In contrast, COPD B (n=29), with eosinophilic or mixed phenotypes, showed EETosis and incipient NETosis. COPD C (n=18) and COPD D groups (n=13) were differentiated from low exacerbation rate-COPD group by the abundant cellular debris, with COPD C group having an eosinophilic pattern and numerous cells undergoing EETosis. A hallmark of this group was the abundant released membranes that often appeared phagocytosed by neutrophils, which coincidentally exhibited early NETosis changes. The COPD D group included patients with a neutrophilic or mixed pattern, with abundant neutrophil extracellular trap-derived material. This study is the first to demonstrate EETosis at different stages of stable COPD. The results suggest a role for eosinophils in COPD pathophysiology, especially at the beginning and during the persistence of the disease, regardless of whether the patient quit smoking, with EETosis debris probably triggering uncontrolled NETosis. The main target of these findings should be young
Pichavant, Muriel; Sharan, Riti; Le Rouzic, Olivier; Olivier, Cécile; Hennegrave, Florence; Rémy, Gaëlle; Pérez-Cruz, Magdiel; Koné, Bachirou; Gosset, Pierre; Just, Nicolas; Gosset, Philippe
Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation. PMID:26870795
Pichavant, Muriel; Sharan, Riti; Le Rouzic, Olivier; Olivier, Cécile; Hennegrave, Florence; Rémy, Gaëlle; Pérez-Cruz, Magdiel; Koné, Bachirou; Gosset, Pierre; Just, Nicolas; Gosset, Philippe
Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.
Velardo, Carmelo; Farmer, Andrew; Tarassenko, Lionel
Background Chronic obstructive pulmonary disease (COPD) is a progressive, chronic respiratory disease with a significant socioeconomic burden. Exacerbations, the sudden and sustained worsening of symptoms, can lead to hospitalization and reduce quality of life. Major limitations of previous telemonitoring interventions for COPD include low compliance, lack of consensus on what constitutes an exacerbation, limited numbers of patients, and short monitoring periods. We developed a telemonitoring system based on a digital health platform that was used to collect data from the 1-year EDGE (Self Management and Support Programme) COPD clinical trial aiming at daily monitoring in a heterogeneous group of patients with moderate to severe COPD. Objective The objectives of the study were as follows: first, to develop a systematic and reproducible approach to exacerbation identification and to track the progression of patient condition during remote monitoring; and second, to develop a robust algorithm able to predict COPD exacerbation, based on vital signs acquired from a pulse oximeter. Methods We used data from 110 patients, with a combined monitoring period of more than 35,000 days. We propose a finite-state machine–based approach for modeling COPD exacerbation to gain a deeper insight into COPD patient condition during home monitoring to take account of the time course of symptoms. A robust algorithm based on short-period trend analysis and logistic regression using vital signs derived from a pulse oximeter is also developed to predict exacerbations. Results On the basis of 27,260 sessions recorded during the clinical trial (average usage of 5.3 times per week for 12 months), there were 361 exacerbation events. There was considerable variation in the length of exacerbation events, with a mean length of 8.8 days. The mean value of oxygen saturation was lower, and both the pulse rate and respiratory rate were higher before an impending exacerbation episode, compared with
Wedzicha, Jadwiga A; Calverley, Peter MA; Rabe, Klaus F
COPD is a progressive condition involving chronic inflammation and parenchymal destruction with resulting airflow limitation. COPD is associated with worsening airflow limitation over time and increased frequency of COPD exacerbations, leading to increased mortality and morbidity. The effects of COPD extend beyond the lungs, as multiple comorbidities may occur with COPD, including cardiovascular disease, diabetes mellitus, osteoporosis, depression, and pneumonia. COPD exacerbations are associated with a rapid worsening of baseline symptoms that requires prompt management and may necessitate hospitalization in the case of a severe episode. Patients with COPD exacerbations require urgent management of symptoms to prevent further worsening, and preventative steps may be taken to help reduce the number and frequency of future exacerbations. Roflumilast is a potent and selective inhibitor of the enzyme phosphodiesterase-4 that targets the systemic inflammation associated with COPD. Roflumilast has a variety of anti-inflammatory effects including decreasing inflammatory mediators and the expression of cell surface markers and inhibition of apoptosis. Several clinical trials evaluating roflumilast in the treatment of COPD have demonstrated significant improvements from baseline versus placebo in lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity. Data suggest that roflumilast reduces moderate to severe exacerbations with the benefit most well established in patients with severe disease. Given this evidence, roflumilast, as part of a combination regimen with long-acting bronchodilators, appears to be a reasonable treatment option for patients with severe to very severe COPD associated with chronic bronchitis and a history of exacerbations. PMID:26792988
Chronic obstructive pulmonary disease (COPD) is a multi-component disease characterised by airflow limitation and airway inflammation. Exacerbations of COPD have a considerable impact on the quality of life, daily activities and general well-being of patients and are a great burden on the health system. Thus, the aims of COPD management include not only relieving symptoms and preventing disease progression but also preventing and treating exacerbations. Attention towards the day-to-day burden of the disease is also required in light of evidence that suggests COPD may be variable throughout the day with morning being the time when symptoms are most severe and patients' ability to perform regular morning activities the most problematic. While available therapies improve clinical symptoms and decrease airway inflammation, they do not unequivocally slow long-term progression or address all disease components. With the burden of COPD continuing to increase, research into new and improved treatment strategies to optimise pharmacotherapy is ongoing - in particular, combination therapies, with a view to their complementary modes of action enabling multiple components of the disease to be addressed. Evidence from recent clinical trials indicates that triple therapy, combining an anticholinergic with an inhaled corticosteroid and a long-acting beta(2)-agonist, may provide clinical benefits additional to those associated with each treatment alone in patients with more severe COPD. This article reviews the evidence for treatment strategies used in COPD with a focus on combination therapies and introduces the 3-month CLIMB study (Evaluation of Efficacy and Safety of Symbicort as an Add-on Treatment to Spiriva in Patients With Severe COPD) which investigated the potential treatment benefits of combining tiotropium with budesonide/formoterol in patients with COPD with regard to lung function, exacerbations, symptoms and morning activities.
Shimizu, Yasuo; Dobashi, Kunio; Kusano, Motoyasu; Mori, Masatomo
Symptomatic differences and the impact of gastroesophageal reflux disease (GERD) have not been clarified in patients with asthma and chronic obstructive pulmonary disease (COPD). The purpose of this study is to assess the differences of GERD symptoms among asthma, COPD, and disease control patients, and determine the impact of GERD symptoms on exacerbation of asthma or COPD by using a new questionnaire for GERD. A total of 120 subjects underwent assessment with the frequency scale for the symptoms of GERD (FSSG) questionnaire, including 40 age-matched patients in each of the asthma, COPD, and disease control groups. Asthma and control patients had more regurgitation-related symptoms than COPD patients (p<0.05), while COPD patients had more dysmotility-related symptoms than asthma patients (p<0.01) or disease control patients (p<0.01). The most distinctive symptom of asthma patients with GERD was an unusual sensation in the throat, while bloated stomach was the chief symptom of COPD patients with GERD, and these symptoms were associated with disease exacerbations. The presence of GERD diagnosed by the total score of FSSG influences the exacerbation of COPD. GERD symptoms differed between asthma and COPD patients, and the presence of GERD diagnosed by the FSSG influences the exacerbation of COPD. PMID:22448100
Vibration response imaging: a novel noninvasive tool for evaluating the initial therapeutic effect of noninvasive positive pressure ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease
Background The popular methods for evaluating the initial therapeutic effect (ITE) of noninvasive positive pressure ventilation (NPPV) can only roughly reflect the therapeutic outcome of a patient’s ventilation because they are subjective, invasive and time-delayed. In contrast, vibration response imaging (VRI) can monitor the function of a patient’s ventilation over the NPPV therapy in a non-invasive manner. This study aimed to investigate the value of VRI in evaluating the ITE of NPPV for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods Thirty-six AECOPD patients received VRI at three time points: before NPPV treatment (T1), at 15 min of NPPV treatment (T2), and at 15 min after the end of NPPV treatment (T4). Blood gas analysis was also performed at T1 and at 2 hours of NPPV treatment (T3). Thirty-nine healthy volunteers also received VRI at T1 and T2. VRI examination at the time point T2 in either the patients or volunteers did not require any interruption of the on-going NPPV. The clinical indices at each time point were compared between the two groups. Moreover, correlations between the PaCO2 changes (T3 vs T1) and abnormal VRI scores (AVRIS) changes (T2 vs T1) were analyzed. Results No significant AVRIS differences were found between T1 and T2 in the healthy controls (8.51 ± 3.36 vs. 8.53 ± 3.57, P > 0.05). The AVRIS, dynamic score, MEF score and EVP score showed a significant decrease in AECOPD patients at T2 compared with T1 (P < 0.05), but a significant increase at T4 compared with T2 (P < 0.05). We also found a positive correlation (R2 = 0.6399) between the PaCO2 changes (T3 vs T1) and AVRIS changes (T2 vs T1). Conclusions VRI is a promising noninvasive tool for evaluating the initial therapeutic effects of NPPV in AECOPD patients and predicting the success of NPPV in the early stage. PMID:22856613
Hansel, Nadia N.; McCormack, Meredith C.; Kim, Victor
Chronic Obstructive Pulmonary Disease (COPD) affects 12–16 million people in the United States and is the third-leading cause of death. In developed countries, smoking is the greatest risk factor for the development of COPD, but other exposures also contribute to the development and progression of the disease. Several studies suggest, though are not definitive, that outdoor air pollution exposure is linked to the prevalence and incidence of COPD. Among individuals with COPD, outdoor air pollutants are associated with loss of lung function and increased respiratory symptoms. In addition, outdoor air pollutants are also associated with COPD exacerbations and mortality. There is much less evidence for the impact of indoor air on COPD, especially in developed countries in residences without biomass exposure. The limited existing data suggests that indoor particulate matter and nitrogen dioxide concentrations are linked to increased respiratory symptoms among patients with COPD. In addition, with the projected increases in temperature and extreme weather events in the context of climate change there has been increased attention to the effects of heat exposure. Extremes of temperature—both heat and cold—have been associated with increased respiratory morbidity in COPD. Some studies also suggest that temperature may modify the effect of pollution exposure and though results are not conclusive, understanding factors that may modify susceptibility to air pollution in patients with COPD is of utmost importance. PMID:26683097
Background Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of the disease that require hospitalization. Current guidelines offer little guidance for identifying patients whose clinical situation is appropriate for admission to the hospital, and properly developed and validated severity scores for COPD exacerbations are lacking. To address these important gaps in clinical care, we created the IRYSS-COPD Appropriateness Study. Methods/Design The RAND/UCLA Appropriateness Methodology was used to identify appropriate and inappropriate scenarios for hospital admission for patients experiencing COPD exacerbations. These scenarios were then applied to a prospective cohort of patients attending the emergency departments (ED) of 16 participating hospitals. Information was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up after admission or discharge home. While complete data were generally available at the time of ED admission, data were often missing at the time of decision making. Predefined assumptions were used to impute much of the missing data. Discussion The IRYSS-COPD Appropriateness Study will validate the appropriateness criteria developed by the RAND/UCLA Appropriateness Methodology and thus better delineate the requirements for admission or discharge of patients experiencing exacerbations of COPD. The study will also provide a better understanding of the determinants of outcomes of COPD exacerbations, and evaluate the equity and variability in access and outcomes in these patients. PMID:22115318
Tashkin, Donald P
Current guidelines recommend inhaled pharmacologic therapy as the preferred route of administration for treating COPD. Bronchodilators (β2-agonists and antimuscarinics) are the mainstay of pharmacologic therapy in patients with COPD, with long-acting agents recommended for patients with moderate to severe symptoms or those who are at a higher risk for COPD exacerbations. Dry powder inhalers and pressurized metered dose inhalers are the most commonly used drug delivery devices, but they may be inadequate in various clinical scenarios (eg, the elderly, the cognitively impaired, and hospitalized patients). As more drugs become available in solution formulations, patients with COPD and their caregivers are becoming increasingly satisfied with nebulized drug delivery, which provides benefits similar to drugs delivered by handheld inhalers in both symptom relief and improved quality of life. This article reviews recent innovations in nebulized drug delivery and the important role of nebulized therapy in the treatment of COPD. PMID:27799757
Blasi, Francesco; Mantero, Marco; Aliberti, Stefano
It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD.
Kazerooni, Ella A.; Lynch, David A.; Liu, Lyrica X.; Murray, Susan; Curtis, Jeffrey L.; Criner, Gerard J.; Kim, Victor; Bowler, Russell P.; Hanania, Nicola A.; Anzueto, Antonio R.; Make, Barry J.; Hokanson, John E.; Crapo, James D.; Silverman, Edwin K.; Martinez, Fernando J.; Washko, George R.
Purpose: To test the hypothesis—given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)—that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease. Materials and Methods: This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a −950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements. Results: In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047). Conclusion: Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10
Song, Rong-rong; Qiu, Yan-ping; Chen, Yong-ju; Ji, Yong
BACKGROUND: Early withdrawal of invasive mechanical ventilation (IMV) followed by noninvasive MV (NIMV) is a new strategy for changing modes of treatment in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with acute respiratory failure (ARF). Using pulmonary infection control window (PIC window) as the switch point for transferring from invasive to noninvasive MV, the time for early extubation can be more accurately judged, and therapy efficacy can be improved. This study aimed to prospectively investigate the clinical effectiveness of fiberoptic bronchscopy (FOB) in patients with AECOPD during sequential weaning of invasive-noninvasive MV. METHODS: Since July 2006 to January 2011, 106 AECOPD patients with ARF were treated with comprehensive medication and IMV after hospitalization. Patients were randomly divided into two groups according to whether fiberoptic bronchoscope is used (group A, n=54) or not (group B, n=52) during sequential weaning from invasive to noninvasive MV. In group A, for sputum suction and bronchoalveolar lavage (BAL), a fiberoptic bronchoscope was put into the airway from the outside of an endotracheal tube, which was accompanied with uninterrupted use of a ventilator. After achieving PIC window, patients of both groups changed to NIMV mode, and weaned from ventilation. The following listed indices were used to compare between the groups after treatment: 1) the occurrence time of PIC, the duration of MV, the length of ICU stay, the success rate of weaning from MV for the first time, the rate of reventilation and the occurrence rate of ventilator-associated pneumonia (VAP); 2) the convenience and safety of FOB manipulation. The results were compared using Student’s t test and the Chi-square test. RESULTS: The occurrence time of PIC was (5.01±1.49) d, (5.87±1.87) d in groups A and B, respectively (P<0.05); the duration of MV was (6.98±1.84) d, (8.69±2.41) d in groups A and B, respectively (P<0.01); the
De Coster, Daan A; Jones, Melvyn
This literature review updates the reader on the new studies regarding steroid therapy over the last year in stable COPD and in exacerbations. In stable COPD, we critique the 2011 update and 2013 revision of the GOLD guidelines, discuss why combining inhaled corticosteroids (ICS) with long-acting beta-agonists (LABA) (ICS/LABA) is preferable over LABA alone and review the literature for intraclass differences, finding that the evidence does not clearly support superiority of any particular ICS/LABA. We also address other comparisons against ICS/LABA, including triple therapy. We briefly review which type of inhaler should be chosen. For exacerbations, we report the REDUCE trial findings favouring a 5-day course of systemic steroids, and other trials addressing which steroid and route to use, including in an intensive care setting. Lastly, the future lies in new anti-inflammatories and re-phenotyping the heterogeneous amalgamation of COPD. A Spanish guideline recommends distinguishing steroid-responsive eosinophilic exacerbators from other phenotypes.
Wei, Li; Yang, Xinyun; Li, Jie; Liu, Lianghui; Luo, Hongying; Zheng, Zeguang
Background Poor adherence leads to a high rate of exacerbation and poor health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD). However, few strategies are acceptable and effective in improving medication adherence. We investigated whether pharmaceutical care by clinical pharmacists could reinforce medication adherence to reduce exacerbation and improve HRQoL. Methods A randomized controlled study was carried out at The First Affiliated Hospital of Guangzhou Medical University from February 2012 to January 2014. Non-adherence patients were randomly assigned to receive pharmaceutical care or to usual care. The pharmaceutical care consisted of individualized education and a series of telephone counseling for 6 months provided by clinical pharmacists. Medication adherence was measured by pill counts plus direct interview at 1- and 6-month pharmaceutical care and one-year follow-up. Severe exacerbations were defined as events that led to hospitalization for acute COPD attack. An interview was conducted to investigate hospital admissions and evaluate severe exacerbations at one-year follow-up. HRQoL was measured by St George’s Respiratory Questionnaire at 6 months. Results At 6-month pharmaceutical care and one-year follow-up, the pharmaceutical care group exhibited higher medication adherence than the usual care group (73.4±11.1 vs. 55.7±11.9, P=0.016 and 54.4±12.5 vs. 66.5±8.6, P=0.039, respectively). There are 60 acute exacerbations resulted in a hospital admission in the usual group while 37 ones in the pharmaceutical care group during one-year follow-up (P=0.01). Hospital admissions due to acute exacerbation in the pharmaceutical care group were 56.3% less than the usual care group (P=0.01). There was a significant difference in the symptoms and impact subscales respectively at 6-month pharmaceutical care between two groups (P=0.032, P=0.018). Conclusions Individualized pharmaceutical care improved medication
Buhl, Roland; Criée, Carl-Peter; Kardos, Peter; Vogelmeier, Claus; Lossi, Nadine; Mailänder, Claudia; Worth, Heinrich
Introduction Randomized interventional trials generally recruit highly selected patients. In contrast, long-term, noninterventional studies can reflect standard of care of real-life populations. DACCORD (Die ambulante Versorgung mit langwirksamen Bronchodilatatoren: COPD-Register in Deutschland [Outpatient Care With Long-Acting Bronchodilators: COPD Registry in Germany]) is an ongoing observational study, conducted in primary and secondary care in Germany, aiming to describe the impact of disease and treatments on real-life patients with chronic obstructive pulmonary disease (COPD). Methods Patients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years, and were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and participation in a randomized clinical trial. Exacerbation data were collected every 3 months. COPD medication, COPD Assessment Test, and forced expiratory volume in 1 second (FEV1) were recorded at the end of the 1 year period. Results In the 6 months prior to baseline, 26.5% of the 3,974 patients experienced ≥1 exacerbation, compared with 26.1% over the 1-year follow-up (annualized rate 0.384). Importantly, only previous exacerbations and not poor lung function alone predicted an increased exacerbation risk. There was a general shift to lower disease severity from baseline to 1 year, predominantly as a consequence of a lower proportion of patients considered at high risk due to exacerbations. COPD Assessment Test mean change from baseline was −1.9, with 48.9% of patients reporting a clinically relevant improvement. Overall persistence to medication was high, with 77.2% of patients still receiving the same class of medication at 1 year. Conclusion DACCORD suggests that in clinical practice, the large majority of COPD patients are symptomatic but seldom exacerbate and that widely used tools and treatment recommendations do not reflect this fully. PMID:27499620
Shen, Wen; Liu, Jia; Zhao, Guohou; Fan, Minjuan; Song, Gao; Zhang, Yang; Weng, Zhiying; Zhang, You
Background Smoking is the leading cause of COPD. Exploring molecular markers and understanding the pathogenic mechanisms of smoking-related COPD are helpful for early clinical diagnosis and treatment of the disease. This study aims to identify specific circulating microRNAs (miRNAs) from the blood of COPD patients with a long history of smoking. Methods Blood samples from four different groups were collected, and miRNA microarray was performed. Differential expression of miRNAs was verified by quantitative polymerase chain reaction. In vitro, THP-1 cells were cultured and stimulated with cigarette smoke extract (CSE) or transfected with miR-149-3p inhibitor/mimics. Protein levels of Toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB) were detected using Western blot and immunofluorescence. Interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were determined by an enzyme-linked immunosorbent assay. Results miRNA profiling revealed that the expression of 56 miRNAs was changed between the four groups. Expression of miR-149-3p in group C (non-smoker non-COPD) was higher than in group S (smoker non-COPD), S-COPD (smoker with stable COPD) and AE-COPD (smoker with acute exacerbation COPD). CSE stimulation down-regulated the expression of miR-149-3p and up-regulated the TLR-4 and NF-κB levels in THP-1 cells. Transfecting miR-149-3p inhibitors in THP-1 cells also increased the expression of its target genes. Furthermore, overexpression of miR-149-3p inhibited the TLR-4/NF-κB signaling pathways and reduced the secretion of IL-1β and TNF-α. Conclusion This study found that smoking can induce differential expression of circulating miR-NAs, such as down-regulation of miR-149-3p. Reducing miR-149-3p may increase the inflammatory response in COPD patients through the regulation of the TLR-4/NF-κB signaling pathway. PMID:28260877
Montes de Oca, Maria; Aguirre, Carlos; Lopez Varela, Maria Victorina; Laucho-Contreras, Maria E; Casas, Alejandro; Surmont, Filip
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
Sundh, Josefin; Janson, Christer; Johansson, Gunnar; Lindén, Anders; Löfdahl, Claes-Göran; Sandström, Thomas; Larsson, Kjell
Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A-D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation
Sundh, Josefin; Janson, Christer; Johansson, Gunnar; Lindén, Anders; Löfdahl, Claes-Göran; Sandström, Thomas; Larsson, Kjell
ABSTRACT Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III–IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A–D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) −0.79 (−1.39 to −0.19), p = 0.010). Conclusion: Most stage III–IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking
Cosio, Borja G.; Soriano, Joan B.; López-Campos, Jose Luis; Calle, Myriam; Soler, Juan José; de-Torres, Juan Pablo; Marín, Jose Maria; Martínez, Cristina; de Lucas, Pilar; Mir, Isabel; Peces-Barba, Germán; Feu-Collado, Nuria; Solanes, Ingrid; Alfageme, Inmaculada
Rationale The Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes. Objective We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. Methods We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes. Results Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year. Conclusions There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use. PMID:27684372
Bagdonas, Edvardas; Raudoniute, Jovile; Bruzauskaite, Ieva; Aldonyte, Ruta
Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet. We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade. Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke. The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied. However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between. Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays.
Bagdonas, Edvardas; Raudoniute, Jovile; Bruzauskaite, Ieva; Aldonyte, Ruta
Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. Despite the fact that COPD is a steadily growing global healthcare problem, the conventional therapies remain palliative, and regenerative approaches for disease management are not available yet. We aim to provide an overview of key reviews, experimental, and clinical studies addressing lung emphysema development and repair mechanisms published in the past decade. Novel aspects discussed herein include integral revision of the literature focused on lung microflora changes in COPD, autoimmune component of the disease, and environmental risk factors other than cigarette smoke. The time span of studies on COPD, including emphysema, chronic bronchitis, and asthmatic bronchitis, covers almost 200 years, and several crucial mechanisms of COPD pathogenesis are described and studied. However, we still lack the holistic understanding of COPD development and the exact picture of the time-course and interplay of the events during stable, exacerbated, corticosteroid-treated COPD states, and transitions in-between. Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. Considerable influx of new data from the clinic, in vivo and in vitro studies stimulate to search for novel concise explanation and holistic understanding of COPD nowadays. PMID:26082624
Vogelmeier, Claus; Worth, Heinrich; Buhl, Roland; Criée, Carl-Peter; Lossi, Nadine S; Mailänder, Claudia; Kardos, Peter
Many patients with chronic obstructive pulmonary disease (COPD) receive inhaled corticosteroids (ICSs) without a clear indication, and thus, the impact of ICS withdrawal on disease control is of great interest. DACCORD is a prospective, noninterventional 2-year study in the primary and secondary care throughout Germany. A subgroup of patients were taking ICS prior to entry – 1,022 patients continued to receive ICS for 2 years; physicians withdrew ICS on entry in 236 patients. Data from these two subgroups were analyzed to evaluate the impact of ICS withdrawal. Patients aged ≥40 years with COPD, initiating or changing COPD maintenance medication were recruited, excluding patients with asthma. Demographic and disease characteristics, prescribed COPD medication, COPD Assessment Test, exacerbations, and lung function were recorded. There were few differences in baseline characteristics; ICS withdrawn patients had shorter disease duration and better lung function, with 74.2% of ICS withdrawn patients not exacerbating, compared with 70.7% ICS-continued patients. During Year 1, exacerbation rates were 0.414 in the withdrawn group and 0.433 in the continued group. COPD Assessment Test total score improved from baseline in both groups. These data suggest that ICS withdrawal is possible with no increased risk of exacerbations in patients with COPD managed in the primary and secondary care. PMID:28203072
Saberi, Farzad; O'Donnell, Denis E
Bronchodilator therapy forms the mainstay of treatment for symptomatic patients with COPD. Long-acting bronchodilators, which maintain sustained airway patency over a 24-hour p