Asthma control in patients treated with inhaled corticosteroids and long-acting beta agonists: A population-based analysis in Germany.

BACKGROUND: The prevalence and the characteristics of poor asthma control among adults treated with combinations of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are not completely understood. METHODS: Data from adult patients in Germany with self-reported asthma treated with an ICS-LABA combination in the National Health and Wellness Survey (NHWS) were analysed. Patients with well-controlled and not well-controlled asthma according to the Asthma Control Test (ACT) score were compared, with respect to socio-demographic characteristics, attitudes, adherence and outcomes. RESULTS: Among the German patients with self-reported asthma (5.2% of the respondents), 16.2% (382 patients) were treated with an ICS-LABA combination and did not report concomitant chronic obstructive pulmonary disease, chronic bronchitis or emphysema. In this subgroup, 55.8% had not well-controlled asthma (ACT < 20). ICS-LABA treated patients with not well-controlled asthma were more likely to report emergency visits (16.4% vs. 8.9%), missed more time from work (absenteeism: 12.9% vs. 4.3%), were more impaired while at work (presenteeism: 29.0% vs. 14.9%) and were more likely to be women (69.0% vs. 57.4%), compared with well-controlled patients. There were no significant differences in age, body mass index, smoking, income, education or self-reported adherence between the two groups, but different attitudes regarding the patient-physician relationship. CONCLUSIONS: A substantial proportion of patients treated with ICS and LABA had not well-controlled asthma. These patients did not differ from well-controlled patients in terms of education or self-reported adherence, but in terms of their attitudes regarding the patient-physician relationship.

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

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

Seasonal distribution of COPD exacerbations in the Prevention of Exacerbations with Tiotropium in COPD trial.

BACKGROUND: There is still a lack of data on the seasonality of exacerbations of COPD based on large randomized studies using COPD exacerbations as primary end points. The objective of this study was to assess the seasonal pattern of moderate and severe exacerbations and analyze the influence of associated baseline factors. We also determined the timing of second exacerbations and the potential impact of the 2009 influenza A(H1N1) pandemic on exacerbations. METHODS: Analyses of exacerbation rates across treatment groups were adjusted for differing times on treatment by means of descriptive statistics based on the 1-year Prevention of Exacerbations with Tiotropium in COPD (POET-COPD) trial, in which exacerbations were the primary end point. RESULTS: Of the 7,376 patients who were randomized, a total of 4,411 exacerbations were reported in 2,691 patients. Mean monthly exacerbation rates during winter were 2.16-fold higher than during summer, regardless of baseline characteristics (age, sex, COPD severity, smoking status, BMI, inhaled corticosteroid use, cardiovascular comorbidity, concomitant cardiovascular medication). Second exacerbations after a previous event in October to March occurred 1 month earlier than during the warmer half of the season. The portion of exacerbation-related hospitalizations remained constant throughout the year. Most exacerbations were treated with antibiotics and reached a peak in the colder season. All-cause mortality showed a seasonal pattern similar to exacerbations. The 2009 A(H1N1) pandemic was not associated with an increase in exacerbation rates or deaths. CONCLUSIONS: This analysis presented a marked impact of season on exacerbation outcomes, antibiotic treatment, timing of second exacerbations, and all-cause mortality.

A practical guide to bioelectrical impedance analysis using the example of chronic obstructive pulmonary disease.

Bioelectrical impedance analysis (BIA) is a simple, inexpensive, quick and non-invasive technique for measuring body composition. The clinical benefit of BIA can be further enhanced by combining it with bioelectrical impedance vector analysis (BIVA). However, there is a substantial lack of information on the practical aspects of BIA/BIVA for those primarily interested in learning how to use and interpret this method in practice. The purpose of this article is to provide some guidance on the use of BIA/BIVA with special attention to practical considerations.This report reflects the authors' practical experience with the use of single-frequency BIA in combination with BIVA, particularly in COPD patients. First, the method and principles of BIA/BIVA are briefly described. Then, a practice-oriented approach to the interpretation and analysis of characteristic examples of altered nutritional and fluid status as seen with BIA/BIVA in COPD patients (e.g. malnutrition in obese and underweight patients with COPD, water retention) is presented.As our examples show BIA/BIVA is an attractive and easy-to-learn tool for quick nutritional assessment and is therefore of great clinical benefit in daily practice.

Tiotropium Respimat® improves physical functioning in chronic obstructive pulmonary disease.

AIM: This observational study with tiotropium Respimat® was performed in a real-life setting to investigate its effectiveness with regard to physical functioning and tolerability. METHODS: Patients with chronic obstructive pulmonary disease (COPD; n = 1,230; mean age, 65.5 years) received tiotropium 5 µg once daily via Respimat® Soft Inhaler for 6 weeks in an open-label observational study. At baseline and week 6, patients completed the Physical Function subdomain [PF-10] of the Short Form (SF) 36 questionnaire. RESULTS: Improvement in standardized PF-10 score of ≥10 points was achieved by 61.5% of patients. Mean (SD) standardized PF-10 scores improved by 13.4 (15.9) points, from 49.0 (24.5) to 62.3 points (23.5; P < 0.001). Results in smokers (n = 435) were not significantly different to those in nonsmokers. The general condition of patients improved during treatment. Adverse events were reported by 4.0% of patients and were chiefly respiratory symptoms and dry mouth. CONCLUSION: In COPD patients receiving tiotropium Respimat® in daily practice, physical function improved rapidly within 6 weeks of treatment, irrespective of smoking status.

Preselection of patients at risk for COPD by two simple screening questions.

BACKGROUND: The Burden of Obstructive Lung Disease study showed that in Germany, to confirm the diagnosis of chronic obstructive lung disease (COPD) in one subject, eight people ≥ 40 years of age have to be screened. The number-needed-to-screen (NNS) increased to 18 for identifying a patient with COPD ≥ GOLD stage II. These high numbers limit the cost-effectiveness of COPD screening by population spirometry. We investigated in a primary care setting whether using two simple questions regarding smoking status and presence of cough and/or dyspnea may help to preselect patients for proper diagnosis of COPD. METHODS: A total of 1088 patients aged ≥ 40 yrs without a history of chronic lung disease, who were either current or ex-smokers and complained of cough and/or dyspnea, were examined by respiratory physicians. Spirometry was carried out to confirm COPD diagnosis and severity. RESULTS: A total of 61.6% of patients were male. Mean smoking history was 31.8 pack-yrs. In 516 patients (47.4%), a diagnosis of COPD was confirmed. Among these, 379 (34.8% of total) had at least GOLD stage II COPD, while 89 (8.2% of total) had advanced disease (GOLD stages III/IV). COPD prevalence was significantly associated with age and the extent of cigarette smoke exposure. CONCLUSIONS: Two questions regarding smoking status and presence of cough and/or dyspnea enabled general practitioners to select patients at risk for COPD for subsequent spirometry. This preselection reduced the NNS to 2.1 for identifying a COPD patient, and to 2.9 for identifying a patient of at least GOLD stage II.

Study design considerations in a large COPD trial comparing effects of tiotropium with salmeterol on exacerbations.

Currently available long-acting inhaled bronchodilators (tiotropium, salmeterol, formoterol) have demonstrated beneficial effects on exacerbations in placebo-controlled trials. However, there have been no direct comparisons of these drugs with exacerbations as the primary outcome and consequently COPD treatment guidelines do not indicate a preference for either bronchodilator. Therefore, an international, randomized, double-blind, double-dummy, parallel-group clinical trial has been designed to investigate the comparative efficacy of 2 long-acting bronchodilators tiotropium 18 microg daily and salmeterol 50 microg bid on exacerbations. The trial will include at least 6800 randomized patients with diagnosis of COPD, >or= 10 pack-year history of smoking, post-bronchodilator FEV(1)

[Clinical value of forced expiratory volume in 1 s (FEV1) in chronic obstructive pulmonary disease]. / Klinische Bedeutung der forcierten Einsekundenkapazität (FEV1) bei chronisch-obstruktiver Lungenerkrankung (COPD).

There is overwhelming evidence from large-scale placebo-controlled trials but also from epidemiologic COPD (chronic obstructive pulmonary disease) studies and meta-analyses supporting FEV(1) (forced expiratory volume in 1 s) as a strong diagnostic and prognostic marker that predicts future morbidity and mortality. Specifically, attenuation of reduced FEV(1) is a powerful indicator of successful medical intervention and vice versa. FEV(1) decline indicates an increasing risk for advanced disease stage eventually leading to further deterioration. However, it remains to be determined whether reducing the frequency of exacerbations or pharmacological improvement of FEV(1) can help to slow lung function decline and consequently improve clinical outcome in these patients. All in all, FEV(1) and its change over time are essential parameters in the assessment of COPD progression and efficacy of therapeutic intervention.

Dose-dependent recruitment of CD25+ and CD26+ T cells in a novel F344 rat model of asthma.

The ovalbumin (OVA)-induced airway inflammation in rats is a commonly used model to explore the pathobiology of asthma. However, its susceptibility varies greatly between rat strains, and presently Brown Norway (BN) rats are preferentially used. Since recruitment of T cells to the lungs depends on the CD26 (dipeptidyl peptidase IV, DPPIV) expression, Fischer 344 strain (F344) rats are a highly relevant rat strain, in particular because CD26-deficient substrains are available. To establish a F344 rat model of asthma, we challenged F344 rats using different doses of aerosolized antigen (0%, 1%, 2.5%, 5%, and 7.5% OVA) and compared these effects with intratracheal instillation of OVA (1.5 mg/0.3 ml). Asthmoid responsiveness was determined by analysis of early airway responsiveness (EAR), antigen-specific IgE levels, as well as airway inflammation including the composition of T cell subpopulations in the bronchoalveolar lavage (BAL) and lung tissue with special respect to the T cell activation markers CD25 and CD26. Even low allergen doses caused allergen-specific EAR and increases of antigen-specific IgE levels. However, EAR and IgE levels did not increase dose dependently. Higher concentrations of OVA led to a dose-dependent increase of several immunological markers of allergic asthma including an influx of eosinophils, T cells, and dendritic cells. Interestingly, a dose-dependent increase of CD4(+)/CD25(+)/CD26(+) T cells was found in the lungs. Summarizing, we established a novel F344 rat model of aerosolized OVA-induced asthma. Thereby, we found a dose-dependent recruitment of cellular markers of allergic asthma including the activated CD4(+)/CD25(+)/CD26(+) T cell subpopulation, which has not been described in asthma yet.

National survey of guideline-compliant COPD management among pneumologists and primary care physicians.

The aim of this survey was to investigate guideline-compliant COPD management among pneumologists and primary care physicians (PCPs). A multiple-choice questionnaire was sent out to 1836 PCPs and 863 pneumologists in Germany. The questions focused on the key aspects of current national and international COPD guidelines. Four hundred eighty-six PCPs and 359 pneumologists participated in the study. It was found that pneumologists held the GOLD guideline in high regard (60.4%), while PCPs tended to follow the German National COPD guideline (66.5%). Differences were also found with regard to diagnosis and classification of COPD on the basis of spirometric and clinical criteria. The current GOLD classification of moderate and severe COPD was used by 36.2% and 23.4% of the pneumologists, respectively, and by 32.1% and 20.2% of the PCPs. Although PCPs and pneumologists endorsed educational measures to help patients quit smoking, implementation was still inadequate. The two most important therapeutic goals were to improve quality of life and prevent exacerbations. Except for the criteria for the use of steroids and the implementation of pulmonary rehabilitation measures, treatment of COPD based on severity class was largely in compliance with guidelines. However, appreciably more PCPs than pneumologists incorrectly assessed the evidence-based clinical benefits of various therapeutic measures. The study shows that, despite the popularity of COPD guidelines, deficits exist among pneumologists and PCPs with respect to diagnosis and treatment of COPD and practical implementation of educational measures. These deficiencies in guideline conformity might be best addressed through targeted continuing-education measures.