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Asthma and COPD are common chronic obstructive respiratory diseases. COPD is associated with increased mortality, but for asthma the results are varying. Their combination has been less investigated, and the results are contradictory. The aim of this prospective study was to observe the overall mortality in obstructive pulmonary diseases and how mortality was related to specific causes using postal questionnaire data. This study included data from 6,062 participants in the FinEsS Helsinki Study (1996) linked to mortality data during a 24-year follow-up. According to self-reported physician diagnosed asthma, COPD, or smoking status, the population was divided into five categories: combined asthma and COPD, COPD alone and asthma alone, ever-smokers without asthma or COPD and never-smokers without asthma or COPD (reference group). For the specific causes of death both the underlying and contributing causes of death were used. Participants with asthma and COPD had the highest hazard of mortality 2.4 (95% CI 1.7–3.5). Ever-smokers without asthma or COPD had a 9.5 (3.7–24.2) subhazard ratio (sHR) related to lower respiratory tract disease specific causes. For asthma, COPD and combined, the corresponding figures were 10.8 (3.4–34.1), 25.0 (8.1–77.4), and 56.1 (19.6–160), respectively. Ever-smokers without asthma or COPD sHR 1.7 (95% CI 1.3–2.5), and participants with combined asthma and COPD 3.5 (1.9–6.3) also featured mortality in association with coronary artery disease. Subjects with combined diseases had the highest hazard of overall mortality and combined diseases also showed the highest hazard of mortality associated with lower respiratory tract causes or coronary artery causes. Abbreviations:Cig Cigarette COPD Chronic obstructive pulmonary disease CVD Cardiovascular disease FEV1 Forced Expiratory Volume in one second FVC Forced Vital Capacity FinEsS Finland, Estonia, and Sweden study on chronic obstructive pulmonary diseases HR Hazard Ratio sHR Subhazard Ratio ICD-10 International Statistical Classifications of Diseases and Related Health Problems (Version 10). publishedVersion

Objective: To investigate the current prevalence of physician-diagnosed obstructive airway diseases by respiratory symptoms and by sex in Sweden and Finland. Method: In 2016, a postal questionnaire was answered by 34,072 randomly selected adults in four study areas: Västra Götaland and Norrbotten in Sweden, and Seinäjoki-Vaasa and Helsinki in Finland. Results: The prevalence of asthma symptoms was higher in Norrbotten (13.2%), Seinäjoki-Vaasa (14.8%) and Helsinki (14.4%) than in Västra Götaland (10.7%), and physician-diagnosed asthma was highest in Norrbotten (13.0%) and least in Västra Götaland (10.1%). Chronic productive cough was most common in the Finnish areas (7.7–8.2% versus 6.3–6.7%) while the prevalence of physician-diagnosed chronic bronchitis (CB) or chronic obstructive pulmonary disease (COPD) varied between 1.7 and 2.7% in the four areas. Among individuals with respiratory symptoms, the prevalence of asthma was most common in Norrbotten, while a diagnosis of COPD or CB was most common in Västra Götaland and Seinäjoki-Vaasa. More women than men with respiratory symptoms reported a diagnosis of asthma in Sweden and Seinäjoki-Vaasa but there were no sex differences in Helsinki. In Sweden, more women than men with symptoms of cough or phlegm reported a diagnosis of CB or COPD, while in Finland the opposite was found. Conclusion: The prevalence of respiratory symptoms and corresponding diagnoses varied between and within the countries. The proportion reporting a diagnosis of obstructive airway disease among individuals with respiratory symptoms varied, indicating differences in diagnostic patterns both between areas and by sex. Accepted author version posted online: 30 May 2020Published online: 13 Jun 2020

International audience; Purpose: Respiratory hazards of farming have been identified for centuries, with little focus on gender differences. We used data from the AGRICOH consortium, a collective of prospective cohorts of agricultural workers, to assess respiratory disease prevalence among adults in 18 cohorts representing over 200,000 farmers, farm workers, and their spouses from six continents.Methods: Cohorts collected data between 1992 and 2016 and ranged in size from 200 to >128,000 individuals; 44% of participants were female. Farming practices varied from subsistence farming to large-scale industrial agriculture. All cohorts provided respiratory outcome information for their cohort based on their study definitions. The majority of outcomes were based on self-report using standard respiratory questionnaires; the greatest variability in assessment methods was associated with chronic obstructive pulmonary disease (COPD).Results: For all three respiratory symptoms (cough, phlegm, and wheeze), the median prevalence in men was higher than in women, with the greatest difference for phlegm (17% vs. 10%). For asthma, women had a higher prevalence (7.8% vs 6.5%), with the difference associated with allergic asthma. The relative proportion of allergic asthma varied among cohorts. In two of eight cohorts for women and two of seven cohorts for men, allergic asthma was more common than non-allergic asthma.Conclusions: These findings indicate that respiratory outcomes are common among farmers around the world despite differences in agricultural production. As women in the general population are at higher risk of asthma, exploring gender differences in occupational studies is critical for a deeper understanding of respiratory disease among agricultural workers.

Background: Many countries in sub-Saharan Africa have the highest risk of developing chronic diseases and are the least able to cope with them.Aims: To assess the current knowledge of the prevalence and impact of asthma and chronic obstructive pulmonary disease (COPD) in sub-Saharan Africa.Methods: A literature search was conducted using Medline (1995-2010) and Google Scholar.Results: Eleven studies of the prevalence of asthma in sub-Saharan Africa were identified, all of which showed a consistent increase, particularly in urban regions. The data on asthma show a wide variation (5.7-20.3%), with the highest prevalence in 'westernised' urban areas. Only two studies of the prevalence of COPD in sub-Saharan Africa have been performed. Nevertheless, COPD has become an increasing health problem in sub-Saharan Africa due to tobacco smoking and exposure to biomass fuels. In most countries of sub-Saharan Africa, 90% of the rural households depend on biomass fuel for cooking and heating, affecting young children (acute lower respiratory infections) and women (COPD). This is the cause of significant mortality and morbidity in the region.Conclusions: Asthma and COPD in sub-Saharan Africa are under-recognised, under-diagnosed, under-treated, and insufficiently prevented. A major priority is to increase the awareness of asthma and COPD and their risk factors, particularly the damage caused by biomass fuel. Surveys are needed to provide local healthcare workers with the possibility of controlling asthma and COPD. (C) 2011 Primary Care Respiratory Society UK. All rights reserved. F van Gemert et al. Prim Care Respir J 2011; 20(3): 240-248 http://dx.doi.org/10.4104/pcrj.2011.00027

Rationale: Smoking has detrimental effects on asthma outcome, such as increased cough, wheezing, sputum production, and frequency of asthma attacks. This results in accelerated lung function decline. The underlying pathological process of smoke-induced deterioration of asthma is unknown.Objectives: To compare bronchial inflammation and remodeling in never-smokers, ex-smokers, and current smokers with asthma.Methods: A total of 147 patients with asthma (66 never-smokers, 46 ex-smokers, and 35 current smokers) were investigated.Measurements and Main Results: Lung function, exhaled nitric oxide levels, and symptom questionnaires were assessed, and induced sputum and bronchial biopsies were obtained for determination of airway inflammation and remodeling. Smokers with asthma had lower FEV(1) and alveolar and bronchial nitric oxide levels than never-smokers. Smokers also had more goblet cells and mucus-positive epithelium, increased epithelial thickness, and a higher proliferation rate of intact and basal epithelium than ex-smokers and never-smokers. Smokers had higher numbers of mast cells and lower numbers of eosinophils than never-smokers. Ex-smokers had similar goblet cell numbers and mucus-positive epithelium, epithelial thickness, epithelial proliferation rate, and mast cell numbers as never-smokers.Conclusions: Smokers with asthma have epithelial changes that are associated with increased asthma symptoms, such as shortness of breath and phlegm production. The fact that epithelial characteristics in ex-smokers are similar to those in never-smokers suggests that the smoke-induced changes can be reversed by smoking cessation.

The pathogenesis of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue-repair and -remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung. The common form of emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD. The mechanism(s) that allow small airways to thicken in such close proximity to lung tissue undergoing emphysematous destruction remains a puzzle that needs to be solved.

Rationale: The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results.Objectives: To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. Methods: An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV1/FVC ratio >= 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV1/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up.Main Results: The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% Cl, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% Cl, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% Cl, 1.44-5.79).Conclusions: The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.

Global estimates suggest that Chronic Obstructive Pulmonary Disease (COPD) is emerging as a leading cause of death in developing countries but there are few spirometry-based general population data on its prevalence and risk factors in sub-Saharan Africa. We used the Burden of Obstructive Lung Disease (BOLD) protocol to select a representative sample of adults aged 40 years and above in Ile-Ife, Nigeria. All the participants underwent spirometry and provided information on smoking history, biomass and occupational exposures as well as diagnosed respiratory diseases and symptoms. Chronic Airflow Obstruction (CAO) was defined as the ratio of post-bronchodilator (BD) one second Forced Expiratory Volume (FEV 1) to Forced Vital Capacity (FVC) below the lower limit of normal (LLN) of the population distribution for FEV 1/FVC. The overall prevalence of obstruction (post-BD FEV 1/FVC < LLN) was 7.7% (2.7% above LLN) using Global Lung Function Initiative (GLI) equations. It was associated with few respiratory symptoms; 0.3% reported a previous doctor-diagnosed chronic bronchitis, emphysema or COPD. Independent predictors included a lack of education (OR 2·5, 95% CI: 1.0, 6.4) and a diagnosis of either TB (OR 23.4, 95% CI: 2.0, 278.6) or asthma (OR 35.4, 95%CI: 4.9, 255.8). There was no association with the use of firewood or coal for cooking or heating. The vast majority of this population (89%) are never smokers. We conclude that the prevalence of CAO is low in Ile-Ife, Nigeria and unrelated to biomass exposure. The key independent predictors are poor education, and previous diagnosis of tuberculosis or asthma.

Background Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation. Objective To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5'-monophosphate (AMP) in COPD. Methods We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean +/- SD, age 63 +/- 8 years, FEV1% predicted 56 +/- 13%), six without BHR (age 60 +/- 6 years, FEV1% predicted 65 +/- 11%) and 11 healthy nonatopic controls without BHR (age 58 +/- 8 years, FEV1% predicted 104 +/- 11%) participated in the study. Results Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm(2); range, 30-1340 vs 280 cells/mm(2); range, 110-450, P = 0.045; and median, 2.7%; range, 0.5-8.5 vs 0.6%; range, 0-0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid. Conclusion We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.

Background Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation.Objective To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5'-monophosphate (AMP) in COPD.Methods We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean +/- SD, age 63 +/- 8 years, FEV1% predicted 56 +/- 13%), six without BHR (age 60 +/- 6 years, FEV1% predicted 65 +/- 11%) and 11 healthy nonatopic controls without BHR (age 58 +/- 8 years, FEV1% predicted 104 +/- 11%) participated in the study.Results Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm(2); range, 30-1340 vs 280 cells/mm(2); range, 110-450, P = 0.045; and median, 2.7%; range, 0.5-8.5 vs 0.6%; range, 0-0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid.Conclusion We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.

BACKGROUND—Inflammatory changes in the airways in chronic obstructive pulmonary disease (COPD) are largely attributed to smoking, yet they may be present even if patients do not currently smoke. The differences in inflammatory cells and the factors contributing to these differences were examined in the airways of patients with COPD who do not currently smoke. METHODS—Eighteen non-atopic subjects with COPD (14 men) of mean (SD) age 62 (8) years and forced expiratory volume in one second (FEV1) 59 (13)% predicted and 11 non-atopic healthy subjects (eight men) of mean (SD) age 58 (8) years, FEV1 104 (11)% predicted were studied. Sputum induction and bronchoscopy with bronchoalveolar lavage (BAL) and biopsies were performed. RESULTS—Patients with COPD had more mucosal EG2+ cells (eosinophils) (median (range) 40 (0-190) versus 5 (0-40) cells/mm2, p = 0.049) and CD68+ cells (1115 (330-2920) versus 590 (450-1580) cells/mm2, p = 0.03), and a tendency towards more CD4+ but not CD8+ lymphocytes than healthy controls. Furthermore, patients with COPD had higher percentages of sputum neutrophils (77 (29-94) versus 36 (18-60)%, p = 0.001) and eosinophils (1.2 (0-8.5) versus 0.2 (0-3.1)%, p= 0.008), BAL fluid eosinophils (0.4 (0-1.7) versus 0.2 (0-0.5)%, p = 0.03), and higher concentrations of sputum eosinophilic cationic protein (ECP) (838 (115-23 760) versus 121 (35-218) ng/ml, p

Background-Inflammatory changes in the airways in chronic obstructive pulmonary disease (COPD) are largely attributed to smoking, yet they may be present even if patients do not currently smoke. The differences in inflammatory cells and the factors contributing to these differences were examined in the airways; of patients with COPD who do not currently smoke. Methods-Eighteen non-atopic subjects with COPD (14 men) of mean (SD) age 62 (8) years and forced expiratory volume in one second (EEV1) 59 (13)% predicted and II non-atopic healthy subjects (eight men) of mean (SD) age 58 (8) years, FEV1 104 (11)% predicted were studied. Sputum induction and bronchoscopy with bronchoalveolar lavage (BAL) and biopsies were performed. Results-Patients with COPD had more mucosal EG2+ cells (eosinophils) (median cells/mm(2), p = 0.049) and CD68+ cells (1115 (330-2920) versus 590 (450-1580) cells/mm(2), p = 0.03), and a tendency towards more CD4+ but not CD8+ lymphocytes than healthy controls. Furthermore, patients with COPD had higher percentages of sputum neutrophils (77 (29-94) versus 36 (18-60)%, p = 0.001) and eosinophils (1.2 (0-8.5) versus 0.2 (0-3.1)%, p = 0.008), BAL fluid eosinophills (0.4 (0-1.7) versus 0.2 (0-0.5)%, p = 0.03), and higher concentrations of sputum eosinophilic cationic protein (ECP) (838 (115-23 760) versus 121 (35-218) ng/ml, p

Background Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H-1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC(20)AMP. Objective To investigate the mechanism of AMP-induced bronchoconstriction in COPD. Methods We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60 +/- 7 years, FEV1 61 +/- 12% of predicted and FEV1/VC 51 +/- 8%, geometric mean [GM] PC(20)methacholine 0.62 mg/mL and GM PC(20)AMP 6.77 mg/mL) participated. PC(20)methacholine and PC(20)AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 mu g of inhaled ipratropium bromide, or placebo. Results GM PC(20)AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (P Conclusion These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC(20)AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.

Background Inhalation of adenosine 5'-monophosphate (AMP) causes bronchoconstriction in patients with asthma and in many patients with chronic obstructive pulmonary disease (COPD). In asthma, AMP-induced bronchoconstriction has been shown to be determined mainly by release of mast cell mediators, and possibly by vagal nerve stimulation, since oral terfenadine (H-1-receptor antagonist) and inhaled ipratropium bromide (muscarinic receptor antagonist) both increase PC(20)AMP.Objective To investigate the mechanism of AMP-induced bronchoconstriction in COPD.Methods We performed a randomized, double-blind, placebo-controlled, crossover trial. Forty-four nonatopic hyperresponsive smokers with COPD (mean age +/- SD: 60 +/- 7 years, FEV1 61 +/- 12% of predicted and FEV1/VC 51 +/- 8%, geometric mean [GM] PC(20)methacholine 0.62 mg/mL and GM PC(20)AMP 6.77 mg/mL) participated. PC(20)methacholine and PC(20)AMP were assessed on 3 days. Before the challenges they used either 180 mg of oral terfenadine, 120 mu g of inhaled ipratropium bromide, or placebo.Results GM PC(20)AMP was 5.44 mg/mL after placebo, increasing with 0.9 doubling concentration (PConclusion These findings indicate that histamine release is important in the pathophysiology of AMP-induced bronchoconstriction in smokers with COPD, whereas vagal nerve stimulation does not play a role. Therefore, PC(20)AMP may be a valuable tool in evaluation of treatments which affect airway histamine release.

Background and Methods Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, pla cebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in subjects with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 mu g of budesonide or placebo, inhaled from a dry-powder inhaler, for three years.Results Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the th ree-year period was 140 ml in the budesonide group and 180 mi in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 mi per year in the budesonide group, as compared with a decline of 81 mi per year in the placebo group (PConclusions In persons with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline. (N Engl J Med 1999;340:1948-53.) (C) 1999, Massachusetts Medical Society.

Background and Methods Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, pla cebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in subjects with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 mu g of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. Results Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the th ree-year period was 140 ml in the budesonide group and 180 mi in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 mi per year in the budesonide group, as compared with a decline of 81 mi per year in the placebo group (P Conclusions In persons with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline. (N Engl J Med 1999;340:1948-53.) (C) 1999, Massachusetts Medical Society.

Airway diseases, predominantly asthma and chronic obstructive pulmonary disease (COPD), are among the world's most prevalent diseases. The prevalence of asthma has been incasing over the past 20 yr in most countries where this has been studied, and it affects up to 10% of the populations of most developed countries. COPD is the sixth cause of death in the world and affects 4-6% of people more than 45 yr of age. In 1985, more than 5.4 million Americans were estimated to have COPD and COPD is the most rapidly rising cause of death among individuals over the age of 65 yr in the United States (1). These diseases constitute a major financial burden to society, wit both direct and indirect costs. Both asthma and COPD are identified by the presence of characteristic symptoms and functional abnormalities, with airway obstruction being the sine qua non of both diseases. The airway obstruction in asthma must be reversible to establish a diagnosis, whereas COPD is defined as a syndrome characterized by abnormal tests of expiratory flow that do not change markedly over periods of several months of observation (2). Both diseases are now known to be caused by lung inflammation induced by different initiating factors, most likely environmental allergens, occupational sensitizing agents, or viral respiratory infections in asthma and cigarette smoking in COPD. However, some patients wit asthma who do not smoke also develop irreversible airway obstruction similar to COPD. Also, the treatments used to manage both diseases resemble each other. This review compares and contrasts asthma and COPD wit regard to the following aspects: the risks for development, th functional and structural abnormalities,the inflammatory activity and the site of the inflammation, animal models of both diseases and current and potential new treatments for the diseases. The review was developed as a result of a workshop held in Whistler, Canada, involving clinical and basic scientists actively working in these two areas. It is hoped that by comparing the two diseases, new insights can be attained about each.

The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'-monophosphate (AMP), to which we hypothesized the existence of greater sensitivity. Additionally, we studied the effects of budesonide on terfenadine and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and histamine. Forty-four hyperresponsive smokers with moderate to severe COPD participated in the study. MCh and AMP challenges were given on three study days, after pretreatment with single doses of ipratropium bromide, terfenadine, or placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600 mu g budesonide or placebo, and the same three study days were repeated. Budesonide, as compared with placebo, did not significantly change PC(20)AMP, PC(20)MCh, or FEV1 after placebo pretreatment. Budesonide increased PC(20)MCh after ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p 0.036). Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p

The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'-monophosphate (AMP), to which we hypothesized the existence of greater sensitivity. Additionally, we studied the effects of budesonide on terfenadine and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and histamine. Forty-four hyperresponsive smokers with moderate to severe COPD participated in the study. MCh and AMP challenges were given on three study days, after pretreatment with single doses of ipratropium bromide, terfenadine, or placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600 mu g budesonide or placebo, and the same three study days were repeated. Budesonide, as compared with placebo, did not significantly change PC(20)AMP, PC(20)MCh, or FEV1 after placebo pretreatment. Budesonide increased PC(20)MCh after ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p 0.036). Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p

In contrast to the numerous studies which show that lymphocytes play an important role in the pathogenesis of asthma, few studies have investigated the role of lymphocytes in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate lymphocyte subsets in peripheral venous blood of smoking and non-smoking COPD patients and healthy controls. The interaction of smoking and IgE has also been assessed, and it was investigated whether a lower level of FEV(1) was associated with changes in lymphocyte subsets.In the present study, peripheral venous blood lymphocyte subsets were investigated in 42 smoking and non-smoking, non-atopic subjects with a clear diagnosis of COPD (43-74 years) who all used bronchodilator therapy only, and in 24 normal, healthy control subjects (40-72 years).No significant differences in lymphocyte subsets were found when either total groups or smoking subjects of both groups were compared. However, the percentage of CD8(+) lymphocytes (suppressor/cytotoxic T-cells) was significantly higher in the non-smoking COPD subjects compared with the non-smoking, healthy control sujiects (PThe present study provides further evidence that the changes in the balance of T-cell subsets and IgE synthesis possibly plays a role in the pathogenesis of COPD.

In contrast to the numerous studies which show that lymphocytes play an important role in the pathogenesis of asthma, few studies have investigated the role of lymphocytes in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate lymphocyte subsets in peripheral venous blood of smoking and non-smoking COPD patients and healthy controls. The interaction of smoking and IgE has also been assessed, and it was investigated whether a lower level of FEV(1) was associated with changes in lymphocyte subsets. In the present study, peripheral venous blood lymphocyte subsets were investigated in 42 smoking and non-smoking, non-atopic subjects with a clear diagnosis of COPD (43-74 years) who all used bronchodilator therapy only, and in 24 normal, healthy control subjects (40-72 years). No significant differences in lymphocyte subsets were found when either total groups or smoking subjects of both groups were compared. However, the percentage of CD8(+) lymphocytes (suppressor/cytotoxic T-cells) was significantly higher in the non-smoking COPD subjects compared with the non-smoking, healthy control sujiects (P The present study provides further evidence that the changes in the balance of T-cell subsets and IgE synthesis possibly plays a role in the pathogenesis of COPD.

In contrast to the numerous studies which show that lymphocytes play an important role in the pathogenesis of asthma, few studies have investigated the role of lymphocytes in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate lymphocyte subsets in peripheral venous blood of smoking and non-smoking COPD patients and healthy controls. The interaction of smoking and IgE has also been assessed, and it was investigated whether a lower level of FEV1 was associated with changes in lymphocyte subsets. In the present study, peripheral venous blood lymphocyte subsets were investigated in 42 smoking and non-smoking, non-atopic subjects with a clear diagnosis of COPD (43-74 years) who all used bronchodilator therapy only, and in 24 normal, healthy control subjects (40-72 years). No significant differences in lymphocyte subsets were found when either total groups or smoking subjects of both groups were compared. However, the percentage of CD8+ lymphocytes (suppressor/ cytotoxic T-cells) was significantly higher in the non-smoking COPD subjects compared with the non-smoking, healthy control subjects (P0.05). In addition, within the group of non-smoking COPD subjects, a higher CD4:CD8 ratio was associated with a higher FEV1 as a percentage of predicted (% pred.) (r = 0.55, P = 0.01) and a lower total serum IgE (r = -0.45, P = 0.04). Within the group of smoking COPD subjects, a higher FEV1 % pred. was associated with a higher percentage of CD19+ lymphocytes (B-cells) (r = 0.65, P0.01). The present study provides further evidence that the changes in the balance of T-cell subsets and IgE synthesis possibly plays a role in the pathogenesis of COPD.

The aim of this study was to determine whether impedance values in children with various chronic respiratory complaints differed from those observed in symptom-free children.Respiratory impedance was measured using the forced oscillation technique in 1,776 Dutch children aged 6-12 yrs. In addition to the commonly used parameters of resistance and reactance, further impedance parameters were obtained by using linear and quadratic regression to describe individual resistance and reactance curves as a function of frequency. Furthermore, the diagnostic value of the individual impedance parameters was evaluated by means of receiver operator characteristic (ROC) curves.Statistically significant differences in impedance values were found in girls with symptoms suggesting asthma compared to symptom-free girls, but not in boys. In children with chronic cough, impedance was not significantly different from the values of symptom-free children. The results obtained by the additional impedance parameters were comparable to those of the commonly used measures.We conclude that the diagnostic value of the impedance parameters appeared to be low, as no cut-off points were found to discriminate clearly between symptomatic and symptom-free children. These findings may reflect absence of functional abnormalities in symptomatic children at this age. (C)ERS Journals Ltd 1997.

The aim of this study was to determine whether impedance values in children with various chronic respiratory complaints differed from those observed in symptom-free children. Respiratory impedance was measured using the forced oscillation technique in 1,776 Dutch children aged 6-12 yrs. In addition to the commonly used parameters of resistance and reactance, further impedance parameters were obtained by using linear and quadratic regression to describe individual resistance and reactance curves as a function of frequency. Furthermore, the diagnostic value of the individual impedance parameters was evaluated by means of receiver operator characteristic (ROC) curves. Statistically significant differences in impedance values were found in girls with symptoms suggesting asthma compared to symptom-free girls, but not in boys. In children with chronic cough, impedance was not significantly different from the values of symptom-free children. The results obtained by the additional impedance parameters were comparable to those of the commonly used measures. We conclude that the diagnostic value of the impedance parameters appeared to be low, as no cut-off points were found to discriminate clearly between symptomatic and symptom-free children. These findings may reflect absence of functional abnormalities in symptomatic children at this age. (C)ERS Journals Ltd 1997.

Study objective: To determine the effectiveness of treatment with corticosteroids in patients with COPD.Methods: In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 mu g/d; inhaled budesonide, 1,600 mu g/d, plus oral prednisolone, 5 mg/d (bud+pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV(1) was assessed by calculating individual regression coefficients from linear regression of FEV(1) on time for each subject.Results: Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the place group (n=5 out of 18) than in the actively treated groups (n=2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV(1) was 60 mL/yr in the plac group, 40 mL/yr in the bud+pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral croticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.Conclusions: Our study shows beneficial effects of long-term daily treatment with inhaled croticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects ar limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.

Study objective: To determine the effectiveness of treatment with corticosteroids in patients with COPD. Methods: In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 mu g/d; inhaled budesonide, 1,600 mu g/d, plus oral prednisolone, 5 mg/d (bud+pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV(1) was assessed by calculating individual regression coefficients from linear regression of FEV(1) on time for each subject. Results: Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the place group (n=5 out of 18) than in the actively treated groups (n=2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV(1) was 60 mL/yr in the plac group, 40 mL/yr in the bud+pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral croticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups. Conclusions: Our study shows beneficial effects of long-term daily treatment with inhaled croticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects ar limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.

Background - Bacterial infections of the lower airways during an exacerbation in patients with asthma or chronic obstructive pulmonary disease (COPD) may be the cause of an exacerbation or the consequence of a viral infection or an increase in airways limitation. To determine whether bacterial infection is an important component in the pathogenesis of an exacerbation, the effects of antimicrobial treatment must be studied. Methods - Patients with asthma or COPD seen in general practice were studied in a double blind randomised manner to investigate whether the antimicrobial drugs amoxicillin (500 mg three times daily), cotrimoxazole (960 mg twice daily), or a placebo, each when added to a short course of oral corticosteroids, can accelerate recovery from exacerbations. Patients were instructed to contact their own physician early in the morning when complaints of increased shortness of breath, wheezing, or exacerbations of cough with or without sputum production occurred. Treatment effects were evaluated over the next 14 days by studying symptom scores (wheeze, dyspnoea, cough with and without mucus production, and awakening with dyspnoea), peak expiratory flow values (PEF, expressed as % predicted), and sublingual temperature. Bacteriological study of the sputum was made at the onset of an exacerbation and 7, 21 and 35 days afterwards. Results - Of 195 patients enrolled 71 (36%) contacted their physician for symptoms of an exacerbation. Symptoms improved in all three groups, improvements ranging from 0.54 to 0.75 points per day on a four point scale. PEF % predicted showed improvements in the three groups after the exacerbation, ranging from 0.34% to 0.78% predicted per day, finally returning to baseline values. Sublingual temperature did not change. Six of 71 patients consulted their physician because of a relapse between four and 24 days after the start of treatment. In only two of the 50 sputum samples, collected during an exacerbation, and which contained equal to or greater than 10(5) bacteria in culture sensitive to the chosen antibiotic given, did any benefit from antimicrobial treatment occur. During the recovery period sputum purulence improved irrespective of antibiotic treatment. Conclusions - Antibiotics given with a short course of oral prednisolone during an exacerbation do not accelerate recovery as measured by changes in peak flow and symptom scores in ambulatory patients with mild to moderate asthma or COPD when treated by their general practitioners. Moreover, antibiotics do not reduce the number of relapses after treating an exacerbation.

Background - Bacterial infections of the lower airways during an exacerbation in patients with asthma or chronic obstructive pulmonary disease (COPD) may be the cause of an exacerbation or the consequence of a viral infection or an increase in airways limitation. To determine whether bacterial infection is an important component in the pathogenesis of an exacerbation, the effects of antimicrobial treatment must be studied.Methods - Patients with asthma or COPD seen in general practice were studied in a double blind randomised manner to investigate whether the antimicrobial drugs amoxicillin (500 mg three times daily), cotrimoxazole (960 mg twice daily), or a placebo, each when added to a short course of oral corticosteroids, can accelerate recovery from exacerbations. Patients were instructed to contact their own physician early in the morning when complaints of increased shortness of breath, wheezing, or exacerbations of cough with or without sputum production occurred. Treatment effects were evaluated over the next 14 days by studying symptom scores (wheeze, dyspnoea, cough with and without mucus production, and awakening with dyspnoea), peak expiratory flow values (PEF, expressed as % predicted), and sublingual temperature. Bacteriological study of the sputum was made at the onset of an exacerbation and 7, 21 and 35 days afterwards.Results - Of 195 patients enrolled 71 (36%) contacted their physician for symptoms of an exacerbation. Symptoms improved in all three groups, improvements ranging from 0.54 to 0.75 points per day on a four point scale. PEF % predicted showed improvements in the three groups after the exacerbation, ranging from 0.34% to 0.78% predicted per day, finally returning to baseline values. Sublingual temperature did not change. Six of 71 patients consulted their physician because of a relapse between four and 24 days after the start of treatment. In only two of the 50 sputum samples, collected during an exacerbation, and which contained equal to or greater than 10(5) bacteria in culture sensitive to the chosen antibiotic given, did any benefit from antimicrobial treatment occur. During the recovery period sputum purulence improved irrespective of antibiotic treatment.Conclusions - Antibiotics given with a short course of oral prednisolone during an exacerbation do not accelerate recovery as measured by changes in peak flow and symptom scores in ambulatory patients with mild to moderate asthma or COPD when treated by their general practitioners. Moreover, antibiotics do not reduce the number of relapses after treating an exacerbation.

Background: Many countries in sub-Saharan Africa have the highest risk of developing chronic diseases and are the least able to cope with them. Aims: To assess the current knowledge of the prevalence and impact of asthma and chronic obstructive pulmonary disease (COPD) in sub-Saharan Africa. Methods: A literature search was conducted using Medline (1995-2010) and Google Scholar. Results: Eleven studies of the prevalence of asthma in sub-Saharan Africa were identified, all of which showed a consistent increase, particularly in urban regions. The data on asthma show a wide variation (5.7-20.3%), with the highest prevalence in 'westernised' urban areas. Only two studies of the prevalence of COPD in sub-Saharan Africa have been performed. Nevertheless, COPD has become an increasing health problem in sub-Saharan Africa due to tobacco smoking and exposure to biomass fuels. In most countries of sub-Saharan Africa, 90% of the rural households depend on biomass fuel for cooking and heating, affecting young children (acute lower respiratory infections) and women (COPD). This is the cause of significant mortality and morbidity in the region. Conclusions: Asthma and COPD in sub-Saharan Africa are under-recognised, under-diagnosed, under-treated, and insufficiently prevented. A major priority is to increase the awareness of asthma and COPD and their risk factors, particularly the damage caused by biomass fuel. Surveys are needed to provide local healthcare workers with the possibility of controlling asthma and COPD. (C) 2011 Primary Care Respiratory Society UK. All rights reserved. F van Gemert et al. Prim Care Respir J 2011; 20(3): 240-248 http://dx.doi.org/10.4104/pcrj.2011.00027

Although most patients with obstructive airways disease show some amelioration with long-term inhaled corticosteroid therapy, the extent of improvement may vary considerably between patients.Patients, with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) less-than-or-equal-to 8 mg-ml-1, and forced expiratory volume in one second (FEV1)Patients had a larger ''immediate'' improvement in their FEV1 with inhaled corticosteroids with each doubling doses lower PC20, with each ten-fold higher immunoglobulin E (IgE), and if they did not smoke. Total IgE proved a better independent predictor of ''immediate'' response than specific IgE for house dust mite, skin tests, or blood eosinophils. A more favourable long-term slope of FEV1 was predicted by a larger baseline bronchodilator response, but not by smoking.In conclusion, PC20, total IgE, and smoking habits are independent predictors of immediate treatment response to inhaled corticosteroids. Bronchodilator response is the single independent predictor of changes in long-term slope of FEV1 with corticosteroid treatment.

Although most patients with obstructive airways disease show some amelioration with long-term inhaled corticosteroid therapy, the extent of improvement may vary considerably between patients. Patients, with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) less-than-or-equal-to 8 mg-ml-1, and forced expiratory volume in one second (FEV1) Patients had a larger ''immediate'' improvement in their FEV1 with inhaled corticosteroids with each doubling doses lower PC20, with each ten-fold higher immunoglobulin E (IgE), and if they did not smoke. Total IgE proved a better independent predictor of ''immediate'' response than specific IgE for house dust mite, skin tests, or blood eosinophils. A more favourable long-term slope of FEV1 was predicted by a larger baseline bronchodilator response, but not by smoking. In conclusion, PC20, total IgE, and smoking habits are independent predictors of immediate treatment response to inhaled corticosteroids. Bronchodilator response is the single independent predictor of changes in long-term slope of FEV1 with corticosteroid treatment.

Background. The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. Methods. In a multicenter trial we compared three inhalation regimens in which a beta2-agonist (terbutaline, 2000 mug daily) was combined with a corticosteroid (beclomethasone, 800 mug daily), an anticholinergic bronchodilator (ipratropium bromide, 160 mug daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. Results. Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P Conclusions. The addition of an inhaled corticosteroid - but not an inhaled anticholinergic agent - to maintenance treatment with a beta2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

Background. The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy.Methods. In a multicenter trial we compared three inhalation regimens in which a beta2-agonist (terbutaline, 2000 mug daily) was combined with a corticosteroid (beclomethasone, 800 mug daily), an anticholinergic bronchodilator (ipratropium bromide, 160 mug daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years.Results. Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; PConclusions. The addition of an inhaled corticosteroid - but not an inhaled anticholinergic agent - to maintenance treatment with a beta2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

Background Short term treatment corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide. Methods Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed. Results At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67-9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4-8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0-67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0-03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant. Conclusions In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the Protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.

Background Short term treatment corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide.Methods Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed.Results At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67-9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4-8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0-67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0-03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant.Conclusions In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the Protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.

Systemic corticosteroids and additional short-acting beta 2-agonists are commonly used in exacerbations of chronic obstructive pulmonary disease (COPD). In this double-blind study, the combination of a high-dose inhaled corticosteroid with a rapid-onset long-acting beta 2-agonist was evaluated in the treatment of out-patient COPD exacerbations. The primary aim was to compare 14-day treatment effects of budesonide/formoterol to placebo on sputum eosinophils and, secondarily, on other indices of inflammation, forced expiratory flow in one second (FEV(1)), symptoms, health status, and adverse events. Forty-five patients not using steroids (37 male, 21/24 currentlex smoker, median packyears 38, age 65 years, FEV(1) 61% predicted), experiencing a COPD exacerbation, were treated at home with budesonide/formoterol (320/9 mu g 4 times daily), prednisolone (30 mg daily), or placebo for 14 days. Sputum eosinophils were significantly reduced by budesonide/formoterol (-57%) compared to placebo (+24%) (p = 0.01). Budesonide/formoterol reduced total symptom scores significantly (p = 0.01) compared to placebo. The increase in FEV(1) by 2 weeks of treatment with budesonide/formoterol (125 ml) was not significantly different from that of placebo (43 ml) (p = 0.07). Budesonide/formoterol treatment did not suppress morning serum cortisol compared to placebo (-16 %; p = 0.50). In conclusion, budesonide/formoterol reduces sputum eosinophils and improves symptoms in the treatment of out-patient COPD exacerbations.

Background Inflammation in the airways and lung parenchyma underlies fixed airway obstruction in chronic obstructive pulmonary disease. The exact role of smoking as promoting factor of inflammation in chronic obstructive pulmonary disease is not clear, partly because studies often do not distinguish between current and ex-smokers. Methods We investigated airway inflammation in sputum and bronchial biopsies of 34 smokers with chronic obstructive pulmonary disease (9 Global initiative for Chronic Obstructive Lung Disease stage 0, 9 stage I, 10 stage II and 6 stage III) and 26 asymptomatic smokers, and its relationship with past and present smoking habits and airway obstruction. Results Neutrophil percentage, interleukin-8 and eosinophilic-cationic-protein levels in sputum were higher in chronic obstructive pulmonary disease (stage I-III) than asymptomatic smokers. Inflammatory cell numbers in bronchial biopsies were similar in both groups. Current smoking correlated positively with macrophages: in bronchial biopsies in both groups, and in sputum in chronic obstructive pulmonary disease. Pack-years smoking correlated positively with biopsy macrophages only in chronic obstructive pulmonary disease. Conclusion Inflammatory effects of current smoking may mask the underlying ongoing inflammatory process pertinent to chronic obstructive pulmonary disease. This may have implications for future studies, which should avoid including mixed populations of smokers and ex-smokers.

Background Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation. Objective To investigate the role of airway inflammation in hyperresponsiveness to adenosine 5'-monophosphate (AMP) in COPD. Methods We investigated inflammatory indices in induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies in subjects with COPD with and without hyperresponsiveness to AMP. Twelve nonatopic subjects with COPD with hyperresponsiveness to AMP (mean +/- SD, age 63 +/- 8 years, FEV1% predicted 56 +/- 13%), six without BHR (age 60 +/- 6 years, FEV1% predicted 65 +/- 11%) and 11 healthy nonatopic controls without BHR (age 58 +/- 8 years, FEV1% predicted 104 +/- 11%) participated in the study. Results Subjects with COPD with BHR had significantly higher numbers of mucosal CD8 + and higher percentages of sputum eosinophils than those without BHR (median, 550 cells/mm(2); range, 30-1340 vs 280 cells/mm(2); range, 110-450, P = 0.045; and median, 2.7%; range, 0.5-8.5 vs 0.6%; range, 0-0.8 %, P = 0.0036, respectively). No differences were observed in BAL fluid. Conclusion We conclude that hyperresponsiveness to AMP in COPD is associated with airway inflammation that is characterized by increased numbers of mucosal CD8 + cells and percentages of sputum eosinophils. Hyperresponsiveness to AMP may be used as a marker of airway inflammation in COPD, but its significance in the clinical course remains to be determined.

Background and Methods Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, pla cebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in subjects with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 mu g of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. Results Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the th ree-year period was 140 ml in the budesonide group and 180 mi in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 mi per year in the budesonide group, as compared with a decline of 81 mi per year in the placebo group (P Conclusions In persons with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline. (N Engl J Med 1999;340:1948-53.) (C) 1999, Massachusetts Medical Society.

The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'-monophosphate (AMP), to which we hypothesized the existence of greater sensitivity. Additionally, we studied the effects of budesonide on terfenadine and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and histamine. Forty-four hyperresponsive smokers with moderate to severe COPD participated in the study. MCh and AMP challenges were given on three study days, after pretreatment with single doses of ipratropium bromide, terfenadine, or placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600 mu g budesonide or placebo, and the same three study days were repeated. Budesonide, as compared with placebo, did not significantly change PC(20)AMP, PC(20)MCh, or FEV1 after placebo pretreatment. Budesonide increased PC(20)MCh after ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p 0.036). Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p

The aim of this study was to determine whether impedance values in children with various chronic respiratory complaints differed from those observed in symptom-free children. Respiratory impedance was measured using the forced oscillation technique in 1,776 Dutch children aged 6-12 yrs. In addition to the commonly used parameters of resistance and reactance, further impedance parameters were obtained by using linear and quadratic regression to describe individual resistance and reactance curves as a function of frequency. Furthermore, the diagnostic value of the individual impedance parameters was evaluated by means of receiver operator characteristic (ROC) curves. Statistically significant differences in impedance values were found in girls with symptoms suggesting asthma compared to symptom-free girls, but not in boys. In children with chronic cough, impedance was not significantly different from the values of symptom-free children. The results obtained by the additional impedance parameters were comparable to those of the commonly used measures. We conclude that the diagnostic value of the impedance parameters appeared to be low, as no cut-off points were found to discriminate clearly between symptomatic and symptom-free children. These findings may reflect absence of functional abnormalities in symptomatic children at this age. (C)ERS Journals Ltd 1997.

Study objective To determine the effectiveness of treatment with corticosteroids in patients with COPD. Methods In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 μg/d; inhaled budesonide, 1,600 μg/d, plus oral prednisolone, 5 mg/d (bud+pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV 1 was assessed by calculating individual regression coefficients from linear regression of FEV 1 on time for each subject. Results Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n=5 out of 18) than in the actively treated groups (n=2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV 1 was 60 mL/yr in the plac group, 40 mL/yr in the bud+pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups. Conclusions Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.

Background - Bacterial infections of the lower airways during an exacerbation in patients with asthma or chronic obstructive pulmonary disease (COPD) may be the cause of an exacerbation or the consequence of a viral infection or an increase in airways limitation. To determine whether bacterial infection is an important component in the pathogenesis of an exacerbation, the effects of antimicrobial treatment must be studied. Methods - Patients with asthma or COPD seen in general practice were studied in a double blind randomised manner to investigate whether the antimicrobial drugs amoxicillin (500 mg three times daily), cotrimoxazole (960 mg twice daily), or a placebo, each when added to a short course of oral corticosteroids, can accelerate recovery from exacerbations. Patients were instructed to contact their own physician early in the morning when complaints of increased shortness of breath, wheezing, or exacerbations of cough with or without sputum production occurred. Treatment effects were evaluated over the next 14 days by studying symptom scores (wheeze, dyspnoea, cough with and without mucus production, and awakening with dyspnoea), peak expiratory flow values (PEF, expressed as % predicted), and sublingual temperature. Bacteriological study of the sputum was made at the onset of an exacerbation and 7, 21 and 35 days afterwards. Results - Of 195 patients enrolled 71 (36%) contacted their physician for symptoms of an exacerbation. Symptoms improved in all three groups, improvements ranging from 0.54 to 0.75 points per day on a four point scale. PEF % predicted showed improvements in the three groups after the exacerbation, ranging from 0.34% to 0.78% predicted per day, finally returning to baseline values. Sublingual temperature did not change. Six of 71 patients consulted their physician because of a relapse between four and 24 days after the start of treatment. In only two of the 50 sputum samples, collected during an exacerbation, and which contained equal to or greater than 10(5) bacteria in culture sensitive to the chosen antibiotic given, did any benefit from antimicrobial treatment occur. During the recovery period sputum purulence improved irrespective of antibiotic treatment. Conclusions - Antibiotics given with a short course of oral prednisolone during an exacerbation do not accelerate recovery as measured by changes in peak flow and symptom scores in ambulatory patients with mild to moderate asthma or COPD when treated by their general practitioners. Moreover, antibiotics do not reduce the number of relapses after treating an exacerbation.

Although most patients with obstructive airways disease show some amelioration with long-term inhaled corticosteroid therapy, the extent of improvement may vary considerably between patients. Patients, with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20) less-than-or-equal-to 8 mg-ml-1, and forced expiratory volume in one second (FEV1) Patients had a larger ''immediate'' improvement in their FEV1 with inhaled corticosteroids with each doubling doses lower PC20, with each ten-fold higher immunoglobulin E (IgE), and if they did not smoke. Total IgE proved a better independent predictor of ''immediate'' response than specific IgE for house dust mite, skin tests, or blood eosinophils. A more favourable long-term slope of FEV1 was predicted by a larger baseline bronchodilator response, but not by smoking. In conclusion, PC20, total IgE, and smoking habits are independent predictors of immediate treatment response to inhaled corticosteroids. Bronchodilator response is the single independent predictor of changes in long-term slope of FEV1 with corticosteroid treatment.

Background Short term treatment corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide. Methods Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed. Results At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67-9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4-8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0-67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0-03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant. Conclusions In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the Protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium.