Echocardiographic consequences of smoking status in middle-aged subjects.

BACKGROUND: Smoking is known to have many short- and long-term cardiovascular effects. Cardiac index (CI), which is cardiac output indexed to body surface area, is considered to be a valid measure of cardiac performance. We investigated whether there were any differences in CI or other echocardiographic variables between never smokers, ex-smokers, and current smokers in a cardiopulmonary healthy population. METHODS: Subjects (n=355) from a previous population-based respiratory questionnaire survey (never smokers, ex-smokers, and current smokers without significant chronic obstructive lung disease) were examined with echocardiography, and CI (L/min/m2 ) was calculated. RESULTS: Current smokers had a higher CI than never smokers 2.61±0.52 L/min/m2 vs. 2.42±0.49 L/min/m2 (P<.01). Ex-smokers had a nonsignificant, numerically higher value for CI than never smokers 2.54±0.54 L/min/m2 vs. 2.42±0.49 L/min/m2 (P>.05). Smoking status had no significant effect on other echocardiographic variables. CONCLUSION: We conclude that currents smokers without known cardiac disease or significant chronic obstructive lung disease show signs of slightly altered hemodynamics.

Inhomogeneity of ventilation in smokers and mild COPD assessed by the ratio of alveolar volume to total lung capacity.

BACKGROUND: Previous studies have shown that the ratio between alveolar volume (VA) and total lung capacity (TLC) reflects ventilation heterogeneity in subjects with chronic obstructive pulmonary disease (COPD). However, the ratio and its correlation to respiratory symptoms had to our knowledge not previously been investigated in subjects with mild chronic airflow obstruction or without airflow obstruction (normal ratio FEV1/VC). The purpose of this study was to investigate potential connection between VA/TLC and respiratory symptoms, smoking habits and lung function parameters in subjects with normal spirometry and with mild chronic airflow obstruction. METHODS: We examined 450 subjects (82 non-smokers with normal spirometry, 298 subjects who smoked or had smoked earlier but had a normal spirometry and 70 subjects with chronical airflow obstruction) with routine lung function tests and a questionnaire regarding respiratory symptoms. RESULTS: This study showed 31 out of 54 subjects with a low VA/TLC had a normal ratio FEV1/VC. Of these subjects, 58.1 % had respiratory symptoms, compared to the group with normal ratio for both VA/TLC and FEV1/VC where 35.8 % had respiratory symptoms (p-value 0.02). CONCLUSION: This study has shown that within the group of subjects with a normal ratio FEV1/VC, those with a decreased ratio VA/TLC had a higher prevalence of respiratory symptoms compared to subjects with a normal VA/TLC ratio. These findings indicate that including the ratio VA/TLC in the evaluation of a pulmonary function test assessment might increase the possibility to identify subjects with early or at risk of lung disease.

Single-nucleotide polymorphisms in the sulfatase-modifying factor 1 gene are associated with lung function and COPD.

Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with COPD, suggesting a role in disease pathogenesis. Sulfatase modifying factor (SUMF1) is a key modifier in connective tissue remodelling, and we have shown previously that several SNPs in SUMF1 are associated with COPD. The aim of this study was to investigate the association between SUMF1 SNPs and advanced lung function characteristics. Never-, former and current smokers with (n=154) or without (n=405) COPD were genotyped for 21 SNPs in SUMF1 and underwent spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (D LCO) measurement and impulse oscillometry. Four SNPs (rs793391, rs12634248, rs2819590 and rs304092) showed a significantly decreased odds ratio of having COPD when heterozygous for the variance allele, together with a lower forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) ratio and an impaired peripheral resistance and reactance. Moreover, individuals homozygous for the variance allele of rs3864051 exhibited a strong association to COPD, a lower FEV1/FVC, FEV1 and D LCO, and an impaired peripheral resistance and reactance. Other SNPs (rs4685744, rs2819562, rs2819561 and rs11915920) were instead associated with impaired lung volumes and exhibited a lower FVC, total lung capacity and alveolar volume, in individuals having the variance allele. Several SNPs in the SUMF1 gene are shown to be associated with COPD and impaired lung function. These genetic variants of SUMF1 may cause a deficient sulfation balance in the extracellular matrix of the lung tissue, thereby contributing to the development of COPD.

Within-session reproducibility of forced oscillometry.

BACKGROUND: The forced oscillation technique (FOT) provides detailed information about the mechanics of the respiratory system, while requiring minimal co-operation by the patient. FOT may be abnormal in subjects with normal spirometry and appears to be more closely related to airway symptoms. It is, therefore, attractive in epidemiological studies, where a large number of different examinations are made in each subjects in a short period of time. Current technical standards recommend the mean of three consecutive measurements to be used, but there is limited information regarding within-session variability of FOT measurements. OBJECTIVE: The purpose of this study was to examine the within-session variability in FOT measurements in a large, population-based sample. METHODS: We performed three consecutive FOT measurements in 700 subjects using the impulse oscillometry system. The first measurement was compared to the mean of three measurements for resistance at 5 and 20 Hz (R5 and R20, respectively), R5-R20, reactance at 5 Hz (X5) and resonant frequency (fres ). RESULTS: The differences between the first and the mean of three measurements (median, interquartile range) were minimal, for example 0.002, -0.008 to 0.014 kPa L-1  s for R5 and -0.001, -0.008 to 0.005 kPa L-1  s for X5. Findings were numerically similar for men and women as well as for subjects with and without airflow obstruction at spirometry. CONCLUSIONS: We conclude that, whereas in clinical situations, three FOT measurements are to be preferred, a single measurement may suffice in epidemiological studies.

A new protocol for exercise testing in COPD; improved prediction algorithm for WMAX and validation of the endurance test in a placebo-controlled double bronchodilator study.

BACKGROUND: Two new protocols have been developed for bicycle exercise testing in chronic obstructive pulmonary disease (COPD) with an individualized cardiopulmonary exercise test (ICPET) and subsequent customized endurance test (CET), which generate less interindividual spread in endurance time compared with the standard endurance test. Main objectives of this study were to improve the prediction algorithm for WMAX for the ICPET and validate the CET by examining treatment effects on exercise performance of indacaterol/glycopyrronium (IND/GLY) compared with placebo. METHODS: COPD patients, with forced expiratory volume in 1 s (FEV1) 40-80% predicted, were recruited. Pooled baseline data from two previous studies (n = 38) were used for the development of an improved WMAX prediction algorithm. Additional COPD patients (n = 14) were recruited and performed the ICPET, using the new prediction formula at visit 1. Prior to the CET at visits 2 and 3, they were randomized to a single dose of IND/GLY (110/50 µg) or placebo. RESULTS: The improved multiple regression algorithm for WMAX includes diffusing capacity for carbon monoxide (DLCO), FEV1, sex, age and height and correlated to measured WMAX (R2 = 0.89 and slope = 0.89). Treatment with IND/GLY showed improvement in endurance time versus placebo, mean 113 s [95% confidence interval (CI): 6-220], p = 0.037, with more prominent effect in patients with FEV1 < 70% predicted. CONCLUSION: The two new protocols for ICPET (including the new improved algorithm) and CET were retested with consistent results. In addition, the CET showed a significant and clinically relevant prolongation of endurance time for IND/GLY versus placebo in a small number of patients.

Genetic and environmental influence on lung function impairment in Swedish twins.

BACKGROUND: The understanding of the influence of smoking and sex on lung function and symptoms is important for understanding diseases such as COPD. The influence of both genes and environment on lung function, smoking behaviour and the presence of respiratory symptoms has previously been demonstrated for each of these separately. Hence, smoking can influence lung function by co-varying not only as an environmental factor, but also by shared genetic pathways. Therefore, the objective was to evaluate heritability for different aspects of lung function, and to investigate how the estimates are affected by adjustments for smoking and respiratory symptoms. METHODS: The current study is based on a selected sample of adult twins from the Swedish Twin Registry. Pairs were selected based on background data on smoking and respiratory symptoms collected by telephone interview. Lung function was measured as FEV1, VC and DLco. Pack years were quantified, and quantitative genetic analysis was performed on lung function data adjusting stepwise for sex, pack years and respiratory symptoms. RESULTS: Fully adjusted heritability for VC was 59% and did not differ by sex, with smoking and symptoms explaining only a small part of the total variance. Heritabilities for FEV1 and DLco were sex specific. Fully adjusted estimates were 10 and 15% in men and 46% and 39% in women, respectively. Adjustment for smoking and respiratory symptoms altered the estimates differently in men and women. For FEV1 and DLco, the variance explained by smoking and symptoms was larger in men. Further, smoking and symptoms explained genetic variance in women, but was primarily associated with shared environmental effects in men. CONCLUSION: Differences between men and women were found in how smoking and symptoms influence the variation in lung function. Pulmonary gas transfer variation related to the menstrual cycle has been shown before, and the findings regarding DLco in the present study indicates gender specific environmental susceptibility not shown before. As a consequence the results suggest that patients with lung diseases such as COPD could benefit from interventions that are sex specific.

Reduced Variability of Endurance Time in New Protocols for Exercise Tests in COPD.

Purpose: For exercise testing of COPD patients, a standard endurance test (ET) with constant workload is recommended. The test suffers from large inter-individual variability and need for large sample sizes in order to evaluate treatment effects. Methods: A new protocol for ET in COPD was designed. In contrast to the standard ET, the new ET involved an increasing workload in order to reduce the standard deviation of endurance time. Two new ETs were compared with the standard ET. In Study A, the new ET started at 75% of the patient's maximum workload (WMAX) and increased stepwise with 3%/2 min until exhaustion. Study B started at 70% of WMAX and increased linearly with 1%/min. Results: In Study A, that included 15 patients, the standard deviation and range for endurance time and work capacity were narrower for the new versus the standard ET. However, the higher mean workload at end and the low mean work capacity relative to the standard ET indicated that the stepwise increase was too aggressive. In Study B, that included 18 patients, with a modified protocol, the averages for endurance time, workload at end and work capacity were similar for new and standard ET, while the standard deviations and ranges for endurance time and work capacity were kept more narrow in the new ET. The variances for endurance time were not equal between the standard ET and the two new ETs (p<0.05 for both according to Levene's test). Conclusion: The new ET reduced the number of patients with extreme endurance times (short and long) compared to the standard test. The new test showed a significant lower variance for endurance time, which potentially can lead to fewer patients needed in comparative studies. The overall best results were observed with a low linear increase during endurance.

Association of coronary calcium score with endothelial dysfunction and arterial stiffness.

BACKGROUND AND AIMS: The aim of the study was to determine potential associations between endothelial dysfunction and arterial stiffness, measured by peripheral arterial tonometry, and coronary artery calcium score (CACS) assessed by computed tomography (CT). METHODS AND RESULTS: The BIG3 study is a prospective longitudinal, non-interventional, pulmonary-cardiovascular cohort study exploring the three major smoking-induced diseases: cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer, in a 45-75 aged cohort (mean 62 years), enriched in smokers. Computed tomography of the chest with assessment of CACS was performed in a selected subset of the participants (n = 2080). Peripheral arterial tonometry (EndoPAT) was used to assess endothelial function and arterial stiffness measured as reactive hyperaemia index (RHI) and augmentation index (AI), respectively. We observed significant associations of CACS, endothelial dysfunction, and arterial stiffness with several risk factors for coronary heart disease including age, sex, BMI, diabetes mellitus, and blood pressure. There was significant association of CACS, classified into three levels of severity, with RHI and AI (p = 0.0005 and p = 0.0009, respectively). For groups of increasing CACS (0, 1-400 and > 400 Agatston score), RHI decreased from median 1.89 (1.58-2.39), and 1.93 (1.62-2.41) to 1.77 (1.51-2.10). AI increased from median 14.3 (5.7-25.2), and 16.4 (8.1-27.6) to 18.0 (9.1-29.2). RHI, but not AI, remained significantly associated with CACS after risk factors adjustment. CONCLUSIONS: In this large study of coronary artery calcium and vascular function, we found an association between CACS and both endothelial dysfunction and arterial stiffness, indicating that they may reflect similar mechanisms for development of cardiovascular disease.

Clinical characteristics of the BREATHE cohort - a real-life study on patients with asthma and COPD.

Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases.

Twins studies as a model for studies on the interaction between smoking and genetic factors in the development of chronic bronchitis.

Smoking is the main risk factor for COPD (chronic obstructive pulmonary disease) but genetic factors are of importance, since only a subset of smokers develops the disease. Sex differences have been suggested both in disease prevalence and response to environmental exposures. Furthermore, it has been shown that acquisition of 'addiction' to smoking is partly genetically mediated. Disease cases and smoking habits were identified in 44919 twins aged >40 years from the Swedish Twin Registry. Disease was defined as self-reported chronic bronchitis or emphysema, or recurrent cough with phlegm. The results showed that chronic bronchitis seems to be more prevalent among females, and that the heritability estimate for chronic bronchitis was a moderate 40% and only 14% of the genetic influences were shared by smoking. In addition, 392 twins have been invited to a clinical investigation to evaluate: (i) to what extent genetic factors contribute to individual differences (variation) in FEV(1) (forced expiratory volume in 1 s), vital capacity and DL(CO) (diffusion capacity), taking sex into consideration, and (ii) whether smoking behaviour and respiratory symptoms influence these estimates.

Traffic exposure associated with allergic asthma and allergic rhinitis in adults. A cross-sectional study in southern Sweden.

BACKGROUND: There is conflicting evidence that traffic-related air pollution is a risk factor for allergic conditions. Few studies have investigated this in adults. In adults, a high proportion of asthma, rhinitis and eczema is triggered by non-allergic factors. We investigated traffic as a risk factor for allergic versus non-allergic asthma and rhinitis, and eczema, in adults. A questionnaire from 2000 (n = 9319, 18-77 years) provided individual data about disease outcome and self-reported traffic exposure. Additional exposure assessments were obtained using Geographical Informations Systems (GIS). Residential addresses were linked to the national Swedish Road Database and to a pollutant database with modelled annual means of NOx (Nitrogen Oxids). RESULTS: Living within 100 m from a road with a traffic intensity of >10 cars/min (24 hour mean) was associated with prevalence of current asthma reported to be triggered by allergic factors (OR = 1.83, 95% CI = 1.23-2.72) and with allergic rhinitis (OR = 1.30, 95%CI = (1.05-1.61). No relation was seen with asthma or rhinitis triggered by other factors. Living within 100 m of a road with >10 cars/min was also associated with hand-eczema during the last 12 months (OR = 1.63, 95% CI = 1.19-2.23), but not with allergic eczema or diagnosed hand-eczema. Consistent results were seen using self-reported traffic, but the associations with NOx were less consistent. CONCLUSION: Exposure to traffic was associated with a higher prevalence of allergic asthma and allergic rhinitis, but not with asthma or rhinitis triggered by non-allergic factors. This difference was suggested by the overall pattern, but only clear using GIS-measured traffic intensity as a proxy for traffic exposure. An association was also found with hand-eczema during the last 12 months. We suggest that asthma and rhinitis should not be treated as homogenous groups when estimating effects from traffic in adults.

Traffic-related air pollution associated with prevalence of asthma and COPD/chronic bronchitis. A cross-sectional study in Southern Sweden.

BACKGROUND: There is growing evidence that air pollution from traffic has adverse long-term effects on chronic respiratory disease in children, but there are few studies and more inconclusive results in adults. We examined associations between residential traffic and asthma and COPD in adults in southern Sweden. A postal questionnaire in 2000 (n = 9319, 18-77 years) provided disease status, and self-reported exposure to traffic. A Geographical Information System (GIS) was used to link geocoded residential addresses to a Swedish road database and an emission database for NOx. RESULTS: Living within 100 m of a road with >10 cars/minute (compared with having no heavy road within this distance) was associated with prevalence of asthma diagnosis (OR = 1.40, 95% CI = 1.04-1.89), and COPD diagnosis (OR = 1.64, 95%CI = 1.11-2.4), as well as asthma and chronic bronchitis symptoms. Self-reported traffic exposure was associated with asthma diagnosis and COPD diagnosis, and with asthma symptoms. Annual average NOx was associated with COPD diagnosis and symptoms of asthma and chronic bronchitis. CONCLUSION: Living close to traffic was associated with prevalence of asthma diagnosis, COPD diagnosis, and symptoms of asthma and bronchitis. This indicates that traffic-related air pollution has both long-term and short-term effects on chronic respiratory disease in adults, even in a region with overall low levels of air pollution.

Interaction between smoking and genetic factors in the development of chronic bronchitis.

RATIONALE: Smoking is a primary risk factor for chronic bronchitis, emphysema, and chronic obstructive pulmonary disease, but since not all smokers develop disease, it has been suggested that some individuals may be more susceptible to exogenous factors, such as smoking, and that this susceptibility could be genetically determined. OBJECTIVES: The aim of the present study was to assess, in a population-based sample of twins, the following: (1) to what extent genetic factors contribute to the development of chronic bronchitis, including emphysema, taking sex into consideration, and (2) whether the genetic influences on chronic bronchitis, including emphysema, are separate from those for smoking behavior. METHODS: Disease cases and smoking habits were identified in 44,919 twins older than 40 years from the Swedish Twin Registry. Disease was defined as self-reported chronic bronchitis or emphysema, or recurrent cough with phlegm. Individuals who had smoked 10 pack-years or more were defined as smokers. Univariate and bivariate structural equation models were used to estimate the heritability specific for chronic bronchitis and that in common with smoking. MEASUREMENTS AND MAIN RESULTS: The heritability estimate for chronic bronchitis was a moderate 40% and only 14% of the genetic influences were shared with smoking. CONCLUSIONS: Genetic factors independent of those related to smoking habits play a role in the development of chronic bronchitis.

Specific nasal symptoms and symptom-provoking factors may predict increased risk of developing COPD.

In a 1992 questionnaire study, we found that certain nasal symptoms and symptom-provoking factors were associated with prevalence of self-reported chronic bronchitis/emphysema (CBE). In this follow-up study, we examined whether any nasal features could predict an increased incidence of self-reported physician's diagnosis of CBE/chronic obstructive pulmonary disease (COPD). In 2000, a survey was performed similar to the one in 1992. Of a paired follow-up group of 4933 participants aged 28-67 years, 4280 (86.8%) returned the questionnaire. Odds ratios (ORs) for cumulative incidence (between 1992 and 2000) of self-reported physician-diagnosed CBE/COPD and asthma, respectively, were calculated by logistic regression with adjustment for age, gender and smoking habits. Reports of thick, yellow nasal discharge and nasal blockage in 1992 predicted incidence of CBE/COPD: OR 2.3 (1.2-4.2) and 1.8 (1.1-2.8) respectively. Moreover, nasal symptoms provoked by exposure to damp/cold air and tobacco smoke predicted CBE/COPD: OR 3.4 (1.9-6.0) and 2.5 (1.4-4.2). Nasal itching and nasal symptoms provoked by exposure to grass pollen and furred animals predicted incidence of asthma. These results suggest that certain nasal symptoms and nasal symptom-provoking exposures, different from those commonly associated with asthma, may predict increased risk of developing CBE/COPD. This supports the possibility of nasal co-morbidity in COPD.

Brain natriuretic peptide levels in middle aged subjects with normal left ventricular function in relation to mild-moderate COPD.

BACKGROUND: Levels of plasma brain natriuretic peptide (BNP) have been shown to be elevated in chronic obstructive pulmonary disease (COPD) especially in connection with cor pulmonale (CP) and the late stages of the disease. BNP is also raised in left sided heart failure which sometimes coincides with COPD. Whether BNP is elevated in subjects with mild-moderate stable COPD and normal left ventricular function is not clear. OBJECTIVE: To investigate BNP levels in subjects with mild-moderate COPD and normal left ventricular function. METHODS: This was a cross sectional study of 450 subjects from a population-based respiratory questionnaire survey. All subjects were examined with echocardiography and spirometry and blood samples were drawn for BNP measurements. Subjects with left sided heart disease (n = 26) or echocardiographic signs of elevated filling pressure (n = 75), COPD stages III and IV (n = 5) or missing data (n = 13) were excluded. RESULTS: In the final study population (n = 331) spirometry identified 86 subjects with COPD (GOLD stage I, n = 65 and GOLD stage II, n = 21). In comparison with the rest of the study population subjects with COPD were significantly older, longer and with a male predominance. In a multivariate linear regression analysis with log-normalized (lnBNP) as the dependent variable a significant correlation was found with age, left atrial volume, body surface area and haemoglobin, but not with any pulmonary variables. Even when comparing groups no significant difference could be found between the plasma levels of lnBNP in normal subjects (1.8 ± 0.7 mean ± SD, pmol/L) subjects and in COPD subjects (1.9 ± 0.7, P = 0.47). CONCLUSIONS: In a population with normal left ventricular function no significant differences in BNP levels between stable mild-moderate COPD subjects and normal individuals could be found.

Fixed ratio or lower limit of normal for the FEV1 /VC ratio: relation to symptoms and extended lung function tests.

There is no general agreement on the spirometric definition of chronic obstructive pulmonary disease (COPD). The global initiative for obstructive lung disease recommends a fixed ratio between forced expiratory volume in one-second (FEV1 ) and forced vital capacity (FVC) of <0·7 (FR) for the diagnosis of COPD. European Respiratory Society and American Thoracic Society favour the use of the fifth percentile of the age-related FEV1 /FVC ratio (the lower limit of normal, LLN). The purpose of this study was to analyse extensive lung function tests in groups of subjects fulfilling none, either or both of the spirometric criteria for COPD. From a previous population-based study, 450 subjects were examined with spirometry, body pletysmography diffusing capacity for CO (DL,CO ), Impulse Oscillometry System (IOS) and answered a questionnaire on respiratory symptoms and diseases. Seventy subjects fulfilled both spirometric COPD criteria (FR+LLN+), 62 subjects the fixed ratio criterion (FR+) only. Of the remaining 318 subjects, 236 were ever smokers (N-ES). Significant differences between all groups were seen for FEV1 and DL,CO . Significant differences between groups were also seen for residual volume (RV) and RV/total lung capacity. For IOS, variables and symptoms increasingly abnormal values were seen from never smokers to FR+LLN+. This study shows that subjects meeting both spirometric COPD criteria frequently have symptoms and findings at extended lung function tests compatible with the diagnosis. Also subjects meeting the fixed ratio criterion only tend to have more symptoms and lung function findings compatible with COPD than ever-smoking subjects with FEV1 /VC > 0·7.

Formoterol used as needed in patients with intermittent or mild persistent asthma.

OBJECTIVE: To study the effectiveness and safety of as-needed treatment of formoterol compared with the short-acting alternative terbutaline. METHODS: Two double-blind, 12-month, parallel-group, non-inferiority trials comparing as-needed use of formoterol (Oxis) 4.5 microg and terbutaline (Bricanyl) 0.5 mg via dry-powder inhaler (Turbuhaler), one in 675 patients with intermittent and one in 455 patients with mild persistent asthma, overall 6-87 years of age. Peak expiratory flow (PEF), symptoms, rescue medication use, exacerbations, airway responsiveness (metacholine challenge; subgroup of 127 patients), systemic effects (high single-dose test; subgroup of 87 patients), and safety (adverse events) were assessed. RESULTS: Formoterol 4.5 microg was as effective as terbutaline 0.5 mg with regard to morning PEF (non-inferiority; lower 95% confidence interval limit above -10 L/min). Metacholine sensitivity, exacerbation rates or use of rescue medication did not differ between treatments. Formoterol 54 microg was shown to give less systemic effects than terbutaline 6 mg. Both treatments were safe and well tolerated. CONCLUSIONS: Formoterol 4.5 microg used as needed was at least as effective and safe as terbutaline 0.5 mg used as needed in intermittent and mild persistent asthma, and was associated with less systemic effects when administered as high single doses.

Formoterol for maintenance and as-needed treatment of chronic obstructive pulmonary disease.

Formoterol is a long-acting beta2-agonist with a rapid onset of effect in patients with chronic obstructive pulmonary disease (COPD), making it potentially suitable for both maintenance and as-needed bronchodilator treatment. To evaluate the efficacy and tolerability of maintenance formoterol in patients with COPD and to compare the effects of additional formoterol as needed with terbutaline. In this 6-month, double-blind study, 657 patients with COPD (40 years, forced expiratory volume in 1s [FEV1] 40-70% predicted normal) were randomized to formoterol 9 microg twice daily (bid) plus terbutaline 0.5 mg as needed (FORM bid), formoterol 9 microg bid plus formoterol 4.5 microg as needed (FORM bid+prn), or placebo bid plus terbutaline 0.5 mg as needed (placebo), all administered via Turbuhaler. Primary efficacy variables were FEV1 and the sum of breathlessness and chest tightness scores combined symptom score. Formoterol significantly (P<0.01) increased FEV(1) compared with placebo: FORM bid 6.5% (95% CI: 2.5, 10.7%); FORM bid+prn 11.8% (95% CI: 7.7, 16.2%). Combined symptom score decreased significantly in both formoterol groups compared with placebo: FORM bid -0.27 (95% CI: -0.49, -0.06; P=0.012); FORM bid+prn -0.32 (95% CI: -0.53, -0.11; P=0.0026). Similar significant (P<0.05) improvements were seen in both formoterol groups for morning peak expiratory flow, cough and sleep scores, and reliever use. In this study, formoterol 9 microg bid via Turbuhaler as maintenance therapy, with either formoterol or terbutaline as rescue medication, provided sustained improvements in lung function and COPD symptoms. Both formoterol regimens were well tolerated with no differences in adverse events or electrocardiogram profiles.

Alcohol-induced upper airway symptoms: prevalence and co-morbidity.

Little is known about effects of alcohol intake on the upper, nasal airways. The present aim was to examine the prevalence of alcohol-induced nasal symptoms (ANS) and to explore associations between ANS and other respiratory diseases. A postal questionnaire focused on respiratory diseases and symptoms was sent to 11,933 randomly selected adult individuals. Subjects with ANS, n = 316 (3.4%) received a second questionnaire focusing on this condition. Nine thousand three hundred and sixteen (78%) subjects answered the first and 228 (72%) the second questionnaire. Two-thirds of the subjects with ANS were women. Red wine and white wine were the most frequent triggers of ANS, reported by 83% and 31% of the subjects, respectively. Nasal blockage was the most prominent symptom, but also sneezing, nasal discharge, as well as lower airway symptoms occurred after intake of alcoholic drinks. Self-reported physician's diagnoses of asthma, chronic bronchitis/emphysema, chronic obstructive pulmonary disease (COPD), as well as allergic rhinitis were more common in subjects with ANS compared with the general population (P < 0.001 for all comparisons). In conclusion, ANS are common and are about twice as frequent in women than in men. ANS seem to be associated with important respiratory diseases such as asthma, chronic bronchitis, COPD, and allergic rhinitis.

Study on risk factors and phenotypes of acute exacerbations of chronic obstructive pulmonary disease in Guangzhou, China-design and baseline characteristics.

BACKGROUND: To describe a study design that focuses on risk factors and patterns of chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: A 2-year, single centre, observational study was conducted in Guangzhou in China. The study enrolled 318 subjects with COPD aged 40-79 years, stratified into different but equally sized groups according to global initiative for chronic obstructive lung disease (GOLD) stage (including Stage 0) and 86 lung healthy controls. An assessment each year was scheduled including questionnaires, lung function testing, Chest X-ray and blood collection. A sub-group, called sub-group X, consisting of 203 subjects with COPD and 51 lung healthy controls, was selected to answer a symptom questionnaire daily (EXACT-PRO) via a BlackBerry Personal Digital Assistant (PDA) device. Upon an alert that indicated a change in daily symptom pattern, the patients were contacted by the clinic to decide whether they had experienced an exacerbation and should have an extra visit within 24-48 hours. At an extra visit, nasal and throat swabs, induced sputum and blood were collected. Air pollution, temperature and humidity were also monitored daily. A subset of sub-group X, called sub-group M that consisted of 52 COPD patients and 15 healthy controls was dedicated to measure muscle strength and a dexa scan. RESULTS: More than 78% of the enrolled patients completed the study successfully. There appeared a difference between the patient groups and the controls in gender, age, body mass index (BMI), forced expiratory volume in 1 second (FEV1), FEV1/FVC and smoking at baseline. In sub-group X 90 out of 203 (44.4%) selected COPD patients developed one or more exacerbations in the 2-year observation period. They were more severe COPD patients according to GOLD stage at study start. On average most exacerbations occurred in the month March and the least number of exacerbations occurred in October. CONCLUSIONS: This study with the obtained patient dataset will allow a better insight in many aspects of exacerbations in COPD (e.g., the identification, the risk factors, phenotypes and the biomarkers).