Is sense of coherence a predictor of lifestyle changes in subjects at risk for type 2 diabetes?

OBJECTIVE: To determine whether the sense of coherence (SOC) could predict the outcome of an 18-month lifestyle intervention program for subjects at risk of type 2 diabetes. METHODS: Subjects at high risk of type 2 diabetes mellitus were recruited to a low-intensity lifestyle intervention program by their general practitioners. Weight reduction ≥ 5% and improvement in exercise capacity of ≥ 10% from baseline to follow-up indicated a clinically significant lifestyle change. SOC was measured using the 13-item SOC questionnaire. RESULTS: The study involved 213 subjects with a mean body mass index of 37 (SD ± 6). Complete follow-up data were obtained for 131 (62%). Twenty-six participants had clinically significant lifestyle changes. There was a 21% increase in the odds of a clinically significant lifestyle change for each point increase in the baseline SOC score (odds ratio = 1.21; confidence interval = 1.11-1.32). The success rate was 14 times higher in the highest SOC score tertile group compared with the lowest. CONCLUSION: High SOC scores were good predictors of successful lifestyle change in subjects at risk of type 2 diabetes. SOC-13 can be used in daily practice to increase clinical awareness on the impact of mastery on the outcome of life-style intervention programs.

No impact of early real-time PCR screening for respiratory viruses on length of stay and use of antibiotics in elderly patients hospitalized with symptoms of a respiratory tract infection in a single center in Norway.

We tested the hypothesis that the results of real-time polymerase chain reaction (PCR) analyses for respiratory viruses would reduce antibiotic treatment and length of stay in elderly patients hospitalized with respiratory infections. Within 24 h of hospital admission, a total of 922 patients aged ≥60 years were interviewed for symptoms of ongoing respiratory tract infection. Symptomatic patients were swabbed for oropharyngeal/nasopharyngeal presence of viral pathogens immediately by members of the study group. During a 2-month period, non-symptomatic volunteers among interviewed patients were swabbed as well (controls). Oropharyngeal/nasopharyngeal swabs were analyzed with real-time PCR for nine common respiratory viruses. A total of 147 out of 173 symptomatic patients and 56 non-symptomatic patients (controls) agreed to participate in the study. The patients were allocated to three cohorts: (1) symptomatic and PCR-positive (S/PCR+), (2) symptomatic and PCR-negative (S/PCR-), or (3) non-symptomatic and PCR-negative (control). There were no non-symptomatic patients with a positive PCR result. A non-significant difference in the frequency of empiric antibiotic administration was found when comparing the S/PCR+ to the S/PCR- cohort; 16/19 (84 %) vs. 99/128 (77 %) (χ(2) = 0.49). Antibiotic treatment was withdrawn in only two patients in the S/PCR+ cohort after receiving a positive viral diagnosis. The length of stay did not significantly differ between the S/PCR+ and the S/PCR- groups. We conclude that, at least in our general hospital setting, access to early viral diagnosis by real-time PCR had little impact on the antimicrobial treatment or length of hospitalization of elderly patients.

Predictors for PaO2 and hypoxemic respiratory failure in COPD-A three-year follow-up.

BACKGROUND: Knowledge about predictors for developing hypoxemia in the course of chronic obstructive pulmonary disease (COPD) progression is limited. The objective of the present study was to investigate predictors for overall PaO2, for a potential change in PaO2 over time, and for first occurrence of hypoxemia. METHODS: 419 patients aged 40-76 years with COPD GOLD stages II-IV underwent clinical and pulmonary function measurements, including repeated arterial blood gases over three years. Airway obstruction, lung hyperinflation, markers of systemic inflammation and cardiovascular health, exacerbation frequency, smoking habits, and body composition were tested as possible predictors of PaO2 and first episode of hypoxemia. RESULTS: In multivariate adjusted longitudinal analyses, forced expiratory volume in 1 second, total lung capacity and functional residual capacity (all in% predicted), resting heart rate and fat mass index were all associated with overall PaO2 (all P < 0.005). We found no change in PaO2 over time (ρ = 0.33), nor did we find evidence that any of the tested variables predicted change in PaO2 over time. In multivariate adjusted survival analyses, functional residual capacity and resting heart rate were predictors of episodic hypoxemia (both ρ < 0.005). CONCLUSIONS: This longitudinal study identified pulmonary, cardiac and metabolic risk factors for overall PaO2 and episodic hypoxemia, but detected no change in PaO2 over time.

A comparison of nasopharyngeal and oropharyngeal swabbing for the detection of influenza virus by real-time PCR.

We tested the hypothesis that swabs from the nasopharynx carry a higher viral load than swabs from the oropharynx in patients with real-time polymerase chain reaction (PCR)-confirmed influenza infection. Using flocked swabs, oropharyngeal and nasopharyngeal samples were harvested from hospital-admitted influenza patients no later than 3 days after the initial detection of influenza virus. Comparison of cycle threshold (CT) values was performed to assess differences in viral load in the specimens. Seventeen patients were diagnosed with influenza B, 14 patients with influenza A(H1N1)pdm09, and one patient with influenza A(H3N2). Nasopharyngeal samples were positive at a lower CT value than the oropharyngeal samples [mean difference in CT 5.75, 95 % confidence interval (CI) 3.8-7.7, p < 0.01], suggesting that, on average, the calculated viral load of the nasopharyngeal samples was 54 times higher (95 % CI 13.7-210.8) than those of the oropharyngeal samples. The corresponding difference in the calculated viral load for influenza A(H1N1)pdm09 virus was 23 times (95 % CI 3.8-136.2, p < 0.01) and for influenza B virus, it was 80 times (95 % CI 9.3-694.6, p < 0.01). In patients with acute influenza, nasopharyngeal swabbing was clearly superior to oropharyngeal swabbing in terms of diagnostic yield by real-time PCR.

Recommendations for epidemiological studies on COPD.

The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.

Candidate genes for COPD in two large data sets.

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV1 % predicted and FEV1/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs.

The purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. Samples were obtained from patients 60 years of age or above who were newly admitted to Sorlandet Hospital Arendal, Norway. The patients were interviewed for current symptoms of a respiratory tract infection. Using rayon swabs and nylon flocked swabs, comparable sets of mucosal samples were harvested from the nasopharynx and the oropharynx. The samples were analysed using real-time polymerase chain reaction (PCR) methods. A total of 223 patients (mean age 74.9 years, standard deviation [SD] 9.0 years) were swabbed and a virus was recovered from 11% of the symptomatic patients. Regardless of the sampling site, a calculated 4.8 times higher viral load (95% confidence interval [CI] 1.3-17, p = 0.017) was obtained using the nylon flocked swabs as compared to the rayon swabs. Also, regardless of the type of swab, a calculated 19 times higher viral load was found in the samples from the nasopharynx as compared to the oropharynx (95% CI 5.4-67.4, p < 0.001). When swabbing for respiratory viruses in elderly patients, nasopharyngeal rather than oropharyngeal samples should be obtained. Nylon flocked swabs appear to be more efficient than rayon swabs.

Socioeconomic risk factors for lung function decline in a general population.

The aim of our study was to examine sex-specific associations between different aspects of socioeconomic status (SES) (educational level, occupational status, income) and lung function in a general adult population. In the Hordaland County Cohort Study, 1,644 subjects aged 26-82 yrs at baseline answered questionnaires and performed post-bronchodilator spirometry both in 1996-1997 and in 2003-2006. We performed adjusted linear regression analysis on the effect of SES on decline in forced experimental volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC. Mean annual decline in FEV(1) from baseline to follow-up was 57 mL (se 1.3) and 48 mL (se 1.0) for males and females, respectively. Males had a larger decline in FVC than females, while females had a larger decline in FEV(1)/FVC. Lower education and low occupational status were associated with larger male lung function decline. SES did not affect female lung function decline. However, marital status was a significant predictor; unmarried females had less decline than both married and widowed females in both FEV(1) (adjusted mean annual difference 8 mL and 16 mL) and FVC (adjusted mean annual difference 8 mL and 18 mL). Low SES was associated with increased lung function decline in males. For females, marital status was more important.

Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study.

Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls. 409 COPD patients and 231 healthy subjects, aged 40-75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of >10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA. After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p<0.05), and higher levels of CRP (p<0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p<0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p<0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p<0.05). The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD.

Body composition and plasma levels of inflammatory biomarkers in COPD.

Previous studies suggest a relationship between systemic inflammation and body composition in chronic obstructive pulmonary disease (COPD). We examined the relationships between body composition (fat free mass index (FFMI) kg·m(-2) and fat mass index (FMI) kg·m(-2)) and three plasma inflammatory markers C-reactive Protein (CRP), soluble tumour necrosis factor receptor 1 (sTNF-R1) and osteoprotegerin (OPG) in 409 stable COPD patients (aged 40-75 yrs, Global Initiative for Obstructive Chronic Lung Disease (GOLD) categories II-IV, 249 male) from the Bergen COPD Cohort Study in Norway. FFMI and FMI were measured by bioelectrical impedance. Plasma CRP (µg·mL(-1)), sTNF-R1 (pg·mL(-1)) and OPG (ng·mL(-1)) were determined by enzyme immunoassays. Correlations and Kruskal-Wallis tests were used for bivariate analyses. Linear regression models were fitted for each of the three markers, CRP, sTNF-R1 and OPG, with FFMI and FMI as explanatory variables including sex, age, smoking habits, GOLD category, hypoxaemia, Charlson Comorbidity Index and inhaled steroid use as potential confounders. CRP and sTNF-R1 levels correlated positively with both FFMI and FMI. The adjusted regression coefficients for an increase in logCRP per unit increase in FFMI was 1.23 (1.14-1.33) kg·m(-2) and 24.9 (11.8-38.1) kg·m(-2) for sTNF-R1. Higher FMI was associated with a lower OPG, with adjusted regression coefficient -0.14 (-0.23- -0.04), whereas FFMI was unrelated to OPG. In conclusion, COPD patients with low FFMI had lower not higher plasma levels of CRP and sTNF-R1, whereas higher fat mass was associated with higher CRP and sTNF-R1 and lower OPG.

Quantitative computed tomography: emphysema and airway wall thickness by sex, age and smoking.

We investigated how quantitative high-resolution computed tomography (HRCT) measures of emphysema and airway wall thickness (AWT) vary with sex, age and smoking history. We included 463 chronic obstructive pulmonary disease (COPD) cases and 431 controls. All included subjects were current or ex-smokers aged > or = 40 yrs, and all underwent spirometry and HRCT examination. The HRCT images were quantitatively assessed, providing indices on lung density and airway dimensions. The median (25-75th percentile) %LAA950 (% low-attenuation area < -950 HU) was 8.9 (3-19) and 4.7 (1-16) in male and female COPD cases, respectively, and 0.71 (0.3-1.6) and 0.32 (0.1-0.8) in male and female controls, respectively. %LAA950 was higher in ex-smokers and increased with increasing age and with increasing number of pack-years. The mean+/-SD standardised AWT was 0.504+/-0.030 and 0.474+/-0.031 in male and female COPD cases, respectively, and 0.488+/-0.028 and 0.463+/-0.025 in male and female controls, respectively. AWT decreased with increasing age in cases, and increased with the degree of current smoking in all subjects. We found significant differences in quantitative HRCT measures of emphysema and AWT between varying sex, age and smoking groups of both control and COPD subjects.

Clinical data discriminating between adults with positive and negative results on bronchodilator testing.

OBJECTIVE: To evaluate how spirometry, symptoms and smoking discriminate between subjects who are responsive to bronchodilator testing and those who are non-responsive, and to examine how cut-off points of positive tests are related to symptoms of chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Subjects aged 47-48 and 71-73 years living in Bergen, Norway, were recruited. The 3506 participants (69%) filled in questionnaires and performed a bronchodilator test using salbutamol. RESULTS: Tests were positive (forced expiratory volume in 1 s [Delta FEV1] >or=200 ml and >or=12%) in 107 subjects (3%). In logistic regression, spirometry (FEV1 < 80%, OR 6.0, 95%CI 3.6-10.2, and FEV1/FVC < 0.70, OR 3.1, 95%CI 1.9-5.2) and pack-years >or= 20 (OR 0.3, 95%CI 0.2-0.7), but not symptoms, predicted the test outcome. FEV1% and FEV1/forced volume capacity (FVC) discriminated equally well between positive and negative tests (area under the receiver operating characteristic [ROC] curve 0.81, 95%CI 0.77-0.85 vs. 0.77, 95%CI 0.72-0.82). The largest likelihood ratio for positive tests was 5.4 (95%CI 3.8-7.8) using FEV1 < 80% and FEV1/FVC < 0.70. CONCLUSIONS: Spirometry and to a lesser extent smoking, but not symptoms, are useful in discriminating between middle-aged and elderly patients with positive and negative bronchodilator tests. Acute responses to salbutamol, expressed by commonly used Delta FEV1 cut-off points, are poorly related to COPD- and asthma-like symptoms.

Self-reported influenza vaccination and protective serum antibody titers in a cohort of COPD patients.

BACKGROUND: COPD patients are advised vaccination against seasonal influenza, yet few studies have evaluated the protective antibody titers obtained in this patient group. AIMS: 1) To describe protective titers in COPD patients who self-reported influenza vaccination compared with vaccinated subjects without COPD and unvaccinated COPD patients, 2) analyze whether clinical parameters predicted influenza-specific antibody titers, and 3) whether antibody titers to influenza A at baseline could predict exacerbation risk or 5 years all-cause mortality. METHODS: Influenza A (H1N1 and H3N2) titers were measured by haemagglutination inhibition assay in serum from 432 COPD patients and 77 controls in the Bergen COPD Cohort Study, at yearly visits between 2006/09. Titers of 40 or above were considered protective. We examined the variables sex, age, body composition, smoking, GOLD stage, yearly exacerbations, inhaled steroids, and Charlson score as predictive of titers, both univariately and in a multivariable model estimated by generalized estimating equations. The exacerbation incidence rate ratios and mortality hazard ratios were assessed by negative binominal and cox regression models respectively. RESULTS: At baseline, 59% of COPD patients reported influenza vaccination during the last season. Levels of predictive titers varied considerably each season, but trended lower in COPD patients compared with controls. Neither sex, age, body composition, smoking, comorbidities, GOLD stage nor use of inhaled steroids consistently predicted titers. Having high titers at baseline did not impact later risk for exacerbations, but seemed to be associated with higher all-cause mortality, even after adjustment for COPD disease characteristics. CONCLUSION: Vaccination coverage for influenza is imperfect for COPD patients in Norway, and there is a concern that immunization is suboptimal.

The incidence of adult asthma: a review.

In recent years, several new studies have estimated the incidence of adult asthma. These studies vary in design and quality. The current paper summarises the findings of major population studies in the adult incidence of asthma. The pooled estimate of the adult incidence of asthma was 4.6 per 1000 person-years in women and 3.6 per 1000 person-years in men. The estimate among only general population cohort studies was higher, respectively 5.9 and 4.4 per 1000 person-years in women and men. The adult incidence of asthma was slightly higher in women than men. In the few studies that allowed the incidence of asthma to be estimated among those aged >50 years, there was a trend towards a higher incidence with age. It is thought likely that this is at least partly explained by misclassification with COPD. However, the current findings from these studies may imply that the incidence of asthma in the elderly has previously been under-estimated. Finally, the review shows that estimates of adult asthma incidence have tended to be higher in later studies, implying a rise in asthma incidence in adults within the timeframe of observation.

Work-related asthma: prevalence estimates by sex, age and smoking habits in a community sample.

SETTING: Two-phased study of a general population sample in Norway. OBJECTIVE: To assess the prevalence of work-related asthma by sex, age and smoking habits. DESIGN: The first phase, a mail questionnaire on asthma to a random sample of the general population of Hordaland County, Norway, gave a 90% response. A stratified sample of the responders (n = 1512) was invited to complete an occupational history questionnaire and performing spirometry and bronchial hyperresponsiveness. The attendance rate was 84%. Asthmatics were defined as having work-related asthma if they answered positively the questions: "Have you ever had respiratory symptoms in relation to your work? Did the symptoms improve on absence from work?" RESULTS: The prevalence of work-related asthma was 0.9% in this population, constituting 28% of all asthmatics (95% confidence interval 25-31). The prevalence of work-related asthma was twice as high in men as in women, and did not differ significantly with age or between smoking groups. CONCLUSION: Work-related asthma amounts to a significant proportion of total asthma in this population. This should be taken into account by health planners as it is by definition a preventable disorder.

Comparison of respiratory symptoms questionnaires.

SETTING: Comparisons in performance of questionnaires are of interest in international comparisons of prevalences and risk factors, after translation and development of new questionnaires. Factors such as sex, age, educational level and smoking habits may influence the performance of questionnaires. OBJECTIVE: 1) To discuss questionnaire comparisons in general, using as an example a Norwegian respiratory symptoms questionnaire compared with a translation of the British Medical Research Council questionnaire on chronic bronchitis; and 2) to examine whether reliability differs in subgroups. DESIGN: A population sample of 935 residents of Hordaland County, Norway, completed two questionnaires in a short interval of time. Agreement and Cohen's kappa were calculated. RESULTS: Prevalences were significantly different between the two questionnaires for most symptoms. Agreement decreased from non-smokers through ex-smokers to smokers, whereas the kappa statistic increased. Agreement increased as the educational level increased, whereas the kappa statistic declined. No significant age and sex effects on agreement and kappa were observed. CONCLUSION: Small changes in the phrasing of a question can have considerable effect on prevalence estimates. Reliability statistics are prevalence dependent. Reliability may differ according to smoking habit and educational level. Questionnaires should be tested in the population that they are to be used in.

Patient satisfaction with healthcare in asthmatics and patients with COPD before and after patient education.

Patient satisfaction with general practitioners (GP) and pulmonary outpatient clinics has not been previously compared in patients with asthma and chronic obstructive pulmonary disease (COPD) in addition to the effect of patient education on this satisfaction. We randomly allocated 78 asthmatics and 62 patients with COPD after ordinary outpatient management to a control or an intervention group. Intervention consisted of educational group sessions and individual sessions administered by a trained nurse and physiotherapist. A self-management plan was developed. A patient satisfaction questionnaire was answered at baseline and at the 1-year follow-up. Before randomization, a higher proportion of asthmatics were satisfied with the overall handling of their disease by the outpatient clinic (86%) compared with their GPs (72%, P=0.027, chi2-test). Equal and high proportions of patients with COPD were satisfied with both their GPs (85%) and the outpatient clinic (87%) and in general seemed more satisfied with their GP than asthmatics (P=0.064). At the 1 year follow-up, 100% of the educated patients with COPD reported overall satisfaction with GPs compared with 78% in the control group (P=0.023), but not for asthmatics (75 and 78%, respectively, P=0.581). We conclude that before being given education, asthmatics are more satisfied with the pulmonary outpatient clinic than with GPs, regarding the overall handling of their disease. Patients with COPD seemed more satisfied with GPs than asthmatics. For patients with COPD, patient education seemed to improve overall patient satisfaction with GPs, but this was not true for asthmatics. At baseline, overall satisfaction with the outpatient clinic was so beneficial that we had little chance of detecting any improvement.

Impact of patient education and self-management on morbidity in asthmatics and patients with chronic obstructive pulmonary disease.

The effect of patient education on morbidity in asthmatics and COPD patients has not previously been investigated in a single study. We randomized 78 asthmatics and 62 COPD patients after ordinary outpatient management. Intervention consisted of educational group sessions and individual sessions administered by a trained nurse and physiotherapist. A self-management plan was developed. The utilization of health resources and absenteeism from work was self-reported monthly. During the 12-month follow-up, approximately two (P= 0.001) and three (P= 0.001) times as many uneducated asthmatics and COPD patients, respectively, visited their general practitioner (GP) compared with educated. The mean reduction in GP consultations for the educated were 73% (P<0.001) and 85% (P<0.0001) for the asthma and COPD group, respectively, compared with uneducated. Fifty percent of uneducated asthmatics reported absenteeism from work compared with 24% of the educated (P = 0.06). The mean reduction in days offwork for the educated was 69% (P = 0.03), compared with uneducated. A positive correlation was observed between St George's Respiratory Questionnaire total score and number of GP visits for both the asthma and COPD group (P < 0.001). We conclude that patient education in asthmatics and COPD patients reduced the need for GP visits and kept a greater proportion of patients independent of their GP. Patient education among asthmatics also reduced the number of days off work and appeared to increase the proportion of patients not reporting absenteeism from work at all. Increasing number of GP visits was correlated with decreased health-related quality of life as measured by the SGRQ for both the asthmatics and the COPD patients.

Factors affecting growth of FEV1.

There is an increasing awareness that also growth in FEV1 may be of importance to development of chronic obstructive lung disease in later life. This paper reviews current knowledge on factors in foetal and childhood life that may reduce lung growth. Passive smoking as well as malnutrition in foetal life is related to impaired lung function in later life. Birth weight is a risk factor to lung growth independent of gestational age and maternal smoking. Active and passive smoking in childhood and adolescence reduces growth. Girls seem to be more vulnerable than boys to the effect of smoking. Also host characteristics like atopy, bronchial hyper responsiveness and asthma are related to impaired growth of FEV1. Lower respiratory tract infections before the age of seven are also related to impaired lung growth in adult life. Although several studies have found socioeconomic status among adults related to chronic obstructive lung disease, it is not known to what extent low socioeconomic status affects growth of lung function after adjusting for risk factors like active and passive smoking and lower respiratory tract infections. Normal lung growth varies with age and between male and female. The importance of the various risk factors may differ depending at what point in the lung growth they come into play. Limited data is available about the interrelationship between the risk factors and the mechanisms through which they work.

Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial.

Background Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting ß(2) agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. Trial design A multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Methods Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 µg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 µg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0-4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV(1)) (23-24 h postdose; day 29) and wm FEV(1) (0-4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 µg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment. Results 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV(1) per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0-4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI -3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV(1) (mean difference 183 ml) and 0-4 h postdose wm FEV(1) (mean difference 236 ml). Conclusion FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD. Trial registration number clinical trials.gov-NCT00731822.