COPD - do the right thing.

A gap exists between guidelines and real-world clinical practice for the management and treatment of chronic obstructive pulmonary disease (COPD). Although this has narrowed in the last decade, there is room for improvement in detection rates, treatment choices and disease monitoring. In practical terms, primary care practitioners need to become aware of the huge impact of COPD on patients, have non-judgemental views of smoking and of COPD as a chronic disease, use a holistic consultation approach and actively motivate patients to adhere to treatment.This article is based on discussions at a virtual meeting of leading Nordic experts in COPD (the authors) who were developing an educational programme for COPD primary care in the Nordic region. The article aims to describe the diagnosis and lifelong management cycle of COPD, with a strong focus on providing a hands-on, practical approach for medical professionals to optimise patient outcomes in COPD primary care.

Prevalence, clinical characteristics and morbidity of the Asthma-COPD overlap in a general population sample.

OBJECTIVE: Although asthma and chronic obstructive pulmonary disease (COPD) have been regarded as distinct conditions, emerging literature suggests that overlapping phenotypes, called asthma-COPD overlap (ACO), exists. The aim of this study was to describe prevalence, patient characteristics and morbidity of ACO. METHODS: From a cross-sectional population sample, the West Sweden Asthma Study, subjects with suspected asthma, chronic bronchitis or COPD, and a random sample, were invited to clinical examinations. ACO was defined as doctor-diagnosed asthma, or clear clinical signs of asthma at examination, with a FEV1/FVC < 0.7. RESULTS: Subjects were categorized as ACO (N = 181), COPD only (N = 89), asthma only (N = 651) or healthy (n = 1036) based on clinical examinations. Prevalence of ACO was 3.4% in the random sample (N = 1172) and 18.1% among asthmatics (N = 138) in the random sample. Subjects with ACO (mean age 59 years, 54% women) had an age and gender distribution in between asthma only (45 years, 63% women) and COPD only (62 years, 41% women). Ever-smoking was reported by 71%, 48% and 74% in the ACO, asthma only and COPD only groups, respectively. Subjects with ACO had worse lung function (mean FEV1% of predicted normal 76%) than asthma only (100%) and COPD only (87%) and reported more respiratory symptoms. Also respiratory related emergency visits were more common in ACO compared to asthma only and COPD only, respectively. CONCLUSIONS: ACO is present in 3.4% of the population and common among subjects with both asthma and COPD. Subjects with ACO had worse lung function and more symptoms than subjects with asthma or COPD only.

Management, morbidity and mortality of COPD during an 11-year period: an observational retrospective epidemiological register study in Sweden (PATHOS).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and a major contributor to morbidity. Longitudinal clinical practice data yielding information on the characteristics of the disease, its natural course, and management are limited. AIMS: To investigate and describe the COPD population from a nationwide perspective during an 11-year period (1999-2009) with a focus on management, co-morbidity, and mortality. METHODS: This observational retrospective epidemiological study linked electronic medical records data from patients with COPD in primary care to mandatory Swedish hospital, drug and Cause of Death registry data from 1999 to 2009 (PATHOS). RESULTS: A total of 21,361 patients with a COPD diagnosis were included (mean age 68.0 years, 53% females). The proportion of patients diagnosed in primary care increased from 59% in 1999 to 81% in 2009 and the mean age at diagnosis decreased from 73 to 66 years. The number of exacerbations decreased from 3.0 to 1.3 and COPD-related hospitalisations decreased from 1.02 to 0.20 per patient per year. Prescriptions of long-acting muscarinic antagonists and fixed combinations of inhaled corticosteroid/long-acting ß2-agonist inhalers increased from 0% to 36% and 37%, respectively. The most common co-morbidities were hypertension, heart failure, ischaemic heart disease, and diabetes. Overall life expectancy was 8.3±6.8 years shorter in patients with COPD than in the general population, and all- cause mortality was 3.5 times higher. CONCLUSIONS: Management of COPD in Sweden has improved during the 11-year study period. Despite this, patients with COPD have a substantially reduced life expectancy than the general population.

High use of short-acting ß2-agonists in COPD is associated with an increased risk of exacerbations and mortality.

Background: Short-acting ß2-agonist (SABA) overuse has been associated with an increased risk of exacerbations in asthma; however, less is known about SABA use in COPD. Our aim was to describe SABA use and investigate potential associations between high SABA use and the risk of future exacerbations and mortality in COPD. Methods: This observational study identified COPD patients in primary care medical records in Sweden. Data were linked to the National Patient Registry, the Prescribed Drug Registry and the Cause of Death Registry. The index date was 12 months after the date of COPD diagnosis. During a 12-month prior to index baseline period, information on SABA use was collected. Patients were followed with respect to exacerbations and mortality for 12 months post index. Results: Of the 19 794 COPD patients included (mean age 69.1 years, 53.3% females), 15.5% and 7.0% had collected ≥3 or ≥6 SABA canisters during the baseline period, respectively. A higher level of SABA use (≥6 canisters) was independently associated with a higher risk of both moderate and severe exacerbations (hazard ratio (HR) 1.28 (95% CI 1.17‒1.40) and 1.76 (95% CI 1.50‒2.06), respectively) during follow-up. In total, 673 (3.4%) patients died during the 12-month follow-up period. An independent association was found between high SABA use and overall mortality (HR 1.60, 95% CI 1.07‒2.39). This association, however, was not found in patients using inhaled corticosteroids as maintenance treatment. Conclusion: In COPD patients in Sweden, high SABA use is relatively common and associated with a higher risk of exacerbations and all-cause mortality.

Exacerbations Predict Severe Cardiovascular Events in Patients with COPD and Stable Cardiovascular Disease-A Nationwide, Population-Based Cohort Study.

Objective: Patients with chronic obstructive pulmonary disease (COPD) commonly present with cardiovascular disease (CVD). We investigated the association between COPD exacerbations and major cardiovascular (CV) events in a COPD population with a history of CVD. Methods: This population-based and register-based cohort study identified all Danish COPD patients aged ≥40 years who visited a hospital-based, pulmonary outpatient clinic for COPD between 1st January, 2010, and 31st December, 2016, from a nationwide COPD registry. Patients with a history of a major CV event 36‒6 months prior to their COPD measurement date and no CV event 6 months before this date were included. During a 6-month assessment period, the risks of a new CV event (hospitalization with fatal/non-fatal stroke, myocardial infarction, or heart failure) and moderate and severe COPD exacerbations were evaluated. Odds ratios with 95% confidence intervals for CV events and death were estimated using adjusted logistic regression models. Results: Of the 1501 COPD patients included, 55% experienced a COPD exacerbation and 13% experienced both an exacerbation and a CV event during follow-up (6 months). The odds of a CV event were 1.5 times higher in patients with a moderate exacerbation and more than 6-times higher in those with a severe exacerbation vs patients with no exacerbation(s). The majority of CV events occurred within 30 days post exacerbation in patients who experienced both an exacerbation and a CV event. In total, 113 patients died during the study period: 28% of deaths were caused by CVD and 72% by reasons other than CVD, mostly COPD. Conclusion: In patients with known CVD, severe COPD exacerbations are associated with increased odds of major CV events that occur within 30 days post exacerbation, highlighting the need to prevent exacerbations in COPD patients with concomitant CVD to potentially improve both respiratory and CV health.

Improved prediction of COPD in at-risk patients using lung function pre-screening in primary care: a real-life study and cost-effectiveness analysis.

BACKGROUND: The importance of identifying chronic obstructive pulmonary disease (COPD) at an early stage is recognised. Improved and easily accessible identification of individuals at risk of COPD in primary care is needed to select patients for spirometry more accurately. AIMS: To explore whether use of a mini-spirometer can predict a diagnosis of COPD in patients at risk of COPD in primary care, and to assess its cost-effectiveness in detecting patients with COPD. METHODS: Primary care patients aged 45-85 years with a smoking history of >15 pack-years were selected. Data were collected on the Clinical COPD Questionnaire (CCQ), Medical Research Council (MRC) dyspnoea scale and smoking habits. Lung function (forced expiratory volume in 1 and 6 s; FEV1 and FEV6, respectively) was measured by mini-spirometer (copd-6), followed by diagnostic standard spirometry (COPD diagnosis post-bronchodilation ratio of FEV1 to forced vital capacity (FVC) <0.7). Time consumed was recorded. Univariate logistic regression and receiver operating characteristic (ROC) curves were used. RESULTS: A total of 305 patients (57% females) of mean (SD) age 61.2 (8.4) years, mean (SD) total CCQ 1.0 (0.8) and mean (SD) MRC 0.8 (0.8) were recruited from 21 centres. COPD was diagnosed in 77 patients (25.2%) by standard diagnostic spirometry. Using the copd-6 device, mean (SD) FEV1/FEV6 was 68 (8)% in patients with COPD and 78 (10)% in patients without COPD. Sensitivity and specificity at a FEV1/FEV6 cut-off of 73% were 79.2% and 80.3%, respectively. The area under the ROC curve was 0.84. Screening with the copd-6 device significantly predicted COPD. Gender, CCQ, and MRC were not found to predict COPD. CONCLUSIONS: Using the copd-6 as a pre-screening device, the rate of COPD diagnoses by standard diagnostic spirometry increased from 25.2% to 79.2%. Although the sensitivity and specificity of the copd-6 could be improved, it might be an important device for prescreening of COPD in primary care and may reduce the number of unnecessary spirometric tests performed.

Disease Trajectories and Impact of One Moderate Exacerbation in Gold B COPD Patients.

Introduction: Studies have shown that exacerbation in chronic obstructive pulmonary disease (COPD) increases the risk of further exacerbations. Our aim was to investigate the impact of a single moderate exacerbation on the odds of subsequent exacerbations and death in GOLD B COPD patients. Methods: This hospital-based nationwide, cohort study in Denmark included all patients ≥40 years of age with an in- and/or outpatient ICD-10 J44 diagnosis (COPD Register, 2008-2014). Index was date of first registered modified Medical Research Council (mMRC) score ≥2; baseline period was 12 months pre-index. At index, patients were grouped as: B0, no exacerbation; and B1, one moderate exacerbation during the previous year, and followed for three consecutive years in 2008-2017 for development of moderate- (short-term use of prednisolone or prednisone) and severe (emergency visit or hospitalization) exacerbations and death. Using B0 as reference, the odds ratio (OR) for exacerbation and death in GOLD B1 was estimated with multinominal logistic regression and a Cox model estimated the hazard ratio for exacerbation accounting for recurrent events. Results: In total, 8,453 patients (mean age 70 years, 51% male) were included, of which GOLD B0 4,545 and GOLD B1 3,908 patients. During the 3-year follow-up, 34.1% and 24.9% of GOLD B0 and B1, respectively, had none or one moderate exacerbation whereas 61.9% and 71.2% of B0 and B1, respectively, had a severe trajectory with multiple moderate and/or a severe exacerbation or died. In B1 patients, the OR for 1 moderate, ≥2 moderate exacerbations, ≥1 severe exacerbation was 1.58 [CI 1.33-1.87], 2.60 [2.19-3.08], 2.08 [1.76-2.45], respectively, and 1.85 [1.57-2.17] for death compared with B0. Conclusion: One moderate exacerbation in COPD patients with high symptom burden increases the odds of subsequent exacerbations and death during the three following years. The results emphasize the importance of preventing exacerbations in GOLD B patients.

What to consider before prescribing inhaled medications: a pragmatic approach for evaluating the current inhaler landscape.

Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs. The reviews of this paper are available via the supplemental material section.

High prevalence of emphysema and its association with BMI: a study of smokers with normal spirometry.

OBJECTIVES: To evaluate to what extent emphysema was evident, as identified by High Resolution Computed Tomography (HRCT), in smokers with normal lung function and to relate age, gender, smoking history, and body mass index (BMI) to the HRCT results. A secondary aim was to study to what extent emphysema was present in smokers with lower normal values of lung function defined as FEV(1)/FVC ratio percentage of predicted value (89-93% of predicted value for males and 90-93% for females) or FEF(50) < or = 60% of predicted compared with smokers without this definition. METHODS: Fifty-nine smokers, with a mean age of 53 years and with normal lung function, were examined with HRCT. RESULTS: Emphysema evidenced visually by HRCT was present in 43% of the subjects. Using a 0-5 grade scale (0=normal finding; 5=emphysema in most slices), the degree of emphysema was almost exclusively 3-4. The type of emphysema was distributed as centrilobular emphysema predominant in 43.5%, paraseptal emphysema predominant in 43.5%, and as an equal mixture of these types in 13%. The presence of emphysema did not differ between the group of smokers with lower normal values of lung function and the rest of the smokers. Smokers with emphysema had significantly lower BMI than those devoid of emphysema, 24 and 27 respectively (p<0.0011). CONCLUSION: There was a high occurrence of visual emphysema in middle-aged smokers with normal lung function. The densitometric quantitative analysis method is inadequate for detecting mild emphysema. High prevalence of emphysema was associated with low BMI.

Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD.

Inhaled corticosteroids (ICSs) treatment combined with long-acting ß2-adrenoceptor agonists (LABAs) reduces the risk of exacerbations in COPD, but the use of ICSs is associated with increased incidence of pneumonia. There are indications that this association is stronger for fluticasone propionate than for budesonide. We have examined systematic reviews assessing the risk of pneumonia associated with fluticasone propionate and budesonide COPD therapy. Compared with placebo or LABAs, we found that fluticasone propionate was associated with 43%-78% increased risk of pneumonia, while only slightly increased risk or no risk was found for budesonide. We have evaluated conceivable mechanisms which may explain this difference and suggest that the higher pneumonia risk with fluticasone propionate treatment is caused by greater and more protracted immunosuppressive effects locally in the airways/lungs. These effects are due to the much slower dissolution of fluticasone propionate particles in airway luminal fluid, resulting in a slower uptake into the airway tissue and a much longer presence of fluticasone propionate in airway epithelial lining fluid.

Need of education for dry powder inhaler storage and retention - a patient-reported survey.

BACKGROUND: Dry powder inhalers (DPIs) are the most commonly used devices in asthma treatment in the Nordic countries. As new DPIs become available, patients are likely to be exposed to more than one type of device, with variable optimal handling. The aim was to examine real life storage and retention of multidose DPIs in patients with asthma. METHODS: This patient-reported survey on real life storage and retention of DPIs included asthma patients using multidose DPIs. Basic patient characteristics, information on inhaler use and storage, check of expiry date, and concurrent inhaler use was examined using an on line questionnaire. RESULTS: A total of 738 patients were included with a median age of 41 years, out of which 83 % were women. Sixty-three per cent reported storage conditions pre-defined as risk locations for their maintenance inhaler and 38 % of the responding patients had more than one maintenance inhaler in use at the same time. Two thirds of the study population checked inhaler expiry date less than monthly or not at all. Use after expiry date was frequently reported. Two thirds of the patients had not received information on DPI storage, either from their doctor and/or nurse or at the pharmacy. CONCLUSIONS: This patient reported survey indicates that two thirds of the patients store their inhaler devices in suboptimal conditions, and only a minority had received instruction regarding inhaler handling. Non awareness of inhalers' expiry dates and use of more than one maintenance inhaler simultaneously was common. As inhaler mishandling may impact device functionality, improved communication and patient education is needed.

Difference in resistance to humidity between commonly used dry powder inhalers: an in vitro study.

Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at -0 °C. Delivered dose (DD) and fine-particle dose (FPD) were tested in vitro before and after storage. BUD inhalers: Turbuhaler and Novolizer showed only small decreases (<15%) in FPD in 40 °C/75% RH, whereas FPD for Easyhaler decreased by >60% (P=0.01) after 1.5 months of storage. Easyhaler also decreased significantly after 6 months of storage in ambient/75%RH by 25% and 54% for DD and FPD, respectively, whereas only small decreases were seen for Turbuhaler and Novolizer (<15%). BUD/FORM inhalers: Turbuhaler and Spiromax DD were unchanged in 40 °C/75% RH, whereas Easyhaler showed a small decrease. FPD (budesonide) decreased for Turbuhaler, Spiromax and Easyhaler by 18%, 10% and 68% (all significant), respectively, at 40 °C/75% RH. In ambient/75%RH, DD was unchanged for all inhalers, whereas FPD (budesonide) decreased for Spiromax (7%, P=0.02) and Easyhaler (34%, (P<0.01)). There are significant differences in device performance after exposure to humid conditions. A clinically relevant decrease of more than half FPD was seen for one of the inhalers, a decrease that may affect patients' clinical outcomes. Prescriber and patient knowledge on device attributes are essential to ensure optimal drug delivery to the lungs.

Early detection of COPD in primary care: screening by invitation of smokers aged 40 to 55 years.

BACKGROUND: The incidence of chronic obstructive pulmonary disease (COPD) is increasing in developed countries, as is the mortality rate. The main cause of COPD is smoking, and COPD is usually diagnosed at a late stage. AIM: To evaluate a method to detect COPD at an early stage in smokers in a young age group (40-55 years). DESIGN OF STUDY: Prospective descriptive study. SETTING: The city of Motala (45,000 inhabitants) and its surrounding rural areas (43,000 inhabitants) in south-east Sweden. Nineteen thousand, seven hundred and fifty subjects were between 40 and 55 years of age. According to Swedish statistics, approximately 27% of this population are smokers. METHOD: Smokers aged between 40 and 55 years were invited to have free spirometry testing in primary healthcare centres. Placards were placed in pharmacies and health centres and advertising was carried out locally twice a year. RESULTS: A total of 512 smokers responded. The prevalence of COPD was 27% (n = 141). The COPD was classified as mild obstruction in 85% (n = 120), moderate in 13% (n = 18) and severe in 2% (n = 3) according to the European Respiratory Society classification. Knowledge of the disease COPD was acknowledged by 39% of the responders to the questionnaire. Logistic regression analysis showed that age, male sex, number of pack years, dyspnoea and symptoms of chronic bronchitis significantly increased the odds of having COPD. The adjusted odds ratio was significant for having > 30 pack years. CONCLUSIONS: This method of inviting relatively young smokers selected a population of smokers with a high incidence of COPD, and may be one way of identifying smokers with COPD in the early stages.

Patient-reported adherence to coprescribed proton pump inhibitor gastroprotection in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis patients using nonsteroidal anti-inflammatory drugs.

BACKGROUND: Patients with osteoarthritis (OA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) are commonly treated with nonsteroidal anti-inflammatory drugs (NSAIDs), sometimes with a concomitant gastroprotective proton pump inhibitor (PPI). The present study examines real-life patient adherence to PPIs when coprescribed with NSAIDs. METHODS: This retrospective medical record survey identified patients diagnosed with OA, RA, or AS who had PPIs coprescribed with NSAIDs for prevention of NSAID-associated gastrointestinal ulcers. Actual NSAID and PPI intake was retrospectively recorded using a self-reported questionnaire. Adherence to PPI treatment was assessed using descriptive statistics. RESULTS: In total, 96 patients (69% female, mean age 67 years, 72% OA, 16% RA, 12% AS) were included. The mean patient-reported adherence to coprescribed PPIs was 73%-81%. The percentage of patients with a self-reported adherence of ≤80% was 26%. No predictive factors for low adherence could be identified. CONCLUSION: Despite doctors' instructions to use PPIs concomitantly with NSAIDs, the mean patient-reported adherence to coprescribed PPIs in this population indicates a risk of a "gastroprotective treatment gap". The patients' adherence to gastroprotective PPIs for the prevention of NSAID-associated upper gastrointestinal ulcers can be improved.

Improvement in COPD management by access to asthma/COPD clinics in primary care: data from the observational PATHOS study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) guidelines emphasize the importance of patient education to improve quality of life and avoid exacerbations. Longitudinal evaluations of structured management of COPD in primary care are lacking. AIM: To evaluate the impact of primary care asthma/COPD clinics on exacerbations, hospitalizations, and associated costs in COPD. METHODS: This population-based, retrospective, observational study, linking primary care medical records data to mandatory Swedish national registries, included patients with COPD from 76 primary healthcare centers (1999-2009). A questionnaire on access to an asthma/COPD clinic was retrospectively answered. Propensity score matching was performed at index (COPD diagnosis) by center type (with and without an asthma/COPD clinic). Poisson regression was used to compare the yearly rate of exacerbations (hospitalization, emergency visits, or prescription for oral steroids or antibiotics) and COPD-related prescriptions at the centers. An economic analysis was performed from the Swedish healthcare perspective using 2011 unit costs and the incremental cost-effectiveness ratio was calculated. RESULTS: The study included 21,361 patients (mean age, 68.0 years; 53% female). Access to asthma/COPD clinics increased from 34% to 85% during the study period. Patients at primary healthcare centers with asthma/COPD clinics had 27% fewer exacerbations (0.71 vs. 0.98) and 37% fewer hospitalizations annually (0.36 vs. 0.58) (p < 0.0001). Asthma/COPD clinics reduced the annual cost of medication and healthcare contacts by 37% (SEK 52,892 [€5858] to SEK 33,410 [€3700] per patient). CONCLUSIONS: Patients at primary healthcare centers with asthma/COPD clinics experienced fewer COPD exacerbations and hospitalizations, and overall treatment costs were substantially reduced. ClinicalTrials.gov identifier: NCT01146392.

Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting ß2 agonist: observational matched cohort study (PATHOS).

OBJECTIVE: To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting ß2 agonist. DESIGN: Observational retrospective pairwise cohort study matched (1:1) for propensity score. SETTING: Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009. PARTICIPANTS: Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol. MAIN OUTCOME MEASURES: Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality. RESULTS: 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each. In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19,170 patient years of follow up. Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively. The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6). The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003). All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59). CONCLUSIONS: There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting ß2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD. TRIAL REGISTRATION: Clinical Trials.gov NCT01146392.

The impact of repeated spirometry and smoking cessation advice on smokers with mild COPD.

BACKGROUND: Smoking cessation is the most important therapeutic intervention in patients with chronic obstructive pulmonary diseases (COPD) and the health benefits are immediate and substantial. Major efforts have been made to develop methods with high smoking cessation rates. OBJECTIVES: To study whether a combination of spirometry and brief smoking cessation advice to smokers with COPD, annually for three years, increased their smoking cessation rate in comparison with groups of smokers with normal lung function. METHOD: Prospective, randomized study in primary care. Smoking cessation rates were compared between smokers with COPD followed-up yearly over a period of three years and smokers with normal lung function followed-up yearly for three years or followed-up only once after three years. RESULTS: The point-prevalence abstinence rate and prolonged abstinence rate at 6 and 12 months increased yearly and in smokers with COPD at year 3 was 29%, 28%, and 25%, respectively. The abstinence rates were significantly higher in smokers with COPD than in smokers with normal lung function. Smoking cessation rates among smokers with normal lung function did not increase with increasing number of follow-ups. CONCLUSION: Smokers diagnosed with COPD stopped smoking significantly more often than those with normal lung function.