Karin Lisspers

Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β 2 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 β2 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 β2 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.

How often is diagnosis of COPD confirmed with spirometry

BACKGROUND Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. Diagnosis is customarily confirmed with spirometry, but there are few studies on documented spirometry use in everyday clinical practice. METHODS In a cross-sectional survey and study of the medical records of primary and secondary care COPD patients aged 18-75 in a Swedish region, patients with COPD were randomly selected from the registers of 56 primary care centres and 14 hospital outpatient clinics. Spirometry data at diagnosis +/-6 months were analyzed. RESULTS From 1114 patients with COPD, 533 with a new diagnosis of COPD during the four-year study period were identified. In 59% (n=316), spirometry data in connection with diagnosis were found in the medical records. Spirometry data with post-bronchodilator forced expiratory volume in 1s (FEV(1))/ vital capacity (VC) ratios were available in 45% (n=241). FEV1/VC ratio <0.70 were found in 160 patients, which corresponds to 30% of the patients with a new diagnosis. Lower age, female gender, current smoking, higher body mass index (BMI) and shorter forced exhalation time were related to COPD diagnosis despite an FEV(1)/VC ratio of >/=0.70. The most common problem in the quality assessment was an insufficient exhalation time. CONCLUSIONS Only a third of Swedish patients with COPD had their diagnosis confirmed with spirometry. Our data indicate that female gender, current smoking, higher BMI and short exhalation time increase the risk of being diagnosed with COPD without fulfilling the spirometric criteria for the disease.

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 β2-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.

The Dyspnoea, Obstruction, Smoking, Exacerbation (DOSE) index is predictive of mortality in COPD

BACKGROUND The Dyspnoea, Obstruction, Smoking, Exacerbation (DOSE) index was designed to assess disease severity and for the clinical management of chronic obstructive pulmonary disease (COPD), but has not been evaluated as a prognostic instrument for mortality in a population including primary care patients. AIMS The aim of this study was to investigate the associations of the DOSE index with mortality in primary and secondary care COPD patients. METHODS Information was collected from 1,111 COPD patients aged 34-75 years randomly selected from 70 Swedish primary and secondary care centres. Data were obtained using patient questionnaires and record review and the Swedish Board of Health and Welfare provided mortality data. The study population included 562 patients with data on all DOSE index components. The DOSE index was calculated using the MRC dyspnoea scale, forced expiratory volume in 1 second (FEV₁) as percentage of predicted (FEV₁%pred), smoking status, and exacerbation rate. The exacerbation rate over 6 months prior to record review was used to estimate the annual rate. Cox regression analyses estimated survival with adjustment for age, sex, and heart disease. RESULTS Over 5 years, 116 patients (20.6%) died. Mortality was higher in patients with DOSE index ≥4 (42.4%) than for lower scores (11.0%) (p<0.0001). Compared with a DOSE index score of 0-3, the hazard ratio for mortality was 3.48 (95% CI 2.32 to 5.22) for a score of 4-5, and was 8.00 (95% CI 4.67 to 13.7) for a score of 6-7. CONCLUSIONS The DOSE index is associated with mortality in COPD patients in primary and secondary care and can be used to assess prognosis in addition to other clinically relevant issues.

Primary Care COPD Patients Compared with Large Pharmaceutically-Sponsored COPD Studies : An UNLOCK Validation Study

Background Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS). There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care. Objective We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials. Methods Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS. In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria. Results Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01). There were large differences in GOLD stage distribution compared to primary care patients. Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant. Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year. The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT). Conclusion Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations. More research is needed to determine the effect of pharmacological treatment in mild to moderate patients. We encourage future guideline makers to involve primary care populations in their recommendations.

The International Primary Care Respiratory Group (IPCRG) Research Needs Statement 2010

AIM Respiratory diseases are a public health issue throughout the world, with high prevalence and morbidity. This Research Needs Statement from the International Primary Care Respiratory Group (IPCRG) aims to highlight unanswered questions on the management of respiratory diseases that are of importance to practising primary care clinicians. METHODS An informal but inclusive consultation process was instigated in 2009. Draft statements in asthma, rhinitis, COPD, tobacco dependence, and respiratory infections were circulated widely to IPCRG members, other recognised experts, and representatives from a range of economic and healthcare backgrounds. An iterative process was used to generate, prioritise and refine research questions in each section. RESULTS Two overarching themes emerged. Firstly, there is a real need for research to be undertaken within primary care, which recruits patients representative of primary care populations, evaluates interventions realistically delivered within primary care, and draws conclusions that will be meaningful to professionals working within primary care. Secondly, international and national guidelines exist, but there is little evidence on the best strategies for implementing recommendations. Disease-specific research questions focus on effective and cost-effective ways to prevent disease, confirm the diagnosis, assess control, manage treatment, and empower selfmanagement. Practical questions about how to deliver this comprehensive agenda in diverse primary care settings are highlighted. CONCLUSIONS We hope that this Research Needs Statement will be used by clinicians and patients campaigning for answers to relevant questions, by researchers seeking funding to provide answers to these questions, and by funding bodies to enable them to prioritise research agendas.

Combination of budesonide/formoterol more effective than fluticasone/salmeterol in preventing exacerbations in chronic obstructive pulmonary disease: the PATHOS study.

Combinations of inhaled corticosteroids (ICSs) and long‐acting β2‐agonists (LABAs) are recommended for patients with moderate and severe chronic obstructive pulmonary disease (COPD). However, it is not known whether different fixed combinations are equally effective. The aim of this study was to investigate exacerbation rates in primary care patients with COPD treated with budesonide/formoterol compared with fluticasone/salmeterol.

Asthma control in primary care in Sweden: a comparison between 2001 and 2005.

AIM To compare the degree of asthma control in 2001 and 2005 in a primary care setting in Sweden. METHOD Two similar questionnaire surveys were performed in 2001 and 2005 with 1,012 and 224 asthma patients aged 18-45 randomly selected from 42 and 56 primary health care centres, respectively. A classification of asthma control similar to the GINA guidelines was made using information obtained from the questionnaire. RESULTS In 2001, 36.6% had achieved asthma control, 23.8% were partly controlled and 39.6% uncontrolled. In 2005, the corresponding figures were 40.2%, 26.8% and 33.0%, respectively, with no difference between the two surveys (p=0.114). Uncontrolled asthma was more common in women (p<0.001 in the first and p<0.05 in the second survey) and smokers (p<0.01 in the first and p<0.01 in the second survey). The use of combination corticosteroid/long-acting bronchodilator inhalers had increased - 34.2% and 48.2%, respectively (p<0.001) - and many patients used their inhaled corticosteroids periodically. CONCLUSION In spite of treatment guidelines many patients in Swedish primary care still have insufficient asthma control.

Co-Morbidity, Body Mass Index and Quality of Life in COPD Using the Clinical COPD Questionnaire

Introduction: Quality of life is an important patient-oriented measure in COPD. The Clinical COPD Questionnaire (CCQ) is a validated instrument for estimating quality of life. The impact of different factors on the CCQ-score remains an understudied area. The aim of this study was to investigate the association of co-morbidity and body mass index with quality of life measured by CCQ. Methods: A patient questionnaire including the CCQ and a review of records were used. A total of 1548 COPD patients in central Sweden were randomly selected. Complete data were collected for 919 patients, 639 from primary health care and 280 from hospital clinics. Multiple linear regression with adjustment for sex, age, level of education, smoking habits and level of care was performed. Subanalyses included additional adjustment for lung function in the subgroup (n = 475) where spirometry data were available. Results: Higher mean CCQ score indicating lower quality of life was statistically significant and independently associated with heart disease (adjusted regression coefficient (95%CI) 0.26; 0.06 to 0.47), depression (0.50; 0.23 to 0.76) and underweight (0.58; 0.29 to 0.87). Depression and underweight were associated with higher scores in all CCQ subdomains. Further adjustment for lung function in the subgroup with this measure resulted in statistically significant and independent associations with CCQ for heart disease, depression, obesity and underweight. Conclusion: The CCQ identified that heart disease, depression and underweight are independently associated with lower health-related quality of life in COPD.

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.