Bernd Lamprecht

COPD in Never Smokers: Results From the Population-Based Burden of Obstructive Lung Disease Study

Background: Never smokers comprise a substantial proportion of patients with COPD. Their characteristics and possible risk factors in this population are not yet well defined. Methods: We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study. Participants were aged ≥ 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines. In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio. Results: Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD. Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD. This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio. Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations. Conclusion: This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD. Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers.

Determinants of Underdiagnosis of COPD in National and International Surveys.

BACKGROUND COPD ranks within the top three causes of mortality in the global burden of disease, yet it remains largely underdiagnosed. We assessed the underdiagnosis of COPD and its determinants in national and international surveys of general populations. METHODS We analyzed representative samples of adults aged ≥ 40 years randomly selected from well-defined administrative areas worldwide (44 sites from 27 countries). Postbronchodilator FEV1/FVC < lower limit of normal (LLN) was used to define chronic airflow limitation consistent with COPD. Undiagnosed COPD was considered when participants had postbronchodilator FEV1/FVC < LLN but were not given a diagnosis of COPD. RESULTS Among 30,874 participants with a mean age of 56 years, 55.8% were women, and 22.9% were current smokers. Population prevalence of (spirometrically defined) COPD ranged from 3.6% in Barranquilla, Colombia, to 19.0% in Cape Town, South Africa. Only 26.4% reported a previous lung function test, and only 5.0% reported a previous diagnosis of COPD, whereas 9.7% had a postbronchodilator FEV1/FVC < LLN. Overall, 81.4% of (spirometrically defined) COPD cases were undiagnosed, with the highest rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, Kentucky (50.0%). In multivariate analysis, a greater probability of underdiagnosis of COPD was associated with male sex, younger age, never and current smoking, lower education, no previous spirometry, and less severe airflow limitation. CONCLUSIONS Even with substantial heterogeneity in COPD prevalence, COPD underdiagnosis is universally high. Because effective management strategies are available for COPD, spirometry can help in the diagnosis of COPD at a stage when treatment will lead to better outcomes and improved quality of life.

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2007 and 2011 staging systems: a pooled analysis of individual patient data

BACKGROUND There is no universal consensus on the best staging system for chronic obstructive pulmonary disease (COPD). Although documents (eg, the Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2007) have traditionally used forced expiratory volume in 1 s (FEV1) for staging, clinical parameters have been added to some guidelines (eg, GOLD 2011) to improve patient management. As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aimed to investigate how individual patients were categorised by GOLD 2007 and 2011, and compare the prognostic accuracy of the staging documents for mortality. METHODS We searched reports published from Jan 1, 2008, to Dec 31, 2014. Using data from cohorts that agreed to participate and had a minimum amount of information needed for GOLD 2007 and 2011, we did a patient-based pooled analysis of existing data. With use of raw data, we recalculated all participant assignments to GOLD 2007 I-IV classes, and GOLD 2011 A-D stages. We used survival analysis, C statistics, and non-parametric regression to model time-to-death data and compare GOLD 2007 and GOLD 2011 staging systems to predict mortality. FINDINGS We collected individual data for 15 632 patients from 22 COPD cohorts from seven countries, totalling 70 184 person-years. Mean age of the patients was 63·9 years (SD 10·1); 10 751 (69%) were men. Based on FEV1 alone (GOLD 2007), 2424 (16%) patients had mild (I), 7142 (46%) moderate (II), 4346 (28%) severe (III), and 1670 (11%) very severe (IV) disease. We compared staging with the GOLD 2007 document with that of the new GOLD 2011 system in 14 660 patients: 5548 (38%) were grade A, 2733 (19%) were grade B, 1835 (13%) were grade C, and 4544 (31%) were grade D. GOLD 2011 shifted the overall COPD severity distribution to more severe categories. There were nearly three times more COPD patients in stage D than in former stage IV (p<0·05). The predictive capacity for survival up to 10 years was significant for both systems (p<0·01) but area under the curves were only 0·623 (GOLD 2007) and 0·634 (GOLD 2011), and GOLD 2007 and 2011 did not differ significantly. We identified the percent predicted FEV1 thresholds of 85%, 55% and 35% as better to stage COPD severity for mortality, which are similar to the ones used previously. INTERPRETATION Neither GOLD COPD classification schemes have sufficient discriminatory power to be used clinically for risk classification at the individual level to predict total mortality for 3 years of follow-up and onwards. Increasing intensity of treatment of patients with COPD due to their GOLD 2011 reclassification is not known to improve health outcomes. Evidence-based thresholds should be searched when exploring the prognostic ability of current and new COPD multicomponent indices. FUNDING None.

Predictors of dyspnoea prevalence: results from the BOLD study

Dyspnoea is a cardinal symptom for cardiorespiratory diseases. No study has assessed worldwide variation in dyspnoea prevalence or predictors of dyspnoea. We used cross-sectional data from population-based samples in 15 countries of the Burden of Obstructive Lung Disease (BOLD) study to estimate prevalence of dyspnoea in the full sample, as well as in an a priori defined low-risk group (few risk factors or dyspnoea-associated diseases). Dyspnoea was defined by the modified Medical Research Council questions. We used ordered logistic regression analysis to study the association of dyspnoea with site, sex, age, education, smoking habits, low/high body mass index, self-reported disease and spirometry results. Of the 9484 participants, 27% reported any dyspnoea. In the low-risk subsample (n=4329), 16% reported some dyspnoea. In multivariate analyses, all covariates were correlated to dyspnoea, but only 13% of dyspnoea variation was explained. Females reported more dyspnoea than males (odds ratio ∼2.1). When forced vital capacity fell below 60% of predicted, dyspnoea was much more likely. There was considerable geographical variation in dyspnoea, even when we adjusted for known risk factors and spirometry results. We were only able to explain 13% of dyspnoea variation. Known predictors and risk factors can only explain 13% of dyspnoea variation http://ow.ly/tHS0H

Using Targeted Spirometry to Reduce Non-Diagnosed Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is increasing worldwide and thus its associated morbidity and mortality. However, COPD often goes undiagnosed. Objectives: We evaluated the rate of non-diagnosed irreversible airway obstruction (AO) and characterized this patient group. We further assessed the possible effects of conducting targeted spirometry in a population sample in Salzburg, Austria, as part of the Burden of Obstructive Lung Disease (BOLD) study. Methods: 1,258 adults ≧40 years of age completed a questionnaire and performed spirometry before and after bronchodilator therapy (post-BD). Irreversible AO was defined as post-BD FEV1/FVC below the lower limit of normal; we used the FEV1% predicted (pred.) to further grade the disease. Participants without a physician diagnosis of COPD who reported respiratory symptoms and a history of risk factors (ever smoking or occupational risk) were defined as eligible for targeted spirometry. Results: 85.9% (171/199) of the participants with irreversible AO did not report a prior diagnosis of COPD. Non-diagnosed AO was inversely related to severity, age, self-reported prior respiratory diseases and cough as a respiratory symptom. 343 participants were eligible for targeted spirometry and irreversible AO was present in 86 (25.1%) participants. Therefore, targeted spirometry could reduce the underdiagnosis of irreversible AO of any severity by 50.3% (86 of 171). The diagnosis of 1 person with FEV1 <80% pred. would require spirometry in 8.4 subjects (95% confidence interval 6.2–11.1). Conclusion: Although several factors are associated with non-diagnosed AO, spirometry in individuals with respiratory symptoms and exposure to risk factors could reduce undiagnosed irreversible AO by half.

Subjects with Discordant Airways Obstruction: Lost between Spirometric Definitions of COPD

Background. Since the FEV1/FVC ratio declines with age, using the fixed ratio of 0.70 leads to overdiagnosis of COPD in older populations and underdiagnosis among young adults. Objective. To evaluate whether discordant obstructive cases (FEV1/FVC < 0.70 but ≥LLN) are a healthy population or have clinical features that would place them at increased risk. Methods. We used post-bronchodilator spirometry data from the population-based Austrian Burden of Obstructive Lung Disease (BOLD) study. Those with post-bronchodilator FEV1/FVC ratio <LLN and <0.70 were defined as concordant obstructive cases. Participants with post-bronchodilator FEV1/FVC ratio ≥LLN but <0.70 were defined as discordant obstructive cases. Results. Discordant obstructive cases were more likely to be older, male and never-smokers. Additionally they had less respiratory symptoms and less severe impairment of FEV1. However, discordant obstructive cases reported significantly more often a diagnosis of heart disease than subjects with normal lung function (27.2% vs 7.3%, P = .015). Conclusion. The clinical profile of discordant obstructive cases includes potentially important comorbid disease.

Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study

Rationale Criteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns. Methods 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airflow obstruction. Results In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (ΔFEV1); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV1i); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV1p). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVCi); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVCp). The proportion who exceeded the above threshold values in the subgroup with spirometrically defined Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV1/FVC <0.7 and FEV1% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV1-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds. Conclusions The results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing.

Die Prävalenz der COPD in Österreich – die erwartete Entwicklung bis 2020

SummaryBACKGROUND: In 2020 Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death world-wide causing considerable health costs. Epidemiological data to estimate the future development of COPD in Austria were not available so far. METHODS: In the context of the international Burden of Obstructive Lung Disease (BOLD) study, a random sample of the population of Salzburg was surveyed to determine the prevalence of COPD. The definition of COPD followed the GOLD classification. A prior physicians diagnosis of COPD, emphysema or chronic bronchitis was evaluated by questionnaire. The age- and sex- specific prevalence of COPD was extrapolated using demographic data of the Austrian population for the years 2005, 2010, 2015 and 2020. Undiagnosed COPD was considered present, whenever irreversible airways obstruction was measured (FEV1/FVC < 0.7), but a doctors diagnosis of COPD, emphysema or chronic bronchitis has not been made. RESULTS: For 2005 1.047.150 Austrians aged 40 years and older were estimated in GOLD stage I–IV. 431.080 persons over 40 years were affected by COPD in GOLD stage II–IV needing therapy. The percentage of undiagnosed COPD was 88,5%. For the years 2010, 2015 and 2020 GOLD stage I–IV COPD was projected to rise by 7,8%, 16.1% and 24%, respectively. CONCLUSION: Measures to prevent COPD are absolutely necessary to forestall the projected burden of this disease in Austria.ZusammenfassungHINTERGRUND: Im Jahr 2020 wird COPD weltweit die dritthäufigste Todesursache sein, und beträchtliche Gesundheitskosten verursachen. Epidemiologische Daten zur künftigen Entwicklung der COPD Prävalenz in Österreich waren bislang nicht verfügbar. METHODEN: Im Rahmen der internationalen Burden of Obstructive Lung Disease (BOLD) Studie wurde für eine Zufallsstichprobe der Salzburger Bevölkerung die Prävalenz der COPD bestimmt. Die Definition der COPD folgte dabei der GOLD Klassifikation. Mittels Fragebogen wurde zudem erhoben, ob jemals zuvor die ärztliche Diagnose COPD, Lungenemphysem oder chronische Bronchitis gestellt worden war. Die alters- und geschlechtsspezifische Prävalenz der COPD wurde auf die Demographie der österreichischen Bevölkerung für die Jahre 2005, 2010, 2015 und 2020 hochgerechnet. Als Dunkelziffer wurde jener Anteil bestimmt, bei dem in der Spirometrie eine irreversible Obstruktion vorlag, jedoch keine der drei ärztlichen Diagnosen (COPD, Lungenemphysem, chronische Bronchitis) bekannt war. ERGEBNISSE: 1.047.150 Österreicher über vierzig Jahre waren unter Verwendung der österreichischen BOLD Daten im Jahr 2005 von COPD im Stadium I–IV betroffen. 431.080 Personen über 40 Jahre waren von COPD im therapiebedürftigen Stadium II–IV betroffen. Die Dunkelziffer für das Jahr 2005 wurde mit 88,5% berechnet. Für die Jahre 2010, 2015 und 2020 ist mit einem Anstieg der an COPD im Stadium I–IV Erkrankten von 7,8%, 16,1% und 24% zu rechnen. KONKLUSION: Maßnahmen zur Prävention sind dringend erforderlich, um die erwartete Epidemie der COPD Erkrankungen in Österreich zu verhindern.

Sex-related differences in respiratory symptoms : results from the BOLD Study

For the same degree of lung function impairment females tend to report more (severe) dyspnoea and cough, but less phlegm http://ow.ly/mp2CF

Detection of Chronic Obstructive Pulmonary Disease in Primary Care in Salzburg, Austria: Findings from the Real World

Background: Chronic obstructive pulmonary disease (COPD) is a major public health burden and profoundly affects individuals suffering from the disease. However, the majority of subjects with COPD are still undiagnosed. Objectives: To evaluate COPD prevalence and detection strategies for COPD in the primary-care setting. Methods: The study was conducted in a random sample of general practitioner (GP) offices in Salzburg (Austria). A questionnaire and post-bronchodilator (PBD) spirometry was administered to patients aged ≥40 years. Nonreversible airway obstruction was considered when PBD FEV1/FVC was <0.70. Severity of spirometrically defined COPD was graded according to the GOLD recommendations. Results: 60 GP offices were randomly selected for study participation, however only 30 (50.0%) were willing to participate. 1,230 of 9,820 (12.52%) patients consented to the protocol. Quality of PBD spirometry was evaluated, and 882 (71.7%) met ATS/ERS quality criteria. 7.5% (95% CI: 5.7-9.4%) of the patients had COPD grade II+ (FEV1/FVC <0.7 and FEV1 <80% of predicted), but only 22.4% of them reported a prior physicians diagnosis of COPD. Similar results were seen for the 2005 Salzburg BOLD (Burden of Obstructive Lung Disease) sample with regard to COPD GOLD II+ prevalence (10.7%) and proportion of underdiagnosis (82.3%). Conclusion: COPD in the primary-care setting is as prevalent and underdiagnosed as reported recently for the BOLD study. The surprisingly low participation rate of GPs and patients indicates that prevention of COPD is not a health priority, and that awareness for COPD has to heightened before case-finding strategies will be successful.