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Understanding normal lung development and aging in health and disease, both in men and in women, is essential to interpreting any therapeutic intervention. We aimed to describe lung function changes in healthy never-smoking males and females, from adolescence to old age, and to determine the effects of smoking and those derived from quitting. Prospective cohort study within all participants of the Framingham Offspring cohort who had two or more valid spirometry measurements during follow-up (n = 4,391; age range at baseline 13 to 71 yr), with a median follow-up time of 23 years. To best fit the curves describing FEV(1) changes with age to raw data, we used a generalized additive model with smooth terms and incorporating the subject-specific (longitudinal) random effects. We found that: (1) healthy never-smoker females achieve full lung growth earlier than males, and their rate of decline with age was slightly, but not significantly, lower; (2) smoking increases the rate of lung function decline, both in males and in females; (3) there is a range of susceptibility to the effects of smoking. The presence of respiratory symptoms at baseline and/or a respiratory diagnosis during follow-up appears to identify a group of susceptible smokers; and (4) quitting smoking has a beneficial effect at any age, but it is more pronounced in earlier quitters. Lung function changes from adolescence to old age differ in males and females, smoking has similar deleterious effects in both sexes, and quitting earlier is better.

Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide, and accurate estimates of the prevalence of this disease are needed to anticipate the future burden of COPD, target key risk factors, and plan for providing COPD-related health services. We aimed to measure the prevalence of COPD and its risk factors and investigate variation across countries by age, sex, and smoking status. Participants from 12 sites (n=9425) completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. COPD prevalence estimates based on the Global Initiative for Chronic Obstructive Lung Disease staging criteria were adjusted for the target population. Logistic regression was used to estimate adjusted odds ratios (ORs) for COPD associated with 10-year age increments and 10-pack-year (defined as the number of cigarettes smoked per day divided by 20 and multiplied by the number of years that the participant smoked) increments. Meta-analyses provided pooled estimates for these risk factors. The prevalence of stage II or higher COPD was 10·1% (SE 4·8) overall, 11·8% (7·9) for men, and 8·5% (5·8) for women. The ORs for 10-year age increments were much the same across sites and for women and men. The overall pooled estimate was 1·94 (95% CI 1·80–2·10) per 10-year increment. Site-specific pack-year ORs varied significantly in women (pooled OR=1·28, 95% CI 1·15–1·42, p=0·012), but not in men (1·16, 1·12–1·21, p=0·743). This worldwide study showed higher levels and more advanced staging of spirometrically confirmed COPD than have typically been reported. However, although age and smoking are strong contributors to COPD, they do not fully explain variations in disease prevalence—other factors also seem to be important. Although smoking cessation is becoming an increasingly urgent objective for an ageing worldwide population, a better understanding of other factors that contribute to COPD is crucial to assist local public-health officials in developing the best possible primary and secondary prevention policies for their regions.

Background: The Global Initiative on Obstructive Lung Disease stages for chronic obstructive pulmonary disease (COPD) uses a fixed ratio of the post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of 0.70 as a threshold. Since the FEV1/FVC ratio declines with age, using the fixed ratio to define COPD may “overdiagnose” COPD in older populations. Objective: To determine morbidity and mortality among older adults whose FEV1/FVC is less than 0.70 but more than the lower limit of normal (LLN). Methods: The severity of COPD was classified in 4965 participants aged ⩾65 years in the Cardiovascular Health Study using these two methods and the age-adjusted proportion of the population who had died or had a COPD-related hospitalisation in up to 11 years of follow-up was determined. Results: 1621 (32.6%) subjects died and 935 (18.8%) had at least one COPD-related hospitalisation during the follow-up period. Subjects (n = 1134) whose FEV1/FVC fell between the LLN and the fixed ratio had an increased adjusted risk of death (hazard ratio (HR) 1.3, 95% CI 1.1 to 1.5) and COPD-related hospitalisation (HR 2.6, 95% CI 2.0 to 3.3) during follow-up compared with asymptomatic individuals with normal lung function. Conclusion: In this cohort, subjects classified as “normal” using the LLN but abnormal using the fixed ratio were more likely to die and to have a COPD-related hospitalisation during follow-up. This suggests that a fixed FEV1/FVC ratio of <0.70 may identify at-risk patients, even among older adults.

Chronic obstructive pulmonary disease (COPD) continues to be an important cause of morbidity, mortality, and health-care costs worldwide. It is a global health issue, with cigarette smoking being an important risk factor universally; other factors, such as exposure to indoor and outdoor air pollution, occupational hazards, and infections, are also important. As the global population ages, the burden of COPD will increase in years to come. Prevalence estimates of the disorder show considerable variability across populations, suggesting that risk factors can affect populations differently. Other advances in our understanding of COPD are increased recognition of the importance of comorbid disease, identification of different COPD phenotypes, and understanding how factors other than lung function affect outcome in our patients. The challenge we will all face in the next few years will be implementation of cost-effective prevention and management strategies to stem the tide of this disease and its cost.

Background Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide. The burden of disease is known to be high, though less is known about those of a younger age. The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort. Methods A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey. Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning. The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale. Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure. Results 64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition. Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41]. The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500]. For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m]. As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54. This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60]. Conclusions Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people. Further efforts to improve COPD diagnosis and management are required.

Abstract Rationale Poor adherence to asthma controller medications results in poor treatment outcomes. Objectives To compare controller medication adherence and clinical outcomes in 612 adults with poorly controlled asthma randomized to one of two different treatment decision-making models or to usual care. Methods In shared decision making (SDM), nonphysician clinicians and patients negotiated a treatment regimen that accommodated patient goals and preferences. In clinician decision making, treatment was prescribed without specifically eliciting patient goals/preferences. The otherwise identical intervention protocols both provided asthma education and involved two in-person and three brief phone encounters. Measurements and Main Results Refill adherence was measured using continuous medication acquisition (CMA) indices—the total days' supply acquired per year divided by 365 days. Cumulative controller medication dose was measured in beclomethasone canister equivalents. In follow-up Year 1, compared with usual care, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.46; P < 0.0001) and long-acting β-agonist adherence (CMA, 0.51 vs. 0.40; P = 0.0225); higher cumulative controller medication dose (canister equivalent, 10.9 vs. 5.2; P < 0.0001); significantly better clinical outcomes (asthma-related quality of life, health care use, rescue medication use, asthma control, and lung function). In Year 2, compared with usual care, SDM resulted in significantly lower rescue medication use, the sole clinical outcome available for that year. Compared with clinician decision making, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.59; P = 0.03) and long-acting β-agonist adherence (CMA, 0.51 vs. 0.41; P = 0.0143); higher cumulative controller dose (CMA, 10.9 vs. 9.1; P = 0.005); and quantitatively, but not significantly, better outcomes on all clinical measures. Conclusions Negotiating patients' treatment decisions significantly improves adherence to asthma pharmacotherapy and clinical outcomes. Clinical trials registered with www.clinicaltrials.gov (NCT00217945 and NCT00149526).

Evidence supporting the association of COPD or airflow obstruction with use of solid fuels is conflicting and inconsistent. To assess the association of airflow obstruction with self-reported use of solid fuels for cooking or heating. We analysed 18,554 adults from the BOLD study, who had provided acceptable post-bronchodilator spirometry measurements and information on use of solid fuels. The association of airflow obstruction with use of solid fuels for cooking or heating was assessed by sex, within each site, using regression analysis. Estimates were stratified by national income and meta-analysed. We carried out similar analyses for spirometric restriction, chronic cough and chronic phlegm. We found no association between airflow obstruction and use of solid fuels for cooking or heating (ORmen=1.20, 95%CI 0.94-1.53; ORwomen=0.88, 95%CI 0.67-1.15). This was true for low/middle and high income sites. Among never smokers there was also no evidence of an association of airflow obstruction with use of solid fuels (ORmen=1.00, 95%CI 0.57-1.76; ORwomen=1.00, 95%CI 0.76-1.32). Overall, we found no association of spirometric restriction, chronic cough or chronic phlegm with the use of solid fuels. However, we found that chronic phlegm was more likely to be reported among female never smokers and those who had been exposed for ≥20 years. Airflow obstruction assessed from post-bronchodilator spirometry was not associated with use of solid fuels for cooking or heating.

In the original 32-item Asthma Quality of Life Questionnaire (AQLQ), five activity questions are selected by patients themselves. However, for long-term studies and large clinical trials, generic activities may be more appropriate. For the standardized version of the AQLQ, the AQLQ(S), we formulated five generic activities (strenuous exercise, moderate exercise, work-related activities, social activities, and sleep) to replace the five patient-specific activities in the AQLQ. In a 9-week observational study, we compared the AQLQ with the AQLQ(S) and examined their measurement properties. Forty symptomatic adult asthma patients completed the AQLQ(S), the AQLQ, the Medical Outcomes Survey Short Form 36, the Asthma Control Questionnaire, and spirometry at baseline, 1, 5, and 9 weeks. Activity domain scores (mean ± SD) were lower with the AQLQ (5.7 ± 0.9) than with the AQLQ(S) (5.9 ± 0.8; p = 0.0003) and correlation between the two was moderate (r = 0.77). However, for overall scores, there was minimal difference (AQLQ, 5.4 ± 0.8; AQLQ(S), 5.5 ± 0.8; r = 0.99). Reliability (AQLQ intraclass correlation coefficient, 0.95; AQLQ(S) intraclass correlation coefficient, 0.96) and responsiveness (AQLQ, p < 0.0001; AQLQ(S), p < 0.0001) were similar for the two instruments. Construct validity (correlation with other measures of health status and clinical asthma) was also similar for the two instruments. The AQLQ(S) has strong measurement properties and is valid for measuring health-related quality of life in asthma. The choice of instrument should depend on the task at hand.

Background Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. Methods Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF 25-75 ) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV 3 /FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV 1 /FVC ≥ LLN). Results Almost a fifth of the participants had spirometric SAO (19% for FEF 25-75 ; 17% for FEV 3 /FVC). Using FEF 25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV 3 /FVC. Isolated spirometric SAO (10% for FEF 25-75 ; 6% for FEV 3 /FVC), was also associated with respiratory symptoms and cardiovascular disease. Conclusion Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF 25-75 and FEV 3 /FVC, in addition to traditional spirometry parameters.

RationaleCriteria 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.Methods10 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.ResultsIn 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.ConclusionsThe results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing.