A. Sonia Buist

International variation in the prevalence of COPD (The BOLD Study): a population-based prevalence study

BACKGROUND 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. METHODS 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. FINDINGS 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). INTERPRETATION 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.

Global burden of COPD: risk factors, prevalence, and future trends

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.

The use of β-agonists and the risk of death and near death from asthma

Abstract Background. Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of β2-agonist bronchodilators. Methods. Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case–control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. Results. The use of β-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence...

The natural history of chronic airflow obstruction revisited: an analysis of the Framingham offspring cohort

RATIONALE Understanding normal lung development and aging in health and disease, both in men and in women, is essential to interpreting any therapeutic intervention. OBJECTIVES 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. METHODS 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. MEASUREMENTS AND MAIN RESULTS 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. CONCLUSIONS 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.

Effects of randomized assignment to a smoking cessation intervention and changes in smoking habits on respiratory symptoms in smokers with early chronic obstructive pulmonary disease : The Lung Health Study

PURPOSE To evaluate the effects of randomly assigning smokers who have early chronic obstructive pulmonary disease (COPD) to a smoking-cessation intervention on the symptoms of chronic cough, chronic phlegm production, wheezing and shortness of breath, and to determine the effects of quitting smoking on these symptoms. SUBJECTS AND METHODS A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [defined as a forced expiratory volume in the first second (FEV1) of 55% to 90% of predicted and FEV1/forced vital capacity (FVC) <0.70] were enrolled in a 5-year clinical trial. Two-thirds of participants were randomly assigned to smoking-intervention groups and one-third to a usual-care group. The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum. One intervention group was treated with ipratropium bromide by inhaler; the other intervention group received placebo inhalers. The usual-care group was advised to stop smoking. All participants were followed annually. Smoking status was biochemically validated by salivary cotinine measurements or exhaled carbon monoxide values. RESULTS Validated 5-year sustained smoking cessation occurred in 22% of participants in the intervention compared with only 5% of participants in the usual-care group. At the end of the study, the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group (P <0.0001). For example, among participants who did not report cough at baseline, 15% of those in the intervention groups had cough at least 3 months during the year, compared with 23% of those in usual care. Sustained quitters had the lowest prevalence of all four symptoms, whereas continuous smokers had the greatest prevalence of these symptoms. Changes in symptoms occurred primarily in the first year after smoking cessation. Respiratory symptoms were associated with greater declines in FEV1 during the study (P <0.001). Ipratropium bromide had no long-term effects on respiratory symptoms. CONCLUSIONS In this prospective randomized trial using an intention-to-treat analysis, smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up.

Chronic Obstructive Pulmonary Disease in the Older Adult: What Defines Abnormal Lung Function?

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.

A pooled analysis of FEV1, decline in COPD patients randomized to inhaled corticosteroids or placebo

BACKGROUND There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). METHODS The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. RESULTS There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. CONCLUSIONS We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.

Case Definitions for Chronic Obstructive Pulmonary Disease

The objective of this study was to evaluate the definitions for classification of chronic obstructive pulmonary disease (COPD) recommended by the American Thoracic Society (ATS) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Using data from the U.S. population-based third National Health and Nutrition Examination Survey (NHANES III), we compared the number of individuals in the U.S. population who met definitions of airflow obstruction based on the fixed ratio of FEV1/FVC < 0.70 criterion and on the ATS lower 95% confidence limit (lower limits of normal LLN) criterion. Further, we evaluated the definitions in the context of physician-diagnosed obstructive airways diseases and respiratory symptoms. In comparison to the FEV1/FVC < LLN and FEV1 < 100% predicted definition, the fixed ratio-based definition for mild COPD underestimates airflow obstruction by 29% in 20–49-year-olds and overestimates it by 58% in 50–80-year-olds. In comparison to the FEV1/FVC < LLN and FEV1 < LLN definition, the fixed ratio-based definition for moderate COPD underestimates airflow obstruction by 31% in 20–49-year-olds and overestimates it by 37% in 50–80 year olds. Based on our estimation, approximately 0.9 million (26%) of symptomatic individuals out of the 3.6 million U.S. adults aged 20–49 years who have airflow obstruction (FEV1/FVC < LLN and FEV1 < LLN definition) may have undiagnosed respiratory disease. In conclusion, using the FEV1/FVC < 0.70 criterion will substantially under-diagnose airway obstruction in younger individuals and substantially over-diagnose COPD in older individuals.

Vitamin C Supplementation for Pregnant Smoking Women and Pulmonary Function in Their Newborn Infants: A Randomized Clinical Trial

IMPORTANCE Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00632476.

Efficacy of Bupropion for Relapse Prevention in Smokers With and Without a Past History of Major Depression

AbstractBACKGROUND: This study evaluated the efficacy of bupropion for relapse prevention in smokers with and without a past history of major depressive disorder. Changes in depressive symptoms were also examined. DESIGN: Data were gathered prospectively from a randomized, double-blind relapse prevention trial of bupropion conducted at five study sites. A total of 784 smokers (54% female, 97% white) were enrolled. Using the Structured Clinical Interview for Depression, 17% of the subjects reported a past history of major depressive disorder at baseline. All subjects received open-label bupropion SR (300 mg/d) for 7 weeks. Subjects abstinent from smoking at the end of 7 weeks (N=429) were randomized to bupropion SR (300 mg/d) or placebo for the remainder of the year and followed for 1 year off medication. The primary outcome measures were median time to relapse to smoking and the 7-day point-prevalence smoking abstinence rate. Self-reported abstinence from smoking was verified by expired air carbon monoxide. The Beck Depression Inventory was used to assess depressive symptoms at baseline and at weeks 8 and 12. RESULTS: Median time to relapse did not differ by past history of major depressive disorder. Bupropion was associated with higher point-prevalence smoking abstinence at the end of medication compared to placebo (P=.007), independent of a past history of major depressive disorder. Moreover, change in depressive symptoms during the double-blind phase did not differ for those with and without a past history of major depressive disorder. CONCLUSIONS: Extended use of bupropion for relapse prevention is effective for smokers with and without a history of major depression.