Restricted spirometry in the Burden of Lung Disease Study.

BACKGROUND: The presence of restrictive lung disease has classically required the measure of total lung capacity to document 'true' restriction, which has limited its detection in large population-based studies. METHODS: We used spirometric data to classify people with restricted spirometry (forced expiratory volume in 1 second [FEV(1)]/forced vital capacity ≥ 0.70 and FEV(1) < 80% predicted) in the Burden of Lung Disease (BOLD) Study and determined the relation between this finding and demographic factors and the presence of chronic diseases, including diabetes mellitus, hypertension and cardiovascular disease. RESULTS: Overall, we found that 11.7% of men (546/4664) and 16.4% of women (836/5098) had restricted spirometry. Prevalence varied widely by site, from a low of 4.2% among males in Sydney, Australia, to a high of 48.7% among females in Manila, The Philippines. Compared to people with normal lung function, those with restricted spirometry had a higher prevalence of diabetes (12.2% vs. 4.6%), heart disease (15.0% vs. 7.7%) and hypertension (38.8% vs. 22.8%). CONCLUSIONS: Restricted spirometry is a common finding in population studies. Additional research is needed to better define and describe the mechanisms that lead to restricted spirometry and potential interventions.

Occupational exposures and COPD: an ecological analysis of international data.

The occupational contribution to chronic obstructive pulmonary disease (COPD) has yet to be put in a global perspective. In the present study, an ecological approach to this question was used, analysing group-level data from 90 sex-specific strata from 45 sites of the Burden of Obstructive Lung Disease study, the Latin American Project for the Investigation of Obstructive Lung Disease and the European Community Respiratory Health Survey follow-up. These data were used to study the association between occupational exposures and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or above. Regression analysis of the sex-specific group-level prevalence rates of COPD at each site against the prevalence of occupational exposure and ever-smoking was performed, taking into account mean smoking pack-yrs and mean age by site, sex, study cohort and sample size. For the entire data set, the prevalence of exposures predicted COPD prevalence (0.8% increase in COPD prevalence per 10% increase in exposure prevalence). By comparison, for every 10% increase in the proportion of the ever-smoking population, the prevalence of COPD GOLD stage II or above increased by 1.3%. Given the observed median population COPD prevalence of 3.4%, the model predicted that a 20% relative reduction in the disease burden (i.e. to a COPD prevalence of 2.7%) could be achieved by a 5.4% reduction in overall smoking rates or an 8.8% reduction in the prevalence of occupational exposures. When the data set was analysed by sex-specific site data, among males, the occupational effect was a 0.8% COPD prevalence increase per 10% change in exposure prevalence; among females, a 1.0% increase in COPD per 10% change in exposure prevalence was observed. Within the limitations of an ecological analysis, these findings support a worldwide association between dusty trades and chronic obstructive pulmonary disease for both females and males, placing this within the context of the dominant role of cigarette smoking in chronic obstructive pulmonary disease causation.

Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD.

Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension. The present study analysed data from 20,296 subjects aged > or =45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for. Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function. Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.

Relationship between lung function impairment and incidence or recurrence of cardiovascular events in a middle-aged cohort.

INTRODUCTION: Lung function impairment may be a risk factor for cardiovascular disease (CVD) events. OBJECTIVE: To determine the relationship between the severity of airflow obstruction based on modified Global Initiative on Obstructive Lung Disease (GOLD) criteria and the prevalence and incidence or recurrence of CVD in a cohort of US adults, aged 45-64 years, from 1987 to 2001. METHODS: We analysed data from 14 681 adults using logistic regression to determine the cross sectional association between lung function impairment and prevalent CVD at baseline and Cox regression to examine the prospective association of lung function impairment at baseline with CVD over 15 years of follow-up. Models were adjusted for age, sex, race, smoking, comorbid hypertension and diabetes, cholesterol levels and fibrinogen level. RESULTS: At baseline, the crude prevalence of CVD was higher among subjects with GOLD 2 (OR 2.9, 95% CI 2.4 to 3.6) and GOLD 3 or 4 chronic obstructive pulmonary disease (COPD) (OR 3.0, 95% CI 2.0 to 4.5), compared with normal subjects. These relative risks were greatly reduced after adjusting for covariates (OR 1.4, 95% CI 1.1 to 1.8 for GOLD 2 and OR 1.3, 95% CI 0.8 to 2.1 for GOLD 3 or 4). Similarly, the association between COPD and risk of incident or recurrent CVD was much stronger in the unadjusted models (hazard ratio (HR) 2.4, 95% CI 2.1 to 2.7 for GOLD 2 and 2.9, 95% CI 2.2 to 3.9 for GOLD 3 or 4) than in the adjusted ones (HR 1.2, 95% CI 1.03 to 1.4 for GOLD 2 and 1.5, 95% CI 1.1 to 2.0 for GOLD 3 or 4). CONCLUSION: We observed a crude association between lung function impairment and prevalent and incident or recurrent CVD that was greatly reduced after adjusting for covariates, including age, sex, race, smoking, comorbid hypertension and diabetes, cholesterol levels and fibrinogen level. These data suggest that this association may be, in part, mediated through established CVD risk factors included in our adjusted models.

Outdoor and indoor air pollution and COPD-related diseases in high- and low-income countries.

Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality in both high- and low-income countries. While active cigarette smoking is the most important preventable risk factor globally, outdoor and indoor air pollutants can cause or exacerbate COPD. In high-income countries, historic air pollution events provide clear evidence that exposure to high levels of outdoor air pollutants is associated with increased mortality and morbidity due to COPD and related cardiorespiratory diseases. Studies in the last 20 years continue to show increased risk associated mainly with particulate matters, even at much lower levels. Populations in low-income countries are largely exposed to indoor air pollutants from the combustion of solid fuels, which contributes significantly to the burden of COPD-related diseases, particularly in non-smoking women. Effective preventive strategies for COPD may vary between countries, and include continued improvements in air cleaning technology, air quality legislation and dissemination of improved cooking stoves. A joint effort from both society and governments is needed for these endeavors.

Global burden of COPD: systematic review and meta-analysis.

The aim of this study was to quantify the global prevalence of chronic obstructive pulmonary disease (COPD) by means of a systematic review and random effects meta-analysis. PubMed was searched for population-based prevalence estimates published during the period 1990-2004. Articles were included if they: 1) provided total population or sex-specific estimates for COPD, chronic bronchitis and/or emphysema; and 2) gave method details sufficiently clearly to establish the sampling strategy, approach to diagnosis and diagnostic criteria. Of 67 accepted articles, 62 unique entries yielded 101 overall prevalence estimates from 28 different counties. The pooled prevalence of COPD was 7.6% from 37 studies, of chronic bronchitis alone (38 studies) was 6.4% and of emphysema alone (eight studies) was 1.8%. The pooled prevalence from 26 spirometric estimates was 8.9%. The most common spirometric definitions used were those of the Global Initiative for Chronic Obstructive Lung Disease (13 estimates). There was significant heterogeneity, which was incompletely explained by subgroup analysis (e.g. age and smoking status). The prevalence of physiologically defined chronic obstructive pulmonary disease in adults aged > or =40 yrs is approximately 9-10%. There are important regional gaps, and methodological differences hinder interpretation of the available data. The efforts of the Global Initiative for Chronic Obstructive Lung Disease and similar groups should help to standardise chronic obstructive pulmonary disease prevalence measurement.

Lung function decline and outcomes in an elderly population.

OBJECTIVE: To determine the risk factors for and outcomes associated with the rapid decline in lung function in a cohort of elderly US adults. METHODS: Data from 4923 adult participants aged 65 years and older at baseline in the Cardiovascular Health Study were analysed. Subjects were classified using a modification of the GOLD criteria for chronic obstructive pulmonary disease (COPD) and a "restricted" category (FEV1/FVC>or=70% and FVC<80% predicted) was added. Cox proportional hazard models were used to determine the risk of lung function decline over 4 years on subsequent mortality and COPD hospital admissions after adjusting for age, race, sex, smoking status, and other factors. RESULTS: Of the participants in the initial cohort, 3388 (68.8%) had spirometric tests at the year 4 visit. Participants with GOLD stages 3 or 4 COPD at baseline were less likely than normal subjects to have follow up spirometric tests (52.7% v 77.9%, p<0.01) and were more likely to be in the most rapidly declining quartile of FEV1 (28.2% v 21.3%, p<0.01) with an annual loss of FEV1 of at least 3.5%. Overall, being in the most rapidly declining quartile of FEV1 from baseline to year 4 was associated with an increased risk of admission to hospital for COPD (adjusted hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3 to 2.0) and all-cause death (adjusted HR 1.5, 95% CI 1.2 to 1.7) over an additional 7 years of follow up. CONCLUSION: More rapid decline in lung function is independently associated with a modest increased risk of hospital admissions and deaths from COPD in an elderly cohort of US participants.

The natural history of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the USA, and it remains one of the few diseases that continues to increase its numbers. The development and progression of COPD can vary dramatically between individuals. A low level of lung function remains the cornerstone of COPD diagnosis and is a key predictor of prognosis. Lung function, however, is not the only factor in determining morbidity and mortality related to COPD, with factors such as body mass index, exercise capability and comorbid disease being important predictors of poor outcomes. Exacerbations of COPD are additional important indicators of both quality of life and outcomes in COPD patients. Definitions of exacerbations can vary, ranging from an increase in symptoms to COPD-related hospitalisations and death. COPD exacerbations are more common in patients with lower levels of lung function and may lead to more rapid declines in lung function. Better understanding of the natural history of COPD may lead to better definitions of specific COPD phenotypes, better interventions and improved outcomes.

Boys with high body masses have an increased risk of developing asthma: findings from the National Longitudinal Survey of Youth (NLSY).

OBJECTIVE: To determine the relation between body mass index and the development of asthma in children. DESIGN: Prospective study of 4393 asthma-free children followed for up to 14 years. SETTING: Children of participants in the National Longitudinal Survey of Youth. METHODS: Analysis was limited to children who were followed from birth and were asthma-free during the first 24 months of life. The outcome was the development of asthma during follow-up (incident asthma). Body mass index (BMI) was our main predictor of interest. Survival analyses, using time to development of asthma as the main endpoint, were stratified by sex and controlled for race/ethnicity, poverty status, and prenatal maternal smoking. RESULTS: Asthma developed in 218 (5.0 %) children during the follow-up period. The relation between BMI and incident asthma varied by sex. A BMI > or =85th percentile at age 2-3 years was a risk factor for subsequent asthma development in boys (hazard ratio (HR) 1.6 95% confidence interval (CI) 1.1, 2.4) but not girls (HR 0.8, 95% CI 0.5, 1.4). Similarly, boys with BMIs always > or =85th percentile were at increased risk for subsequent asthma development (HR 2.4, 95% CI 1.4, 4.4) but not girls (HR 1.5, 95% CI 0.7, 2.9). CONCLUSION: Boys with high body masses may be at an increased risk for developing asthma.

Risk factors for prevalence of and mortality related to restriction on spirometry: findings from the First National Health and Nutrition Examination Survey and follow-up.

OBJECTIVE: To define risk factors for both restriction on spirometry and subsequent mortality in a national cohort of US adults. METHODS: Participants in the First National Health and Nutrition Examination Survey (NHANES I) were followed for up to 22 years. Subjects were classified using the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), and the FEV1/FVC ratio into subgroups with and without restriction on spirometry. Regression models were developed to determine risk factors for restriction on spirometry and death. RESULTS: Our final cohort consisted of 4320 subjects, of whom 481 (10.3 weighted %) had restriction on spirometry. The largest risk factors for restriction on spirometry were a cardiothoracic ratio of >55% (OR 4.3, 95%CI 3.1-5.9), race other than black or white (OR 3.7, 95%CI 1.8-7.8), and a history of stroke or paralysis (OR 1.8, 95%CI 1.1-2.9). The overall mortality rate was increased in subjects with restriction on spirometry (25.7 vs. 10.3 deaths per 1000 person-years). CONCLUSIONS: Restriction on spirometry is associated with comorbid disease and increased mortality, and is present in a significant proportion of the population.

Body mass index and asthma incidence among USA adults.

The aim of this study was to examine the association between body mass index (BMI) and asthma incidence. Data from the baseline examination conducted during 1971-1975, and the first follow-up conducted during 1982-1984, of the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (a cohort study) was used. Asthma was self-reported or reported by proxies. BMI was calculated from measured height and weight obtained during the baseline examination. Among 9,456 participants aged 25-74 yrs who were free of asthma at baseline, 317 participants reported a diagnosis of asthma during the follow-up interview. Compared with participants with a BMI of 18.5-<25.0 kg.m(-2), the odds ratio (OR) for those with a BMI of > or =35 kg x m(-2) was 1.87 (95% confidence interval (CI) 1.12-3.13). ORs were similar for males and females. However, only 125 of the 298 participants who recalled a date of onset reported a diagnosis that occurred after their baseline examination. Among this group of participants, BMI was not significantly associated with asthma incidence (OR 1.52, 95% CI 0.62-3.77). In conclusion, although obese people reported more "incident" asthma during follow-up, it remains unclear whether this represents reactivation of previously diagnosed asthma or the onset of new cases, and whether these new cases actually represent true asthma or respiratory symptoms misdiagnosed as asthma.

Risk factors for asthma incidence. A review of recent prospective evidence.

AIM: The aim of this study is to determine what factors have been shown, in prospective studies, to predict the incidence of asthma. METHODS: We performed a systematic review of peer-reviewed literature from 1994 to 2004 to determine what factors predict the development of asthma in both children and adults. This search strategy yielded 40 studies, with 36 providing some estimate of asthma incidence for the total sample and or a specific subgroup. RESULTS: Annual estimated incidence of physician-diagnosed asthma ranged from 0.6 to 29.5 per 1000 persons. Risk factors for incident asthma among children included: male sex, atopic sensitization, parental history of asthma, early-life stressors and infections, obesity, and exposure to indoor allergens, tobacco smoke and outdoor pollutants. Risk factors for adult-onset asthma included female sex, airway hyperresponsiveness, lifestyle factors, and work-related exposures. CONCLUSION: Risk factors for asthma include both modifiable and nonmodifiable ones, and they vary between children and adults. This review of prospective evidence supports tobacco and smoke avoidance as an intervention for the primary prevention of childhood asthma. During adolescence and adulthood, targeting lifestyle factors like obesity and smoking or reducing occupational exposures are the best opportunities for asthma prevention. Before specific public health recommendations can be made, however, additional longitudinal research is needed to better characterize target populations and identify appropriate settings for multifaceted asthma interventions.

Urinary cadmium levels predict lower lung function in current and former smokers: data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: A study was undertaken to determine the relation between urinary cadmium levels and lung function in a nationally representative cohort of current, former, and never smokers in the US. Urinary cadmium levels reflect the total body burden of cadmium. METHODS: The following data from the Third National Health and Nutrition Examination Survey were analysed: urinary cadmium (adjusted for urinary creatinine), lung function, sex, race/ethnicity, age, education level, job category, body mass index, serum cotinine level, and smoking history. Linear regression models were developed to predict lung function using urinary cadmium as the main predictor, adjusting for other covariates and stratified by smoking status. RESULTS: Data were available on 16 024 adults. Current smokers had higher mean (SE) urinary cadmium/creatinine levels (0.46 (0.01) micro g/g) than former (0.32 (0.01) micro g/g) or never smokers (0.23 (0.01) micro g/g). Higher levels of urinary cadmium were associated with significantly lower forced expiratory volumes in 1 second (FEV(1)) in current (-2.06%, 95% confidence interval (CI) -2.86 to -1.26 per 1 log increase in urinary cadmium) and former smokers (-1.95%, 95% CI -2.87 to -1.03) but not in never smokers (-0.18%, 95% CI -0.60 to 0.24). Similar results were obtained for forced vital capacity (FVC) and FEV(1)/FVC. CONCLUSIONS: Cadmium, which is known to cause emphysema in occupational settings, may also be important in the development of tobacco related lung disease.

Obstructive and restrictive lung disease and functional limitation: data from the Third National Health and Nutrition Examination.

OBJECTIVE: To determine functional limitations in adults with obstructive or restrictive lung disease or respiratory symptoms. DESIGN: Cross-sectional study. SUBJECTS: Adult participants in phase 2 of the Third National Health and Nutrition Examination Survey, 1991-94. METHODS: We classified subjects using spirometric criteria into the following mutually exclusive categories using the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC), the FEV1/FVC ratio and the presence of respiratory symptoms: severe obstruction, moderate obstruction, mild obstruction, respiratory symptoms only, restrictive lung disease and no lung disease. We developed regression models to predict functional limitations (unable to walk a quarter of a mile, unable to lift 10 pounds, needs help with daily activities) that controlled for age, race, sex, education, smoking status, body mass index and comorbid conditions. RESULTS: Severe and moderate obstruction were associated with an increased risk of being unable to walk a quarter of a mile [odds ratio (OR) 8.4, 95% confidence interval (CI) 3.6, 19.9 and OR 2.4, 95% CI 1.4, 4.0]. Restrictive lung disease and the presence of respiratory symptoms in the absence of lung function impairment were also associated with an increased risk of this outcome (OR 2.8, 95% CI 1.4, 5.6 and OR 2.8, 95% CI 2.0, 3.9). Similar results were obtained for the outcomes of being unable to lift 10 pounds or needing help with daily activities. CONCLUSIONS: The presence of obstructive or restrictive lung disease, or respiratory symptoms in the absence of lung function impairment is associated with increased functional impairment.