David B. Coultas

An Official American Thoracic Society Public Policy Statement: Novel Risk Factors and the Global Burden of Chronic Obstructive Pulmonary Disease

RATIONALE Although cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), a substantial proportion of COPD cases cannot be explained by smoking alone. OBJECTIVES To evaluate the risk factors for COPD besides personal cigarette smoking. METHODS We constituted an ad hoc subcommittee of the American Thoracic Society Environmental and Occupational Health Assembly. An international group of members was invited, based on their scientific expertise in a specific risk factor for COPD. For each risk factor area, the committee reviewed the literature, summarized the evidence, and developed conclusions about the likelihood of it causing COPD. All conclusions were based on unanimous consensus. MEASUREMENTS AND MAIN RESULTS The population-attributable fraction for smoking as a cause of COPD ranged from 9.7 to 97.9%, but was less than 80% in most studies, indicating a substantial burden of disease attributable to nonsmoking risk factors. On the basis of our review, we concluded that specific genetic syndromes and occupational exposures were causally related to the development of COPD. Traffic and other outdoor pollution, secondhand smoke, biomass smoke, and dietary factors are associated with COPD, but sufficient criteria for causation were not met. Chronic asthma and tuberculosis are associated with irreversible loss of lung function, but there remains uncertainty about whether there are important phenotypic differences compared with COPD as it is typically encountered in clinical settings. CONCLUSIONS In public health terms, a substantive burden of COPD is attributable to risk factors other than smoking. To prevent COPD-related disability and mortality, efforts must focus on prevention and cessation of exposure to smoking and these other, less well-recognized risk factors.

Passive smoking and risk of adult asthma and COPD: an update

The number of published studies on passive smoking as a risk factor for adult onset asthma and chronic obstructive pulmonary disease (COPD) is small compared with the number on the adverse health effects of passive smoking on childhood respiratory symptoms and diseases. The paucity of research among adults may partly be due to a number of factors that make it difficult to design studies of these non-malignant respiratory diseases. The potential for misclassification of smoking status, with former or current smokers categorised as passive smokers, has been a longstanding concern in studies that rely on self reports of past smoking habits. Measuring past passive smoke exposure presents a major challenge in studies of chronic diseases that may become clinically apparent only after 20 or more years of exposure. Over-reporting of symptoms that subjects attribute to passive smoking is increasingly likely as public awareness of passive smoking increases. Also, it is difficult to measure lifetime exposure to the number of other confounding agents that are risk factors, which must be controlled for in studies of passive smoking. While causation of asthma and COPD from passive smoking may not be directly demonstrable, it is possible to infer causal relationships from the concordance of scientific evidence, and Hill’s nine criteria for causal association provide a useful guide for evaluating available evidence.1 The nine criteria include strength of association, consistency, specificity, temporality, dose-response, plausibility, coherence, experimental evidence, and analogy. Of these criteria, plausibility, coherence, and analogy are fulfilled in relation to COPD by the established association of active cigarette smoking with chronic airflow obstruction. However, the criteria of specificity and experimental evidence have little relevance for human diseases associated with cigarette smoking.2 Of the remaining criteria, strength of association, consistency, temporality, and dose-response have the greatest relevance for evaluating the evidence on …

Idiopathic pulmonary fibrosis: survival in population based and hospital based cohorts

BACKGROUND To ascertain whether findings from hospital based clinical series can be extended to patients with idiopathic pulmonary fibrosis (IPF) in the general population, the survival of patients with IPF in a population based registry was compared with that of a cohort of patients with IPF treated at major referral hospitals and the factors influencing survival in the population based registry were identified. METHODS The survival of 209 patients with IPF from the New Mexico Interstitial Lung Disease Registry and a cohort of 248 patients with IPF who were participating in a multicentre case-control study was compared. The determinants of survival for the patients from the Registry were determined using life table and proportional hazard modelling methods. RESULTS The median survival times of patients with IPF in the Registry and case-control cohorts were similar (4.2 years and 4.1 years, respectively), although the average age at diagnosis of the Registry patients was greater (71.7 years versus 60.6 years, p < 0.01). After adjusting for differences in age, sex, and ethnicity, the death rate within six months of diagnosis was found to be greater in the Registry patients (relative hazard (RH) 6.32, 95% CI 2.19 to 18.22) but more than 18 months after diagnosis the death rate was less (RH 0.35, 95% CI 0.19 to 0.66) than in the patients in the case-control study. Factors associated with poorer prognosis in the Registry included advanced age, severe radiographic abnormalities, severe reduction in forced vital capacity, and a history of corticosteroid treatment. CONCLUSIONS The adjusted survival of patients with IPF in the general population is different from that of hospital referrals which suggests that selection biases affect the survival experience of referral hospitals.

A personal monitoring study to assess workplace exposure to environmental tobacco smoke.

We enrolled 15 nonsmoking volunteers to evaluate the feasibility of measuring personal exposure to environmental tobacco smoke (ETS) at work and to characterize workplace exposures. During one workshift, we obtained questionnaires on exposure, saliva and urine for cotinine, and personal air samples for respirable particles and nicotine. The levels of cotinine, respirable particles, and nicotine varied widely with self-reports of exposure to ETS, but on average increased with increasing exposure.

Ethnic differences in the prevalence of nonmalignant respiratory disease among uranium miners.

OBJECTIVES This study (1) investigates the relationship of nonmalignant respiratory disease to underground uranium mining and to cigarette smoking in Native American, Hispanic, and non-Hispanic White miners in the Southwest and (2) evaluates the criteria for compensation of ethnic minorities. METHODS Risk for mining-related lung disease was analyzed by stratified analysis, multiple linear regression, and logistic regression with data on 1359 miners. RESULTS Uranium mining is more strongly associated with obstructive lung disease and radiographic pnuemoconiosis in Native Americans than in Hispanics and non-Hispanic Whites. Obstructive lung disease in Hispanic and non-Hispanic White miners is mostly related to cigarette smoking. Current compensation criteria excluded 24% of Native Americans who, by ethnic-specific standards, had restrictive lung disease and 4.8% who had obstructive lung disease. Native Americans have the highest prevalence of radiographic pneumoconiosis, but are less likely to meet spirometry criteria for compensation. CONCLUSIONS Native American miners have more nonmalignant respiratory disease from underground uranium mining, and less disease from smoking, than the other groups, but are less likely to receive compensation for mining-related disease.

Undiagnosed airflow obstruction: prevalence and implications.

Conditions associated with airflow obstruction are often over- and underdiagnosed. Prevalence estimates of undiagnosed airflow obstruction (UDAO) range from 3 to 12%. UDAO is a nonspecific physiologic abnormality that may be caused by a number of factors (eg, cigarette smoking) and can be the manifestation of many different disorders. The higher occurrence of UDAO among men, current or former smokers, and with advancing age provide preliminary evidence on probable causes and diagnoses (ie, chronic obstructive pulmonary disease). While cigarette smoking is associated with UDAO, a substantial proportion of persons have never smoked, particularly among women. Few studies suggest that this condition is associated with increased morbidity and mortality. While there is currently no evidence to support screening for UDAO, case-finding may have a role among persons with respiratory symptoms, who have ever smoked, with a family history of respiratory disease, or with occupational exposures to dusts or fumes.

Silicosis and lung cancer risk in underground uranium miners

The presence of radiographic silicosis as a risk factor for lung cancer was assessed in a case-control study conducted within a study cohort of New Mexico underground uranium miners. Chest radiographs were interpreted for the presence of silicosis for 65 lung cancer cases and 216 controls. The presence of silicosis on the chest radiograph taken closest to the start of employment or on the latest radiograph available was not associated with lung cancer risk after adjustment for cumulative exposure to radon progeny. The odds ratio associated with the presence of any type of opacity indicative of pneumoconiosis on the chest x ray closest to the start of employment was 1.33 (95% confidence interval, 0.31-5.72). For the most recent available chest x ray, the corresponding odds ratio was 1.16 (95% confidence interval, 0.35-3.84). Although the findings are limited by the relatively small number of subjects, the lack of association of silicosis with lung cancer suggests that silica exposure should not be regarded as a major uncertainty in extrapolating radon risk estimates from miners to the general population.

Use of chest radiographs in epidemiological investigations of pneumoconioses.

The International Labour Organisation (ILO) classification of radiographs of pneumoconioses was developed to limit variation in classification of parenchymal abnormalities. In this study the manner in which chest radiographs were interpreted in 134 investigations reported in four peer reviewed journals during the five year period 1985-90 was examined. The approach for applying the ILO system was poorly described in most studies. For example, of 86 investigations using more than one reader, 66.3% described the method of reconciliation, but methods were not consistent among investigations. Our results indicate a number of potential problems in application of the ILO system, and gaps in existing recommendations that should be considered.

Patterns and Economic Burden of Hospitalizations and Exacerbations Among Patients Diagnosed with Idiopathic Pulmonary Fibrosis

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a rare and fatal restrictive respiratory disease under the idiopathic lung disease (ILD) class. IPF is a form of chronic, progressive fibrosing interstitial pneumonia and has more scarring, less inflammation, and poorer prognosis than most other ILD forms. Exacerbation of IPF is rapid, with unpredictable deterioration of lung function, and is associated with short-term mortality. The American Thoracic Society (ATS) evidence-based guidelines for diagnosis and management of IPF reports that the incidence of acute exacerbations is between 5%-10%. Limited real-world evidence has been identified in the United States that assesses patterns of hospitalization, exacerbation of IPF, and the associated economic burden. OBJECTIVES To (a) characterize patients newly diagnosed with IPF and (b) examine incidence rates and costs of all-cause hospitalizations, IPF-related hospitalizations, and exacerbations. METHODS A retrospective analysis was performed with a national commercial claims database from calendar years 2006 to 2011. Newly diagnosed IPF patients were identified with either ≥ 2 claims for idiopathic fibrosing alveolitis (IFA) or ≥ 1 claim for IFA and ≥ 1 claim for postinflammatory pulmonary fibrosis and a lung biopsy or thoracic high-resolution computed tomography within 90 days of the first claim for IFA (index date). IPF-related hospitalizations and possible IPF exacerbations were defined based on diagnoses recorded on event claims. Frequency, incidence rate, duration of events, and associated costs from the third-party payers perspective were estimated. RESULTS Among 1,735 identified IPF patients, 38.6% had at least 1 all-cause hospitalization; 10.8% had IPF-related hospitalizations; 4.6% had suspected IPF exacerbations leading to hospitalization; and 72.1% had suspected IPF exacerbations leading to urgent outpatient visits during the 1-year post-index period. Incident rates for these 4 events were 83 (95% CI = 79-88), 17 (95% CI = 14-19), 7 (95% CI = 6-9), and 277 (95% CI = 269-286) per 100 person-years, respectively. Average costs per event were

Healthcare resource utilization among patients diagnosed with idiopathic pulmonary fibrosis in the United States

13,987 (SD =