Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease

Artículo publicado en "The NEW ENGLAND JOURNAL of MEDICINE"

Podéis ver el artículo completo en: https://www.nejm.org/doi/10.1056/NEJMoa1411532

Abstract

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1?could also lead to COPD in persons whose maximally attained FEV1?is less than population norms.

METHODS

We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1?≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1?over time among the participants according to their FEV1?at cohort inception and COPD status at study end.

RESULTS

Among 657 persons who had an FEV1?of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1?of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1?before 40 years of age and had a rapid decline in FEV1?thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV1?in early adulthood and a subsequent mean decline in FEV1?of 27±18 ml per year (P<0.001), despite similar smoking exposure.

CONCLUSIONS

Our study suggests that low FEV1?in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1?is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.)

Chronic obstructive pulmonary disease (COPD) is a major cause of illness and death worldwide.1?Since the research by Fletcher and colleagues in the 1970s,2,3?the prevailing paradigm of COPD pathogenesis has been that, in susceptible persons, exposure to particulate matter — especially tobacco smoke — leads to clinical disease through acceleration of the age-related decline in lung function, as assessed by the forced expiratory volume in 1 second (FEV1). Subsequent population studies supported this paradigm and led to therapeutic trials aimed at reducing the rapid decline in FEV1.4-11?Surprisingly, the observed declines in FEV1?in these trials and in observational cohorts of patients with COPD have been variable and smaller than anticipated, particularly among persons with the most severe airflow limitation.4-16?These observations question the notion that COPD always follows a trajectory of rapid decline in FEV1?and are consistent with the hypothesis that low maximally attained lung function in early adulthood can also result in COPD later in life, even when the rate of decline in FEV1?is within the normal range.17-21?In fact, this alternative course was already suggested by Fletcher and Peto3?and emphasized by Burrows et al.22?but was never explored in a long-term, prospective investigation. We used data from three large cohort studies to investigate this issue.

• Peter Lange, M.D., Dr. Med. Sc.,?Bartolome Celli, M.D.,?Alvar Agustí, M.D., Ph.D.,?Gorm Boje Jensen, M.D., Dr. Med. Sc.,?Miguel Divo, M.D.,?Rosa Faner, Ph.D.,?Stefano Guerra, M.D., Ph.D.,?Jacob Louis Marott, M.Sc.,?Fernando D. Martinez, M.D.,?Pablo Martinez-Camblor, Ph.D.,?Paula Meek, R.N., Ph.D.,?Caroline A. Owen, M.D., Ph.D.,?Hans Petersen, Ph.D,?Victor Pinto-Plata, M.D.,?Peter Schnohr, M.D., Dr. Med. Sc.,?Akshay Sood, M.D., M.P.H.,?Joan B. Soriano, M.D.,?Yohannes Tesfaigzi, Ph.D.,?and J?rgen Vestbo, M.D., Dr. Med. Sc.