Origins of Chronic Obstructive Pulmonary Disease

Posted by • September 1st, 2016

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The conventional thinking about chronic obstructive pulmonary disease (COPD) is that exposures in adult life, such as smoking, lead to a low FEV1:FVC ratio, the physiological hallmark of COPD (a frequent cause of illness and death). Although smoking is still considered a major culprit, it is now known that genetic, environmental, and developmental factors that are associated with diverse biologic mechanisms and that exert their effects during the growing years can both diminish the maximally attained forced expiratory volume in 1 second (FEV1) and accelerate FEV1 decline in adult life, thus increasing the risk of COPD. In this new Review Article, the effect of early-life exposures on the lung that could lead to expiratory airflow limitation is reviewed.

Clinical Pearl

• What has been the prevailing theory regarding the development of COPD?

Until recently, the prevailing concept was that during development (i.e., from birth to approximately 25 years of age), all people — those destined to have no lung disease and those destined to have COPD — reached the same plateau for lung function as measured by the FEV1. It was thought that whether COPD developed was determined by the rate of subsequent decline in the FEV1 level.

Clinical Pearl

How are previous theories about the development of COPD being revised?

Emerging evidence has radically challenged the concept of a single natural history for COPD, indicating that the spectrum of patients presenting with chronic respiratory symptoms and irreversible airway obstruction (as assessed by an abnormally low FEV1) is much more heterogeneous than previously thought. Results from longitudinal cohort studies have shown that in a considerable proportion of patients with COPD the decline in the FEV1 was not steeper than that in healthy adults. It has also been shown that some people with COPD who do not show excessive lung-function decline reach a lower FEV1 level early in adult life than those with future rapid decline and normal populations. These findings thus implicate an entirely different pathway leading to the diagnosis of COPD from the rapid-decline form, one in which smoking can certainly play a role, especially in the clinical expression of the disease, but in which the central derangement is already present early in adult life. What emerges is a fundamentally new concept of COPD, in which the factors that determine the maximal (or “plateau”) FEV1 level attained during the third decade of life become major elements in the pathogenesis of the disease.

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Morning Report Questions

Q: What are some of the factors that may influence the maximal FEV1 level attained in early adulthood?

A: Approximately 10% of all births in the United States occur prematurely (i.e., before 37 weeks of gestation), and preterm birth has been shown to have profound effects on long-term lung function. Although the most severe consequences are observed in newborns with bronchopulmonary dysplasia, premature infants without the disorder also have FEV1 levels later in life that are 7.2% lower than those of children born at term. Several longitudinal studies have shown that children who have lower respiratory tract illnesses in early life are at increased risk for subsequent chronic respiratory symptoms and FEV1 deficits, which often persist into adult life. The largest deficits have been observed in adults who had radiologically ascertained pneumonia before 3 years of age, who had an FEV1:FVC ratio that was lower by approximately 0.04 than those with no early-life respiratory illnesses, whereas those with lower respiratory tract illnesses but no pneumonia had less severe impairment in the FEV1:FVC ratio. There is now convincing evidence that exposure to airborne contaminants is associated with reduced growth in lung function during adolescence and lower maximally attained FEV1 levels.

Q: What are some examples of childhood exposures that influence the effects of smoking in adult life? 

A: There is increasing evidence from longitudinal studies that childhood events and exposures can accelerate the rate of decline in the FEV1 level and induce early expression of chronic respiratory symptoms in both smokers and nonsmokers. Prenatal and postnatal parental smoking increases susceptibility to the ill effects of active smoking in adult life, with smokers who were exposed to parental smoking having greater deficits in FEV1 than those whose parents did not smoke. Smokers who had lower respiratory illnesses due to respiratory syncytial virus before 3 years of age are more likely to receive a diagnosis of asthma in the third decade of life than smokers without such an early-life history. Women who as young girls lived through the so-called Dutch famine, a circumscribed episode of severe human starvation that occurred between October 1944 and May 1945 in the Netherlands, were more likely to be hospitalized for COPD before 60 years of age than their age peers who were not exposed to famine. These effects were particularly noticeable among active smokers, suggesting that postnatal malnutrition may increase susceptibility to the deleterious effects of smoking.

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