Lung Development and Aging

Abstract

The onset of chronic obstructive pulmonary disease (COPD) can arise either from failure to attain the normal spirometric plateau or from an accelerated decline in lung function. Despite reports from numerous big cohorts, no single adult life factor, including smoking, accounts for this accelerated decline. By contrast, five childhood risk factors (maternal and paternal asthma, maternal smoking, childhood asthma and respiratory infections) are strongly associated with an accelerated rate of lung function decline and COPD. Among adverse effects on lung development are transgenerational (grandmaternal smoking), antenatal (exposure to tobacco and pollution), and early childhood (exposure to tobacco and pollution including pesticides) factors. Antenatal adverse events can operate by causing structural changes in the developing lung, causing low birth weight and prematurity and altered immunological responses. Also important are mode of delivery, early microbiological exposures, and multiple early atopic sensitizations. Early bronchial hyperresponsiveness, before any evidence of airway inflammation, is associated with adverse respiratory outcomes. Overlapping cohort studies established that spirometry tracks from the preschool years to late middle age, and those with COPD in the sixth decade already had the worst spirometry at age 10 years. Alveolar development is now believed to continue throughout somatic growth and is adversely impacted by early tobacco smoke exposure. Genetic factors are also important, with genes important in lung development and early wheezing also being implicated in COPD. The inescapable conclusion is that the roots of COPD are in early life, and COPD is a disease of childhood adverse factors interacting with genetic factors.

Birth weight and prematurity with lung function at ~17.5 years: “Children of 1997” birth cohort

“…The DOHaD hypothesis that early life is the critical period for respiratory health also does not consider evolutionary biology life history trade-offs, where early survival to reproductive age could trade-off against adult health including respiratory function. Lung function tracks throughout life 21 . Observationally, birth weight is inversely associated with indicators of restrictive lung function (forced vital capacity (FVC)) but evidence is weaker for the association of indicators of obstructive patterns (lower FEV 1 /FVC) in adults 5 .…”

Airway epithelial barrier dysfunction in the pathogenesis and prognosis of respiratory tract diseases in childhood and adulthood

“…89 Genetic factors are also relevant, with genes important in lung development and early wheezing also being implicated in COPD. 90 Further evidence suggesting that COPD has origins in early childhood was provided by the PIAMA and ALSPAC studies, which demonstrated associations between important COPD-associated genes. 91 They found that at least 3 COPD genes were involved in lung growth and development and were involved in antenatal and early-life responses to tobacco smoke exposure.…”

No fire without smoke: Are the children really out of the woods?

“…There is increasing recognition that the time between conception and the first day at school represents a period of vulnerability for the developing respiratory tract. Antenatal and early life exposure to pollutants, including nicotine and air pollution, leads to impaired lung function, which largely tracks into the sixth decade . It is increasingly realized that chronic obstructive pulmonary disease (COPD) will not be prevented by adult life interventions; the action occurs very early on.…”