Respiratory health from a life course perspective

Abstract

Background: Most chronic respiratory diseases are irreversible and incurable, which contributes to years of life lost and loss of quality of life. Effective preventive measures implemented before the development of irreversible and incurable chronic respiratory diseases are needed. A life course perspective informed by the developmental origins of health and diseases (DOHaD) hypothesis and more broadly by evolutionary biology may help identify intervention points during development and enable prevention before respiratory disease occurs. However, previous evidence, mainly from observational studies conducted in Western settings, is still controversial due to the possibility of bias from residual confounding. Objectives: To examine the association of life course exposures relevant to growth and development with respiratory health indicated by lung function and asthma. Methods: Based on the large, population-representative Chinese “Children of 1997” birth cohort in Hong Kong (n=8327), in which maternal overweight or maternal smoking, birth weight and gestational age have little social patterned, the association of ambient air pollutants (nitric oxide (NO), nitrogen dioxide (NO2), sulfur dioxide (SO2) and particulate matter with an aerodynamic diameter of <10μm (PM10)) in utero, in infancy and toddlerhood (ages <2 years) and in childhood (ages 2-8 years), gestational age, birth weight, and pubertal timing with lung function (forced vital capacity (FVC), forced expiratory volume measured in the first second of exhalation (FEV1), FEV1/FVC, forced expiratory flow between 25% and 75% of the pulmonary volume (FEF25%-75%) and asthma at 17.5 years was examined. Sex-specific associations were examined where possible to assess whether these early life factors could contribute to long-term differences in life expectancy by sex. As validation, Mendelian Randomization, a robust method free from the confounding, was also used to examine the association of maternal effects on birth weight (independent of fetal genetics) and pubertal timing (age at menarche and voice breaking) with respiratory health indicated by lung function (FEV1, FVC and peak expiratory flow (PEF)) and with asthma. Results: Higher prenatal and early postnatal exposure to NO and NO2, but not SO2 or PM10, was associated with lower airway function indicated by FEV1, FEV1/FVC and FEF25%-75%, higher risk of wheezing, but not with asthma. Birth weight was positively associated with lung capacity indicated by FVC, FEV1, and FEF25%-75%, with a stronger association in boys than girls. Prematurity was associated with lower airway function indicated by FEV1/FVC and FEF25%-75%. Using MR, maternal genetically predicted effects birth weight was positively associated with FVC and FEV1, but not with PEF or asthma. Earlier pubertal timing indicated by age at menarche and voice breaking was associated with poorer lung capacity, indicated by FVC and FEV1, and higher risk of asthma, but these associations were obviated by adjusting for adulthood height and BMI. Conclusion: Intrauterine and early life are critical periods for lung development, which are susceptible to adverse effects of air pollution, as well as to exposures that result in prematurity or lower birth weight, possibly with greater effects in boys. The overall costs and benefits of corresponding interventions to promote early lung development needs to be assessed.