The natural history of lung function - A longitudinal analysis based on the Dunedin Multidisciplinary Health and Development Study
Lung function is related to health and mortality throughout the lifetime. Lung function impairment has been associated with earlier onset of respiratory, cardiovascular, and metabolic conditions and higher all-cause mortality. Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease affecting more than 251 million people worldwide and is the third leading cause of mortality. In New Zealand, it is estimated to affect 15% of adults aged over 45 years and is the fourth leading cause of mortality. Longitudinal evidence suggests that COPD can develop by mid-late adult life as a result of failure to attain the normal peak lung function in early adulthood and/or from, usually smoking-related, accelerated adult lung function decline. Investigating the longitudinal development of lung function in the general population would make important contributions to the epidemiology of COPD and potentially help to identify targets for prevention and early intervention. Normally, the maximal spirometric lung volumes are attained between ages 20 and 25 years in men and several years earlier in women, then stay stable for several years in the plateau phase, before starting to gradually decline with age due to physiological lung ageing. There is heterogeneity in the patterns of lung function growth and decline, mainly because lung function development is a very complex process which may be affected by numerous genetic and environmental factors across the lifespan. Previous studies have attempted to identify the risk factors associated with impaired lung function growth or accelerated lung function decline, and the distinct trajectories of lung function. However, to date, few studies have sufficient high-quality data to examine the development of lung function from early life to mid-late adulthood in the general population. In this thesis, the longitudinal development of lung function was investigated using unique data from the Dunedin Multidisciplinary Health and Development Study (Dunedin Study) – a prospective population-based birth cohort (n=1,037) with repeated assessments of lung function from age 9 to 45 years. Generalised estimating equations (GEE) and multiple linear regression were used to examine longitudinal associations between potential risk factors and development of lung function. Latent profile analysis (LPA) was conducted to identify distinct trajectories of lung function from age 9 to 45 years. Finally, multinomial logistic regression and penalised logistic regression were employed to relate early life factors and mid-adulthood COPD outcomes to identified trajectories. The findings suggest that to attain the normal plateau lung function in early adulthood or prevent accelerated lung function decline during early-mid adulthood, targeted interventions could be focused on the better management of persistent asthma and airway hyperresponsiveness (AHR), prevention/reduction of cigarette smoking, and maintenance of a healthy body weight. A number of distinct trajectories of lung function (10 for FEV1, 9 for FVC, and 10 for FEV1/FVC) were identified in the cohort. For most Study members (79% in the FEV1 trajectories, 80% in the FVC trajectories, and 72% in the FEV1/FVC trajectories), their adult lung function trajectory appeared to be already established before age 9 years, with two exceptions: a smoking-related accelerated decline trajectory and a childhood AHR/asthma-associated persistently low trajectory, which started low and diverged from the other trajectories as age increased. Importantly, the three most adverse FEV1 trajectories (19% of the Study population) contributed more than half (55%) of the COPD outcomes at age 45 years. This thesis provides novel insights into the natural history of lung function from childhood to the fifth decade of life in the general population. It highlights the longitudinal adverse effects of asthma and AHR, cigarette smoking, and obesity on lung function development. It also confirms the existence of distinct trajectories of lung function from childhood to mid-adult life in the general population. Most importantly, it delivers an important respiratory and public health message: for most people, their adult lung function trajectory may be already established before adolescence, therefore it is critical to maximise lung function growth in early life. To promote healthy lifetime lung function development and reduce COPD risk in mid-late adult life, intervention strategies could be developed and investigated with goals of maximising lung function growth in early childhood, better managing asthma and AHR, and avoiding cigarette smoking in adult life.
Advisor: Hancox, Bob; Gray, Andrew
Degree Name: Doctor of Philosophy
Degree Discipline: Preventive and Social Medicine
Publisher: University of Otago
Keywords: lung function; development; trajectories; COPD; birth cohort; Dunedin Study; New Zealand; spirometry; longitudinal analysis; risk factor
Research Type: Thesis