Genetic epidemiology of pulmonary function

Respiratory diseases are major threats to human health. It is believed that chronic obstructive pulmonary disease (COPD) is both environmental and genetic ; however, specific genetic factors in the development of COPD have not been clearly identified, except for protease inhibitor types. Alpha1-antitrypsin deficiency is rare in the general population 5 and accounts for less than 2% of the cases of COPD. 7 The molecular genetics of COPD has recently been reviewed by Barnes. Pulmonary function measures are the most important phenotypes of COPD. The respiratory muscles, the thorax, and the lungs are the components of the ventilatory apparatus which can be evaluated by appropriate function tests. The dynamic functional capacity of the ventilatory apparatus can be assessed by the volumetime or flow-volume manoeuvres. Airflow rates and volumes inhaled or exhaled over specific time intervals provide information on the flow resistive properties of the airways. These pulmonary function measures predict the development of lung diseases and overall mortality. While the environmental determinants of pulmonary function have been extensively studied—for example, smoking and ambient air pollution—the genetic determinants have recently received increasing attention. Genetic epidemiological studies of pulmonary function are of potential importance in understanding normal pulmonary function and the aetiology and prevention of COPD and other respiratory diseases. This paper reviews the familial aggregation and segregation of pulmonary function and presents evidence for different influences of heredity on airway function, lung volume, and airway-parenchymal dysanapsis (relative airway size to lung size). Some methodological issues related to segregation analysis are also discussed.