Articles for this Review were identified from searches of PubMed, Medline, our personal archives, and references from relevant articles, for articles published from Jan 1, 1985, to Sept 1, 2013. We searched for papers published in English with the search terms “COPD”, “small airways”, “emphysema” “chronic bronchitis”, “risk”, “risk factors”, hyperresponsiveness”, “phenotypes”, “phenotyping”, “early origins”, “lung development”, “airway development”, “alveolar development”, “in utero”,
ReviewRisk factors and early origins of chronic obstructive pulmonary disease
Section snippets
Background
Chronic obstructive pulmonary disease, which is largely a smoking-related disease, affects millions of people worldwide. At present, it is the fourth leading cause of death worldwide, and between 1990 and 2010 the proportion of disability-adjusted life-years attributable to the disorder increased by 34% in the USA, where it ranks second in the top 30 contributing diseases.1, 2 For decades, chronic obstructive pulmonary disease has been characterised by incompletely reversible and usually
Disease phenotypes and the course of lung function over a lifetime
Any discussion of the risk factors that drive the development of chronic obstructive pulmonary disease and whether or not the disease has its origins in early life first needs a definition of the disease itself. GOLD guidelines have defined chronic obstructive pulmonary disease by incompletely reversible airways obstruction—that is, a ratio of the post-bronchodilator forced expiratory volume in 1 s to the forced vital capacity (FEV1:FVC ratio) of less than 70%.5 However, the normal range of
Normal airway development
The lung bud initially develops as an outpouching of the fetal foregut at 6 weeks' gestation. By the end of the first trimester of pregnancy, airway generations down to the bronchiolar level and their accompanying vessels have been formed. Type 2 cell differentiation and the first appearance of surfactant occurs at around 23 weeks' gestation. Pre-acinar vessels follow airway development, whereas intra-acinar vessels follow the development of alveoli. Recent transcriptomic approaches have
Epidemiology of risk factors for chronic obstructive pulmonary disease, and relation with its early origins
The main risk factor for the development of chronic obstructive pulmonary disease is smoking.45 However, it is not the only risk factor, since recent studies have shown that many people develop the disease without ever having smoked.46 Therefore, other factors besides personal smoking, such as indoor and outdoor air pollution and other environmental triggers, such as second-hand smoke during pregnancy or early childhood, might also be important, as are dietary factors.45, 47, 48, 49 Indeed, one
Conclusions
Chronic obstructive pulmonary disease is a heterogeneous disease in its clinical expression, and so far epidemiological and genetic studies have mainly focused on the determinants of low lung function in the disease. Only a few studies have investigated measurements of small airways function, chronic bronchitis, and emphysema with respect to their endogenous, genetic, and environmental risk factors. Strong circumstantial evidence suggests that both genetic factors and environmental factors in
Search strategy and selection criteria
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