An estimated 12.6 million deaths each year are attributable to unsanitary environments. Of these deaths, 7 million are caused by air pollution leading to chronic respiratory diseases, which are considered one of the leading causes of environment-related deaths.
Among these chronic respiratory diseases, COPD and CF are two highly debilitating diseases that are of particular interest to consider in parallel in a human exposome study. Indeed, the two diseases share common characteristics, including modification of lung function trajectories, yet their roots seem to be opposite: COPD appears to be intricately related to the exposome and CF not.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
COPD is a major non-communicable disease, currently the third leading cause of death in the world, accounting for 5.3% of all deaths, with no treatment available to date. In 2015, 3.2 million people died of COPD worldwide, which represents an increase of 11.6 percent compared with 1990. The annual cost for COPD alone is almost €50 billion, which represents the largest economic burden on health services in terms of respiratory diseases and loss of production in the EU. COPD is characterized by persistent and usually progressive airflow limitation resulting from a combination of a diffuse disease of small airways and the destruction of the pulmonary parenchyma (emphysema). However, COPD patients present multiple variations of their phenotype that may imply different origins and underlying pathophysiological mechanisms, and which increases the complexity of medical treatment.
The main risk factor for developing COPD is smoking; about 40-50% of lifetime smokers will develop COPD. However, at equivalent tobacco consumption, not all smokers develop clinically significant COPD, suggesting that other risk factors should be taken into account, such as occupational exposures, air pollution (indoor/outdoor), as well as genetic factors that may modify the individual risk of developing COPD.
Overall, COPD can no longer be considered as a single entity caused by susceptibility to cigarette smoke, but rather as a syndrome, encompassing several phenotypes. The genetic and environmental determinants identified for a COPD phenotype may not be common to all COPD phenotypes.
CYSTIC FIBROSIS (CF)
CF is the most common autosomal recessive inherited genetic disorder in the Caucasian population (1 in 2500 births). Although probably under-reported in developing countries, CF affects at least 70,000 persons worldwide, including about 36,000 individuals in the EU. CF places a very heavy burden on people in terms of morbidity, health care utilization, and mortality. In the United Kingdom (U.K.), the average annual cost of CF treatment was between 49,000 and 76,000 euros (in 2012) per patient.
Although advances in basic science and clinical therapeutics have decreased mortality, CF remains an incurable disease and the average life expectancy of a person with CF remains significantly reduced below 50. CF causes lung, pancreatic, digestive and hepatic disorders that express at different levels of severity, therefore leading to a great phenotypic variability of the disease. Obstructive pulmonary disease in CF patients is currently their leading cause of morbidity and accounts for about 80% of mortality. CF is associated with a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, leading to dysfunction of the CFTR protein. To date, more than 2,000 mutations have been identified in the CFTR gene. Importantly, the genotypic variability associated with CF does not fully explain the phenotypic variability. Indeed, although CF is a monogenic disease, there is a wide clinical diversity in patients; the evidence suggests that some manifestations of the disease are related to the severity of the underlying CFTR mutations as well as environmental and genetic modifiers, which currently remain of an overall unknown nature.
Lung function trajectories
Lung function development is critical to lung health at adulthood.
The development of lung function begins in utero and continues throughout childhood, with maximum lung function being reached at the age of 20-25 years. This lung function plateau has long been considered identical to all healthy individuals (i.e. without respiratory symptoms). However, the height of this plateau is now considered highly dependent on events occurring earlier in life; lung function may already be compromised at a very early age (e.g. maternal smoking during pregnancy which results in low birth weight, prematurity, and is associated with poor lung growth and/or broncho-pulmonary dysplasia in the most preterm infants, etc.), and/or by events during childhood and/or adolescence. In addition to the complexity of the global picture, some infants can catch-up lung function while others do not, and there is currently no clue to explain such lung function evolution.
A relatively new concept in COPD pathophysiology is that even if the disease becomes clinically apparent around the age of 40 to 50, its origins are very early in life, namely before birth and in early childhood.