Authors: Alessandro Marcon
Categories: Editorials
Source: American Journal of Respiratory and Critical Care Medicine
Cough and mucus hypersecretion are common respiratory symptoms in adults. Persistence of these symptoms, driven by chronic airway epithelial inflammation and mucus metaplasia, can lead to a diagnosis of chronic bronchitis, a condition associated with reduced quality of life, increased risk for chronic obstructive pulmonary disease (COPD), and higher mortality rates (1). Exposure to air pollution has been linked to a higher prevalence and incidence of chronic bronchitis and bronchitic symptoms in adults (1–3). The adverse effects of air pollution on the lungs are linked to diverse pathogenetic processes, including the activation of proinflammatory signaling cascades in airway epithelial cells and the generation of reactive oxygen species (1).
There is increasing awareness that chronic diseases have their origins early in life. Childhood disadvantage factors, including maternal smoking, can accelerate lung function decline and increase COPD risk (4). Lifelong consequences of early-life air pollution exposure have been documented for several respiratory outcomes. The Dutch Prevention and Incidence of Asthma and Mite Allergy (or, PIAMA) study found a higher incidence of asthma up to age 20 in children and young adults who were exposed to higher levels of air pollution at their birth residential address (5). Higher exposures to particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) and ozone (O3) in the first decade of life were related to increased asthma attacks in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study, which was performed in North European countries with low to moderate air pollution levels (6). Research conducted in diverse populations (Poland, Sweden, Norway, and Australia) using various study designs indicates that childhood air pollution exposure can lead to lower FEV1 and FVC in adolescence and young adulthood (6–9). The FEV1/FVC ratio appears to be less affected by air pollution (7, 9), suggesting an early alteration of lung development that tracks with age rather than faster lung function decline. With regard to low lung function, the Swedish BAMSE study identified the first year of life as a period of greater susceptibility compared with ages 1–8 years and 8–16 years (8).
In this issue of the Journal, Garcia and colleagues (pp. 1025–1034) advance our understanding of how early life exposures impact respiratory health in adulthood (10). They investigated the association between childhood air pollution exposure and the risk of reporting bronchitic symptoms in adult life. The study sample consisted of 1,308 individuals (mean age in 32 ± 5), from 16 southern Californian communities, who took part in an online follow-up survey. These were part of the 2,267 participants in the Southern California Children’s Health Study, originally recruited when they were 5 to 10 years old and previously assessed up to the age of 17 ± 2 years. The authors reconstructed residential histories and assigned annual exposures to particulate matter with an aerodynamic diameter ≤10 μm (PM10) and nitrogen dioxide (NO2) (daily 24-hour mean concentrations), and to O3 , 26.1 ppb for NO(daily maximum 8-hour mean concentrations) to the geocoded addresses. Mean exposures to air pollutants were 41.9 μg/m^3^ for PM102 (U.S. Environmental Protection Agency 49.1 μg/m^3^), and 49.1 ppb for O3 (96.7 μg/m^3^), largely exceeding the annual air quality guideline levels recommended by the World Health Organization in 2021 (11).
Approximately 25% of adult participants reported having had one or more of four bronchitic symptoms. Of them, 62% reported usual congestion in the chest or bringing up phlegm; bronchitis or persistent cough in the morning or at other times of the day during the previous 12 months were each reported by ∼30% of the participants. Higher mean exposures to PM10 and NO2 between birth and age 17 were associated with a higher risk of reporting bronchitic symptoms, with an estimated 69% and 51% increased odds per SD increase in PM10 and NO2 concentrations, respectively. This result was consistent, considering different adjustment sets and across a number of sensitivity analyses. Estimated associations were not affected by further adjustment for childhood exposure to O3, which, on the other hand, was not associated with bronchitic symptoms.
Childhood air pollution exposures and adult bronchitic symptoms were associated through pathways that did not directly involve increased childhood asthma or childhood bronchitis, which indicates that other, less obvious, pathways for the lifelong consequences of early-life exposures need to be sought. Nonetheless, stronger associations were estimated among participants with childhood asthma, a subgroup of the population at greater benefit from exposure reduction.
Conducting a prospective analysis of a well-established cohort, on the basis of a monthly reconstruction of participants’ residential histories through extensive follow-up data, is certainly a major strength of the article. Care was taken to rule out confounding by air pollution exposures at different susceptibility windows. In fact, the authors further adjusted for prenatal and current air pollution exposures in a subset of participants with available data, obtaining similar results. Exposure assignment was based on spatial interpolation of air quality data from the dense monitoring network of the U.S. Environmental Protection Agency. Interpolation is generally deemed to be a coarse exposure assignment strategy. The most up-to-date methods combine land use regression techniques and air dispersion modeling (12). As opposed to land use regression, interpolation does not take advantage of available spatial data, such as street network cartography, population density, or other Geographic Information System data. Similarly, it does not take into account emission data, as compared with air dispersion modeling. Nonetheless, spatial interpolation is believed to reasonably catch regional background air pollution concentrations, which represent average exposures in the population satisfactorily.
What are the possible future developments of this research? A follow-up of the study population would provide valuable data on the risk that bronchitic symptoms would progress to accelerated lung function decline and COPD. Future research based on biomarkers should investigate plausible disease pathways from childhood exposures to adult chronic respiratory diseases, aimed at devising evidence-based preventative actions. New causal inference methods are becoming available to improve our comprehension of the complex relationship between exposures over different susceptibility windows and diseases at different stages of life while accounting for the hierarchical structure of data and the clustering of observations within communities and families (13). Given the impressive monthly reconstruction of exposures from birth to age 17, the dataset compiled for the present article could be further exploited to identify the periods of greater vulnerability between pregnancy and adulthood (8). Distributive lag nonlinear models are now being applied for this purpose (14).
In conclusion, the article by Garcia and colleagues represents a significant contribution to life course respiratory epidemiology, a research paradigm that, coupled with state-of-the-art statistical methods, could change the way in which the causes of chronic respiratory diseases are understood and tackled (15). Nonetheless, it is imperative to recognize that the urgency to combat air pollution on a global scale does not require further evidence. The time for action is now.