Worldwide, IPF constitutes the most common and severe form of ILD with a median survival of 24–36 months [
31]. The two outcome measures deciding survival in IPF include the lung function that is forced vital capacity (FVC) and acute exacerbations. Acute exacerbation is defined as worsening dyspnea with concomitant new parenchymal shadows (including ground glass shadows or consolidation) on high-resolution computed tomography (HRCT) and is an event associated with poor outcomes. There have been few studies postulating the role of air pollution in either the pathogenesis of IPF or exacerbation of pre-existing IPF [
11,
32]. A significant association between PM10 levels and the rate of decline in their FVC was documented in 135 patients with IPF in a single-center cohort study [
11]. A 1-unit increase in PM10 leads to 46 cc/year additional decline in FVC (
p < 0.05). However, the study was limited by selection bias, environmental confounders, and reliance on regional pollutant monitoring centers. Both O
3 and PM 2.5 have been found to accelerate the natural course of the disease as well as exacerbations [
32]. Another study showed a positive correlation of acute exacerbations with short-term exposure of environmental O
3 levels [
33]. They studied data from a South Korean group of 436 IPF patients and found a positive correlation between increased levels of O
3 and NO
2 (including mean levels, maximum levels, and the number of exceedances above accepted standards) and acute exacerbations of underlying IPF [
33]. However, this was a retrospective analysis of data and the pollutants data again were collected from regional monitoring stations. Thus, the individual exposure to pollutants varied depending on the time the subject spent indoors or traveled to other places. Mortality in IPF patients has been found to be significantly associated with long-term exposure to PM10 and PM2.5 levels (
p < 0.01). Pre-publication recent data of 325 patients of IPF found that lung function decline was evident in those patients exposed to air pollution [
34]. The degree of lung function decline varied according to the type of air pollutant, possibly suggesting the varied pathways adopted by different pollutants to manifest diseases. A more recent systematic review even analyzed studies regarding the effect of air pollution on ILD. They found that outcomes of IPF and fibrotic ILD like mortality and exacerbations in all the studies were associated with ambient air pollutant levels [
35]. The review admitted that there was heterogeneity in the study designs. Also, the exposure quantification was not accurate in the studies, as data about pollutants were captured through regional monitoring centers with varied distances from the residence. Conti et al., in their retrospective analysis of data from Lombardy, Italy, studied the correlation of air pollution with the incidence of IPF [
36]. They found a positive significant correlation between air pollution levels and incident cases of IPF. The study relied on hospital records for documenting the incident cases, thus errors in disease coding could have occurred. Moreover, IPF patients who did not present to hospitals would have been missed from the study pool. In a small prospective study of 25 IPF patients, home spirometry was used to follow up the patients [
37]. It was observed that lower FVC levels were associated with higher NO
2 levels, but the weekly changes in FVC did not depend on air pollution exposure. The small sample size and limited follow-up of the study failed to capture the acute exacerbations of IPF; thus, remained the limitations of the study.
Though IPF is essentially an idiopathic disease with no known cause, the possible link with air pollution may help in better understanding the pathogenesis of this complex disease. There are a few caveats in this possible association. Other ILDs are often misdiagnosed as IPF, so the association of air pollution with IPF may be spurious. Second, air pollution may exacerbate all ILDs irrespective of their subtypes.