Prognostic Impact of Mediastinal Lymph Nodes in Interstitial Lung Diseases: Is Environmental Exposure the Offender?

To the Editor:

We read with great interest the work of Adegunsoye and colleagues showing a significant association between enlarged mediastinal lymph nodes (MLNs) on chest computed tomography and survival in patients with interstitial lung diseases (ILDs) (1). They report a 66% prevalence of enlarged MLNs according the type of ILD, with various potential causes of development as previously pointed out. The authors raise the hypothesis that enlarged MLNs may be reflective of underlying immunologic phenomena in lung tissue, which in turn contribute to the pathophysiology of disease progression in pulmonary fibrosis. However, we suggest that the potential involvement of environmental exposures in ILDs, particularly anthracosis, should be discussed. Anthracosis caused by coal dust and other environmental factors such as air pollution, biomass fuels used extensively for cooking (“hut lung”), and cigarette smoking is also known to be a source of damage in MLNs (2).

A broad array of inhaled exposures are risk factors for developing an ILD, particularly idiopathic pulmonary fibrosis (IPF) in genetically susceptible patients (3). Inhaled agents are known to induce a series of lesions in alveolar epithelial cells, causing a biochemical oxidant injury and thereafter an immunological response when healing mechanisms (e.g., inflammation, coagulation, and epithelial repair) are put in place, resulting in pulmonary fibrosis. It is very likely that MLNs are involved in this process. Indeed, autopsy studies have revealed higher levels of inorganic particles, such as silicon and aluminum, in the MLNs of patients with IPF compared with controls (3).

Interestingly, inhalation of occupational dusts may be an aggravating factor associated with a poor prognosis in several diseases, and particularly in IPF. In a large Korean cohort of patients with IPF, Lee and colleagues evaluated the prognosis of IPF according to the patients’ work and found that the wood or chemical dust–exposure group showed the worst outcomes (4). This group displayed a greater annual decline in FVC% and a higher mortality compared with nonexposed patients, with a hazard ratio of 1.813 (95% confidence interval [CI], 1.049–3.133, P = 0.033) (4). Based on U.S. death certificates from 1999 to 2003, Pinheiro and colleagues identified three industry categories with potential exposure to wood and metal dust that were associated with statistically significant risk estimates for IPF mortality: fabricated structural metal products (mortality odds ratio [MOR], 1.7 [95% CI, 1.0–3.1]), metal mining (MOR, 2.2 [95% CI, 1.1–4.4]), and wood buildings and mobile homes (MOR, 5.3 [95% CI, 1.2–23.8]) (5). Gold and colleagues examined potential associations of occupational exposures with the risk of mortality from systemic autoimmune diseases, using U.S. death certificates from 26 states (6). Farming occupation was associated with death from any systemic autoimmune disease (odds ratio [OR], 1.3 [95% CI, 1.2–1.4]), mining machine operators were at increased risk of death from systemic lupus erythematosus (OR, 1.8 [95% CI, 1.2–2.7]), and risk of death from systemic sclerosis was associated with usual occupation as industrial machinery repairers (OR, 2.3 [95% CI, 1.4–3.9]).

Enlarged MLNs in ILDs may be at least in part a marker of occupational or environmental exposure. Thus, we may hypothesize that the prognostic impact of MLNs observed in the study by Adegunsoye and colleagues could be related to the negative effects of unrecognized exposures. It would have been interesting to look at the patients’ occupational potential exposures, and ideally to perform a cytological analysis of MLNs to verify the presence or absence of lymph node anthracosis or anthracofibrosis in these patients.