Inhalational Exposures associated with interstitial lung disease: a systematic review and meta-analysis by C. Lee et al. published in Thorax (2025) https://doi.org/10.1136/thorax-2024-222306 

Lay Summary

Why We Did This Study:

Interstitial lung diseases (ILDs) are a group of lung diseases involving inflammation and scarring of the lung tissue. Breathing in certain substances from the environment or workplace may increase the risk of developing an ILD, however how these risks may cause disease is not well understood. Also, new potential exposures are identified every year, making it difficult for doctors to know which ones are most important to ask about or suggest avoiding. An up-to-date, evidence-based list of exposures linked to increased risk of ILD could help doctors ask the right questions to better identify possible causes of a person’s lung disease. This study combined results from previously published studies to identify which inhaled exposures were linked to higher risk of developing ILD, and how strongly each exposure was associated with lung disease.

Study Goals:

The goal of this study was to identify workplace and environmental exposures linked to an increased risk of getting ILD.

The second goal was to compare how strongly each exposure was associated with risk of getting ILD.

How The Study Was Done:

The researchers searched large medical databases for English-language studies published between 1990 to April 2022. In total, they reviewed 96 studies involving 295,000 people with ILD, and over 40 million without ILD for comparison. Studies were published across Europe, North America, Asia and other continents. 54 studies with number estimates of risk were combined to make one large study, and the quality of each study was assessed, using recommended methods for quality assessment. Similar inhaled exposures, such as dusts, metals, asbestos, and air pollution were grouped together so researchers could better compare results across studies.

Note: The review excluded ILD types where inhaled exposures are already known to contribute to the disease onset, such as asbestosis (known to be caused by asbestos), and silicosis (known to be caused by silica), as well as sarcoidosis. No specific inhaled exposures were excluded.

Findings:

By combining results from the 54 identified studies, researchers found that several inhaled exposures increased a person’s risk of developing ILD. These included smoking, organic exposures (such as mould, agricultural / farming exposures, and plant or wood materials), metals, dusts, and asbestos. Smoking showed the strongest risk with ILD. Compared with people who did not smoke, smokers were almost 70% more likely to be diagnosed with ILD. These associations were seen across several different types of ILD, including idiopathic pulmonary fibrosis (IPF).

A note on the increased risk of ILD: increased risk does not mean an outcome is likel yor guaranteed to occur. For example, driving in bad weather increases your chance (risk) of a car crash, but most people still arrive safely. In the same way, breathing in certain exposures can increase the risk of a disease while most people exposed will still not develop the disease.

Interpretation:

These findings suggest that inhaled exposures may be important risk factors for someone developing any type of ILD. Therefore, asking patients about workplace and environmental exposures is an important part of assessing ILD. Importantly, if these risks are known, people should be advised avoid these exposures, and workplaces and other environments must be made safer to reduce these exposures. While the results show associations, they do not prove that these exposures directly cause ILD.

The strongest associations between exposure and ILD onset were with smoking and organic exposures. Smoking was associated with both IPF and other types of ILD. While the link between smoking and IPF has already been described, its association with other types of ILD has not previously been recognized. This highlights the need to improve how inhaled exposures are assessed across different types of ILD, and the ongoing importance of public health efforts to reduce smoking.

However, the studies analyzed within this paper, differed greatly in how exposures were measured, and many relied on people reporting their own exposures, therefore limitations remain and results should be interpreted recognizing these limits.

Summary:

This study reviewed previously published peer-reviewed research from 1990 to 2022 to better understand the relationship between inhaled exposures and ILD. Researchers found that exposures to cigarette smoking, organic materials, metals, dusts, and asbestos were associated with a higher likelihood of someone getting ILD. Future research is needed to better identify specific harmful domestic and workplace exposures and understand how reducing these exposures could help prevent ILD onset and worsening.  

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