Ambient sulfur dioxide (SO2) exposure and genetic susceptibility appear to be key risk factors for developing incident idiopathic pulmonary fibrosis (IPF), according to findings from a large-scale, national prospective cohort study conducted in China and published in the journal Chemosphere.

Because effective therapies for patients with IPF are limited, it is vital to explore the risk factors associated with the disorder. It has been well recognized that ambient air pollution is an environmental risk factor for a variety of respiratory conditions, including asthma, lung cancer, and pneumonia. In fact, the adverse effects of ambient air pollution on pulmonary diseases have been reported in locales with air pollution levels that are below those in the current World Health Organization air quality guidelines.

Recognizing that evidence on the impact of low levels of air pollution, particularly SO2, is limited, and that the combined effect and interaction between genetic susceptibility and ambient SO2 on IPF remains to be elucidated, the researchers sought to explore the following:

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  • Whether long-term ambient SO2 exposure or genetic susceptibility is associated with the risk for incident IPF; and
  • Possible interaction effects between genetic susceptibility and ambient SO2 on risk for incident IPF.

Read more about experimental therapies for patients with IPF

Data from the UK Biobank were used in the current study. In the UK Biobank, more than 500,000 individuals between 37 and 73 years of age were recruited from 22 centers in England, Scotland, and Wales from 2006 through 2010. All participants were followed up from the date of study recruitment until their initial IPF diagnosis, death, loss to follow-up, or conclusion of the study period—whichever occurred first. The study outcome was “incident IPF cases recorded during follow-up.”

Ambient SO2 exposure was divided into 1 of 3 levels:

  • Tertile 1: low SO2 pollution
  • Tertile 2: moderate SO2 pollution
  • Tertile 3: high SO2 pollution

At study recruitment, the mean participant age was 56.41±8.04 years. Overall, 53.34% of the participants were females. During a median follow-up of 11.78 years, a total of 2562 cases of incident IPF were identified.

The mean age at IPF diagnosis was 70.39 years; the mean duration between enrollment in the study cohort and diagnosis of IPF was 8.14 years. The mean concentration of SO2 was 2.53 μg/m3 in patients with incident IPF compared with 2.25 μg/m3 among those without incident IPF.

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Study results revealed that each 1 μg/m3 increment in ambient SO2 was positively associated with the risk for incident IPF (hazard ratio [HR], 1.83; 95% CI, 1.73-1.92). The association was constant in both the basic model (HR, 1.81; 95% CI, 1.72-1.91) and the fully adjusted model (HR, 1.67; 95% CI, 1.58-1.76).

Further, a higher genetic risk was associated with an elevated risk for IPF (HR, 1.68; 95% CI, 1.47-1.92 in those with an intermediate genetic risk vs HR, 3.78; 95% CI, 3.30-4.34 in those with a high genetic risk). In addition, individuals with a high genetic risk and high ambient SO2 exposure exhibited a higher risk for development of IPF (HR, 7.48; 95% CI, 5.66-9.90).

“These findings emphasize the need to consider the potential health effects of SO2 exposure and the necessity for stricter air quality standard,” the authors concluded.


Wang X, Deng X, Wu Y, et al. Low-level ambient sulfur dioxide exposure and genetic susceptibility associated with incidence of idiopathic pulmonary fibrosis: a national prospective cohort study. Chemosphere. Published online July 4, 2023. doi:10.1016/j.chemosphere.2023.139362