Genetics, Lifestyle Jointly Impact IPF Risk

Unhealthy lifestyle was a significant contributor to the risk for idiopathic pulmonary fibrosis, especially in those genetically predisposed, based on data from more than 400,000 individuals.

The etiology of idiopathic pulmonary fibrosis (IPF) remains unclear, patient prognosis is generally poor, and the global incidence of IPF is rising, wrote Yudiyang Ma, PhD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues.

More research is needed to identify potentially modifiable risk factors for IPF, they said. Lifestyle factors have been established as contributors to other age-related diseases, but associations between lifestyle and IPF have not been well studied, they added.

In a study published this month in the journal Chest, the researchers explored the relationship between lifestyle and IPF risk by constructing a lifestyle score. The score was based on national guidelines and classified lifestyle variables as “healthy” or “unhealthy.” Healthy variables were scored as 1, and unhealthy variables were scored as 0. The total scores ranged from 0 to 9, with higher scores suggesting a favorable lifestyle. Participants were classified into three groups of unhealthy lifestyle (scores of 0-3), intermediate lifestyle (scores 4-6), and favorable lifestyle (scores 7-9).

The study population included 407,615 participants who were enrolled in the UK Biobank, a population-based prospective cohort study. The average age of the participants was 56 years, and 53% were female.

A total of 1248 incident IPF cases occurred over a median follow-up period of 12 years that included 4.8 million person-years. Compared with the favorable lifestyle group, both intermediate lifestyle and unhealthy lifestyle were significantly associated with an increased risk for IPF before and after adjusting for age and sex (adjusted hazard ratios 1.53 and 2.82, respectively; P for trend < .001).

Specific lifestyle factors associated with IPF included smoking, excessive alcohol consumption, unhealthy diet, and lower levels of physical activity. On further adjustment for variables including education, ethnicity, body mass index, employment status, hypertension, diabetes, and hyperlipidemia, the incident IPF risk was 38.4% higher and 127.1% higher among those with intermediate and unfavorable lifestyles, respectively, compared to the favorable lifestyle group.

The researchers also used 13 single nucleotide polymorphisms (SNPs) associated with IPF to construct a polygenic risk score (PRS) for each participant. Participants were categorized as having low, medium, or high genetic risk based on the tertiles of the PRS scores. The risk for incident IPF was 39.7% higher for those with medium genetic risk and 210.9% higher in those with high genetic risk compared with those with low genetic risk.

The combined effect of unfavorable lifestyle and high genetic risk was associated with a greater than sevenfold increased risk for IPF compared with favorable lifestyle and low genetic risk (HR, 7.79), and 32.7% of IPF risk was attributable to this combination, the researchers said.

Both intermediate and unfavorable lifestyle were associated with increased risk for incident IPF across the age groups, but there was no significant interaction between age and lifestyle with favorable lifestyle as the reference, or between age and genetic risk with low genetic risk as the reference.

The study findings were limited by several factors, including the use of self-reported questionnaires to collect information on lifestyle variables and by the lack of data on other lifestyle factors (stress, drug use, other dietary variables, etc.) not accounted for in the study, the researchers noted. In addition, the study population was mainly White and European, and the association between genetics and lifestyle may not generalize to other populations, they said.

However, the results add evidence that genetic susceptibility could increase the association of lifestyle with incident IPF risk, and highlight the need to encourage a healthy lifestyle to reduce IPF risk, especially for those with a genetic predisposition, they concluded.

The study received no outside funding. The researchers report no relevant financial relationships.  

Chest. Published online April 12, 2023. Abstract

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