Associations Found Between Frailty, Chronic Lung Conditions Such as COPD, Asthma

Chronic obstructive pulmonary disease (COPD) and asthma are leading causes of global mortality and morbidity, and the conditions have increased in prevalence due to population aging and exposure to risk factors. Although an association between frailty and obstructive lung conditions has been made, it is unclear how significant the association is. In a study published in Archives of Gerontology and Geriatrics, investigators used a bidirectional, 2-sample Mendelian randomization (MR) approach to evaluate the relationship between frailty and prominent obstructive lung diseases, such as asthma and COPD.

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The meta-analysis investigated both the effect of the frailty index (FI) on COPD and asthma risk as well as the effect of COPD and asthma on FI score. Genome-wide association study (GWAS) summary statistics were examined to extract leading single nucleotide polymorphisms (SNPs) associated with frailty or COPD and asthma as genetic instrumental variables. Further, the study utilized GWAS data to identify genetic instruments for the FI and the same data were used to measure the FI outcome.

In addition, the definitions of COPD and asthma were based on analyses that were adjusted for age, sex, 10 principal components, and a genotype batch using mixed-model logistic regression. FI was defined based on self-reported items on symptoms, disabilities, and diagnosed diseases, with resulting scores ranging from 0 to 27. Further, MR is dependent on the naturally random assortment of genetic variants during conception to yield impartial estimations of their impact of an exposure on an outcome.

The MR analysis results presented significantly positive associations between genetically predicted FI and both COPD (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.29-2.36) and asthma (OR 2.10, 95% CI 1.44-3.16), according to the investigators. In addition, reverse direction analyses have provided evidence that suggests genetic susceptibility to COPD (beta 0.06, 95% CI 0.01-0.10) and asthma (beta 0.08, 95% CI 0.06-0.11) is linked to higher FI. The investigators note that the findings suggest a bidirectional, causal relationship between frailty and obstructive lung diseases.

According to the study authors, prior research has explored the association between frailty and other chronic conditions, such as cardiovascular conditions, stroke, and type 2 diabetes. Although prior research has found an association between frailty and COPD and asthma, the severity was undetermined.

The current study findings indicate that frailty syndrome may be caused by both COPD and asthma, which is consistent with other research. The incidence of frailty and COPD increases as the population ages, and the heightened risk of frailty in patients with COPD is higher than in those without. Although asthma is a serious condition that can affect people of all ages to varying degrees, there are fewer examples that show a strong association of frailty and asthma.

According to prior research, a correlation between the cumulative dosages of oral corticosteroids and frailty exists in elderly patients with asthma; however, the current analysis only suggests that an association between COPD and asthma may lead to an increase in FI and does not conclusively state that frailty occurs as a direct result. In addition, asthma may be associated with other chronic diseases that have links to frailty, although that is currently unknown. Further, multiple inflammatory markers were detected in individuals with frailty, of which some are also present in individuals who are diagnosed with asthma.

A limitation of the study is the enrolled population being individuals with COPD and asthma in European countries, therefore, the results may not be generalizable to other populations. The authors also note that the sample size may lead to inaccurate estimates with wide confidence intervals, potentially leading to misinterpretations in results. In addition, the authors note that the identification of all pleiotropic SNPs were challenging due to the intricate relationships between certain phenotypes, resulting in an incomplete comprehension.

The investigators emphasize that frailty is more likely to advance poor outcomes in patients with COPD and asthma, and interventions should be made to reverse frailty to reduce or delay the onset of chronic lung conditions. In addition, frailty screenings and assessments for patients with COPD and asthma to identify related issues and create personalized interventions can help improve patient outcomes.

Reference

Qu J, Liang Y, Rao Y, et al. Causal Relationship between Frailty and Chronic Obstructive Pulmonary Disease or Asthma: a two sample bidirectional Mendelian Randomization Study. Arch Gerontol Geriatr. 2023:105310. doi:10.1016/j.archger.2023.105310