Is Dynamic Change in Lung Function Linked to Lung Cancer Development?

A rapid rate of decline in forced expiratory volume in 1 second (FEV₁) may be a biomarker for lung cancer development, according to a South Korean longitudinal, observational study published in Chest.

Impaired lung function has been linked to a higher risk of developing lung cancer. Earlier studies have shown that a lower FEV₁ also correlates with a higher risk of lung cancer development. The current study explored the relationship between an accelerated decline in lung function and lung cancer using epidemiological data from 2 population-based studies that were part of the Korean Genome Epidemiology Study.

The researchers evaluated participants aged 40 to 69 years twice yearly from 2001 through 2019 and performed spirometry at each follow-up. Participants who experienced a decline in FEV₁ greater than 60 ml per year were classified, for study purposes, as “decliners.”

Of the 8549 qualified participants, 1287 (15.1%) experienced rapid FEV₁ decline, and 48 (0.6%) developed new cases of lung cancer. After adjusted Cox regression using covariates that included age, sex, smoking history, FEV₁/forced vital capacity (FVC), and white blood cell count, rapid FEV₁ decliners were found to have lost 76.8 ml and 2.6% of FEV₁ per year compared with their baseline lung function, whereas non-rapid FEV₁ decliners lost 28.0 ml and 1.0% of FEV₁ per year relative to baseline.

Additionally, researchers found that the risk of developing lung cancer development climbed in individuals 45 years or older who had 30 or more pack/years of smoking, low baseline FEV₁/FVC, low forced expiratory flow at 25% to 75% of the pulmonary volume (FEF_25-75), rapid FEV₁ decline, and increased white blood cell count.

A rapid FEV₁ decline was shown to be an independent risk factor for lung cancer development (adjusted hazard ratio, 2.44; 95% CI, 1.30-4.57; P =.006). Analysis of time-dependent net reclassification improvement (NRI) at 18 years showed that the FEV₁ decline rate was useful in finding individuals at risk of lung cancer when added to conventional practice (categorical time-dependent NRI, 0.32 [95% CI, 0.00-0.64]; continuous time-dependent NRI, 0.83 [95% CI, 0.14-1.25).

Unlike earlier studies, this investigation revealed the connection between lung cancer development and dynamic changes in lung function, rather than simple baseline lung function.

Limitations of the study include an inability to identify which histologic type of lung

cancer was most associated with lung function decline; a lack of data about occupational or environmental exposure to carcinogens; underestimation of the incidence of underlying chronic lung disease; and the small number of lung cancers detected, leading to reduced generalizability of the results.

“Since the acceleration of FEV₁ decline has already occurred before the detection of lung function impairment, individual risk evaluation is necessary even in patients in the pre-COPD stage,” the authors stated. “Our study suggests that even subjects without comorbid chronic lung disease may have a high risk of lung cancer if the FEV₁ decline rate is accelerated,” they added, noting that the rate of FEV₁ decline is an easily obtained potential biomarker for detecting lung cancer development.

Reference

Lee HW, Lee HJ, Lee JK, Park TY, Heo EY, Kim DK. Rapid FEV₁ decline and lung cancer incidence in Korea. Chest. Published online March 19, 2022. doi:10.1016/j.chest.2022.03.018