Predisease State of COPD: Early Indicator of COPD Risk and Progression

Young adults with early signs of chronic bronchitis and subtle lung impairment are clearly at a higher risk for both developing COPD and progressing to more severe stages in due course of time, according to a study published online Sept. 1, 2024 in The American Journal of Respiratory and Critical Care Medicine.

The aim of the study was to investigate if young adults with chronic bronchitis and early, subtle impairment in lung function are more likely to develop COPD in the future. For this they enrolled participants without COPD from different smoking eras; 5497subjects, without COPD, from Copenhagen General Population Study (2003) and 2609 from the Copenhagen City Heart Study (1976-1978) and followed them for 10 and 25 years. The main outcome measures were the incidence of COPD (FEV1/FVC <0.70), and more specifically, moderate to severe COPD (GOLD Stages 2-4) (additionally, FEV1 <80% predicted).

After a decade of follow-up, 28% of individuals identified as susceptible developed COPD, compared to only 8% in those without susceptibility. Thirteen percent of the susceptible group developed moderate to severe COPD (COPD GOLD Stages 2-4), compared to just 1% in those without susceptibility. After 25 years, the development of COPD was slightly reduced in the susceptible group (22%), but still significantly higher compared to the non-susceptible group (13%). The incidence of moderate to severe COPD (COPD GOLD Stages 2-4) rose to 20% in the susceptible group, compared to 8% in those without susceptibility.

More than half of the new cases of COPD were individuals identified as susceptible. After 10 years, the odds of developing COPD in those susceptible were 3.42 times higher (95% CI: 2.78-4.21) compared to those without susceptibility. The odds of developing moderate to severe COPD (GOLD Stages 2-4) were even higher, at 10.1 times. After 25 years, the odds of developing COPD remained elevated but decreased to 1.54. The odds of developing COPD GOLD Stages 2-4 were still significantly higher at 2.12.

A risk score combining the state of susceptibility with smoking and asthma had a high predictive ability for COPD development later on in life.

This study highlights the predisease state of COPD, which can help clinicians in early identification of high-risk individuals and prevent disease progression. Of note was the observation that even though the rate of COPD development in susceptible individuals decreased after 25 years, the rate of progression continued to increase.

Although the 2024 GOLD guideline has introduced the term pre-COPD, most current COPD guidelines, including GOLD, generally focus on treating the disease once it has developed. Hence, these findings could have an impact on current COPD guidelines.

GOLD 2024 has defined pre-COPD as presence of “structural lung lesions (e.g., emphysema) and/or physiological abnormalities (including low FEV, gas trapping, hyperinflation, reduced lung diffusing capacity and/or rapid FEV1 decline) without airflow obstruction (FEV1/FVC ≥ 0.7 post-bronchodilation).”  COPD has been viewed mainly as a disease of old age. But of significance is the fact that individuals with pre-COPD could be “of any age”. 

It further states that “not all individuals with pre-COPD will eventually develop fixed airflow obstruction over time (and hence COPD) but they should be considered “patients” (because they already suffer symptoms and/or have functional and/or structural abnormalities) and, as such, they deserve care and treatment.”

Preventive measures taken in this phase could significantly alter the disease trajectory for many at-risk individuals, especially in those with risk factors like smoking cessation and asthma.

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