The role of chronic symptoms as early biomarkers of COPD development

Research findings over the years have suggested that the presence of chronic symptoms is not directly associated with the development of airflow limitation. Their course over a patient’s life is rather unstable as they may appear, disappear, and reappear over the years. Dr James Allinson (Imperial College London, UK) discussed the available evidence on the role of symptoms in early COPD in his lecture at the ATS 2020 [1].

Formerly, GOLD 0 was a classification describing people with normal lung function, but the presence of chronic symptoms would indicate an increased risk of developing COPD [1,2]. Those symptoms were chronic chough and sputum, also referred to as chronic bronchitis/chronic mucus hypersecretion (CMH). CMH has been associated with poor outcomes like mortality or FEV₁ decline in smokers with and without COPD [3,4]. “But definitely linking GOLD 0 with a subsequent development of airflow limitation has proven quite difficult,” argued Dr Allinson. For example, the Copenhagen City Heart Study found that GOLD 0 was not suitable to identify subjects at risk for COPD because most subjects with developing COPD did not previously have a GOLD 0 classification [5]. Gold 0 has since been removed from the classification of COPD by severity and, as such, will not appear in the current GOLD report 2020 [6]. “But that’s not quite the end of the story, because other studies have shown that CMH can actually predict COPD development,” Dr Allinson stated.

To assess the possible association between CMH and COPD, Dr Allinson proposed 2 important considerations: the phase of life and the period of time assessed in studies [1,7]. When evaluating the impact of chronic bronchitis on later airflow limitation according to life stage, results have shown that its presence under the age of 50 years entails a significant risk of consecutive airflow limitation (HR 2.24; 95% CI 1.33-3.76), as opposed to having chronic bronchitis at age ≥50 (HR 0.92; 95% CI 0.59-1.43) [8]. This is in line with results of a cohort study observing a 3.7-4.11 times increased likelihood of smokers with chronic symptoms at ages 36-43 developing airflow limitation in later life compared with those without chronic symptoms during midlife [9].

To understand how COPD evolves, considering the course of symptoms over a longer period of time seems to be important because chronic symptoms seem to be dynamic [1]. “People move from being asymptomatic to having the first incidents of CMH, to having either ongoing symptoms or remission or in fact relapse after remission,” Dr Allinson explained. A longer presence of CMH is linked to a greater FEV₁ decline [9]. In a cohort study, 50% of individuals with airflow limitation aged 60-64 years, were in CMH remission after they had already had CMH events during adulthood [9]. “There can even be persons with COPD in later life without chronic symptoms and their development of COPD may be linked to an earlier phase of those symptoms at that time already resolved.” said Dr Allinson. He saw no straightforward association between CMH and decline in lung function as the life course is very complex. “So, rather than being a binary phenotype, this clinical marker seems to be a biomarker of developing and progressing disease,” Dr Allinson stated.

 

1. 
   
   1. Allinson JP. Early COPD: Do Symptoms predict the development of COPD? Session A3, ATS 2020 Virtual, 5-10 Aug.
   2. Pauwels RA, et al. Am J Respir Crit Care Med. 2001;163:1256-1276.
   3. Vestbo J, t al. Am J Respir Crit Care Med. 1996;153:1530-1535.
   4. Lange P, et al. Thorax. 1990;45:579-585.
   5. Vestbo J, et al. Am J Respir Crit Care Med. 2002;166:329-332.
   6. 2020 Global Strategy for Prevention, Diagnosis and Management of COPD. Retrieved from: https://goldcopd.org/gold-reports/ [Accessed on 2 Oct 2020].
   7. Allinson JP, et al. Ann Am Thorac Soc. 2018;15:1241-1242.
   8. Guerra S, et al. Thorax. 2009;64:894-900.
   9. Allinson JP, et al. Am J Respir Crit Care Med. 2016;193:662-672.

 



Posted on 29 October 202028 March 2024