Tobacco Is Not the Only Risk Factor for COPD: Let's Not Forget the Genetic Factor!!!

Short communication

Chronic obstructive pulmonary disease (COPD) is a major health problem as it causes increasing mortality and morbidity in all countries of the world. Its pathogenetic aspect is characterized by progressive irreversible airflow limitation. However, the disease is also a chronic inflammatory disease of the bronchopulmonary tissue with systemic consequences [1]. Cigarette smoking is the major risk factor implicated in the genesis of COPD. It is the most studied risk factor in the literature, however only a minority of cigarette smokers develops symptomatic disease. Indeed, only 10%–20% of all heavy cigarette smokers develop COPD [1]. Studies of families and twins suggest that genetic factors also contribute to the development of COPD. These findings suggest the presence of other risk factors implicated in the development of COPD and which are poorly studied as the genetic factor and its role in the genesis of COPD [1,2]. We report here the case of homozygous twin brothers, aged 54, with no notable pathological history, both consulting for respiratory symptoms. The attached table 1 reports their clinical and spirometric data. It should be noted that the smoking twin is more symptomatic (cough and expectoration) but the dyspnea is more severe in twin who is a teacher than twin 1 who is a taxi driver. The twins have the same grade of spirometric ventilator defect (severe obstructive ventilator defect (OVD)). Thus, the genetic factor in the pathophysiology of COPD should not be overlooked since it can lead to bronchial obstruction as severe as that obtained by smoking. Although one is a smoker and the other twin is non-smoker, they both developed COPD confirmed by spirometry and bronchodilation test with the same grade of severity GOLD III. wilk et al. [3] highlighted the important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction [3]. Sandford et al. [4] have shown that variants in genes involved in xenobiotic metabolism, antioxidation, and the inflammatory response have been associated with COPD. Thus all the elements of the pathophysiology of COPD (clinical signs, bronchial and systemic inflammation, bronchial obstruction, severity of COPD and response to treatment) can be encoded by specific genes for each element.

References

1. GOLD Pocket guide to COPD. Diagnosos, managemenent, and prevention. A guide for health care professionals. Report 2020.

2. Korytina GF, Akhmadishina LZ, Kochetova OV, Aznabaeva YG, Zagidullin SZ, Victorova TV. Polymorphic variants of glutamate receptor (GRIK5, GRIN2B) and serotonin receptor (HTR2A) genes are associated with chronic. Molecular Biology. 2017; 51(4): 533-42.

3. Wilk JB, Shrine NRG, Loehr LR, Zhao JH, Manichaikul A, Lopez LM, et al. Genome-Wide Association Studies IdentifyCHRNA5/3andHTR4in the Development of Airflow Obstruction. Am J Respir Crit Care Med. 2012; 186(7): 622-32.

4. Sandford AJ, Joos L, Paré PD. Genetic risk factors for chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2002; 8(2): 87- 94.

Ai-Young Lee. Tobacco Is Not the Only Risk Factor for COPD: Let's Not Forget the Genetic Factor!!!. Annals of Clinical and Medical Case Reports 2021