Comparative analysis of pathophysiological parameters between emphysematous smokers and emphysematous patients with COPD

Abstract

emphysematous smokers with normal spirometry form a considerable proportion of the clinical population. However, despite presenting with respiratory symptoms and activity limitation, they cannot be diagnosed with chronic obstructive lung disease (copD) according to current criteria. thus, we aimed to determine whether emphysema in smokers has a different pathogenesis from that in patients with COPD. We compared 12 pairs of lung tissue samples from emphysematous patients with normal spirometry and copD, and determined the degree of emphysema using computed tomography. With a focus on COPD-related pathogenesis, we independently assessed inflammatory response, protease-antiprotease balance, oxidative stress, and apoptosis in both groups. Both groups showed similar pathological changes at a comparable degree of emphysema; the expression of inflammatory factors was comparable, with overexpression of proteases and decreased levels of antiproteases. Moreover, there was no significant difference in the activities of glutathione and superoxide dismutase, and expression of apoptosis-related factors. in conclusion, emphysema in smokers with normal spirometry and in patients with COPD had similar pathogenesis. Forced expiratory volume in 1 second cannot be used as the sole diagnostic criterion in patients with copD; early intervention is of great importance to such patients. Chronic obstructive lung disease (COPD) is a chronic respiratory airway disease, with symptoms such as cough, sputum, and shortness of breath 1. The two most prominent pathological changes associated with COPD are the structural destruction of lung tissue and airway remodelling 2. Currently, spirometry is the sole diagnostic criterion for COPD 1,3. Forced expiratory volume in 1 second (FEV1) primarily reflects airflow obstruction and is therefore not suitable for assessing COPD symptoms such as emphysema 4-8. Studies have shown that there is a poor correlation between FEV1 and COPD symptoms 5,6 , as well between FEV1 and the degree of emphysema, as assessed by computed tomography (CT) 7,8. Patients with COPD show high heterogeneity in terms of clinical symptoms, structural destruction, and airway damage 9,10. In some patients, structural destruction of lung tissue is more prominent, and their emphysema severity develops progressively 11. These patients are termed emphysema phenotype of COPD 12,13 , and their structure destruction can be assessed with chest CT scans 14,15. However, chest CT scans have revealed that a considerable number of smokers with obvious emphysema and lung tissue damage show preserved pulmonary function 14-16. According to the current diagnostic criteria, such emphysematous smokers cannot be diagnosed with COPD. If they have same pathogenesis as patients with emphysematous COPD, appropriate interventions to reduce the clinical symptoms and block emphysema progression would be challenging in emphysematous smokers 5,17. In this study, we hypothesized that emphysematous smokers with normal spirometry and emphysematous patients with COP...

Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model

“…Our results demonstrated that Bcl-2 expression was significantly lower in COPD patients than in non-COPD smokers. Interestingly, Bai et al [ 31 ] found that Bcl-2 expression was similar between emphysematous smokers and emphysematous patients. Almost all non-COPD smokers in our study did not experience emphysema, suggesting that Bcl-2 might specifically be involved in emphysema rather than other pathogenic processes of COPD.…”

Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model

“…Our results demonstrated that Bcl-2 expression was signi cantly lower in COPD patients than in non-COPD smokers. Interestingly, Bai et al [31] found that Bcl-2 expression was similar between emphysematous smokers and emphysematous patients. Almost all non-COPD smokers in our study did not experience emphysema, suggesting that Bcl-2 might speci cally be involved in emphysema rather than other pathogenic processes of COPD.…”

Identification of Proteomic Signatures in Chronic Obstructive Pulmonary Disease Emphysematous Phenotype

“…Patients with COPD were recruited based on the criteria previously described ( Bai et al, 2020 ). In brief, the inclusion criteria were as follows: 40- to 80-year-old patients diagnosed with COPD, more than 10 pack-years of smoking history, preparing for chest surgery, and read and signed informed consent.…”

“…In contrast to patients with other COPD phenotypes, those with emphysematous phenotype typically manifest symptoms such as severe dyspnea, decreased exercise tolerance, and physiological complications. Moreover, patients with emphysematous phenotype have a higher mortality than those with non-emphysematous phenotype ( Fan et al, 2014 ; Criner et al, 2018 ; Bai et al, 2020 ). Some emphysematous smokers do not exhibit airflow limitation ( Oelsner et al, 2014) , despite showing similar pathophysiological features to those with COPD ( Bai et al, 2020 ).…”

“…Moreover, patients with emphysematous phenotype have a higher mortality than those with non-emphysematous phenotype ( Fan et al, 2014 ; Criner et al, 2018 ; Bai et al, 2020 ). Some emphysematous smokers do not exhibit airflow limitation ( Oelsner et al, 2014) , despite showing similar pathophysiological features to those with COPD ( Bai et al, 2020 ). Unfortunately, there are few biomarkers that could be useful to predict the emphysema phenotype in COPD patients.…”