Inflammatory parameters and pulmonary biomarkers in smokers with and without chronic obstructive pulmonary disease (COPD)

Abstract

Background: We organized this study in order to investigate differences in serum inflammatory profiles and circulating serum pneumoproteins between smokers with and without chronic obstructive pulmonary disease (COPD).

Methods: Patients aged 35-70 years with COPD and a smoking history ≥10 pack-years (cases, n=38) and 38 participants with the same smoking history without COPD (controls) were included in a comparative study conducted as part of a population-based cross-sectional study with 2,388 individuals in northwestern Russia. Cases and controls were matched for age and smoking history. Airflow obstruction (AO) was defined using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 and/or FEV1/FVC < lower limit of the normal cut-off values. Patients at risk for COPD were reassessed using a standardized diagnostic work-up protocol. Several parameters, among which four inflammatory biomarkers [the high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) levels] and two pneumoproteins [surfactant protein D (SP-D) and Clara cell secretory protein 16 (CC16)], were measured in the peripheral blood. Systemic inflammation was defined as at least 2 or more elevated biomarker levels.

Results: Out of all smokers, 57.9% with normal spirometry and 36.8% with COPD did not have systemic inflammation, whereas 44.7% of the patients with COPD and 5.3% of the patients without AO demonstrated at least two elevated biomarker levels. No difference in age, gender, and smoking history, environmental and occupational exposure was found between the non-inflamed and the inflamed smokers. Of all risk factors studied, only COPD was associated with systemic inflammation [odds ratio (OR) 11.42, 95% confidence interval (CI): 2.13-58.84].

Conclusions: Our study describes the systemic inflammatory network pattern associated with COPD and how it differs from the pattern in smokers with normal lung function. Systemic inflammation is not present in all smokers with COPD; in contrast, some non-obstructed smokers are characterized by systemic inflammation. From this perspective, smoking itself could be seen as a disease and studied accordingly.

Trial registration: NCT02307799.

Keywords: Inflammome; airflow obstruction; smoking; systemic inflammation.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-20-1580). The authors have no conflicts of interest to declare.

2021 Journal of Thoracic Disease. All rights reserved.

Figures

Figure 1

The RESPECT case-control study flow diagram. BD, bronchodilator; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; GLI-LLN, lower limit of normal determined as the 5th percentile of the z-scores of the reference population using the Lambda-Mu-Sigma approach; COPD, chronic obstructive pulmonary disease; ACO, asthma-COPD overlap; MI; myocardial infarction.

Figure 2

Box plot (log scale) for inflammatory biomarkers in smokers with COPD (cases) and without AO (controls). AO, airflow obstruction; COPD, chronic obstructive pulmonary disease; IL, interleukin; TNF-α, tumor necrosis factor-α; hs-CRP, high-sensitivity C-reactive protein; WBC, white blood cell; NS, non-significant.

Figure 3

The percentage of persons in the both groups that exceeded the 90th percentile of the values of the healthy non-smokers for cytokines (A) and pulmonary pneumoproteins and other biomarkers (B) in smokers with COPD (cases) and without AO (controls). COPD, chronic obstructive pulmonary disease; AO, airflow obstruction; TNF-α, tumor necrosis factor-α; hs-CRP, high-sensitivity C-reactive protein; MMP9, matrix metallopeptidase 9; TIMP, tissue inhibitor of metalloproteinases; CC16, Clara cell secretory protein 16; SP-D, surfactant protein D.

Figure 4

Network model for the cigarette smoking-induced immune response for selected biomarkers in non-smokers (n=35), smokers without AO (n=38) and smokers with COPD (n=38). Notes: each node of the network corresponds to 1 of the 6 cytokines determined in the study (see color code), and its size is proportional to the prevalence of abnormal values (90th percentile of healthy non-smokers) of that particular biomarker in that particular group of subjects (precise figure shown inside of each node). Two nodes are linked if more than 1% of subjects in the network share abnormal values of these two biomarkers, its width being proportional to that proportion. The inflammatory (such as IL-6, IL-8, TNF-α) and anti-inflammatory (such as IL-4, IL-10) pathways are interlinked each other through molecular mediators (such as IL-6 and IL-10). AO, airflow obstruction; COPD, chronic obstructive pulmonary disease; hs-CRP, high-sensitivity C-reactive protein; IL, interleukin; TNF-α, tumor necrosis factor-α.