Heavy smoking triggers systemic inflammation and vascular damage in new biomarker study

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.May 26 2025

New research uncovers how heavy smoking rapidly disrupts blood and airway biology, revealing the hidden damage that accelerates disease risk in otherwise healthy adults.

Study: The effects of heavy smoking on oxidative stress, inflammatory biomarkers, vascular dysfunction, and hematological indices. Image Credit: CGN089 / Shutterstock

In a recent study in the journal Scientific Reports, researchers comprehensively evaluated the effects of heavy smoking across a range of oxidative stress, inflammatory, vascular dysfunction, and hematological biomarkers. They analyzed and compared bronchial biopsy samples and blood samples of male heavy smokers (n = 104) against their age and body mass index (BMI)-matched non-smoking counterparts (n = 94) in Erbil, Iraq.

Biomarker analyses revealed that heavy smokers present significantly higher oxidative stress markers, inflammatory biomarkers, and neutrophil counts than non-smokers. The study also found that heavy smokers exhibited higher red and white blood cell (RBC and WBC) counts and lower platelet counts compared to non-smokers. Hemoglobin (Hb) levels, however, did not significantly differ between the groups. Immunohistochemical analyses corroborated these findings, highlighting that neutrophil and eosinophil activity in heavy smokers is substantially elevated beyond baseline (non-smoker) values. Notably, lymphocyte counts and the neutrophil-to-lymphocyte ratio remained unchanged between smokers and non-smokers. These findings outline the biological impacts of heavy smoking and serve as a foundation for future anti-smoking interventions.

Importantly, blood samples were collected from all study participants (n = 198), including both smokers and non-smokers, rather than from smokers only. Bronchial biopsy samples were obtained from a subset of 35 individuals (19 smokers and 16 controls).

Background

Smoking is a significant health concern, associated with several severe medical conditions, including systemic inflammation, cancers, cardiovascular diseases (CVDs), respiratory infections, and endothelial dysfunction. Reports estimate that 8 million people die every year due to smoking-associated causes, a staggering 1.3 million of whom die from secondhand smoke.

Decades of research have established the physiological impacts of toxic cigarette components, including heavy metals, nicotine, and carbon monoxide. Unfortunately, most studies have focused on specific populations and only one or a few inflammation or oxidative stress biomarkers. In comparison, hematological, biochemical, and immunohistochemical markers remain understudied. A comprehensive analysis of a spectrum of smoking-associated biomarkers would provide future researchers with a holistic understanding of the habit’s systemic effects, paving the way for effective anti-smoking interventions.

About the study

The present study aims to address this knowledge gap by investigating the effects of heavy smoking on several oxidative stress, inflammatory, vascular dysfunction, and hematological biomarkers. The study was conducted between April and May 2024 and leveraged a cohort of 198 male participants (104 heavy smokers; age = 18 to 60 yrs) recruited by Par Private Hospital in Erbil, Iraq.

Heavy smoking was defined as smoking 20 or more cigarettes daily over an extended period (minimum 5 years). Heavy smokers were age and body mass index (BMI) matched with healthy (non-smoker) controls (n = 94). To minimize genetic confounds, all participants were of Kurdish ethnicity. All participants (n = 198) provided blood samples, and a subset of 35 (19 smokers and 16 controls) provided bronchial biopsy samples for experimental assays.

Oxidative stress was assessed via spectrometer measurements of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) activity. Inflammatory biomarkers, including serum endothelin-1 and interleukin-8 (IL-8), were quantified using Enzyme-Linked Immunosorbent Assay (ELISA).

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Myeloperoxidase-positive cells and eosinophilic granule 2-positive eosinophils, proxies for neutrophil and eosinophil activity, were investigated using immunohistochemical analysis. These activity profiles were supplemented with hematological data, specifically neutrophil and lymphocyte counts, red and white blood cell counts, platelet count, and hemoglobin levels. Systolic blood pressure was also measured, with no significant differences found between smokers and non-smokers.

Study findings

Spectrophotometer sample absorbance assays revealed significantly higher levels of oxidative stress markers in heavy smokers compared to their non-smoking counterparts. Specifically, malondialdehyde (MDA) and nitric oxide (NO) levels were elevated (p = 0.002 for both), while superoxide dismutase (SOD) activity was markedly reduced (p < 0.0001). All these markers are indicative of increased oxidative stress.

Spearman correlation heatmap among oxidative stress markers, inflammatory mediators, and granulocyte-related biomarkers in smokers. The figure illustrates the strength and direction of correlations between superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), endothelin-1, neutrophils, interleukin-8 (IL-8), EG2-positive eosinophils, and myeloperoxidase (MPO)-positive cells. Strong positive correlations were observed between EG2-positive cells and endothelin-1, IL-8, and MPO-positive cells, highlighting a potential interplay between oxidative stress and eosinophilic inflammation in smoking-associated pathophysiology. Significant correlations (p < 0.05) are indicated in the figure

ELISA assays revealed that inflammatory biomarkers were similarly elevated, with serum endothelin-1 and interleukin-8 (IL-8) levels significantly higher (p < 0.0001) in smokers than healthy males, suggesting enhanced vascular inflammation. Immunohistochemical analysis corroborated these findings, demonstrating heightened neutrophil and eosinophil activity.

Hematological analysis indicated elevated neutrophil counts in smokers (4.620 ± 0.152 (10⁹/l) vs. 3.996 ± 0.116 (10⁹/l)). In addition, heavy smokers had increased red and white blood cell counts and decreased platelet counts compared to controls. However, there was no significant difference in hemoglobin levels. Lymphocyte counts and the neutrophil-to-lymphocyte ratio remained unchanged. Notably, IL-8, endothelin-1, EG2-positive cells, and MPO-positive cells were found to be significantly correlated with one another. These findings collectively elucidate that heavy smoking is associated with systemic oxidative stress, inflammation, and vascular dysfunction.

Correlation analysis revealed significant positive relationships among IL-8, endothelin-1, myeloperoxidase-positive cells, and EG2-positive eosinophils, indicating coordinated inflammatory and immune responses in heavy smokers.

Conclusions

The present study highlights the observably and measurably detrimental impacts of heavy smoking on systemic health, demonstrating substantial elevations in oxidative stress markers, inflammatory biomarkers, and vascular dysfunction indicators. The study further identified a characteristic hematological profile in heavy smokers, including increased red and white blood cell counts and reduced platelet count. These markers have been previously associated with several communicable and non-communicable conditions, highlighting smokers’ increased susceptibility to various diseases and emphasizing the need for targeted public health interventions.

The study further provides valuable insights into the biological mechanisms underlying the health risks of heavy smoking, thereby providing a foundation for future studies to investigate and develop targeted strategies to combat smoking-related health issues. However, the authors note several limitations, including the cross-sectional study design, the exclusion of female participants due to cultural constraints, the relatively small number of bronchial biopsies, and the restriction to Kurdish ethnicity, which may limit generalizability.