Effect of Smoking on Macrophage Polarization in Periodontitis

NCT ID: NCT07323277

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2025-11-04

Brief Summary

This observational case-control study investigates the effect of smoking on macrophage polarization in the pathogenesis of periodontitis. Adult participants who were either systemically healthy smokers or non-smokers, and who met the clinical criteria for periodontal health or periodontitis, were included. Gingival tissue samples were collected during periodontal procedures performed after completion of Phase I periodontal therapy, and the expression levels of macrophage polarization markers (iNOS and Arginase-1) were analyzed using ELISA. In addition, comprehensive clinical periodontal measurements-including probing pocket depth, clinical attachment level, bleeding on probing, Plaque Index, and Gingival Index-were recorded to evaluate the relationship between smoking status, inflammatory burden, and macrophage phenotype. The study aims to clarify how smoking modulates the balance between M1 and M2 macrophage responses in periodontal tissues.

Detailed Description

Periodontitis is a chronic inflammatory disease in which macrophage polarization plays a key regulatory role in the host immune response. Smoking is a well-established risk factor that alters inflammatory pathways and immune cell behavior. This study was designed to examine how smoking influences macrophage polarization-specifically the balance between M1 (iNOS-mediated) and M2 (Arginase-1-mediated) phenotypes-in periodontal tissues.

Systemically healthy adult participants were recruited and categorized into four groups based on smoking status and periodontal condition: (1) healthy non-smokers, (2) periodontitis non-smokers, (3) healthy smokers, and (4) periodontitis smokers. Gingival tissue samples (approximately 2×2 mm) were collected during periodontal surgical procedures performed after completion of Phase I periodontal therapy, immediately stored at -80 °C, and processed for biochemical analysis. Comprehensive clinical periodontal measurements-including probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), Plaque Index (PI), and Gingival Index (GI)-were recorded on the same day to evaluate periodontal status and inflammatory burden. ELISA was used to quantify iNOS and Arginase-1 levels in gingival tissues.

The primary objective of this study is to determine whether smoking shifts the macrophage phenotype toward a more pro-inflammatory M1 profile or suppresses M2-associated regulatory pathways in the context of periodontitis. The findings are expected to contribute to a better understanding of smoking-related alterations in periodontal immune mechanisms.

Conditions

Periodontitis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Healthy Non-Smokers

Systemically healthy individuals who do not smoke and present with clinically healthy periodontal status. Gingival tissue samples were collected after completion of Phase I periodontal therapy during routine periodontal procedures.

No interventions assigned to this group

Periodontitis Non-Smokers

Systemically healthy individuals diagnosed with periodontitis who do not smoke. Gingival tissue biopsies were obtained after completion of Phase I periodontal therapy during periodontal surgical procedures.

No interventions assigned to this group

Healthy Smokers

Systemically healthy individuals who smoke (≥10 cigarettes/day) and exhibit clinically healthy periodontal status. Gingival tissue samples were collected after completion of Phase I periodontal therapy during periodontal procedures.

Smoking Exposure

Intervention Type: OTHER

Exposure to cigarette smoking, defined as smoking ≥10 cigarettes per day. Participants were classified as smokers or non-smokers based on self-reported smoking status.

Periodontitis Smokers

Systemically healthy individuals who smoke (≥10 cigarettes/day) and are clinically diagnosed with periodontitis. Gingival tissue samples were collected after completion of Phase I periodontal therapy during periodontal surgical procedures.

Smoking Exposure

Intervention Type: OTHER

Exposure to cigarette smoking, defined as smoking ≥10 cigarettes per day. Participants were classified as smokers or non-smokers based on self-reported smoking status.

Interventions

Smoking Exposure

Exposure to cigarette smoking, defined as smoking ≥10 cigarettes per day. Participants were classified as smokers or non-smokers based on self-reported smoking status.

Intervention Type: OTHER

Eligibility Criteria

Exclusion Criteria

• Individuals who did not consent to participate in the study
• History of any periodontal treatment within the past 6 months
• Use of systemic antibiotics within the past 3 months
• Pregnancy or lactation
• Psychological or physical conditions that may interfere with cooperation during clinical examination
• History of substance or alcohol abuse
• Presence of severe malocclusion or ongoing orthodontic treatment
• Acute dental pain due to caries, abscess, or other odontogenic infections
• Presence of systemic diseases with oral manifestations or any systemic condition known to affect periodontal tissues
• History of malignancy
• Use of medications that can influence periodontal parameters (e.g., anti-inflammatory drugs) within the past 3 months
• Participation in another scientific or clinical research study within the past 3 months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Suleyman Demirel University

OTHER

Sponsor Role: lead

Responsible Party

Asli Ege Ozdamar

PhD Candidate / Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zuhal YETKİN AY, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Süleyman Demirel University, Faculty of Dentistry, Department of Periodontology

Locations

Süleyman Demirel University Faculty of Dentistry, Department of Periodontology

Isparta, Isparta, Turkey (Türkiye)

Countries

Turkey (Türkiye)

Other Identifiers

TDK-2024-9512

Identifier Type: OTHER

Identifier Source: secondary_id

SDU-Perio-iNOS-ARG1-01

Identifier Type: -

Identifier Source: org_study_id