Unmasking the Silent Threat: Periodontal Health's Impact on COPD Severity and Hospitalization.

OBJECTIVE: This study investigated the relationship between chronic obstructive pulmonary disease (COPD) and periodontitis, focusing on how periodontal health impacts COPD airflow limitation, exacerbations, and hospitalization. BACKGROUND: Periodontitis, a multifactorial inflammatory disease, is characterized by destruction of tooth-supporting structures, while COPD is a global pulmonary disorder with high mortality. METHODS: A total of 199 COPD patients aged over 40 years underwent lung function tests (spirometry), 6 min walk test, and St George's Respiratory Questionnaire-COPD (SGRQ-C) to assess lung health. Periodontal indices such as probing depth (PD), clinical attachment loss (CAL), and plaque index (PI) were assessed. RESULTS: We found a significant negative correlation between periodontal disease severity and lung function (lower FEV1, FVC, and FEV1/FVC ratio) after adjusting for smoking. Likewise, periodontal parameters (PPD, PI, and CAL) exhibited negative correlations with lung function. These periodontal indices were independently associated with airflow limitation severity, exacerbations frequency, and prior-year hospitalization. Linear regression indicated that each unit increase in PPD, PI, and CAL corresponded to estimated increases in GOLD airflow limitation grading (0.288, 0.718, and 0.193, respectively) and number of exacerbations (0.115, 0.041, and 0.109, respectively). In logistic regression, PPD, PI, and CAL adjusted odds ratios (ORs) were estimated to increase by 1.29 (95%CI: 1.03-1.62), 3.04 (95%CI: 1.28-7.2), and 1.26 (95%CI: 1.06-1.49), respectively, for hospitalization in previous year. CONCLUSION: Periodontitis is associated with COPD airflow limitation, exacerbation, and hospitalization, with PI being the most clinically relevant periodontal factor. Dentists and physicians should monitor and increase awareness among COPD patients to maintain oral hygiene for prevention of periodontal diseases and mitigate its effect on COPD progression.

The Assessment of Serum Fibronectin Levels as a Potential Biomarker for the Severity of Drug-Sensitive Pulmonary Tuberculosis: A Pilot Study.

BACKGROUND: Tuberculosis (TB) is a global health burden caused by Mycobacterium tuberculosis (Mtb) infection. Fibronectin (Fn) facilitates Mtb attachment to host cells. We studied the Fn levels in smear-positive TB patients to assess its correlation with disease severity based on sputum smears and chest X-rays. METHODS: Newly detected consecutive sputum AFB-positive pulmonary TB patients (n = 78) and healthy control subjects (n = 11) were included. The mycobacterial load in the sputum smear was assessed by IUATLD classification, ranging from 0 to 3. The severity of pulmonary involvement was assessed radiologically in terms of both the number of zones involved (0-6) and as localized (up to 2 zones), moderate (3-4 zones), or extensive (5-6 zones). The serum human fibronectin levels were measured by using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Catalogue No: CK-bio-11486, Shanghai Coon Koon Biotech Co., Ltd., Shanghai, China). RESULTS: The PTB patients showed lower Fn levels (102.4 ± 26.7) compared with the controls (108.8 ± 6.8), but they were not statistically significant. Higher AFB smear grades had lower Fn levels. The chest X-ray zones involved were inversely correlated with Fn levels. The Fn levels, adjusted for age and gender, decreased with increased mycobacterial load and the number of chest radiograph zones affected. A Fn level <109.39 g/mL predicted greater TB severity (sensitivity of 67.57% and specificity of 90.38%), while a level <99.32 pg/mL predicted severity based on the chest radiology (sensitivity of 84.21% and specificity of 100%). CONCLUSIONS: The Fn levels are lower in tuberculosis patients and are negatively correlated with severity based on sputum mycobacterial load and chest radiographs. The Fn levels may serve as a potential biomarker for assessing TB severity, which could have implications for early diagnosis and treatment monitoring.

Pilot study investigating diagnostic utility of serum MMP-1 and TGF-ß1 in asthma in 'real world' clinical practice in India.

AIMS: At a tissue level, matrix metalloproteinase-1 (MMP-1) and transforming growth factor-beta 1 (TGF-ß1) contribute to allergic airway inflammation, tissue remodelling and disease severity in asthma via different pathways. Their peripheral blood levels and role in diagnosis and therapeutic monitoring has not been adequately explored. We investigated the association between MMP-1 and TGF-ß in moderate and severe persistent asthma and evaluated their performance characteristics by constructing receiver operating characteristic curves. METHODS: Serum MMP-1 and TGF-ß1 were measured using ELISA in 75 adults; moderate persistent asthma (n=25), severe persistent asthma (n=25) and healthy community controls (n=25). Severity of asthma was determined as per Global Initiative for Asthma guidelines. Subjects were followed up for 3 months and treatment responsiveness was assessed by spirometry and symptom response. RESULTS: Serum MMP-1 and TGF-ß1 were significantly elevated in asthmatics compared with controls (p<0.0001 and p<0.01). While serum MMP-1 was elevated in severe asthma compared with moderate asthma (p<0.05), TGF-ß1 was lower in severe asthma compared with moderate asthma (p<0.05). The performance characteristics of serum MMP-1 and TGF-ß1 were promising in this cohort with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 82%, 100%, 100% and 99% and 62%, 100%, 100% and 97.8%, respectively; sensitivity of MMP-1 being superior. CONCLUSION: This pilot study showed that serum MMP-1 and TGF-ß1 levels are elevated in chronic asthma and may serve as a useful adjunct in differentiating moderate from severe asthma. A large multicentre study in well characterised cohort of asthmatics is warranted to investigate their role in diagnosis and therapeutic monitoring.

Circulating Secretoglobin Family 1A Member 1 (SCGB1A1) Levels as a Marker of Biomass Smoke Induced Chronic Obstructive Pulmonary Disease.

Secretoglobin family 1A member 1 (SCGB1A1) alternatively known as club cell protein 16 is a protective pneumo-protein. Decreased serum levels of SCGB1A1 have been associated with tobacco smoke induced chronic obstructive pulmonary disease (TS-COPD). Exposure to biomass smoke (BMS) is an important COPD risk factor among women in low and lower-middle income countries. Therefore, in a cross-sectional study (n = 50/group; total 200 subjects) we assessed serum SCGB1A1 levels in BMS-COPD subjects (11 male, 39 female) compared to TS-COPD (all male) along with TS-CONTROL (asymptomatic smokers, all male) and healthy controls (29 male, 21 female) in an Indian population. Normal and chronic bronchitis like bronchial mucosa models developed at the air-liquid interface using human primary bronchial epithelial cells (3 donors, and three replicates per donor) were exposed to cigarette smoke condensate (CSC; 0.25, 0.5, and 1%) to assess SCGB1A1 transcript expression and protein secretion. Significantly (p < 0.0001) decreased serum SCGB1A1 concentrations (median, interquartile range, ng/mL) were detected in both BMS-COPD (1.6; 1.3-2.4) and TS-COPD (1.8; 1.4-2.5) subjects compared to TS-CONTROL (3.3; 2.9-3.5) and healthy controls (5.1; 4.5-7.2). The levels of SCGB1A1 were positively correlated (r = 0.7-0.8; p < 0.0001) with forced expiratory volume in 1 s, forced vital capacity, their ratios, and exercise capacity. The findings are also consistent within the BMS-COPD sub-group as well. Significantly (p < 0.03) decreased SCGB1A1 concentrations were detected with severity of COPD, dyspnea, quality of life, and mortality indicators. In vitro studies demonstrated significantly (p < 0.05) decreased SCGB1A1 transcript and/or protein levels following CSC exposure. Circulating SCGB1A1 levels may therefore also be considered as a potent marker of BMS-COPD and warrant studies in larger independent cohorts.

Inflammatory Biomarkers Interleukin 1 Beta (IL-1ß) and Tumour Necrosis Factor Alpha (TNF-α) Are Differentially Elevated in Tobacco Smoke Associated COPD and Biomass Smoke Associated COPD.

Chronic obstructive pulmonary disease (COPD), the leading cause of mortality and morbidity worldwide, is characterized by abnormal activation of inflammatory cells. The increased pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), further amplify the inflammation. We evaluated the dose response relationship of IL-1ß and TNF-α levels and severity of airflow limitation, and differential responses in IL-1ß and TNF-α between biomass COPD (BMS-COPD) and tobacco smoke COPD (TS-COPD) using a case control design in 160 subjects. Patients with COPD had higher serum levels of both IL-1ß and TNF-α compared to healthy controls. A large difference in TNF-α was observed between TS-COPD and BMS-COPD, where TS-COPD patients had much higher levels. Serum IL-1ß levels were higher in BMS-COPD. Levels of IL-1ß correlated better with severity of airflow limitation than TNF-α levels. Both TNF-α and IL-1ß levels had a negative linear relationship with Forced Expiratory Volume in 1st second (FEV1) and six-minute walk distance. The correlations were stronger with FEV1 than six-minute walk distance. The correlations of TNF-α and IL-1ß with St George Respiratory Questionnaire (SGRQ) scores and body mass index (BMI) were not significant. In conclusion, the levels of pro-inflammatory cytokines TNF-α and IL-1ß are differently elevated in TS-COPD and BMS-COPD, respectively.

Vitamin D deficiency is associated with chronic obstructive pulmonary disease and exacerbation of COPD.

INTRODUCTION: Low Vitamin D levels have been associated with Chronic Obstructive Pulmonary Disease (COPD) and acute exacerbations. OBJECTIVES: There is a paucity of data on Vitamin D and COPD, its severity and exacerbations in populations that are exposed to sunlight regularly with high levels of physical activity most of their lives. METHODS: Serum levels of 25-OH-Vitamin-D were assessed in 100 COPD subjects and 100 age- and gender-matched controls from the rural community-based MUDHRA cohort in South India. Levels of <20 ng/mL were defined as Vitamin D deficiency. Smoking habits, occupation, Charlson co-morbidity index, Standard of living index(SLI), body mass index(BMI), 6-minute walking distance were examined for associations with logistic regression between controls and COPD subjects. Unconditional logistic regression was used to examine the association with exacerbation of COPD. RESULTS: Vitamin D deficiency was observed in 64.5% (95%CI 57.7-70.8) of the subjects in spite of regular exposure to sunlight. Subjects with COPD had higher risk of Vitamin D deficiency (Adjusted OR: 5.05; 95%CI 1.4-17.8) as compared to controls. Amongst subjects with COPD, Vitamin D deficient subjects were three times more likely to have exacerbations in the previous year (Adjusted OR:3.51; 95%CI 1.27-9.67) as compared to COPD subjects without Vitamin D deficiency. Levels of Vitamin D <20.81 ng/mL and <18.45 ng/mL had the highest levels of combined sensitivity and specificity for COPD and acute exacerbation of COPD (AECOPD) respectively. CONCLUSION: In a rural population exposed to sunlight many hours a day throughout their lives, low Vitamin D levels were associated with COPD and exacerbations of COPD.

The Mysuru stUdies of Determinants of Health in Rural Adults (MUDHRA), India.

Between 2006 and 2010, in 16 randomly selected villages in rural areas of Mysore district, in south India, 8,457 subjects aged 30 and above were screened for symptoms of chronic respiratory disease. Of the 8,457 subjects, 1,692 were randomly invited for further evaluation of lung function and chronic obstructive pulmonary disease (COPD) by spirometry, and 1,085 of these subjects underwent lung function assessments for prevalent COPD and its risk factors. These 1,085 subjects, who were then aged between 35 and 80 years, constituted the Mysuru stUdies of Determinants of Health in Rural Adults (MUDHRA) cohort. Among other findings, threshold of biomass fuel smoke exposure suitable for use as a dichotomous risk factor for the diagnosis of chronic bronchitis was established, with a minimum biomass smoke exposure index of 60 found to be significantly associated with an elevated risk of developing chronic bronchitis. Five years later (between 2014 and 2016), 869 of the 1,085 participants were followed up with repeat lung function assessments for incident COPD and all-cause mortality. A subset of these participants (n=200) underwent blood tests for vitamin D levels, antioxidant activity, an assessment for anxiety and depression, and another subset (n=98) underwent a bioplex assay for 40 serum cytokines.

Putative Systemic Biomarkers of Biomass Smoke-Induced Chronic Obstructive Pulmonary Disease among Women in a Rural South Indian Population.

RATIONALE: Exposure to biomass smoke (BMS) has been implicated in chronic obstructive pulmonary disease (COPD). About 3 billion people worldwide use biomass fuel for cooking and heating. Women in rural communities of low- and lower-middle-income countries are disproportionately exposed to massive amounts of BMS during active cooking hours (4-6 h/day). Therefore, BMS exposure is considered as a risk factor for COPD in the same order of magnitude as tobacco smoke. In rural India, due to cultural reasons, women are the primary cook of the family and are mostly nonsmokers. Thus, BMS-induced COPD is predominant among rural Indian women. However, BMS-COPD remains a relatively unexplored health problem globally. Therefore, we investigated the serum chemokine and cytokine signatures of BMS-COPD and tobacco smoke-induced COPD (TS-COPD) patients compared to their control in a rural South Indian population for this field study. METHODS: Concentrations of 40 serum chemokines and cytokines were measured using a multiplexed immunoassay. The study cohort consisted of BMS-COPD (female; n = 29) and BMS-exposed subjects without COPD (BMS-CONTROL; female; n = 24). For comparison, data from TS-COPD patients (male, n = 23) and tobacco smokers without COPD (TS-CONTROL; male, n = 22) were investigated. Subjects were matched for age, sex, and biomass exposure. Tobacco consumption was slightly higher in TS-COPD subjects compared to TS-CONTROL. BMS-exposed and TS-exposed subjects (currently exposed) were from the same locality with similar dwelling habits and socioeconomic status. A validated structured questionnaire-based survey and spirometry was performed. An additional control group with no tobacco and BMS exposure (TS-BMS-CONTROL; n = 15) was included. Statistical significance was set at p ≤ 0.01. RESULTS: Serum median concentrations (pg/ml) of CCL15 [8799.35; 5977.22], CCL27 [1409.14; 1024.99], and CXCL13 [37.14; 26.03] were significantly higher in BMS-CONTROL compared to BMS-COPD subjects. Nine analytes exhibited higher concentrations in TS-CONTROL compared to TS-COPD subjects. Comparison of chemokine and cytokine concentrations among BMS-COPD versus TS-COPD and BMS-CONTROL versus TS-CONTROL subjects also revealed distinct molecular signatures. CONCLUSION: Our data identifies CCL27 and CXCL13 as putative, plausibly homeostatic/protective biomarkers for BMS-COPD within the investigated population that warrants validation in larger and multiple cohorts. The findings further indicate exposure-specific systemic response of chemokines and cytokines.