Prevalence of Antineutrophil Cytoplasmic Antibodies and Antinuclear Antibodies in Patients with Pulmonary Tuberculosis: A Tertiary Care Center Experience from North India

Background: Tuberculosis (TB) can have manifestations closely mimicking autoimmune diseases. The prevalence of autoantibodies in TB varies among different populations. Objectives: To study the prevalence of anti-neutrophilic cytoplasmic antibodies (ANCA) and antinuclear antibodies (ANA) in pulmonary tuberculosis (PTB). Methods: This was a cross-sectional, observational study. Subjects with microbiologically confirmed PTB, either via smear or culture positivity on sputum or bronchoalveolar lavage (BAL) fluid, or positive rapid diagnostic tests were included. ANCA against proteinase-3 (PR3), myeloperoxidase (MPO), lactoferrin, and elastase were tested using an enzyme-linked immunosorbent assay (ELISA). ANA was detected using indirect immunofluorescence (IIF). Results: Eighty-nine subjects with a median [interquartile range (IQR)] age of 28 (20–46) years, 67.4% males, were recruited. Eighty-one subjects had microbiological confirmation on sputum examination, and eight required examination of BAL fluid. Sera were drawn from 62 treatment-naïve subjects, the rest (27) were on antitubercular therapy (ATT). Eighty-six (96.6%) subjects tested positive for anti-elastase antibody, seven of which were also positive for anti-PR3. None were positive for anti-MPO and anti-lactoferrin. Six (6.7%) subjects tested positive for ANA. None of the subjects had features of underlying connective tissue disease or vasculitis. Conclusion: PTB patients showed a high prevalence of anti-elastase and a low prevalence of ANA and anti-PR3 antibodies. ANCA positivity should be interpreted with caution in TB endemic areas. The role of anti-elastase antibodies in differentiating TB from ANCA-associated vasculitis (AAV) needs further research.

Feasibility and impact of screening for venous thromboembolism in treatment?naive lung cancer patients–Results of a prospective cohort study

Background: Venous thromboembolism (VTE) in cancer remains underdiagnosed. This prospective study aimed to evaluate the feasibility of screening for VTE in lung cancer (LC) patients. We assess the incidence of VTE, its risk factors, and effects on overall survival (OS). Methods: Consecutive treatment?naive LC patients were screened for deep venous thrombosis (DVT) with compression ultrasonography and pulmonary thromboembolism (PTE) with computed tomography pulmonary angiography (CTPA) at diagnosis and after 3 months of treatment. The incidence rate of VTE (DVT and/or PTE) was calculated. Risk factors associated with VTE were assessed using logistic regression analysis. All participants were followed?up to 1 year after enrollment. OS was compared in LC subjects with and without VTE, using the Cox proportional hazard analysis. Results: Around 301 subjects with LC (stages IIIB?IV accounted for 83.1%) were enrolled, of which 16 had VTE (5.3%). The incidence rate of VTE was 90 per 1000 person?years (PY). PTE was asymptomatic in 27.3% of cases while all DVT episodes were symptomatic. The incidence rate of asymptomatic PTE identified during the screening was 17 per 1000 PY. The median duration from LC diagnosis to the VTE event was 96.5 days. Median OS was significantly less in VTE patients [161 versus 311 days; P = 0.007] and death was attributable to VTE in 50%. After adjusting for covariates, VTE (hazard ratio [HR] = 2.1), smoking (HR = 1.7), and Eastern cooperative oncology group performance status ?2 (HR = 1.6) were independently associated with poor OS in LC. Conclusions: VTE occurs in approximately 1 in 20 newly?diagnosed patients with LC and is associated with decreased OS. Screening for PTE may be considered even in resource?limited settings

A study on the effect of mobile phone use on sleep

Background & objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Results: Of the 566 participants, 128 (22.61%) had PSQI ?5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. Interpretation & conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study

Does awareness of diagnosis influence health related quality of life in north Indian patients with lung cancer.

Background & objectives: Several patients with cancer in India are not aware of their diagnosis. We evaluated the impact of awareness of cancer diagnosis on health-related quality of life (HRQL) in newly diagnosed patients with lung cancer. Methods: A total of 391 treatment-naïve patients with lung cancer, seen at the Lung Cancer Clinic of a tertiary care hospital in north India, were categorized into those aware of their diagnosis (group A) and those not aware (group B). All patients answered Hindi versions of abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-Bref) and European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), and its lung cancer module, EORTC QLQ-LC13. Various domain scores were computed and compared between the two groups. Analysis of covariance was used to determine significance of differences after adjustment for potential confounding factors. Results: Only 117 (29.9%) patients were aware of their diagnosis. Of all, 302 (77.2%) patients had non-small cell lung cancer, and 301 (77.0%) had advanced disease. All HRQL domain scores were similar between the two groups, except that group B patients had significantly poorer median (interquartile range) Physical [39.3 (28.6-50.0) vs 46.4 (28.6-57.1)] and Environment [46.9 (40.6-56.3) vs 53.1 (0.6-65.6)] domain scores of WHOQOL-Bref, and Physical function [60.0 (40.0-73.3) vs 66.7 (46.7-80.0)] and Fatigue [66.7 (55.6-77.8) vs 66.7 (44.4-66.7)] scores of QLQ-C30. After adjusting for gender, age, education, family income, and tumour extent, these differences were not significant. Interpretation & conclusions: Disclosure of cancer diagnosis, or lack of it, had no significant impact on HRQL in patients with lung cancer after adjustment of potential confounders.

Clinical experience on use of oral EGFR-TKIs as first-line treatment of advanced NSCLC from a tertiary care centre in North India and implications of skin rash.

Background. Limited data are available from India on treatment outcomes with oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in newly diagnosed non-small cell lung cancer (NSCLC). We studied the demographic profile and treatment outcomes of patients with NSCLC, receiving first-line treatment with oral EGFR-TKIs. Methods. Retrospective study of newly diagnosed NSCLC patients treated with oral EGFR-TKIs over a 4-year period at a tertiary care institute in North India. Results. Of 76 patients studied, females and non-smokers constituted 32.9% and 48.7%, respectively. Majority of patients had adenocarcinoma (59.2%), stage IV (64.5%) disease and Karnofsky performance status <70 (74.5%). Gefitinib was the most frequently used EGFR-TKI (92.1%). Most common indication for the use of EGFR-TKIs was poor performance status (65.8%). Among assessable patients, disease control and progressive disease were evident in 66% and 34%, respectively. Most common side effects were skin rash (17%) and diarrhoea (10.6%). Patients with and without skin rash differed significantly in relation to objective response to treatment (100% versus 23.1%) and overall survival (median not reached versus 178 days). On multivariate logistic regression analysis, malignant pleural effusion was associated with occurrence of rash (odds ratio=0.19; 95% confidence interval = 0.04-0.95; p=0.04). Conclusions. Oral EGFR-TKIs appear to be useful for the treatment of clinically selected patients with advanced NSCLC. Occurrence of skin rash was independently associated with treatment response and better survival in the current study.

Passive smoking, Indoor air pollution and Childhood tuberculosis: A case control study.

Background: Passive smoking and biomass fuel use most probably are more harmful to children than adults for two reasons. The first one is children’s respiratory and immune systems are not fully developed. Secondly, they spend more time at home and are, therefore, likely to experience more intense and prolonged smoke exposure. Aims: This study was planned to find out if there is any association between childhood tuberculosis and exposure to passive smoking and biomass fuel. Methods: A hospital-based case control study was done. All registered consecutive newly diagnosed pediatric tuberculosis cases (0-14 years) from the outpatient department of a tertiary care hospital were recruited as cases. Age and sex matched controls were recruited from a public general hospital of the same locality. A semi-structured, pre-coded interview schedule was administered to parents or legal caregivers of all subjects after obtaining informed written consent. Results: A total of 200 cases and 200 controls were recruited in the study period. The factors which were significantly associated with development of tuberculosis were education of the mother, (OR 1.411, 95% CI 0.888-2.243, p-0.001), a family member having tuberculosis in the last two years and residing in the same house (OR 2.797, 95% CI 1.353-5.789; p-0.004), being a passive smoker (OR 1.725, 95% CI 1.142-2.605; p-0.009). No association between biomass cooking fuel use and development of tuberculosis was found. Conclusion: Passive smoking is associated with development of childhood tuberculosis. This requires health education programmes and medical antitobacco advice and services.

Domestic cooking fuel exposure and tuberculosis in Indian women.

Background. A case-controlled study was undertaken to find out the possible relationship of biomass fuel and pulmonary tuberculosis. Methods. Ninety-five non-smoking females with sputum positive tuberculosis (TB) and 109 healthy controls were interviewed using a questionnaire to obtain detailed information on type of fuel used in homes, duration of cooking, passive smoking, location of kitchen, socio-economic status, adequacy of ventilation, number of people per room and respiratory symptoms occurring during cooking. Odds ratio (OR) was ascertained by logistic regression analysis. Results. The cases were from a low socio-economic status and the kitchens used by them were inadequately ventilated. Controls had less smoke accumulation in the rooms while cooking and cases had associated respiratory symptoms more often. Logistic regression analysis revealed that TB was significantly influenced by the location of the kitchen (OR 0.201, 95% confidence interval [CI] 0.08-0.51) and the presence of respiratory symptoms while cooking (OR 10.70, 95% CI 2.90- 39.56). The odds of having TB did not differ significantly among various fuel types either on univariate (OR 0.99, 95% CI 0.45- 2.22) or multivariate analysis (OR 0.60, 95% CI 0.22-1.63). Conclusions. No association was found between type of fuel used and TB. However, low socio-economic status, smoky rooms, location of the kitchen, ventilation and associated respiratory symptoms during cooking are likely to be important contributors.

Inflammatory cytokine levels in induced sputum and bronchoalveolar lavage fluid in pulmonary sarcoidosis.

BACKGROUND: The immune inflammatory process in patients with sarcoidosis is not only compartmentalized within the alveolar walls, but also involves the bronchial airways. Analysis of induced sputum has been used as a non-invasive tool for investigating the airways and may reflect the endobronchial and parenchymal inflammation in patients with sarcoidosis. This present study was designed to measure the soluble pro-inflammatory cytokine levels interleukin-1 (IL-1), interleukin-6 (IL-6), tumuor necrosis factor-alpha (TNF-alpha) and percentage of macrophages expressing these cytokines in induced sputum and bronchoalveolar lavage (BAL) fluid in patients with pulmonary sarcoidosis. METHODS: Sputum induction and BAL was carried out in 27 patients with newly diagnosed sarcoidosis. Control group consisted of six patients with a normal chest radiograph (three patients with carcinoma esophagus and three patients with doubtful history of hemoptysis). Induced sputum was also obtained from 10 non-smoking, non-atopic healthy controls. RESULTS: Percentage of macrophages expressing pro-inflammatory cytokines and soluble cytokine levels in induced sputum were higher in patients with sarcoidosis compared to both groups of controls. There was good correlation between IL-6 and TNF-alpha levels (r = 0.49, 0.58 p < 0.05) and percentage of macrophages expressing all three cytokines (r = 0.56-0.71, p < 0.01) between induced sputum and BAL fluid. Mild positive correlation between cytokine levels in sputum and age was also noted (r = 0.33-0.38, p < 0.05). CONCLUSIONS: Induced sputum may reflect changes in cytokine milieu in BAL in sarcoidosis.

Urinary levels of nicotine & cotinine in tobacco users.

BACKGROUND & OBJECTIVES: Of the various biochemical markers used to validate the smoking status of a person, nicotine and continine are considered as good markers for both active and passive smoking. In the present study an attempt was made to estimate urinary levels of nicotine and cotinine in healthy individuals from north India using different types of tobacco to identify and validate the smoking status. METHODS: Twenty four hour urine sample of 130 healthy volunteers (smokers=70, passive smokers=20, tobacco chewers=20, non smokers=20) were analyzed by high-pressure liquid chromatography (HPLC) assay. Smokers were divided into different groups, viz., cigarette, bidi and hooka smokers. RESULTS: The mean values of nicotine (ng/ml) and cotinine (ng/ml) in urine were highest in cigarette smokers (nicotine=703.50+/-304.34; cotinine=2736.20+/-983.29), followed by hooka smokers (nicotine 548.0+/-103.47 and cotinine 2379.0+/-424.25), and bidi smokers (nicotine=268.53+/-97.62, cotinine=562.60+/-249.38). There was no correlation of nicotine or cotinine values with smoking index. In passive smokers (nicotine=109.75+/-22.33, cotinine=280.75+/-86.30) and in nonsmokers, the values were much lower (nicotine=55.00+/-13.71, cotinine=7.30+/-2.47) compared to smokers. In tobacco chewers, the values for nicotine and cotinine were 447.75+/-145.09 and 2178.30+/-334.29 respectively. INTERPRETATION & CONCLUSION: All forms of tobacco users had significantly higher values compared to passive smokers and nonusers. Thus, cotinine and nicotine levels in urine may be considered as good indicators to assess the exposure to tobacco in our population.