Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Diagnoses and management of adult cough: An Indian Environmental Medical Association (EMA) position paper.

BACKGROUND: Cough is a common yet distressing symptom that results in significant health care costs from outpatient visits and related consultations. OBJECTIVE: The understanding of the pathobiology of cough in recent times has undergone an evolution with Cough hypersensitivity syndrome (CHS) being suggested in most cases of dry cough. However, in the case of productive cough, ancillary mechanisms including impaired Mucociliary clearance, in addition to hypermucosecretory bronchospastic conditions of Smoker's cough, asthma-COPD overlap, bronchiectasis, and allergic bronchopulmonary aspergillosis, need to be critically addressed while optimizing patient care with symptomatic therapy in outpatient settings of India. METHODS: In this review, evidence-based graded recommendations on use of antitussives - & protussives as a Position Paper were developed based on the Level and Quality of Scientific evidence as per Agency for Health Care and Quality (AHRQ) criteria listing and Expert opinions offered by a multidisciplinary EMA panel in India. RESULTS: Management of acute or chronic cough involves addressing common issues of environmental exposures and patient concerns before instituting supportive therapy with antitussives or bronchodilatory cough formulations containing mucoactives, anti-inflammatory, or short-acting beta-2 agonist agents. CONCLUSION: The analyses provides a real world approach to the management of acute or chronic cough in various clinical conditions with pro- or antitussive agents while avoiding their misuse in empirical settings.

Estrogen receptor gene 1 expression in caprine and its effect on fertility.

The present study was undertaken to analyze the expression pattern of estrogen receptor 1 gene (ESR1) in Barbari bucks (fertile and non-fertile) identified on the basis of seminal quality traits and fertility trials. RNA was extracted from the spleen by Trizol method. The expression pattern of ESR1 gene was analyzed using real time polymerase chain reaction (RT-PCR). The expression pattern of ESR1 gene was analyzed by RT-PCR (Roche LC-480). Relative quantification by RT-PCR indicated that the ESR1 gene expression showed more fold in fertile bucks as compared to non-fertile.

Molecular expression of caprine estrogen receptor gene 1 in reproductive and non-reproductive tissues.

During the last decades, physiological effects of oestrogens have been increasingly explored by scientists and biotechnologists. Estrogens exert a wide range of effects on a large variety of cell types. Oestrogen and its receptors are essential for sexual development and reproduction. Estrogen receptor alpha is a nuclear receptor activated by the hormone oestrogen. In male, ERα is encoded by the gene estrogen receptor gene 1 (ESR1), responsible for better fertility. The ESR1 is involved in the reabsorption of luminal fluid during the transit of spermatozoa from the testis to the head of the epididymis which is important for their survival and maturation during epididymal storage. The absence of ESR1 leads to reduced epididymal sperm content, reduced sperm motility and fertilizing ability. Therefore, this is a good startby to study the expression pattern of estrogen receptor 1 gene in high-fertile (G1) and low-fertile (G2) bucks of Jamunapari and Barbari breeds identified on the basis of seminal quality traits and fertility trials. RNA was extracted from the tissues by TRIzol method. The identification and expression pattern of caprine ESR1 gene was analysed by real-time PCR (Roche LC-480). Our work shows that the relative quantification by RT-PCR indicates more fold in head of epididymis as compared to spleen of caprine ESR1 gene. Furthermore, the RT-PCR indicated that fertile bucks of Jamunapari breed have more fold value as compared to Barbari breed in respect of reproductive organ.

Effects of smoking on asthma.

Tobacco smoking has several adverse associations with asthma.The odds ratios for prevalence of asthma are high for both active smoking and ETS exposures. In-utero exposure of foetus from maternal smoking, as well as its tertiary exposure from maternal passive-smoking are also known to be responsible for development of asthma in childhood. Smoking adversely affects the health and treatment-outcomes of asthma. There are increased requirements of drugs for smoker and ETS exposed asthmatics. Smoking is also an important factor in the development of airway remodelling, fixed airway obstruction and an exaggerated lung function decline.

Assessment of health-related quality of life in patients with pulmonary tuberculosis under programme conditions.

SETTING: Newly diagnosed pulmonary tuberculosis (PTB) patients starting treatment under the Revised National Tuberculosis Control Programme (RNTCP) in a North Indian city. OBJECTIVE: To quantify impairment in health-related quality of life (HRQoL) of PTB patients at the time of diagnosis and during treatment, and to assess the utility of these assessments as a measure of outcome under programme conditions. DESIGN: HRQoL was assessed using the Hindi version of the 26-item World Health Organization Quality of Life (WHOQOL-BREF) scale at the start and end of the intensive phase and at completion of treatment. Four domain scores-physical, psychological, social relationships and environment-were calculated and compared between groups, based on different patient and disease characteristics. Psychometric evaluation was conducted by assessing acceptability, validity and responsiveness of the questionnaire. RESULTS: A total of 2654 HRQoL assessments were performed among 1034 patients. Domain scores were generally better among men, urban residents, younger patients, patients with higher socio-economic status and those with less severe disease. The WHOQOL-BREF demonstrated good psychometric properties, and domain scores improved with treatment. Residual HRQoL impairment was noted in some patients even at treatment completion. CONCLUSION: HRQoL is impaired in patients with PTB, and improves rapidly and significantly with programme-based treatment. HRQoL assessment can be used as an adjunct outcome measure for patients treated by the RNTCP.

Tuberculous lymphadenopathy: a multicentre operational study of 6-month thrice weekly directly observed treatment.

SETTING: Eight operational locations for the Revised National Tuberculosis Control Programme in six Indian states. OBJECTIVE: To assess the 6-month efficacy of an intermittent thrice-weekly directly observed treatment (DOT) regimen for tuberculous peripheral adenopathy and the need for prolongation of treatment to 9 months for non-resolution of lymphadenopathy. DESIGN: Patients aged >5 years with tuberculous lymphadenopathy were included in the study. Patients were evaluated for resolution at repeat visits following treatment. Those with poor resolution at 6 months were randomised to extended treatment up to 9 months or observation without additional treatment. RESULTS: Resolution of lymphadenopathy was observed at the end of 6 months in 517/551 (93.8%) patients. There was a significant difference in response among patients with and those without the presence of systemic symptoms. There was no association between treatment response and number, size, site, consistency and matting of lymphadenopathy. No differences in response were seen in the remaining 34 patients with or without extended treatment. CONCLUSION: The operational efficacy of 6-month thrice-weekly DOT for peripheral tubercular lymphadenopathy was satisfactory. There was no evidence of additional benefits of prolonging treatment to 9 months.

Indian study on epidemiology of asthma, respiratory symptoms and chronic bronchitis in adults (INSEARCH).

SETTING: Field sites in 12 districts in different parts of India. OBJECTIVE: To determine the nationwide population prevalence of and risk factors for asthma and chronic bronchitis (CB) in adults. DESIGN: A standardised validated questionnaire based on the International Union Against Tuberculosis and Lung Disease's 1984 questionnaire was used to assess asthma and CB prevalence. Multivariate logistic regression analyses were performed to determine the risk factor associations. Estimates standardised to the 2011 population projection estimates for India were used to calculate the national disease burden. RESULTS: A total of 85,105 men and 84,470 women from 12 urban and 11 rural sites were interviewed. One or more respiratory symptoms were present in 8.5% of individuals. The overall prevalence of asthma and CB was respectively 2.05% (adults aged ≥15 years) and 3.49% (adults aged ≥35 years). Advancing age, smoking, household environmental tobacco smoke exposure, asthma in a first-degree relative, and use of unclean cooking fuels were associated with increased odds of asthma and CB. The national burden of asthma and CB was estimated at respectively 17.23 and 14.84 million. CONCLUSION: Asthma and CB in adults pose an enormous health care burden in India. Most of the associated risk factors are preventable.

Medical thoracoscopy for undiagnosed pleural effusions: experience from a tertiary care hospital in north India.

BACKGROUND AND AIMS: Medical thoracoscopy, also called pleuroscopy, has received renewed interest in the recent past for diagnostic as well as therapeutic uses. In this study, we describe our experience with thoracoscopy for undiagnosed pleural effusions. METHODS: In a retrospective analysis of thoracoscopic procedures we performed between January 2007 and December 2008, yield of thoracoscopic pleural biopsy for achieving a diagnosis in undiagnosed pleural effusions, defined as pleural effusions with adenosine deaminase (ADA) levels less than 70 IU/L and negative pleural fluid cytology for malignancy on three occasions was evaluated. Complications of thoracoscopy were also analysed. RESULTS: Overall diagnostic yield of thoracoscopic pleural biopsy was 74.3% in patients with undiagnosed pleural effusions. Pleural malignancy was diagnosed in 48.6% of patients. There was only one case of mesothelioma and the rest were due to pleural metastasis. Lung cancer and breast cancer were the most common sites of primary malignancy. Tuberculosis was diagnosed with pleural biopsy in 22.8% of patients. We had low complication rate after thoracoscopy. Only two cases of empyema were observed. CONCLUSION: Medical thoracoscopy is a safe procedure and has good diagnostic yield in patients with undiagnosed pleural effusions.

Is tobacco smoking protective for sarcoidosis? A case-control study from North India.

BACKGROUND: While tobacco smoking is commonly believed to be negatively associated with the occurrence of sarcoidosis, the relationship of environmental tobacco smoke (ETS) exposure with sarcoidosis is largely un-explored. We studied the impact of active smoking and ETS exposure on disease severity in newly diagnosed cases of sarcoidosis from India. METHODS: Data on demographic variables, smoking habits and exposure to environmental tobacco smoke (ETS) among non-smoker sarcoidosis patients was collected prospectively. Presence of smoking and ETS exposure were compared among cases and controls. Among the sarcoidosis patients, clinical manifestations, radiology, spirometry and histopathological grading of lung biopsy were compared between the smokers vs. non-smokers and ETS exposed vs. not-exposed. RESULTS: We studied 98 newly diagnosed cases of sarcoidosis and 196 age, sex and religion- matched healthy volunteers. The study group comprised of 62 (63%) men and 36 (37%) women. The prevalence of smoking was similar in cases and controls (12.2% vs. 15.3%, p = 0.48). Among the never smoker patients with sarcoidosis, 20 (23%) reported ETS exposure vis-a-vis 57 (34%) in the matched controls. A conditional logistic regression analyses showed insignificant negative association with active smoking (OR 0.75; 95% CI, 0.35-1.56) or ETS exposure (OR 0.58; 95% CI, 0.32-1.06) after adjusting for age, gender, religion, and education. There were no differences in the clinical manifestations, radiological staging, spirometry and histopathological grading of lung biopsy in any of the group comparisons studied. CONCLUSION: Smoking or ETS exposure may not have significant negative association with sarcoidosis. Also, tobacco smoke might not have any effect on the clinical behavior or disease severity in sarcoidosis. The belief that smoking is protective for sarcoidosis is not substantiated in this study and appears to be misfounded.

Computed tomographic pulmonary angiography: utility in acute pulmonary embolism in providing additional information and making alternative clinical diagnosis.

OBJECTIVE: To evaluate the role of computed tomographic (CT) pulmonary angiography (CT-PA) in detecting additional information that may help in making an alternative clinical diagnosis in patients referred to CT for a suspected acute pulmonary embolism (PE). MATERIALS AND METHODS: 50 patients (34 males, 16 females) in the age group of 18-72 years (mean 42.3 years), having high clinical suspicion of PE, underwent CTPA over a 2 year period. Chest x-ray, arterial blood gas (ABG) analysis, echocardiography were done in all patients. All patients underwent at least one other imaging examination besides CTPA: ventilation perfusion scan, Doppler ultrasound or compression ultrasound (for DVT). All patients were followed for 3 months after completion of the diagnostic work up at baseline. The final diagnosis was achieved by a combination of clinical, imaging, and laboratory analysis, after adequate imaging, laboratory tests, and follow up. RESULT: CTPA helped correctly identify 29 of 30 patients with PE. In the remaining 20 patients (with no evidence of PE), CT-PA provided additional information (that suggested or confirmed alternate clinical diagnosis) in 15 patients (75%): pleural effusion (n=8), mediastinal or hilar lymphadenopathy (6), pneumonia/airspace consolidation (5), atelectasis/collapse (2), aspergilloma (1), malignancy (1), and others (2). CONCLUSION: CT-PA is highly specific and sensitive for diagnosis of PE. In addition, in a majority of patients who do not have PE, it also provides important ancillary additional information and helps in making an alternative clinical diagnosis.

Fulminant parvovirus B19-associated pancarditis with haemophagocytic lympho-histiocytosis in an immunocompetent adult.

Myocarditis is a common cardiac disease that is identified on routine postmortem examinations. Initially, coxsackie viruses, other enteroviruses and adenoviruses were thought to be more common causes of myocarditis; however, recently, parvovirus B19 (PVB19) as well as human herpesvirus 6 (HHV6) have entered the arena. We describe autopsy findings of a patient who had a lethal myocarditis with haemophagocytic lympho-histiocytosis in a course of systemic PVB19 infection. The present case illustrates the unusually severe and rapid course of PVB19 myocarditis with associated haemophagocytic lympho-histiocytosis leading to death.

Validation of a structured questionnaire for COPD and prevalence of COPD in rural area of Mysore: A pilot study.

BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is increasing in India and there is a need to study the prevalence of COPD, particularly in the rural areas, which may be most affected due to their lifestyle. MATERIALS AND METHODS: FIRST STAGE: Validation of the questionnaire-105 consecutive patients underwent administration of the structured questionnaire and spirometry was used as a gold standard for the diagnosis of COPD. Second stage: Adults above 40 years (n = 900) in two villages of Mysore district were administered with the validated questionnaire, Knowledge and Attitude questionnaire and Fagerstorm questionnaire, to assess nicotine dependency. RESULTS: The questionnaire was found to have a sensitivity of 62.5% and specificity of 87.6% to diagnose COPD. Of the total 900 adults surveyed (Males: 453, Females: 447), the total prevalence of COPD was 7.1%. Males had a higher prevalence (11.1%) compared to females (4.5%). The prevalence of smoking was very high among men at 71.9% and all the women were nonsmokers. The prevalence of COPD was 14.7% in smokers, 19.3% had mild to moderate nicotine dependency and 12.8% were highly dependent. Of the women exposed to regular biomass fuels, the prevalence of COPD was 3.9%, which increased to 4.8% on addition of regular passive smoking. In smoking, male gender and age were significantly associated with COPD (P < 0.05). CONCLUSION: The structured questionnaire is a useful tool for the screening of COPD in field studies. Smoking and biomass fuel exposure are important risk factors for COPD.

Combined effect of GSTM1, GSTT1 and GSTP1 polymorphisms on histological subtypes of lung cancer.

Genetic polymorphisms are natural genetic variations in the gene sequence that occur at a frequency of >1% in the population. This genetic variability (polymorphisms) can be a factor in cancer risk. The functional polymorphisms in GST genes play an important role in susceptibility to lung cancer. In our previous study, we reported that the combination of certain genotypes of GSTM1, GSTT1 and CYP1A1 is associated with lung cancer. The study has been extended to investigate the potential role of polymorphism in GSTP1 alone or in combination with the status of GSTM1 and GSTT1 genes in the likelihood of development of lung cancer. A total of 302 subjects (151 cases and 151 controls) were evaluated. Using a case-control design, individuals were genotyped for GSTs using multiplex polymerase chain reaction and restriction fragment length polymorphism techniques. The data obtained were analyzed using multiple logistic regression. The combined 'at risk' genotypes of GSTM1 null and GSTT1 null in comparison with 'wild-type' genotypes seems to be associated with a greater risk of lung cancer, but the results are not significant (odds ratio (OR) 2.0, 95% confidence interval (CI) 0.68-5.96) and for squamous cell carcinoma (SqCC) it was 1.6-fold (OR 1.6, 95% CI 0.49-5.68). In summary, our case-control study of lung cancer revealed that the effect of these polymorphisms is not very marked for different genotypic combinations of GSTP1, GSTM1 and GSTT1 in the context of developing lung cancer in a north Indian population. However, the increased risk was limited to SqCC, and was not found for other histological subtypes. Further analyses on this topic are needed.