Surinder K. Jindal

Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis

The aetiology of sarcoidosis is currently unknown. Due to the clinical and histological similarities between sarcoidosis and tuberculosis, the role of mycobacteria has been repeatedly investigated as an aetiological agent for sarcoidosis. The current meta-analysis aimed to evaluate the available molecular evidence on the possible role of mycobacteria in the development of sarcoidosis. The MEDLINE, EMBASE, CINAHL, DARE and CENTRAL databases were searched for relevant studies published from 1980 to 2006, and studies evaluating the presence of mycobacteria using molecular techniques in biological samples of patients with sarcoidosis were included in the current analysis. The 95% confidence intervals (CI) were calculated for the expected proportion (of individual studies); the data was then pooled to obtain a summary success rate with 95% CI. The odds ratio (95% CI) was also calculated in order to assess the presence of mycobacteria in samples of patients with sarcoidosis versus those from nonsarcoidosis control samples. The database search yielded 31 studies. All studies used polymerase chain reaction for nucleic acid amplification followed by identification of nucleic acid sequences specific for different types of mycobacteria. Overall, 231 out of the 874 patients were positive for mycobacteria with a positive signal rate of 26.4 (23.6–29.5%), and the odds of finding mycobacteria in samples of patients with sarcoidosis versus controls were 9.67 (4.56–20.5%) using the random effects model and 19.49 (11.21–35.54%) using the exact method. There was methodological and statistical heterogeneity and evidence of publication bias. The results of the current study illustrate a demonstrable mycobacterial presence in sarcoidosis lesions suggesting an association between mycobacteria and some cases of sarcoidosis. To avoid methodological diversity, larger multicentre trials with a central laboratory for sample testing should be designed.

Acute exacerbation of idiopathic pulmonary fibrosis: A systematic review

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a clinical entity defined by rapid deterioration of IPF during the course of the disease that is not due to infections, pulmonary embolism, or heart failure. The condition needs to be differentiated from acute interstitial pneumonia (or Hamman-Rich syndrome), which occurs in patients with no underlying lung disease. The exact etiology and pathogenesis remain unknown, but the condition is characterized by diffuse alveolar damage (on a background of IPF) that probably occurs as a result of a massive lung injury due to some unknown etiologic agent. High-resolution computed tomography can help in prognostication and management of this condition. Once infections and other causes of worsening have been excluded, treatment involves enhanced immunosuppression with pulse doses of methylprednisolone and cytotoxic agents. Our systematic review shows that the outcome, however, is poor, with 1-month and 3-month mortality around 60% and 67%, respectively. Few studies have shown beneficial effects of cyclosporine, pirfenidone, and anticoagulants in the management and prevention of AE-IPF. The etiology, risk factors, pathogenesis, therapy, prognosis, and predictors need to be studied and the potential role of newer agents in the management and prevention of AE-IPF needs to be further clarified.

Genetic polymorphism of the CYP1A1, CYP2E1, GSTM1 and GSTT1 genes and lung cancer susceptibility in a north indian population.

CYP1A1, CYP2E1, GSTM1 and GSTT1 polymorphisms were evaluated in north Indian lung cancer patients and controls. The estimated relative risk for lung cancer associated with the CYP1A1*2C allele was 2.68. Apart from the CYP1A1*2C genotype, there was no attributable risk in relation to other genotypes when analyzed singly. However, in the presence of a single copy of the variant CYP1A1 (CYP1A1*1/2A) and null GSTT1 genes, there was a three-fold increased risk for lung cancer; when stratified histologically the relative risk increased to 3.7 in case of SQCC. Similarly individuals carrying the mutant CYP1A1*2C genotype and single copy of the variant CYP1A1 Msp1 allele, had a relative risk of 2.85 for lung cancer. In case of the GSTM1 and CYP1A1 genotypes, null GSTM1 and variant Msp1 alleles had two-fold elevated risk for SQCC. On the other hand CYP1A1*2C and null GSTM1 genotype had a 3.5-fold elevated risk for SCLC. Stratified analysis indicated a multiplicative interaction between tobacco smoking and variant CYP1A1 genotypes on the risk for SQCC and SCLC. The heavy smokers (BI < 400) with CYP1A1*2C genotype were at a very high risk to develop SCLC with an OR of 29.30 (95% CI = 2.42–355, p= 0.008). Taken together, these findings, the first to be analyzed in north Indian population, suggest that combined GSTT1, GSTM1 and CYP1A1 polymorphisms could be susceptible to lung cancer induced by bidi (an Indian cigarette) smoking (Mol Cell Biochem 266: 1–9, 2004)

Passive smoking and lung cancer in Chandigarh, India

The aim of this study is to assess the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers, a case-control study among lifetime non-smokers was conducted in Chandigarh, India. Cases consisted of 58 non-smoking histologically confirmed lung cancer patients; two controls for each case were selected, one among other patients admitted to the wards and one among the visitors to hospital patients. Subjects were asked about ETS exposure from different tobacco products in childhood and in adulthood at home, at the work place and in vehicles. Multivariate logistic regression analysis was used to assess the effects of the ETS exposure variables on lung cancer. Exposure to ETS during childhood was strongly associated with lung cancer (odds ratio (OR) = 3.9; 95% confidence interval (CI) = 1.9-8.2), the effect mostly arising from exposure to cigarettes smoke. The excess risk was observed with either a smoking father or mother. An increasing risk was found with increasing number of smokers and duration of exposure. Restricting the analysis to women produced higher estimates of the risk. No increased risk was found with exposure to a smoking spouse, except for those exposed only to cigarette smoke (OR = 5.1; 95% CI = 1.5-17). A weak association was seen between lung cancer and ETS exposure at the workplace, which increased with the number of years of exposure. Exposure in vehicles also was detected as a risk factor for lung cancer in non-smokers. This study suggests that ETS exposure may be a strong risk factor for lung cancer also in India, a country with low prevalence of smoking and, therefore, low rates of lung cancer. Other studies need to be conducted in similar settings to confirm the role played by ETS exposure early in life in the causation of lung cancer.

Inhaled Corticosteroids vs Placebo for Preventing COPD Exacerbations: A Systematic Review and Metaregression of Randomized Controlled Trials

BACKGROUND Inhaled corticosteroids (ICS) have been shown to decrease the occurrence of COPD exacerbations. However, the relationship of baseline lung function and reduction of exacerbations with the use of ICS remains unknown. Herein, we perform a metaregression to evaluate the efficacy of ICS in preventing COPD exacerbations. METHODS We searched the PubMed, EmBase, and Cochrane Central Database of Controlled Trials databases (1988-2008) for studies that have reported the efficacy of ICS vs placebo in preventing COPD exacerbations. We pooled the risk ratio (RR) and 95% CIs from individual studies using a random-effects model to assess the exacerbations in the two groups. We also performed a weighted random effects metaregression using baseline FEV(1) values. RESULTS Our search yielded 11 studies (8,164 patients). The use of ICS was associated with reduction in the occurrence of exacerbations (RR, 0.82; 95% CI, 0.73-0.92). There was the presence of significant statistical heterogeneity but no evidence of publication bias. Sensitivity analysis revealed benefit of ICS only in patients with FEV(1) < 50% (RR, 0.79; 95% CI, 0.69-0.89) with persistence of statistical heterogeneity. Metaregression showed that the percentage risk reduction in exacerbations with the use of ICS is invariant across the severity of COPD (assessed by FEV(1)). CONCLUSION There is only a modest benefit of ICS in preventing COPD exacerbations, which is not related to the level of baseline lung function on metaregression analysis. The benefits of ICS in preventing COPD exacerbations thus seem to be overstated.

Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis

BACKGROUND AND AIMS The total serum IgE level is a marker of immunological activity in allergic bronchopulmonary aspergillosis (ABPA), and a 35% decline beyond six weeks is traditionally taken as criteria for remission. The aim of this study was to evaluate the magnitude and clinical significance of decline in serum IgE levels at six weeks in patients with ABPA. METHODS All consecutive patients with ABPA presenting to the Chest Clinic were followed up with clinical evaluation, total IgE levels and chest x-ray every six weeks for three months. We analyzed the percentage decline in IgE levels and correlated it with clinical outcomes of relapse and complete remission. RESULTS Of the 242 asthmatics, 54 were diagnosed with ABPA (29 males, 25 females; mean age-34 years). There was clinical and radiological improvement at six weeks in all patients receiving glucocorticoid therapy. The IgE levels fell by a mean of 38.8%, and the decline was significantly higher in patients with baseline IgE levels >2500IU/mL than with levels <or=2500IU/mL (44% vs. 26%). Twenty-two patients did not attain a 35% decline in IgE levels, and this number was significantly higher in patients with IgE levels <2500IU/mL. On multivariate analysis, the decline in IgE levels at six weeks did not predict clinical outcomes. CONCLUSIONS A 35% decline in serum IgE levels at six weeks is not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE levels <2500IU/mL. The quantum decline in serum IgE levels does not predict clinical outcomes.

Is the Mortality Higher in the Pulmonary vs the Extrapulmonary ARDS?: A Metaanalysis

BACKGROUND AND AIM ARDS can occur from the following two pathogenetic pathways: a direct pulmonary injury (ARDSp); and an indirect injury (ARDSexp). The predisposing clinical factor can influence the pathogenesis and clinical outcome of ARDS. This metaanalysis was aimed at evaluating whether there is any difference in mortality between the two groups. METHODS We searched the MEDLINE, EMBASE, and CINAHL databases for relevant studies published from 1987 to 2007, and included studies that have reported mortality in the two groups of ARDS. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess mortality in patients with ARDSp vs patients with ARDSexp and pooled the results using three different statistical models. RESULTS Our search yielded 34 studies. In all, the studies involved 4,311 patients with 2,330 patients in the ARDSp group and 1,981 patients in the ARDSexp group. The OR of mortality in ARDSp group compared to the ARDSexp group was 1.11 (95% CI, 0.88 to 1.39), as determined by the random-effects model; 1.04 (95% CI, 0.92 to 1.18), as determined by the fixed-effects model; and 1.04 (95% CI, 0.92 to 1.18), as determined by the exact method, indicating that mortality is similar in the two groups. The mortality was no different whether the studies were classified as prospective (OR, 1.15; 95% CI, 0.87 to 1.51) or retrospective (OR, 1.01; 95% CI, 0.61 to 1.69); small (OR, 1.11; 95% CI, 0.77 to 1.60) or large (OR, 1.1; 95% CI, 0.82 to 1.49); or observational (OR, 1.10; 95% CI, 0.82 to 1.49) or interventional (OR, 0.97; 95% CI, 0.79 to 1.19). There was methodological and statistical heterogeneity (I(2), 50.9%; 95% CI, 21.3 to 66.2%; chi(2) statistic, 67.22; p = 0.0004). CONCLUSIONS The results of this study suggest that there is no difference in mortality between these two groups. Further studies should focus on specific etiologies within the subgroups rather than focusing on the broader division of ARDSp and ARDSexp.

Aspergillus hypersensitivity in patients with chronic obstructive pulmonary disease: COPD as a risk factor for ABPA?

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus which primarily complicates the course of asthma and cystic fibrosis. There is a theoretical possibility that patients with chronic obstructive pulmonary disease (COPD) can also develop Aspergillus hypersensitivity (AH) and/or ABPA. The aim of this prospective case-control study conducted in the Chest Clinic was to evaluate the prevalence of AH/ABPA in patients with COPD. Two hundred subjects with COPD (17, 62, 74, 47; GOLD guidelines stages I–IV respectively) and 100 healthy volunteers were screened with an Aspergillus skin test. Patients were said to have AH if they demonstrated immediate cutaneous hyperreactivity to A. fumigatus antigen and those with positive responses were further investigated for ABPA. Of this patient population there were 179 (89.5%) males and 21 (10.5%) females with a mean age of 57.1 in the COPD arm and 88 males and 12 females with a mean age of 52.3 in the control arm. AH was found in 17 (8.5%) patients with COPD as compared to none in the control group. Two (1.0%) COPD patients fulfilled the serologic criteria for the diagnosis of ABPA. On univariate analysis, age of the patient, duration of COPD, smoking index and the COPD severity did not predict the occurrence of AH. On the basis of this study we concluded that AH/ABPA can occur in patients with COPD, and it is probable that COPD could be a predisposing factor for AH/ABPA. The clinical significance of AH and ABPA in COPD remains unclear.

Radioisotope scintigraphy in the diagnosis of hepatic hydrothorax.

Background: Pleural effusion in cirrhotic patients (hepatic hydrothorax) may result from migration of ascitic fluid across defects in the diaphragm. Biochemical analysis of ascitic and pleural fluid provides only indirect information about the nature and origin of the effusion. The present study was performed in order to demonstrate the presence/absence of peritoneo–pleural communication by radioisotope imaging.

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 Diseases 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.