Digambar Behera

Eight‐year study of allergic bronchopulmonary aspergillosis in an Indian teaching hospital

Summary.  A total of 651 patients with clinically suspected allergic bronchopulmonary aspergillosis (ABPA) were evaluated during the 8‐year period from January 1991 to December 1998. Overall, 338 cases (51.9%) were positive either by sputum microscopy/culture (66 of 203 patients), by skin reactivity (150 of 309 cases), or by precipitating antibodies (122 of 338 patients) against Aspergillus species. However, in 89 patients, diagnosis of ABPA was confirmed on the basis of Rosenbergs criteria. Clinical profile and laboratory findings of those patients were analysed. The disease was found to be more common among males. Poor control of asthma, constitutional symptoms, mucopurulent expectoration, increased dyspnoea and wheezing and rhonchi were the main presenting features. Skin reactivity against aspergillin was seen in 73 (82%), precipitating antibodies against Aspergillus species were positive in 64 (72%) and sputum microscopy/culture was positive in 56 (63%) of those 89 patients. Central bronchiectasis and fleeting shadows were the most common radiological findings. This study highlights the importance of ABPA in north India and draws attention to the need for further analysis of criteria to use in the diagnosis of patients with ABPA.

Linezolid: an effective, safe and cheap drug for patients failing multidrug-resistant tuberculosis treatment in India

Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB.

LipC (Rv0220) Is an Immunogenic Cell Surface Esterase of Mycobacterium tuberculosis

ABSTRACT We have reported previously the identification of novel proteins of Mycobacterium tuberculosis by the immunoscreening of an expression library of M. tuberculosis genomic DNA with sera obtained from M. tuberculosis-infected rabbits at 5 weeks postinfection. In this study, we report the further characterization of one of these antigens, LipC (Rv0220). LipC is annotated as a member of the Lip family based on the presence of the consensus motif “GXSXG” characteristic of esterases. Although predicted to be a cytoplasmic enzyme, we provide evidence that LipC is a cell surface protein that is present in both the cell wall and the capsule of M. tuberculosis. Consistent with this localization, LipC elicits strong humoral immune responses in both HIV-negative (HIV−) and HIV-positive (HIV+) tuberculosis (TB) patients. The absence of anti-LipC antibodies in sera from purified protein derivative-positive (PPD+) healthy subjects confirms its expression only during active M. tuberculosis infection. Epitope mapping of LipC identified 6 immunodominant epitopes, 5 of which map to the exposed surface of the modeled LipC protein. The recombinant LipC (rLipC) protein also elicits proinflammatory cytokine and chemokine responses from macrophages and pulmonary epithelial cells. rLipC can hydrolyze short-chain esters with the carbon chain containing 2 to 10 carbon atoms. Together, these studies demonstrate that LipC is a novel cell surface-associated esterase of M. tuberculosis that is highly immunogenic and elicits both antibodies and cytokines/chemokines.

Unchanging clinico-epidemiological profile of lung cancer in North India over three decades

OBJECTIVE In the recent past, adenocarcinoma has become the commonest histological type of lung cancer (LC) in the developed countries. The present study was conducted to assess the change in epidemiology of LC, if any, in North India. METHODS Prospectively collected data on 250 newly diagnosed LC patients presenting to a tertiary care institute was analyzed. Results were compared with the previously published data from this center. RESULTS No significant differences were observed in the demographical, histological or smoking profiles of LC patients compared to those seen three decades earlier. The mean [standard deviation] age was 57.9 [+/-11.3] years (previously 54.3 years). Male to female ratio was 4.43:1 (previously 4.48:1; p=0.952) while the smoker to non-smoker ratio was 2.67:1 (previously 2.68:1; p=0.980). The commonest histological types were squamous cell (34.8%), adenocarcinoma (26.0%) and small cell (18.4%) while previously these were 34.3%, 25.9% and 20.3%, respectively; p=0.916. However, in the present study, significant differences were observed between smokers and non-smokers in relation to distribution of gender, histology and disease stage. CONCLUSIONS There has been no significant change in the epidemiology of LC in North India over the past three decades. An absence of change in the smoking pattern of the population could be a possible reason.

Utility and Safety of Endoscopic Ultrasound With Bronchoscope-Guided Fine-Needle Aspiration in Mediastinal Lymph Node Sampling: Systematic Review and Meta-Analysis

BACKGROUND: The use of endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) has been described in the evaluation of mediastinal lymphadenopathy. Herein, we conduct a meta-analysis to estimate the overall diagnostic yield and safety of EUS-B-FNA combined with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), in the diagnosis of mediastinal lymphadenopathy. METHODS: The PubMed and EmBase databases were searched for studies reporting the outcomes of EUS-B-FNA in diagnosis of mediastinal lymphadenopathy. The study quality was assessed using the QualSyst tool. The yield of EBUS-TBNA alone and the combined procedure (EBUS-TBNA and EUS-B-FNA) were analyzed by calculating the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for each study, and pooling the study results using a random effects model. Heterogeneity and publication bias were assessed for individual outcomes. The additional diagnostic gain of EUS-B-FNA over EBUS-TBNA was calculated using proportion meta-analysis. RESULTS: Our search yielded 10 studies (1,080 subjects with mediastinal lymphadenopathy). The sensitivity of the combined procedure was significantly higher than EBUS-TBNA alone (91% vs 80%, P = .004), in staging of lung cancer (4 studies, 465 subjects). The additional diagnostic gain of EUS-B-FNA over EBUS-TBNA was 7.6% in the diagnosis of mediastinal adenopathy. No serious complication of EUS-B-FNA procedure was reported. Clinical and statistical heterogeneity was present without any evidence of publication bias. CONCLUSIONS: Combining EBUS-TBNA and EUS-B-FNA is an effective and safe method, superior to EBUS-TBNA alone, in the diagnosis of mediastinal lymphadenopathy. Good quality randomized controlled trials are required to confirm the results of this systematic review.

A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma

Whether use of high-dose steroids in acute-stage allergic bronchopulmonary aspergillosis (ABPA) is associated with superior outcomes is not known. Herein, we compare the efficacy and safety of two glucocorticoid protocols in ABPA. Treatment-naive ABPA subjects randomly received either high-dose or medium-dose oral prednisolone. The primary outcomes were exacerbation rates and glucocorticoid-dependent ABPA after 1 and 2 years, respectively, of treatment. The secondary end-points were composite response rates after 6 weeks, improvement in lung function, time to first exacerbation, cumulative dose and adverse effects. 92 subjects (high-dose n=44, medium-dose n=48) were included in the study. The numbers of subjects with exacerbation after 1 year (high-dose 40.9% versus medium-dose 50%, p=0.59) and glucocorticoid-dependent ABPA after 2 years (high-dose 11.4% versus medium-dose 14.6%, p=0.88) were similar in the two groups. Although composite response rates were significantly higher in the high-dose group, improvement in lung function and time to first exacerbation were similar in the two groups. Cumulative glucocorticoid dose and side-effects were significantly higher in the high-dose group. Medium-dose oral glucocorticoids are as effective and safer than high-dose in treatment of ABPA. Medium-dose glucocorticoids are as effective as high-dose in treatment of allergic bronchopulmonary aspergillosis http://ow.ly/TLt4N

Incidence and Risk Factors for Extensively Drug-Resistant Tuberculosis in Delhi Region

Background India with a major burden of multidrug-resistant tuberculosis (MDR-TB) does not have national level data on this hazardous disease. Since 2006, emergence of extensively drug-resistant TB (XDR-TB) is considered a serious threat to global TB control. This study highlights the demographic and clinical risk factors associated with XDR-TB in Delhi. Methods The study was conducted during April 2007 to May 2010. Six hundred eleven MDR-TB suspects were enrolled from four tertiary care hospitals, treating TB patients in Delhi and the demographic details recorded. Sputum samples were cultured using rapid, automated liquid culture system (MGIT 960). Drug susceptibility testing (DST) for Rifampicin (RIF) and Isoniazid (INH) was performed for all positive M. tuberculosis (M.tb) cultures. All MDR-TB isolates were tested for sensitivity to second-line drugs [Amikacin (AMK), Capreomycin (CAP), Ofloxacin (OFX), Ethionamide (ETA)]. Results/Findings Of 611, 483 patients were infected with MDR M. tuberculosis (M.tb) strains. Eighteen MDR-TB isolates (3.7%) were XDR M.tb strains. Family history of TB (p 0.045), socioeconomic status (p 0.013), concomitant illness (p 0.001) and previous intake of 2nd line injectable drugs (p 0.001) were significantly associated with occurrence of XDR-TB. Only two of the patients enrolled were HIV seropositive, but had a negative culture for M. tuberculosis. 56/483 isolates were pre-XDR M. tuberculosis, though the occurrence of pre-XDR-TB did not show any significant demographical associations. Conclusions The actual incidence and prevalence rate of XDR-TB in India is not available, although some scattered data is available. This study raises a concern about existence of XDR-TB in India, though small, signaling a need to strengthen the TB control program for early diagnosis of both tuberculosis and drug resistance in order to break the chains of transmission.

Peptide-Based Antibody Detection for Tuberculosis Diagnosis

ABSTRACT Tuberculosis (TB) is a major cause of morbidity and mortality, especially in developing countries. Despite significant limitations, microscopy remains the cornerstone of the global TB control strategy. As the TB epidemic escalates, new diagnostic methods that are accurate and also economical and simple to manufacture and deploy are urgently needed. Although several promising antigens have been identified and evaluated in recent years, the reproducible production of high-quality recombinant mycobacterial proteins with minimal batch-to-batch variation is difficult, laborious, and expensive. To determine the feasibility of devising a synthetic peptide-based diagnostic test for TB, we have delineated the immunodominant epitopes of three candidate antigens, Ag85B, BfrB, and TrxC, that were previously identified to be immunogenic in TB patients. The results demonstrate that combinations of carefully selected synthetic peptides derived from highly immunogenic proteins can be the basis for devising an immunodiagnostic test for TB.

Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins.

The differences in specificity of human lung and peripheral lymphocytes for mycobacterial antigens (Ag) need to be evaluated in order to identify vaccine candidates against pulmonary tuberculosis (TB). Therefore, the present study examined the response to low molecular weight secretory proteins of Mycobacterium tuberculosis in bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) from minimal pulmonary TB and non-TB patients. Ag85A, Ag85B, culture filtrate protein (CFP)-31, CFP-22.5, CFP-21, M. tuberculosis protein-64 and an as yet uncharacterised 19 kDa protein were found to be predominantly recognised by BAL cells of TB patients on the basis of lymphocyte proliferation and significant interferon-γ release. However, recognition of CFP-8, 6-kDa early secreted antigenic target, CFP-10, CFP-14.5, M. tuberculosis secretory protein-17 and five other as yet uncharacterised low molecular weight polypeptides was found to be high on the basis of lymphocyte proliferation at the level of PBMCs. Furthermore, BAL macrophages, and not blood monocytes, were found to produce nitric oxide (NO) in response to mycobacterial Ags. Among polypeptides predominantly recognised by BAL lymphocytes, only Ag85A and Ag85B were found to induce both NO and interleukin-12 (p40) by alveolar macrophages. In conclusion, the present results indicate heterogeneity in antigen recognition by bronchoalveolar lavage cells and peripheral mononuclear blood cells of minimal tuberculosis patients, and also suggest the utility of antigen 85 complex polypeptides for the development of a future mucosal antituberculous vaccine.

Diagnostic Yield and Safety of Cryoprobe Transbronchial Lung Biopsy in Diffuse Parenchymal Lung Diseases: Systematic Review and Meta-Analysis.

BACKGROUND: Transbronchial lung biopsy with flexible forceps is the most commonly used technique in diagnosis of diseases diffusely involving the lung parenchyma. Recently, transbronchial lung biopsy using the flexible cryoprobe (cryo-transbronchial lung biopsy) has also been reported. Herein, we perform a systematic review and meta-analysis describing the efficacy and safety of cryo-transbronchial lung biopsy. METHODS: The PubMed and EMBASE databases were searched for studies reporting the outcomes of cryo-transbronchial lung biopsy in subjects with diffuse parenchymal lung involvement. The quality of individual studies was assessed using the QualSyst tool. The pooled diagnostic yield of cryo-transbronchial lung biopsy was calculated using proportion meta-analysis (random effects model). Heterogeneity was evaluated using the I2 test and Cochran Q test. Publication bias was determined using both statistical and graphical methods. RESULTS: Our search yielded 14 studies (1,183 subjects). The pooled diagnostic yield of cryo-transbronchial lung biopsy was 76.9% (95% CI 67.2–85.3) if only definitive diagnoses were considered and 85.9% (95% CI 78.2–92.2) if both definitive and probable diagnoses were considered. Four studies (321 subjects) the performance of flexible forceps biopsy and cryo-transbronchial lung biopsy. The diagnostic yield of cryo-transbronchial lung biopsy (86.3, 95% CI 80.2–90.8) was significantly higher than that of flexible forceps biopsy (56.5%, 95% CI 27.5–83.2) with an odds ratio of 6.7 (95% CI 3.6–12.4) and a number needed to treat of 4. Lung tissue was obtained in 98% of all samples with cryo-transbronchial lung biopsy and was free of compression artifacts. The size of samples obtained with cryo-transbronchial lung biopsy was significantly bigger compared with flexible forceps biopsy (20.4 vs 4.3 mm2, P = .005). The complications of cryo-transbronchial lung biopsy included pneumothorax (6.8%), severe bleeding (0.3%), and death (0.1%). Clinical and statistical heterogeneity was present, and there was evidence of publication bias. CONCLUSIONS: Cryo-transbronchial lung biopsy is a relatively safe procedure with good diagnostic yield in diseases diffusely involving the lung parenchyma.