Inderpaul Singh Sehgal

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

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.

Foreign Body Inhalation in the Adult Population: Experience of 25,998 Bronchoscopies and Systematic Review of the Literature

BACKGROUND: Foreign body aspiration is an uncommon entity in adults. Herein, we describe our experience with flexible bronchoscopy in the removal of tracheobronchial foreign bodies in adults. We also conducted a systematic review of the literature on the topic of foreign body inhalation in adults managed with flexible bronchoscopy. METHODS: The bronchoscopy database (from 1979 to 2014) was reviewed for subjects > 12 y of age with a history of foreign body aspiration managed with flexible bronchoscopy. Demographic, clinical, and bronchoscopy data were collected and analyzed. PubMed was reviewed for studies describing the use of flexible bronchoscopy for foreign body extraction in adults. RESULTS: During the study period, a total of 25,998 flexible bronchoscopies were performed. Of these, 65 subjects (mean age of 32.8 y, 49 males) were identified who had undergone bronchoscopy for foreign body aspiration. Nonresolving pneumonia (30.6%), direct foreign body visualization (24.6%), and segmental collapse (18.4%) were the most common radiological abnormalities. Foreign bodies were identified in 49 cases during bronchoscopy and successfully removed in 45 (91.8%) subjects with no major complications. Metallic (41%) and organic (25.6%) foreign bodies were the most common. Shark-tooth (44.9%) and alligator (32.6%) were the most commonly used forceps in retrieving the foreign bodies. The systematic review yielded 18 studies (1,554 subjects with foreign body inhalation). In adults, the proportion of flexible bronchoscopy (6 studies, 354/159,074 procedures) performed for the indication of foreign bodies among the total flexible bronchoscopies was 0.24% (95% CI 0.18–0.31). The overall success of flexible bronchoscopy (18 studies, 1,185 subjects) for foreign body extraction was 89.6% (95% CI 86.1–93.2). CONCLUSIONS: Foreign body aspiration is a rare indication for flexible bronchoscopy in adults. Flexible bronchoscopy has a high success rate in removal of inhaled foreign body and can be considered the preferred initial procedure for management of airway foreign bodies in adults.

Guidelines for diagnosis and management of chronic obstructive pulmonary disease: Joint ICS/NCCP (I) recommendations

Chronic obstructive pulmonary disease (COPD) is a major public health problem in India. Although several International guidelines for diagnosis and management of COPD are available, yet there are lot of gaps in recognition and management of COPD in India due to vast differences in availability and affordability of healthcare facilities across the country. The Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) of India have joined hands to come out with these evidence-based guidelines to help the physicians at all levels of healthcare to diagnose and manage COPD in a scientific manner. Besides the International literature, the Indian studies were specifically analyzed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (a) definitions, epidemiology, and disease burden; (b) disease assessment and diagnosis; (c) pharmacologic management of stable COPD; (d) management of acute exacerbations; and (e) nonpharmacologic and preventive measures. The modified grade system was used for classifying the quality of evidence as 1, 2, 3, or usual practice point (UPP). The strength of recommendation was graded as A or B depending upon the level of evidence.

Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis

The role of total and specific IgE in monitoring treatment responses in allergic bronchopulmonary aspergillosis (ABPA) remains poorly studied. Here in, we evaluate the utility of total and Aspergillus fumigatus specific IgE in the follow‐up of ABPA. Eighty‐one consecutive treatment‐naïve patients of ABPA (acute stage) with pulmonary infiltrates and bronchiectasis underwent measurement of total and A. fumigatus specific IgE at baseline, after 8 weeks of glucocorticoid therapy, and during exacerbations. There was clinical and radiological improvement after treatment with median decline of total IgE by 51.9%. The total IgE declined by at least 35%, 25% and 20% in 69 (85.2%), 76 (93.6%) and 78 (96.3%) patients, respectively. On the other hand, the A. fumigatus specific IgE increased in 42 (51.9%) subjects, and the mean increase was 1.4%, after 8 weeks. Among 13 patients with exacerbation, 12 (92.3%) had a rise of total IgE by >50%. The A. fumigatus specific IgE increased in only five (38.5%) subjects during exacerbation. Thus, the total IgE is a useful test in monitoring treatment responses in ABPA while A. fumigatus specific IgE has limited utility.

Diagnostic Performance of Xpert MTB/RIF in Tuberculous Pleural Effusion: Systematic Review and Meta-analysis

ABSTRACT A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and specificities of Xpert MTB/RIF were 51.4% and 98.6%, respectively, with culture used as a reference standard and 22.7% and 99.8%, respectively, with a composite reference standard (CRS) used as the benchmark. Xpert MTB/RIF has low sensitivity but excellent specificity in the diagnosis of TPE.

Developments in the diagnosis and treatment of allergic bronchopulmonary aspergillosis

ABSTRACT Introduction: Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder characterized by recurrent episodes of wheezing, fleeting pulmonary opacities and bronchiectasis. It is the most prevalent of the Aspergillus disorders with an estimated five million cases worldwide. Despite six decades of research, the pathogenesis, diagnosis and treatment of this condition remains controversial. The International Society for Human and Animal Mycology has formed a working group to resolve the controversies around this entity. In the year 2013, this group had proposed new criteria for diagnosis and staging, and suggested a treatment protocol for the management of this disorder. Since then, several pieces of new evidence have been published in the investigation and therapeutics of this condition. Areas covered: A non-systematic review of the available literature was performed. We summarize the current evidence in the evaluation and treatment of this enigmatic disorder. We suggest modifications to the existing criteria and propose a new scoring system for the diagnosis of ABPA. Expert commentary: All patients with asthma and cystic fibrosis should routinely be screened for ABPA using A. fumigatus-specific IgE levels. Glucocorticoids should be used as the first-line of therapy in ABPA, and itraconazole reserved in those with recurrent exacerbations and glucocorticoid-dependent disease.

Role of Aspergillus fumigatus-specific IgG in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis

Few studies have evaluated the utility of Aspergillus fumigatus‐specific IgG in allergic bronchopulmonary aspergillosis (ABPA). Herein, we evaluate the role of specific IgG in diagnosis and monitoring treatment response in ABPA. Forty‐eight control subjects with A. fumigatus‐associated asthma underwent A. fumigatus‐specific IgG measurements at baseline, while specific IgG was assayed in 102 treatment‐naïve subjects of ABPA at baseline, after eight weeks of glucocorticoid therapy, and during exacerbations. For determining the cut‐off of A. fumigatus‐specific IgG, we randomly classified two‐thirds of the study subjects (cases and controls) as the derivation cohort, while the remaining one‐thirds were labelled as the validation cohort. The best cut‐off value of A. fumigatus‐specific IgG in the derivation cohort was 26.9 mgA/L (sensitivity: 88%; specificity: 100%). Using this limit, the sensitivity and specificity of A. fumigatus‐specific IgG in diagnosis of ABPA was 89% and 100%, respectively, in the validation cohort. In contrast, the sensitivity of Aspergillus precipitins was only 27.4%. Following treatment, the A. fumigatus‐specific IgG increased in 38 (37.2%) subjects, while it decreased in three (23.1%) of the 13 subjects experiencing an exacerbation. The A. fumigatus‐specific IgG was found to be an extremely useful test in the diagnosis and differential diagnosis of ABPA but is unreliable in monitoring treatment response in this disorder.

Performance of serum galactomannan in patients with allergic bronchopulmonary aspergillosis

Few studies have evaluated the performance of serum galactomannan (GM) in patients with allergic bronchopulmonary aspergillosis (ABPA). Herein, we analyse the diagnostic performance of serum GM in ABPA. Consecutive subjects with ABPA and asthma underwent GM estimation using the Platelia assay (Bio‐Rad Laboratories). An optical density index of >0.5 was considered positive. One hundred and twenty subjects (70 ABPA, 50 asthma) with a mean (SD) age of 33.0 (13.1) were included in the study. The serum GM antigen was positive in 18 (25.7%) subjects with ABPA compared to 9 (18%) subjects with asthma without ABPA (P = 0.32). The sensitivity of the serum GM antigen test in patients with ABPA was 25.7% [95% confidence intervals (CI), 16–38] while the specificity was 82% (95% CI, 69–91). The positive and negative predictive values were 66.7% (95% CI, 46–84%) and 44.1% (95% CI, 34–55), respectively. The area under the ROC curve was 0.54 (95% CI, 0.44–0.64). The sensitivity increased and the specificity decreased with decreasing the serum GM cutoff, and vice versa. The results of this study suggest that serum GM estimation has a limited role in the diagnostic workup of patients with ABPA.

A pilot randomized trial of nebulized amphotericin in patients with allergic bronchopulmonary aspergillosis.

Abstract Background and aim: Nebulized amphotericin B (NAB) has been used in the management of acute stage and exacerbations of allergic bronchopulmonary aspergillosis (ABPA). Whether NAB can prevent exacerbations of ABPA is not known. Herein, we evaluate the efficacy and safety of NAB in subjects with ABPA complicating asthma. Methods: Consecutive subjects of ABPA with recurrent exacerbations were randomized to receive either NAB plus nebulized budesonide (NEB) or NEB alone. The primary outcome was the time-to-first exacerbation of ABPA. The secondary outcomes were the number of subjects with ABPA exacerbations, ACQ7 scores, lung function, IgE levels, and adverse effects of treatment. Results: Twenty-one subjects (14 men; mean age, 32.3 years) were randomized to either the NAB (n = 12) or the NEB (n = 9) arm. The baseline characteristics were similar in the two groups. The time-to-first exacerbation was similar in the two groups. At one year, the numbers of patients experiencing exacerbation was significantly lower in the NAB arm (1/12 [8.3%] vs. 6/9 [66.7%]; p = 0.016). The other secondary end points were not different between the two groups. There were no major adverse events leading to discontinuation of any of the study drugs. Three patients experienced bronchospasm after first dose of NAB; however, the subsequent doses were well tolerated. Conclusions: NAB seems to be beneficial in decreasing the frequency of exacerbations in patients with ABPA complicating asthma. Larger trials are required to confirm our study results.