Mandeep Garg

Diagnostic Performance of Various Tests and Criteria Employed in Allergic Bronchopulmonary Aspergillosis: A Latent Class Analysis

Aim The efficiency of various investigations and diagnostic criteria used in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) remain unknown, primarily because of the lack of a gold standard. Latent class analysis (LCA) can provide estimates of sensitivity and specificity in absence of gold standard. Herein, we report the performance of various investigations and criteria employed in diagnosis of ABPA. Methods Consecutive subjects with asthma underwent all the following investigations Aspergillus skin test, IgE levels (total and A.fumigatus specific), Aspergillus precipitins, eosinophil count, chest radiograph, and high-resolution computed tomography (HRCT) of the chest. We used LCA to estimate the performance of various diagnostic tests and criteria in identification of ABPA. Results There were 372 asthmatics with a mean age of 35.9 years. The prevalence of Aspergillus sensitization was 53.2%. The sensitivity and specificity of various tests were Aspergillus skin test positivity (94.7%, 79.7%); IgE levels>1000 IU/mL (97.1%, 37.7%); A.fumigatus specific IgE levels>0.35 kUA/L (100%, 69.3%); Aspergillus precipitins (42.7%, 97.1%); eosinophil count>1000 cells/µL (29.5%, 93.1%); chest radiographic opacities (36.1%, 92.5%); bronchiectasis (91.9%, 80.9%); and, high-attenuation mucus (39.7%, 100%). The most accurate criteria was the Patterson criteria using six components followed by the Agarwal criteria. However, there was substantial decline in accuracy of the Patterson criteria if components of the criteria were either increased or decreased from six. Conclusions A.fumigatus specific IgE levels and high-attenuation mucus were found to be the most sensitive and specific test respectively in diagnosis of ABPA. The Patterson criteria remain the best diagnostic criteria however they have good veridicality only if six criteria are used.

Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature.

Patients with aspergilloma can be safely managed with supportive therapy in absence of massive haemoptysis. We hypothesised that chronic cavitary pulmonary aspergillosis (CCPA) could also be managed on similar grounds. The aim of this prospective, randomised controlled trial was to evaluate the efficacy and safety of itraconazole in CCPA. Consecutive patients of CCPA with presence of chronic pulmonary/systemic symptoms; and pulmonary cavities; and presence of Aspergillus (immunological or microbiological) were randomised to receive either supportive treatment alone or itraconazole 400 mg daily for 6 months plus supportive therapy. Response was assessed clinically, radiologically and overall after 6 months therapy. A total of 31 patients (mean age, 37 years) were randomised to itraconazole (n = 17) or the control (n = 14) group. The number of patients showing overall response was significantly higher in the itraconazole group (76.5%) vs. the control (35.7%) group (P = 0.02). The numbers of patients demonstrating clinical or radiological response were also significantly higher in the itraconazole group (P = 0.016 and 0.01 respectively). Adverse events were noted in eight patients in the itraconazole group, however, none was serious or led to discontinuation of the study drug. Itraconazole was found to be superior to standard supportive treatment alone in stabilising cases of CCPA. (clinicaltrials.gov; NCT01259336).

Pictorial essay: Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is the best-known allergic manifestation of Aspergillus-related hypersensitivity pulmonary disorders. Most patients present with poorly controlled asthma, and the diagnosis can be made on the basis of a combination of clinical, immunological, and radiological findings. The chest radiographic findings are generally nonspecific, although the manifestations of mucoid impaction of the bronchi suggest a diagnosis of ABPA. High-resolution CT scan (HRCT) of the chest has replaced bronchography as the initial investigation of choice in ABPA. HRCT of the chest can be normal in almost one-third of the patients, and at this stage it is referred to as serologic ABPA (ABPA-S). The importance of central bronchiectasis (CB) as a specific finding in ABPA is debatable, as almost 40% of the lobes are involved by peripheral bronchiectasis. High-attenuation mucus (HAM), encountered in 20% of patients with ABPA, is pathognomonic of ABPA. ABPA should be classified based on the presence or absence of HAM as ABPA-S (mild), ABPA-CB (moderate), and ABPA-CB-HAM (severe), as this classification not only reflects immunological severity but also predicts the risk of recurrent relapses.

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

Cut-off values of serum IgE (total and A. fumigatus -specific) and eosinophil count in differentiating allergic bronchopulmonary aspergillosis from asthma

The cut‐off values of immunological tests employed in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) have never been validated. Herein, we compare the immunological findings in patients with ABPA and asthma using receiver operating characteristic analysis. Consecutive asthmatic subjects underwent all the following investigations: Aspergillus skin test, IgE levels (total and A. fumigatus‐specific), Aspergillus precipitins, eosinophil count, chest radiograph and CT chest. There were 372 subjects (179 men, mean age 35.9 years) with a mean asthma duration of 8 years. ABPA was diagnosed in 76 patients (64 bronchiectasis, 12 without bronchiectasis). ABPA was separated from asthma using the best cut‐off values of total IgE, A. fumigatus IgE and total eosinophil count of 2347 IU ml−1, 1.91 kUA l−1 and 507 cells per μl respectively. The sensitivity/specificity of these parameters were 87/81%; 99/87%; and, 79/76% respectively. The corresponding AUC values were 0.95, 0.90 and 0.82 respectively. The combination of these three tests at the aforementioned cut‐offs provided 100% specificity. Our study provides evidence‐based cut‐off values of IgE (total and A. fumigatus‐specific) and eosinophil counts in differentiating ABPA from asthma. As this is a single centre retrospective study, further studies from different centres are required, as these values could vary by ethnicity and environmental exposure.

Serologic allergic bronchopulmonary aspergillosis (ABPA-S): long-term outcomes.

BACKGROUND AND AIM ABPA is radiologically classified on the presence or absence of central bronchiectasis (CB) as ABPA-CB and serologic ABPA (ABPA-S) respectively. Few studies have described the follow-up of patients with ABPA-S. The aim of this retrospective study was to describe the outcomes of ABPA-S. METHODS Patients were diagnosed as ABPA-S if they met all the following criteria: asthma, immediate cutaneous hyperreactivity to Aspergillus fumigatus antigen, total IgE levels >1000 IU/mL, A. fumigatus specific IgE levels >0.35 kUA/L and normal HRCT of the chest. They were treated with glucocorticoids and followed up with history, physical examination, chest radiograph and total IgE levels every 6 weeks to 3 months. In addition, an annual spirometry and a biennial HRCT chest were performed in all patients. RESULTS Of the 55 patients with ABPA-S, 41 (17 men, 24 women; mean age, 38.3 years) consented for performance of repeat HRCT scans. The median duration of asthma prior to diagnosis of ABPA was six years. The duration of follow-up ranged from 24 to 77 months with the mean (SD) follow-up duration being 43.7 (10.1) months. There was improvement in FEV(1) but not the FVC values during the follow-up period (p values = 0.001 and 0.5 for FEV(1) and FVC respectively). There was no development of CB in any patient. Sixteen patients had a relapse during the follow-up period, and six patients were classified as glucocorticoid-dependent ABPA. CONCLUSIONS Although relapses are frequently seen, the long-term outcome of ABPA-S is good with no patient developing CB.

A Combination of Shape and Texture Features for Classification of Pulmonary Nodules in Lung CT Images

Classification of malignant and benign pulmonary nodules is important for further treatment plan. The present work focuses on the classification of benign and malignant pulmonary nodules using support vector machine. The pulmonary nodules are segmented using a semi-automated technique, which requires only a seed point from the end user. Several shape-based, margin-based, and texture-based features are computed to represent the pulmonary nodules. A set of relevant features is determined for the efficient representation of nodules in the feature space. The proposed classification scheme is validated on a data set of 891 nodules of Lung Image Database Consortium and Image Database Resource Initiative public database. The proposed classification scheme is evaluated for three configurations such as configuration 1 (composite rank of malignancy “1” and “2” as benign and “4” and “5” as malignant), configuration 2 (composite rank of malignancy “1”,“2”, and “3” as benign and “4” and “5” as malignant), and configuration 3 (composite rank of malignancy “1” and “2” as benign and “3”,“4” and “5” as malignant). The performance of the classification is evaluated in terms of area (Az) under the receiver operating characteristic curve. The Az achieved by the proposed method for configuration-1, configuration-2, and configuration-3 are 0.9505, 0.8822, and 0.8488, respectively. The proposed method outperforms the most recent technique, which depends on the manual segmentation of pulmonary nodules by a trained radiologist.

Chest radiographic and computed tomographic manifestations in allergic bronchopulmonary aspergillosis

AIM To investigate the chest radiographic and high resolution computed tomography (HRCT) chest manifestations in glucocorticoid-naïve allergic bronchopulmonary aspergillosis (ABPA) patients. METHODS This is a prospective observational study and includes 60 consecutive glucocorticoid-naïve patients with ABPA who underwent chest radiography and HRCT of the chest (1.25 mm every 10 mm) in the routine diagnostic workup for ABPA. RESULTS Chest radiographs were normal in 50% of cases. Of the remainder, most patients demonstrated permanent findings in the form of parallel line and ring shadows suggesting bronchiectasis. Consolidation was detected in 17 cases but in the majority, the corresponding HRCT chest scan showed mucus-filled bronchiectatic cavities. Chest HRCT was normal in 22 patients, while central bronchiectasis (CB) was demonstrated in the remaining 38 patients. Bronchiectasis extended to the periphery in 33%-43% depending on the criteria used for defining CB. The other findings observed on HRCT were mucoid impaction, centrilobular nodules and high-attenuation mucus in decreasing order of frequency. CONCLUSION Patients with ABPA can present with normal HRCT chest scans. Central bronchiectasis cannot be considered a characteristic feature of ABPA as peripheral bronchiectasis is commonly observed. Consolidation is an uncommon finding in ABPA.

Cavitary Pulmonary Zygomycosis Caused by Rhizopus homothallicus

ABSTRACT We report the first two proven cases of cavitary pulmonary zygomycosis caused by Rhizopus homothallicus. The diagnosis in each case was based on histology, culture of the causal agent, and the nucleotide sequence of the D1/D2 region of the 28S ribosomal DNA.

Clinical relevance of peripheral blood eosinophil count in allergic bronchopulmonary aspergillosis

BACKGROUND AND AIMS Currently, there is not a uniform consensus regarding the number of criteria or specific cut-off values for the variety of tests that are used to diagnose allergic bronchopulmonary aspergillosis (ABPA). Traditionally, an eosinophil count >1000 cells/μl is considered an important criterion in the diagnosis of ABPA. The goal of this study was to delineate the significance of the peripheral blood eosinophil count in the diagnosis of ABPA, and the relationship between eosinophil counts and lung function and immunological and radiological parameters. METHODS This study was a retrospective analysis of the data from ABPA patients who were managed in our chest clinic. Based on their eosinophil count, the patients were classified into the following three categories: <500, 500-1000 and >1000 cells/μl. The spirometric, immunological and radiological characteristics were also assessed. RESULTS We studied 108 males and 101 females with a combined mean (±SD) age of 34.1±12.5years. The median (IQR) eosinophil count at diagnosis was 850 (510-1541)cells/μl, and 60% of the patients had an eosinophil count of <1000 cells/μl. We found no relationship between eosinophil count and lung function using spirometry and other immunological parameters. The median eosinophil count was higher in patients with an high resolution computed tomography (HRCT) chest finding of bronchiectasis (986 vs. 620, p<0.001) vs. those without and in patients with high-attenuation mucus (1200 vs. 800, p<0.001) compared to those without high-attenuation mucus. CONCLUSIONS A peripheral blood eosinophil count has limited utility in the diagnosis of ABPA, and there is no relationship between eosinophil count and lung function or other immunological parameters. The higher eosinophil count that we observed in patients with central bronchiectasis or high-attenuation mucus suggests that eosinophils are primary mediators of inflammatory activity in ABPA.