Bronchiectasis Severity Index and FACED scores in patients with allergic bronchopulmonary aspergillosis complicating asthma: do they correlate with immunological severity or high-attenuation mucus?

BACKGROUND: The utility of two disease-severity indices, namely bronchiectasis severity index (BSI) and FACED score in allergic bronchopulmonary aspergillosis (ABPA) remains unknown. OBJECTIVE: To correlate the BSI and FACED scores with immunological parameters (serum IgE [total and A. fumigatus-specific], A. fumigatus-specific IgG, blood eosinophil count), and high-attenuation mucus on chest computed tomography in ABPA. The secondary objectives were to evaluate the correlation between BSI and FACED scores and correlate the BSI/FACED scores with the bronchiectasis health questionnaire (BHQ) and Saint George's Respiratory Questionnaire (SGRQ). METHODS: We included treatment-naïve ABPA subjects with bronchiectasis in a prospective observational study. We computed the BSI and FACED scores for each subject before initiating treatment. The subjects also completed two quality-of-life questionnaires (BHQ and SGRQ). RESULTS: We included 91 subjects. The mean (standard deviation) BSI and FACED scores were 3.43 (3.39) and 1.43 (1.27). We found no correlation between BSI or FACED with any immunological parameter or high-attenuation mucus. There was a strong correlation between BSI and FACED scores (r = 0.76, p < 0.001). We found a weak correlation between BSI and BHQ/SGRQ and FACED and SGRQ. CONCLUSION: We found no correlation between BSI and FACED with immunological parameters in ABPA. However, we found a significant correlation between BSI and FACED and a weak correlation between SGRQ and BHQ. ABPA likely requires a separate disease-severity scoring system.

Clinical Manifestation and Treatment of Allergic Bronchopulmonary Aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to airway colonization by Aspergillus fumigatus in patients with asthma and cystic fibrosis. The pathophysiology of ABPA involves a complex interplay between the fungus and the host immune response, which causes persistent inflammation and tissue damage. Patients present with chronic cough, wheezing, and dyspnea due to uncontrolled asthma. Characteristic symptoms include the expectoration of brownish mucus plugs. Radiographic findings often reveal fleeting pulmonary infiltrates, bronchiectasis, and mucus impaction. However, the definitive diagnosis of ABPA requires a combination of clinical, radiological, and immunological findings. The management of ABPA aims to reduce symptoms, prevent disease progression, and minimize the future risk of exacerbations. The treatment approach involves systemic glucocorticoids or antifungal agents to suppress the inflammatory response or fungal growth and prevent exacerbations. Biological agents may be used in patients with severe disease or glucocorticoid dependence. This review provides an overview of the clinical manifestations and current treatment options for ABPA.

Chronic Pulmonary Aspergillosis as a Considerable Complication in Post-Tuberculosis Lung Disease.

Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.

Identification of distinct immunophenotypes in chronic pulmonary aspergillosis using cluster analysis.

BACKGROUND: Whether chronic pulmonary aspergillosis (CPA) has different immunophenotypes remains unknown. OBJECTIVE: To identify different CPA immunophenotypes using cluster analysis. METHODS: We used a subject-centred multivariate clustering approach without prior assumptions to identify CPA phenotypes. We retrospectively included the data of treatment-naïve subjects with CPA and excluded subjects with asthma and allergic bronchopulmonary aspergillosis (ABPA). We performed a scalable two-step cluster analysis using the log-likelihood distance measures to identify CPA phenotypes based on the blood immunological profile (total IgE, eosinophil count and Aspergillus-specific IgE and IgG). RESULTS: We included 351 CPA subjects and found two clusters. Cluster 2 (n = 118) had significantly higher serum total IgE, peripheral blood eosinophil count, and serum A. fumigatus-specific IgE and IgG than cluster 1 (n = 233). Cluster 2 subjects had a lower FEV1:FVC ratio on spirometry and were more likely to have a fungal ball (88 [74.6%] vs. 145 (62.2%), p = .023) on the CT thorax than cluster 1. After treatment discontinuation, cluster 2 had a longer median (interquartile range) time to relapse than cluster 1 (11.5 [7.3-27.4] vs. 4 [1.1-8.9] months, p = .005). CONCLUSION: We identified two distinct CPA phenotypes, type-2 dominant and non-type-2, with different clinical and radiological findings and treatment outcomes. Future studies should confirm our findings and investigate different treatment strategies based on CPA phenotypes.

Corticosteroids for Non-severe COVID-19: Primum Non Nocere.

Muthu V, Sehgal IS, Dhooria S, Prasad KT, Aggarwal AN, Agarwal R. Corticosteroids for Non-severe COVID-19: Primum Non Nocere. Indian J Crit Care Med 2022;26(3):403-404.

Obstructive lung diseases and allergic bronchopulmonary aspergillosis.

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis (ABPA) is a disease frequently complicating asthma and cystic fibrosis. ABPA is increasingly recognized in other obstructive lung diseases (OLDs), including chronic obstructive pulmonary disease (COPD) and noncystic fibrosis bronchiectasis. Herein, we summarize the recent developments in ABPA complicating OLDs. RECENT FINDINGS: Recent research has described the clinical features and natural history of ABPA complicating asthma in children and the elderly. We have gained insights into the pathophysiology of ABPA, especially the role of eosinophil extracellular trap cell death and mucus plugs. The utility of recombinant fungal antigens in the diagnosis of ABPA has been established. Newer, more sensitive criteria for the diagnosis of ABPA have been proposed. Although ABPA is uncommon in COPD and noncystic fibrosis bronchiectasis, aspergillus sensitization is more common and is associated with a higher exacerbation rate. SUMMARY: Several advances have occurred in the diagnosis and treatment of ABPA in recent years. However, there is an unmet need for research into the genetic predisposition, pathophysiology, and treatment of ABPA. Apart from asthma and cystic fibrosis, patients with other OLDs also require evaluation for Aspergillus sensitization and ABPA.

Should Flexible Bronchoscopy be Routinely Performed in Aspiration Pneumonitis: Non Liquet.

How to cite this article: Sehgal IS, Dhooria S, Agarwal R. Should Flexible Bronchoscopy be Routinely Performed in Aspiration Pneumonitis: Non Liquet. Indian J Crit Care Med 2021;25(2):113-114.

Etiology and Outcomes of ARDS in the Elderly Population in an Intensive Care Unit in North India.

BACKGROUND: Whether age would impact the outcomes in subjects with acute respiratory distress syndrome (ARDS) remains unclear. Herein, we study the effect of age as a predictor of mortality in ARDS. MATERIALS AND METHODS: We categorized consecutive subjects with ARDS as either ARDSelderly (age >65 years) or ARDSnonelderly (age ≤65 years) admitted to the respiratory intensive care unit (ICU) of a tertiary care hospital in North India between January 2007 and December 2019. We compared the baseline clinical and demographic characteristics, lung mechanics, and mortality between the two groups. We also analyzed the factors predicting ICU survival using multivariate logistic regression analysis. RESULTS: We included 625 patients (ARDSelderly, 140 [22.4%] and ARDSnonelderly, 485 [77.6%]) with a mean (standard deviation) age (56.3% males) of 40.6 (17.8) years. The ARDSelderly were more likely (p = 0.0001) to have the presence of any comorbid illness compared to ARDSnonelderly. The elderly subjects had significantly higher pulmonary ARDS than the younger group. The severity of ARDS was however, similarly distributed between the two study arms. There were 224 (35.8%) deaths, and the mortality was significantly higher (p = 0.012) in the ARDSelderly than the to ARDSnonelderly (ARDSelderly vs ARDSnonelderly, 45 vs 33.2%). On multivariate logistic regression analysis, the baseline sequential organ failure assessment scores, presence of pulmonary ARDS, and the development of new organ dysfunction were the independent predictors of mortality. CONCLUSION: The outcomes in subjects with ARDS are dependent on the severity of illness at admission and the etiology of ARDS rather than the age alone. HOW TO CITE THIS ARTICLE: Sehgal IS, Agarwal R, Dhooria S, Prasad KT, Muthu V, Aggarwal AN. Etiology and Outcomes of ARDS in the Elderly Population in an Intensive Care Unit in North India. Indian J Crit Care Med 2021;25(6):648-654.

Therapeutic Plasma Exchange: A Lifesaving Therapy in Case of ANCA-associated Vasculitis with Diffuse Alveolar Hemorrhage.

How to cite this article: Tripathi PP, Sharma RR, Chhabria B, Hans R, Sehgal IS. Therapeutic Plasma Exchange: A Lifesaving Therapy in Case of ANCA-associated Vasculitis with Diffuse Alveolar Hemorrhage. Indian J Crit Care Med 2021;25(7):828-829.

Therapeutic whole blood exchange in the management of methaemoglobinemia: Case series and systematic review of literature.

BACKGROUND: Therapeutic whole blood exchange (TWBE) has been used as an alternative when methylene blue (MB) fails in severe methaemoglobinemia. However, there are limited data on the efficacy and safety of TWBE. OBJECTIVES: Our aim was to report our institutional experience with TWBE. We also perform a systematic review of published literature. METHODS: We retrospectively reviewed our respiratory intensive care unit database to identify cases of methaemoglobinemia managed with TWBE. A systematic review of the PubMed database was performed to identify similar cases (≥12 years). We report the indications, utility, and safety of therapeutic exchange in methaemoglobinemia. The procedural details were also noted. RESULTS: We identified five subjects who received TWBE for methaemoglobinemia (median methaemoglobin level 39%; range 19.6-42.4%). TWBE was successful in all five cases and no adverse events were encountered. Our review identified 27 additional subjects. The median methaemoglobin level was 37.5% (range 3.7-81%). The most common indication (n = 24, 75%) for therapeutic exchange was a lack of response to MB. A majority of the subjects (n = 26/32, 81.2%) survived. No procedure-related complications were reported. CONCLUSION: TWBE is a safe and effective salvage modality for adults with methaemoglobinemia, when MB is either contraindicated or ineffective. Future studies should standardise therapeutic exchange in the management of methaemoglobinemia.

Allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by immunologic reactions initiated against Aspergillus fumigatus colonizing the airways of patients with asthma and cystic fibrosis. The common manifestations include treatment-resistant asthma, transient and fleeting pulmonary opacities and bronchiectasis. It is believed that globally there are about five million cases of ABPA, with India alone accounting for about 1.4 million cases. The occurrence of ABPA among asthmatic patients in special clinics may be as high as 13 per cent. Thus, a high degree of suspicion for ABPA should be entertained while treating a patient with bronchial asthma, particularly in specialized clinics. Early diagnosis and appropriate treatment can delay (or even prevent) the onset of bronchiectasis, which suggests that all patients of bronchial asthma should be screened for ABPA, especially in chest clinics. The current review summarizes the recent advances in the pathogenesis, diagnosis and management of ABPA.

Barrier Protection during Airway Intubation.

How to cite this article: Sehgal IS, Yaddanapudi LN, Dhooria S, Thurai Prasad K, Puri GD, Muthu V, et al. Barrier Protection during Airway Intubation. Indian J Crit Care Med 2020;24(6):485-486.

Challenging cases in fungal asthma.

Fungal asthma broadly encompasses the presence of fungal sensitization or fungal allergy in patients with asthma. The clinical presentation of fungal asthma can vary from fungal-sensitized asthma at one end to allergic bronchopulmonary mycosis at the other end of the spectrum. Here we present five cases that illustrate some of the most challenging aspects of the diagnosis and management of fungal asthma. The cases are aimed at elucidating complex clinical presentations in fungal asthma such as allergic bronchopulmonary mycosis presenting with normal immunoglobulin E (IgE) values, the role of several different fungi in causing allergic mycosis, newer treatments like omalizumab (and mepolizumab), and a complication of long-standing allergic bronchopulmonary aspergillosis, namely, chronic pulmonary aspergillosis.

Vitamin D levels in asthmatic patients with and without allergic bronchopulmonary aspergillosis.

Vitamin D deficiency is believed to be a pathogenetic factor in patients with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. Whether vitamin D deficiency is also prevalent in ABPA complicating asthma, remains unknown. Herein, we evaluated vitamin D levels in asthmatic patients with and without ABPA. In a prospective study, plasma vitamin D (25[OH]D) levels were measured in consecutive subjects with asthma (n = 75), ABPA (n = 158) and healthy volunteers (n = 50). Vitamin D levels <20 ng/mL were considered as vitamin D deficiency. There was no difference in mean (95% CI) vitamin D levels between healthy controls (15.3 [12.7-17.9]), asthmatics (19.2 [16.3-22.1]) and subjects with ABPA (18.9 [16.9-20.8]) (P = .22). Vitamin D deficiency was encountered in 70%, 64% and 65% of the healthy controls, asthmatics and ABPA subjects, respectively, and was not different between the groups (P = .79). There was no difference in the asthma control, pulmonary function, immunological findings and the severity of bronchiectasis, in patients with ABPA, with and without vitamin D deficiency. Vitamin D deficiency is equally prevalent in asthmatic patients with or without ABPA in the Indian subcontinent, and does not appear to play a major role in the pathogenesis of ABPA complicating asthma.

Chronic obstructive pulmonary disease and malnutrition in developing countries.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disorder characterized by progressive, poorly reversible airflow limitation. In addition to its pulmonary manifestations, COPD is also associated with several systemic expressions including anemia, osteoporosis, coronary artery disease, and malnutrition. In COPD, malnutrition is a consequence of reduced nutritional intake and muscle loss, further compounded by systemic inflammation. In the developing world, malnutrition is a significant problem by itself, even without any systemic illness. It is likely that the occurrence and consequence of malnutrition in COPD may be even more profound in developing countries. In this review, we discuss the relationship between malnutrition and COPD and their overall impact in the developing world. RECENT FINDINGS: COPD is highly prevalent in developing countries with an estimated 15-43 million patients suffering from COPD. The pooled prevalence of malnutrition in COPD was found to be 47.6% [95% confidence interval (CI), 23.5-71.5%] with the prevalence being higher in acute exacerbations of COPD compared to stable COPD. SUMMARY: There is a need for generating good quality evidence from the developing world regarding the prevalence of malnutrition in COPD, the role of nutritional supplementation and its impact on exercise capacity, and overall health-related quality of life in patients with COPD.

Training and proficiency in endobronchial ultrasound-guided transbronchial needle aspiration: A systematic review.

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is currently the modality of choice for evaluation of mediastinal lymphadenopathy. However, there is still uncertainty regarding the training methodology and the number of procedures required to attain proficiency in EBUS. Herein, we performed a systematic review of studies selected from PubMed, EmBase and Scopus databases describing the training and assessment of proficiency during EBUS, specifically studies investigating various methods for training, its outcome and the number of procedures required to overcome the learning curve for EBUS. Twenty-seven (simulator-based learning (n = 8), tools for assessing competence in EBUS-TBNA (n = 5) and threshold numbers needed to attain proficiency in EBUS-TBNA (n = 16)) studies were identified. An EBUS simulator accurately stratified individuals based on the level of experience in performing EBUS. Training received on a simulator was comparable with traditional apprentice-based training. Importantly, skills acquired on a simulator could be transferred to real-world patients. The number needed to overcome the initial learning curve of EBUS varied from 10 to 100 in individual studies with a mean of 37-44 procedures. Tools such as EBUS-STAT (EBUS skill and task assessment tool) and EBUSAT (EBUS skill and assessment tool) were effective in evaluating the EBUS trainees. We conclude that an EBUS simulator or EBUS assessment tools can objectively assess the training of an EBUS trainee. Simulator-based training is a useful modality in EBUS training. The number of procedures needed to overcome the initial learning curve is about 40. Centres involved in EBUS training could incorporate simulator-based training in their curriculum before allowing operators to perform EBUS on patients.

Aspergillus sensitisation in bidi smokers with and without chronic obstructive lung disease.

Recent studies have described fungal sensitisation in patients with chronic obstructive pulmonary disease (COPD). However, no study has evaluated fungal sensitisation specifically in bidi smokers. Herein, we evaluate the prevalence of Aspergillus sensitisation in bidi smokers. Bidi smokers with and without COPD underwent chest radiography, spirometry, Aspergillus skin test, A. fumigatus precipitins, A. fumigatus-specific IgE and total IgE. Aspergillus sensitisation was defined as the presence of either immediate cutaneous hyperreactivity to Aspergillus antigen or raised A. fumigatus-specific IgE level >0.35 kUA/L. Bidis were obtained from a subset of cases and controls and cultured for the growth of any fungus. Two hundred subjects with COPD and 72 chronic bidi smokers without COPD were included in the study (258 men; mean age, 56.8 years). Aspergillus sensitisation was found to be significantly higher in bidi smokers without COPD (27.8%) compared to the COPD cases (16%). Age, COPD, lung function, severity of smoking and current smoking were not associated with Aspergillus sensitisation, on a multivariate logistic regression analysis. We found a high prevalence of Aspergillus sensitisation in bidi-smoking subjects. More studies are required to confirm the findings of our study.

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.

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.