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.

Prevalence of Aspergillus sensitization and Allergic Bronchopulmonary Aspergillosis in bronchial asthma: A systematic review of Indian studies.

Background: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma. Methods: We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression. Results: Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence. Conclusions: There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA.

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.

Clinical profile of COVID-19 patients and their length of stay: Tertiary care hospital experience.

Background: SARSCoV-2, a coronavirus that causes COVID-19, is spreading rapidly. By the middle of August-2021, it has affected over 3 million confirmed cases in India. The main aim of this study was to examine the clinical profile of COVID-19 patients and their length of stay during treatment in a hospital. Materials and Methods: It was a hospital-based retrospective study conducted by using a total enumeration technique in July-August 2021 at Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER) in India. The present study was conducted on 72 COVID-19 patients who took treatment in 4C and 5C wards. Structured questionnaires were used to collect data, which included bio-demographic factors and questions about their treatment and length of stay. Results: The majority of the 72 COVID-19 positive patients were men (62%), belonged to the age group of 41-60 years (35%), had SpO2 levels ranging from 91%-95% (45%), and received room air O2 therapy (63%) during their treatment in the hospital. Female patients had a longer length of stay (7.33 days), patients under the age of 20 years had the longest hospital stay (11.5 days), patients with SpO2 less than 70% had the longest hospital stay (8 days), and patients who received oxygen using a non-rebreathing mask had the longest hospital stay (11 days). Conclusion: To avoid panic situations, regular admission and discharge of patients was essential due to the considerable increase in cases during the second wave. Patient length of stay was reduced as a consequence of collaboration and cooperation among all physicians, residents, staff nurses, and paramedics, with the goal of discharging the patient after a room air trial and follow up if needed.

A brief report on the mutational landscape in non-small cell lung cancer of South Asian patients: Comparison at a US and an Indian Institution.

Background: Various molecular underpinnings of lung cancer have been noted in Asian populations, especially with targetable oncogenic drivers such as EGFR mutations and ALK rearrangements, although they have been lesser described in South Asian/Indian patients. Methods: Tumour molecular testing results from non-small cell lung cancer (NSCLC) patients with a name of South Asian origin and diagnosed from 2005 to 2019 at the Stanford Cancer Center in the United States were retrospectively reviewed and compared to the results of molecular testing from PGIMER in Chandigarh, India, from the patients diagnosed from 2011 to 2019. Results: We identified 72 patients of South Asian (largely Indian) origin, of whom 64 patients (51% female) had mutational testing at Stanford. Of the tested patients, 33% of cases harboured either an EGFR exon 19 deletion or exon 21 L858R mutation, and 12.5% had ALK rearrangements. At PGIMER, a larger sample of 1,264 patients was identified (33% female), with 22.5% of patients having two main EGFR activating mutations, and 9.5% harbouring an ALK rearrangement. Conclusions: South Asian, largely Indian, patients with NSCLC appear to have a higher chance of harbouring EGFR mutations and ALK translocation as compared to Caucasians. The percentage of South Asian patients with these molecular abnormalities was largely similar in two different geographical locations. These findings corroborate prior single-institution findings and emphasise the importance of molecular testing.

Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India.

BACKGROUND: Chronic pulmonary aspergillosis has a 5-year mortality of 50-80% globally, and the optimal duration of treatment for chronic pulmonary aspergillosis remains unclear. We aimed to compare the effect of 6-months of oral itraconazole with 12-months of oral itraconazole on chronic pulmonary aspergillosis clinical outcomes. METHODS: In this single-centre, open-label, randomised controlled trial conducted in one chest clinic in Chandigarh, India, we screened consecutive patients with chronic pulmonary aspergillosis who were naive to antifungal treatment and randomised eligible patients, using block randomisation, to receive a starting dose of 400 mg/day of oral itraconazole for either 6 months or 12 months. There was no masking of participants or investigators. We excluded patients who were unable to provide informed consent; had an intake of any antifungal drugs for more than 3 weeks in the preceding 6 months; had active Mycobacterium tuberculosis or non-tuberculous mycobacterial pulmonary disease; and had allergic, subacute, or invasive forms of aspergillosis. The primary outcome was the proportion of patients having relapse 2 years after treatment initiation. We performed an intention-to-treat analysis for all outcomes. The study is registered with ClinicalTrials.gov, NCT03920527. FINDINGS: We recruited participants between July 1, 2019, and Aug 31, 2021. We screened 250 patients, of which 164 were included in the trial. 81 patients were randomised to the 6-month group and 83 patients were randomised to the 12-month group. The study population was 78 (48%) women and 86 (52%) men, and the mean age of participants was 44·3 (SD 13·3) years. The proportion of patients experiencing relapse was significantly lower in the 12-month group, 31 (38%) had a relapse in the 6-month group compared with 8 (10%) in the 12-month group, with an absolute risk reduction of 0.29 [95% CI 0·16-0·40]. The mean time to first relapse was 23 months in the 12-month group, which is significantly longer than the mean of 18 months in the 6-month group (p<0.0001). There were 16 deaths in total, eight in each group. Ten (12%) of 81 patients in the 6-months group and 18 (22%) of 83 patients in the 12-months group had adverse effects, with none requiring treatment modification. Nausea and anorexia were the most common adverse events in both groups. INTERPRETATION: Treatment of chronic pulmonary aspergillosis with 12 months of oral itraconazole was superior to 6 months of oral itraconazole in reducing relapses at 2 years. Itraconazole should be given for at least 12 months for treating chronic pulmonary aspergillosis. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Allergic Bronchopulmonary Aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a complex allergic disorder caused by immune reactions against Aspergillus fumigatus. ABPA most commonly complicates the course of patients with poorly controlled asthma. Patients commonly present with uncontrolled asthma, fleeting pulmonary opacities, and bronchiectasis. Pathogenetically, ABPA is characterized by the persistence of A. fumigatus in the airways and an exaggerated type-2 immune response. The interest in ABPA stems from the fact that bronchiectasis in ABPA can be prevented if the disorder is diagnosed timely and treated appropriately. Herein, we summarize the current concepts in the epidemiology, pathogenesis, diagnosis, and treatment of ABPA.

Feasibility and impact of screening for venous thromboembolism in treatment-naive lung cancer patients-Results of a prospective cohort study.

Background: Venous thromboembolism (VTE) in cancer remains underdiagnosed. This prospective study aimed to evaluate the feasibility of screening for VTE in lung cancer (LC) patients. We assess the incidence of VTE, its risk factors, and effects on overall survival (OS). Methods: Consecutive treatment-naive LC patients were screened for deep venous thrombosis (DVT) with compression ultrasonography and pulmonary thromboembolism (PTE) with computed tomography pulmonary angiography (CTPA) at diagnosis and after 3 months of treatment. The incidence rate of VTE (DVT and/or PTE) was calculated. Risk factors associated with VTE were assessed using logistic regression analysis. All participants were followed-up to 1 year after enrollment. OS was compared in LC subjects with and without VTE, using the Cox proportional hazard analysis. Results: Around 301 subjects with LC (stages IIIB-IV accounted for 83.1%) were enrolled, of which 16 had VTE (5.3%). The incidence rate of VTE was 90 per 1000 person-years (PY). PTE was asymptomatic in 27.3% of cases while all DVT episodes were symptomatic. The incidence rate of asymptomatic PTE identified during the screening was 17 per 1000 PY. The median duration from LC diagnosis to the VTE event was 96.5 days. Median OS was significantly less in VTE patients [161 versus 311 days; P = 0.007] and death was attributable to VTE in 50%. After adjusting for covariates, VTE (hazard ratio [HR] = 2.1), smoking (HR = 1.7), and Eastern cooperative oncology group performance status ≥2 (HR = 1.6) were independently associated with poor OS in LC. Conclusions: VTE occurs in approximately 1 in 20 newly-diagnosed patients with LC and is associated with decreased OS. Screening for PTE may be considered even in resource-limited settings.

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.

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.

Thyroid dysfunction in non-small cell lung cancer patients treated with epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors: Results of a prospective cohort.

OBJECTIVES: Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitors (TKIs) are the preferred treatment option for patients with advanced/metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations and ALK rearrangements respectively. TKIs can theoretically induce thyroid dysfunction via actions on many levels of the hypothalamic-pituitary-thyroid axis. However, there are no published studies on occurrence of thyroid dysfunction related to use of EGFR/ALK TKIs in lung cancer. The current study aimed to prospectively and comprehensively evaluate incidence of thyroid dysfunction in NSCLC patients treated with EGFR and ALK inhibitors. METHODS: This prospective observational study at a tertiary care referral hospital included histologically/cytologically proven advanced/metastatic NSCLC patients treated with EGFR and ALK inhibitors over a period of 15 months. Thyroid function tests (including anti-TPO antibody) were done at baseline and repeated every month for first three months and then every three monthly for 12 months. RESULTS: Six different drugs (EGFR and ALK inhibitors) were used for treatment of 50 NSCLC patients enrolled. Of these, four drugs caused thyroid dysfunction (EGFR inhibitors erlotinib, gefitinib and ALK inhibitors ceritinib, crizotinib). Thyroid dysfunction typically occurred at 1 month following start of TKI treatment. Prevalence of thyroid dysfunction was 8%. Distribution of subclinical (not requiring treatment) and overt thyroid dysfunction (requiring specific treatment) was 4% each. All patients were asymptomatic. Both patients with overt thyroid dysfunction had hypothyroidism while subclinical dysfunction was equally distributed between hypo- and hyper- thyroidism. All patients who developed thyroid dysfunction derived expected clinical benefit and none required TKI dose interruption or stoppage. CONCLUSIONS: NSCLC patients may need to be monitored for occurrence of thyroid dysfunction during treatment with EGFR and ALK TKIs.

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.

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.

Diagnostic Utility and Safety of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration in the Elderly.

BACKGROUND: There is limited evidence regarding the effect of age on the specimen adequacy, positivity rate of specimen on cytology (PR), and safety of endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA). The aim of this study was to investigate the utility of EBUS-TBNA in the elderly. METHODS: This was a retrospective study of subjects who underwent EBUS-TBNA. We compare the specimen adequacy, PR, and the incidence of complications in the elderly (age 65 y and above) versus the younger subjects (age younger than 65 y). A multivariate logistic regression analysis was performed to identify the factors affecting the diagnostic yield. RESULTS: Of the 1816 subjects, 258 (14.2%) were elderly. The specimen adequacy was similar between the old and the young (93.5% vs. 96.3%, P=0.053). The PR in the elderly (48.8%) was lower (P<0.001) than the younger subjects (66.7%). Among those with a definite diagnosis made on EBUS-TBNA, 55.4% of the older subjects had malignancy, while 82.4% of the young had granulomatous disorders. The incidence of complications was similar in the 2 groups (3.9% vs. 4.4%, P=0.87). The specimen adequacy, PR and complications were also similar among the different age groups within the older population (65 to 69, 70 to 74, 75 to 79, and 80 y and above). On multivariate logistic regression analysis, older age, the number of lymph nodes sampled, the lymph node size, and needle reuse influenced the PR. CONCLUSION: EBUS-TBNA appears to have a similar specimen adequacy and safety but a lower PR in the elderly as compared with the younger individuals.