Pulmonary Langerhans Cell Histiocytosis: Diagnosis in Bronchoalveolar Lavage Liquid-based Cytology Samples.

INTRODUCTION: Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease characterized by the accumulation of Langerhans cells within the lung tissue. The diagnosis of PLCH traditionally involves clinical, radiological, and lung biopsy histopathological evaluations. CASE PRESENTATION: We present two cases where the diagnosis of PLCH was confirmed through the analysis of bronchoalveolar lavage (BAL) fluid cytology using immunoperoxdase technique, highlighting the significance of this minimally invasive technique in the diagnostic process. Clinical and radiological examination suggested advanced interstitial lung disease characterized by a fibrocystic pattern in both cases. The cytologic analysis of the BAL fluid revealed typical histiocytes with longitudinal grooves and eosinophils, which was better seen on liquid-based cytology (LBC) smears. ICC with a CD1a, Langerin, and S-100 confirmed the diagnosis of PLCH. CONCLUSION: Detecting PLCH through the examination of BAL cytology poses challenges, yet it is achievable, particularly with the assistance of LBC and ICC.

Pleural effusion guidelines from ICS and NCCP Section 1: Basic principles, laboratory tests and pleural procedures.

Pleural effusion is a common problem in our country, and most of these patients need invasive tests as they can't be evaluated by blood tests alone. The simplest of them is diagnostic pleural aspiration, and diagnostic techniques such as medical thoracoscopy are being performed more frequently than ever before. However, most physicians in India treat pleural effusion empirically, leading to delays in diagnosis, misdiagnosis and complications from wrong treatments. This situation must change, and the adoption of evidence-based protocols is urgently needed. Furthermore, the spectrum of pleural disease in India is different from that in the West, and yet Western guidelines and algorithms are used by Indian physicians. Therefore, India-specific consensus guidelines are needed. To fulfil this need, the Indian Chest Society and the National College of Chest Physicians; the premier societies for pulmonary physicians came together to create this National guideline. This document aims to provide evidence based recommendations on basic principles, initial assessment, diagnostic modalities and management of pleural effusions.

Innate and adaptive immune responses in subjects with CPA secondary to post-pulmonary tuberculosis lung abnormalities.

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%-25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. METHODS: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. RESULTS: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets. CONCLUSION: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.

Bronchial Valves for Persistent Air Leak: A Systematic Review and Meta-analysis.

BACKGROUND: Patients with persistent air leak (PAL) pose a therapeutic challenge to physicians, with prolonged hospital stays and high morbidity. There is little evidence on the efficacy and safety of bronchial valves (BV) for PAL. METHODS: We systematically searched the PubMed and Embase databases to identify studies evaluating the efficacy and safety of BV for PAL. We calculated the success rate (complete resolution of air leak or removal of intercostal chest drain after bronchial valve placement and requiring no further procedures) of BV for PAL in individual studies. We pooled the data using a random-effects model and examined the factors influencing the success rate using multivariable meta-regression. RESULTS: We analyzed 28 observational studies (2472 participants). The pooled success rate of bronchial valves in PAL was 82% (95% confidence intervals, 75 to 88; 95% prediction intervals, 64 to 92). We found a higher success rate in studies using intrabronchial valves versus endobronchial valves (84% vs. 72%) and in studies with more than 50 subjects (93% vs. 77%). However, none of the factors influenced the success rate of multivariable meta-regression. The overall complication rate was 9.1% (48/527). Granulation tissue was the most common complication reported followed by valve migration or expectoration and hypoxemia. CONCLUSION: Bronchial valves are an effective and safe option for treating PAL. However, the analysis is limited by the availability of only observational data.

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.

Diagnostic Yield and Safety of the 19-Gauge versus 22-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle in Subjects with Sarcoidosis (GUESS).

INTRODUCTION: Observational data suggest that the 19-gauge (G) needle for endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) offers a higher diagnostic yield than the 22-G needle in sarcoidosis. No randomized trial has compared the yield of the two needles. METHODS: We randomized consecutive subjects with suspected sarcoidosis and enlarged thoracic lymph nodes to undergo EBUS-TBNA with either the 19-G or the 22-G needle. We compared the study groups for diagnostic sensitivity (primary outcome) assessed by the yield of granulomas in subjects finally diagnosed with sarcoidosis. We also compared the sample adequacy, difficulty performing the needle puncture assessed on a visual analog scale (VAS), the subject's cough intensity on an operator-rated VAS, and procedure-related complications (secondary outcomes). RESULTS: We randomized 150 (mean age, 43.0 years; 55% women) subjects and diagnosed sarcoidosis in 116 subjects. The diagnostic sensitivity of the 19-G needle (45/60, 75.0%) was not higher (p = 0.52) than the 22-G needle (39/56, 69.6%). We obtained adequate aspirates in 90.0% and 85.7% of subjects in the respective groups (p = 0.48). The operators had greater difficulty puncturing lymph nodes with the 19-G needle (p = 0.03), while the operator-assessed cough intensity was similar in the groups (p = 0.41). Transient hypoxemia was the only complication encountered during EBUS-TBNA (two subjects in either group). CONCLUSION: We did not find the 19-G needle superior to the 22-G in diagnostic sensitivity, specimen adequacy, or safety of EBUS-TBNA in sarcoidosis. Puncturing the lymph nodes was more difficult with the 19-G needle.

Sensitivity and specificity of LDBio Aspergillus ICT lateral flow assay for diagnosing allergic bronchopulmonary aspergillosis in adult asthmatics.

BACKGROUND: Aspergillus fumigatus-specific IgG estimation is crucial for diagnosing allergic bronchopulmonary aspergillosis (ABPA). A point-of-care LDBio immunochromatographic lateral flow assay (LFA) had 0%-90% sensitivity to detect IgG/IgM antibodies against A. fumigatus. OBJECTIVE: To assess the accuracy of LDBio-LFA in diagnosing ABPA, using the modified ISHAM-ABPA working group criteria as the reference standard. The secondary objective was to compare the diagnostic performance between LDBio-LFA and A. fumigatus-specific IgG (cut-offs, 27 and 40 mgA/L), using a multidisciplinary team (blinded to A. fumigatus-IgG and LDBio-LFA results) diagnosis of ABPA as the reference standard. METHODS: We prospectively enrolled adult subjects with asthma and ABPA. We performed the LDBio-LFA per the manufacturer's recommendations. We used the commercially available automated fluorescent enzyme immunoassay for measuring serum A. fumigatus-specific IgG. We used the same serum sample to perform both index tests. The tests were performed by technicians blinded to the results of other tests and clinical diagnoses. RESULTS: We included 123 asthmatic and 166 ABPA subjects, with a mean ± SD age of 37.4 ± 14.4 years. Bronchiectasis and high-attenuation mucus were seen in 93.6% (146/156) and 24.3% (38/156) of the ABPA subjects. The sensitivity and specificity of LDBio-LFA in diagnosing ABPA were 84.9% and 82.9%, respectively. The sensitivity of serum A. fumigatus-specific IgG ≥27 mgA/L was 13% better than LDBio-LFA, with no difference in specificity. There was no significant difference in sensitivity and specificity between LDBio-LFA and serum A. fumigatus-IgG ≥40 mgA/L. CONCLUSION: LDBio-LFA is a valuable test for diagnosing ABPA. However, a negative test should be confirmed using an enzyme immunoassay.

Incidence and prevalence of chronic pulmonary aspergillosis in patients with post-tuberculosis lung abnormality: Results from a community survey in North India.

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for developing chronic pulmonary aspergillosis (CPA). However, the prevalence and incidence of CPA in PTLA patients in India remain unknown. OBJECTIVES: We aimed to ascertain the incidence and prevalence of CPA in subjects with PTLA. METHODS: We identified a cohort of pulmonary tuberculosis who completed anti-tuberculosis therapy (ATT) before November 2019 from the records of the 12 tuberculosis treatment centers attached to the national program. We recorded the clinical and demographic details. We performed computed tomography (CT) of the chest and estimated serum A. fumigatus-specific IgG. We categorised subjects as PTLA with or without CPA using a composite of clinical, radiological, and microbiological features. We resurveyed the subjects at 6 months (or earlier) for the presence of new symptoms. We calculated the prevalence and the incidence rate (per 100-person years) of CPA. RESULTS: We included 117 subjects with PTLA, with a median of 3 years after ATT completion. Eleven subjects had CPA in the initial survey, and one additional case developed CPA during the second survey. The prevalence of CPA in PTLA subjects was 10.3% (12/117). The total observation period was 286.7 person-years. The median (interquartile range) time to develop CPA after ATT completion was 12.5 (5-36.7) months. We found the CPA incidence rate (95% confidence interval) of 4.2 (1.8-6.5) per 100-person years. CONCLUSION: Chronic pulmonary aspergillosis complicates 10% of PTLA subjects after successful outcomes with ATT. Four new CPA cases may develop per 100-persons years of observation after ATT completion. We suggest screening patients with PTLA who develop new symptoms for CPA.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Burden, clinical features, and outcomes of post-tuberculosis chronic obstructive lung diseases.

PURPOSE OF REVIEW: Post-tuberculosis lung disease (PTLD) is an increasingly recognized and debilitating consequence of pulmonary tuberculosis (PTB). In this review, we provide a comprehensive overview of PTLD with airflow obstruction (PTLD-AFO), focusing on its burden, pathophysiology, clinical manifestations, diagnostic methods, and management strategies. RECENT FINDINGS: The relationship between PTLD and airflow obstruction is complex and multifactorial. Approximately 60% of the patients with PTLD have some spirometric abnormality. Obstruction is documented in 18-22% of PTLD patients. The host susceptibility and host response to mycobacterium drive the pathogenic mechanism of PTLD. A balance between inflammatory, anti-inflammatory, and fibrotic pathways decides whether an individual with PTB would have PTLD after microbiological cure. An obstructive abnormality in PTLD-AFO is primarily due to destruction of bronchial walls, aberrant healing, and reduction of mucosal glands. The most common finding on computed tomography (CT) of thorax in patients with PTLD-AFO is bronchiectasis and cavitation. Therefore, the 'Cole's vicious vortex' described in bronchiectasis applies to PTLD. A multidisciplinary approach is required for diagnosis and treatment. The disability-adjusted life-years (DALYs) attributed to PTLD represent about 50% of the total estimated burden of DALYs due to tuberculosis (TB). Patients with PTLD require comprehensive care that includes psychosocial support, pulmonary rehabilitation, and vaccination against respiratory pathogens. In the absence of trials evaluating different treatments for PTLD-AFO, therapy is primarily symptomatic. SUMMARY: PTLD with airflow obstruction has considerable burden and causes a significant morbidity and mortality. However, many aspects of PTLD-AFO still need to be answered. Studies are required to evaluate different phenotypes, especially concerning Aspergillus -related complications. The treatment should be personalized based on the predominant phenotype of airflow obstruction. Extensive studies to understand the exact burden, pathogenesis, and treatment of PTBLD-AFO are needed.

Evaluation of Dynamic Contrast-Enhanced and Oxygen-Enhanced Functional Lung Magnetic Resonance Imaging in Chronic Obstructive Pulmonary Disease Patients.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by obstruction of airways and emphysematous lung tissue damage, with associated hypoxic vasoconstriction in the affected lung parenchyma. In our study, we evaluate the role of oxygen-enhanced (OE) MRI and dynamic contrast enhanced (DCE)-MRI in COPD patients for assessment of ventilation and perfusion defects and compared their severity with clinical severity. A total of 60 patients with COPD (diagnosed based on clinical and spirometry findings) and 2 controls with normal spirometry and no history of COPD were enrolled. All patients underwent MRI within 1 month of spirometry. OE-MRI was performed by administering oxygen at 12 L/min for 4 min to look for ventilation defects. DCE-MRI was performed by injecting intravenous gadolinium contrast, and perfusion abnormalities were detected by subtracting the non-enhanced areas from the first pass perfusion contrast images. A total of 87% of the subjects demonstrated ventilation and perfusion abnormalities on MRI independently. The lobe-wise distribution of ventilation and perfusion abnormalities correlated well with each other and was statistically significant in all lobes (p < 0.05). The severity of ventilation-perfusion defects also correlated well with clinical severity, as their median value (calculated using a Likert rating scale) was significantly lower in patients in the Global initiative for chronic Obstructive Lung Disease (GOLD) I/II group (3.25) compared to the GOLD III/IV group (7.25). OE- and DCE-MRI provide functional information about ventilation-perfusion defects and their regional distribution, which correlates well with clinical severity in patients with COPD.

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.

High-dose (40†mg) versus low-dose (20†mg) prednisolone for treating sarcoidosis: a randomised trial (SARCORT trial).

BACKGROUND: Current guidelines recommend 20-40 mg·day-1 of oral prednisolone for treating pulmonary sarcoidosis. Whether the higher dose (40 mg·day-1) can improve outcomes remains unknown. METHODS: We conducted an investigator-initiated, single-centre, open-label, parallel-group, randomised controlled trial (ClinicalTrials.gov identifier NCT03265405). Consecutive subjects with pulmonary sarcoidosis were randomised (1:1) to receive either high-dose (40 mg·day-1 initial dose) or low-dose (20 mg·day-1 initial dose) oral prednisolone, tapered over 6 months. The primary outcome was the frequency of relapse or treatment failure at 18 months from randomisation. Key secondary outcomes included the time to relapse or treatment failure, overall response, change in forced vital capacity (FVC, in litres) at 6 and 18 months, treatment-related adverse effects and health-related quality of life (HRQoL) scores using the Sarcoidosis Health Questionnaire and Fatigue Assessment Scale. FINDINGS: We included 86 subjects (43 in each group). 42 and 43 subjects completed treatment in the high-dose and low-dose groups, respectively, while 37 (86.0%) and 41 (95.3%), respectively, completed the 18-month follow-up. 20 (46.5%) subjects had relapse or treatment failure in the high-dose group and 19 (44.2%) in the low-dose group (p=0.75). The mean time to relapse/treatment failure was similar between the groups (high-dose 307 days versus low-dose 269 days, p=0.27). The overall response, the changes in FVC at 6 and 18 months and the incidence of adverse effects were also similar. Changes in HRQoL scores did not differ between the study groups. INTERPRETATION: High-dose prednisolone was not superior to a lower dose in improving outcomes or the HRQoL in sarcoidosis and was associated with similar adverse effects.