Sex Differences in Allergic Bronchopulmonary Aspergillosis and its Impact on Exacerbations.

The impact of sex on allergic bronchopulmonary aspergillosis (ABPA) outcomes remains uncertain. We retrospectively included ABPA subjects per the revised International Society for Human and Animal Mycology ABPA working group criteria over 13 years. We compared the clinical features, lung function, immunological tests, imaging, and ABPA exacerbation rates between men and women. Our primary objective was to assess whether women experience higher ABPA exacerbations than men. We included 731 ABPA subjects (mean age, 34.5 years; 49.5% women). Women with ABPA were older and had underlying asthma more frequently than men. There was no difference in lung function, immunological investigations, and imaging between men and women. ABPA exacerbations occurred in a slightly higher proportion of women than men (44.5% vs. 38.2%) but did not reach statistical significance (p = 0.09). We did not find a significant sex difference in ABPA exacerbation rates. Prospective studies should confirm our findings.

Xpert MTB/RIF Ultra as a diagnostic tool for pleural tuberculosis: a study at Indian tertiary care centre.

Despite the advent of Xpert MTB/RIF, pleural tuberculosis (TB) diagnosis in pleural fluid is still difficult. Hence, we assessed the diagnostic efficacy of its advanced version, Xpert MTB/RIF Ultra for pleural TB diagnosis using pleural fluid as sample. Tuberculosis pleuritis (TBP) suspects (n = 261) were enrolled in the study of which 29 were excluded. The remaining patients (n = 232) were categorized into definite TBP (n = 31), probable TBP (n = 28), and non-TB controls (n = 173) based on composite reference standard consisting of smear, culture, histopathology, and Xpert MTB/RIF as well as follow up/clinical response to anti-tuberculosis therapy. Among the TBP suspects, 59 were diagnosed as TBP patients. The sensitivity of Xpert MTB/RIF Ultra (52.5%) using pleural fluid for TBP diagnosis was higher than sensitivity obtained with smear (22.4%), culture (17.6%), and Xpert MTB/RIF (25%) alone, carried using either pleural fluid or pleural biopsy or both the samples. In cases of probable TBP, where none of the laboratory tests were positive, Xpert MTB/RIF Ultra use led to an increased diagnostic percentage of definite TBP from 52.5% to 69.4% Overall, the Xpert MTB/RIF Ultra showed promising results for a definitive diagnosis of TBP in pleural fluid samples.

Population prevalence of aspergillus sensitization and allergic bronchopulmonary aspergillosis in COPD subjects in North India.

BACKGROUND: Sensitization to Aspergillus fumigatus (AS) has been recently described in chronic obstructive pulmonary disease (COPD) patients. However, there is no data on the community prevalence of AS in COPD. OBJECTIVES: To assess the prevalence of AS among COPD subjects. The secondary objectives were to (1) assess the prevalence of allergic bronchopulmonary aspergillosis (ABPA) in COPD and (2) compare the lung function in COPD subjects with and without AS. METHODS: We conducted a cross-sectional study in rural (29 villages) and urban (20 wards) communities in North India. We identified individuals with respiratory symptoms (IRS) through a house-to-house survey using a modified IUATLD questionnaire. We then diagnosed COPD through specialist assessment and spirometry using the GOLD criteria. We assayed A.fumigatus-specific IgE in COPD subjects. In those with A. fumigatus-specific IgE ≥0.35 kUA/L (AS), ABPA was diagnosed with raised serum total IgE and raised A.fumigatus-specific IgG or blood eosinophil count. RESULTS: We found 1315 (8.2%) IRS among 16,071 participants >40 years and diagnosed COPD in 355 (2.2%) subjects. 291 (82.0%) were men and 259 (73.0%) resided in rural areas. The prevalence of AS and ABPA was 17.7% (95% CI, 13.9-21.8) and 6.6% (95% CI, 4.4-8.8). We found a lower percentage predicted FEV1 in COPD subjects with AS than those without (p =.042). CONCLUSIONS: We found an 18% community prevalence of AS in COPD subjects in a specific area in North India. Studies from different geographical areas are required to confirm our findings. The impact of AS and ABPA on COPD requires further research.

Xpert MTB/XDR assay: rapid TB drug resistance detection.

PURPOSE: To assess the Xpert MTB/XDR assay's efficiency in promptly detecting resistance to isoniazid, fluoroquinolones, ethionamide, and second-line injectable drugs among tuberculosis (TB) patients. METHODS: From August 2020 to July 2021, TB suspected patient samples were enrolled at a tertiary care center for our study. We conducted mycobacterial culture, phenotypic DST using proportion method in liquid culture at WHO-recommended concentrations, and the line probe assay (LPA). Simultaneously, the Index test, Xpert MTB/XDR, was performed following the manufacturer's instructions. RESULTS: Among 360 samples, 107 were excluded due to incomplete information. Resistance to isoniazid, levofloxacin and moxifloxacin was found in 45/251, 21/251 and 20/251 samples, respectively by phenotypic DST. The diagnostic accuracy of Index test, taking phenotypic DST as a reference standard, was 95.8%, 99.04%, and 99.05% for isoniazid, levofloxacin, and moxifloxacin, respectively. The Index test assay demonstrated a specificity of 99.1% for detecting SLID resistance, yielding a diagnostic accuracy of 99.2. Comparing the Index test with LPA revealed a significant enhancement in sensitivity for detecting isoniazid resistance (86.7% vs. 82.2%). CONCLUSIONS: The Index test exhibited promising outcomes in identifying resistance to isoniazid and fluoroquinolones, surpassing the performance of the LPA. This could be valuable for promptly initiating treatment in cases of drug-resistant tuberculosis.

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.

Safety and Efficacy of 25 mg/kg and 35 mg/kg vs 10 mg/kg Rifampicin in Pulmonary TB: A Phase IIb Randomized Controlled Trial.

Background: Globally, no trial data are available on head-to-head comparison between 10 mg/kg and 25/35 mg/kg rifampicin in treating pulmonary tuberculosis during study initiation. Methods: A multicentric, phase IIb randomized trial recruited 333 new culture-positive, drug-sensitive adult patients with pulmonary tuberculosis to compare safety and efficacy of high-dose rifampicin (R25/R35), against conventional dose (R10) given daily for 8 weeks followed by standard doses for 16 weeks. Main outcomes were treatment-emergent grade 3/4 adverse events (AEs) and time-to-culture conversion in liquid media, assessed by division of AIDS system for grading the severity of adverse events division of AIDS criteria and Kaplan-Meier methods. Results: In a modified intention-to-treat population of 323 patients (R10: 105/R25: 112/R35: 106), grade 3/4 AEs were reported in 34 patients (R10: 9.5% [10/105], R25: 9.8% [11/112], R35: 12.3% [13/106]) during the intensive phase. Among 23 patients (R10: 3.8% [4/105], R25: 6.3% [7/112], R35: 11.3% [12/106]) with grade 3/4 hepatotoxicity, 15 (R10: 1.9% [2/105], R25: 3.6% [4/112], R35: 8.5% [9/106]) had grade 3/4 hyperbilirubinemia and 9 patients (R10: 1.0% [1/105], R25: 0.9% [1/112], R35: 6.6% [7/106]) developed clinical jaundice. Significant differences observed only between R10 and R35 with hepatotoxicity (P = .039), hyperbilirubinemia (P = .031), clinical jaundice (P = .032), and treatment interruption (P = .039). Eighteen serious AEs and 6 deaths (R10: 3/R25: 1/R35: 2) occurred during study period. Time to stable culture conversion in liquid media was faster in R25 (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.26-2.31 [solid: 1.97; 95% CI, 1.46-2.67]) and R35 (1.81; 95% CI, 1.33-2.48 [solid: 2.24; 95% CI, 1.64-3.06]), than R10 (34 vs 44 days). R25 had no failure/relapse. Conclusions: Hepatotoxicity, clinical jaundice, and treatment interruptions occurred significantly higher with R35 than R10. Because R25 was comparably safe as R10 and also highly efficacious than R10, it may be considered for implementation. Clinical Trials Registration. CTRI/2017/12/010951.

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.

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.

In-vivo expressed mycobacterial transcripts as diagnostic targets for pulmonary tuberculosis.

The nucleic acid amplification tests (NAATs) such as Xpert MTB/RIF have transformed the TB diagnostic field by significantly increasing the case detection. However, newer improved diagnostic assays are still needed to meet the WHO targets to end TB. Present study is based on a novel approach of utilizing the in-vivo expressed specific mycobacterial transcriptomic biomarkers for the diagnosis of pulmonary tuberculosis (PTB). Total 61 subjects were recruited including smear positive (smear+; n = 15), smear negative (smear-; n = 30) PTB patients and disease controls (n = 16). Transcripts of three mycobacterial genes Rv0986, Rv0971c and Rv3121 were analyzed using real time PCR (qRT-PCR) in sputum samples. qRT-PCR with Rv0986, Rv0971c and Rv3121 identified smear + PTB patients with 100 %, 78.6 % and 86.7 % sensitivity respectively. In smear- PTB patients, both Rv0986 and Rv0971c based qRT-PCR resulted in 63 %, sensitivity whereas Rv3121 identified these patients with ∼40 % sensitivity only. The sensitivity of the assay for smear-patients increased to 85 % when combinatorial analysis of qRT-PCR data for all the three genes was used. Thus, in-vivo expressed mycobacterial transcripts have promising potential as biomarkers for PTB diagnosis.

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.

Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is complicated by exacerbations in more than one-third of the subjects. Whether nebulized amphotericin B (NAB) therapy prevents ABPA exacerbations remains unclear. OBJECTIVES: The primary objective of this systematic review and meta-analysis was to determine the frequency of subjects remaining exacerbation-free, one year after initiating NAB. The key secondary objectives were the time to first exacerbation and the safety of NAB therapy. METHODS: We searched the PubMed and Embase databases for studies evaluating ≥5 subjects of ABPA managed with NAB. We report the pooled proportion of ABPA subjects remaining exacerbation free after one year. For the randomized controlled trials (RCTs), we estimate the pooled risk difference (RD) of exacerbation-free status at one year with NAB versus the control arm. RESULTS: We included five studies for our analysis; three were observational (n = 28) and two RCTs (n = 160). The pooled proportion (95% confidence interval [CI]) of subjects remaining exacerbation free with NAB at one year was 76% (62-88). The pooled RD (95% CI) of an exacerbation-free status at one year was 0.33 (-0.12 to 0.78) and was not significantly different between the NAB and control arms. The time to first exacerbation was longer with NAB than with the standard therapy. No serious adverse events were reported with NAB. CONCLUSION: NAB does not improve exacerbation-free status at one year; however, weak evidence suggests it delays ABPA exacerbations. More research using different dosing regimens is required.

Meta-analysis of Cerebrospinal Fluid Cell Count and Biochemistry to Diagnose Meningitis in Infants Aged < 90 Days.

OBJECTIVE: Cerebrospinal fluid (CSF) white blood cell (WBC) count, protein, and glucose (cytochemistry) are performed to aid in the diagnosis of meningitis in young infants. However, studies have reported varying diagnostic accuracies. We assessed the diagnostic accuracy of CSF cytochemistry in infants below 90 days and determined the certainty of evidence. STUDY DESIGN: We searched PubMed, Embase, Cochrane Library, Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases in August 2021. We included studies that evaluated the diagnostic accuracy of CSF cytochemistry compared with CSF culture, Gram stain, or polymerase chain reaction in neonates and young infants <90 days with suspected meningitis. We pooled data using the hierarchical summary receiver operator characteristic (ROC) model. RESULTS: Of the 10,720 unique records, 16 studies were eligible for meta-analysis, with a cumulative sample size of 31,695 (15 studies) for WBC, 12,936 (11 studies) for protein, and 1,120 (4 studies) for glucose. The median (Q1, Q3) specificities of WBC, protein, and glucose were 87 (82, 91), 89 (81, 94), and 91% (76, 99), respectively. The pooled sensitivities (95% confidence interval [CI]) at median specificity of WBC count, protein, and glucose were 90 (88, 92), 92 (89, 94), and 71% (54, 85), respectively. The area (95% CI) under ROC curves were 0.89 (0.87, 0.90), 0.87 (0.85, 0.88), and 0.81 (0.74, 0.88) for WBC, protein, and glucose, respectively. There was an unclear/high risk of bias and applicability concern in most studies. Overall certainty of the evidence was moderate. A bivariate model-based analysis to estimate the diagnostic accuracy at specific thresholds could not be conducted due to a paucity of data. CONCLUSION: CSF WBC and protein have good diagnostic accuracy for the diagnosis of meningitis in infants below 90 days of age. CSF glucose has good specificity but poor sensitivity. However, we could not identify enough studies to define an optimal threshold for the positivity of these tests. KEY POINTS: · Median specificity of CSF leucocyte count, protein and glucose are similar in young infants.. · At median specificity, CSF leukocyte count and protein are more sensitive than glucose.. · Owing to inadequate data, bivariate modelling to suggest optimal diagnostic thresholds is not possible..

Evaluation of immunodominant peptides of in vivo expressed mycobacterial antigens in an ELISA-based diagnostic assay for pulmonary tuberculosis.

Non-sputum-based biomarker assay is urgently required as per WHO's target product pipeline for diagnosis of tuberculosis. Therefore, the current study was designed to evaluate the utility of previously identified proteins, encoded by in vivo expressed mycobacterial transcripts in pulmonary tuberculosis, as diagnostic targets for a serodiagnostic assay. A total of 300 subjects were recruited including smear+, smear- pulmonary tuberculosis (PTB) patients, sarcoidosis patients, lung cancer patients and healthy controls. Proteins encoded by eight in vivo expressed transcripts selected from previous study including those encoded by two topmost expressed and six RD transcripts (Rv0986, Rv0971, Rv1965, Rv1971, Rv2351c, Rv2657c, Rv2674, Rv3121) were analyzed for B-cell epitopes by peptide arrays/bioinformatics. Enzyme-linked immunosorbent assay was used to evaluate the antibody response against the selected peptides in sera from PTB and controls. Overall 12 peptides were selected for serodiagnosis. All the peptides were initially screened for their antibody response. The peptide with highest sensitivity and specificity was further assessed for its serodiagnostic ability in all the study subjects. The mean absorbance values for antibody response to selected peptide were significantly higher (p<0.001) in PTB patients as compared to healthy controls; however, the sensitivity for diagnosis of PTB was 31% for smear+ and 20% for smear- PTB patients. Thus, the peptides encoded by in vivo expressed transcripts elicited a significant antibody response, but are not suitable candidates for serodiagnosis of PTB.

Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open-label randomized controlled trial.

BACKGROUND: The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. METHODS: In this open-label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3-5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response ('success' [complete or partial response] or 'failure' [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90-day mortality. We performed a modified intention-to-treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. RESULTS: Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus (n = 27; 16/27 were COVID-19-associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty-nine subjects experienced any AE, but none discontinued treatment. The 90-day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). CONCLUSION: Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.

Role of Diffusion-Weighted Magnetic Resonance Imaging for Characterization of Mediastinal Lymphadenopathy.

BACKGROUND: To assess the diagnostic performance of diffusion-weighted (DW) magnetic resonance imaging (MRI) in the characterization of mediastinal lymph nodes and compare them with morphological parameters. METHODS: A total of 43 untreated patients with mediastinal lymphadenopathy underwent DW and T2 weighted MRI followed by pathological examination in the period from January 2015 to June 2016. The presence of diffusion restriction, apparent diffusion coefficient (ADC) value, short axis dimensions (SAD), and T2 heterogeneous signal intensity of the lymph nodes were evaluated using receiver operating characteristic curve (ROC) and forward step-wise multivariate logistic regression analysis. RESULTS: The ADC of malignant lymphadenopathy was significantly lower (0.873 ± 0.109 × 10-3 mm2/s) than that of benign lymphadenopathy (1.663 ± 0.311 × 10-3 mm2/s) (p = 0.001). When an ADC of 1.0955 × 10-3 mm2/s was used as a threshold value for differentiating malignant from benign nodes, the best results were obtained with a sensitivity of 94%, a specificity of 96%, and an area under the curve (AUC) of 0.996. A model combining the other three MRI criteria showed less sensitivity (88.9%) and specificity (92%) compared to the ADC-only model. CONCLUSION: The ADC was the strongest independent predictor of malignancy. The addition of other parameters failed to show any increase in sensitivity and specificity.

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.