Ritesh Agarwal

Allergic bronchopulmonary aspergillosis (ABPA) is a type 2 inflammatory disorder resulting from an exaggerated immune response to Aspergillus species, most frequently A. fumigatus, and occurring most commonly in patients with asthma. Systemic corticosteroids, antifungal agents, and increasingly biologic therapies modify the underlying inflammatory response; however, no single biomarker reliably reflects disease activity across all treatment classes. This review summarizes current evidence on treatment-associated changes in inflammatory biomarkers in patients with asthma and ABPA. Serum total IgE remains the most widely used biomarker for monitoring treatment response. A decline of ≥ 20% from baseline supports treatment response, whereas a ≥ 50% increase from the post-treatment baseline, accompanied by compatible clinical or radiological worsening, indicates an ABPA exacerbation. Accordingly, current guidelines incorporate total IgE into a multidimensional assessment rather than interpreting it in isolation. Nevertheless, changes in total IgE may be discordant with clinical and radiological improvement and can be difficult to interpret during anti-IgE therapy or biologics targeting interleukin (IL)-4/IL-13 or thymic stromal lymphopoietin pathways. A. fumigatus-specific IgE and IgG show inconsistent treatment-related trajectories. Peripheral blood eosinophil counts and fractional exhaled nitric oxide are strongly dependent on treatment mechanisms and may reflect pharmacodynamic target engagement rather than overall ABPA activity. Emerging biomarkers, including recombinant A. fumigatus allergens, thymus and activation-regulated chemokine, periostin, eotaxin, carcinoembryonic antigen, and eosinophil-derived neurotoxin, provide additional mechanistic insights. However, none have demonstrated sufficient longitudinal validation for routine monitoring. Overall, biomarker trajectories in ABPA are strongly influenced by treatment mechanisms and may be dissociated from clinical benefit. Although several inflammatory markers decline with treatment, no individual marker is sufficiently sensitive and specific to serve as a universal marker of immune response. Treatment response should be assessed by integrating clinical and radiological improvement with appropriately interpreted immunological biomarkers rather than relying on a single laboratory measurement. Future studies should develop and validate treatment-specific biomarker signatures that distinguish pharmacodynamic target engagement from genuine control of ABPA activity.

Summary: ABPA diagnostic criteria contribute markedly unequal diagnostic information. Continuous laboratory data modelling preserved diagnostic information better than an integer point score.

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Background: No therapies are approved for allergic bronchopulmonary aspergillosis (ABPA), which affects an estimated 4.8 million asthmatic individuals worldwide. Current treatment with oral corticosteroids or oral itraconazole is limited by systemic toxicities, drug-drug interactions, and suboptimal airway drug concentrations. PUR1900 is a novel inhaled itraconazole formulation designed to achieve high airway concentrations with minimal systemic exposure. Methods: We conducted a phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Adults with asthma and ABPA were randomized (2:2:1) to receive inhaled PUR1900 20 mg, PUR1900 40 mg, or placebo once daily for 16 weeks. Key eligibility criteria included serum total IgE ≥1000 kU·L ⁻¹ , Asthma Control Questionnaire (ACQ)-7 score >1.5, and pre-bronchodilator FEV ₁ 50–85% predicted. The study had no prespecified primary endpoint and evaluated multiple exploratory outcomes across lung function, immunological, and patient-reported domains. Results: We randomized 43 participants (20 mg, n=18; 40 mg, n=16; placebo, n=9); 39 completed treatment. Baseline characteristics were balanced. At week 16, PUR1900 40 mg was associated with placebo-adjusted improvements in FEV ₁ (LSM +0.28 L; 95% CI: 0.02, 0.53) and ACQ-7 (LSM −0.51 points; 95% CI: −0.97, −0.06), with reductions in serum total IgE (LSM −2619 kU·L ⁻¹ ; 95% CI: −5342, 105). No placebo-adjusted effects were observed with PUR1900 20 mg. Adverse events occurred in 31%, 39%, and 44% of participants receiving 40 mg, 20 mg, and placebo, respectively; none were serious. Conclusions: PUR1900 40 mg was associated with improvements across key clinical domains in ABPA, with a favorable safety profile, supporting further phase 3 evaluation.

Allergic broncho-pulmonary aspergillosis (ABPA) shares clinical and immunologic features with helminth infections. We investigated helminth seropositivity among ABPA patients in a retrospective cross-sectional study. Our findings highlight the need for parasitic evaluation in ABPA patients in helminth-endemic regions, particularly with incomplete treatment response or atypical features.

Whether allergic bronchopulmonary aspergillosis (ABPA) causes bronchiectasis or merely represents Aspergillus fumigatus colonisation of damaged airways remains debated. Establishing causality is challenging because airway damage is predominantly driven by host immune responses rather than by direct fungal invasion. We systematically evaluate four competing hypotheses: (i) ABPA causes bronchiectasis, (ii) reverse causation, with bronchiectasis predisposing to ABPA, (iii) a shared underlying factor independently producing both conditions and (iv) a spurious association. We evaluate radiological, pathological, immunological, temporal and therapeutic evidence in relation to these hypotheses. The characteristic radiological phenotype (central bronchiectasis and high‐attenuation mucus), eosinophil‐dominant histopathology and disease‐specific immunological profile (typically absent in other forms of bronchiectasis despite Aspergillus colonisation) distinguish ABPA from incidental colonisation. Randomised controlled trials demonstrating that antifungal treatment or anti‐inflammatory therapy (glucocorticoids and biological agents) improve clinical and immunological outcomes argue against a purely spurious association. Temporal observations indicate that ABPA precedes bronchiectasis in many cases. While uncertainty remains and host susceptibility is likely essential, the available evidence suggests that ABPA contributes to bronchiectasis through antigen‐driven immune injury, supporting the use of appropriate antifungal and immunomodulatory therapy in selected patients.

Introduction: Allergic bronchopulmonary aspergillosis (ABPA) affects millions worldwide, yet current treatment approaches remain suboptimal due to a one-size-fits-all model that fails to account for the significant heterogeneity across affected populations. While corticosteroids and itraconazole are commonly prescribed, there are associated risks and uncertainties regarding efficacy. Additionally, the efficacy of alternatives such as newer and higher activity triazole antifungals, or the place of “biologic” therapies like anti-IL5 antagonists, has not been thoroughly investigated. Objectives: This review will assess treatment outcomes in patients with ABPA (Population) receiving antifungal or biologic therapies (Intervention) compared with corticosteroids, placebo, or alternative active treatments (Comparator), evaluating lung function (FEV₁), serological markers, exacerbation frequency, patient-reported outcomes, steroid-sparing effects, and adverse events (Outcomes) through a systematic review and network meta-analysis of published peer-reviewed studies. Inclusion criteria: All articles using the Population, Exposure/Intervention, Comparator, Outcomes, Duration, and Results (PECODR) framework related to human patients published in English from inception to the date of undertaking the study (present) will be included. Materials and methods: The following literature databases will be searched: MEDLINE, EMBASE, Cochrane Library Trials database, PubMed Central, Web of Science, and Scopus from inception to the present in collaboration with an experienced librarian. The primary researcher will screen the titles and abstracts; deduplication will be performed using Covidence®, and inclusion will be validated by a second checker. Quantitative analyses will be performed to summarise the results as means, frequency tables, and odds ratios of outcomes. Where there is sufficient data, a network meta-analysis will be conducted. The systematic review and network meta-analysis will be undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-analysis (PRISMA-NMA) framework. Systematic review registration: PROSPERO CRD42024443073.

Allergic bronchopulmonary aspergillosis (ABPA) is a severe asthma endotype arising from dysregulated immune responses to Aspergillus fumigatus in susceptible individuals. ABPA is characterized by exaggerated type 2 immune responses, markedly elevated serum total IgE and A. fumigatus-specific IgE and IgG levels, peripheral blood eosinophilia, and imaging abnormalities, including bronchiectasis and mucus impaction. Genetic predisposition involving HLA genotypes and immune-related polymorphisms contributes to disease susceptibility. The 2024 International Society of Human and Animal Mycology guidelines provide standardized criteria that integrate clinical, immunological, and radiological parameters to identify ABPA and distinguish it from overlapping diagnoses. Management employs a dual approach: anti-inflammatory therapy with systemic corticosteroids targets dysregulated immunity, while antifungal therapy with triazoles reduces airway fungal burden. The relapsing-remitting disease course necessitates systematic monitoring using clinical assessment, total IgE levels, and serial imaging to detect relapses, distinguish them from asthma exacerbations or infections, and optimize treatment intensity. Despite substantial progress in understanding the pathobiology of ABPA, high-quality evidence for optimal management strategies remains limited. Future research should focus on precision medicine approaches, novel biomarkers, and inhaled antifungal therapies to improve outcomes in this severe asthma phenotype. This review provides clinicians with comprehensive information on the pathobiology, diagnosis, classification, and evidence-based management strategies for ABPA, aiming to improve outcomes for patients with this severe asthma endotype. Plain Language Summary: Allergic bronchopulmonary aspergillosis (ABPA) is a serious lung condition that develops in some asthma patients when the common environmental mould Aspergillus fumigatus persists in the airways. The fungus is found everywhere in the environment, but most people tolerate exposure without problems. However, individuals with ABPA develop excessive immune responses to the fungus, causing severe asthma symptoms and progressive damage to the airways (bronchiectasis). ABPA affects approximately 11% of asthma patients worldwide and represents one of the most serious asthma phenotypes. Unlike typical asthma, which responds well to inhaled steroids, ABPA often requires treatment with oral corticosteroids or antifungal medications (or both) to control both the immune overreaction and the fungal burden in the lungs. Early diagnosis is crucial in preventing irreversible lung damage. Diagnosis requires demonstrating sensitization to the fungus by blood tests showing elevated total IgE levels and Aspergillus-specific antibodies, combined with elevated eosinophils and characteristic findings on lung imaging, such as bronchiectasis. Universal screening of all asthma patients for fungal sensitization enables early detection, timely treatment, and prevents disease progression. Early treatment with oral corticosteroids or antifungal medications can prevent progressive lung damage and improve long-term outcomes. Because ABPA tends to relapse, patients require regular monitoring with blood tests measuring IgE levels and periodic lung imaging to detect relapses early and adjust treatment intensity accordingly. This comprehensive approach ensures better disease control and quality of life for ABPA patients.