Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by Aspergillus fumigatus (Af), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, Af proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and Af infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and Af colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.

Bronchiolitis obliterans syndrome (BOS) is a severe form of chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic cell transplant (HCT), with a 5-year survival rate of 40%. Currently, there is no curative therapy for BOS. Preclinical data suggest that pirfenidone, an antifibrotic drug, may benefit small airway fibrosis in HCT-associated BOS. A single-arm, open-label, 56-week phase 1 trial with 56-month extension evaluated pirfenidone’s tolerability, safety, and efficacy in patients with BOS. Efficacy was measured using pulmonary function tests (PFTs), quantitative computed tomography (qCT) scans, patient-reported outcomes (PROs), cGVHD indices, and laboratory tests. Lung function trajectory was assessed by change in regression slopes before and during treatment. Baseline qCT metrics, including percentage normal lung, air trapping, volume change (Jacobian), and heterogeneity of volume change (Jacobian variance), were analyzed by participant response. Of 30 participants, 25 completed the 56-week trial, and 10 continued into the extension. Overall, 63% tolerated the recommended dose without safety concerns. There was significant improvement in the percent predicted forced expiratory volume in 1 second (P = .00267) when analyzing all participants, and improvement in individual PFT trend for 41.3% of participants. qCT analysis by lobe showed healthier lungs in the upper lobes of responders. Significant improvements were noted in liver function tests, PROs related to physical functioning and shortness of breath, and cGVHD skin indices. These findings indicate that pirfenidone is safe and tolerable in patients with BOS after HCT and may improve lung function and symptoms. Further trials are warranted to evaluate the efficacy of pirfenidone as a treatment for BOS after HCT. This trial was registered at www.ClinicalTrials.gov as #NCT03315741.

Bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is associated with substantial morbidity and mortality. Quantitative computed tomography (qCT) can help diagnose advanced BOS meeting National Institutes of Health (NIH) criteria (NIH-BOS) but has not been used to diagnose early, often asymptomatic BOS (early BOS), limiting the potential for early intervention and improved outcomes. Using pulmonary function tests (PFTs) to define NIH-BOS, early BOS, and mixed BOS (NIH-BOS with restrictive lung disease) in patients from 2 large cancer centers, we applied qCT to identify early BOS and distinguish between types of BOS. Patients with transient impairment or healthy lungs were included for comparison. PFTs were done at month 0, 6, and 12. Analysis was performed with association statistics, principal component analysis, conditional inference trees (CITs), and machine learning (ML) classifier models. Our cohort included 84 allogeneic HCT recipients, 66 with BOS (NIH-defined, early, or mixed) and 18 without BOS. All qCT metrics had moderate correlation with forced expiratory volume in 1 second, and each qCT metric differentiated BOS from those without BOS (non-BOS; P < .0001). CITs distinguished 94% of participants with BOS vs non-BOS, 85% of early BOS vs non-BOS, 92% of early BOS vs NIH-BOS. ML models diagnosed BOS with area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.74-0.94) and early BOS with AUC of 0.84 (95% CI, 0.69-0.97). qCT metrics can identify individuals with early BOS, paving the way for closer monitoring and earlier treatment in this vulnerable population.