Elizabeth A. Belloli

Hypersensitivity pneumonia (HP) is an interstitial lung disease (ILD) caused by sensitization to an inhaled antigen. The exact prevalence is unknown and may vary geographically. HP is likely clinically under-recognized. The broad range of presenting symptoms, radiologic, and lung biopsy findings, and lack of validated diagnostic criteria makes diagnosis difficult, and has hindered progress of research investigating treatment modalities. HP as an ILD is unique in its heterogeneous disease phenotypes and clinical outcomes. Many patients experience complete recovery, while others have persistent symptoms with progression to end-stage fibrosis and death. There is disagreement on how to phenotypically classify HP patients at the time of diagnosis. This Pulmonary Perspectives will review HP clinical manifestations and phenotypes, evidence for methods of establishing the diagnosis, and treatment strategies, with a focus on fibrotic HP.

Rationale: The predominant cause of chronic lung allograft failure is small airway obstruction arising from bronchiolitis obliterans. However, clinical methodologies for evaluating presence and degree of small airway disease are lacking. Objectives: To determine if parametric response mapping (PRM), a novel computed tomography voxel-wise methodology, can offer insight into chronic allograft failure phenotypes and provide prognostic information following spirometric decline. Methods: PRM-based computed tomography metrics quantifying functional small airways disease (PRMfSAD) and parenchymal disease (PRMPD) were compared between bilateral lung transplant recipients with irreversible spirometric decline and control subjects matched by time post-transplant (n = 22). PRMfSAD at spirometric decline was evaluated as a prognostic marker for mortality in a cohort study via multivariable restricted mean models (n = 52). Measurements and Main Results: Patients presenting with an isolated decline in FEV1 (FEV1 First) had significantly higher PRMfSAD than control subjects (28% vs. 15%; P = 0.005), whereas patients with concurrent decline in FEV1 and FVC had significantly higher PRMPD than control subjects (39% vs. 20%; P = 0.02). Over 8.3 years of follow-up, FEV1 First patients with PRMfSAD greater than or equal to 30% at spirometric decline lived on average 2.6 years less than those with PRMfSAD less than 30% (P = 0.004). In this group, PRMfSAD greater than or equal to 30% was the strongest predictor of survival in a multivariable model including bronchiolitis obliterans syndrome grade and baseline FEV1% predicted (P = 0.04). Conclusions: PRM is a novel imaging tool for lung transplant recipients presenting with spirometric decline. Quantifying underlying small airway obstruction via PRMfSAD helps further stratify the risk of death in patients with diverse spirometric decline patterns.