Background

The prognostic value of patterns and quantitative measures of lung fibrosis on high-resolution computed tomography (HRCT) in patients identified as having progressive pulmonary fibrosis (PPF) has not been established. We investigated whether HRCT patterns and quantitative scores were associated with risk of progression in patients with PPF.

Methods

Patients enrolled in the ILD-PRO Registry had an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis, reticular abnormality and traction bronchiectasis, and met criteria for ILD progression. HRCT images taken between 24 months prior to enrollment and 90 days after enrollment were analyzed using a machine learning algorithm to derive quantitative scores. Associations were assessed between HRCT pattern (usual interstitial pneumonia [UIP]-like versus other patterns) and tertiles of quantitative scores and measures of disease severity at enrollment, and between these patterns/tertiles at enrollment and ILD progression (relative decline in forced vital capacity [FVC] % predicted ≥ 10%, lung transplant, or death) over a median follow-up of 17.3 months.

Results

Among 395 patients, 178 (45.1%) had a UIP-like pattern on HRCT. A UIP-like pattern did not associate with worse disease severity at enrollment or an increased risk of ILD progression (HR 1.01 [95% CI: 0.71, 1.44]). The highest quantitative lung fibrosis (QLF) score tertile (≥ 20.5%) was associated with worse disease severity. In unadjusted analyses, patients with QLF scores in the highest tertile had a significantly increased risk of ILD progression versus the middle tertile (HR [95% CI] 1.63 [1.07, 2.49] and a numerically increased risk versus the lowest tertile (HR 1.46 [0.97, 2.18]); however, after adjustment for sex, age, FVC % predicted and oxygen use at enrollment, there were no significant differences. There were no significant associations between tertiles of quantitative ILD score, quantitative ground glass score, or quantitative honeycomb cysts score and risk of ILD progression in unadjusted or adjusted analyses.

Conclusions

In a real-world cohort of patients with PPF, QLF score associated with subsequent risk of ILD progression, while HRCT pattern did not. The QLF score did not provide additional prognostic information beyond clinical variables.

Trial registration

ClinicalTrials.gov; No: NCT01915511; registered August 5, 2013; URL: www.

Clinicaltrials

gov .

Rationale

The clinical course of chronic lung allograft dysfunction (CLAD) is heterogeneous. Forced vital capacity (FVC) loss at onset, which may suggest a restrictive phenotype, was associated with worse survival for bilateral lung transplant recipients in one previously published single-center study.

Objectives

We sought to replicate the significance of FVC loss in an independent, retrospectively identified cohort of bilateral lung transplant recipients and to investigate extended application of this approach to single lung recipients.

Methods

FVC loss and other potential predictors of survival after the onset of CLAD were assessed using Kaplan-Meier and Cox proportional hazards models.

Measurements and main results

FVC loss at the onset of CLAD was associated with higher mortality in an independent cohort of bilateral lung transplant recipients (hazard ratio [HR], 2.75; 95% confidence interval [CI], 2.02-3.73; P < 0.0001) and in a multicenter cohort of single lung recipients (HR, 1.80; 95% CI, 1.09-2.98; P = 0.02). Including all subjects, the deleterious impact of FVC loss on survival persisted after adjustment for other relevant clinical variables (HR, 2.36; 95% CI, 1.77-3.15; P < 0.0001). In patients who develop CLAD without FVC loss, chest computed tomography features suggestive of pleural or parenchymal fibrosis also predicted worse survival in both bilateral (HR, 2.01; 95% CI, 1.16-5.20; P = 0.02) and single recipients (HR, 2.47; 95% CI, 1.24-10.57; P = 0.02).

Conclusions

We independently validated the prognostic significance of FVC loss for bilateral lung recipients and demonstrated that this approach to CLAD classification also confers prognostic information for single lung transplant recipients. Improved understanding of these discrete phenotypes is critical to the development of effective therapies.

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics.