Prognostic and Clinical Value of Cluster Analysis in Idiopathic Pleuroparenchymal Fibroelastosis Phenotypes

Abstract

Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a distinctive interstitial pneumonia with upper lobe predominance that shows unique morphological features among idiopathic interstitial pneumonias (IIPs). Affected patients have a variety of clinical presentations with heterogeneous clinical courses. Cluster analysis is a valuable tool for identifying distinct clinical phenotypes under heterogeneous conditions. This study aimed to identify the phenotypes of patients with idiopathic PPFE. Using cluster analysis, novel PPFE phenotypes were identified among subjects from our multicenter cohort, and outcomes were stratified according to phenotypic clusters. Among the subjects with baseline data (N = 84), four clusters were identified. Cluster 1 included younger male subjects with coexisting non-UIP-like patterns. Cluster 2 included elderly female nonsmokers with low body mass index (BMI). Cluster 3 included elderly male smokers with a coexisting IP-like pattern. Cluster 4 included younger male smokers without lower lobe lesions. Patients in cluster 3 had significantly worse survival outcomes than those in clusters 1, 2, and 4 (p < 0.001, p = 0.0041, and p = 0.0155, respectively). Among idiopathic PPFE patients, cluster analysis using baseline characteristics identified four distinct clinical phenotypes that might predict survival outcomes.

Prognostic significance of radiological pleuroparenchymal fibroelastosis inMycobacterium aviumcomplex lung disease: a multicentre retrospective cohort study

“…As a result, 818 patients were enrolled in the study cohort to estimate the prognostic significance of radiological PPFE. Previous studies reported that approximately 20%–80% of patients with idiopathic PPFE also had findings of interstitial lung disease (ILD), such as reticular opacities in the lobes other than the upper lobes 14 19 21–25. To minimise the impact of coincidental coexistence of idiopathic PPFE and/or ILD in patients with MAC lung disease and evaluate the prognostic significance of radiological PPFE, we differentiated patients with ILD in lobes other than the upper lobes (ie, patients already diagnosed with ILD before the diagnosis of MAC lung disease or patients with ILD findings confirmed by chest HRCT) from patients without ILD, and we focused on patients without ILD.…”

“…PPFE can present as an idiopathic interstitial pneumonia (IIP), but cases secondary to post-lung/bone marrow transplantation and autoimmune diseases have also been reported 10–12. Patients with PPFE have unique chest high-resolution CT (HRCT) findings characterised by dense subpleural consolidation with traction bronchiectasis and architectural distortion, primarily in the upper lobes of the lungs 13–15. Such HRCT features, which are radiological PPFE, coexisted in patients with an IIP other than idiopathic PPFE and those with various pulmonary diseases, including hypersensitivity pneumonitis 10 16–18.…”

Pleuroparenchymal Fibroelastosis: A Review with a Focus on a Non-Infectious Complications after Hematopoietic Stem Cell Transplant

“…Finally, serum levels of surfactant protein D (SPD) have been shown to be elevated in PPFE patients in several small studies [ 8 , 35 , 36 , 37 , 38 ]. Although elevated, no studies have shown a correlation between SPD levels and baseline physiologic values or demographics in PPFE.…”

A proposed prognostic prediction score for pleuroparenchymal fibroelastosis

“…Clinically, patients with PPFE have some unique features that are uncommon in other ILDs, such as progressive weight loss and restrictive ventilatory impairment with increased residual volume (RV) [ 6 – 8 ]. The vast majority of PPFE patients die of chronic respiratory failure [ 9 ], and their 5-year survival rate was reported to be 23.3–58.9% [ 8 , 10 – 12 ]. Although the clinical course of PPFE shows considerable variation among patients, there are no established models for predicting the prognosis of PPFE.…”

“…Although the clinical course of PPFE shows considerable variation among patients, there are no established models for predicting the prognosis of PPFE. Previous studies have suggested several promising prognostic factors, including older age [ 13 ], male sex [ 9 , 12 , 14 , 15 ], dyspnea [ 12 ], pneumothorax events [ 16 ], lower body mass index (BMI) [ 17 ], coexistent ILD [ 7 , 8 , 10 , 15 , 18 ] or usual interstitial pneumonia (UIP) pattern in the lower lobes [ 8 , 13 , 18 – 20 ], lower elector spinae muscle attenuation on computed tomography (CT) [ 14 ], lower arterial blood oxygenation [ 17 ], lower forced vital capacity (FVC) [ 13 , 19 ], lower diffusing capacity of the lung for carbon monoxide (DL CO ) [ 13 ], and higher serum levels of Krebs von den Lungen-6 (KL-6) [ 8 , 13 , 21 ], and higher serum latent TGF-β binding protein-4 (LTBP-4) levels [ 22 ].…”