Proposed Clinical Algorithm for Pleuroparenchymal Fibroelastosis (PPFE)

Abstract

Pleuroparenchymal fibroelastosis (PPFE) is characterized by fibrosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobes. As PPFE appears to occur in patients with heterogeneous etiologies, the disease course is thus also heterogenous, with some patients showing rapid progression while others have slow progression. Therefore, it is very difficult to predict prognosis with PPFE. Needless to say, this problematic matter has influenced the treatment strategy of PPFE patients. In fact, until now no evidence has been shown for use in creating an appropriate management algorithm for PPFE. We speculate that "uncoordinated breathing" is the most important reason for dyspnea in PPFE patients. Because monitoring of physique and not just pulmonary function and radiological evaluation is also very important, particularly in PPFE patients, this review focused on the characteristics of PPFE through an overview of previous studies in this field, and we proposed an algorithm as precision medicine based on the current evidence. Multiple views by the pulmonologist are needed to standardize a clinical algorithm that is necessary to correctly assess PPFE patients under the premise of maintenance of physique by providing appropriate nutritional care and pulmonary rehabilitation.

Keywords: clinical algorithm; interstitial lung disease; pleuroparenchymal fibroelastosis.

Figure 1

Summary of clinical characteristics reported by seven different studies [7,8,13,14,15,16,17] of patients with idiopathic pleuroparenchymal fibroelastosis (PPFE). BMI, body mass index; DL_CO, diffusing capacity for carbon monoxide; FVC, forced vital capacity; RV, residual volume; TLC, total lung capacity; lower UIP, lower-lobe usual interstitial pneumonia.

Figure 2

Mechanism of respiratory discomfort in patients with PPFE. Along with the progressive disease course, diminution of the upper lobes causes volume loss and decreased range of motion of the rib cage and diaphragm, which increases end-expiratory air trapping. Mainly, dyspnea due to dominant upper-lobe volume loss affects the “effort to breathe”, whereas air trapping and decreased range of motion of the rib cage and diaphragm lead to dyspnea experienced as “air hunger”. These factors often interact in diverse ways and may be the most important reasons for respiratory discomfort.

Figure 3

Surgical lung biopsy specimen from a patient with PPFE with fibrotic hypersensitivity pneumonitis. (A) High-magnification photomicrograph shows subpleural fibroelastosis (closed arrows) (Elastic van Gieson staining). (B) A high-power magnification view of the circled area in (A) shows mild centriacinar organization and fibrosis with multinucleated giant cells (thick arrows) (hematoxylin and eosin staining).

Figure 4

Causes of death reported by seven different studies [7,8,50,54,55,60,61] of patients with idiopathic PPFE. ILD, interstitial lung disease.

Figure 5

Disease course of a patient with refractory pneumothorax complicated by pleuroparenchymal fibroelastosis (PPFE). Chest X-ray at the diagnosis of idiopathic PPFE (A). After 4 months, chest X-ray showed bilateral pneumothorax (B). Immediately after insertion of a chest drain in the right intrathoracic space, a left-sided pneumothorax developed (C), which required insertion of a chest drain on the left side (D). However, persistent air leakage was noted in the right-sided drainage tube during repeated pleurodesis procedures (E), and the patient ultimately underwent surgical repair. After the surgical procedure managed with positive pressure ventilation, the patient’s bilateral pneumothorax worsened rather than improved (F). A lung specimen obtained during the surgical repair from near the suspected site of leakage showed a combination of visceral pleural fibrosis and intraalveolar fibrosis with elastosis ((G): Elastic van Gieson staining, (H): hematoxylin and eosin staining).

Figure 6

A patient with pleuroparenchymal fibroelastosis in whom the complication of pulmonary aspergillosis developed. ((A): upper row) The initial chest X-ray and computed tomography (CT) images showed pleural thickening, elevation of hilar opacities, and bullae in the upper lung fields. Consolidation with traction bronchiectasis was apparent in the lower lobe. ((B): lower row) Three years and 8 months later (following corticosteroid administration for 3 months), reticular and nodular opacities extended in the bilateral upper lung fields, and hilar opacities were further elevated. CT of the upper lung showed a fungus ball (thick arrow) at the location of the bullae, which was diagnosed as pulmonary aspergillosis. Despite this, the patient’s respiratory symptoms and consolidation shadows on CT partially improved (dashed ellipse) thanks to the corticosteroid.

Figure 7

A patient with pleuroparenchymal fibroelastosis in whom acute exacerbation developed. (A) Chest X-ray. Bilateral consolidation with traction bronchiectasis and enlarged ground-glass opacities are shown on chest computed tomography (B–D). A small bilateral pleural effusion was also detected.

Figure 8

Proposed management algorithm for PPFE. PPFE, pleuroparenchymal fibroelastosis; HP, hypersensitivity pneumonitis; CTDs, connective tissue diseases; BMI, body mass index; GNRI, Geriatric Nutritional Risk Index; FVC, forced vital capacity; DL_CO, diffusing capacity for carbon monoxide; KL-6, Krebs von den Lungen-6; NLR, neutrophil-lymphocyte ratio; 3D-CT, three-dimensional computed tomography; UIP, usual interstitial pneumonia; NTM, nontuberculous mycobacteria; ILD, interstitial lung disease.

Figure 9

A patient with pleuroparenchymal fibroelastosis (PPFE) who experienced improvement of respiratory-induced symptoms such as palpitations and tachycardia on exertion following low-dose β-blocker treatment. (A) Initial diagnosis of PPFE. (B) At 4 years and 7 months later as the disease extent of PPFE further progressed, the patient complained of palpitations due to anatomical changes of thinning of the chest wall and compression of the right ventricle (RV) (arrows).