Pleuroparenchymal Fibroelastosis Research Articles

Proposed Clinical Algorithm for Pleuroparenchymal Fibroelastosis (PPFE).

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.

Outcomes of lung transplantation for pleuroparenchymal fibroelastosis: A French multicentric retrospective study

BackgroundPleuroparenchymal fibroelastosis (PPFE) has no currently available specific treatment. Benefits of lung transplantation (LT) for PPFE are poorly documented. MethodsWe conducted a nation-wide multicentric retrospective study in patients who underwent lung or heart-lung transplantation for chronic end-stage lung disease secondary to PPFE between 2012 and 2022 in France. ResultsThirty-one patients were included. At transplantation, median age was 48 years [IQR 35 – 55]. 64.5% were women. Twenty-one (67.7%) had idiopathic PFFE. Sixteen (52%) had bilateral LT, 10 (32%) had single LT, 4 (13%) had lobar transplantation and one (3%) had heart-lung transplantation. Operative mortality was 3.2%. Early mortality (< 90 days or during the first hospitalization) was 32%. Eleven patients (35.5%) underwent reoperation for hemostasis. Eight (30.8%) experienced bronchial complications. Mechanical ventilation time was 10 days [IQR 2–55]. Length of stay in intensive care unit and hospital were 34 [IQR 18–73] and 64 [IQR 36–103] days, respectively. Median survival was 21 months. Post-transplant survival rates after 1, 2, and 5 years were 57.9%, 42.6% and 38.3% respectively. Low albuminemia (p=0.046), FVC (p=0.021), FEV1 (p=0.009) and high emergency lung transplantation (p=0.04) were associated with increased early mortality. Oversized graft tended to be correlated to a higher mortality (p=0.07). ConclusionLT for PPFE is associated with high post-operative morbi-mortality rates. Patients requiring high emergency lung transplantation with advanced disease, malnutrition, or critical clinical status experienced worse outcomes. ClinicalTrials.gov IdentifierNCT05044390.

Pleuroparenchymal fibroelastosis as a late complication of childhood cancer therapy: A case series.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial pneumonia with distinct clinicopathologic features. It has been associated with exposure to hematopoietic stem cell transplantation (HSCT) and classical alkylating agents. Here, we highlight PPFE as a late complication of childhood cancer therapy by describing the cases of four survivors of childhood cancer with a diagnosis of treatment-related PPFE. All patients received high-dose alkylating agents. PPFE should be considered in the differential diagnosis of restrictive lung disease in patients with history of exposure to alkylating agents or HSCT. Development of PPFE-specific, noninvasive diagnostic tools and disease-modifying therapies will clinically benefit these patients.

Platythorax increases residual volume/total lung capacity in idiopathic pleuroparenchymal fibroelastosis.

Platythorax significantly contributes to the increase in residual volume/total lung capacity ratio in patients with idiopathic pleuroparenchymal fibroelastosis https://bit.ly/3uZ0rmP.

Genetic Testing Goes Beyond Imaging and Histological Evaluation in Pleuroparenchymal Fibroelastosis

BackgroundLung biopsy remains the gold standard in the diagnosis of fibrotic interstitial lung disease (F-ILD), but there is a growing appreciation of the role of pathogenic gene variants in telomere and surfactant protein genes, especially in familial pulmonary fibrosis (FPF). Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that can coexist with different patterns of F-ILD, including FPF. It can be progressive and often leads to respiratory failure and death. This study tested the hypothesis that genetic testing goes beyond radiological and histological findings in PPFE and other F-ILD further informing clinical decision-making for patients and affected family members by identifying pathological gene variants in telomere and surfactant protein genes.MethodsThis is a retrospective review of 70 patients with F-ILD in the setting of FPF or premature lung fibrosis. Six out of 70 patients were diagnosed with PPFE based on radiological or histological characteristics. All patients underwent telomere length evaluation in peripheral blood by Flow-FISH or genetic testing using a customized exome-based panel that included telomere and surfactant protein genes associated with lung fibrosis.ResultsHerein, we identified six individuals where radiographic or histopathological analyses of PPFE were linked with telomere biology disorders (TBD) or variants in surfactant protein genes. Each case involved individuals with either personal early-onset lung fibrosis or a family history of the disease. Assessments of telomere length and genetic testing offered insights beyond traditional radiological and histopathological evaluations.ConclusionDetecting anomalies in TBD-related or surfactant protein genes can significantly refine the diagnosis and treatment strategies for individuals with PPFE and other F-ILD.

Obstructive and Restrictive Lung Disease After Hematopoietic Stem Cell Transplantation

Pulmonary complications are frequently encountered by clinicians in patients who have undergone hematopoietic stem cell transplantation and are associated with increased morbidity and mortality in these patients. Complications involving the lung are caused by both infectious and non-infectious etiologies, with non- infectious complications associated with significant long-term effect on the quality of life and can occur several years after transplantation. One manifestation of non-infectious post-transplant complication is a change in pulmonary function testing compared to pre-transplant testing. These changes can either be of an obstructive or restrictive pattern with each being associated with specific post-transplant complications. An improved understanding of obstructive and restrictive lung disease after hematopoietic stem cell transplant is necessary for both primary care physicians and specialists to recognize these diseases early in their course in order to facilitate work-up, treatment, and necessary follow-up. This review will provide an overview of obstructive and restrictive lung disease after hematopoietic stem cell transplant focusing on the etiologies, diagnosis, treatment, and outcomes. We will highlight bronchiolitis obliterans syndrome as an example of obstructive disease after transplant and will discuss pleuroparenchymal fibroelastosis as a cause for restrictive findings on pulmonary function testing. Improvements in the knowledge of the underlying etiologies and pathophysiology of obstructive and restrictive lung disease after hematopoietic stem cell transplant will allow for the identification of novel biomarkers to facilitate the diagnosis of these patients and will assist in the design of future targeted therapies to improve treatment and prognosis.

Pleuro-Parenchymal Fibroelastosis (PPFE)-A Case Report

Pleuro-parenchymal fibroelastosis (PPFE) is a rare form of interstitial lung disease with pleural and parenchymal components in the form of fibrosis and elastosis. This is often missed due to its rarity and nonspecific symptoms. Most of the cases were attributed to trivial respiratory infections in the past. Here we present a case of an elderly female who is symptomatic after COVID-19 infection and has characteristic radiological patterns in high-resolution computed tomogram (HRCT) to suggest a diagnosis of PPFE.

Neutrophil–lymphocyte ratio in patients with idiopathic pleuroparenchymal fibroelastosis

BackgroundIdiopathic pleuroparenchymal fibroelastosis (iPPFE), a progressive fibrotic disease, is characterised by upper lobe–dominant lung fibrosis involving the pleura and subpleural lung parenchyma. However, no prognostic markers have been established for...

Anti-fibrotic effects of nintedanib on lung fibroblasts derived from patients with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)

The tyrosine kinase inhibitor nintedanib has been recently approved for the treatment of Interstitial Lung Diseases (ILDs) that manifest a progressive fibrosis phenotype other than Idiopathic pulmonary Fibrosis (IPF).Nintedanib reduces the development of lung fibrosis in various animal models resembling features of PF-ILD and in vitro, it inhibits the fibrosing phenotype of human lung fibroblasts (HLFs) isolated from patients with IPF. To get insight on the cellular and molecular mechanisms that drive the clinical efficiency of nintedanib in patients with non-IPF PF-ILD, we investigated its effects on the fibrosing functions of HLFs derived from patients with PF-hypersensitivity pneumonitis (PF-HP, n = 7), PF-sarcoidosis (n = 5) and pleuroparenchymal fibroelastosis (PPFE, n = 4).HLFs were treated with nintedanib (10 nM-1 μM) and then stimulated with PDGF-BB (25–50 ng/ml) or TGF-β1 (1 ng/ml) for 24–72 h to assess proliferation and migration or differentiation.At nanomolar concentrations, nintedanib reduced the levels of PDGF receptor and ERK1/2 phosphorylation, the proliferation and the migration of PF-HP, PF-sarcoidosis and PPFE HLFs stimulated with PDGF-BB. Moreover, nintedanib also attenuates the myofibroblastic differentiation driven by TGF-β1 but only when it is used at 1 μM. The drug reduced the phosphorylation of SMAD2/3 and decreased the induction of collagen, fibronectin and α-smooth muscle actin expression induced by TGF-β1.In conclusion, our results demonstrate that nintedanib counteracts fundamental fibrosing functions of lung fibroblasts derived from patients with PF-HP, PF-sarcoidosis and PPFE, at concentrations previously reported to inhibit control and IPF HLFs. Such effects may contribute to its clinical benefit in patients suffering from these irreversible ILDs.

Prognostic impact of the cross-sectional area of the erector spinae muscle in patients with pleuroparenchymal fibroelastosis

Pleuroparenchymal fibroelastosis (PPFE) progresses slowly but sometimes relatively quickly, leading to decreased activities of daily living (ADL) and muscle weakness. Skeletal muscle atrophy and muscle weakness in chronic obstructive pulmonary disease (COPD) patients may be caused by cachexia and are associated with reduced ADLs and increased risk of death. However, the association between skeletal muscle mass and the prognosis of PPFE patients remains unknown. We retrospectively analysed the clinical significance of the cross-sectional area of the erector spinae muscle (ESMCSA), a skeletal muscle index, and predictors of mortality within 3 years in PPFE 51 patients, idiopathic pulmonary fibrosis (IPF) 52 patients and COPD 62 patients. PPFE patients had significantly lower ESMCSA than IPF or COPD patients, and lower ESMCSA (< 22.57 cm2) was associated with prognosis within 3 years (log-rank test; p = 0.006), whereas lower body mass index (BMI) showed no association. Multivariate analysis showed that ESMCSA was an independent predictor of mortality within 3 years in PPFE patients (hazard ratio, 0.854; 95% confidence interval: 0.737–0.990, p = 0.036). These results suggest the importance of monitoring ESMCSA in PPFE patients and that assessing ESMCSA in PPFE patients could be a more useful prognostic indicator than BMI.

ЭФФЕКТИВНОСТЬ КРАТКОСРОЧНОЙ РАР-ТЕРАПИИ У БОЛЬНЫХ ФИБРОЗИРУЮЩИМИ ИНТЕРСТИЦИАЛЬНЫМИ ЗАБОЛЕВАНИЯМИ ЛЕГКИХ

The results of the use of non-invasive lung ventilation (NIV) with the creation of positive airway pres-sure (Positive Airway Pressure) or PAP-therapy in patients with fibrosing interstitial lung diseases (FILD) are presented. The assessment of the initial functional status and the dynamics of changes was carried out using a cardiopulmonary exercising test (CPET). Objective: to evaluate the effectiveness of PAP-therapy, as one of the methods of respiratory support, in patients with FILD using CPET. Materi-als and Methods: The study included 35 patients with clinically-radiologically or histologically veri-fied FILD, among them, 60% were idiopathic pulmonary fibrosis, 31 % – exogenous fibrosing-type allergic alveolitis, 9 % – pleuroparenchymal fibroelastosis. All patients underwent CPET at baseline, after which they were randomized into 2 groups: the main group A – 18 people who received PAP-therapy for 1 month and the control group B – 17 people who did not receive respiratory therapy. A month later, all patients repeated CPET in dynamics. Results of the study: after 1 month of PAP-therapy in patients of the study, the main group A, there was a statistically significant change in some indicators of CPET, such as an improvement in the ventilation-perfusion ratio, in the form of a de-crease in the VD/VT (p = 0,09), an increase efficiency of the work performed (decrease in VO2/WR(p=0,02)), increase in the power of the work performed (MET (p=0,02), wt/kg (p=0,03)). In patients of the control group B after 1 month no statistically significant changes in CPET indicators were found. Comparative analysis between groups also confirmed more efficient oxygen delivery in group A. Conclusion: we can assume a positive effect of a short-term course of NIV respiratory sup-port on the functional status of the respiratory system in FILD patients, in particular, an improvement in the ventilation-perfusion balance at rest and during exercise, as well as an increase in exercise toler-ance.

High prevalence of upper lung field pulmonary fibrosis radiologically consistent with pleuroparenchymal fibroelastosis in patients with round atelectasis

BackgroundUpper-lung field pulmonary fibrosis (upper-PF), radiologically consistent with pleuroparenchymal fibroelastosis (PPFE), was reported to develop in patients with a history of asbestos exposure and tuberculous pleurisy, indicating that chronic pleuritis is correlated with upper-PF development. Round atelectasis reportedly emerges after chronic pleuritis. This study aimed to clarify the association between round atelectasis and upper-PF. MethodsWe examined the radiological reports of all consecutive patients with round atelectasis between 2006 and 2018 and investigated the incidence of upper-PF development. ResultsAmong 85 patients with round atelectasis, 21 patients (24.7%) were confirmed to finally develop upper-PF lesions. Upper-PF was diagnosed after round atelectasis recognition in more than half of the patients (13/21, 61.9%), whereas upper-PF and round atelectasis were simultaneously detected in the remaining 8 patients. At the time of round atelectasis detection, almost all patients (19/21, 90.5%) had diffuse pleural thickening and round atelectasis was commonly observed in non-upper lobes of 19 patients (90.5%). Fourteen patients had round atelectasis in unilateral lung, and the remaining 7 patients had round atelectasis in bilateral lungs. Among all 14 patients with unilateral round atelectasis, upper-PF developed on the same (n = 11) or both sides (n = 3). Thus, upper-PF emerged on the same side where round atelectasis was present (14/14, 100%). The autopsy of one patient revealed a thickened parietal-visceral pleura suggestive of chronic pleuritis. Subpleural fibroelastosis was also observed. ConclusionsUpper-PF occasionally develops on the same side of round atelectasis. Upper-PF may develop as a sequela of chronic pleuritis.

Establishing quantitative radiographic criteria for the diagnosis of pleuroparenchymal fibroelastosis

PurposePleuroparenchymal Fibroelastosis (PPFE) is a type of pulmonary fibrosis most commonly occurring at the apices. Patients with PPFE have an increased risk of adverse effects from lung biopsy and in the post-surgical setting. Here, we investigated simple and reproducible measurements on chest CT to evaluate their predictive value in diagnosing PPFE. MethodsWe analyzed a cohort of patients with histologically-proven PPFE and compared them to a cohort of patients diagnosed with “biapical scarring” (BAS) on chest CT. We measured plueuroparenchymal thickness using several independent parameters on chest CT. We also assessed other radiologic and clinical characteristics to identify if any were predictive of PPFF. ResultsOur analysis demonstrated the average greatest apical thickness with a cut off of 4.5 mm yielded a sensitivity of 94.4% and a specificity of 88.9%, and an area under the curve of 97.2%. Single greatest apical thickness with a cut off of 7.5 mm had a sensitivity of 100% and a specificity of 88.9%, with the area under the curve of 97.8%. Average greatest upper lobe thickness with a cut off of 8.0 mm had a sensitivity of 88.9% and a specificity of 100%, with an area under the curve of 98.2%. Single greatest upper lobe thickness with a cut off of 8.5 yielded both a sensitivity and specificity of 94.4% and an area under the curve of 94.3%. ConclusionMeasurements described above are highly sensitive and specific for the diagnosis of PPFE and warrant investigation with a larger cohort of patients.

Case Report: Idiopathic pleuroparenchymal fibroelastosis

Background: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a very rare and a slowly conspicuous progressing chronic lung disease, which usually involves the upper lobes of the lung. This unusual disease, first recognized as a rare idiopathic interstitial pneumonia in 2013, is characterized by dense fibrosis of the visceral pleura and the subjacent lung parenchyma accompanied by elastosis predominating in the subpleural alveolar walls. In the interest of improving our understanding of this uncommon disease, we report a case of IPPFE established by pathology results. Case report: A 73-year-old male patient, smoker, with a medical history of chronic obstructive pulmonary disease, presented since January 2022 with a gradual worsening of dyspnea on exertion and productive cough with weight loss. The chest X-ray detected a thoracic distention. The chest high resolution computed tomography revealed biapical subpleural parenchymatous condensations with tractive bronchiectasis and pleural retraction in the right upper lobe and diffuse bilateral cento-lobular emphysema. A scan-guided trans-parietal lung biopsy showed lung parenchyma tattooed with anthracosic deposits, largely remodeled by fibrous tissue, intermingled with numerous wavy and refractive dyselastotic structures in polarized light. The orcein staining confirmed the presence of excess elastosic fibers within these lesions. All etiological investigations were negative. His lung function studies revealed a reversible obstructive ventilatory disorder. Following a multidisciplinary discussion, the diagnosis of IPPFE was confirmed on the basis of the distribution in the upper lungs on chest computed tomography combined with pathology pattern. Conclusions: This case emphasizes the atypical misleading radiological presentation of IPPFE and the key role of pathological results in establishing the diagnosis. Hence, further studies are needed to improve our understanding of this uncommon disease and to establish clear-cut guidelines for IPPFE diagnosis and management.

Overcoming the challenges of a misdiagnosed rare lung disease - Idiopathic pleuroparenchymal fibroelastosis.

Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterized by pleural and subpleural lung fibroelastosis with an upper lobe predominance. We present the third case of idiopathic pleuroparenchymal fibroelastosis (IPPFE) from India, as well as the second antemortem diagnosis. A 27-year-old man presented with a one-year history of mMRC class II dry cough and shortness of breath. He described a fifteen-kilogram weight loss. After a clinico-radiological diagnosis, he was given anti-tubercular treatment and referred because he showed no improvement. A high-resolution computed tomography of the chest revealed bilateral upper lobe bullae, parenchymal and subpleural fibrosis, and irregular pleural thickening. PPFE was found in surgical lung and pleural biopsies. He was given systemic glucocorticoids but did not respond clinically or radiologically. Pirfenidone and a lung transplant were out of reach for him. He died nine months after being diagnosed with his condition. Finally, IPPFE is an extremely rare entity, with only three cases reported from our subcontinent. As a result, it is easily underdiagnosed or misdiagnosed; clinician awareness of this condition is critical for better diagnosis and management.

Diagnoses and treatments for participants with interstitial lung abnormalities detected in the Yorkshire Lung Screening Trial

IntroductionInterstitial lung abnormalities (ILA) are relatively common incidental findings in participants undergoing low-dose CT screening for lung cancer. Some ILA are transient and inconsequential, but others represent interstitial lung disease...

A commonly misdiagnosed rare pulmonary disease: Idiopathic pleuroparenchymal fibroelastosis

A commonly misdiagnosed rare pulmonary disease: Idiopathic pleuroparenchymal fibroelastosis

Clinical significance of para-carinal air cysts in patients with pleuroparenchymal fibroelastosis: The relationship with pneumomediastinum and pneumothorax.

Para-tracheal or para-carinal air cysts (PACs) are often asymptomatic and usually detected incidentally by methods such as computed tomography. Their clinical significance is unclear in patients with pleuroparenchymal fibroelastosis (PPFE). We evaluated the clinical significance of PACs in PPFE and their relationship with pneumomediastinum or pneumothorax. In total, 50 patients had PPFE and 34 (68%) had PACs. Most PACs were para-carinal (n = 30). A para-tracheal air cyst was detected in only nine patients, which included five patients having both para-carinal and para-tracheal air cysts. Overall median survival was 24.7months. Survival was not significantly different between the patients with [PACs(+)] and without PACs (P = 0.268). A high frequency (64%) of the complication of pneumomediastinum or pneumothorax occurred in the overall population during follow-up. Pneumomediastinum/pneumothorax occurred significantly more frequently in patients with PACs(+) than in those without (76.5% vs. 37.5%; P = 0.012). PACs(+) was the only significant risk factor for pneumomediastinum/pneumothorax. Our data showed that PACs commonly occur in patients with PPFE, and most PACs were para-carinal air cysts. Additionally, PACs(+) was a significant risk factor for pneumomediastinum/pneumothorax; therefore, clinicians should be more aware of these complications during follow-up examination, particular in PACs(+) patients with PPFE.

Imaging Features of Idiopathic Interstitial Lung Diseases.

Idiopathic interstitial pneumonias (IIPs) are a group of diffuse parenchymal lung diseases of unclear etiology and are distinguished from diffuse parenchymal lung diseases of known cause, such as connective tissue disease-related interstitial lung diseases or hypersensitivity pneumonitis by history, physical exam, imaging, serologic testing, and, when necessary, histopathology. The 2013 American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines are the most widely accepted classification of IIPs and include the following diagnoses: idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, idiopathic lymphocytic interstitial pneumonia, idiopathic pleuro-parenchymal fibroelastosis, respiratory bronchiolitis-interstitial lung disease, and desquamative interstitial pneumonia. The gold standard for diagnosis of IIP involves multidisciplinary discussion among pulmonologists, radiologists, and pathologists. The focus of this review will be to discuss the imaging features of the most common IIPs and the role of multidisciplinary discussion as the gold standard for diagnosis.

Autopsy findings in a case of idiopathic pleuroparenchymal fibroelastosis: A rare entity with review of literature

Idiopathic pleuroparenchymal fibroelastosis is a rare idiopathic interstitial pneumonia which mainly affects the upper lobe of lungs resulting in intra alveolar fibrosis, elastosis and visceral pleural fibrosis. For definite diagnosis, radiographic findings as well as histopathology findings are required. The overlap with interstitial lung diseases seen usually, makes it challenging to diagnose. There are no guidelines available for the diagnosis and appropriate management of this disease and only a few cases reported in the literature. We report a case of pleuroparenchymal fibroelastosis in autopsy in a 32-year-old female who allegedly died of heart failure with review of literature.