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Background: "Progressive destroyed lung (PDL)" refers to a state in which the normal structure and function of the lung are permanently disrupted owing to repeated inflammation. After lung cancer surgery, the remaining lung tissue can experience progressive destruction; however, the exact cause remains unclear. In this study, we retrospectively analyzed cases in which the remaining lung deteriorated after lung cancer surgery and investigated the associated risk factors. Methods: A case-control study was conducted on 31 cases of PDL and 247 cases of non-PDL among 1,234 patients who underwent surgery for primary lung cancer from 2006 to 2021. The following factors were analyzed: age, sex, medical history, smoking status, surgical procedure, lung cancer histology, surgical approach, postoperative complications, chemotherapy, radiation therapy, and lung cancer recurrence. Patients were matched 1:1 based on preoperative factors, and postoperative risk factors were evaluated using multivariate logistic regression analysis. Results: A higher proportion of men and higher prevalence of chronic lung diseases, smokers, squamous cell carcinoma (SCC), postoperative acute pneumonia, chronic pneumonia, air leak, and history of radiation therapy were noted in the PDL group than in the non-PDL group. In the analysis following propensity score matching, chronic pneumonia [odds ratio (OR): 10.1, 95% confidence interval (CI): 2.9 to 35.8] was identified as an independent risk factor for PDL. Conclusions: In this study, PDL after lung cancer surgery was associated with postoperative chronic pneumonia, including Aspergillus infection and aspiration pneumonia.

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OBJECTIVE: Endocardial fibroelastosis (EFE) is a major effector in the maldevelopment of the heart in patients with congenital heart disease. Despite successful surgical removal, EFE can redevelop, but the underlying cause of EFE recurrence remains unknown. HYPOTHESIS: This study aimed to identify hemodynamic predictors and genetic links to epithelial/endothelial-to-mesenchymal transition (EMT/EndMT) alterations for preoperative risk assessment. METHODS: We assessed the impact of preoperative hemodynamic parameters on EFE recurrence in a cohort of 92 patients with congenital heart disease who underwent left ventricular (LV) EFE resection between January 2010 and March 2021. Additionally, whole-exome sequencing in 18 patients was used to identify rare variants (minor allele frequency <10-5) in high-expression heart genes (HHE) related to cardiac EMT/EndMT and congenital heart disease. RESULTS: EFE recurred in 55.4% of patients, within a medium 2.2 years post-surgery. Multivariable analysis revealed specific hemodynamic parameters (mitral valve inflow and area, LV filling pressure, and aortic valve gradient and diameter) as predictors, forming a predictive model with an AUC of 0.782. Furthermore, 89% of the patients exhibited damaging variants in HHE, with 38% linked to cardiac EMT/EndMT GO processes and 22% associated with known CHD genes. Notably, HHE genes associated with cardiac EMT/EndMT were significantly associated with faster EFE recurrence in multivariate analysis (HR 3.56, 95% CI 1.24-10.17, p=0.018). CONCLUSIONS: These findings established a predictive scoring system using preoperative hemodynamic parameters for EFE recurrence risk assessment. Alterations in HHE genes, particularly those linked to cardiac EMT/EndMT, exacerbate the risk of recurrence.

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Cardiac disorders exhibit considerable heterogeneity, and understanding their genetic foundations is crucial for their diagnosis and treatment. Recent genetic analyses involving a growing number of participants have uncovered novel mutations within both coding and non-coding regions of DNA, contributing to the onset of cardiac conditions. The NEXN gene, encoding the Nexilin protein, an actin filament-binding protein, is integral to normal cardiac function. Mutations in this gene have been linked to cardiomyopathies, cardiovascular disorders, and sudden deaths. Heterozygous or homozygous variants of the NEXN gene are associated with the development of endocardial fibroelastosis (EFE), a rare cardiac condition characterized by excessive collagen and elastin deposition in the left ventricular endocardium predominantly affecting infants and young children. EFE occurs both primary and secondary to other conditions and often leads to unfavorable prognoses and outcomes. This review explores the role of NEXN genetic variants in cardiovascular disorders, particularly EFE, revealing that functional mutations are not clustered in a specific domain of Nexilin based on the cardiac disorder phenotype. Our review underscores the importance of understanding genetic mutations for the diagnosis and treatment of cardiac conditions.

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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.

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BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has no currently available specific treatment. Benefits of lung transplantation (LT) for PPFE are poorly documented. METHODS: We 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. RESULTS: Thirty-one patients were included. At transplantation, median age was 48 years [IQR 35-55]. About 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). CONCLUSION: LT 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. GOV IDENTIFIER: NCT05044390.

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Airway-centered fibroelastosis is characterized by peribronchovascular fibroelastosis, predominantly in the upper lobes, with little-to-no pleural involvement. In this study, we describe two cases of airway-centered fibroelastosis diagnosed based on radiological and pathological findings. The first case comprised a 44-year-old man whose forced vital capacity improved over three months following treatment with nintedanib. The second case involved a 50-year-old woman who was treated with oral corticosteroids but yielded an unfavorable outcome. An effective treatment for airway-centered fibroelastosis has not yet been identified; therefore, this study may help contribute to a more thorough discussion regarding treatment strategies for this disease.

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Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.

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Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD), characterized by predominantly upper lobe pleural and subjacent sub-pleural parenchymal fibrosis. Its name refers to a combination of fibrosis involving the visceral pleura with fibroelastotic changes, predominantly in the subpleural lung parenchyma. We describe the case of a 67-year-old lady who presented to the accident and emergency department of Weston General Hospital with worsening shortness of breath (SOB) and cachexia of six to eight months' duration. The initial imaging studies showed bilateral spontaneous pneumothoraces on a background of pleural-based consolidation and fibrotic changes. A subsequent high-resolution CT (HRCT) chest showed evidence of pleuroparenchymal fibroelastosis in the background. She was not considered for anti-fibrotic medications due to the advanced stage of the disease and was managed with supportive measures, including oxygen support, oral steroids and antibiotics to cover for any infections. After initial management of symptoms and long discussions with the patient, family and the palliative team, she was discharged home with community follow-up.

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OBJECTIVES: To uncover the clinical course of fetal isolated non-immune mediated second-degree AVB and determine the factors associated with the spontaneous recovery for fetal non-immune second-degree atrioventricular block (AVB). METHODS: A total of 20 fetuses with isolated, non-immune mediated second-degree AVB were prospectively recruited between 2014 and 2022. These fetuses were divided into the spontaneous recovery group (n=12) and the non-spontaneous recovery group (n=8). Maternal and fetal basic characteristics, intrauterine and postnatal outcomes were compared between groups. RESULTS: Twelve fetuses restored 1:1 atrioventricular conduction in utero and did not recur during the postnatal follow-up period. The residual eight fetuses maintained as second-degree AVB and six of them were aborted due to parental request in utero. Of the two live children with second-degree AVB, one of them progressed to complete AVB at the latest follow up at the age of 34 months, but without any symptoms, heart enlargement or dysfunction. The residual one progressed to complete AVB and was finally diagnosed with type 2 long-QT syndrome. Fetuses in the spontaneous recovery group presented with earlier gestational age at diagnosis (20.0[17.0-26.0] vs. 24.5[18.0-35.0] weeks, p=0.004) and higher atrial rate (147[130-160] vs 138.00[125.00-149.00] bpm, p=0.006) in comparison with the non-spontaneous recovery group. A cut-off value of 22.5 weeks of gestational age and 144 bpm of atrial rate at diagnosis could predict the failure of spontaneous recovery, with sensitivities of 87.5%, 75%, and specificities of 92.0%, 87.5%, respectively. CONCLUSIONS: The outcome of fetal non-immune second-degree AVB was favorable. Earlier gestational age at diagnosis and higher atrial rate were related to spontaneous reversion for isolated non-immune-mediated second-degree AVB. However, prenatal gene test should be performed for those with persistent AVB to exclude the heritable disorders including LQTS. These findings may provide important references for clinical management and prenatal counseling. This article is protected by copyright. All rights reserved.

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Endocardial fibroelastosis (EFE) is a thickening of the endocardial layer by accumulation of collagen and elastic fibers. Endothelial to mesenchymal transformation is proposed to be the underlying mechanism of formation. Although EFE can occur in both right and left ventricles, this article will focus on management of left ventricular EFE. Through its fibrous, nonelastic manifestation EFE restricts the myocardium leading to diastolic and systolic ventricular dysfunction and prevents ventricular growth in neonates and infants. The presence of EFE may be a marker for underlying myocardial fibrosis as well. The extent of EFE within the left ventricular cavity can be variable ranging from patchy to confluent distribution. Similarly the depth of penetration and degree of infiltration into myocardium can be variable. The management of EFE is controversial, although resection of EFE has been reported as part of the staged ventricular recruitment therapy. Following resection, EFE recurs and infiltrates the myocardium after primary resection. Herein we review the current experience with EFE resection.

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BACKGROUND: This study explored long-term outcome and functional status of patients born with critical aortic stenosis (CAS) following neonatal surgical or catheter interventions. METHODS: A 40-year retrospective review of all consecutive patients within a large, single-center referral unit who required neonatal (<30 days) intervention for CAS. Additional detailed evaluation of surviving patients >7 years age was performed, with clinical assessment, objective cardiopulmonary exercise testing and state-of-the-art characterization of myocardial function (advanced echocardiography and cardiac MRI). RESULTS: Between 1970 and 2010, ninety-six neonates underwent CAS intervention (mean age 9 ± 7.5 days). Early death occurred in 19 (19.8%) and late death in 10 patients. Overall survival at 10 and 30 years was 70.1% and 68.5%, freedom from reintervention was 41.8% and 32.9% respectively. Among the 25 long-term survivors available for detailed assessment (median age 15.7 ± 6.4 years), 55% exhibited impaired peak oxygen uptake. Mean left ventricle (LV) ejection fraction was 65 ± 11.2%, with a mean LV end-diastolic volume z-score of 0.02 ± 1.4. Mean LV outflow tract Vmax was 2.3 ± 1.02 m/s. CAS patients had reduced LV longitudinal and increased radial strain (p = 0.003, p < 0.001 respectively). Five patients had severe LV diastolic dysfunction associated with endocardial fibroelastosis (EFE) (p = 0.0014). CONCLUSION: Despite high early mortality rate, long-term survival of patients with CAS is reasonable at the expense of high reintervention rate. With successful intervention, there remained long-term clinical and subclinical LV myocardial impairment, of which EFE was one marker. Long-term follow-up of all CAS patients is crucial, involving detailed myocardial functional assessment to help elucidate physiology and optimise management.

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This case-control study examined cognitive function in patients with mild idiopathic pulmonary fibrosis (IPF), in comparison with controls or moderate-to-severe IPF. Ten mild IPF, 10 moderate-to-severe IPF, and 16 controls were enrolled, and performance on seven different cognitive function tests was compared in each group. IPF showed decreased cognitive function compared to controls in verbal memory, cognitive flexibility and information processing speed. As the scores were lower even in mild IPF, this study suggests that cognitive function declines early in the disease process of IPF. Thus, occupational therapy for IPF should require an assessment of cognitive function and assistance appropriate to the client's function.

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Gangliosidosis (ORPHA: 79255) is an autosomal recessive lysosomal storage disease (LSD) with a variable phenotype and an incidence of 1:200000 live births. The underlying genotype is comprised GLB1 mutations that lead to ß-galactosidase deficiency and subsequently to the accumulation of monosialotetrahexosylganglioside (GM1) in the brain and other organs. In total, two diseases have been linked to this gene mutation: Morquio type B and Gangliosidosis. The most frequent clinical manifestations include dysmorphic facial features, nervous and skeletal systems abnormalities, hepatosplenomegaly, and cardiomyopathies. The correct diagnosis of GM1 is a challenge due to the overlapping clinical manifestation between this disease and others, especially in infants. Therefore, in the current study we present the case of a 3-month-old male infant, admitted with signs and symptoms of respiratory distress alongside rapid progressive heart failure, with minimal neurologic and skeletal abnormalities, but with cardiovascular structural malformations. The atypical clinical presentation raised great difficulties for our diagnostic team. Unfortunately, the diagnostic of GM1 was made postmortem based on the DBS test and we were able to correlate the genotype with the unusual phenotypic findings.

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BACKGROUND: Lung 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. METHODS: This 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. RESULTS: Herein, 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. CONCLUSION: Detecting anomalies in TBD-related or surfactant protein genes can significantly refine the diagnosis and treatment strategies for individuals with PPFE and other F-ILD.

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The typical pleuroparenchymal fibroelastosis (PPFE) after hematopoietic stem cell transplantation (HSCT) is characterized by late-onset progressive pulmonary complication within 5 years. PPFE shows a poor prognosis without definitive standard care other than lung transplantation. Our case indicated an over 20 years late-onset and aggressively exacerbating PPFE.

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This article reports the clinical course and imaging findings of three cases of suspected pleuroparenchymal fibroelastosis (PPFE) after allogeneic hematopoietic cell transplantation (HCT). All patients complained of dyspnea more than 5 years after HCT, had progressive restrictive deficits on respiratory function tests, and presented with pneumothorax, pleural thickening, or exacerbation of consolidation in the upper lobe of the lung. Though lung biopsy was not done in all three cases, the clinical findings and results of spirometry were compatible with those of PPFE. PPFE has been sporadically reported as a pulmonary complication of allogeneic HCT; however, clinical diagnostic criteria other than histological diagnosis and treatment methods have not yet been established. The accumulation of more cases is necessary to improve the prognosis of PPFE complications.

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Elastin is a long-lived fibrous protein that is abundant in the extracellular matrix of the lung. Elastic fibers provide the lung the characteristic elasticity during inhalation with recoil during exhalation thereby ensuring efficient gas exchange. Excessive deposition of elastin and other extracellular matrix proteins reduces lung compliance by impairing ventilation and compromising gas exchange. Notably, the degree of elastosis is associated with the progressive decline in lung function and survival in patients with interstitial lung diseases. Currently there are no proven therapies which effectively reduce the elastin burden in the lung nor prevent dysregulated elastosis. This review describes elastin's role in the healthy lung, summarizes elastosis in pulmonary diseases, and evaluates the current understanding of elastin regulation and dysregulation with the goal of guiding future research efforts to develop novel and effective therapies.

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BACKGROUND: Upper-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. METHODS: We examined the radiological reports of all consecutive patients with round atelectasis between 2006 and 2018 and investigated the incidence of upper-PF development. RESULTS: Among 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. CONCLUSIONS: Upper-PF occasionally develops on the same side of round atelectasis. Upper-PF may develop as a sequela of chronic pleuritis.

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