Intra-alveolar Fibrosis Research Articles

Pleuroparenchymal Fibroelastosis: Case Study

Pleuroparenchymal fibroelastosis is a rare and recently recognized condition, first described by Amitani et al. in the 1990s as fibrosis of the upper lobes and later recognized as a new clinicopathological entity by Frankel. In 2013, idiopathic pleuroparenchymal fibroelastosis was classified as a rare subtype in the international classification of idiopathic interstitial pneumonias. The disease can occur at any age, and the diagnosis issuspected in a patient with dyspnea and radiological presentation, characterized by fibrosis of the upper lobe of the pleural and subpleural pulmonary parenchyma. A definitive diagnosis is histopathological, characterized by dense intra-alveolar fibrosis with elastosis of the alveolar walls and fibrous thickening of the subpleural pleura, predominantly in the upper lobes. The disease progresses, with a poor prognosis, and currently, the only therapeutic option is lung transplantation. We describe a rare case of pleuroparenchymal fibroelastosisdiagnosed radiologically in an 83-year-old man

Alveolar fibroblast lineage orchestrates lung inflammation and fibrosis.

Fibroblasts are present throughout the body and function to maintain tissue homeostasis. Recent studies have identified diverse fibroblast subsets in healthy and injured tissues1,2, but the origins and functional roles of injury-induced fibroblast lineages remain unclear. Here we show that lung-specialized alveolar fibroblasts take on multiple molecular states with distinct roles in facilitating responses to fibrotic lung injury. We generate a genetic tool that uniquely targets alveolar fibroblasts to demonstrate their role in providing niches for alveolar stem cells in homeostasis and show that loss of this niche leads to exaggerated responses to acute lung injury. Lineage tracing identifies alveolar fibroblasts as the dominant origin for multiple emergent fibroblast subsets sequentially driven by inflammatory and pro-fibrotic signals after injury. We identify similar, but not completely identical, fibroblast lineages in human pulmonary fibrosis. TGFβ negatively regulates an inflammatory fibroblast subset that emerges early after injury and stimulates the differentiation into fibrotic fibroblasts to elicit intra-alveolar fibrosis. Blocking the induction of fibrotic fibroblasts in the alveolar fibroblast lineage abrogates fibrosis but exacerbates lung inflammation. These results demonstrate the multifaceted roles of the alveolar fibroblast lineage in maintaining normal alveolar homeostasis and orchestrating sequential responses to lung injury.

Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID.

Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.

The anti-inflammatory effects of NaCl with KCl as a potent graphene exfoliator in a patients with interstitial pneumonia by epithelial-mesenchymal transition

A 72-year-old man with normal pressure hydrocephalus to our hospital with a history of productive cough, sputum, fever, dyspnea combined with nasal cannula oxygen therapy, chest radiography, vital signs: Total leukocyte count of 11800/cmm and Erythrocyte Sedimentation Rate (ESR) 53 mm in the first hour using Westergren method, C-reactive protein (CRP) 11.2 mg/dl [1]. The intravenous infusion of a solution consisting of 250mL normal saline with of potassium chloride (KCl) over 6 h , vitamin C intake with supportive care resulted in recovery, intramuscular injections of the graphene previously [2,3]. After the injection, ESR, CRP was 40-1.91 and segmental neutrophil was 79.6%. Alveolar epithelial cells underwent Epithelial-Mesenchymal Transition (EMT) in the progression of Acute Interstitial Pneumonia (AIP). AIP is characterized by acute respiratory prodrome including sore throat, headache, cough, dyspnea, and often fever with abrupt onset and short duration . AIP was defined Diffuse Alveolar Damage (DAD). The pathologic progress of DAD three phases: acute exudative phase, characterized by interstitial edema, hyaline membrane, and acute interstitial inflammation accumulation; proliferative phase,characterized by in alveolar spaces; and fibrotic phase,characterized by enlarged fibrotic septa and laminated intra-alveolar fibrosis. Epithelial-mesenchymal transition defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype [4].

Prognostic significance of radiological pleuroparenchymal fibroelastosis in Mycobacterium avium complex lung disease: a multicentre retrospective cohort study

BackgroundMycobacterium avium complex (MAC) causes chronic respiratory infectious diseases with diverse clinical features and prognoses. Pleuroparenchymal fibroelastosis (PPFE) is a rare disease characterised by pleural fibrosis with subjacent intra-alveolar fibrosis...

Does Gender Difference Effect Radiation-Induced Lung Toxicity? An Experimental Study by Genetic and Histopathological Predictors.

Several studies have reported differences in radiation toxicity between the sexes, but these differences have not been tested with respect to histopathology and genes. This animal study aimed to show an association between histopathological findings of radiation-induced lung toxicity and the genes ATM, SOD2, TGF-β1, XRCC1, XRCC3 and HHR2. In all, 120 animals were randomly divided into 2 control groups (male and female) and experimental groups comprising fifteen rats stratified by sex, radiotherapy (0 Gy vs. 10 Gy), and time to sacrifice (6, 12, and 24 weeks postirradiation). Histopathological evaluations for lung injury, namely, intra-alveolar edema, alveolar neutrophils, intra-alveolar erythrocytes, activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis, and collapse were performed under a light microscope using a grid system; the evaluations were semi quantitatively scored. Then, the alveolar wall thickness was measured. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to determine gene expression differences in ATM, TGF-β1, XRCC1, XRCC3, SOD2 and HHR2L among the groups. Histopathological data showed that radiation-induced acute, subacute, and chronic lung toxicity were worse in male rats. The expression levels of the evaluated genes were significantly higher in females than males in the control group, but this difference was lost over time after radiotherapy. Less toxicity in females may be attributable to the fact that the expression of the evaluated genes was higher in normal lung tissue in females than in males and the changes in gene expression patterns in the postradiotherapy period played a protective role in females. Additional data related to pulmonary function, lung weights, imaging, or outcomes are needed to support this data that is based on histopathology alone.

A PUZZLING CASE OF RECURRENT PNEUMONIA: PLEUROPARENCHYMAL FIBROELASTOSIS

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pleuroparenchymal fibroelastosis (PPFE) is a fibroelastic process mainly affecting the visceral pleura and subpleural spaces with a propensity towards the upper lobes. It has unique clinical, pathological and radiological features1. CASE PRESENTATION: An 80 year old female with history of recurrent pneumonias and remote granulomatous disease presented with progressive dyspnea and fatigue. She denied other symptoms including chronic cough or sputum production or fever or chills. Chest X-ray showed extensive parenchymal and pleural fibrotic changes of the upper lobes. Pulmonary function tests suggested a restrictive pattern with reduced diffusion capacity (DLCO). Echocardiogram showed no significant abnormalities. Serial CT scans of the chest done over two years showed worsening pleuroparenchymal fibrotic changes of the upper lobes in a pattern very consistent with PPFE, with no evidence of honeycombing. This was likely idiopathic but potentially related to prior pneumonias and felt less likely to be related to her remote minimal parakeet exposure associated hypersensitivity pneumonitis. Her ANA titers were mildly elevated at 1:160 but further workup for auto-antibodies were negative including RF and CCP antibodies. ESR and CRP were minimally elevated. A bronchoscopy was offered to evaluate for infectious or other etiologies but she opted to wait. Her CT findings were however very consistent with PPFE and a provisional diagnosis of the same was made. DISCUSSION: PPFE is a rare but under-diagnosed type of interstitial lung disease. It is mostly idiopathic in nature but sometimes occurs as a late complication after lung transplantation. Although similar findings may be sometimes described in patients with autoimmune or connective tissue disease, it usually presents as a late complication and in certain patients with hypersensitivity pneumonitis, the idiopathic ones are best classified as PPFE1. PPFE is mostly seen in patients aged 40 to 70 years and presents as progressive dyspnea with or without cough. PPFE has to be differentiated from other upper lobe diseases like hypersensitivity pneumonia, sarcoidosis, idiopathic interstitial pneumonitis, non-tuberculous mycobacterial infection, pneumoconiosis, malignancy and apical pleural cap. High resolution CT scan remains the best diagnostic modality to show diffuse fibroelastic process predominantly affecting pleura and upper lobe parenchyma1. Pulmonary function test shows a restrictive pattern with reduced DLCO. No specific laboratory tests are diagnostic2. Surgical biopsies although not required for diagnosis can demonstrate intra-alveolar fibrosis and elastosis2. CONCLUSIONS: The prognosis of PPFE remains poor as no treatment is proven to be effective except therapeutic lung transplantation1. Further studies to understand pathogenesis, diagnostic markers and treatment modalities for this rare progressive disease are much warranted. REFERENCE #1: Chua F, Desai SR, Nicholson AG, et al. Pleuroparenchymal fibroelastosis. A review of clinical, radiological and pathological characteristics. Ann Am Thorac Soc 2019;16:1351-9. REFERENCE #2: Reddy TL, Tominaga M, Hansell DM, von der Thusen J, Rassl D, Parfrey H, Guy S, Twentyman O, Rice A, Maher TM, Renzoni EA, Wells AU, Nicholson AG. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes. Eur Respir J. 2012 Aug;40(2):377-85. DISCLOSURES: No relevant relationships by Ansaam Daoud, source=Web Response No relevant relationships by Palak Rath, source=Web Response No relevant relationships by Lokesh Venkateshaiah, source=Web Response

MULTIPLE CHEST CT FINDINGS IN A POST-TRANSPLANT PATIENT

SESSION TITLE: Fellows Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary complications are common in hematopoietic stem cell transplantation recipients. Late complications occur more than 100 days after HSCT. During this time frame noninfectious causes are more common than infectious complications. CASE PRESENTATION: 57 y/o Panamanian female never-smoker with history of Common Variable Immune Deficiency, and recurrent non-Hodgkin lymphoma status post-chemotherapy and autologous stem cell transplant 2015 followed by allogeneic bone marrow transplant in 2017 presented with dyspnea and non-productive cough. She had presumed pneumonia two months prior but denied infectious or constitutional symptoms. Initial CT chest demonstrated diffuse bilateral GGOs and PFTs had a restrictive pattern with decreased DLCO. PET CT lacked findings suggesting recurrent lymphoma and connective tissue disease. Initial differential diagnosis included infection, organizing pneumonia, and eosinophilic lung disease. The patient underwent bronchoscopy with bronchoalveolar lavage (negative cultures and cytology). Prednisone therapy for presumed cryptogenic organizing pneumonia was initiated. Shortly after she developed worsening dyspnea, tachycardia and new exertional hypoxia and was found to have pneumomediastinum. Bronchoscopy was repeated and again cultures and cytology negative and TTE demonstrated only mild diastolic dysfunction. Without an alternative diagnosis treatment for PCP was provided for 21 days and 50 mg prednisone continued. At completion of treatment there was no improvement on her CT. A surgical lung biopsy was performed, and multidisciplinary radiologic-pathologic diagnosis of pleuroparenchymal fibroelastosis (PPFE) was rendered. DISCUSSION: Predominant findings such as the GGO and pneumomediastinum, can overshadow less conspicuous features such as PPFE which can be confounding. PPFE is a rare disorder usually occurring between age 40 to 70. Numerous potential risk factors for the development of PPFE have been described most common of which are bone marrow, hematopoietic stem cell and lung transplant along with CTD, familial, post infectious, and idiopathic. Clinical features include exertional dyspnea, insidious dry cough, and weight loss. Typically a restrictive ventilatory defect and reduced DLCO are noted. In 2012 Reddy and colleagues proposed diagnostic criteria integrating histopathologic and radiographic features included bilateral upper zone pleural thickening with associated subpleural fibrosis on CT and intraalveolar fibrosis and elastosis on histopathological exam. Pneumothorax and pneumomediastinum are frequent complications of PPFE. CONCLUSIONS: PPFE is a rare condition but should be considered in patients a history of transplant. Treatment remains a clinical challenge and lung transplant is an option. In our patient, possible contributing factors for the development of PPFE were recurrent pulmonary infection and late-onset complication following HSCT. Reference #1: Pena E, Souza CA, Escuissato DL, et al. Noninfectious pulmonary complications after hematopoietic stem cell transplantation: practical approach to imaging diagnosis. Radiographics 2014; 34: 663–683 Reference #2: Chua, F, Desai, SR, Nicholson, AG, et al. Pleuroparenchymal fibroelastosis: a review of clinical, radiological and pathological characteristics. Ann Am Thorac Soc 2019; 16: 1351–1359 Reference #3: Reddy TL, Tominaga M, Hansell DM, von der Thusen J Jr, Rassl D, Parfrey H, Guy S, Twentyman O, Rice A, Maher TM, et al. Pleuroparenchymal fibroelastosis: a spectrum of histopathological and imaging phenotypes. Eur Respir J 2012;40:377–385 DISCLOSURES: No relevant relationships by Sally Delvecchio, source=Web Response No relevant relationships by Teri Franks, source=Web Response No relevant relationships by Jeffrey Galvin, source=Web Response No relevant relationships by Michael Luca, source=Web Response

PULMONARY PATHOLOGY OF NEW CORONAVIRUS DISEASE (COVID-
 19). THE PRELIMINARY ANALYSIS OF POST-MORTEM FINDINGS

Background. Currently, the patho- and morphogenesis of a new coronavirus infection (COVID-19) is being studied in depth. Conducting a comparative analysis of the morphological changes in the lungs of deceased patients at various time periods after the onset of the first clinical symptoms. Clinical and morphological comparisons should help to increase qualified medical care for patients in the resuscitation profile and reduce hospital mortality. The aim of the study was to formulate a working hypothesis of a conceptual scheme of clinical and morphological forms of development of a new coronavirus infection (COVID-19). Methods. An analysis of 80 fatal cases was carried out in the COVID-center of the Federal Research Clinical Center of FMBA of Russia. Along with the assessment of macro- and microscopic changes in the respiratory tract, an additional histochemical staining according to van Gieson was applied and immunohistochemical studies were performed to assess the condition of the lungs with COVID-19. Results. The revealed features of diffuse alveolar damage in case of a new coronavirus infection (COVID-19) made it possible to present a working hypothesis of the pathomorphogenesis of specific acute coronavirus (COVID-19) alveolitis (pneumonitis). It goes through 3 stages-forms: fulminant, persistent and fibrotic. Each stage is conditionally limited by certain time parameters and is characterized by certain morphological characters. Dysregulatory activation of monocytic phagocytes, development of generalized microthrombosis, persistent signs of the exudative phase, pathological repair, progressive intraalveolar and interstitial fibrosis are the main links in the pathomorphogenesis of specific acute coronavirus (COVID-19) alveolitis (pneumonitis).

Long-Term Sequelae of Smoking and Cessation in Spontaneously Hypertensive Rats.

Smoking is a major risk factor for heart attack, stroke, and lung cancer. Tobacco smoke (TS) causes bronchitis, emphysema, persistent cough, and dyspnea. Smoking cessation minimizes risks of TS-related disease. To determine whether smoking cessation could reverse TS-induced pulmonary changes, 10-week-old male spontaneously hypertensive rats were exposed to TS or filtered air (FA) for 39 weeks and allowed to live out their normal lifespan. Significantly (P ≤ .05) decreased survival was noted by 21 months in TS versus FA rats. In TS rats, persistent peribronchiolar, perivascular, alveolar, and subpleural inflammation were observed with pervasive infiltration of pigmented foamy macrophages and plausible intra-alveolar fibrosis and osseous metaplasia. Alveolar airspace was significantly (P ≤ .05) increased in TS versus FA rats as was the volume of stored epithelial mucosubstances in the left central axial airway. Increased mucin contributes to airflow obstruction and increased lung infection risks. Findings suggest TS-induced changes do not attenuate with smoking cessation but result in irreversible damage similar to chronic obstructive pulmonary disease. The observed persistent pulmonary changes mirror common TS effects such as chest congestion, sputum production, and shortness of breath long after smoking cessation and represent important targets for treatment of former smokers.

28. Acute pulmonary arterial hypertension in primary Sjögren’s syndrome with known cryptogenic organising pneumonia

28. Acute pulmonary arterial hypertension in primary Sjögren’s syndrome with known cryptogenic organising pneumonia

Pleuroparenchymal fibroelastosis secondary to autologous hematopoietic stem cell transplantation: A case report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease. Although an increased number of PPFE cases have been reported recently, the characteristics of this condition have not been well described. The present study reports on the case of a 34-year-old male patient who presented with unilateral lung abnormalities. The patient was admitted due to a 9-year history of progressive cough and exertional dyspnea, as well as a history of Hodgkin's lymphoma treated by autologous hematopoietic stem cell transplantation (HSCT). The patient had been initially diagnosed with tuberculosis and received regular anti-tuberculosis therapy for 18 months; however, the symptoms progressed. Serial chest computed tomography scans indicated a gradually worsening diffuse pleural thickening, dense subpleural opacification and volume loss, associated with evidence of fibrosis in the right lung. On physical examination the patient was cachectic, with a body mass index of 18.5 kg/m2, and he had a flattened thoracic cage. Arterial blood gas analysis revealed hypoxia. Pulmonary function tests revealed restrictive ventilation dysfunction and decreased diffusion capacity. The microbiological and cytological examinations were negative. Lung biopsy revealed a thickened pleura consisting of large amounts of collagen and elastic fibers, coexisting with subpleural intra-alveolar fibrosis with alveolar septal elastosis, without inflammatory infiltrates. The patient was diagnosed with PPFE secondary to HSCT and eventually succumbed to respiratory failure and infection while waiting for a lung transplant. Physicians should be aware of the typical and atypical characteristics of this rare disease, as its clinical and radiological characteristics may lead to misdiagnosis, particularly as chronic infections. The prognosis remains poor without effective long-term treatment.

PLEUROPARENCHYMAL FIBROELASTOSIS: A RARE CASE OF INTERSTITIAL LUNG DISEASE AND PNEUMOTHORACES

SESSION TITLE: Diffuse Lung Disease 2 SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/07/2018 04:45 pm - 05:45 pm INTRODUCTION: In 1992, an interstitial lung disease with upper lobe predominant fibrosis was first described in Japan; approximately 20 years later, the disease entity was coined as Pleuroparenchymal Fibroelastosis (PPFE). To date, there have been approximately 120 cases reported world-wide in the literature. The most common presenting complaints are shortness of breath, significant weight loss, pneumothorax, or chest pain. The pathogenesis remains unclear and the disease is often rapidly progressive with a poor prognosis. CASE PRESENTATION: We present a 65 year old female with a history of interstitial lung disease complicated by multiple pneumothoraces and GERD was admitted to our hospital with worsening shortness of breath. The patient’s history was significant for three years of profound weight loss (BMI 14), chest pain, and shortness of breath at rest and with exertion that were unresponsive to prednisone. The patient had previously worked in a many different factories, but was a lifetime non-smoker and had no other known exposure history. The physical exam was significant for a seven liter oxygen requirement, cachexia, decreased breath sounds at the apices and diffuse fine dry crackles, without skin or nail changes. CT chest revealed changes of interstitial lung disease with septal thickening and cystic changes, as well as traction bronchiectasis and ground glass opacities with upper lobe predominance and subpleural distribution, as well as bilateral apical pneumothoraces. Pulmonary function testing was consistent with a severe restrictive defect, while autoimmune and infectious work-up were unrevealing. The decision was made to perform an open lung biopsy for definitive diagnosis, which revealed features consistent with idiopathic PPFE. DISCUSSION: Idiopathic PPFE is a rare fibrosing lung disease with an upper lobe predilection that has recently been described as a distinct clinicopathological entity with definite radiological and pathological characteristics. Due in part to the heterogeneous spectrum of clinical presentation, course, and overlap with other interstitial lung disease, it remains difficult to diagnosis and lung transplantation remains the only definitive treatment. As was the case for our patient, open lung biopsy can be crucial for diagnosis and typically reveals fibrous thickening of the visceral pleura and homogeneous, dense intra-alveolar fibrosis with septal elastosis, sharply separated from the adjacent lung parenchyma. CONCLUSIONS: PPFE should be considered in the differential diagnosis of interstitial lung diseases, especially in cases where imaging reveals subpleural fibrosis and upper lobe predominance or in patients with a history of pneumothorax, as was the case with our patient. Raising awareness of this disease entity will be crucial in the future, as the prognosis is poor and early referral for lung transplantation remains the only definitive treatment. Reference #1: English JC, Mayo JR, Levy R, Yee J, Leslie KO. Pleuroparenchymal fibroelastosis: a rare interstitial lung disease. Respirology Case Reports. 2015;3(2):82-84. https://doi.org/10.1002/rcr2.108. Reference #2: Bonifazi M, Montero MA, Renzoni EA. Idiopathic Pleuroparenchymal Fibroelastosis. Current Pulmonology Reports. 2017;6(1):9-15. https://doi.org/10.1007/s13665-017-0160-5. Reference #3: Hong SK, Khoon C, Chuah L. Pleuroparenchymal Fibroelastosis: A Review. Archives of Pathology & Laboratory Medicine. 2016;140(8):849-853 DISCLOSURES: No relevant relationships by Vijayalakshmi Ananthanarayanan, source=Web Response No relevant relationships by Aaron Muhlbauer, source=Web Response No relevant relationships by Katie Young, source=Web Response

Changes in the pattern of fibrosis in the rat lung with repetitive orotracheal instillations of gastric contents: evidence of persistent collagen accumulation.

Recurrent aspiration of gastric contents has been associated with several interstitial lung diseases. Despite this association, the pathogenic role of aspiration in these diseases has been poorly studied and little is known about extracellular matrix (ECM) changes in animal models of repetitive events of aspiration. Our aim was to study the repair phase of lung injury induced by each of several instillations of gastric fluid in Sprague-Dawley rats to evaluate changes in ECM and their reversibility. Anesthetized animals received weekly orotracheal instillations of gastric fluid for 1, 2, 3, and 4 wk and were euthanized at day 7 after last instillation. For reversibility studies, another group received 7 weekly instillations and was euthanized at day 7 or 60 after last instillation. Biochemical and histological measurements were used to evaluate ECM changes. Lung hydroxyproline content increased progressively and hematoxylin and eosin, Masson's trichrome, and alpha-SMA stains showed that after a single instillation, intra-alveolar fibrosis predominated, whereas with repetitive instillations this fibrosis pattern became less prominent and interstitial fibrosis progressively became evident. Both type I and III collagen increased in intra-alveolar and interstitial fibrosis. Imbalance between matrix metalloproteinase-2 (MMP-2) activity and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression was observed, favoring either collagen degradation or accumulation depending on the number of instillations. Caspase-3 activation was also dose dependent. ECM changes were partially reversible at long-term evaluation, since Masson bodies, granulomas, and foreign body giant cells disappeared, whereas interstitial collagen accumulated. In conclusion, repetitive lung instillations of gastric fluid induce progressive fibrotic changes in rat lung ECM that persist at long-term evaluation.

Restrictive allograft syndrome and idiopathic pleuroparenchymal fibroelastosis: do they really have the same histology?

Restrictive allograft syndrome (RAS) and idiopathic pleuroparenchymal fibroelastosis (IPPFE) are two different diseases reported to share the same histology. RAS relates to chronic allograft dysfunction in lung transplantation, with IPPFE being a rare condition in native lungs. Our aim is to compare their histologies alongside biopsies of usual interstitial pneumonia (UIP), to determine if there are differences that might help to elucidate the pathogenesis. We selected four postmortem allograft lungs from patients who developed a clear clinical RAS pattern, five biopsies diagnosed as IPPFE, five UIP biopsies and five sections of normal lung. Histopathological features were described without knowledge of clinical and radiological features. Both RAS allografts and IPPFE biopsies showed intra-alveolar fibrosis and elastosis (IAFE), but RAS allografts also showed concomitant obliterative bronchiolitis, vascular lymphoplasmacytic inflammation within fibrointimal thickening, less fibroblastic foci (FF) at the advancing edge of the fibrosis (one against 14.4 FF in 2 mm2 ) and a slight reduction of the capillary network compared to UIP (P = 0.07) and controls (P = 0.06). The main differences seen in UIP were the lack of IAFE and the presence of honeycomb change. RAS and PPFE histopathology both show IAFE, but display various differences, particularly in their vascular morphology that may allow further understanding of pathogenesis.

Pleuroparenchymal Fibroelastosis of the Lung: A Review.

Described in Japan by Amitani et al in 1992, the entity of idiopathic upper lobe fibrosis was subsequently given the name pleuroparenchymal fibroelastosis (PPFE) in the English-speaking world. Pleuroparenchymal fibroelastosis is believed to be a rare disease characterized by a fibrosing process affecting the pleura and the subpleural lung parenchyma, with a predilection for the upper lobes. Uniquely, the fibrosing process is elastotic in nature, being associated with intra-alveolar fibrosis. The etiology of PPFE is unclear at this juncture, with many cases being considered as idiopathic forms of the disease. Conditions associated with PPFE include infections, bone marrow transplantation, and autoimmunity. In this review, we explore the clinical, radiologic, and pathologic features associated with PPFE in light of current understanding of the disease. Recent studies implicated that PPFE may not be as uncommon as claimed. The various differential diagnoses and implications of diagnosing PPFE are discussed.

Idiopathic pulmonary fibrosis in a captive lion (Panthera leo): case report

Spontaneous idiopathic pulmonary fibrosis (IPF) was observed in a captive felid. Very little is known of this condition in captive wildlife. Conventional diagnostic tools including histological techniques were often employed in the diagnosis. This communication presents the first case of idiopathic pulmonary fibrosis in a captive lion in Ibadan, Nigeria. The lion was recumbent and inactive with random episodes of dyspnoea. On necropsy, the carcass was in a poor body condition. Grossly, the lung was non-collapsed, mottled and rubbery to firm in texture with numerous fine nodules (1–3 mm diameter). Cytology showed abundance of mononuclear cells. There was diffuse alveolar damage, interstitial and intra-alveolar fibrosis and marked proliferation of fibroblasts with multiple myofibroblastic foci in interstitium and airspaces. The cause of IPF could not be easily ascertained; however, it is known that certain environmental factors and exposures to allergens increase the risk in man and cats. This report would further improve the screening of wildlife health.

Rare idiopathic interstitial pneumonias: LIP and PPFE and rare histologic patterns of interstitial pneumonias: AFOP and BPIP.

In the 2013 reclassification of the idiopathic interstitial pneumonias (IIPs), two rare IIPs (idiopathic lymphoid interstitial pneumonia (LIP), idiopathic pleuroparenchymal fibroelastosis (IPPFE)) and two rare histologic patterns (acute fibrinous and organizing pneumonia (AFOP), bronchiolocentric pattern of interstitial pneumonia (BPIP)) are described. All these entities are rare with small series published to date, mostly containing primary and secondary forms of disease. LIP is histologically characterized by diffuse polyclonal lymphoid cell infiltrate surrounding the airways and expanding the interstitium. Thin-walled cysts and diffuse ground glass are considered the typical radiologic features. The clinical course is highly variable with corticosteroid responsiveness evident in approximately half of cases. IPPFE is defined histologically by coexisting upper lobe pleural and intra-alveolar fibrosis with elastosis. Dense subpleural irregular fibrosis and consolidation are the cardinal radiologic features. A history of recurrent lower respiratory tract infection is frequent. Responses to immunomodulation have not been reported and the rate of progression appears to be highly variable. AFOP is a rare histologic pattern lying within the spectrum of acute/subacute lung injury, characterized by organizing pneumonia and intra-alveolar fibrin deposition without hyaline membranes. BPIP is characterized histologically by fibrosis and/or inflammation confined to the alveolar interstitium around bronchovascular bundles, overlapping with peribronchial metaplasia and fibrosis in some series. Currently, AFOP and BPIP are both best viewed as histological entities rather than true clinical disorders, in the absence of characteristic associated imaging patterns and clinical features.

Histopathological and ultra structural studies of ovine pulmonary adenocarcinoma (Jaagsiekte)

The Ovine Pulmonary adenocarcinoma (OPA) is also known as Jaagsiekte, is a contagious transmissible lung tumor of sheep caused by Jaagsiekte Sheep Retrovirus (JSRV). In the present study, 3698 lungs collected from slaughtered sheep in and around Tirupati, AP, India and examined morphologically. 396 lungs were showed different pneumonic lesions. Among 396 lung lesions 39 (9.85%) were diagnosed as Pulmonary adenocarcinoma. Grossly, all the lungs congested, increase in size, weight and oedematous. Consistency varied from granular to meaty appearance and many of them revealed nodules ranging from very small to 2.5 cm in diameter and serous exudate on cut surface of lung. Histologically, Papillary projections of epithelium into either alveolar or bronchiolar lumen. Intra alveolar fibrosis was prominent in many cases. Alveolar macrophages were consistently found within alveolar spaces. OPA also associated with different types of pneumonias. Ultrastructurally, proliferation of type II pneumocytes (Type B cells) having microvilli and well developed junctional complexes. Non ciliated bronchiolar epithelial cells (Clara cells) with electron dense cytoplasmic granules without any surrounding membrane and microvilli and no virus particles were traced.

Chronic Pleuropulmonary Fibrosis and Elastosis of Aged Donkeys: Similarities to Human Pleuroparenchymal Fibroelastosis

Donkey pulmonary fibrosis (DPF) is a spontaneous syndrome of aged donkeys with a high prevalence (35%). No previous detailed characterization of DPF has been performed. We sought to determine the similarities between DPF and recognized patterns of human pulmonary fibrosis. Whole lungs were collected from 32 aged donkeys at routine necropsy. Gross examination revealed pulmonary fibrosis in 19 donkeys (DPF cases), whereas 13 (control cases) had grossly normal lungs. Eighteen whole inflated ex vivo lungs (11 DPF cases, seven control cases) were imaged with high-resolution CT (HRCT) scan, whereas the remainder were sectioned and photographed. Tissue samples were collected from all lungs for histopathologic evaluation using a standardized protocol. HRCT images and histology sections underwent independent blinded review. Lung tissue was analyzed for herpes virus, fungal hyphae, mycobacteria, and dust content. Ten of 19 DPF lungs were categorized as being consistent with pleuroparenchymal fibroelastosis (PPFE) according to previously defined histologic and imaging criteria. All 10 PPFE-like lungs had marked pleural and subpleural fibrosis, predominantly within the upper lung zone, with accompanying intraalveolar fibrosis and elastosis. Asinine herpesvirus was ubiquitously expressed within control and DPF lung tissue. No other etiologic agents were identified. Many cases of DPF share key pathologic and imaging features with human PPFE, a rare interstitial pneumonia. Consequently, further study of DPF may help to elucidate the etiopathogenesis of human PPFE.