Intra-alveolar Fibrin Deposition Research Articles

COVID-19 and Thrombosis: Clinical Aspects.

In coronavirus disease 2019 (COVID-19), thrombus formation is related to the pathogenesis of acute respiratory distress syndrome (ARDS) and the progression of clinical symptoms. Severe damage to vascular endothelial cells and the associated cytokine storm after SARS-CoV-2 infection cause thrombogenesis and contribute to the development of more severe and unique thromboses compared to other infectious diseases. Thromboses occur more often in critically ill patients. In addition to pulmonary thromboembolism (PE) and deep vein thrombosis, acute myocardial infarction, peripheral arterial thrombosis, and aortic thrombosis have also been reported. In PE, thrombi develop in both pulmonary arteries and alveolar capillaries. These, together with intraalveolar fibrin deposition, interfere with effective gaseous exchange in the lungs and exacerbate the clinical symptoms of ARDS in patients with COVID-19. Pharmacological thromboprophylaxis is recommended for all hospitalized patients to prevent both thrombosis and aggravation of ARDS, and other organ failures. Although the pediatric population is mostly asymptomatic or develops mild disease after SARS-CoV-2 infection, a new inflammatory disorder affecting the cardiovascular system, multisystem inflammatory syndrome in children (MIS-C), has been reported. Similar to Kawasaki disease, acute myocarditis, coronary vasculitis, and aneurysms are typically seen in MISC, although these two are now considered distinct entities. A similar acute myocarditis is also observed in young male adults, in which a hyperinflammatory state after SARS-CoV-2 infection seems to be involved. Several side effects following vaccination against COVID-19 have been reported, including vaccine-induced immune thrombotic thrombocytopenia and acute myocarditis. Although these could be serious and life-threatening, the cases are very rare, thus, the benefits of immunization still outweigh the risks.

Clinical features and long-term prognosis of acute fibrinous and organizing pneumonia histologically confirmed by surgical lung biopsy

BackgroundAcute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia characterized by intra-alveolar fibrin deposition and organizing pneumonia. The clinical manifestations and long-term prognosis of AFOP are unclear. Our objective was to investigate the clinical features and prognosis of AFOP.MethodsWe identified patients diagnosed with AFOP by surgical lung biopsy between January 2011 and May 2018 at Seoul National University Bundang Hospital. We retrospectively reviewed clinical and radiologic findings, treatment, and outcomes of AFOP.ResultsFifteen patients with histologically confirmed lung biopsies were included. The median follow-up duration was 2.4 (range, 0.1–82) months. The median age was 55 (range, 33–75) years, and four patients were immunocompromised. Fever was the most common clinical presentation (86.7%). Patchy ground-glass opacities and/or consolidations were the most predominant findings on chest computed tomography images. Nine patients (60%) received mechanical ventilator care, and eight patients (53.3%) died. The non-survivors tended to have slightly higher body mass index (BMI) and a long interval between symptom onset and diagnosis than the survivors, but these findings were not statistically significant. Among seven survivors, five patients were discharged without dyspnea and oxygen supplement.ConclusionsThe clinical course of AFOP was variable. Although AFOP was fatal, most of the patients who recovered from AFOP maintained normal life without supplemental oxygen therapy and respiratory symptoms.

Acute fibrinous and organizing pneumonia: two case reports and literature review

BackgroundAcute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern characterized by the intra-alveolar fibrin deposition and organizing pneumonia. Its clinical characteristics are still not well known and there is no consensus on treatment yet.Case presentationWe report two female cases in their fifties diagnosed with AFOP confirmed by a second lung biopsy. Case 1 was idiopathic AFOP with manifestation of 6-week fever, dyspnea, and cough, while case 2 was secondary to systemic lupus erythematosus and fever was the major symptom. Their chest CT scans revealed bilateral multiple consolidations, predominantly in the lower lobes. Both cases were initially diagnosed with pneumonia, but did not improve after treatment with broad-spectrum antibiotics. In both cases, transbronchial biopsy and bronchoalveolar lavage fluid examination were inconclusive and the pathological diagnosis was confirmed by percutaneous lung biopsy. Both patients had a good clinical response to prednisone.ConclusionsWe report two rare AFOP cases to highlight the importance of awareness of this disease. We further perform the most comprehensive review to date in AFOP, including 150 patients since 2002. Consolidation was the most common imaging pattern, followed by ground-glass opacity and nodules. A lung biopsy is required for a definitive diagnosis. Corticosteroids is recommended as the most effective therapy, but treatment options should depend on the etiology and disease severity.

Clinical features of acute fibrinous and organizing pneumonia: An early histologic pattern of various acute inflammatory lung diseases.

BackgroundAcute fibrinous and organizing pneumonia (AFOP) is a rare histologic pattern of acute lung involvement with intra-alveolar fibrin deposition. However, the clinical significance of the pathological findings of AFOP remains unclear. This study aimed to explore the clinical significance of AFOP through a comprehensive clinical examination.MethodsThe medical records of patients with lung diseases accompanied by the pathological finding of intra-alveolar organization between January 2010 and December 2019 were retrospectively reviewed. The clinical and radiological findings were compared between the groups with and without the histologic pattern of AFOP.ResultsWe identified 34 patients with AFOP (AFOP group) and 143 without AFOP (non-AFOP group). The underlying diseases of the AFOP group were as follows: 19 patients had cryptogenic organizing pneumonia (OP), 5 had connective tissue diseases, 3 had radiation pneumonitis, 3 had chronic eosinophilic pneumonia, 2 had myelodysplastic syndromes, and 2 had drug-induced pneumonia. Fever was more common, the time from symptom onset to biopsy was shorter, and the serum C-reactive protein level was higher in the AFOP group than in the non-AFOP group. On high-resolution computed tomography, 85% of patients had OP pattern, and halo sign was more common in the AFOP group. Corticosteroids were effective in 94% of the patients in the AFOP group; however, recurrences were more frequent, and a higher corticosteroid dose was needed during recurrence.ConclusionsAFOP might be an early phase of a histologic pattern associated with known etiologies. In addition, it could be a marker indicating intense inflammatory diseases with a tendency of recurrence.

COVID-19: effects on the lungs and heart

Neben der jährlich saisonal auftretenden Influenzaendemie stellt das sich pandemisch verbreitende SARS-CoV-2-Virus die weltweiten Gesundheitssysteme als vaskuläre Multiorganerkrankung COVID-19 vor ganz neue medizinische und sozioökonomische Herausforderungen. Bei beiden Viruserkrankungen kommt es insbesondere bei schweren Krankheitsverläufen zu einem fulminanten Lungenversagen, dem „acute respiratory distress syndrome“ (ARDS), welchem morphologisch meist ein unspezifischer diffuser Alveolarschaden mit hyalinen Membranen, Fibrinexsudaten und einem intraalveolären Ödem zugrunde liegt. Neben einer Infektion des Alveolarepithels und von Makrophagen durch das SARS-CoV-2-Virus scheint die COVID-19-Erkrankung zusätzlich durch eine vaskulozentrische Entzündungsreaktion mit Mikroangiopathie und aberranter Blutgefäßneubildung durch die sog. intussuszeptive Angiogenese charakterisiert zu sein. Zudem finden sich wahrscheinlich auf dem Boden dieser primär systemischen angiozentrischen Entzündung in vielen weiteren Organen, z. B. dem Herzen, im unterschiedlichen Ausmaß Gewebeschädigungen.

COVID-19: Where we are in Bangladesh

Five hundred premature infants were treated on a randomized double-blind basis with human plasminogen or placebo. We found that in premature infants plasminogen levels are low; thus, defense against intra-alveolar fibrin deposition during birth trauma is reduced. A significant decrease in the incidence of respiratory distress syndrome-hyaline membrane disease and death was seen in the treated infants. Infants with established respiratory distress syndrome were treated with human plasmin or placebo. A significant decrease in death rate was found in the treated infants. Decreased plasminogen and anti-thrombin III (AT-III) levels were found in patients with adult respiratory distress syndrome and/or septic shock. These levels returned to normal within 14 days in survivors, but remained depressed in those who died. It was thought that these parameters may have diagnostic and predictive values. In experimental animals, injection of E. coli endotoxin or oleic acid produced an adult respiratory distress syndrome type phenomenon. This was also accompanied by decreases in plasminogen levels, with recovery in the survivors. It is suggested that plasminogen and anti-thrombin III should be explored as auxiliary therapeutic agents in adult respiratory distress syndrome.

Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD

AimsDiffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID‐19)‐related deaths, but recent reports have also described additional atypical findings, including vascular changes. An aim of this study was to assess lung autopsy findings in COVID‐19 inpatients, and in untreated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive individuals who died in the community, in order to understand the relative impact of medical intervention on lung histology. Additionally, we aimed to investigate whether COVID‐19 represents a unique histological variant of DAD by comparing the pathological findings with those of uninfected control patients.Methods and resultsLung sections from autopsy cases were reviewed by three pulmonary pathologists, including two who were blinded to patient cohort. The cohorts included four COVID‐19 inpatients, four cases with postmortem SARS‐CoV‐2 diagnoses who died in the community, and eight SARS‐CoV‐2‐negative control cases. DAD was present in all but one SARS‐CoV‐2‐positive patient, who was asymptomatic and died in the community. Although SARS‐CoV‐2‐positive patients were noted to have more focal perivascular inflammation/endothelialitis than control patients, there were no significant differences in the presence of hyaline membranes, fibrin thrombi, airspace organisation, and ‘acute fibrinous and organising pneumonia’‐like intra‐alveolar fibrin deposition between the cohorts. Fibrinoid vessel wall necrosis, haemorrhage and capillaritis were not features of COVID‐19‐related DAD.ConclusionsDAD is the primary histological manifestation of severe lung disease in COVID‐19 patients who die both in hospital and in the community, suggesting no contribution of hyperoxaemic mechanical ventilation to the histological changes. There are no distinctive morphological features with which to confidently differentiate COVID‐19‐related DAD from DAD due to other causes.

Fisiología de la hemostasia y su alteración por la coagulopatía en COVID-19

COVID-19 global pandemic caused by Sars-CoV-2 virus, has worried to health care providers due to the high mortality rate related to coagulopathy in many patients. COVID-19 coagulopathy is mainly thrombotic, first locally in lungs but later on it becomes micro and macrovascular systemic coagulopathy. It has been associated to endothelial damage, inflammation, neutrophil-extracellular traps, monocyte and macrophage activation, cytokines storm that induce a vicious cycle of thrombosis and inflammation. The increased levels of prothrombotic factors as tissue factor, Von Willebrand factor, fibrinogen, VIII factor and the decreased levels of antithrombotic factos, such as: antithrombin and Protein S have been reported in COVID-19 patients. Insufficiency of fibrinolysis because of the increased levels of PAI-1 (plasminogen activator inhibitor 1) have been reported also. During this disease there are intraalveolar fibrin deposits that needs to be degraded. Fibrinolysis of thrombus and fibrin intraalveolar degradation are responsible for the high increase of D-dimers levels that are an important predictor of severity of the disease. In this report, the physiology of hemostasis, thromboinflamation secondary to Sars-CoV-2 infection are reviewed, as well as the clinical evidence and the physiopathology of COVID-19 coagulopathy from the basic sciences point of view. Keywords:Hemostasis; coagulation; thrombosis; coagulopathy; Sars-CoV-2; COVID-19.

Structural Integrity of the Alveolar–Capillary Barrier in Cynomolgus Monkeys Challenged with Fully Virulent and Toxin-Deficient Strains of Bacillus anthracis

Inhalational anthrax, a disease caused by inhaling Bacillus anthracis spores, leads to respiratory distress, vascular leakage, high-level bacteremia, and often death within days. Anthrax lethal toxin and edema toxin, which are composed of protective antigen (PA) plus either lethal factor (LF) or edema factor (EF), respectively, play an important yet incompletely defined role in the pulmonary pathophysiology. To better understand their contribution, we examined the structural integrity of the alveolar-capillary barrier in archival formalin-fixed lungs of cynomolgus monkeys challenged with the fully virulent B. anthracis Ames wild-type strain or the isogenic toxin-deficient mutants ΔEF, ΔLF, and ΔPA. Pulmonary spore challenge with the wild-type strain caused high mortality, intra-alveolar hemorrhages, extensive alveolar septal sequestration of bacteria and neutrophils, diffuse destabilization of epithelial and endothelial junctions, increased markers of coagulation and complement activation (including tissue factor and C5a), and multifocal intra-alveolar fibrin deposition. ΔEF challenge was lethal and showed similar alveolar-capillary alterations; however, intra-alveolar hemorrhages, bacterial deposition, and markers of coagulation or complement were absent or markedly lower. In contrast, ΔLFor ΔPA challenges were nonlethal and showed no signs of alveolar bacterial deposition or alveolar-capillary changes. These findings provide evidence that lethal toxin plays a determinative role in bacterial dissemination and alveolar-capillary barrier dysfunction, and edema toxin may significantly exacerbate pulmonary pathologies in a systemic infection.

The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.

ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA: A RARE CAUSE OF INTERSTITIAL LUNG DISEASE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare cause of interstitial lung disease that is commonly misdiagnosed in patients presenting with diffuse alveolar opacities. Here we present a case of a 60-year-old previously healthy man who presented with fevers, shortness of breath and cough and was eventually diagnosed with steroid-responsive AFOP. CASE PRESENTATION: A 60-year-old otherwise healthy man presented to the hospital with shortness of breath, dry cough and recurrent fevers as high as 40C of two weeks duration. Physical exam was significant for a respiratory rate of 22, oxygen saturation on room air of 94% and bibasilar crackles. Lab work-up revealed elevated white blood cell count at 12K, erythrocyte sedimentation rate and C-reactive protein were highly elevated at >120mm and 190 mg/L, respectively. Respiratory viral panel and atypical respiratory bacterial culture were negative. Chest x-ray showed left basilar and right lower lobe opacities. After 4 days of broad-spectrum antibiotics, the patient failed to improve with paroxysmal high fevers and hypoxemia, requiring 3-5L of oxygen with nasal cannula. A high-resolution CT of the chest (Figure 1) showed worsening multi-focal parenchymal consolidation in the lower lobes and new patchy involvement in the upper lobes. Antibiotics were discontinued after bronchoscopy & bronchoalveolar lavage showed the absence of infectious organisms. Work-up for collagen vascular disease was negative. Biopsy of the lung parenchyma was done and showed prominent intra-alveolar fibrin, scattered inflammatory cells, and patchy intraluminal connective tissue consistent with AFOP. The patient was started on high dose oral prednisone of 80mg daily with a plan for a prolonged taper over 8 weeks. Over the next few days, his symptoms, oxygen requirements and chest X-ray findings all improved. The patient was discharged home with no oxygen supplementation. DISCUSSION: One of the rare histologic interstitial pneumonias, AFOP was first reported in 2002 (1). It is defined as a subgroup of idiopathic interstitial lung disease with acute lung injury characterized by intra-alveolar fibrin deposition and organization of loose connective tissue (2). Patients with AFOP tend to present with pulmonary as well as extra-pulmonary symptoms. Cough, both productive and non-productive, has been found to be the most common symptom, followed by dyspnea and fever. While AFOP can present as an idiopathic disease process, it has been found to be associated with other disease processes as well including autoimmune, infectious and connective tissue diseases.Treatment consists of systemic glucocorticoids and immunosuppression (3). CONCLUSIONS: AFOP is a rare histopathological diagnosis that requires a high degree of clinical suspicion for diagnosis. Increasing awareness of this entity might lead to earlier diagnosis and more prompt initiation of appropriate therapy. Reference #1: Beasley MB, Franks TJ, Galvin JR, et al. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med 2002;126:1064. Reference #2: Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med 2013;188(6):733–48. Reference #3: Bhatti S, Hakeem A, Torrealba J, et al. Severe acute fibrinous and organizing pneumonia (AFOP) causing ventilatory failure: successful treatment with mycophenolate mofetil and corticosteroids. Respir Med 2009;103:1764. DISCLOSURES: No relevant relationships by Shameek Gayen, source=Web Response No relevant relationships by Xiang Liu, source=Web Response No relevant relationships by Mahmoud Madi, source=Web Response

AN UNUSUAL CAUSE OF ACUTE EOSINOPHILIC PNEUMONIA

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: We report an unusual case of interstitial lung disease in a patient suffering from alcoholism. CASE PRESENTATION: A 44 year old woman with a history of alcoholism presented with a 5 day history of shortness of breath, fevers and malaise. She was found to be hypoxemic and computed tomography of the chest showed bilateral patchy ground glass opacities with interlobular septal thickening and subpleural sparing. She had no exposures and her only medication was monthly subcutaneous naltrexone to maintain sobriety. She had received 4 doses, the most recent being the day of her onset of symptoms. Laboratory testing was significant for leukocytosis and elevated peripheral eosinophilia. Additional testing was negative for autoimmune or vasculitis markers, and parasitic or filarial presence. Bronchoalveolar lavage (BAL) was performed and revealed eosinophilic predominance of 49%. Pathology from transbronchial biopsies demonstrated eosinophilic pneumonia with intra-alveolar fibrin deposition. Steroids were initiated and her imaging abnormalities and oxygen requirement resolved within 48 hours. All of the above findings were felt to be most consistent with acute eosinophilic pneumonia secondary to naltrexone. The patient was cautioned to not be re-exposed to the same medication again. DISCUSSION: Acute eosinophilic pneumonia (AEP) is a febrile illness with hypoxemic respiratory failure and eosinophilic infiltration of the pulmonary parenchyma (1). Characteristic BAL shows marked eosinophilia in the absence of infection, atopy or asthma. AEP is mostly idiopathic but other causes include hypersensitivity to drugs, inhaled agents, or environmental exposures (2). Naltrexone acts by blocking the mu-opioid receptor and modifying the hypothalamic-pituitary-adrenal axis to suppress alcohol consumption. The subcutaneous form of this medication is thought to aid in adherence as it is administered once monthly and achieves a steady therapeutic level. In a randomized control trial showing the efficacy of long-acting injectable naltrexone, there was one serious adverse event of AEP judged to possibly be related to the study medication (3). In AEP, patients typically present with an acute onset of fever, nonproductive cough and dyspnea of less than 4 weeks duration. Diffuse bilateral pulmonary infiltrates are seen on imaging. Pathologic features include acute and organizing diffuse alveolar damage, as well as interstitial and alveolar eosinophils. The mainstay of treatment is systemic glucocorticoids. Most patients improve rapidly in response to glucocorticoids within 24-48 hours (2). CONCLUSIONS: In our case, the patient’s clinical history, radiographic, laboratory and BAL findings were consistent with AEP. Other causes were ruled out and thus AEP was determined to be secondary to long-acting injectable naltrexone. Providers should recognize that AEP is an extremely rare, but reported adverse effect of this drug. Reference #1: Allen JN, Pacht ER, Gadek JE, et al. Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure. N Engl J Med.1989;321:569–574. Reference #2: Rhee CK, Min KH, Yim NY, Lee JE, Lee NR, Chung MP, Jeon K. Clinical characteristics and corticosteroid treatment of acute eosinophilic pneumonia. Eur Respir J. 2013;41(2):402 Reference #3: Garbutt JC, Kranzler HR, O’Malley SS, et al. Efficacy and Tolerability of Long-Acting Injectable Naltrexone for Alcohol Dependence: A Randomized Controlled Trial. JAMA. 2005;293(13):1617–1625. DISCLOSURES: No relevant relationships by Jeannine Foster, source=Web Response No relevant relationships by Thoris Pan, source=Web Response No relevant relationships by Haala Rokadia, source=Web Response

The Prognostic Value of Fibrin and Organizing Pneumonia in Transbronchial Biopsies from Lung Transplant Patients

Purpose Acute fibrinous and organizing pneumonia (AFOP) after lung transplantation has recently gained attention as it may result in a rapid decline in respiratory function and death; or chronic lung allograft dysfunction (CLAD) in patients surviving the acute onset. We investigated the effect of fibrin deposition and organizing pneumonia (OP) in transbronchial biopsies (TBB) from lung transplant patients on graft survival and CLAD-free survival. Methods We reviewed all pathology reports of TBB obtained from 468 patients who underwent lung transplantation in the University Hospital Leuven between 2011 and 2017 (follow-up until 9/2018). The presence of intra-alveolar fibrin deposition or OP was assessed and defined as early ( 3 months). CLAD was defined as a persistent FEV1 decline ( 10% decline in total lung capacity and the presence of persistent radiological opacities. Results The presence of early and late fibrin deposition or OP was detected in 23 (5%) and 28 (6%) patients, respectively. CLAD was diagnosed in 107 (22.9%) of 468 patients (median time to CLAD = 2.90y, IQR [1.41-4.78]), in 4 of 23 patients (17.4%) with early fibrin or OP (1 RAS +), and in 16 of 28 patients (57.1%) with late fibrin or OP (12 RAS +). CLAD-free survival was significantly lower in patients with late fibrin or OP (p 7.68y and >7.64y, respectively). The presence of late fibrin or OP significantly increased the risk of later RAS (OR: 13.31; CI [3.871 - 40.2], p 7.81y and >7.77y, respectively). Patients with late fibrin or OP mostly died from CLAD (n=10, 9 RAS +), humoral rejection (n=2), sepsis (n=1), or tuberculosis (n=1). Conclusion The pathologist should actively search for fibrin and OP in TBB, as it is associated with worse prognosis and a high risk of subsequent CLAD development, specifically RAS. This indicates that the presence of late fibrin and OP in TBB could be an early pathologic manifestation of later RAS development.

A Rare Case of Interstitial Pneumonia

SESSION TITLE: Student/Resident Case Report Poster - Lung Pathology II SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare interstitial pneumonia histologically characterized by intra-alveolar fibrin deposits. First described in 2002, it can be associated with conditions such as collagen vascular diseases and hypersensitivity pneumonitis.Patients present with acute to subacute non-specific symptoms of cough, dyspnea and fever;imaging findings show lobar consolidation and ground glass opacities, which are seen in other interstitial pneumonias.Given this, diagnosis of AFOP remains challenging.Timely diagnosis is crucial as acute presentation is associated with a rapidly progressive and potentially fatal course, with patients requiring ventilatory support.We report a unique case of idiopathic AFOP, diagnosed with transbronchial lung biopsy. CASE PRESENTATION: A 70 year-old incarcerated male presented with two week history of cough, dyspnea, hemoptysis, fever and night sweats.Initial assessment was significant for tachypnea (26bpm), and hypoxia (88%).Physical exam showed an ill-appearing male, with respiratory exam revealing diffuse crackles.Chest X-ray showed diffuse interstitial opacities; CT scan of the chest showed bilateral upper lung consolidations with ground glass opacities, diffuse reticulonodular opacities and mediastinal lymphadenopathy.Given his presentation, the suspicion for tuberculosis was high and the patient was placed on empiric rifampin, isoniazid, pyrazinamide, ethambutol, and broad-spectrum antibiotics.Tuberculosis treatment was discontinued on hospital day four when sputum cultures were noted to be negative for AFB.Due to respiratory deterioration, the patient underwent endobronchial ultrasound with transbronchial biopsy.Biopsy results showed acute fibrinous and organizing pneumonia.He failed post-procedure extubation and remained on ventilator support for several days. He was started on treatment for AFOP with IV methylprednisolone and transitioned to Prednisone 80mg twice daily post-extubation.No secondary cause for AFOP was identified on further evaluation. He was discharged with a two-month steroid taper and supplemental oxygen.One month post-discharge, the patient reported symptomatic improvement and chest X-ray showed resolution of bilateral interstitial opacities. Despite this, the patient has suffered several relapses of AFOP and continued to require supplemental oxygen. DISCUSSION: AFOP is a rare interstitial pneumonia with limited reports in the literature.In comparison to other interstitial pneumonias, it is associated with a higher relapse rate and longer duration of treatment.As evidenced in the present case, diagnosis requires keen suspicion given the risk for rapidly progressive respiratory compromise. CONCLUSIONS: This case highlights the importance of considering AFOP when evaluating interstitial pneumonias. Reference #1: Kuza C, Matheos T, Kathman D, et al. Journal of Critical Care. 2016;31(1):255-261. Reference #2: Beasley MB., Franks TJ, Galvin JR, et al. Arch Pathol Lab Med. 2002;126:1064-1070 DISCLOSURE: The following authors have nothing to disclose: Deepthi Sudhakar No Product/Research Disclosure Information

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.

Acute Fibrinous Organizing Pneumonia: A Case Report and Literature Review

Acute fibrinous organizing pneumonia (AFOP) is a distinct histopathologic pattern of lung injury with the hallmark feature of intra-alveolar fibrin deposits with associated organizing pneumonia, type II pneumocyte hyperplasia, and a patchy lymphohistiocytic proliferation. We describe the case of a previously healthy 47-year-old man who presented with a 4-day history of worsening dyspnea, cough, and nocturnal fevers and miliary nodules on chest imaging. Subsequently, there was an indication of AFOP when he underwent open lung biopsy. AFOP has been associated with a variety of underlying conditions including rheumatologic diseases, medications, and infections, and several cases were idiopathic. This case highlights the importance for radiologists to be aware of this uncommon pattern of lung injury and to consider it in the differential when encountering bilateral miliary infiltrates on chest imaging.

Clinical significance of intra-alveolar fibrin deposition in transbronchial lung biopsy in patients with organizing pneumonia.

This study examined the clinical significance of intra-alveolar fibrin deposition (IAFD) in transbronchial lung biopsy specimens obtained from patients with organizing pneumonia. Pathological reports of transbronchial lung biopsies performed between 2004 and 2012 were reviewed to identify cases of intra-alveolar organization with or without fibrin deposition. Clinical charts, computed tomography images, and transbronchial lung biopsy specimens from these cases were examined retrospectively. Diagnosis of organizing pneumonia was reevaluated based upon the consensus of a respiratory physician, a radiologist, and a pathologist. Transbronchial lung biopsy results of the reviewed patients with organizing pneumonia found seven patients who had IAFD, and 34 who did not. Seven patients' conditions were associated with collagen vascular disease (CVD), and 34 were cryptogenic. IAFD was significantly associated with high C-reactive protein (CRP) values (>5 mg/dl) (p = 0.0012) and underlying CVD (p = 0.0099). Multivariate analysis revealed that IAFD was independently associated with high CRP values (p = 0.0184). Three of 31 patients and six of 27 patients experienced a relapse of organizing pneumonia within 6 months and 1 year, respectively. IAFD (p = 0.0044) and high CRP values (p = 0.0207) were significantly related to relapse within 6 months, while only CRP was significantly related to relapse within 1 year (p = 0.0007). In patients with organizing pneumonia, IAFD was significantly associated with high CRP values. High CRP values and/or IAFD predicted relapse of organizing pneumonia within 6 months to 1 year.

Therapeutic Modulation of Coagulation and Fibrinolysis in Acute Lung Injury and the Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by excessive intraalveolar fibrin deposition, driven, at least in part by inflammation. The imbalance between activation of coagulation and inhibition of fibrinolysis in patients with ALI/ARDS favors fibrin formation and appears to occur both systemically and in the lung and airspace. Tissue factor (TF), a key mediator of the activation of coagulation in the lung, has been implicated in the pathogenesis of ALI/ARDS. As such, there have been numerous investigations modulating TF activity in a variety of experimental systems in order to develop new therapeutic strategies for ALI/ARDS. This review will summarize current understanding of the role of TF and other proteins of the coagulation cascade as well the fibrinolysis pathway in the development of ALI/ARDS with an emphasis on the pathways that are potential therapeutic targets. These include the TF inhibitor pathway, the protein C pathway, antithrombin, heparin, and modulation of fibrinolysis through plasminogen activator- 1 (PAI-1) or plasminogen activators (PA). Although experimental studies show promising results, clinical trials to date have proven unsuccessful in improving patient outcomes. Modulation of coagulation and fibrinolysis has complex effects on both hemostasis and inflammatory pathways and further studies are needed to develop new treatment strategies for patients with ALI/ARDS.

The Role of Plasminogen Activator Inhibitor-1 and Angiotensin-Converting Enzyme Gene Polymorphisms in Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a multifactorial disease of preterm infants that is characterized by airway injury, inflammation, and parencymal remodeling. Activation of the coagulation cascade leads to intraalveolar fibrin deposition in many inflammatory pulmonary disorders. Increased fibrin formation or decreased fibrinolysis may cause extravascular fibrin deposition. Extravascular fibrin deposits in septae and alveoli due to the altered fibrin turnover are the pathological hallmarks of BPD, which strongly indicate the importance of the imbalance in the competing activities of coagulation and fibrinolysis. We investigated the predictive value of variations in plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes as molecular determinants for BPD in neonates. The study group comprised 98 preterm infants with BPD and a control group including 94 preterm infants without BPD. Restriction fragment size analyses were performed by visualizing digested polymerase chain reaction products for ACE and PAI-1 genotypes. No significant associations were found between ACE, PAI-1 gene polymorphisms, and BPD phenotype in our population. The two gene polymorphisms (PAI-1 and ACE) had no role in the development of BPD in our study. Further studies with other genes are required for the identification of molecular predisposing factors for BPD that may help in the development of new treatments.

Acute fibrinous and organizing pneumonia in systemic lupus erythematosus: A case report and review of the literature

Pulmonary manifestations of systemic lupus erythematosus (SLE) typically include pleuritis, alveolar hemorrhage, and infectious pneumonia due to immunosuppression with less common entities including bronchiolitis, interstitial pneumonia, and pulmonary fibrosis. More rare manifestations include organizing pneumonia (OP) and diffuse alveolar damage (DAD). A similar but distinct entity of acute fibrinous and organizing pneumonia (AFOP), characterized by intra-alveolar fibrin deposition and associated organizing pneumonia, has been reported in association with connective tissue disorders, but has not been described in association with SLE. Reported herein is a patient with SLE and accompanying antiphospholipid syndrome with recent pulmonary embolism, persistent respiratory symptomology, and persistent radiographic abnormalities who underwent lung biopsy displaying features of AFOP. This case in conjunction with previous literature indicates that AFOP can be a manifestation of connective tissue disease including SLE and may be an underreported variant of medical lung disease due to overlap in histological characteristics with OP and DAD.