Development Of Diffuse Alveolar Damage Research Articles

Bystander CD8 + T cells may be involved in the acute phase of diffuse alveolar damage.

Acute respiratory distress syndrome (ARDS) is a serious complication of systemic inflammatory response syndrome, and diffuse alveolar damage (DAD) is a histological manifestation of ARDS. Endothelial cell injury is mainly responsible for ARDS. Many neutrophils and macrophages/monocytes, which are inflammatory cells that play a role in innate immunity, infiltrate the lung tissue in DAD. In recent years, it has become clear that CD8 plays an important role not only in the acquired immune system, but also in the innate immune system. Non-antigen-activated bystander CD8 + T cells express the unique granzyme B (GrB) + /CD25-/programmed cell death-1 (PD-1)-phenotype. The involvement of bystander CD8 + T cells in lung tissue in DAD is an unexplored field. This study aimed to determine whether bystander CD8 is involved in DAD. Twenty-three consecutive autopsy specimens were retrieved from patients with DAD, and the phenotypes of infiltrating lymphocytes in the DAD lesions were evaluated using immunohistochemistry. In most cases, the number of CD8 + T cells was higher than that of CD4 + T cells, and many GrB + cells were also observed. However, the number of CD25 + and PD-1 + cells was low. We conclude that bystander CD8 + T cells may be involved in cell injury during the development of DAD.

ANOTHER BLOODY PNEUMONIA? DIFFUSE ALVEOLAR HEMORRHAGE RESULTING FROM IDIOPATHIC THROMBOCYTOPENIC PURPURA

TYPE: Case Report TOPIC: Diffuse Lung Disease INTRODUCTION: Diffuse alveolar haemorrhage (DAH) is a rare life-threatening pulmonary bleeding manifestation of Idiopathic thrombocytopenic purpura (ITP). CASE PRESENTATION: A 74-year-old gentleman presented to the emergency triage with haemoptysis, worsening shortness of breath, and desaturation. X-ray and CT chest revealed opacifications suggestive of pulmonary haemorrhage. Platelet count was found to be 5,000/μL. Further history revealed he was recently weaned off his usual steroid dose for ongoing ITP. He was initiated on CPAP and received 1 platelet pool. Prednisolone dose was escalated to 1mg/kg once-daily with a stat dose of IVIG(1g/kg). His breathing improved with elevation of platelet count to 37,000/μL. Unfortunately, developed hypoxic respiratory failure again within next couple of days as his platelet count dropped down to 7,000/μL. He was started on eltrombopag along with a repeat platelet transfusion and another dose of IVIG(1g/kg). Clinico-radiological improvement was noted. Platelet count returned to normal by week 6 after admission. DISCUSSION: There is a poor correlation between the degree of thrombocytopenia and bleeding; however, platelet count <10,000/μL is associated with serious bleeding. Histopathologic findings in DAH vary from pulmonary capillaritis, bland hemorrhage to eventual development of diffuse alveolar damage, and hemosiderin-laden macrophages. Immunosuppressive agents are the mainstay of treatment. CONCLUSIONS: We reiterate to keep in mind the possible association between ITP and DAH in the appropriate clinical context. Reference 1: Ioachimescu, O.C. Diffuse alveolar hemorrhage: Diagnosing it and finding the cause. Clevel. Clin. J. Med. 2008 Reference 2: Newsome, B.R.; Morales, J.E. Diffuse alveolar hemorrhage. South. Med. J. 2011, 104, 269–274 DISCLOSURE: Nothing to declare. KEYWORD: diffuse alveolar haemorrhage, idiopathic thrombocytopenic purpura

Deep Learning Localization of Pneumonia: 2019 Coronavirus (COVID-19) Outbreak.

Deep Learning Localization of Pneumonia: 2019 Coronavirus (COVID-19) Outbreak.

A novel swine model of ricin-induced acute respiratory distress syndrome.

ABSTRACTPulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS.

Histopathological Evaluation of the Diversity of Cells Susceptible to H5N1 Virulent Avian Influenza Virus

Patients infected with highly pathogenic avian influenza A H5N1 viruses (H5N1 HPAIV) show diffuse alveolar damage. However, the temporal progression of tissue damage and repair after viral infection remains poorly defined. Therefore, we assessed the sequential histopathological characteristics of mouse lung after intranasal infection with H5N1 HPAIV or H1N1 2009 pandemic influenza virus (H1N1 pdm). We determined the amount and localization of virus in the lung through IHC staining and in situ hybridization. IHC used antibodies raised against the virus protein and antibodies specific for macrophages, type II pneumocytes, or proliferating cell nuclear antigen. In situ hybridization used RNA probes against both viral RNA and mRNA encoding the nucleoprotein and the hemagglutinin protein. H5N1 HPAIV infection and replication were observed in multiple lung cell types and might result in rapid progression of lung injury. Both type II pneumocytes and macrophages proliferated after H5N1 HPAIV infection. However, the abundant macrophages failed to block the viral attack, and proliferation of type II pneumocytes failed to restore the damaged alveoli. In contrast, mice infected with H1N1 pdm exhibited modest proliferation of type II pneumocytes and macrophages and slight alveolar damage. These results suggest that the virulence of H5N1 HPAIV results from the wide range of cell tropism of the virus, excessive virus replication, and rapid development of diffuse alveolar damage.

Viral Tropism and the Pathogenesis of Influenza in the Mammalian Host

Influenza viruses, single-stranded negative-sense RNA viruses within the family Orthomyxoviridae, remain an important cause of human morbidity and mortality worldwide. Despite effective vaccines, more than 200,000 individuals in the United States are hospitalized each year for influenza, and approximately 35,000 succumb to disease.1 Seasonal epidemics arise through antigenic variation and recombination events from existing and currently circulating human strains, which initially target the upper respiratory tract with extension to a bronchointerstitial pneumonia in a subset of affected individuals. Disease is often more severe in older and debilitated patients, producing a characteristic distribution in age-related mortality within the affected population.2 In contrast to seasonal epidemics, pandemics arise when antigenically novel viruses emerge and are readily transmissible within the naive human population. Such events are rare and occur after zoonotic transmission of viruses through recombination events between established human and avian strains or possibly through direct adaptation of avian strains for efficient human to human transmission.3 Concerns over an avian influenza pandemic have risen since 1997 with the recognition of H5N1 as a cause of fulminant disease in humans.4,5 Pathologically fatal H5N1 causes diffuse alveolar damage and progression to multiple organ dysfunction with a case fatality rate estimated at more than 50%. Although H5N1 disease is severe, transmission rates have been low, and viral adaptation to efficient human to human transmission has not occurred. Understanding viral and host barriers that prevent transmission may be critical in establishing rational control measures as well as predicting and stratifying risk for individual strains of influenza. In this issue of The American Journal of Pathology, van Riel et al6 examine the viral binding distribution in pulmonary tissue of a number of avian and human influenza strains to elucidate the role of tropism in transmission and pathogenesis.

Fas/FasL and perforin/granzyme pathway in acute rejection and diffuse alveolar damage after allogeneic lung transplantation-a human biopsy study.

Acute rejection and diffuse alveolar damage are major problems during the early time after transplantation. Against this background, lung biopsies after allogeneic lung transplantation were studied using immunohistochemistry. Biopsies with acute rejection, diffuse alveolar damage and morphological inconspicuous biopsies were chosen. The objectives of this study were to ascertain: (a) if and how CD4 and CD8 T cells contribute to allograft rejection and diffuse alveolar damage, (b) whether there is a correlation of the chemoattractant regulated on activation normal T cells (RANTES) with the mononuclear infiltrate and (c) whether perforin/granzyme and Fas/FasL pathways contribute to lung injury after lung transplantation. Our results show that CD4(+) and CD8(+) T cells were increased in biopsies with acute rejection and, to a minor extent, also in biopsies with diffuse alveolar damage due to reperfusion injury. RANTES expression of T cells was increased in biopsies with acute rejection. Perforin seemed to have a dual role in the alloimmune response. In one regard, it had a cytolytic function in the acute rejection process, and, in contrast, it may be responsible for downregulating both CD4- and CD8-mediated alloimmune responses. The FasL/Fas pathway is not only important for induction of apoptosis during rejection but is also a mechanism of lung injury in the development of diffuse alveolar damage.

Respiratory Reovirus 1/L Induction of Diffuse Alveolar Damage: Pulmonary Fibrosis Is Not Modulated by Corticosteroids in Acute Respiratory Distress Syndrome in Mice

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage (DAD) secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. We have previously described a unique animal model in which CBA/J mice infected with reovirus 1/L develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consist of the overlapping phases of exudation, including the formation of hyaline membranes, regeneration, and healing via repair with fibrosis. In this report, we show that the development of DAD in the acute phase of the disease and intraalveolar fibrosis in the late phase of the disease was not modulated by treatment with methylprednisolone (MPS). In the presence or absence of MPS, the majority of cells infiltrating the lungs after reovirus 1/L infection were polymorphonuclear leukocytes and macrophages. A number of key proinflammatory and anti-inflammatory cytokines/chemokines that are observed in the BAL fluid of ARDS patients were also found in the lungs of mice after reovirus 1/L infection and were not modulated by MPS. These include interferon-γ, interleukin-10, and monocyte chemoattractant protein. The histopathology, cytokine/chemokine expression, and response to corticosterids in reovirus 1/L-induced ARDS are similar to what is observed in human patients, making this a clinically relevant model.