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      Pathological and ultrastructural analysis of surgical lung biopsies in patients with swine‐origin influenza type A/H1N1 and acute respiratory failure

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          Abstract

          BACKGROUND:

          Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co‐infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment.

          OBJECTIVE:

          To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1.

          METHODS:

          Lung specimens underwent microbiologic analysis, and examination by optical and electron microscopy. Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS.

          RESULTS:

          The pathological features observed were necrotizing bronchiolitis, diffuse alveolar damage, alveolar hemorrhage and abnormal immune response. Ultrastructural analysis showed viral‐like particles in all cases.

          CONCLUSIONS:

          Viral‐like particles can be successfully demonstrated in lung tissue by ultrastructural examination, without confirmation of the virus by RT‐PCR on nasopharyngeal aspirates. Bronchioles and epithelium, rather than endothelium, are probably the primary target of infection, and diffuse alveolar damage the consequence of the effect of airways obliteration and dysfunction on innate immunity, suggesting that treatment should be focused on epithelial repair.

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          Most cited references69

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          Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico.

          In late March 2009, an outbreak of a respiratory illness later proved to be caused by novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in Mexico. We describe the clinical and epidemiologic characteristics of persons hospitalized for pneumonia at the national tertiary hospital for respiratory illnesses in Mexico City who had laboratory-confirmed S-OIV infection, also known as swine flu. We used retrospective medical chart reviews to collect data on the hospitalized patients. S-OIV infection was confirmed in specimens with the use of a real-time reverse-transcriptase-polymerase-chain-reaction assay. From March 24 through April 24, 2009, a total of 18 cases of pneumonia and confirmed S-OIV infection were identified among 98 patients hospitalized for acute respiratory illness at the National Institute of Respiratory Diseases in Mexico City. More than half of the 18 case patients were between 13 and 47 years of age, and only 8 had preexisting medical conditions. For 16 of the 18 patients, this was the first hospitalization for their illness; the other 2 patients were referred from other hospitals. All patients had fever, cough, dyspnea or respiratory distress, increased serum lactate dehydrogenase levels, and bilateral patchy pneumonia. Other common findings were an increased creatine kinase level (in 62% of patients) and lymphopenia (in 61%). Twelve patients required mechanical ventilation, and seven died. Within 7 days after contact with the initial case patients, a mild or moderate influenza-like illness developed in 22 health care workers; they were treated with oseltamivir, and none were hospitalized. S-OIV infection can cause severe illness, the acute respiratory distress syndrome, and death in previously healthy persons who are young to middle-aged. None of the secondary infections among health care workers were severe. 2009 Massachusetts Medical Society
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            An expanded definition of the adult respiratory distress syndrome.

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              Severe respiratory disease concurrent with the circulation of H1N1 influenza.

              In the spring of 2009, an outbreak of severe pneumonia was reported in conjunction with the concurrent isolation of a novel swine-origin influenza A (H1N1) virus (S-OIV), widely known as swine flu, in Mexico. Influenza A (H1N1) subtype viruses have rarely predominated since the 1957 pandemic. The analysis of epidemic pneumonia in the absence of routine diagnostic tests can provide information about risk factors for severe disease from this virus and prospects for its control. From March 24 to April 29, 2009, a total of 2155 cases of severe pneumonia, involving 821 hospitalizations and 100 deaths, were reported to the Mexican Ministry of Health. During this period, of the 8817 nasopharyngeal specimens that were submitted to the National Epidemiological Reference Laboratory, 2582 were positive for S-OIV. We compared the age distribution of patients who were reported to have severe pneumonia with that during recent influenza epidemics to document an age shift in rates of death and illness. During the study period, 87% of deaths and 71% of cases of severe pneumonia involved patients between the ages of 5 and 59 years, as compared with average rates of 17% and 32%, respectively, in that age group during the referent periods. Features of this epidemic were similar to those of past influenza pandemics in that circulation of the new influenza virus was associated with an off-season wave of disease affecting a younger population. During the early phase of this influenza pandemic, there was a sudden increase in the rate of severe pneumonia and a shift in the age distribution of patients with such illness, which was reminiscent of past pandemics and suggested relative protection for persons who were exposed to H1N1 strains during childhood before the 1957 pandemic. If resources or vaccine supplies are limited, these findings suggest a rationale for focusing prevention efforts on younger populations. 2009 Massachusetts Medical Society
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                Author and article information

                Journal
                Clinics (Sao Paulo)
                Clinics
                Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
                1807-5932
                1980-5322
                December 2010
                : 65
                : 12
                : 1229-1237
                Affiliations
                [I ]Pathology ‐ Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil.
                [II ]Thoracic Surgery Unit‐ Hospital de Base do Distrito Federal ‐ Brasilia, Brazil.
                [III ]Thoracic Surgery‐ Instituto de Infectologia Emílio Ribas ‐ São Paulo, SP, Brazil.
                [IV ]Intensive Care Unity‐ Hospital Israelita Albert Einstein ‐, São Paulo, SP, Brazil.
                [V ]Anatomy‐ Hospital das Clinicas da faculdade de Medicina da Universidade de São Paulo, Sao Paulo, SP, Brazil.
                Author notes
                E-mail: erparra2003@ 123456yahoo.com.br Tel.: 55 11 3826‐1422
                Article
                cln_65p1229
                10.1590/S1807-59322010001200003
                3020331
                21340209
                1c04aa60-c0df-4a81-a4ef-f09bc9a271a4
                Copyright © 2010 Hospital das Clínicas da FMUSP

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 July 2010
                : 2 August 2010
                : 7 September 2010
                Page count
                Pages: 9
                Categories
                Clinical Science

                Medicine
                innate immunity,diffuse alveolar damage,acute lung injury,electron microscopy,virus,open lung biopsy

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