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Yuh Fukuda - One of the best experts on this subject based on the ideXlab platform.
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quantitative diagnosis of Diffuse Alveolar Damage using extravascular lung water
Critical Care Medicine, 2013Co-Authors: Takashi Tagami, Motoji Sawabe, Shigeki Kushimoto, Paul E Marik, Makiko Mieno, Takanori Kawaguchi, Takashi Kusakabe, Ryoichi Tosa, Hiroyuki Yokota, Yuh FukudaAbstract:OBJECTIVES: Acute respiratory distress syndrome is characterized by Diffuse Alveolar Damage and increased extravascular lung water levels. However, there is no threshold extravascular lung water level that can indicate Diffuse Alveolar Damage in lungs. We aimed to determine the threshold extravascular lung water level that discriminates between normal lungs and lungs affected with Diffuse Alveolar Damage. DESIGN: A retrospective analysis of normal lungs and lungs affected with Diffuse Alveolar Damage was performed. SETTING: Normal lung cases were taken from published data. Lung cases with Diffuse Alveolar Damage were taken from a nationwide autopsy database. All cases of autopsy followed hospital deaths in Japan from more than 800 hospitals between 2004 and 2009; complete autopsies with histopathologic examinations were performed by board-certified pathologists authorized by the Japanese Society of Pathology. PATIENTS: Normal lungs: 534; lungs with Diffuse Alveolar Damage: 1,688. INTERVENTIONS: We compared the postmortem weights of both lungs between the two groups. These lung weights were converted to extravascular lung water values using a validated equation. Finally, the extravascular lung water value that indicated Diffuse Alveolar Damage was estimated using receiver operating characteristic analysis. MEASUREMENTS AND MAIN RESULTS: The extravascular lung water values of the lungs showing Diffuse Alveolar Damage were approximately two-fold higher than those of normal lungs (normal group, 7.3±2.8 mL/kg vs Diffuse Alveolar Damage group 13.7±4.5 mL/kg; p<0.001). An extravascular lung water level of 9.8 mL/kg allowed the diagnosis of Diffuse Alveolar Damage to be established with a sensitivity of 81.3% and a specificity of 81.2% (area under the curve, 0.90; 95% CI, 0.88-0.91). An extravascular lung water level of 14.6 mL/kg represented a 99% positive predictive value. CONCLUSIONS: This study may provide the first validated quantitative bedside diagnostic tool for Diffuse Alveolar Damage. Extravascular lung water may allow the detection of Diffuse Alveolar Damage and may support the clinical diagnosis of acute respiratory distress syndrome. The best extravascular lung water cut-off value to discriminate between normal lungs and lungs with Diffuse Alveolar Damage is around 10 mL/kg.
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Quantitative diagnosis of Diffuse Alveolar Damage using extravascular lung water.
Critical care medicine, 2013Co-Authors: Takashi Tagami, Motoji Sawabe, Shigeki Kushimoto, Paul E Marik, Makiko Mieno, Takanori Kawaguchi, Takashi Kusakabe, Ryoichi Tosa, Hiroyuki Yokota, Yuh FukudaAbstract:OBJECTIVES Acute respiratory distress syndrome is characterized by Diffuse Alveolar Damage and increased extravascular lung water levels. However, there is no threshold extravascular lung water level that can indicate Diffuse Alveolar Damage in lungs. We aimed to determine the threshold extravascular lung water level that discriminates between normal lungs and lungs affected with Diffuse Alveolar Damage. DESIGN A retrospective analysis of normal lungs and lungs affected with Diffuse Alveolar Damage was performed. SETTING Normal lung cases were taken from published data. Lung cases with Diffuse Alveolar Damage were taken from a nationwide autopsy database. All cases of autopsy followed hospital deaths in Japan from more than 800 hospitals between 2004 and 2009; complete autopsies with histopathologic examinations were performed by board-certified pathologists authorized by the Japanese Society of Pathology. PATIENTS Normal lungs: 534; lungs with Diffuse Alveolar Damage: 1,688. INTERVENTIONS We compared the postmortem weights of both lungs between the two groups. These lung weights were converted to extravascular lung water values using a validated equation. Finally, the extravascular lung water value that indicated Diffuse Alveolar Damage was estimated using receiver operating characteristic analysis. MEASUREMENTS AND MAIN RESULTS The extravascular lung water values of the lungs showing Diffuse Alveolar Damage were approximately two-fold higher than those of normal lungs (normal group, 7.3±2.8 mL/kg vs Diffuse Alveolar Damage group 13.7±4.5 mL/kg; p
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Two forms of Diffuse Alveolar Damage in the lungs of patients with acute respiratory distress syndrome
Human pathology, 2009Co-Authors: Dedong Kang, Tomoko Nakayama, Mayuko Togashi, Masuki Yamamoto, Mikiko Takahashi, Shinobu Kunugi, Masamichi Ishizaki, Yuh FukudaAbstract:Acute respiratory distress syndrome is a severe disease, the treatment and pathophysiology of which are not completely established. The pathology of acute respiratory distress syndrome involves Diffuse Alveolar Damage, which comprises severe Alveolar epithelial cell Damage, hyaline membrane formation, and festinate myofibroblast proliferation and fibrosis in the intra-Alveolar spaces. We performed a clinicopathologic investigation of 26 autopsy cases of Diffuse Alveolar Damage. Three cases of them were diagnosed as acute interstitial pneumonia that is idiopathic illness and resembles pathologically organizing Diffuse Alveolar Damage. Immunohistochemical staining for types I and IV collagen, alpha-smooth muscle actin, and Ki-67 was carried out, and the sites of myofibroblast proliferation and type I collagen production were examined. All Diffuse Alveolar Damage cases in the proliferative phase showed intra-Alveolar myofibroblast proliferation. When Diffuse Alveolar Damage was diagnosed pathologically as being due to severe infection, all 7 patients showed multiple organ dysfunction syndrome, whereas only 2 of 7 patients showed interstitial myofibroblast proliferation. When Diffuse Alveolar Damage was attributed to tumor treatment with chemotherapy or to drug toxicity, 3 of 16 patients showed multiple organ dysfunction syndrome; 15 of 16 showed interstitial myofibroblast proliferation, 3 of 3 acute interstitial pneumonia patients did not show multiple organ dysfunction syndrome; and 3 of 3 acute interstitial pneumonia showed marked interstitial myofibroblast proliferation. These results suggest that the pathophysiologic mechanism of Diffuse Alveolar Damage caused by severe infection is one of systemic circulation disturbance, although the mechanism underlying Diffuse Alveolar Damage due to tumor with chemotherapy or drug toxicity appears to involve interstitial pneumonia-like lesions that are similar to acute interstitial pneumonia.
Moritaka Suga - One of the best experts on this subject based on the ideXlab platform.
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Diffuse Alveolar Damage after ZD1839 therapy in a patient with non-small cell lung cancer.
Lung cancer (Amsterdam Netherlands), 2003Co-Authors: Isamu Okamoto, Kazuhiko Fujii, Mitsuhiro Matsumoto, Yasuhiro Terasaki, Nanae Kihara, Hirotsugu Kohrogi, Moritaka SugaAbstract:ZD1839 is an orally active inhibitor selective for the epidermal growth factor receptor tyrosine kinase and has shown promise in the treatment of non-small cell lung cancer (NSCLC). We now present a case of Diffuse Alveolar Damage (DAD) that developed in a 67-year-old man treated with ZD1839. On day 8 of ZD1839 administration, the patient complained of dyspnea and a new-ground glass opacity was apparent on a chest X-ray and computed tomography scan. Despite high-dose steroid therapy, the patient died 13 days after the first administration of ZD1839. Postmortem analysis of lung tissue revealed a pattern of DAD. No evidence of infection or of other specific etiologies was apparent. This case is the first reported of respiratory failure after ZD1839 treatment in a patient with NSCLC. Physicians should therefore be aware of the potential pulmonary toxicity of ZD1839.
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Case report Diffuse Alveolar Damage after ZD1839 therapy in a patient with non-small cell lung cancer
2003Co-Authors: Isamu Okamoto, Kazuhiko Fujii, Mitsuhiro Matsumoto, Yasuhiro Terasaki, Nanae Kihara, Hirotsugu Kohrogi, Moritaka SugaAbstract:ZD1839 is an orally active inhibitor selective for the epidermal growth factor receptor tyrosine kinase and has shown promise in the treatment of non-small cell lung cancer (NSCLC). We now present a case of Diffuse Alveolar Damage (DAD) that developed in a 67-year-old man treated with ZD1839. On day 8 of ZD1839 administration, the patient complained of dyspnea and a new-ground glass opacity was apparent on a chest X-ray and computed tomography scan. Despite high-dose steroid therapy, the patient died 13 days after the first administration of ZD1839. Postmortem analysis of lung tissue revealed a pattern of DAD. No evidence of infection or of other specific etiologies was apparent. This case is the first reported of respiratory failure after ZD1839 treatment in a patient with NSCLC. Physicians should therefore be aware of the potential pulmonary toxicity of ZD1839. # 2003 Elsevier Science Ireland Ltd. All rights reserved.
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hyperoxia induced Diffuse Alveolar Damage in pigs correlation between thin section ct and histopathologic findings
Radiology, 2000Co-Authors: Kazuya Ichikado, Osamu Honda, Takeshi Johkoh, Moritaka Suga, Yasuhiro Gushima, Kazuhiro Iyonaga, Toshimi Yokoyama, Yoshihisa Shigeto, Seiji Tomiguchi, Mutsumasa TakahashiAbstract:PURPOSE: To determine whether lung abnormalities at thin-section computed tomography (CT) in experimental hyperoxic lung injury correlate with the pathologic phases of Diffuse Alveolar Damage (DAD). MATERIALS AND METHODS: Eighteen juvenile pigs were exposed to more than 80% oxygen—for 24, 48, 72, 96, or 120 hours—or room air in sealed cages. Their removed lungs were inflated with air infused through the trachea and examined with thin-section CT. Two independent observers, without knowledge of the exposure times, compared 63 areas selected on the CT scans with the corresponding pathologic and histologic findings, which were evaluated independently by two pathologists. RESULTS: CT findings correlated well with histologic findings (ρ = 0.86, P < .001), which corresponded to the pathologic phases of DAD. All areas of normal CT attenuation, eight of nine spared regions within areas of opacity, and two of 15 areas of ground-glass opacity corresponded to the early exudative pathologic phase of DAD. All areas tha...
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Hyperoxia-induced Diffuse Alveolar Damage in pigs: correlation between thin-section CT and histopathologic findings.
Radiology, 2000Co-Authors: Kazuya Ichikado, Osamu Honda, Takeshi Johkoh, Moritaka Suga, Yasuhiro Gushima, Kazuhiro Iyonaga, Toshimi Yokoyama, Yoshihisa Shigeto, Seiji Tomiguchi, Mutsumasa TakahashiAbstract:PURPOSE: To determine whether lung abnormalities at thin-section computed tomography (CT) in experimental hyperoxic lung injury correlate with the pathologic phases of Diffuse Alveolar Damage (DAD). MATERIALS AND METHODS: Eighteen juvenile pigs were exposed to more than 80% oxygen—for 24, 48, 72, 96, or 120 hours—or room air in sealed cages. Their removed lungs were inflated with air infused through the trachea and examined with thin-section CT. Two independent observers, without knowledge of the exposure times, compared 63 areas selected on the CT scans with the corresponding pathologic and histologic findings, which were evaluated independently by two pathologists. RESULTS: CT findings correlated well with histologic findings (ρ = 0.86, P
Annaluise A Katzenstein - One of the best experts on this subject based on the ideXlab platform.
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Proliferative activity in fibrosing lung diseases: a comparative study of Ki-67 immunoreactivity in Diffuse Alveolar Damage, bronchiolitis obliterans-organizing pneumonia, and usual interstitial pneumonia.
Human pathology, 2009Co-Authors: Ola El-zammar, Paula Rosenbaum, Annaluise A KatzensteinAbstract:Summary Because Diffuse Alveolar Damage, bronchiolitis obliterans–organizing pneumonia, and usual interstitial pneumonia are all related to acute lung injury, we postulated that the proliferative activity of fibroblasts and epithelium would be similar in all 3, and that of fibroblasts would be similar to skin scars. Ki-67 staining was assessed in 16 usual interstitial pneumonia, 9 bronchiolitis obliterans–organizing pneumonia, and 8 Diffuse Alveolar Damage cases, 5 incidental fibroblast foci, 5 skin scars, and 5 keloids. The proliferative activity of Alveolar macrophages was also measured and compared with that of 10 respiratory bronchiolitis cases. The greatest proliferative activity was found in fibroblasts and epithelium of Diffuse Alveolar Damage (25.8% and 41.9%), and it was significantly greater ( P = .000) than in usual interstitial pneumonia (1.88% and 2.6%), bronchiolitis obliterans–organizing pneumonia (4.07% and 1.55%), and incidental fibroblast foci (2.9% and 0.44%). The proliferative activity in fibroblasts of Diffuse Alveolar Damage was significantly higher than that of fibroblasts in skin scars ( P = .024). In contrast, the proliferative rate of fibroblasts in bronchiolitis obliterans–organizing pneumonia, usual interstitial pneumonia, and incidental fibroblast foci was significantly lower than that in skin scars ( P = .000, P = .000, and P = .001) but similar to keloids ( P = 1.000). Usual interstitial pneumonia macrophages showed an unexpectedly high proliferative rate (19.5%) that was significantly greater than that in bronchiolitis obliterans–organizing pneumonia (5.5%, P = .000), Diffuse Alveolar Damage (9.01%, P = .007), incidental fibroblast foci (9.5%, P = .036), and respiratory bronchiolitis (11.45%, P = .031). Our results suggest different reactions to acute injury in usual interstitial pneumonia and bronchiolitis obliterans–organizing pneumonia compared with Diffuse Alveolar Damage. The similar low proliferative activity of fibroblasts in usual interstitial pneumonia and keloids supports the hypothesis of abnormal wound healing in usual interstitial pneumonia. The high proliferative activity of macrophages in usual interstitial pneumonia suggests a role in the pathogenesis of usual interstitial pneumonia.
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Diffuse Alveolar Damage and recurrent respiratory failure: report of 6 cases.
Human pathology, 2001Co-Authors: Dana Savici, Annaluise A KatzensteinAbstract:We report 6 patients in whom Diffuse Alveolar Damage (DAD) was found on 1 or more lung biopsy specimens and who experienced recurrent episodes of acute respiratory failure. The patients ranged in age from 43 to 55 years. Two to five episodes of respiratory failure occurred in each over a period of 4 months to 2 years. One patient developed evidence of chronic lung disease; while the others remained well between episodes. Lung biopsies showed the acute stage of DAD in 3, overlapping acute and organizing stages in 3, and the organizing stage in 2. A definite cause was not identifiable in any. However, 4 had been treated with narcotics for chronic pain before the first episode, and 1 received this treatment before the recurrent episode. Three also were receiving psychotropic drugs for anxiety and depression. Five patients had evidence of gastroesophageal reflux disease (GERD) and/or hiatal hernia, 2 of whom underwent Nissen fundoplication in hopes of preventing future recurrences. Although a definite cause of the recurrent DAD was not identified, the findings suggest the possibility of a reaction to narcotics and/or psychotropic drugs in some patients, with a possible additional effect of GERD. A drug history should be carefully elicited in patients with recurrent DAD, and all potentially toxic drugs should be stopped.
Jose A Lorente - One of the best experts on this subject based on the ideXlab platform.
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Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship
Annals of the American Thoracic Society, 2017Co-Authors: Pablo Cardinal-fernández, Jose A Lorente, Aida Ballén-barragán, Gustavo Matute-belloAbstract:Acute respiratory distress syndrome (ARDS) is a major clinical problem with high morbidity and mortality. Diffuse Alveolar Damage (DAD) is considered the histological hallmark for the acute phase of ARDS. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation, followed by an organizing phase with Alveolar septal fibrosis and type II pneumocyte hyperplasia. Given the difficulties in obtaining a biopsy in patients with ARDS, the presence of DAD is not required to make the diagnosis. However, biopsy and autopsy studies suggest that only one-half of patients who meet the clinical definition of ARDS also have DAD. The other half are found to have a group of heterogeneous disorders, including pneumonia. Importantly, the subgroup of patients with ARDS who also have DAD appears to have increased mortality. It is possible that the response of these patients to specific therapies targeting the molecular mechanisms of ARDS may differ from patients without DAD. Therefore, it may be imp...
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acute respiratory distress syndrome in patients with and without Diffuse Alveolar Damage an autopsy study
Intensive Care Medicine, 2015Co-Authors: Jose A Lorente, Pablo Cardinalfernandez, D Munoz, Fernando Frutosvivar, Arnaud W Thille, C Jaramillo, Aida Ballenbarragan, J M Rodriguez, Oscar PenuelasAbstract:Objective To demonstrate that among patients with acute respiratory distress syndrome (ARDS), the presence of Diffuse Alveolar Damage (DAD) at histological examination, as compared to its absence, defines a specific subphenotype.
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chronology of histological lesions in acute respiratory distress syndrome with Diffuse Alveolar Damage a prospective cohort study of clinical autopsies
The Lancet Respiratory Medicine, 2013Co-Authors: Arnaud W Thille, Jose A Lorente, J M Rodriguez, Andres Esteban, Pilar Fernandezsegoviano, Joseantonio Aramburu, Patricio Vargaserrazuriz, Ana Martinpellicer, Fernando FrutosvivarAbstract:Summary Background Diffuse Alveolar Damage is the histological hallmark of acute respiratory distress syndrome (ARDS). However, the chronology of histological lesions is not well established. We aimed to determine the time to onset of exudative or proliferative changes and end-stage fibrosis in ARDS. Methods We analysed all patients who died between Jan 1, 1991, and Dec 31, 2010, in the intensive-care unit at the Hospital Universitario de Getafe, Madrid, Spain, and who had a clinical autopsy. Patients had to have clinical criteria for ARDS at time of death and histological features of Diffuse Alveolar Damage at autopsy examination. Capillary congestion and intra-Alveolar oedema characterised the exudative phase whereas proliferation of Alveolar cell type 2 or fibroblasts, or fibrosis characterised the proliferative phase. Findings We analysed 159 patients. The prevalence of exudative changes decreased over time, being reported in 74 (90%) of 82 patients with ARDS of less than 1 week duration, 40 (74%) of 54 patients with disease of 1–3 week duration, and only four (17%) of 23 patients with disease of longer than 3 weeks' duration (p Interpretation Histological features of the lungs were related to duration of ARDS. Within the first week of evolution, exudative changes were predominant and fibrosis was rarely noted. Beyond the third week of evolution, proliferative changes were noted in all patients and fibrosis in two-thirds of them. Treatments with a potential effect on inflammation or fibrosis, or both, should probably focus on the first week after the onset of ARDS. Funding None.
Pablo Cardinal-fernández - One of the best experts on this subject based on the ideXlab platform.
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Airway Pathological Alterations Selectively Associated With Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage - Narrative Review.
Archivos de bronconeumologia, 2018Co-Authors: Guillermo Ortiz, Manuel Garay, Vera Luiza Capelozzi, Pablo Cardinal-fernándezAbstract:Acute respiratory distress syndrome (ARDS) is a frequent and life-threatening entity. Recently, it has been demonstrated that Diffuse Alveolar Damage (DAD), which is considered the histological hallmark in spite of presenting itself in only half of living patients with ARDS, exerts a relevant effect in the ARDS outcome. Despite the fact that the bronchial tree constitutes approximately 1% of the lung volume, discovering a relation between DAD and bronchial tree findings could be of paramount importance for a few reasons; (a) it could improve the description of ARDS with DAD as a clinical-pathological entity, (b) it could subrogate DAD findings with the advantage of their more accessible and safer analysis and (c) it could allow the discovery of new therapeutic targets. This narrative review is focused on pathological airway changes associated to Diffuse Alveolar Damage in the context of Acute Respiratory Distress Syndrome. It is organized into five sections: main anatomical and functional features of the human airway, why it is necessary to study airway features associated to DAD in patients with ARDS, pathological airway changes associated with DAD in animal models of ARDS, pathological airway changes associated with DAD in patients with ARDS, and the newest techniques for studying the histology of the bronchial tree and lung parenchyma.
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What every intensivist should know about acute respiratory distress syndrome and Diffuse Alveolar Damage.
Revista Brasileira de terapia intensiva, 2017Co-Authors: Fernando Rios, Teresa Iscar, Pablo Cardinal-fernándezAbstract:Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is Diffuse Alveolar Damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with Diffuse Alveolar Damage constitutes a specific clinical-pathological entity. Given that Diffuse Alveolar Damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for Diffuse Alveolar Damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and Diffuse Alveolar Damage, (b) how Diffuse Alveolar Damage could be surrogated in the clinical setting and
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What every intensivist should know about acute respiratory distress syndrome and Diffuse Alveolar Damage
2017Co-Authors: Fernando Rios, Teresa Iscar, Pablo Cardinal-fernándezAbstract:ABSTRACT Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is Diffuse Alveolar Damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with Diffuse Alveolar Damage constitutes a specific clinical-pathological entity. Given that Diffuse Alveolar Damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for Diffuse Alveolar Damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and Diffuse Alveolar Damage, (b) how Diffuse Alveolar Damage could be surrogated in the clinical setting and (c) how enrichment in Diffuse Alveolar Damage may improve the results of pharmacological clinical trials tried out on patients with acute respiratory distress syndrome.
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Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship
Annals of the American Thoracic Society, 2017Co-Authors: Pablo Cardinal-fernández, Jose A Lorente, Aida Ballén-barragán, Gustavo Matute-belloAbstract:Acute respiratory distress syndrome (ARDS) is a major clinical problem with high morbidity and mortality. Diffuse Alveolar Damage (DAD) is considered the histological hallmark for the acute phase of ARDS. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation, followed by an organizing phase with Alveolar septal fibrosis and type II pneumocyte hyperplasia. Given the difficulties in obtaining a biopsy in patients with ARDS, the presence of DAD is not required to make the diagnosis. However, biopsy and autopsy studies suggest that only one-half of patients who meet the clinical definition of ARDS also have DAD. The other half are found to have a group of heterogeneous disorders, including pneumonia. Importantly, the subgroup of patients with ARDS who also have DAD appears to have increased mortality. It is possible that the response of these patients to specific therapies targeting the molecular mechanisms of ARDS may differ from patients without DAD. Therefore, it may be imp...