Hemorragia alveolar pulmonar como presentación poco frecuente de infección por Leptospira spp: una enfermedad ocupacional del personal militar en zonas tropicales / Pulmonary alveolar hemorrhage as an unusual presentation of Leptospira spp: an occupational-disease of military personnel in tropical zones

Resumen La leptospirosis es una de las zoonosis endémicas más importantes en el mundo con un aumento de la incidencia en los últimos años. En el personal militar podría ser catalogada como una enfermedad ocupacional dado sus actividades específicas en áreas rurales. Su presentación clínica es variable siendo en la mayoría de los casos una enfermedad febril autolimitada. De acuerdo con diversos factores dependientes del patógeno y del hospedero pueden presentarse manifestaciones severas de la enfermedad dentro de la cual destaca el compromiso pulmonar con una alta tasa de mortalidad. Existe evidencia del uso de esteroide sistémico como parte del tratamiento de esta complicación. Presentamos el caso de un paciente joven, militar, que debuta con síndrome de hemorragia alveolar difusa secundario a leptospirosis y presenta una excelente respuesta al tratamiento con altas dosis de metilprednisolona, con una discusión del proceso diagnóstico y aspectos fisiopatológicos de esta condición.

Leptospirosis is one of the most important endemic zoonoses in the world with an increase in incidence in recent years. In military personnel it could be classified as an occupational disease given their specific activities in rural areas. Its clinical presentation is variable being in most cases a self-limited febrile disease. According to various factors dependent on the pathogen and the host, severe manifestations of the disease may occur within which the pulmonary involvement with a high mortality rate stands out. There is evidence of systemic steroid use as part of the treatment of this complication. We present a case of a young, military patient who debuts with diffuse alveolar hemorrhage syndrome secondary to leptospirosis and presents an excellent response to treatment with high doses of methylprednisolone, with a discussion of the diagnostic process and pathophysiological aspects of this condition.

Apoptotic mechanisms in rabbits with blast-induced acute lung injury

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

O que todo intensivista deve saber a respeito da síndrome do desconforto respiratório agudo e dano alveolar difuso? / What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage

RESUMO A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.

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.

Effects of oxygen in lungs of rats

PURPOSE: To analyze microscopically the effects of different concentrations of oxygen in the lungs of rats. METHODS: There were 20 rats distributed in three experimental groups (concentration of oxygen to 40%, 70% and 100%) and a control group. The animals were exposed to the oxygen in a chamber of acrylic during three days and after exposition, the animals were submitted to median thoracotomia to remove the lungs. The lung tissue of all of the animals was analyzed as regards presence of acute and chronic inflammation, capillary congestion, alveolar walls thick, interstitial and alveolar edema, alveolar hemorrhage, denudation capillary and alveolar endothelium areas and atelectasis. RESULTS: The analysis histopathologic revealed significant statistics difference for acute and chronic inflammation, capillary congestion, alveolar walls thick, interstitial and alveolar edema, alveolar hemorrhage, denudation capillary and alveolar epithelium areas. CONCLUSIONS: Exposition to the oxygen during 72 hours in the concentration of 40% does not produce significant histopathologic alterations in the lung tissue; in the concentration of 70%, can promotes the alveolar walls thick and capillary congestion and in the concentration of 100% can cause death and originate diffuse pulmonary lesion. .

Modeling pulmonary fibrosis by abnormal expression of telomerase/apoptosis/collagen V in experimental usual interstitial pneumonia

Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis.

Progressão microestrutural e molecular da lesão pulmonar em um modelo de Síndrome do Desconforto Respiratório Agudo / Microstructural and molecular progression of the pulmonary injury in a model of Acute Respiratory Distress Syndrome (ARDS)

Introdução: O padrão de distribuição da lesão pulmonar na síndrome do desconforto respiratório agudo (SDRA) tem sido alvo de interesse de estudos com tomografia computadorizada. Entretanto, pouca informação é disponível quanto a distribuição e progressão histológica da lesão pulmonar na SDRA. Objetivos: Caracterizar a distribuição e progressão histológica da lesão pulmonar em modelo experimental de SDRA em suínos pela quantificação de parâmetros estruturais, inflamatórios e de remodelamento da matriz extracelular (MEC) e correlacioná-los com variáveis funcionais e de tomografia de impedância elétrica (TIE). Métodos: Vinte e três porcas da raça Landrace foram divididos em três grupos: 1) Sham (n=5): animais submetidos ao preparo e monitorização; 2) Lesão (n=9): animais submetidos ao protocolo de lesão e eutanasiados após 3 horas; 3) Lesão+MV: animais submetidos ao protocolo de lesão e eutanasiados após 40 horas de ventilação mecânica (VM) segundo a "estratégia ARDSnet". Os parâmetros histológicos foram mensurados por análise de imagem e incluíam: área alveolar, índice de espessamento septal, densidade neutrofílica, membrana hialina, hemorragia, edema intraalveolar e proporção de fibras colágenas. As medidas de cada parâmetro foram normalizadas pela mediana do grupo Sham. Expressão gênica de proteínas da MEC (colágeno tipo I e tipo III, versican, biglican e decorin) foram quantificados por PCR em tempo real. A ventilação regional foi mensurada por TIE. Foram analisadas regiões anteriores e posteriores do pulmão para cada variável. Resultados: A densidade neutrofílica foi menor no grupo Lesão+VM (p=0,02). A análise da área alveolar no grupo Lesão+VM mostrou que as regiões posteriores apresentaram menor área que as regiões anteriores (p=0,012). Entretanto, o espessamento septal foi maior no grupo Lesão+VM, especialmente nas regiões anteriores, quando comparado ao grupo Lesão (p <= 0,01)...

Introduction: The pattern of lesion distribution in acute respiratory distress syndrome (ARDS) has been addressed in computed tomography studies. However, there is little information concerning the progression and distribution of histological lung injury in ARDS. Objectives: To characterize the histological progression and distribution of lung injury in a pig ARDS model by the quantification of structural, inflammatory and extracellular matrix (ECM) remodeling parameters and to correlate them with functional and electrical impedance tomography (EIT) variables . Methods: Twenty-three healthy female Landrace pigs were divided into three groups: 1) Sham (n=5): animals subjected to preparation and monitoring; 2) Injury (n=9): animals subjected to the injury protocol and euthanized after 3 hours. 3) Injury+MV (n=9): animals subjected to the injury protocol and euthanized after 40 hours of ARDSnet mechanical ventilation. Histological parameters measured by image analysis included: alveolar area, septal thickening index, neutrophils density, hyaline membrane, hemorrhage, alveolar edema and collagen fibers content. The parameters values were normalized by Sham group median values. Gene expression of ECM proteins (collagen type I and type III, versican, biglycan and decorin) was quantified by Real Time-PCR. Regional ventilation was measured by EIT. For each variable the anterior and posterior regions of the lung were analyzed. Results: Density neutrophil was lesser in the Injury+MV group (p=0.02). Alveolar area in the posterior regions of the Injury+MV group was lesser than the anterior regions (p=0.012). However, the septal thickening was higher in Injury+MV group, especially in the anterior regions, when compared to the Injury group (p <= 0.01)...

Sandstorm Appearance of Pulmonary Alveolar Microlithiasis Incidentally Detected in a Young, Asymptomatic Male

Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of symptoms in contrast to the imaging findings. We present a case of a 24-year-old Malay man having an incidental abnormal pre-employment chest radiograph of dense micronodular opacities giving the classical "sandstorm" appearance. High-resolution computed tomography of the lungs showed microcalcifications with subpleural cystic changes. Open lung biopsy showed calcospherites within the alveolar spaces. The radiological and histopathological findings were characteristic of PAM.

Hemorragia alveolar difusa no lúpus sistêmico: adversário duro, não imbatível / Diffuse alveolar hemorrhage in the systemic lupus erythematosus: a hard, but not invincible opponent

Hemorragia alveolar é afecção clínica grave e com alta taxa de mortalidade. Pode ocorrer em indivíduos com lúpus eritematoso sistêmico e a instituição de imunossupressão precoce é medida salvadora. Como é de diagnóstico difícil, sua condução clínica é um desafio. No presente artigo relata-se a experiência recente com dois pacientes e as recomendações de terapêutica, segundo revisão de literatura médica.

Alveolar hemorrhage is a severe clinical disease with high rate of mortality. It can affect individuals with systemic lupus erythematosus, and early immunosuppression is a life-saving measure. However, the difficulty of diagnosis is a challenge for clinical handling of the disease. This paper reports on a recent experience with two patients, and provides treatment recommendations drawing on a review of the literature.

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 ± 1.11) to UIP (23.45 ± 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

Acute and subchronic toxicological evaluation of Echinophora platyloba DC (Apiaceae) total extract in Wistar rats

OBJECTIVE: Echinophora platyloba DC is a widely used herbal medicine and food seasoning in Iran. It is claimed to exert antimicrobial, antifungal, and antispasmodic effects. Despite the prevalent use of this plant as a food and medicine, there are no reports on its possible toxic effects. To evaluate the safety of E. platyloba, we tested its acute and sub-chronic toxicity in male and female Wistar rats. METHODS: Rats were orally treated with four different single doses of E. platyloba total extract and screened for signs of toxicity two weeks after administration. In the sub-chronic toxicity study, E. platyloba was administered for 45 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological markers were monitored during the study. RESULTS: We found no mortality and no abnormality in clinical signs, body weight, or necropsy findings in any of the animals in the acute study. The results of the subchronic study showed no significant difference in hematological parameters in either sex. There was a significant increase in lactate dehydrogenase in the female groups. A significant increase in the relative lung weight of female rats was noted at 500 mg/kg. Histopathological examinations revealed intra-alveolar hemorrhage in the male rats (500 mg/kg). In the females, congestion of the alveolar capillaries (at 500 mg/kg) and liver bridging necrosis (at 200 mg/kg) were significantly increased. CONCLUSION: The no observed adverse effect level of E. platyloba was determined to be 200 and 50 mg/kg for male and female rats, respectively.

Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure: demographics, etiologic and pulmonary histologic analysis

OBJECTIVES: Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life. METHODS: This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression. RESULTS: In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported.

Modeling the deposition of bioaerosols with variable size and shape in the human respiratory tract - a review

The behavior of bioaerosol particles with various size and shape in the human respiratory tract was simulated by using a probabilistic model of the lung and an almost realistic mathematical approach to particle deposition. Results obtained from the theoretical computations clearly show that biogenic particle deposition in different lung compartments does not only depend on physical particle properties, but also on breathing mode [nose or mouth breathing] and inhalative flow rate [= tidal volume x breathing frequency/30]. Whilst ultrafine [< 100 nm] and large [> 5 micron] particles tend to accumulate in the extrathoracic region and the uppermost airways of the tracheo-bronchial tree, particles with intermediate size are characterized by higher penetration depth, leading to their possible accumulation in the lung alveoli. Due to their deposition in deep lung regions and insufficient clearance, some bioaerosol particles may induce severe lung diseases ranging from infections, allergies, and toxic reactions to cancer

A Case of Pulmonary Alveolar Microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease with unknown etiology and pathogenesis. It is characterized by diffuse, innumerable, and minute calculi, called microlithiasis in the alveoli. More than half of reported cases are asymptomatic at the time of diagnosis. We describe the first case of PAM in Korea. A 19-yr-old man without respiratory symptoms presented with interstitial thickening on the chest radiograph. His chest high resolution CT scan showed diffusely scattered, ill defined tiny micronodules and interstitial thickening. Open lung biopsy confirmed the diagnosis of PAM. He was followed up for 6 months without treatment, and no progression was noticed.

Hemosiderosis pulmonar idiopática en adultos: presentación de tres casos y revisión de la literatura / Idiopathic pulmonary hemosiderosis in adults: a report of three cases and literature review

La hemosiderosis pulmonar idiopática (HPI) es una enfermedad rara de etiología desconocida, caracterizada por episodios recurrentes de hemorragia alveolar difusa (HAD). Existen múltiples condiciones asociadas con HAD, la mayoría de los casos ocurren en asociación con enfermedades sistémicas autoinmunes. La HPI es un diagnóstico de exclusión que se utiliza para describir los casos de HAD en los que no se encuentra una condición asociada. El objetivo del siguiente trabajo es la presentación de tres casos de HPI en mujeres adultas, revisión de la bibliografía disponible y por ultimo, remarcar la importancia de la biopsia pulmonar en el diagnostico definitivo de la HAD.

Idiopathic pulmonary hemosiderosis (IPH) is a rare lung disease of unknown etiology, characterized by recurrent episodes of diffuse alveolar hemorrhage (DAH). There are several conditions associated with DAH and most of them occur in association with systemic autoimmune diseases. IPH is diagnosed after other identifiable causes of alveolar bleeding have been excluded. The objectives of this paper is to present three cases of IPH in adult women, to review the literature and to underline the importance of lung biopsy in the definitive diagnosis of the DAH.

Plasma exchange with immunosuppression in pulmonary alveolar haemorrhage due to leptospirosis.

Background & objectives: Pulmonary involvement due to leptospirosis carries high case fatality rate and is the commonest cause of death due to leptospirosis. Immune mechanisms play a key role in the pathogenesis of leptospiral pulmonary haemorrhage. As other immune pulmonary haemorrhages due to non leptospiral causes are treated with plasma exchange and cyclophosphamide we evaluated their efficacy in patient with leptospiral pulmonary haemorrhage. Methods: Of the 602 confirmed patients of leptospirosis, 236 (39.2%) had pulmonary haemorrhage. Of these,144 had mild haemorrhage (acute lung injury score < 2.5) and were included in the study. One hundred and fourteen patients were given two cycles of plasma exchange, 24 h apart, 25 ml/kg body weight of plasma was removed in each cycle. Cyclophosphamide (20 mg/kg body weight) was given after the first plasma exchange cycle. The remaining 30 patients were not given this treatment, and used as control. Results: In the control group only 5 (16.6%) patients survived while in the treatment group 70 (61.40%) patients survived. Thrombocytopenia was observed in 111 (77.08%) patients. Renal and hepatic involvement was seen but did not account for mortality. Minor complications were seen in group I patients after plasma exchange and cyclophosphamide treatment, but none were serious. Interpretation & conclusions: Our findings showed that plasma exchange with immunosuppression improved survival in patients of pulmonary alveolar haemorrhage due to leptospirosis, suggesting that immune mechanisms play a key role in the pathogenesis of the disease.