Acute respiratory distress syndrome and blastomycosis: presentation of nine cases and review of the literature

Mississippi has the highest prevalence of blastomycosis in the country. In 20 years and 5 months there were 123 patients treated for blastomycosis at the University of Mississippi Medical Center. Among these, 107 patients had lung involvement and nine patients (8.4%) developed acute respiratory distress syndrome. Seven of the nine patients (78%) died of respiratory failure. In six patients, the lungs were the only organs involved. The three other patients had involvement of other organs as well. Average survival after the onset of acute respiratory distress syndrome was 6.9 days (range, 2 to 17 days). Acute respiratory distress syndrome can be triggered by pulmonary infections caused by bacterial diseases and other fungi. Massive proliferation of yeasts in the pulmonary parenchyma is the typical finding of patients with blastomycosis and acute respiratory distress syndrome. Underlying diseases that lead to immunodepression were present in only one patient and probable partial immunodepression was present in two other patients. Data from 19 other cases reported in the literature are discussed. Ann Diagn Pathol 5:1-9, 2001.     

The importance of surfactant on the development of neonatal pulmonary diseases

Pulmonary surfactant is a substance composed of a lipoprotein complex that is essential to pulmonary function. Pulmonary surfactant proteins play an important role in the structure, function, and metabolism of surfactant; 4 specific surfactant proteins have been identified: surfactant proteins-A, surfactant proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical, epidemiological, and biochemical evidence suggests that the etiology of respiratory distress syndrome is multifactorial with a significant genetic component. There are reports about polymorphisms and mutations on the surfactant protein genes, especially surfactant proteins-B, that may be associated with respiratory distress syndrome, acute respiratory distress syndrome, and congenital alveolar proteinosis. Individual differences regarding respiratory distress syndrome and acute respiratory distress syndrome as well as patient response to therapy might reflect phenotypic diversity due to genetic variation, in part. The study of the differences between the allelic variants of the surfactant protein genes can contribute to the understanding of individual susceptibility to the development of several pulmonary diseases. The identification of the polymorphisms and mutations that are indeed important for the pathogenesis of the diseases related to surfactant protein dysfunction, leading to the possibility of genotyping individuals at increased risk, constitutes a new research field. In the future, findings in these endeavors may enable more effective genetic counseling as well as the development of prophylactic and therapeutic strategies that would provide a real impact on the management of newborns with respiratory distress syndrome and other pulmonary diseases.     

The novel coronavirus disease (COVID-19) complicated by pulmonary embolism and acute respiratory distress syndrome

Acute respiratory distress syndrome and coagulopathy played an important role in morbidity and mortality of severe COVID-19 patients. A higher frequency of pulmonary embolism (PE) than expected in COVID-19 patients was recently reported. The presenting symptoms for PE were untypical including dyspnea, which is one of the major symptoms in severe COVID-19, especially in those patients with acute respiratory distress syndrome (ARDS). We reported two COVID-19 cases with coexisting complications of PE and ARDS, aiming to consolidate the emerging knowledge of this global health emergency and raise the awareness that the hypoxemia or severe dyspnea in COVID-19 may be related to PE and not necessarily always due to the parenchymal disease.     

去甲肾上腺素对山羊急性呼吸窘迫综合征吸入一氧化氮疗效及肺损伤的影响

目的：观察去甲肾上腺素(NE)对山羊感染性急性呼吸窘迫综合征(ARDS)吸入一氧化氮(NO)疗效(血流动力学和肺氧合)及肺损伤的影响。 方法： 静脉注入小剂量内毒素诱导山羊感染性ARDS模型6只，吸入40×10－6 NO 30 min后，联合静脉泵入NE 0.5 μg·kg-1·min-1。通过股动脉、Swan-Ganz导管分别取动脉血、混合静脉血分析血气，测定或计算基础、ARDS、NO吸入治疗30 min和联合NE静脉泵入治疗30 min后血流动力学和肺氧合参数，直视下取右下肺组织，光镜观察肺损伤变化。 结果： NO吸入治疗显著降低ARDS山羊的平均肺动脉压(MPAP，P<0.01)，增加动脉氧分压(PaO2，P<0.01)、减少肺泡动脉氧分压差［P(A-a)O2］和肺内分流率(Qs/Qt，均P<0.05)，基本不影响混合静脉血氧分压(PvO2)；联合NE静脉泵入不影响吸入NO后降低的MPAP，增加吸入NO后升高PaO2(P<0.05)，降低NO吸入后减少的P(A-a)O2和Qs/Qt(均P<0.05)，亦不影响PvO2升高吸入NO后无改变的平均动脉压(P<0.05)；吸入NO及联合应用NE治疗均不改变ARDS山羊的心排血量；吸入NO不能减轻ARDS肺损伤，联合小剂量NE静脉泵入则能减轻。 结论： 静脉注入小剂量NE增强吸入NO改善感染性ARDS肺氧合的疗效并减轻肺损伤。     

Decreased angiotensin-converting enzyme in the adult respiratory distress syndrome.

Using hippuryl-L-histidyl-L-leucine as substrate, serum angiotensin-converting enzyme was measured in 13 patients who had adult respiratory distress syndrome, eight patients with respiratory failure without adult respiratory distress syndrome, and two groups of controls: 24 healthy blood donors and 24 hospitalized patients with a variety of conditions but without respiratory failure or adult respiratory distress syndrome. Serum angiotensin-converting enzyme expressed in units/ml was 14.60 +/- 5.60 for adult respiratory distress syndrome compared with 28.92 +/- 6.60 for the blood donors, 20.76 +/- 5.87 for the patients with respiratory failure without adult respiratory distress syndrome and 20.20 +/- 5.94 in the hospitalized patients without respiratory failure or adult respiratory distress syndrome. These differences were significant, P less than .001 when adult respiratory distress syndrome was tested against the blood donors and P less than .01 against the other two groups. The significance of these findings is not clear, but the possibility is raised that the decrease of angiotensin-converting enzyme in adult respiratory distress syndrome results from a loss of pulmonary endothelial cells, which are known both to produce angiotensin-converting enzyme and to be damaged in adult respiratory distress syndrome.     

吸入一氧化氮输送与监测系统的研究

吸人低浓度一氧化氮（NO）气体能有效地治疗新生儿持续肺动脉高压（PPHN）、急性呼吸窘迫综合征（ARDS）和肺水肿等疾病。为满足临床上使用NO进行治疗的需要，世界各国都在研究一种性能可靠、治疗安全的吸入NO输送与监测系统。本文依据NO气休相对于呼吸机引入的位置，分别阐述了呼吸机后引入NO气体、呼吸机前引入NO气体、智能化呼吸机后引入NO气体和独立供给NO气休的旧类吸入NO输送与监测系统的工作原理及各自的优缺点，并结合当前吸入NO输送与监测系统研究所存在的问题．展望了其未来研究的发展趋势。     

Acute respiratory distress syndrome: Pulmonary and extrapulmonary not so similar

Acute respiratory distress syndrome (ARDS) is characterized by acute onset respiratory failure with bilateral pulmonary infiltrates and hypoxemia. Current evidence suggests different respiratory mechanics in pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) with disproportionate decrease in lung compliance in the former and chest wall compliance in the latter. Herein, we report two patients of ARDS, one each with ARDSp and ARDSexp that were managed using real-time esophageal pressure monitoring using the AVEA ventilator to tailor the ventilatory strategy.     

缺氧时心肌血流量的变化及一氧化氮和内皮素-1的调节作用

目的探讨一氧化氮和内皮素-1在缺氧时对心肌血流量的调节作用。方法大鼠随机分为平原组和急性缺氧组,用99mTc标记蟾蜍红细胞测定心肌血流量,用Gess法和放免法分别测量血浆和心肌NO2-、内皮素-1（endothelin-1,ET-1）含量,用双波长分光光度法测量一氧化氮氧合酶（nitric oxide synthase,NOS）活性。结果急性缺氧导致左右心室心肌血流量、血浆和心肌血NO2-、ET-1含量、NOS活性明显增高（P〈0.05）,左右心室心肌血管阻力和心肌ET-1/NO2-比值明显下降（P〈0.05）,血球压积（Hct）及心室重量指数无明显变化。结论急性缺氧时,左右心室心肌血流量增加,ET-1/NO参与了急性缺氧时心肌血流量的调节,以NO的扩血管作用为主。     

Acute respiratory failure in scrub typhus patients

Respiratory failure is a serious complication of scrub typhus. In this prospective study, all patients with a diagnosis of scrub typhus were included from a single center Intensive Care Unit (ICU). Demographic, clinical characteristics, laboratory, and imaging parameters of these patients at the time of ICU admission were compared. Of the 55 scrub typhus patients, 27 (49%) had an acute respiratory failure. Seventeen patients had acute respiratory distress syndrome, and ten had cardiogenic pulmonary edema. Respiratory supported patients were older had significant chronic lungs disease and high severity illness scores (Acute Physiology and Chronic Health Evaluation-II and Sequential Organ Failure Assessment score). At ICU admission, these patients presented with more deranged laboratory markers, including high bilirubin, high creatine kinase, high lactate, metabolic acidosis, low serum albumin, and presence of ascites. The average ICU and hospital stay were 4.27 ± 2.74 and 6.53 ± 3.52 days, respectively, in the respiratory supported group. Three patients died in respiratory failure group, while only one patient died in nonrespiratory failure group.Key words: Acute respiratory distress syndrome, respiratory failure, scrub typhus     

急性肺损伤/急性呼吸窘迫综合征与NF-κB信号转导关系的研究进展

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)是临床上最常见的急危重症,其发病机制错综复杂,缺乏主动性治疗措施,病死率高。研究表明,核因子κB(NF-κB)为一种诱导型核转录因子,在ALI/ARDS发展过程中发挥极为广泛的功能,并与炎症反应具有密切的关系。现就ALI/ARDS、NF-κB信号转导通路及两者的关系作一简要的论述。     

Pulmonary Involvement in Leptospirosis

 The objective of this study was to assess the incidence of pulmonary involvement in a cohort of 26 patients in whom a diagnosis of leptospirosis had been made. Seventeen of the 26 patients had respiratory symptoms. Of these 17 patients, 13 had radiographs showing pulmonary abnormality. The most frequent finding was a bilateral patchy alveolar-acinar pattern in six patients. Three patients developed acute respiratory distress syndrome and died due to multiorgan failure. Only cigarette smoking was significantly associated with respiratory involvement (odds ratio, 19.2; 95% CI, 1.7–250;P<0.001). The results indicate that pulmonary manifestations are observed in a high percentage of patients with leptospirosis. Cigarette smoking is a risk factor for the development of pulmonary involvement in human leptospirosis.     

Organizing pneumonia and pulmonary lymphatic architecture in diffuse alveolar damage

Diffuse alveolar damage represents the pathologic basis of most cases of the acute respiratory distress syndrome. Diffuse alveolar damage reflects injury to the pulmonary alveolar wall and microvasculature, leading to the exudation of water and plasma proteins that can overwhelm the local lymphatic drainage. Organizing pneumonia is a prominent histopathologic feature in some cases of diffuse alveolar damage. We examined whether diffuse alveolar damage-organizing pneumonia and changes in lymphatic architecture might be indicators of clinical outcome in acute respiratory distress syndrome. Formalin-fixed lung sections (n = 26) from thoracoscopic lung biopsies of patients with diffuse alveolar damage in the fibroproliferative phase, with or without organizing pneumonia, were immunostained with anti-CD31 and anti-D240, markers of vascular and lymphatic endothelium, respectively, and examined by morphometric analysis. Positively staining vessels were enumerated and maximal luminal diameters recorded in randomly selected low-power fields. Patients with diffuse alveolar damage-organizing pneumonia showed greater survival than those with diffuse alveolar damage (67% versus 33%, P = .03). The maximal luminal diameter of D240+ lymphatic vessels was larger for diffuse alveolar damage-organizing pneumonia than diffuse alveolar damage (28 +/- 4 versus 59 +/- 16 microm, P = .02). In addition, larger lymphatic luminal diameters (28 +/- 4 versus 47 +/- 11 microm) were associated with increased survival (P = .12). We conclude that lung biopsy histopathology and pulmonary lymphatic morphology may predict survival in acute respiratory distress syndrome.     

肺复张对肺内、外源性ARDS模型犬氧代谢和血流动力学的影响

目的: 探讨肺复张对肺内、外源性急性呼吸窘迫综合征(ARDS)模型犬氧代谢和血流动力学的影响。方法: 健康杂种犬12只,随机分为肺外源性ARDS(ARDSexp)组和肺内源性ARDS(ARDSp)组,每组6只。股静脉注射油酸复制ARDSexp模型,盐酸灌肺复制ARDSp模型。制模成功后,行机械通气,采用肺保护通气策略(LPVS)并给予1次肺复张(RM)。RM采用压力控制通气(PCV),压力上限为高位转折点(UIP), 呼气末正压(PEEP)为低位转折点(LIP)+2 cmH₂O, 维持时间60 s,RM后继续原方案通气。观察不同阶段氧代谢指标和血流动力学的变化。结果: RM后两组动脉血氧分压(PaO₂)、静脉血氧分压(PvO₂) 、混合静脉血氧饱和度(SvO₂)和氧输送量(DO₂)明显升高,氧摄取率(ERO₂) 逐渐降低;ARDSexp组的PaO₂、PvO₂、SvO₂和DO₂高于ARDSp组,ERO₂则低于ARDSp组。RM时两组平均肺动脉压(MPAP)、中心静脉压(CVP)、肺动脉嵌压(PAWP)均显著增加,ARDSp组与ARDSexp组相比较无显著性差异,但RM结束后两组均逐渐恢复至基础水平。RM时两组平均动脉压(MAP)和心脏指数(CI)下降,但很快恢复至基础水平,ARDSp组下降幅度更为显著。结论: RM可以提高氧输送和改善组织缺氧,ARDSexp组的效果优于ARDSp组;RM对血液动力学会造成短暂的影响,ARDSp组受到的影响大于ARDSexp组。     

Follow-up after acute respiratory distress syndrome caused by influenza a (H1N1) virus infection

BACKGROUND:

There are no reports on the long-term follow-up of patients with swine-origin influenza A virus infection that progressed to acute respiratory distress syndrome.

METHODS:

Four patients were prospectively followed up with pulmonary function tests and high-resolution computed tomography for six months after admission to an intensive care unit.

RESULTS:

Pulmonary function test results assessed two months after admission to the intensive care unit showed reduced forced vital capacity in all patients and low diffusion capacity for carbon monoxide in two patients. At six months, pulmonary function test results were available for three patients. Two patients continued to have a restrictive pattern, and none of the patients presented with abnormal diffusion capacity for carbon monoxide. All of them had a diffuse ground-glass pattern on high-resolution computed tomography that improved after six months.

CONCLUSIONS:

Despite the marked severity of lung disease at admission, patients with acute respiratory distress syndrome caused by swine-origin influenza A virus infection presented a late but substantial recovery over six months of follow-up.     

Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with the adult respiratory distress syndrome

The possible contribution of metabolites of arachidonic acid to the increased permeability of the alveolar-capillary barrier in the adult respiratory distress syndrome was examined by quantifying the pulmonary edema fluid concentrations of lipoxygenase and cyclooxygenase products. The concentration of leukotriene D₄ in pulmonary edema fluid of 10 patients with the adult respiratory distress syndrome (18.5±6.8 pmol/ml; mean±SD), assessed by specific radioimmunoassay after isolation of the mediator, was significantly higher (P<0.001) than that of five patients with cardiogenic pulmonary edema (4.4±1.1 pmol/ml). The concentrations of leukotrienes B₄ and C₄, prostaglandin E₂, and thromboxane B₂ in edema fluid were not significantly different in the adult respiratory distress syndrome patients than in the other subjects with pulmonary edema. The edema fluid concentration of leukotriene D₄ correlated with the ratio of edema fluid to plasma concentrations of albumin (r=0.64). Leukotriene D₄ thus may contribute to the permeability defect which allows an accumulation of proteinrich alveolar fluid in the adult respiratory distress syndrome.This work was supported in part by Grants HL31809, HL25816, HL19155, and AI19784 from the National Institutes of Health.     

A rare case of leptospirosis with isolated lung involvement

Leptospirosis is a zoonosis caused by a pathogenic spirochete “leptospira interrogans.” Severe form of leprospira infection is usually associated with jaundice and renal involvement, leading to major hemorrhagic complications. Lung involvement can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome (ARDS). We recently managed a case of leptospirosis with isolated lung involvement as alveolar hemorrhage and ARDS. Our patient had acute febrile illness with respiratory symptoms associated with radiological picture of pulmonary hemorrhage. Patient was managed with noninvasive ventilation with high flow oxygen, antibiotic and pulse steroids therapy. In conclusion, leptospirosis can present with predominant pulmonary involvement, instead of the classical triad of Weil disease. High index of suspicion should be kept in acute febrile illness patients with respiratory symptoms and alveolar hemorrhage. Early diagnosis and management with oxygenation, antibiotics and immunosuppresents can prevent complications and mortality.     

胸外科术后急性呼吸窘迫综合征的临床分析

目的：探讨胸外科术后急性呼吸窘迫综合征的防治措施。方法：回顾性分析21例开胸术后发生急性呼吸窘迫征患者的临床资料。结果：综合治疗为胸外科术后急性呼吸窘迫综合征的有效方法,有效率85．71％。治疗前后的生理指标改善明显。结论：早期和综合治疗对胸外科术后急性呼吸窘迫综合征具有重要意义。     

Possible role of nitric oxide in the pathogenesis of pulmonary hypertension in broilers: a synopsis.

Nitric oxide (NO) produced by vascular endothelial cells is an important determinant of the basal tone of small arteries and arterioles. Impaired endothelial NO production has been implicated in the pathophysiology of pulmonary hypertension in humans. Available data suggest that reduction of endothelial NO synthesis, with evidence of reduced endothelial NO synthase expression in pulmonary arterioles, is associated with increased pulmonary vasomotor tone and vascular remodelling in hypertensive broilers. Supplemental l-arginine, a precursor of NO, has been shown to induce flow-dependent pulmonary vasodilation, to prevent reduced endothelial NO synthase expression and to inhibit vascular remodelling in broilers with pulmonary hypertension. Nevertheless, its effect on pulmonary hypertension syndrome incidence is limited. It appears that impaired production of NO is a secondary rather than a causative factor in the pathogenesis of pulmonary hypertension in broilers.     

SARS-CoV virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues.

These studies attempt to understand more fully the host response and pathogenesis associated with severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) by monitoring gene expression using formalin-fixed paraffin-embedded (FFPE) pulmonary autopsy tissues. These tissues were from patients in different hospitals in Singapore who were diagnosed with various microbial infections, including SARS-CoV, that caused acute respiratory distress syndrome (ARDS). Global expression patterns showed limited correlation between end-stage ARDS and the initiating pathogen, but when focusing on a subset of genes implicated in pulmonary pathogenesis, molecular signatures of pulmonary disease were obtained and appeared to be influenced by preexisting pulmonary complications and also bacterial components of infection. Many factors detected during pulmonary damage and repair, such as extracellular matrix (ECM) components, transforming growth factor (TGF) enhancers, acute-phase proteins, and antioxidants, were included in the molecular profiles of these ARDS lung tissues. In addition, differential expression of cytokines within these pulmonary tissues were observed, including notable genes involved in the interferon (IFN) pathway, such as Stat1, IFN regulatory factor-1 (IRF-1), interleukin-6 (IL-6), IL-8, and IL-18, that are often characterized as elevated in ARDS patients.     

Surfactant protein A enhances Mycobacterium avium ingestion but not killing by rat macrophages

Mycobacterium avium complex (MAC) is a significant cause of opportunistic infection in patients with acquired immunodeficiency syndrome. Although the major route of entry of MAC is via the gastrointestinal tract, MAC can infect humans through the respiratory tract and eventually encounter alveolar macrophages within the lung. Once in the lung, MAC can potentially interact with surfactant protein A (SP-A), an important component of the pulmonary innate-immune response. Previous work on other pulmonary pathogens including Mycobacterium bovis Bacillus Calmette-Guerin (BCG) suggests that SP-A participates in promoting efficient clearance of these organisms by alveolar macrophages. In the present study, we investigated the role of SP-A in clearance of MAC by cultured rat macrophages. SP-A bound to MAC organisms and enhanced the ingestion of the mycobacteria by macrophages. Infection of macrophages with SP-A-MAC complexes induced the production of nitric oxide (NO) and tumor necrosis factor-alpha. However, intracellular survival of MAC was not altered by preopsonization with SP-A. In addition, inhibitors of inducible NO synthase did not alter MAC clearance. These results suggest that SP-A can bind to and enhance the uptake of MAC by alveolar macrophages, similar to previous findings with BCG and Mycobacterium tuberculosis.However, unlike BCG and other pulmonary pathogens that are cleared effectively in the presence of SP-A via a NO-dependent pathway, macrophage-mediated clearance of MAC is not enhanced by SP-A.