Alveolar cells in cyclophosphamide-induced lung injury. II. Pathogenesis of experimental endogenous lipid pneumonia.

An ultrastructural and histological study was made to analyse the structural and cellular features of the pulmonary lesions produced in Wistar rats by intraperitoneal (i.p.) administration of cyclophosphamide (two i.p. doses of 150 mg CP/1 kg bw/1 ml PBS). Rats exposed to cyclophosphamide (CP) developed a condition whose morphological picture corresponded to endogenous lipid pneumonia and/or pulmonary alveolar proteinosis-like changes. Damage to the endothelium and neutrophil accumulation in lung vascular bed were found to be potential initiators of endogenous lipid pneumonia-type changes. The possibility of the evolution of the acute lung injury into endogenous lipid pneumonia-type changes and into alveolar proteinosis-like changes was demonstrated. The results of the study supplement the existing theories of pulmonary alveolar proteinosis pathogenesis.     

Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia

Recently, we demonstrated that pulmonary CYP2J4 content, a prominent source of EETs and HETEs formation in rat lungs, is reduced in pneumonia. Therefore, the purpose of this study was to determine the role of iNOS-derived NO in reduced pulmonary CYP2J4 protein content and decreased CYP metabolites in pneumonia. Rats were randomized to control, control plus 1400W (iNOS inhibitor), pneumonia, and pneumonia plus 1400W groups. Pseudomonas organisms were injected into lungs of pneumonia rats. At 40 h after surgery, rats were treated with either saline or 1400W for 4 h before death. Venous plasma samples were obtained for measuring nitrites/nitrates (NOx). There was no significant effect of 1400W on blood pressure measured in control or pneumonia rats, whereas 1400W reduced the elevated plasma NOx levels in pneumonia rats by half. CYP primary metabolites of AA formed at significantly lower rates in pulmonary microsomes from pneumonia rats compared with control rats. Treatment of pneumonia rats with 1400W resulted in a significant increase in the rate of formation of pulmonary EETs and omega-terminal HETEs compared with untreated pneumonia rats. The reduction in CYP2J4 protein content in pneumonia lung microsomes was also partially prevented by 1400W. Therefore, excess NO from iNOS decreases the pulmonary production of EETs and omega-HETEs in acute pneumonia. Inhibition of iNOS restores CYP2J4 protein content and CYP activity in acute pneumonia, indicating an important NO-CYP interaction in pulmonary responses to infection. We speculate CYP2J4 and its AA metabolites are involved in the modulation of pulmonary function in health and disease.     

支原体肺炎患儿细胞免疫功能及肺功能状态变化的临床研究

目的:研究支原体肺炎患儿细胞免疫及肺功能状态的变化情况。方法:选取2014年10月~2015年10月于本院进行诊治的68例支原体肺炎患儿为观察组,以同期68名体检健康儿童为对照组。观察并比较两组儿童的细胞免疫及肺功能,以及不同程度肺炎患儿的细胞免疫及肺功能指标。结果:观察组患儿细胞免疫指标及肺功能指标均低于对照组,差异具有统计学意义(P0.05);观察组重度肺炎患儿的细胞免疫指标及肺功能指标均低于中度及轻度患儿,差异具有统计学意义(P0.05);观察组中度肺炎患儿的细胞免疫指标及肺功能指标均低于轻度患儿,差异具有统计学意义(P0.05)。结论:支原体肺炎患儿细胞免疫及肺功能呈异常状态,且不同严重程度肺炎患儿的差异明显。     

肺腺癌发生阻塞性肺炎的临床分析

目的研究阻塞性肺炎与肺腺癌发病的关系以及对预后的影响。方法对2003年12月至2013年1月于大连医科大学附属二院确诊的436例肺腺癌患者病历进行回顾,根据患者临床特征进行分组,并进行统计学分析。结果晚期肺腺癌患者更易出现阻塞性肺炎（χ2=5．662,P=0．017）;中心型肺腺癌较周围型更易出现阻塞性肺炎（χ2=4．432,P=0．035）;在肺腺癌中,性别、年龄、吸烟史以及体重下降与否与阻塞性肺炎的发生经比较差异无统计学意义（P〉0．05）。结论阻塞性肺炎的发生与晚期肺腺癌以及中心型肺腺癌有关,重视筛查对肺腺癌的诊断和预后有重要意义。     

肺炎型肺癌的影像学特点及误诊分析

目的:探讨肺炎型肺癌影像学特点,深入肺炎型肺癌认识,提高诊断水平,降低临床误诊率。方法:随机选取2013年1月份至2014年2月份我院胸外科住院治疗的36例肺炎型肺癌患者作为研究对象,回顾性分析全部患者的影像学资料及病理检查结果。结果:患者病变部位在各肺段均有分布,局限性及弥漫性分布均可见,其中局灶性分布较大,未出现跨越肺段侵袭肺叶的病例。影像表现主要为边缘不清云絮状肿块影、云絮状影伴结节、肺段实变影、肺实变伴空泡及蜂窝状影、肺炎纤维样化及混合阴影。其中,单纯性磨玻璃影10例;磨玻璃结节肿块10例;肺段分布实变影7例;肺叶及肺段实变伴空泡或蜂窝状影6例;肺炎样纤维化及肿块10例;混合阴影(4种或4种以上阴影并存)3例。结论:肺炎型肺癌患者影像学检查结果多具有肺炎样改变,极易误诊肺炎性疾病,临床诊断中结合活检检查技术,有利于改善临床诊断正确率。     

儿童肺炎肺实变住院患儿支气管肺泡灌洗液病原分析

本研究分析肺炎肺实变患儿支气管肺泡灌洗液病原谱构成,旨在为临床经验性抗感染治疗提供指导。收集2019年1月-2020年1月复旦大学附属儿科医院纤维支气管镜室诊治的住院肺炎病例临床资料,其中肺实变的诊断基于影像学证据,依托国家儿童医学中心病原学检测平台,并参考感染传染科医生解读,本研究对肺炎伴肺实变患儿支气管肺泡灌洗液标本的病原学检测结果进行回顾性分析。结果显示,286例肺炎患儿的286份支气管肺泡灌洗液标本被纳入研究,平均年龄5.5(5.8±3.1)岁,其中195例(68.2%)存在肺炎伴肺实变。总病原体检出率为76.6%(219/286),肺实变和无肺实变肺炎患儿病原体检出率分别为77.9%(152/195)和73.6%(67/91),差异无统计学意义;检出的前5种病原体均为肺炎支原体、腺病毒、鼻病毒、呼吸道合胞病毒和副流感病毒3型。5周岁及以上患儿肺炎支原体检出率达最高77.0%(127/165),肺实变病例和无肺实变病例肺炎支原体检出率分别为67.2%(131/195)和61.5%(56/91),差异无统计学意义。本研究结果提示,肺炎支原体、腺病毒、鼻病毒、呼吸道合胞病毒和副流感病毒3型是导致本研究目标人群患病的主要病原体;病原体检出率高低与是否肺实变无关。     

乌司他丁可降低重症肺炎患者的血清炎性因子水平并改善肺功能

为探讨乌司他丁对重症肺炎血清炎性指标、肺功能的影响,为临床应用提供有利的支持,本研究选取2015年1月至2017年6月期间在我院治疗的重症肺炎患者150例作为本次研究的对象,其中接受常规治疗联合乌司他丁治疗的患者83例(乌司他丁组),只接受常规治疗的患者67例(对照组)。比较两组患者治疗前后血清抗炎介质及促炎介质水平,并比较治疗前后的肺功能相关指标、肺表面活性蛋白水平,分析乌司他丁对重症肺炎血清炎性指标、肺功能改善情况。结果表明,治疗前两组患者的血清抗炎及促炎介质指标,差异无统计学意义(p>0.05),而治疗7 d后,乌司他丁组均明显低于对照组,且乌司他丁组肺功能相关指标明显优于对照组,肺表面活性蛋白水平明显低于对照组,差异具有统计学意义(p<0.05);本研究表明,乌司他丁可降低重症肺炎患者的血清炎性因子水平,改善肺功能,具有一定的临床推广价值。     

A Further Application of the Nitroblue Tetrazolium Test

The nitroblue tetrazolium (N.B.T.) test was performed on patients in whom a differential diagnosis of pulmonary thromboembolism or lobar pneumonia existed. The mean N.B.T. score in healthy subjects was 6·4% (range 1%-15%). Patients with uncomplicated pulmonary thromboembolism showed a mean N.B.T. value of 7·5% (range 3%-12%). In patients with lobar pneumonia the mean N.B.T. score was 42·4% (range 21%-85%). These results suggest that the N.B.T. test is of value in the differential diagnosis of pulmonary thromboembolism and lobar pneumonia.     

婴幼儿重症肺炎潮气呼吸肺功能、D-二聚体水平的变化及盐酸氨溴索的干预效果研究

摘要 目的：探讨婴幼儿重症肺炎潮气呼吸肺功能、D-二聚体水平的变化及盐酸氨溴索的干预效果研究。方法：2016年1月至2019年12月期间我院收治的重症肺炎婴幼儿122例作为肺炎组,另选取同期来我院行健康体检的婴幼儿100例作为对照组,肺炎组患儿采用随机数字表法分为A组（n=61,常规治疗）和B组（n=61,常规治疗基础上联合盐酸氨溴索治疗）,对比对照组、肺炎组潮气呼吸肺功能、D-二聚体水平,对比A组、B组两组的疗效、潮气呼吸肺功能、D-二聚体、症状缓解时间及不良反应。结果：肺炎组呼吸频率（RR）、D-二聚体水平高于对照组,潮气量（VT）、达峰时间（TPTEF）、吸气时间（TI）、呼气时间（TE）短于对照组（P<0.05）。B组治疗1周后的总有效率高于对照组（P<0.05）。两组治疗1周后RR、D-二聚体水平均下降,且B组低于A组（P<0.05）,两组治疗1周后VT、TPTEF、TI、TE均升高,且B组高于A组（P<0.05）。B组退热时间、咳嗽缓解时间、气促缓解时间、啰音消失时间均短于A组（P<0.05）。A组、B组两组患儿不良反应总发生率对比未见差异（P>0.05）。结论：D-二聚体以及潮气呼吸肺功能检测可作为婴幼儿重症肺炎治疗效果、病情程度评价的重要指标,经盐酸氨溴索干预后患儿D-二聚体及潮气呼吸肺功能均可得到显著改善,临床症状可有效缓解,疗效肯定,且不增加不良反应发生。     

CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung

CD1d-restricted T cells are implicated as key players in host defense against various microbial infections. However, the mechanisms involved and the role they play, if any, at the mucosal surfaces where pathogenic infections are initiated is unknown. In a murine pneumonia model established by intranasal application of Pseudomonas aeruginosa, CD1d(-/-) mice showed markedly reduced pulmonary eradication of P. aeruginosa compared with wild-type mice; this was associated with significantly lower amounts of macrophage inflammatory protein-2 and reduced numbers of neutrophils within the bronchoalveolar lavage fluid. Corollarily, treatment of mice with alpha-galactosylceramide--a lipid that activates CD1d-restricted T cells--increased the amount of interferon-gamma; this was associated with rapid pulmonary clearance through enhanced phagocytosis of P. aeruginosa by alveolar macrophages. These results reveal a crucial role played by CD1d-restricted T cells in regulating the antimicrobial immune functions of macrophages at the lung mucosal surface.     

Computed tomography in the x-ray diagnosis of pneumonia

Experience in the use of CT in combined radiodiagnosis of pneumonia was analysed. It has been concluded that CT objectively reflects morphological inflammatory pulmonary changes and permits their all-round assessment over time. The diagnosis of pneumonia in CT is based on classical x-ray symptoms. As compared to survey radiography CT reveals symptoms of pneumonia to the full at earlier stages. CT is an important additional method of investigation of inflammatory pulmonary diseases, but it should not be used separately without survey radiography. In a majority of cases when CT is performed there is no need in x-ray tomography.     

Feasibility and Safety of Local Treatment with Recombinant Human Tissue Factor Pathway Inhibitor in a Rat Model of Streptococcus pneumoniae Pneumonia

Pulmonary coagulopathy is intrinsic to pulmonary injury including pneumonia. Anticoagulant strategies could benefit patients with pneumonia, but systemic administration of anticoagulant agents may lead to suboptimal local levels and may cause systemic hemorrhage. We hypothesized nebulization to provide a safer and more effective route for local administration of anticoagulants. Therefore, we aimed to examine feasibility and safety of nebulization of recombinant human tissue factor pathway inhibitor (rh-TFPI) in a well-established rat model of Streptococcus (S.) pneumoniae pneumonia. Thirty minutes before and every 6 hours after intratracheal instillation of S. pneumonia causing pneumonia, rats were subjected to local treatment with rh-TFPI or placebo, and sacrificed after 42 hours. Pneumonia was associated with local as well as systemic activation of coagulation. Nebulization of rh-TFPI resulted in high levels of rh-TFPI in bronchoalveolar lavage fluid, which was accompanied by an attenuation of pulmonary coagulation. Systemic rh-TFPI levels remained undetectable, and systemic TFPI activity and systemic coagulation were not affected. Histopathology revealed no bleeding in the lungs. We conclude that nebulization of rh-TFPI seems feasible and safe; local anticoagulant treatment with rh-TFPI attenuates pulmonary coagulation, while not affecting systemic coagulation in a rat model of S. pneumoniae pneumonia.     

When is pneumonia not pneumonia: a clinicopathologic study of the utility of lung tissue biopsies in determining the suitability of cadaveric tissue for donation

Healthcare-associated pneumonia (HCAP) represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic culture results. It is often difficult to distinguish between pneumonia, underlying pulmonary disease, or conditions with pulmonary complications; this is compounded by the often-subjective clinical diagnosis of pneumonia. We conducted this study to determine the utility of post-mortem lung biopsies for diagnosing pneumonia in tissue donors diagnosed with pneumonia prior to death. Subjects were deceased patients who had been hospitalized at death and diagnosed with pneumonia. Post-mortem lung biopsies were obtained from the anatomic portion of the cadaveric lung corresponding to chest radiograph abnormalities. Specimens were fixed, stained with hematoxylin and eosin, and read by a single board-certified pathologist. Histological criteria for acute pneumonia included intense neutrophilic infiltration, fibrinous exudates, cellular debris, necrosis, or bacteria in the interstitium and intra-alveolar spaces. Of 143 subjects with a diagnosis of pneumonia at time of death, 14 (9.8 %) had histological evidence consistent with acute pneumonia. The most common histological diagnoses were emphysema (53 %), interstitial fibrosis (40 %), chronic atelectasis (36 %), acute and chronic passive congestion consistent with underlying cardiomyopathy (25 %), fibro-bullous disease (12 %), and acute bronchitis (11 %). HCAP represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic testing. We found that attending physician-diagnosed pneumonia did not correlate with post-mortem pathological diagnosis. We conclude that histological examination of cadaveric lung tissue biopsies enables ascertainment or rule out of underlying pneumonia and prevents erroneous donor deferrals.     

Pulmonary cytochrome P-450 2J4 is reduced in a rat model of acute Pseudomonas pneumonia

We previously reported that the levels of epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are depressed in microsomes prepared from lungs of rats with acute Pseudomonas pneumonia. We also showed a potential role for cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) in contractile responses of both normal pulmonary arteries and pulmonary arteries from rats with pneumonia. The CYP2J subfamily enzymes (endogenous source of EETs and HETEs) are constitutively expressed in human and rat lungs where they are localized in vascular smooth muscle and endothelium. The purpose of this study was to determine if CYP2J proteins are modified in pneumonia. Pseudomonas organisms were injected via a tracheostomy in the lungs of rats. Later (44 h), lungs were frozen, and microsomes were prepared from pneumonia and control rat lung homogenates. Lung microsomal proteins were then immunoblotted with anti-CYP2B1/2B2, anti-CYP4A, anti-CYP2J9pep2 (which reacts with rat CYP2J3), anti-CYP2J6pep1 (which reacts with rat CYP2J4), anti-CYP2J2pep4, or anti-CYP2J2pep3 (both of which react with all known CYP2J isozymes). Western blotting revealed a prominent 55-kDa band with anti-CYP2J2pep3, anti-CYP2J2pep4, and anti-CYP2J6pep1 (but not anti-CYP2J9pep2) that was reduced in pneumonia compared with control lung microsomes. The CYP2B bands (51-52 kDa) were less prominent and not different between pneumonia and control lungs. CYP4A proteins (20-HETE sources) were not detected in rat lung microsomes. Therefore, rat lung contains a protein with immunological characteristics similar to CYP2J4, and this CYP is reduced after pneumonia. We speculate that CYP2J (but not CYP2B) enzymes and their AA metabolic products (EETs) are involved in the modulation of pulmonary vascular tone in pneumonia in rats.     

Use of the kinetic treatment table to prevent the pulmonary complications of multiple trauma.

The kinetic treatment table (KTT) has been developed to prevent and treat complications of immobility. Because atelectasis and pneumonia may be related to immobility, we studied the effect of the KTT on the prevention and treatment of pulmonary complications in a prospective randomized study of 30 patients with severe traumatic injuries. All were receiving mechanical ventilation and were randomly assigned to treatment with a KTT or a conventional bed. Both groups received conventional medical-surgical therapy while pulmonary function, chest roentgenograms, and the presence or absence of lung infection were monitored for one week. In the patients who began the study with a clear chest roentgenogram, atelectasis and pneumonia were significantly less frequent in those treated with a KTT (P less than .05). Thus, the KTT can reduce pulmonary complications in selected patients with multiple trauma. The effect of this benefit on overall outcome is uncertain.     

Clove cigarettes. The basis for concern regarding health effects.

The smoking of clove cigarettes has been associated with 13 cases of serious illness in the United States, including hemorrhagic pulmonary edema, pneumonia, bronchitis, and hemoptysis. We describe a patient in whom, after she smoked a clove cigarette, pneumonia complicated by lung abscess developed. Her lung disease may have been caused by aspiration pneumonia as a consequence of pharyngolaryngeal anesthesia from clove cigarette smoke. Clove cigarettes appeal to adolescents experimenting with smoking practices and may influence the development of later smoking habits.     

Delayed rectifier potassium channels contribute to the depressed pulmonary artery contractility in pneumonia.

We investigated the role of K(+) channels in the attenuated pulmonary artery (PA) contractility characteristic of acute Pseudomonas pneumonia. Contractility of PA rings from the lungs of control or pneumonia rats was assessed in vitro by obtaining cumulative concentration-response curves to the contractile agonists KCl, phenylephrine, or PGF(2 alpha) on PA rings before and after treatment with K(+) channel blockers. In rings from pneumonia rats, paxilline (10 microM), tetraethylammonium (2 mM) (blockers of large-conductance Ca(2+)-activated K(+) channels), and glybenclamide (ATP-sensitive K(+) channel blocker, 80 microM) had no significant effect on the attenuated contractile responses to KCl, phenylephrine, and PGF(2 alpha). However, 4-aminopyridine (2 mM), a blocker of voltage-gated K(+) channels (delayed rectifier K(+) channel) reversed this depressed contractility. Therefore, large-conductance Ca(2+)-activated K(+) and ATP-sensitive K(+) channels do not contribute to the attenuated PA contractility observed in this model of acute pneumonia. In contrast, 4-aminopyridine enhances contraction in PA rings from pneumonia lungs, consistent with involvement of a voltage-gated K(+) channel in the depressed PA contractility in acute pneumonia. Unraveling the precise mechanism of attenuated contractility in pneumonia could lead to innovative therapies for the pulmonary vascular abnormalities associated with this disease.     

A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia

The normal fibrinolytic activity within the alveolar space is suppressed in fibrotic lung diseases in part because of increased levels of plasminogen activator inhibitor-1 (PAI-1). Studies with animals have shown that inhibition of the plasminogen system by PAI-1 increases the generation of pulmonary fibrosis. To determine if a similar relationship occurs in human fibrotic lung diseases, we took advantage of a polymorphism (4G/5G) that occurs in the promoter region of the human PAI-1 gene and influences the expression of PAI-1. We hypothesized that the 4G/4G genotype, because of its association with higher levels of PAI-1, would occur in patients with idiopathic interstitial pneumonia more frequently than in a control population. PAI-1 promoter genotype was determined in 88 well-characterized patients with idiopathic interstitial pneumonia consisting of 62 patients with usual interstitial pneumonia and 26 with nonspecific interstitial pneumonia. DNA was extracted from paraffin-embedded biopsy tissue and the genotype identified by polymerase chain reaction and restriction endonuclease digestion. We found that the distribution of PAI-1 genotypes in the idiopathic interstitial pneumonia population was similar to that of a large control population. However, subgroup analysis showed that patients with nonspecific interstitial pneumonia were more likely than the control population to have the promoter genotype (4G/4G) that is associated with higher levels of PAI-1. A similar pattern in PAI-1 polymorphism was not seen in the usual interstitial pneumonia subgroup. The results of this study support the conclusion that PAl-1 expression influences the development of nonspecific interstitial pneumonia in a similar manner to what occurs in animal models of pulmonary fibrosis. Patients with usual interstitial pneumonia did not show the same relationship with PAl-1 genotype.     

Acute pneumonia reversibly inhibits hypoxic vasoconstriction in isolated rat lungs.

Pneumonia was induced in rats by instillation of carrageenin (0.5 ml of 0.7% solution) into the trachea. Three or four days after instillation, the lungs were isolated, perfused with blood of healthy rat blood donors, and ventilated with air + 5% CO2 or with various hypoxic gas mixtures. Pulmonary vascular reactivity to acute hypoxic challenges was significantly lower in lungs of rats with pneumonia than in lungs of controls. The relationship between O2 concentration in the inspired gas and Po2 in the blood effluent from the preparation was shifted significantly to lower Po2 in lungs with pneumonia compared to control ones. These changes were not present in rats allowed to recover for 2-3 weeks after carrageenin instillation. We suppose that blunted hypoxic pulmonary vasoconstriction may contribute to hypoxaemia during acute pulmonary inflammation. Decreased Po2 in the blood effluent from the isolated lungs with pneumonia implies significant increase of oxygen consumption by the cells involved in the inflammatory process.