Reduced phagocytic activity of human alveolar macrophages infected with Mycobacterium avium complex

IntroductionCo-infection of nontuberculous mycobacteria (NTM) with other bacteria is associated with increased frequency of hospitalization and reduced quality of life. However, the clinical significance of co-infection with NTM and other bacteria remains unclear. Here, we investigated the distribution of alveolar macrophage populations, characterized their phagocytic function in bronchoalveolar lavage fluid (BALF), and assessed the bactericidal function of macrophages infected with NTM using cell lines.MethodsBALF samples were prospectively obtained from 30 patients with suspected NTM lung disease to evaluate phagocytic activities of macrophages using immunostaining. Bactericidal activities of Staphylococcus aureus (S. aureus) and Mycobacterium intracellulare (M. intracellulare)-infected or -non-infected macrophages were evaluated using macrophage cell lines.ResultsEleven patients with Mycobacterium avium complex (MAC) infection and 19 patients with chronic lower respiratory tract infections except for NTM infection (controls) were enrolled. The percentage of non-polarized (HLA-DR⁺, CD40^?, and CD163^?) macrophages in patients infected with MAC was significantly higher than that in controls; non-polarized macrophages demonstrated an impaired ability to phagocytose S. aureus. In vitro experiments revealed higher intracellular S. aureus colony-forming unit counts and proinflammatory cytokine levels in M. intracellulare-infected macrophages than in non-NTM-infected macrophages. Electron microscopy showed morphologically damaged macrophages and M. intracellulare and S. aureus growing in the same phagosome.ConclusionThe proportion of alveolar macrophages (HLA-DR⁺, CD40^?, and CD163^?) with impaired phagocytosis increased in MAC-infected individuals. M. intracellulare-infected macrophages reduced bactericidal activity in vitro. Dysfunction of alveolar macrophages may contribute to persistent infection by other bacteria, leading to MAC lung disease progression.     

不同采样技术对呼吸机相关性肺炎的诊断价值

目的比较不同采样技术对呼吸机相关性肺炎(VAP)的诊断价值及安全性。方法对30例呼吸机相关性肺炎同时行支气管镜下支气管肺泡灌洗(BAL)及经人工气道吸痰做定量培养。结果 BAL阳性率86.7%(26/30),经人工气道吸痰阳性率为46.7%(14/30)。两组间阳性率有显著性差异。结论 BAL能提高呼吸机相关性肺炎的病原学诊断率,而且安全、可重复进行。     

荧光定量PCR测定支气管肺泡灌洗液中TbDNA诊断肺结核的临床价值

目的探讨纤支镜肺泡灌洗液中结核分枝杆菌DNA在肺结核诊断中的价值。方法对187例初治肺结核患者及41例肺炎患者分别应用荧光定量聚合酶链反应(FQ-PCR)技术检测结核分枝杆菌DNA、肺泡灌洗液结核菌培养、纤维支气管镜刷片抗酸染色。结果肺结核患者肺泡灌洗液结核分枝杆菌DNA阳性率为:78.6%、肺泡灌洗液结核菌培养阳性率为28.8%、刷片抗酸染色阳性率为21.9%。肺炎患者肺泡灌洗液结核分枝杆菌DNA、肺泡灌洗液结核菌培养、刷片抗酸染色均阴性。结论荧光定量聚合酶链反应检测肺泡灌洗液结核分枝杆菌DNA,特异性高,用于肺结核诊断可提高肺结核诊断的敏感性和准确性,明显优于纤维支气管镜刷片抗酸染色,亦较肺泡灌洗液结核菌培养诊断灵敏、快速,可作为肺结核诊断较可靠指标。     

Anti-asthmatic effects of Angelica dahurica against ovalbumin-induced airway inflammation via upregulation of heme oxygenase-1

Asthma is a chronic immune inflammatory disease characterized by variable airflow obstruction. The present study was undertaken to assess the effects of an Angelica dahurica Bentham et Hooker ethanolic extract (AD) on airway inflammation in an ovalbumin (OVA)-induced airway inflammation model. Mice that received AD displayed significantly lower airway eosinophilia, cytokine levels, including interleukin (IL)-4, IL-5, and tumor necrosis factor (TNF)-alpha levels, mucus production and immunoglobulin (Ig)E, compared with OVA-induced mice. In our experiments, AD treatment reduced airway inflammation and suppressed oxidative stress in the OVA-induced asthma model, partly via induction of heme oxygenase (HO)-1. The effects of AD on OVA-induced HO-1 induction were partially reversed by the HO-1 inhibitor, tin protoporphyrin (SnPP). Our results clearly indicate that AD is a suppressor of airway allergic inflammation, and may thus be effectively used as an anti-inflammatory drug in the treatment of asthma.     

神经生长因子抗体对哮喘模型大鼠肺中趋化素样因子1表达的影响

目的观察神经生长因子(NGF)抗体对OVA诱导的哮喘模型大鼠肺中趋化因子CKLF1的表达变化。方法采用OVA诱导的大鼠哮喘模型,通过腹腔给予NGF(8 ng.kg-1)及NGF抗体(0.1 mg.L-1),采用Western blot、ELISA和免疫组化观察CKLF1在支气管肺泡灌洗液(BALF)及肺组织中的表达变化。结果 CKLF1在OVA诱导的哮喘模型大鼠肺组织中的蛋白表达升高(P<0.05);NGF抗体能够降低CKLF1的表达;CKLF1在哮喘大鼠BALF中的含量升高(P<0.05),NGF抗体能够降低BALF中CKLF1的含量(P<0.05);NGF对肺组织及BALF中CKLF1的表达没有明显的影响。结论 NGF抗体能够抑制哮喘模型大鼠肺组织及支气管肺泡灌洗液中CKLF1的表达和释放,改善哮喘症状。     

Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors

The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB₁ and CB₂ receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB_1/2 receptors in this setting, we used pharmacological blockade of CB₁ and/or CB₂ receptors by the selective antagonists and moreover CB₁/CB₂ receptor double-knockout mice (CB₁^−/−/CB₂^−/−) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB₁/CB₂ receptor-independent signalling seems likely in the observed results.     

Prior exposure to acrolein accelerates pulmonary inflammation in influenza A-infected mice

The combustion product acrolein contributes to several smoke-related health disorders, but whether this immunomodulatory toxicant alters pulmonary susceptibility to viruses has received little attention. To study the effects of prior acrolein dosing on the severity of influenza A viral infection, male BALB/c mice received acrolein (1mg/kg) or saline (control) via oropharyngeal aspiration either 4- or 7-days prior to intranasal inoculation with either influenza A/PR/8/34 virus or vehicle. At 0, 2, 4 and 7 days post-inoculation, lung samples were assessed for histological changes while pulmonary inflammation was monitored by estimating immune cell numbers and cytokine levels in bronchoalveolar lavage fluid (BALF). After viral challenge, animals that were exposed to acrolein 4 days previously experienced greater weight loss and exhibited an accelerated inflammatory response at 2 days after viral inoculation. Thus compared to saline-pretreated, virus-challenged controls, BALF recovered from these mice contained higher numbers of macrophages and neutrophils in addition to increased levels of several inflammatory cytokines, including IL-1α, IL-1β, IL-6, TNF, IFN-γ, KC, and MCP-1. The acrolein-induced increase in viral susceptibility was suppressed by the carbonyl scavenger bisulphite. These findings suggest acute acrolein intoxication "primes" the lung to mount an accelerated immune response to inhaled viruses.     

Comparison of bronchoscopic and non-bronchoscopic techniques for diagnosis of ventilator associated pneumonia

Background:

The diagnosis of ventilator associated pneumonia (VAP) remains a challenge because the clinical signs and symptoms lack both sensitivity and specificity and the selection of microbiologic diagnostic procedure is still a matter of debate.

Aims and Objective:

To study the role of various bronchoscopic and non-bronchoscopic diagnostic techniques for diagnosis of VAP.

Settings and Design:

This prospective comparative study was conducted in a medical ICU of a tertiary care center.

Materials and Methods:

Twenty-five patients, clinically diagnosed with VAP, were evaluated by bronchoscopic and non-bronchoscopic procedures for diagnosis. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of various bronchoscopic and non-bronchoscopic techniques were calculated, taking clinical pulmonary infection score (CPIS) of ≥6 as reference standard.

Results:

Our study has shown that for the diagnosis of VAP, bronchoscopic brush had a sensitivity, specificity, PPV and NPV of 94.9% [confidence interval (CI): 70.6–99.7], 57.1% (CI: 13.4–86.1), 85% (CI: 61.1–96) and 80% (CI: 21.9–98.7), respectively. Bronchoscopic bronchoalveolar lavage (BAL) had a sensitivity, specificity, PPV and NPV of 77.8% (CI: 51.9–92.6), 71.8% (CI: 24.1–94), 87.3% (CI: 60.4–97.8) and 55.5% (CI: 17.4–82.6), respectively. Sensitivity, specificity, PPV and NPV for non–bronchoscopic BAL (NBAL) were 83.3% (CI: 57.7–95.6), 71.43% (CI: 24.1–94), 88.2% (CI: 62.3–97.4) and 62.5% (CI: 20.2–88.2), respectively. Endotracheal aspirate (ETA) yield was only 52% and showed poor concordance with BAL (κ-0.351; P-0.064) and NBAL (k-0.272; P-0.161). There was a good microbiologic concordance among different bronchoscopic and non-bronchoscopic distal airway sampling techniques.

Conclusion:

NBAL is an inexpensive, easy, and useful technique for microbiologic diagnosis of VAP. Our findings, if verified, might simplify the approach for the diagnosis of VAP.     

Evaluation of interleukin-6 and interleukin-10 in lung transplant patients with human cytomegalovirus infection

Abstract:  We hypothesized that interleukin-6 (IL-6) in plasma and bronchoalveolar lavage (BAL) might serve as additional diagnostic parameter in lung transplant patients with human cytomegalovirus (HCMV) infection. Therefore, we compared IL-6 levels in HCMV-positive vs. HCMV-negative patients. IL-6 was measured by ELISA in plasma and BAL in 111 patients. Furthermore, we investigated the influence of IL-10 on IL-6 production in HCMV-positive patients. For HCMV–DNA detection in plasma and BAL a quantitative polymerase chain reaction (PCR) assay was used. IL-6 levels were significantly higher in the HCMV-positive group (n = 39; BAL p = 0.045; plasma p = 0.017) in comparison to the HCMV-negative group (n = 72). IL-10 did not correlate with IL-6 concentration (p = 0.146). Donor (D) or recipient (R) HCMV-constellation did not influence IL-6 concentration. IL-6 levels were not influenced by elevated levels of HCMV copies. Our data suggest that IL-6 does not serve as a good diagnostic parameter for existence of HCMV infection in lung transplant patients. Because of the wide range of the IL-6 levels in both groups, we were not able to find a breakpoint differentiating between infected and not-infected patients. Another important finding was that IL-6 production is not dependent of the HCMV status of D/R.     

Lung disease in Niemann-Pick disease

BACKGROUND: Lung involvement in children with Niemann-Pick disease has rarely been studied systematically. OBJECTIVE: To assess the involvement of the lung and the value of bronchoalveolar lavage in children with Niemann-Pick diseases. DESIGN: Retrospective analysis of patient records. PATIENTS: Thirteen patients, with type A (n = 1), type B (n = 10), and type C (n = 2) Niemann-Pick disease, aged 2 months to 9 years at diagnosis, were included in the study. INTERVENTIONS: Lung involvement was assessed by clinical evaluation, chest radiograph, lung computed tomography (CT) scan, pulmonary function tests, and bronchoalveolar lavage fluid analysis. RESULTS: Respiratory symptoms were present at diagnosis in 10 patients and developed during follow up in the three other patients. All patients showed signs of interstitial lung disease on chest X-ray and lung CT scan. Bronchoalveolar lavage fluid analysis (n = 7) revealed a marked accumulation of foamy macrophages (Niemann-Pick cells) in all patients. At follow up, one patient died of respiratory failure, five patients required long term oxygen therapy and seven other patients presented a chronic obstructive pulmonary disease (n = 6) or chronic cough (n = 1). CONCLUSION: Lung disease was observed in all the patients included in the present study. Bronchoalveolar lavage may be useful in Niemann-Pick diseases by showing the presence of characteristic Niemann-Pick cells.