Clinical validation of a new olfactory test

A new approach to clinical olfactometry is presented using nasal sprays. A special dosage valve was used to standardize an aerosol size to 40 μm. For evaluation a 6 × 6 matrix (substance/olfactory quality) with verbal associative clues was used according to test psychological findings. Validation took place in three steps after determining smell-associated thresholds in preliminary examinations. Recognition of different aromas administered either by spraying into the open mouth from a distance of 5 cm using nasal sprays or sniffing opened bottles was compared in 50 subjectively normosmic subjects. Findings showed that the correspondence between the two procedures was relatively high, with global identification of odorous substances as high as 98.4% in the spray test. The number of substances used was next reduced to those six substances providing the most reproducible results in an investigation with 56 normosmic and 55 hyposmic subjects. Verbal associative clues were also tested. In a last step 50 patients with hyposmia of various origin and 110 normosmic subjects were tested, allowing previous results to be reproduced regardless of the cause of hyposmia. The spray test was shown to be easily performed and was suitable as a screening test, with a sensitivity of 88% and a specificity of 100%. Received: 29 September 1997 / Accepted: 11 February 1998     

雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎的效果和安全性分析

目的：评估雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎的效果和安全性。方法将56例鲍曼不动杆菌呼吸机相关肺炎患者随机分为对照组和研究组各28例。对照组在头孢哌酮舒巴坦钠（3.0 g,1次/12 h）阿米卡星注射液（7.5 mg/kg,1次/d）静脉治疗的同时予生理盐水（5 ml,1次/d）呼吸机雾化吸入,研究组在头孢哌酮舒巴坦钠（3.0 g,1次/12 h）静脉治疗的同时予阿米卡星注射液（7.5 mg/kg,1次/d）呼吸机雾化吸入,分析治疗8 d后两组的支气管肺泡灌洗液培养结果转阴率、急性生理与慢性健康评分Ⅱ（APACHEⅡ）、临床肺部感染评分（CPIS）、氧合指数（PaO2/FiO2）、尿量及血肌酐（Cr）水平的变化,随访28 d,记录死亡率。结果治疗后,研究组与对照组支气管肺泡灌洗液培养转阴率分别为82.1%（23/28）、53.6%（15/28）,差异有统计学意义（P＜0.05）。治疗后,两组APACHEⅡ、CPIS较治疗前均下降,PaO2/FiO2均明显提高（P﹤0.05）。与治疗前相比,对照组尿量减少,Cr水平升高（P＜0.05）;而研究组尿量增多,血肌酐无明显变化（P＞0.05）。治疗后对照组的尿量明显少于研究组,Cr水平明显高于研究组,差异有统计学意义（P＜0.05）。研究组和对照组28 d死亡率分别为21.4%（6/28）、25.0%（7/28）,差异无统计学意义（P＞0.05）。结论雾化吸入阿米卡星治疗鲍曼不动杆菌呼吸机相关肺炎效果好,肾脏毒性小,能减少全身静脉应用抗生素的剂量。     

Booster immune response in children 6–7 years of age,randomly assigned to four groups with two MMR vaccines applied by aerosol or by injection

Importance

Aerosol immunization may be a useful tool to reach and sustain the elimination of measles, rubella, and congenital rubella syndrome. We compared booster seroresponses to aerosolized or injected MMR vaccines containing different strains of measles (Attenuvax or Edmonston–Zagreb) and mumps (Jeryl–Lynn or Leningrad–Zagreb).

Objective

To assess the safety and immunogenicity of two MMR: Vaccines administered by aerosol.

Methods

A randomized and controlled clinical trial was conducted to evaluate the safety and booster responses to the MMR SII (Serum Institute of India) and MMR II (Merck Sharp & Dhome) vaccines, both of which were administered by aerosol (ae) or injection (inj) to Mexican children aged 6–7 years in elementary schools. The seroresponses were evaluated by PRN (measles) and ELISA (rubella and mumps). Adverse events were followed-up for 28 days after the immunization.

Results

Two hundred and fifty-three of 260 children completed the one-month follow-up. All participants reached protective seropositivity for measles and rubella after immunization, and 98.3 to 100% reached protective seropositivity for mumps (p = 0.552). The proportions of the seroresponses (a 2-fold rise from the baseline antibody titers) to measles were 38.3% for MMR SII (ae), 31.3% for MMR II (ae), 37.5% for MMR SII (inj), and 44.6% for MMR II (inj) (p = 0.483). The seroresponses for rubella were 26.7% for MMR SII (ae), 31.3% for MMR II (ae), 46.9% for MMR SII (inj), and 40.0% for MMR II (inj) (p = 0.086). The seroresponse to mumps were 31.7% for MMR SII (ae), 25.0% for MMR II (ae), 48.4% for MMR SII (inj), and 53.9% for MMR II (inj) (p = 0.002). The difference in the seroresponse of a 4-fold rise from the baseline antibody titers was not statistically significant. Only mild adverse events were noted.

Conclusion

Aerosolized vaccines were as safe and as immunogenic as injected vaccines.

Protocol registration

CMN 2010-005 (National Regulatory Authority).     

Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis

Invasive pulmonary mucormycosis is a life-threatening fungal infection encountered in immunocompromised patients. An intravenous high-dose lipid formulation of amphotericin B, such as liposomal amphotericin B (L-AMB), is the recommended treatment. The efficacy of inhaled L-AMB against mucormycosis has not been evaluated.We evaluated the efficacy of inhaled aerosolized L-AMB in murine invasive pulmonary mucormycosis. ICR female mice were immunosuppressed with cortisone acetate and cyclophosphamide and challenged on day 0 with 1 × 10⁶ conidia of Rhizopus oryzae (TIMM 1327) intratracheally. Infected mice were assigned to one of the following 3 treatment groups: (i) control, (ii) treatment only (aerosolized L-AMB from day 1–5 after challenge), and (iii) prophylaxis followed by treatment (aerosolized L-AMB from day −2 to 5 before and after challenge). Survival was monitored until 12 days after challenge. For fungal-burden and histopathological examination, mice were sacrificed 4 h after treatment on day 3. Numbers of colony-forming units per lung were calculated. To study the distribution of AMB after inhalation of L-AMB, immunohistochemical studies using AMB antibody were performed.Aerosolized L-AMB significantly improved survival rate and decreased fungal burden compared with control group, and histopathology findings were superior to those of control group. However, no significant differences were detected between the treatment-only and prophylaxis followed by treatment groups. Immunohistochemical analysis showed that L-AMB was promptly distributed in lung tissue after inhalation therapy.Aerosolized L-AMB showed modest efficacy against R. oryzae infection in mice treated after fungal challenge. Prophylaxis with aerosolized L-AMB was not effective in this animal model.     

Intravenous plus inhaled versus intravenous colistin monotherapy for lower respiratory tract infections: A systematic review and meta-analysis

Objective

To evaluate whether intravenous plus inhaled combination (IV/INHCC) compared to intravenous monotherapy (IVCM) was associated with patient outcomes and identify factors influencing study outcomes.

黏菌素静脉联合雾化吸入治疗呼吸机相关性肺炎安全性与有效性的Meta分析

目的 循证评价黏菌素静脉联合雾化吸入治疗VAP 的有效性与安全性。方法 检索时间从建库截止至2018 年 3 月。计算机检索数据库：Pubmed、Embase (Ovid)、Cochrane library (2018 年3 期)， 中国知网(China National Knowledge Infrastructure, CNKI)、维普数据库(VIP Database for Chinese Technical Periodicals, VIP)、万方数据库(Wan Fang Data)，中国生物 医学文献数据库(Chinese Biomedical Literature Database, CBM)，收集关于黏菌素静脉联合吸入治疗VAP 的临床对照研究。采用 Mircosoft Excel、RevMan 5.3 进行数据分析。结果 有效性方面：①临床治愈率：静脉联合雾化吸入组总有效率显著增加[RR=1.23, 95%CI (1.07,1.41), P=0.003]；②微生物根除率：两组患者微生物根除率差异无统计学意义[RR=1.07, 95%CI(0.92,1.24), P=0.38]；③ 死亡率：相比对照组，试验组死亡率虽降低，但差异无统计学意义[RR=0.93, 95%CI(0.79,1.09), P=0.37]。安全性方面：①急性肾 损伤发生率：两组患者发生急性肾损伤的风险无明显差异(P=0.97)。结论 由此可知，IV+AS 联合方案在VAP 治疗过程中有一 定优势，但在降低死亡率、减少急性肾损伤的发生及根除微生物方面无显著差异，鉴于本研究的局限性，该结论尚待进一步验证。     

Prevention of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in human immunodeficiency virus infected patients: a clinical approach comparing aerosolized pentamidine and pyrimethamine/sulfadoxine

Summary The incidence of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis (TE) was analyzed in 83 human immunodeficiency virus (HIV)-infected patients who inhaled aerosolized pentamidine (AP) either for primary prophylaxis (group la) or secondary prophylaxis (group IIa) of PCP. These cohorts were compared with two historical groups of patients who took Fansidar (pyrimethamine/sulfadoxine) for primary prophylaxis (group lb) or secondary prophylaxis (group IIb) of PCP. The follow-up was 3—41 months (median 8 months). PCP did not occur in group la but was seen in 1 patient of group Ib (5%). TE was observed in 3 patients of group Ia (7.3%) and in 1 patient of group Ib (5%). PCP relapses were seen in 5 patients of group IIa (11.9%) and in 3 patients of group Ilb (6.9%), whereas TE occurred in 13 patients of group IIa (30.9%) and in 1 patient of group IIb (2.3%). 20.3% of patients with CD4⁺ counts < 100/l and only 7.7% of those with CD4⁺ counts > 100/l developed toxoplasmosis. In conclusion, Fansidar rather than AP prophylaxis should be recommended for patients with a history of PCP or toxoplasmosis and for all HIV-infected patients with CD4⁺ counts 100/l. In patients with CD4⁺ lymphocyte counts between 100 and 200/l, AP prophylaxis appears appropriate.Abbreviations AIDS acquired immunodeficiency syndrome - AP aerosolized pentamidine - FDA Food and Drug Administration - HIV human immunodeficiency virus - IgG immunoglobulin G - PCP Pneumocystis carinii pneumonia - TE toxoplasmic encephalitis - TMP/SMX trimethoprim/sulfamethoxazole     

氯胺酮雾化吸入对哮喘模型大鼠肺泡灌洗液白细胞介素-4浓度的影响

目的　通过建立大鼠支气管哮喘模型 ,观察不同浓度氯胺酮对大鼠肺泡灌洗液白细胞介素 4 (IL 4 )浓度的影响。方法　SD大鼠随机分成对照组 (N组 )、哮喘模型组 (A组 )和不同浓度氯胺酮预处理组 (分别为K1组、K2组和K3组 ) ,每组 8只。A组大鼠用卵白蛋白辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏 ,2周后雾化吸入卵蛋白激发哮喘 ;氯胺酮处理组大鼠用同样方法致敏 ,但在激发前分别给予雾化吸入氯胺酮 12 5g/L(K1组 )、2 5 g/L(K2组 )和 5 0 g/L(K3组 ) ;N组用生理盐水替代卵蛋白进行注射和吸入。结果　A组支气管肺泡灌洗液中IL 4浓度显著增高 ;K2、K3组支气管肺泡灌洗液中IL 4浓度明显低于A组 (P <0 0 5 )。结论　 2 5 g/L或 5 0g/L的氯胺酮雾化吸入对致敏原所激发的哮喘模型鼠的气道炎症及组织损伤有保护作用。     

关于雾化吸入抗生素对呼吸机相关性肺炎的治疗

呼吸机相关性肺炎(ventilator-associated pneumonia,VAP)是机械通气患者常见的并发症,有着极高的病死率,全身静脉使用抗生素作为VAP的主要治疗措施,临床治愈率有限.从理论上讲,雾化吸入抗生素于局部达到较高的药物浓度,联合静脉使用抗生素,可取得更好的临床效果,特别是在VAP伴多重耐药菌感染及某些静脉抗生素效果不佳的治疗中.     

硝普钠雾化吸入对肺动脉高压的影响

目的:观察硝普钠(SNP)雾化吸入对肺动脉高压的影响。方法:选择慢性肺源性心脏病肺动脉高压病人20例,静息30分钟,用惠普5500型心脏超声仪测量肺动脉压(PAP)、左心室射血分数(LVEF),用水银柱血压计测量肱动脉平均压(MAP),而后行生理盐水雾化吸入20分钟,停吸10分钟;再行SNP雾化吸入(SNP50mg+生理盐水50ml)20分钟;分别于两者吸入5分钟、10分钟、15分钟、20分钟以及停吸5分钟、10分钟时测量上述各项指标,然后进行比较分析。结果:生理盐水雾化吸入全程各指标无明显变化,SNP雾化吸入5分钟时,PAP由66.76±10.24mmHg降至56.44±11.22mmHg(P<0.01);LVEF由0.50±0.04%升至0.56±0.06%(P<0.01);10分钟时,PAP继续下降至53.26±10.62mmHg(与5分钟比较P<0.05);LVEF继续上升至0.58±0.06%(与5分钟比较P<0.05);吸入至20分钟,PAP、LVEF与10分钟比较无明显变化;停止吸入5分钟,PAP即回升至63.22±10.44mmHg、LVEF降至0.53±0.04%(P均<0.01);停吸100分钟均恢复至吸入前的状态;MAP全程无明显变化。结论:硝普钠雾化吸入可明显降低肺动脉压,提高左心室射血分数,对平均动脉压无明显影响。