异丙托溴铵雾化吸入治疗重型颅脑损伤合并创伤性湿肺疗效观察

目的分析并探讨异丙托溴铵雾化吸入治疗重型颅脑损伤合并创伤性湿肺的临床效果。方法选取来我院接受治疗的重型颅脑损伤合并创伤性湿肺患者50例,随机分为观察组与对照组,每组25例。两组患者均给予常规的支持治疗,在此基础上,观察组给予异丙托溴铵联合雾化治疗,对照组仅给予雾化吸入治疗。观察两组患者治疗前后血气分析指标和机械通气时间,计算氧和指数。结果观察组治疗后氧和指数为(354.76±31.71)mmHg,机械通气时间为(219.54±35.63)h。对照组治疗后氧和指数为(314.76±30.68)mmHg,机械通气时间为(254.29±36.74)h。观察组治疗后氧和指数明显高于对照组,且机械通气时间短于对照组。经统计学检验,差异具有统计学意义(P0.05)。两组患者治疗后各项血气指标均有明显改善,观察组PaO_2指标与对照组相比,改善更加明显。经统计学检验,差异具有统计学意义(P0.05)。结论异丙托溴铵联合雾化治疗重型颅脑损伤合并创伤性湿肺的临床效果显著。     

Effective aerosol delivery during high‐frequency ventilation in neonatal pigs

Background and objective: Pulmonary delivery of aerosols during high‐frequency oscillatory ventilation (HFOV) has not been studied in vivo. This study investigated the pulmonary delivery of aerosolized gadopentetate dimeglumine (Gd‐DTPA) in a HFOV circuit in piglets using MRI to visualize contrast excretion in the kidneys. Methods: Four ventilated piglets (3–7 days old, 1.7–2.4 kg at birth) received aerosolized Gd‐DTPA in a HFOV circuit for different durations of time (60, 30, 20 and 10 min). Aerosols were generated using the MiniHeart jet nebulizer. As MR‐compatible HFOV was not available, aerosolized Gd‐DTPA was administered in the HFOV circuit outside the MR suite followed by MRI 10–20 min later. T1‐weighted spin echo sequences were obtained using the Bruker/Siemens 4T MR scanner. Results: Enhancement of the kidneys was observed 10 min after aerosol initiation in piglets who received Gd‐DTPA aerosol for 60, 30 and 20 min in the HFOV circuit but not in the piglet who received aerosol for 10 min. Renal concentration of Gd‐DTPA, determined from the signal intensity, increased linearly with time until 40 min post Gd‐DTPA delivery. Conclusions: Effective pulmonary aerosol delivery during HFOV was confirmed by contrast visualization in the kidneys within 30 min of aerosol initiation reflecting, alveolar absorption, glomerular filtration and renal concentration.     

Determination of the bioavailability of gentamicin to the lungs following inhalation from two jet nebulizers

AIMS: To determine the bioavailability of gentamicin to the lung following inhalation from two jet nebulizers. METHODS: Serial urine samples were obtained from 10 volunteers after a 80 mg dose given orally, nebulized from a Pari LC + (PARI) and MicroNeb III (MN) devices, or after a 40 mg intravenous dose. In vitro aerodynamic characteristics of the nebulized doses were also determined. RESULTS: The mean (SD) absolute gentamicin lung bioavailalibility following delivery by PARI and MN devices was 1.4 (0.4) and 1.7 (0.5) %. The mass median aerodynamic diameter (MMAD) of the drug particles from the PARI and MN systems was 8.6 (0.6) and 6.7 (0.5) microm and the corresponding fine particle doses (FPD) were 10.2 (2.8) and 11.7 (1.5) mg. CONCLUSIONS: The MMAD and FPD data reflect the poor lung deposition of gentamicin identified by urinary excretion.     

Investigating cascade impactor performance using a modified 3D printed induction port

Based on a computer tomographic scan of a human trachea, a modified induction port (mIP), for use with the Next Generation Cascade Impactor, was manufactured using 3D printing technology. Standard United States Pharmacopoeia IP (USPIP) was compared to the mIP and a 3D printed version of the USPIP (USP3DIP) by analyzing different types of commercial salbutamol formulations for inhalation. Increased retention of particles in the mIP was found analyzing a pMDI formulation, leading to a decrease in the FPF from 28.8 ± 2.0% to 14.2 ± 1.2%, which correlates better to in vivo deposition data from literature. Increased deposition was found to be based on geometrical factors only. The impact of surface related effects was investigated by (a) comparing results obtained with the USPIP and USP3DIP (all formulations) and (b) generating another model IP (USP3DSEIP) with a surface area equivalent to the mIP but maintaining the geometry of the USPIP (pMDI only). USPIP, USP3DIP, and USP3DSEIP were found to perform equivalently. The impact of different geometries on airflow velocities in the USPIP and mIP was assessed using a computational fluid dynamics (CFD) model. Conclusively, this study shows that replacing the USP IP by the mIP can provide additional information in formulation assessment and in in vitro/in vivo correlation, when applied on pMDI formulations.     

Efficient management and maintenance of ultrasonic nebulizers to prevent microbial contamination

AIM: To seek the cause of Burkholderia cepacia complex (Bcc) infection outbreak and evaluate the efficacy of new methods for nebulizer maintenance.METHODS: We investigated the annual number of Bcc isolates recovered from clinical samples in our hospital between 1999 and 2013. Swab samples were randomly collected for bacterial culture before patient use from 10 each of the two machine types in August 2001; these included 20 samples from each of the following: Drain tubes, operating water chambers, oscillators, and nebulizing chambers. In addition, 10 samples each of nebulizer solutions before and after use were cultured. For environmental investigation, 10 samples were collected from sinks in the nurse stations of the wards where patients positive for Bcc were hospitalized. Numbers of Bcc isolates were compared before and after introduction of new methods for nebulizer maintenance in October 2001. In addition, randomly amplified polymorphic DNA (RAPD) assay was applied to find the genetic divergence of the Bcc isolates obtained from clinical samples and nebulizers.RESULTS: From January 1999 to December 2013, a total of 487 Bcc isolates were obtained from clinical specimens from 181 patients. Notably, 322 (66.1%) Bcc isolates were obtained from clinical specimens from 1999 to 2001, including 244 (115 patients) from sputum and 34 (11 patients) from blood. During this period, 14 isolates were obtained from nebulizer components. Among these, six were derived from nebulizer drain tubes, five from operating water chambers, and one from the oscillator before patient use, and two from nebulizer solutions after patient use. When Bcc was isolated from the nebulizer solution after patient use, Bcc was simultaneously detected in other parts of the nebulizer. Bcc was not isolated from any nebulizer solution before use. RAPD assays revealed similar DNA profiles in isolates obtained from patients and nebulizers. Investigation revealed damaged diaphragms in many nebulizers. The new maintenance methods for nebulizers, including restriction of the usage period, thorough disinfection, and routine check for diaphragm breakage, remarkably reduced Bcc isolation (165 isolates from patients in 12 years and 0 isolate from nebulizers in periodical sampling). In particular, Bcc has been isolated from blood from only one patient since the new methods were introduced.CONCLUSION: Appropriate maintenance of ultrasonic nebulizers is crucial for preventing Bcc contamination of nebulizers and subsequent respiratory tract and blood infections.     

Nebulization as a delivery method for mAbs in respiratory diseases

Introduction: The pulmonary route is not invasive and can be used to target drugs directly to the lungs, limiting the exposure of secondary organs. It is, thus, an attractive alternative to the intravenous route, for the delivery of mAbs, which display limited transfer from blood into the lungs.

Areas covered: This review provides an overview of the pharmacological properties of antibody-based treatments, describes those for respiratory diseases and discusses preclinical/clinical results of aerosolized antibody-based therapeutics. The advantages and limitations of aerosol devices and the formulation for the administration of aerosolized mAbs are also detailed.

Expert opinion: Overall, the inhalation of mAbs for therapeutic purposes is both appropriate and feasible. The size and structure of the biotherapeutic molecule are important properties to be taken into account when trying to achieve long-term retention. Mesh nebulizers currently appear to be the most appropriate devices for the safe delivery of large amounts of active mAb into the lungs. mAbs should be formulated so as to prevent their degradation and possible immunogenicity. General guidelines can be given for mAb aerosolization, but the formulation and device combination should be adapted for each therapeutic and clinical application.     

Influence of Impactor Operating Flow Rate on Particle Size Distribution of Four Jet Nebulizers

When a nebulizer is evaluated by the Andersen Cascade Impactor (ACI), the flow rate is generally maintained at 28.3 L/min, as recommended by the manufacturer. However, the nebulizer flow rate that a patient inhales is only around 18 L/min. Because the drive flow of a nebulizer is approximately 6–8 L/min, the nebulized drug is mixed with outside air when delivered. Evaluating impactor performance at the 28.3 L/min flow rate is less than ideal because an additional 10 L/min of outside air is mixed with the drug, thereby affecting the drug size distribution and dose before inhalation and deposition in the human lung. In this study we operated the ACI at an 18.0 L/min flow rate to test whether the effect of the changing ambient humidity was being exaggerated by the 28.3 L/min flow rate. The study was carried out at three different relative humidity levels and two different impactor flow rates with four commercially available nebulizers. The mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD) of the droplets were found to increase when the impactor was operated at a flow rate of 18 L/min compared to that of 28.3 L/min. The higher MMAD and GSD could cause the patient to inhale less of the drug than expected if the nebulizer was evaluated by the ACI at the operating flow rate of 28.3 L/min.     

医用中心雾化治疗系统的研发及临床应用

目的：设计一套对多人同时进行雾化治疗系统替代单人使用的雾化治疗器。方法：采用大型空气压缩机组将恒压并处理过的空气通过连接管路引入到雾化室内的多个设备带终端。患者将雾化药杯的管子接入设备终端就可进行雾化治疗。结果：该系统完全达到设计要求,能够同时对40~100人进行雾化治疗,疗效稳定可靠,治疗效率大幅提升。结论：该系统安全稳定、高效、可靠,适合在医院推广使用。