吸入速尿平喘的临床观察及机理

目的：观察速尿雾化及吸入对支气管哮喘患者平喘疗效,并对其机理进行探讨。方法：对４６例支气管哮喘病人以速尿４０ｍｇ＋α－糜蛋白酶２０００＋生理盐水５ｍｌ雾化吸入为第一组;另外４７例在以上方案基础上去速尿为第二组,结果：第一组显效３５例,显效率为７３．９１％,总有效率为９０％,第二组明效１５例,显效率为３１．９％,总有效率为５３．１９％,两组比较差异显著（Ｐ〈０．０１）,结论：速尿可能成为一种新的非激素类抗炎药,吸入速尿抗哮喘作用的研究,开辟了哮喘治疗的新途径。     

普米克气雾吸入对咳嗽变异型哮喘患者气道高反应性及肺功能的影响

采用普米克气雾吸入治疗 48例咳嗽变异型哮喘患者。结果表明 :治疗组气道高反应性显著降低 (P <0 .0 0 1) ,肺功能显著改善 ( P <0 .0 0 1) ,与对照组比较差异有显著性 ( P <0 .0 1)。证实普米克吸入对改善咳嗽变异型哮喘病人肺功能及降低气道高反应性疗效肯定 ,有积极意义     

Global Estimates of Ambient Fine Particulate Matter Concentrations from Satellite-Based Aerosol Optical Depth: Development and Application

Background

Epidemiologic and health impact studies of fine particulate matter with diameter < 2.5 μm (PM_2.5) are limited by the lack of monitoring data, especially in developing countries. Satellite observations offer valuable global information about PM_2.5 concentrations.

Objective

In this study, we developed a technique for estimating surface PM_2.5 concentrations from satellite observations.

Methods

We mapped global ground-level PM_2.5 concentrations using total column aerosol optical depth (AOD) from the MODIS (Moderate Resolution Imaging Spectroradiometer) and MISR (Multiangle Imaging Spectroradiometer) satellite instruments and coincident aerosol vertical profiles from the GEOS-Chem global chemical transport model.

Results

We determined that global estimates of long-term average (1 January 2001 to 31 December 2006) PM_2.5 concentrations at approximately 10 km × 10 km resolution indicate a global population-weighted geometric mean PM_2.5 concentration of 20 μg/m³. The World Health Organization Air Quality PM_2.5 Interim Target-1 (35 μg/m³ annual average) is exceeded over central and eastern Asia for 38% and for 50% of the population, respectively. Annual mean PM_2.5 concentrations exceed 80 μg/m³ over eastern China. Our evaluation of the satellite-derived estimate with ground-based in situ measurements indicates significant spatial agreement with North American measurements (r = 0.77; slope = 1.07; n = 1057) and with noncoincident measurements elsewhere (r = 0.83; slope = 0.86; n = 244). The 1 SD of uncertainty in the satellite-derived PM_2.5 is 25%, which is inferred from the AOD retrieval and from aerosol vertical profile errors and sampling. The global population-weighted mean uncertainty is 6.7 μg/m³.

Conclusions

Satellite-derived total-column AOD, when combined with a chemical transport model, provides estimates of global long-term average PM_2.5 concentrations.     

RP－HPLC测定喘立舒中沙丁胺醇及异丙阿托品的含量

采用ＲＰ－ＨＰＬＣ，同时测定喘立舒气雾剂中沙丁胺醇和异丙阿托品的含量。沙丁胺醇和异丙阿托品的回收率分别为１００．１０％（ＲＳＤ＝２．４３％）和９８．３０％（ＲＳＤ＝１．８４％）。本方法用于喘立舒气雾剂的分析，方法简单，快速准确。     

Characterization of Suspension-Based Metered Dose Inhaler Formulations Composed of Spray-Dried Budesonide Microcrystals Dispersed in HFA-134a

PURPOSE: To assess the physicochemical characteristics and aerosol properties of suspensions of lipid-coated budesonide microcrystals dispersed in HFA-134a. METHODS: Lipid-coated budesonide microcrystals were prepared by spray-drying an emulsion-based feedstock. Physicochemical characteristics of spray-dried particles were assessed by electron microscopy, laser diffraction, and differential scanning calorimetry. Purity and content were determined by reverse-phase HPLC. Particle aggregation and suspension stability were assessed visually, and aerosol performance was assessed by Andersen cascade impaction and dose content uniformity. RESULTS: Spray-drying of micronized budesonide microcrystals in the presence of phospholipid-coated emulsion droplets results in the production of low-density lipid-coated microcrystals with low surface energy. These spray-dried particles form stable suspensions in HFA-134a. This translates into good uniformity in the metered dose across the contents of the inhaler and acceptable aerodynamic particle size distributions (MMAD = 3.2 to 3.4 microm). The formulation was observed to maintain its performance over 6 months at 40 degrees C/75% RH and 16 months at 25 degrees C/60% RH. No effect of storage orientation was observed on the content of first sprays following storage (i.e., no Cyr effect). The fine particle dose was found to be linear out to suspension concentrations of about 2% wt/vol, and FPD(4.7 microm) values approaching 400 microg can be delivered in a single inhalation. CONCLUSIONS: Engineered particles comprised of lipid-coated microcrystals may provide an acceptable alternative formulation technology for metered dose inhalers in the new hydrofluoroalkane propellants.     

Targeted drug delivery strategies to treat lung metastasis

Background: Most cancer patients die of metastatic disease, and in a high proportion of cases, from lung metastasis. Methods to target therapy to metastatic disease in general and specifically to lung metastasis are required. Objective: To describe the current and potential tools for the treatment of lung metastasis. Methods: Literature search tools were used with no predefined limitations to encompass the main tumor targeting methods. Methods in standard clinical use, in clinical trials and in preclinical development are reviewed. Data about treatment of lung metastasis and solid tumors are emphasized. Results: Physically targeting therapies to lung metastasis is feasible by aerosol-carried agents, magnetic targeting and intravascular devices. Biological targeting includes methods such as polymers and liposomes, which are based on the principle of enhanced permeability and retention of large molecules in tumor vascular field. Ligand-targeted treatments depend on cancer-specific antibodies or receptors. Few of these methods are in clinical trials or in standard clinical use. However, promising techniques are in advanced preclinical or early clinical studies. The authors believe that targeted treatments will be one the major anticancer tools in the near future.     

Dry powder inhalers for pulmonary drug delivery

The pulmonary route is an interesting route for drug administration, both for effective local therapy (asthma, chronic obstructive pulmonary disease or cystic fibrosis) and for the systemic administration of drugs (e.g., peptides and proteins). Well-designed dry powder inhalers are highly efficient systems for pulmonary drug delivery. However, they are also complicated systems, the the performance of which relies on many aspects, including the design of the inhaler (e.g., resistance to air flow and the used de-agglomeration principle to generate the inhalation aerosol), the powder formulation and the air flow generated by the patient. The technical background of these aspects, and how they may be tuned in order to obtain desired performance profiles, is reviewed. In light of the technical background, new developments and possibilities for further improvements are discussed.     

Ultrasonic nebulization platforms for pulmonary drug delivery

Importance of the field: Since the 1950s, ultrasonic nebulizers have played an important role in pulmonary drug delivery. As the process in which aerosol droplets are generated is independent and does not require breath-actuation, ultrasonic nebulizers, in principle, offer the potential for instantaneously fine-tuning the dose administered to the specific requirements of a patient, taking into account the patient’s breathing pattern, physiological profile and disease state. Nevertheless, owing to the difficulties and limitations associated with conventional designs and technologies, ultrasonic nebulizers have never been widely adopted, and have in recent years been in a state of decline.

Areas covered in this review: An overview is provided on the advances in new miniature ultrasonic nebulization platforms in which large increases in lung dose efficiency have been reported.

What the reader will gain: In addition to a discussion of the underlying mechanisms governing ultrasonic nebulization, in which there appears to be widely differing views, the advantages and shortcomings of conventional ultrasonic nebulization technology are reviewed and advanced state-of-the-art technologies that have been developed recently are discussed.

Take home message: Recent advances in ultrasonic nebulization technology demonstrate significant potential for the development of smart, portable inhalation therapy platforms for the future. Nevertheless, there remain considerable challenges that need to be addressed before such personalized delivery systems can be realized. These have to be addressed across the spectrum from fundamental physics through to in vivo device testing and dealing with the relevant regulatory framework.     

Laboratory evaluation of a prototype photochemical chamber designed to investigate the health effects of fresh and aged vehicular exhaust emissions

Laboratory experiments simulating atmospheric aging of motor vehicle exhaust emissions were conducted using a single vehicle and a photochemical chamber. A compact automobile was used as a source of emissions. The vehicle exhaust was diluted with ambient air to achieve carbon monoxide (CO) concentrations similar to those observed in an urban highway tunnel. With the car engine idling, it is expected that the CO concentration is a reasonable surrogate for volatile organic compounds (VOCs) emissions. Varying the amount of dilution of the exhaust gas to produce different CO concentrations, allowed adjustment of the concentrations of VOCs in the chamber to optimize production of secondary organic aerosol (SOA) needed for animal toxicological exposures. Photochemical reactions in the chamber resulted in nitric oxide (NO) depletion, nitrogen dioxide (NO₂) formation, ozone (O₃) accumulation, and SOA formation. A stable SOA concentration of approximately 40 μg m^?3 at a chamber mean residence time of 30?min was achieved. This relatively short mean residence time provided adequate chamber flow output for both particle characterization and animal exposures. The chamber was operated as a continuous flow reactor for animal toxicological tests. SOA mass generated from the car exhaust diluted with ambient air was almost entirely in the ultrafine mode. Chamber performance was improved by using different types of seed aerosol to provide a surface for condensation of semivolatile reaction products, thus increasing the yield of SOA. Toxicological studies using Sprague-Dawley rats found significant increases of in vivo chemiluminescence in lungs following exposure to SOA.     

Antibody persistence in young adults 1 year after MMR immunization by aerosol or by subcutaneous route

Information on antibody persistence after aerosol revaccination with MMR components is limited. Thus, antibody titers were determined in 283 adult participants in a MMR vaccine trial 12 months after revaccination. One group had received aerosolized Triviraten vaccine while two other groups received either injected Triviraten or MMR II vaccine. Both MMR vaccines contained the same rubella strain, but different measles and mumps strains. Seropositivity to measles persisted in 98% of aerosolized vaccine recipients, 92% of injected Triviraten, and 95% of injected MMR II. All participants in the three groups retained seropositivity to rubella, while less than 50% remained seropositive to mumps.