Effects of hydrofluoroalkane and dry powder-formulated corticosteroids on sputum inflammatory markers in asthmatic patients.
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BACKGROUND: Inhaled corticosteroids are powerful drugs that can suppress airway inflammation in asthmatic patients. Deposition of most of the inhaled corticosteroid occurs mainly in the central airways. However, a new hydrofluoroalkane formulation of beclomethasone dipropionate (HFA-BDP) is preferentially deposited in the distal airways. Inflammatory characteristics of induced sputum have been shown to differ in samples collected early after sputum induction compared with later. OBJECTIVE: To compare the effects of HFA-BDP and budesonide in a dry powder inhaler (DPI-BUD) on inflammatory cells and inflammatory cytokine expression in early and late induced sputa compared with placebo. METHODS: Seventeen patients with mild, intermittent bronchial asthma were randomly assigned to two treatment groups: eight patients received HFA-BDP and nine patients received DPI-BUD. Each patient was treated with one of the active treatments and placebo (for four weeks), with a two-week washout interval in between. Inflammatory cells and expression of interleukin (IL)-4 and IL-5 were measured in early and late induced sputa before and after active treatment, as well as before and after placebo treatment using immunocytochemistry and in situ hybridization. RESULTS: Compared with placebo, eosinophils were significantly reduced in both early and late induced sputa after HFA-BDP treatment (P<0.05), whereas DPI-BUD had a significant effect only on early induced sputum. Both HFA-BDP and DPI-BUD decreased IL-4 expression in early and late induced sputa, but the effect was more prominent with HFA-BDP. IL-5 expression was reduced in both early and late induced sputa after HFA-BDP treatment. DPI-BUD significantly decreased IL-5 expression in early but not in late induced sputum. The number of lymphocytes was not altered by either treatment. CONCLUSIONS: HFA-BDP reduced eosinophilic inflammation and T helper 2-type cytokine expression in both early and late induced sputa, whereas the effect of DPI-BUD on inflammation was predominantly demonstrated in early induced sputum. (+info)
Neurobehavioral effects and hormones profile among spray painters.
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A cross-sectional study was conducted in 25 spray painters and 35 control subjects to evaluate neurobehavioral function, and thyroid and reproductive hormones profile. This study indicated higher prevalence of psychological and neurological symptoms, and clinical findings among spray painters when compared with controls. Levels of TSH were significantly (p<0.01) elevated in spray painters over the control group (3.04 +/- 1.53 vs 1.88 +/- 1.07 microIU/ml, mean +/- SD), respectively. Two of the 25 spray painters acquired sub-clinical hypothyroidism, and one subject was detected with overt hypothyroidism. T4 levels were significantly (p<0.05) suppressed in spray painters while T3 was not changed significantly in both the groups. Reproductive hormones (LH, FSH, and testosterone) showed no significant changes in control and spray-painting group. However, two spray painters had abnormally high level of LH (26.43 and 12.22 IU/l; normal range 0.5-10 IU/l). These subjects were also found to have abnormally higher level of FSH (38.63 and 14.11 IU/l; normal range 1.3-11.5 IU/l). An isolated higher level of FSH (39.94 IU/l) was also observed in one spray painter. No abnormality in the level of LH was observed in control group while 3 subjects from this group had abnormally high level of FSH. Testosterone levels were under the normal range (3-12 ng/ ml) in both the groups. This study might suggest that spray painters are at risk of developing neurobehavioral, thyroid and reproductive problems. (+info)
The importance of nonelectrostatic materials in holding chambers for delivery of hydrofluoroalkane albuterol.
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INTRODUCTION: Electrostatic attraction of aerosolized particles to the inner walls of an aerosol holding chamber (HC) made from a nonconducting material can reduce medication delivery, particularly if there is a delay between actuation and inhalation. OBJECTIVE: Compare total emitted mass and fine-particle mass (mass of particles < 4.7 microm) of hydrofluoroalkane-propelled albuterol from similar-sized HCs manufactured from conductive material (Vortex), charge-dissipative material (AeroChamber Max), and nonconductive material (OptiChamber Advantage, ProChamber, Breathrite, PocketChamber, and ACE), with and without wash/rinse pretreatment of the HC interior with ionic detergent, and with 2-s and 5-s delays between actuation and inhalation. METHODS: All the HCs were evaluated (1) directly from their packaging (with no wash/rinse pretreatment) and (2) after washing with ionic detergent and rinsing and drip-drying. We used an apparatus that interfaced between the HC mouthpiece and the induction port of an 8-stage Andersen cascade impactor to simulate a poorly coordinated patient, with delays of 2 s and 5 s between actuation and inhalation/sampling, at 28.3 L/min. RESULTS: With the 2-s delay, the delivered fine-particle mass per actuation, before and after (respectively) wash/rinse pretreatment was: AeroChamber Max: 23.8 +/- 4.8 microg, 21.5 +/- 3.2 microg; Vortex: 16.2 +/- 1.7 microg, 15.5 +/- 2.0 microg; OptiChamber Advantage: 2.6 +/- 1.2 microg, 6.7 +/- 2.3 microg; ProChamber: 1.6 +/- 0.4 microg, 5.1 +/- 2.5 microg; Breathrite: 2.0 +/- 0.9 microg, 3.2 +/- 1.8 microg; PocketChamber: 3.4 +/- 1.6 microg, 1.7 +/- 1.6 microg; ACE: 4.5 +/- 0.9 microg, 5.4 +/- 2.9 microg. Similar trends, but greater reduction in aerosol delivery, were observed with the 5-s delay. Significantly greater fine-particle mass was delivered from HCs made from conducting or charge-dissipative materials than from those made from nonconductive polymers, even after wash/rinse pretreatment (p < 0.01). The fine-particle mass was also significantly greater from the AeroChamber Max than from the Vortex, irrespective of wash/rinse pretreatment or delay interval (p < 0.01). CONCLUSION: HCs made from electrically conductive materials emit significantly greater fine-particle mass, with either a 2-s or 5-s delay, than do HCs made from nonconducting materials, even with wash/rinse pretreatment. (+info)
Levalbuterol aerosol delivery with a nonelectrostatic versus a nonconducting valved holding chamber.
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BACKGROUND: Hydrofluoroalkane-propelled levalbuterol (Xopenex) aerosol is a recently approved formulation for delivery via metered-dose inhaler for the treatment or prevention of bronchospasm in adults, adolescents, and children > or = 4 years of age who have reversible obstructive airway disease. Valved holding chambers (VHCs) made from conventional polymers are susceptible to accumulation of electrostatic charge, which can be minimized by prewashing with ionic detergent, but it may be desirable to be able to use the product straight from the package, without pretreatment, especially during an exacerbation. METHODS: We studied the performance of the AeroChamber Plus and AeroChamber Max VHCs in delivering hydrofluoroalkane-propelled levalbuterol. Both VHCs were prewashed, rinsed, and drip-dried before testing. The AeroChamber Max is manufactured from charge-dissipative material and was therefore also evaluated without prewashing. Aerosol samples were collected at 28.3 L/min with an Andersen 8-stage cascade impactor, per the procedure specified in Chapter 601 of the United States Pharmacopeia. RESULTS: The mean +/- SD fine-particle mass (mass of aerosol particles < 4.7 microm aerodynamic diameter) values were 33.5 +/- 1.4 microg and 36.3 +/- 1.1 microg with the AeroChamber Max, without and with wash/rinse pretreatment, respectively, and 28.5 +/- 2.4 microg with the prewashed AeroChamber Plus. CONCLUSIONS: We think the small differences we observed are unlikely to be of clinical importance, given the inter-patient variability seen with inhaled drug delivery. The performance of the AeroChamber Max was substantially comparable whether or not it was prewashed. (+info)
Heliox-driven albuterol nebulization for asthma exacerbations: an overview.
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Our understanding of albuterol nebulization driven by helium-oxygen mixture (heliox) has matured with recent advances in clinical therapy, delivery systems, and understanding of dosing; this has led to substantial improvements in delivery as well as refinements of research protocols for asthma exacerbations. This review begins with heliox inhalation therapy and then addresses heliox as a driving gas for nebulization. Technical considerations are reviewed, including optimal gas mixtures, flow-rate adjustment factors, and nebulizer setup. (+info)
A method for increasing jet nebulizer delivery efficiency for aerosol drug delivery in ventilated newborns: an in vitro study.
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BACKGROUND: A substantial percentage of the aerosol produced by a nebulizer is lost down the expiratory limb of the ventilator circuit. We describe a method for the capture, return, and re-aerosolization of that undelivered aerosol. METHODS: We designed an expiratory-limb setup in which an "entraining jet" of gas accelerates unused aerosol and propels it toward an impaction surface. The deposited solution is then returned to the nebulizer reservoir via a feedback tube. As a result, more of the initial dose is delivered to the patient. The fraction of the dose delivered to a filter connected to a passive neonatal test lung was measured with and without the aerosol-recycling components activated. We used a deltaP (difference between the peak inspiratory pressure and the positive-end-expiratory pressure) of approximately 7.5 cm H2O, tidal volume of approximately 6 mL, respiratory rate of 40 breaths/min, and an inspiratory-expiratory ratio of 1:2.3. RESULTS: There was a statistically significant improvement with the feedback return to the reservoir, with up to nearly 60% more aerosol delivered. CONCLUSION: This improvement in aerosol delivery is encouraging, but more comprehensive studies are needed before such a device could be implemented clinically. (+info)
Pharmacokinetics of beclomethasone dipropionate in an hydrofluoroalkane-134a propellant system in Japanese children with bronchial asthma.
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BACKGROUND: Hydrofluoroalkane-134a (HFA) has been shown to be a safe replacement for chlorofluorocarbons (CFCs) as a pharmaceutical propellant, with the advantage that it has no ozone-depleting potential. This is the first report of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized solution formulation using an HFA propellant system (HFA-BDP) in Japanese children with bronchial asthma. METHODS: Plasma concentrations of beclomethasone 17-monopropionate (17-BMP),a major metabolite of BDP, following an inhaled dose of HFA-BDP (200 microg as four inhalations from 50 microg/actuation) in five Japanese children with bronchial asthma were quantified and analyzed by a non-compartmental analysis to obtain pharmacokinetic parameters. RESULTS: The area under the concentration-time curve from time zero to the last quantifiable time (AUC(0-t)) was 1659 +/- 850 pg x h/mL (arithmetic mean +/- standard deviation (SD)), the maximum concentration observed (C(max)) was 825 +/- 453 pg/mL and the apparent elimination half-life (t(1/2)) was 2.1 +/- 0.7 hours. The time to reach Cmax Tmax was 0.5 hours in all patients. No special relationship was observed between these parameters and age or body weight. These parameters were compared with the previously reported parameters of American children with bronchial asthma. The Japanese/American ratio of the geometric means of each parameter was 1.36 for AUC(0-t), 1.04 for Cmax and 1.4 for t(1/2). The median of Tmax was 0.5 hours in American patients as well as Japanese patients. CONCLUSIONS: The pharmacokinetics of HFA-BDP in Japanese children with bronchial asthma are reported for the first time and a similarity to those in American children is suggested. (+info)
Inhalation aspects of therapeutic aerosols.
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The pulmonary route of drug delivery can provide an excellent alternative to other routes both for local lung disease as well as systemic delivery. The year 2006 marks the 50th year since the invention of metered dose inhalers, yet inhalation is a very much underutilized route of delivery, possibly because inhalation drug development is perceived as being too difficult and expensive. However with proper knowledge these purported difficulties can be overcome. The process begins with identifying the target tissue and then utilizing technologies such as particle size adjustments through formulation techniques and delivery devices to most efficiently deliver the desired dose. There are a variety of new and existing inhaled excipients available to accomplish this goal. The active molecule can also be modified to increase solubility, decrease immunogenicity, and protect it from unwanted metabolism using PEGylation. Sustained release of an inhaled drug is also possible using biocompatible matrices such as oligolactic acid. (+info)