Aerosolized bronchodilator drugs are commonly used for treatment of horses with chronic obstructive pulmonary disease. Relative efficacy of sympathomimetic and parasympatholytic bronchodilators for relief of acute airway obstruction and improvement of pulmonary gas exchange was compared in 6 horses with COPD. Physical examination, arterial and venous blood gas analysis and measurement of end-tidal CO₂ tension were performed at time zero, 30 minutes, 1, 2, 3 and 4 hours after administration of aerosol ipratropium (0.35 μg/kg), albuterol (1 μg/kg) or placebo via an equine Aeromask and metered dose inhaler. Physiologic shunt fraction (QS/QT), alveolar dead space fraction (VD/VT) and alveolar to arterial oxygen tension difference (p(A-a)O₂) were calculated using standard formulas. At time zero, horses demonstrated severe respiratory compromise and marked alterations in pulmonary gas exchange, indicative of alveolar hypoventilation, VA/Q mismatching and diffusion impairment. Ipratropium treatment significantly (p< 0.05) reduced arterial CO₂ tension and end-tidal CO₂ tension toward normal, but significantly increased p(A-a)O₂ from baseline. The change in paCO₂ after ipratropium treatment was significantly different from albuterol and placebo treatment groups. There were no significant changes in response variables after albuterol and there were no treatment by time interactions. These results indicate that, under the conditions of this study, ipratropium (0.35 μg/kg) improved alveolar ventilation and had superior bronchodilator efficacy than albuterol (1 μg/kg) in horses with severe COPD. Marked impairment of pulmonary gas exchange persisted after bronchodilators, emphasizing that anti-inflammatory therapy and environmental control are also necessary for effective treatment of severe equine COPD. / Master of Science

No description available.

Class of 2015 Abstract / Objectives: American residents travel to Mexico to purchase medications, like albuterol inhalers, for 1/3 to 1/5 of the US price without prescription requirements. A previous bioequivalence study found clinical differences (P less than 0.05) between Ventolin and Assal, two Mexican manufactured albuterol inhaler brands. What other differences are there among such inhalers when we test more brands and analyze pharmaceutical qualities like respirable mass? This study seeks to provide some reasonable expectations for a medical tourist of Mexico who purchases albuterol metered dose inhalers (MDIs) by comparing the product performance of some of the brands available to the consumers in Mexico. Methods: This study examined the performance of albuterol MDIs obtained from pharmacies in Nogales, Mexico. At least two units were purchased for each of the following brands: Xeneric-S, Victory, Ventolin (GlaxoSmithKline), Assal, and Sacrusyt. At least two lot numbers of each brand were included, with the exception of Sacrusyt, for which a second lot was unavailable at the purchase times. Sample MDIs were compared to US-purchased albuterol inhalers, Proventil and Ventolin. Total dose and respirable mass were determined for each MDI. These parameters were measured by actuating each inhaler into a USP throat, coupled to a cascade impactor, which separates drug particles based on aerodynamic particle size. Particles with an aerodynamic diameter larger than 4.7 micrometers are considered non-respirable, while particles less than 4.7 micrometers are considered respirable and the total of respirable and non-respirable particles is the respirable mass. The total dose delivered is determined by calculating the amount of drug that deposits onto the throat and the impactor. Quantification of albuterol was determined by high performance liquid chromatography (HPLC). In brief, the HPLC assay utilized an Apollo C18 column with a mobile phase of 1 percent phosphoric acid:methanol (77:23) at a flow rate of 0.75mL/min; UV detection was at 225 nm. Results: Every inhaler was sold in a Spanish-labeled box containing a single page instruction insert and every inhaler label had a visible lot number, expiration date, and noted a 100 microgram dose. Listed manufacturing locations included China, Mexico, India, and Spain. All of the MDIs were purchased for about $3 to $5 each except for non-US Ventolin ($10-$20 each). The measurements of total dose and respirable mass among the five Mexican purchased brands of inhalers varied widely. The MDIs’ average total doses ranged from 57 to 75 micrograms per actuation, while the average total dose of the US purchased MDIs was 79 to 82 micrograms. The respirable mass of the non-US MDIs was more similar. Among the study MDIs, respirable mass ranged from 28 to 41 micrograms, which compares to 38 to 42 micrograms for the two US branded albuterol inhalers. To further investigate the variability among the study MDIs, student t-tests were performed to compare the mean respirable mass for each brand to that of the other four brands. All comparisons were significantly different (p less than 0.05) except for two (Sacrusyt vs Assal, p equals 0.89; Xeneric vs Ventolin, p equals 0.98). Conclusions: Since significant pharmaceutical variability was found among the albuterol MDIs evaluated in this study, clinicians and patients should be conscious of possible differences in quality, therapeutic efficacy, and safety for albuterol MDIs obtained in Mexico. Sample MDIs compared to each other were statistically different in total dose and respirable mass. Thus a patient who has used US MDIs before can’t necessarily expect to get the same dose from non-US brands.

Class of 2012 Abstract / Specific Aims: We sought to determine the influence of genetic variation of ADRB2 on the airway response to albuterol in patients with CF when compared to matched healthy controls at baseline and at 60 minutes following the administration of albuterol (2.5mg diluted in 3ml normal saline). Methods: Baseline pulmonary function (forced vital capacity, FVC, forced expiratory flow in 1-second, FEV1, mid-maximal expiratory flow, MMF, and forced expiratory flow at 50% of the FVC) was assessed in 17 patients with CF and 31 healthy subjects. Main Results: As expected, the healthy group had higher baseline pulmonary function when compared to the CF group (FVC=97±3 vs. 83±5; FEV1=95±3 vs. 72±6; MMF=90±4 vs. 54±8, % predicted for healthy and CF, respectively, mean±SE, p<0.05 for all. We compared Arg16Arg to Arg16Gly/Gly16Gly subjects. There was no effect of genotype on the response to albuterol in healthy subjects. However, in the CF group, we found that the Arg16Arg group (n=6) had an attenuated response to β-agonist when compared to the Gly-containing group (n=11) (FVC=0±0.9 vs. 6±3: FEV1=3±1 vs. 7±4: MMF=12±3 vs. 12±5 % change, for Arg16Arg and Gly-containing groups, respectively, p<0.05 for FVC, p=0.06 for FEV1). Conclusions: These results demonstrate a differential response to β-agonists according to genetic variation of the ADRB2 at amino acid 16. Due to the differences in FVC and FEV1 but not in MMF, these data suggest that the genetic difference in airway function is primarily in bronchodilation of the larger airways.

Background: Evidence on aerosol delivery via tracheostomy is lacking. The purpose of this study was to evaluate the effect of aerosol device and administration technique on drug delivery in a simulated spontaneously breathing pediatric model with tracheostomy. Methods: Delivery efficiencies during spontaneous breathing with assisted and unassisted administration techniques were compared using the jet nebulizer (JN- MicroMist), vibrating mesh nebulizer (VMN- Aeroneb Solo) and pressurized metered-dose inhaler (pMDI- ProAirHFA). The direct administration of aerosols in spontaneously breathing patients (unassisted technique) was compared to administration of aerosol therapy via a manual resuscitation bag (assisted technique) attached to the aerosol delivery device and synchronized with inspiration. An in-vitro lung model consisted of an uncuffed tracheostomy tube (4.5 mmID) was attached to a collecting filter (Respirgard) which was connected to a dual-chamber test lung (TTL) and a ventilator (Hamilton). The breathing parameters of a 2 years-old child were set at an RR of 25 breaths/min, a Vt of 150 mL, a Ti of 0.8 sec and PIF of 20 L/min. Albuterol sulfate was administered with each nebulizer (2.5 mg/3 ml) and pMDI with spacer (4 puffs, 108 µg/puff). Each aerosol device was tested five times with both administration techniques (n=5). Drug collected on the filter was eluted with 0.1 N HCl and analyzed via spectrophotometry. Results: The amount of aerosol deposited in the filter was quantified and expressed as inhaled mass and inhaled mass percent. The pMDI with spacer had the highest inhaled mass percent, while the VMN had the highest inhaled mass. The results of this study also found that JN had the least efficient aerosol device used in this study. The trend of higher deposition with unassisted versus assisted administration of aerosol was not significant (p>0.05). Conclusions: Drug deposited distal to the tracheostomy tube with JN was lesser than either VMN or pMDI. Delivery efficiency was similar with unassisted and assisted aerosol administration technique in this in vitro pediatric model.

Hypertension, or chronic blood pressure elevation, affects approximately a third of American adults and is responsible for $70 billion dollars annually in medical costs. Recent studies have attempted to identify genetic variants that influence cardiopulmonary function, including blood pressure regulation. This study seeks to determine whether a polymorphism in position -182 of the gene encoding the phenylethanolamine N-methyltransferase (PNMT) enzyme, which converts norepinephrine to epinephrine, influences catecholamine levels and cardiovascular function. Secondly, this study seeks to explore whether a polymorphism at amino acid position 16 of the beta-2 adrenergic receptor (B2AR) affects the cardiovascular response to albuterol in healthy individuals; this study also explores the pulmonary response to albuterol in healthy subjects and patients with cystic fibrosis according to B2AR genotype. All subjects were genotyped and stratified according to genotype. Baseline measurements were taken. Albuterol was administered via nebulizer. Cardiopulmonary measurements were taken again at 30-, 60-, and 90- minutes post-albuterol administration. This study found that the PNMT polymorphism at position -182 influences circulating epinephrine, the epinephrine:norepinephrine ratio, and cardiac output. The B2AR polymorphism at amino acid position 16 affects the percent change in systemic vascular resistance in response to albuterol administration in healthy subjects. Furthermore, this study found that the B2AR polymorphism at amino acid 16 affects the change in forced vital capacity following albuterol administration in cystic fibrosis subjects.

Class of 2012 Abstract / Specific Aims: We sought to determine the influence of genetic variation of ADRB2 on the airway response to albuterol in patients with CF when compared to matched healthy controls at baseline and at 60 minutes following the administration of albuterol (2.5mg diluted in 3ml normal saline). Methods: Baseline pulmonary function (forced vital capacity, FVC, forced expiratory flow in 1-second, FEV1, mid-maximal expiratory flow, MMF, and forced expiratory flow at 50% of the FVC) was assessed in 17 patients with CF and 31 healthy subjects. Main Results: As expected, the healthy group had higher baseline pulmonary function when compared to the CF group (FVC=97±3 vs. 83±5; FEV1=95±3 vs. 72±6; MMF=90±4 vs. 54±8, % predicted for healthy and CF, respectively, mean±SE, p<0.05 for all. We compared Arg16Arg to Arg16Gly/Gly16Gly subjects. There was no effect of genotype on the response to albuterol in healthy subjects. However, in the CF group, we found that the Arg16Arg group (n=6) had an attenuated response to β-agonist when compared to the Gly-containing group (n=11) (FVC=0±0.9 vs. 6±3: FEV1=3±1 vs. 7±4: MMF=12±3 vs. 12±5 % change, for Arg16Arg and Gly-containing groups, respectively, p<0.05 for FVC, p=0.06 for FEV1). Conclusions: These results demonstrate a differential response to β-agonists according to genetic variation of the ADRB2 at amino acid 16. Due to the differences in FVC and FEV1 but not in MMF, these data suggest that the genetic difference in airway function is primarily in bronchodilation of the larger airways.

No description available.

Tong Hoi Yee. / "July, 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 237-253). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Estudamos o efeito do tratamento com salbutamol em dois regimes: diário (DS) e administrado a intervalos de 96 horas (IS) em camundongos balb/c sensibilizados com injeções intraperitoneais de uma solução de ovoalbumina (OVA) adsorvida em hidróxido de alumínio, e desafiada com inalações de ovoalbumina a 1%. O grupo controle SAL recebeu injeções i.p. de salina e desafios inalatórios de sallina. A partir do 34o dia, os animais OVA foram tratados com salbutamol via inalatória 10 mg/ml durante 15 minutos nos dois regimes descritos. Os animais foram sacrificados no 60o dia, que corresponde a 48 horas após o último desafio antigênico. Após os camundongos serem anestesiados com pentobarbital sódico via i.p., eles foram traqueostomizados e entubados e sacrificados com secção da Aorta abdominal. Então, procedeu-se com a coleta do lavado broncoalveolar para a quantificação de leucócitos. Coletamos os tecidos pulmonares para a avaliação do processo inflamatório por quantificação de células linfomononucleares (LMN) e eosinófilos EPO+, essa última com marcação citoquímica. Além disso, estudamos a influência do tratamento adrenérgico sobre o IgE anafilático. O modelo de inflamação (grupo OVA) produziu significativo aumento do número de células totais, de eosinófilos e de neutrófilos observados na avaliação de lavado broncoalveolar. Além disso, houve nesse grupo processo inflamatório na parede de vias aéreas, caracterizada por um infiltrado linfomononuclear e com presença de eosinófilos. O nosso processo de indução de inflamação também recrutou eosinófilos para o septo alveolar. O tratamento com salbutamol diário produziu uma queda significativa do processo inflamatório no BAL, principalmente de neutrófilos e eosinófilos, enquanto que o tratamento intermitente produziu redução significativa apenas de neutrófilos. O tratamento com salbutamol a cada 96 horas (IS) promoveu uma queda significativa de células LMN quantificadas no septo alveolar, mas não atingindo valores do grupo salina (NS). Ambos os tratamentos com salbutamol produziu redução significativa de células EPO+ no parênquima pulmonar (P < 0,05). Apesar das alterações no processo celular, o salbutamol não influenciou na expressão de anticorpos IgE anafiláticos a OVA. Assim, podemos concluir que o salbutamol apresenta atividade imunomoduladora, observada por redução de eosinófilos no BAL e no parênquima pulmonar, apesar de não atingir valores semelhantes aos animais do grupo salina / We studied the effects of salbutamol treatment in two regimen: diary (DS) and at interval of 96 hours (IS) in ovalbumin sensitized (OVA) balb/c mice. The control group (NS) received i.p. injections and aerosol challenge with normal saline. Starting at day 34 the OVA animals were treated with 10mg/ml salbutamol by inhalation during 15 minutes per day in both regimen: DS and IS. The mice were sacrificed at day 60 that corresponded the fourthly eight hours after last OVA and/or salbutamol exposure. At experimental day, mice were anesthetized with i.p. injection of sodium pentobarbital, tracheostomized, entubed and the abdominal aorta sectioned. We followed with collecting of bronchoalveolar lavage (BAL) and lungs to histopathology studies. In the BAL, total cells and differential leukocytes were quantified, while in the lung sections, the EPO+ and LMN in airways wall and parenchyma septa were evaluated. Also, we sampled the blood to evaluate the effects of salbutamol on anaphylactic IgE antibodies expression. The inflammatory model (OVA animals) produced a significant increase of BAL total cells, BAL eosinophils and neutrophils, and LMN cells and EPO+ eosinophils in the airways and in the parenchyma. Diary salbutamol treatment decrease significantly BAL eosinophils and neutrophils, while the IS group showed a diminution of BAL neutrophils and LMN cells in the alveolar septum. Both salbutamol treatments produced significant decline of EPO+ cells in the lung parenchyma. Despite the changes in the cellular patterns, the salbutamol did not affect the IgE antibodies expression. So, we can concluded that salbutamol present an immunomodulatory activity observed by reduction of eosinophils in the BAL and lung parenchyma, but did not achieve the values of saline control group