ABSTRACT
BACKGROUND AND OBJECTIVE: Inhaled medication administered via a metered dose inhaler (MDI) is often used to treat asthma. Hydrofluoroalkane (HFA) has replaced chlorofluorocarbons (CFC) as the propellant and these new MDI may contain alcohol. This raises concerns that their use may transiently increase breath ethanol concentration (BEC), thereby interfering with random breath testing. It was hypothesized that HFA-ethanol MDI may contribute to raising BEC above the legal limit. METHODS: The effect of a HFA-ethanol MDI on BEC was compared with that of CFC and placebo MDI and the effect of ingesting a standard amount of alcohol was also investigated. Asthmatic (n = 16) and normal control subjects (n = 15) were recruited for the double-blind, placebo-controlled study. Each subject used the three MDI in random sequence. BEC was measured at baseline and at 2, 5 and 15 min after inhalation of each MDI, using the Lion Alcometer SD-400TM. Spirometry was performed at baseline and 20 min after the last inhalation. An identical procedure was followed after alcohol consumption. RESULTS: Use of the HFA-ethanol MDI resulted in a significant increase in BEC from 0.002 to 0.0138 mg/100 mL (28 mg/100 mL of blood, P = 0.001) in asthmatics, and from 0.001 mg/100 mL to 0.016 mg/100 mL (33 mg/100 mL of blood, P = 0.002) in normal subjects. By 5 min, there were no significant differences in BEC of asthmatics (0.0031 mg/100 mL) and normal subjects (0.003 mg/100 mL), when compared with baseline (P > 0.2). CONCLUSIONS: BEC are transiently elevated after inhalation of HFA-ethanol MDI; however, by 5 min, BEC had already returned to baseline levels. Thus the effect of HFA-ethanol MDI on BEC is transient and would be negligible after 5 min.
Subject(s)
Aerosol Propellants/pharmacology , Asthma/drug therapy , Breath Tests , Ethanol/analysis , Hydrocarbons, Fluorinated , Nebulizers and Vaporizers , Substance Abuse Detection , Adult , Aged , Alcohol Drinking/blood , Australia , Chlorofluorocarbons , Double-Blind Method , Ethanol/blood , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Reproducibility of ResultsABSTRACT
This pilot study was designed to assess whether a synthetic matrix metalloproteinase (MMP) inhibitor has anti-inflammatory properties in mild asthma. Tumor necrosis factor alpha (TNFalpha) has been shown to be an important cytokine in the pathogenesis of allergic airway inflammatory responses, and its release can be inhibited by MMP inhibitors. Twelve atopic asthmatic subjects received the MMP inhibitor marimastat (5 mg) or placebo, twice daily for 3 weeks, separated by a 6-week washout period in a randomized, double-blind, cross-over manner. All subjects underwent an allergen inhalation provocation test to Dermatophagoides pteronyssinus before and after each study phase. Spirometry, exhaled NO (eNO) levels, differential sputum cell counts, an asthma symptom questionnaire, peak flow, and beta(2)-agonist usage were measured. Nine subjects completed the study, and, when compared with placebo, marimastat reduced bronchial hyper-responsiveness to inhaled allergen in these subjects from an allergen PC(20) of 22.2 AU/ml (95%CI 11.7-32.6) to 17.0 AU/ml (95%CI 7.6-26.4, P = 0.02). The marimastat phase showed a nonsignificant fall in sputum inflammatory cells. Marimastat did not modify eNO, FEV(1), asthma symptoms, or albuterol usage. In conclusion, airway responsiveness to allergen may be modified by a MMP inhibitor, perhaps via TNFalpha playing a role in airway inflammation and remodeling.
