No effect of inhaled budesonide on the response to inhaled ozone in normal subjects.

Inhalation of ozone in normal subjects causes a neutrophilic inflammatory response in the airways. Pretreatment with inhaled corticosteroids reduces the inflammatory response to inhaled ozone in dogs. We undertook a double-blind, randomized, placebo-controlled, crossover study to investigate the effects of 2 wk of treatment with inhaled budesonide 800 microg twice daily or placebo prior to ozone exposure in humans. Fifteen (six male; mean age, 31.1 +/- 2.1 yr) healthy nonsmokers were exposed to 400 parts per billion (ppb) ozone for 2 h with intermittent exercise. Spirometry, exhaled carbon monoxide (CO) and nitric oxide (NO) levels, measurement of methacholine reactivity, and collection of exhaled air condensate and induced sputum samples were performed at baseline, preexposure, and at intervals up to 24 h postexposure. Ozone exposure led to significant decreases in spirometry and increased methacholine reactivity and sputum neutrophils and myeloperoxidase (MPO). There were no changes in exhaled NO and CO levels, or exhaled breath nitrite after ozone exposure. There were no differences in any of the parameters after treatment with budesonide compared with placebo, and no differences in the response to ozone between treatment groups. We conclude that a high dose of inhaled corticosteroid does not protect against the effects of ozone exposure in normal subjects.

[1]  J. Fahy,et al.  The effect of methacholine challenge on the cellular composition of induced sputum. , 1999, The Journal of allergy and clinical immunology.

[2]  I. Horváth,et al.  Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma. , 1998, American journal of respiratory and critical care medicine.

[3]  P. Barnes,et al.  Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stress , 1998, Thorax.

[4]  B. Beghé,et al.  Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease , 1998, Thorax.

[5]  K. Chung,et al.  Effect of inhaled endotoxin on induced sputum in normal, atopic, and atopic asthmatic subjects , 1998, Thorax.

[6]  H. Magnussen,et al.  Changes in sputum composition between two inductions performed on consecutive days. , 1998, Thorax.

[7]  P. Barnes,et al.  Effect of repeated sputum induction on cell counts in normal volunteers. , 1998, Thorax.

[8]  P. Barnes,et al.  Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. , 1997, American journal of respiratory and critical care medicine.

[9]  J. M. Cousin,et al.  Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. , 1996, Journal of immunology.

[10]  C. Scannell,et al.  Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation. , 1996, American journal of respiratory and critical care medicine.

[11]  P. Barnes,et al.  Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. , 1996, American journal of respiratory and critical care medicine.

[12]  P. Sterk,et al.  Effect of ozone exposure on maximal airway narrowing in non-asthmatic and asthmatic subjects. , 1995, Clinical science.

[13]  P. O'Byrne,et al.  The effects of an inhaled corticosteroid on oxygen radical production by bronchoalveolar cells after allergen or ozone in dogs. , 1995, European journal of pharmacology.

[14]  K. Chung,et al.  Expression of inducible nitric oxide synthase mRNA in Brown Norway rats exposed to ozone: effect of dexamethasone. , 1995, European journal of pharmacology.

[15]  H. Boushey,et al.  Analysis of induced sputum after air and ozone exposures in healthy subjects. , 1995, Environmental research.

[16]  D M Hansell,et al.  Elevated levels of exhaled nitric oxide in bronchiectasis. , 1995, American journal of respiratory and critical care medicine.

[17]  D. Yates,et al.  Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections. , 1995, The European respiratory journal.

[18]  P. O'Byrne,et al.  Effect of inhaled budesonide on ozone-induced airway hyperresponsiveness and bronchoalveolar lavage cells in dogs. , 1994, Journal of applied physiology.

[19]  D. Laskin,et al.  Production of nitric oxide by rat type II pneumocytes: increased expression of inducible nitric oxide synthase following inhalation of a pulmonary irritant. , 1994, American journal of respiratory cell and molecular biology.

[20]  P. J. Barnes,et al.  Increased nitric oxide in exhaled air of asthmatic patients , 1994, The Lancet.

[21]  D. Laskin,et al.  Enhanced production of nitric oxide by rat alveolar macrophages after inhalation of a pulmonary irritant is associated with increased expression of nitric oxide synthase. , 1993, Journal of immunology.

[22]  J. Balmes,et al.  Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy. , 1993, The American review of respiratory disease.

[23]  M. Currie,et al.  A fluorometric assay for the measurement of nitrite in biological samples. , 1993, Analytical biochemistry.

[24]  E. Weitzberg,et al.  Increased amount of nitric oxide in exhaled air of asthmatics. , 1993, The European respiratory journal.

[25]  C. Cross,et al.  Corticosteroid administration modifies ozone-induced increases in sheep airway blood flow. , 1992, The American review of respiratory disease.

[26]  S Moncada,et al.  Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. , 1991, Biochemical and biophysical research communications.

[27]  D. House,et al.  Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung. , 1991, American journal of respiratory cell and molecular biology.

[28]  D. House,et al.  Ozone-induced inflammation in the lower airways of human subjects. , 1989, The American review of respiratory disease.

[29]  H. Boushey,et al.  O3-induced change in bronchial reactivity to methacholine and airway inflammation in humans. , 1986, Journal of applied physiology.

[30]  D. House,et al.  Pulmonary effects of ozone exposure during exercise: dose-response characteristics. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[31]  H. Boushey,et al.  Effect of ozone on bronchial reactivity in atopic and nonatopic subjects. , 2015, The American review of respiratory disease.

[32]  S. Spector,et al.  Standardization of bronchial inhalation challenge procedures. , 1975, The Journal of allergy and clinical immunology.