mometasone-furoate and Bronchial-Hyperreactivity

Exhaled nitric oxide (F(ENO)) and exhaled breath condensate (EBC) are noninvasive markers that directly measure airway inflammation and may potentially be useful in assessing asthma control and response to therapy.. To examine the time-dependent effects of inhaled corticosteroids on F(ENO) and EBC markers concomitantly with lung function and bronchial hyperresponsiveness.. Eleven steroid-naive adults with mild-to-moderate persistent asthma were treated with mometasone furoate dry powder inhaler, 400 microg/d, for 8 weeks, followed by a 4-week washout. Forced expiratory volume in 1 second (FEV1), the concentration of methacholine calculated to cause a 20% decline in FEV1 (PC20), F(ENO), EBC pH, and EBC nitrite measurements before, during, and after treatment were analyzed and compared.. The mean (SEM) FEV1 increased from 3.01 (0.13) L (82% predicted) to 3.24 (0.18) L (87% predicted) by week 8 (P < .05). The PC20 level increased from 1.28 (0.31) mg/mL to 2.99 (0.51) mg/mL by treatment week 8 (P < .05) and remained relatively stable through washout week 4 (P < .05). The F(ENO) level decreased from 31.1 (4.1) ppb to 20.6 (4.5) ppb by treatment week 1 (P < .01), remained low through treatment week 8 (P < .01), then trended back to the baseline level by washout week 1 (P < .01). The median EBC pH increased from 7.81 (interquartile range, 7.49-8.09) to 8.02 (interquartile range, 7.87-8.12) by treatment week 4, but did not achieve statistical significance. The EBC nitrite level decreased from 17.6 (1.6) microM to 9.3 (0.9) microM by treatment week 8 (P < .01), and remained low throughout washout week 4 (P < .05). There was a negative correlation between F(ENO) and PC20 (Spearman rank correlation coefficient = -0.50, P < .001).. The F(ENO) level responded the earliest to treatment and withdrawal of inhaled corticosteroids, whereas changes in EBC markers were delayed but more sustained.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Breath Tests; Bronchial Hyperreactivity; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Humans; Hydrogen-Ion Concentration; Inflammation; Lung; Male; Methacholine Chloride; Middle Aged; Mometasone Furoate; Nitrates; Nitric Oxide; Pregnadienediols; Young Adult

Controversy still exists as to whether or not inhaled beta (2)-adrenoceptor agonists and corticosteroids act synergistically in vivo. In this study, we have used a murine model of lung inflammation to study the synergistic effect of an inhaled beta (2)-adrenoceptor agonist (formoterol) and an inhaled corticosteroid (mometasone).. Actively sensitized mice were challenged with aerosolized ovalbumin, once a day, for three consecutive days. Three days after the last of the three challenges, a final allergen challenge was given. Allergen-induced increase in Penh was measured 4 h after the last challenge. A day after the last challenge, increased airway sensitivity to aerosolized methacholine was demonstrated and this was concomitant with an influx of inflammatory cells in the bronchoalveolar lavage fluids.. Mometasone (0.1 to 3 mg kg(-1)) given intranasally either an hour before or after the last allergen challenge, dose-dependently inhibited all parameters. When given intranasally either one or three hours after the last allergen challenge, but not an hour before, formoterol (1.5 to 150 microg kg(-1)) also dose-dependently inhibited most of the parameters to different degree. A synergistic effect on the allergen-induced increase in Penh was demonstrated for mometasone and formoterol given in combination, an hour after the challenge, at the following doses: mometasone/formoterol (in microg kg(-1)) 1/10, 1/100, 5/10, and 5/100.. Our results support the hypothesis that when given as a fixed combination, inhaled corticosteroid and beta (2)-adrenoceptor agonist act synergistically in vivo.

Topics: Administration, Intranasal; Adrenergic beta-Agonists; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoconstrictor Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Ethanolamines; Female; Formoterol Fumarate; Methacholine Chloride; Mice; Mice, Inbred BALB C; Mometasone Furoate; Ovalbumin; Pregnadienediols; Respiratory Function Tests; Respiratory Hypersensitivity; Time Factors