Time-dependent effects of inhaled corticosteroids on lung function, bronchial hyperresponsiveness, and airway inflammation in asthma

Ann Allergy Asthma Immunol. 2009 Jul;103(1):31-7. doi: 10.1016/S1081-1206(10)60140-8.

Abstract

Background: 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.

Objective: To examine the time-dependent effects of inhaled corticosteroids on F(ENO) and EBC markers concomitantly with lung function and bronchial hyperresponsiveness.

Methods: 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.

Results: 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).

Conclusion: The F(ENO) level responded the earliest to treatment and withdrawal of inhaled corticosteroids, whereas changes in EBC markers were delayed but more sustained.

Trial registration: ClinicalTrials.gov NCT00711165.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / pharmacology*
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Anti-Allergic Agents / adverse effects
  • Anti-Allergic Agents / pharmacology
  • Anti-Allergic Agents / therapeutic use
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma / drug therapy
  • Asthma / metabolism
  • Asthma / physiopathology
  • Breath Tests
  • Bronchial Hyperreactivity / drug therapy
  • Bronchial Hyperreactivity / metabolism
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Female
  • Forced Expiratory Volume / drug effects
  • Forced Expiratory Volume / physiology
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / physiology
  • Male
  • Methacholine Chloride / pharmacology
  • Middle Aged
  • Mometasone Furoate
  • Nitrates / metabolism
  • Nitric Oxide / metabolism
  • Pregnadienediols / adverse effects
  • Pregnadienediols / pharmacology
  • Pregnadienediols / therapeutic use
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Anti-Allergic Agents
  • Anti-Inflammatory Agents
  • Nitrates
  • Pregnadienediols
  • Mometasone Furoate
  • Methacholine Chloride
  • Nitric Oxide

Associated data

  • ClinicalTrials.gov/NCT00711165