PMID- 12464950
OWN - NLM
STAT- MEDLINE
DCOM- 20030109
LR  - 20190723
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 110
IP  - 6
DP  - 2002 Dec
TI  - Changes in sputum counts and airway hyperresponsiveness after budesonide: 
      monitoring anti-inflammatory response on the basis of surrogate markers of airway 
      inflammation.
PG  - 855-61
AB  - BACKGROUND: Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum 
      eosinophils might be useful in the individual adjustment of long-term asthma 
      management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) 
      provide greater protection against specific surrogate markers of airways 
      inflammation than other means. In addition, detailed longitudinal assessment of 
      changes in airway response with inhaled GCSs has never been carried out. 
      OBJECTIVES: We compared changes in AHR to inhaled methacholine and adenosine 
      5'-monophosphate (AMP) after budesonide treatment in a randomized, double-blind, 
      placebo-controlled, crossover study of patients with mild-to-moderate asthma. 
      Subsequently, we undertook a separate study to examine the time course of the 
      changes in AHR in more detail and the changes in sputum cell counts in relation 
      to budesonide treatment. METHODS: In the phase 1 of the study, patients undertook 
      bronchial provocation studies with increasing doubling concentrations of 
      methacholine (0.06 to 16 mg/mL) and AMP (3.125 to 800 mg/mL) before and after 
      budesonide 0.8 mg/daily for 3 weeks. The bronchial responses to the inhaled 
      agonists were expressed as the provocative concentration causing a 20% decline in 
      FEV(1) (PC(20)). In phase 2 of the study, patients attended the laboratory on 12 
      separate occasions to investigate changes in PC(20) methacholine, PC(20) AMP, and 
      sputum cell counts before, during, and after withdrawal of therapy with inhaled 
      budesonide 0.8 mg/daily for 6 weeks. RESULTS: Budesonide treatment for 3 weeks 
      significantly attenuated the constrictor response by 0.8 +/- 0.3 doubling doses 
      for methacholine and by 2.6 +/- 0.5 doubling doses for AMP. These changes were 
      significantly different from each other (P =.003). Significant variation in 
      PC(20) methacholine (P <.05) value, PC(20) AMP (P <.001) value, percentage of 
      sputum eosinophils (P <.001), and percentage of sputum epithelial cells (P <.001) 
      were observed throughout the longitudinal assessment of changes in airway 
      response to budesonide. Compared with the other surrogate markers, PC(20) AMP 
      appears to be useful in promptly detecting early inflammatory changes of the 
      asthmatic airways; a significant change of 1.6 +/- 0.3, 2.2 +/- 0.3, and 2.8 +/- 
      0.3 doubling doses of PC(20) AMP was observed at 1, 4, and 6 weeks, respectively, 
      in the course of budesonide treatment. CONCLUSIONS: The present findings 
      underline the exquisite selectivity of diverse surrogate markers of airway 
      inflammation in response to inhaled budesonide. When compared with that to the 
      other markers, AHR to inhaled AMP is an early and sensitive indicator of the 
      beneficial anti-inflammatory effects of topical GCSs.
FAU - Prosperini, Gaetano
AU  - Prosperini G
AD  - Dipartimento di Medicina Interna e Specialistica, University of Catania, Catania, 
      Italy.
FAU - Rajakulasingam, Kajakulasingam
AU  - Rajakulasingam K
FAU - Cacciola, Rossella R
AU  - Cacciola RR
FAU - Spicuzza, Lucia
AU  - Spicuzza L
FAU - Rorke, Steuart
AU  - Rorke S
FAU - Holgate, Stephen T
AU  - Holgate ST
FAU - Di Maria, Giuseppe U
AU  - Di Maria GU
FAU - Polosa, Riccardo
AU  - Polosa R
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0W5ETF9M2K (Methacholine Chloride)
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - 51333-22-3 (Budesonide)
SB  - IM
MH  - Adenosine Monophosphate/pharmacology
MH  - Adult
MH  - Asthma/*drug therapy/physiopathology
MH  - Bronchial Hyperreactivity/*drug therapy
MH  - Budesonide/*therapeutic use
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Female
MH  - Forced Expiratory Volume
MH  - Humans
MH  - Male
MH  - Methacholine Chloride/pharmacology
MH  - Middle Aged
MH  - Sputum/*cytology
EDAT- 2002/12/05 04:00
MHDA- 2003/01/10 04:00
CRDT- 2002/12/05 04:00
PHST- 2002/12/05 04:00 [pubmed]
PHST- 2003/01/10 04:00 [medline]
PHST- 2002/12/05 04:00 [entrez]
AID - S0091674902014665 [pii]
AID - 10.1067/mai.2002.130050 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2002 Dec;110(6):855-61. doi: 10.1067/mai.2002.130050.