title: Airway hyperresponsiveness to mannitol and methacholine and exhaled nitric oxide in children with asthma.
abstract: OBJECTIVE
  Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and obstruction. AHR to stimuli that indirectly cause bronchial smooth muscle (BSM) contractions via release of endogenous mediators is thought to better reflect airway inflammation than AHR to stimuli that act directly on BSM. Fractional exhaled nitric oxide (FeNO) is a useful parameter for noninvasive clinical airway inflammation assessments. Accordingly, this study aimed to examine the relationships of mannitol and methacholine challenge test outcomes with FeNO and the influence of inhaled corticosteroid treatment in children with asthma.
  
  
  METHODS
  One hundred thirty-four asthmatic children (89 males; ages: 5-17 years, median: 9 years) underwent spirometry, FeNO measurement, serum total/specific IgE testing, and blood eosinophil count. All subjects were challenged with mannitol dry powder (MDP; AridolH, Pharmaxis, Australia) and methacholine at 7-day intervals. Data of steroid-treated and steroid-naïve children were compared.
  
  
  RESULTS
  Positive responses to MDP and methacholine challenge tests were observed in 74.6% and 67.2% of total subject group, respectively, and 72 children had positive response to both challenge tests. The median FeNO level, response-dose ratio (RDR) of PC20methacholine, and RDR of PD15MDP were significantly higher in the steroid-treated group than in the steroid-naïve group (p < 0.001, 0.226, and 0.004, respectively). FeNO levels associated significantly with PD15MDP and RDR PD15MDP in total subject populations (p = 0.016 and 0.003, respectively); however, a significant correlation between FeNO and RDR PD15MDP was observed only in the steroid-naïve group.
  
  
  CONCLUSIONS
  Compared with AHR to methacholine, AHR to MDP more closely reflected the level of FeNO in steroid-naïve asthmatic children.
authors.affiliation: a Department of Pediatrics , Severance Children's Hospital , Seoul , Republic of Korea.
authors.forename: Young A
authors.initials: YA
authors.lastname: Park
authors.affiliation: a Department of Pediatrics , Severance Children's Hospital , Seoul , Republic of Korea.
authors.forename: Hyun Bin
authors.initials: HB
authors.lastname: Park
authors.affiliation: b Gangnam Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , Republic of Korea.
authors.forename: Yoon Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: a Department of Pediatrics , Severance Children's Hospital , Seoul , Republic of Korea.
authors.forename: In Sook
authors.initials: IS
authors.lastname: Sul
authors.affiliation: a Department of Pediatrics , Severance Children's Hospital , Seoul , Republic of Korea.
authors.forename: Seo Hee
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: a Department of Pediatrics , Severance Children's Hospital , Seoul , Republic of Korea.
authors.forename: Hye Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: a Department of Pediatrics , Severance Children's Hospital , Seoul , Republic of Korea.
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.affiliation: b Gangnam Severance Hospital, Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , Republic of Korea.
authors.forename: Kyu-Earn
authors.initials: KE
authors.lastname: Kim
authors.affiliation: a Department of Pediatrics , Severance Children's Hospital , Seoul , Republic of Korea.
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Sohn
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001315:Australia; D001944:Breath Tests / Q000379:methods*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D016210:Methacholine Chloride / Q000008:administration & dosage; D009569:Nitric Oxide / Q000032:analysis*; D013147:Spirometry
chemical_list: D000305:Adrenal Cortex Hormones; D016210:Methacholine Chloride; D009569:Nitric Oxide; D007073:Immunoglobulin E; D008353:Mannitol
keywords: Airway hyperresponsiveness; childhood asthma exhaled nitric oxide; mannitol dry powder; methacholine