AMP-BPT and His-BPT for Assessment of Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional

Summary: 
      Adenosine monophosphate (AMP) may reflect airway inflammation and hyperresponsiveness, but
      relationship between AMP and histamine (His, a conventional stimulus) bronchial provocation
      test (BPT) in asthma is not fully elucidated.

      The investigators aimed to compare both BPTs and determine their usefulness in reflecting
      changes of asthmatic symptoms.

      BPTs were performed in cross-over fashion, at 2-4day intervals. Cumulative doses eliciting
      20% FEV1fall (PD20FEV1), diagnostic performance and adverse events were compared. Patients
      with PD20FEV1 lower than geometric mean were defined as responders, otherwise poor
      responders. Patients with uncontrolled and partly controlled asthma, who maintained their
      original inhaled corticosteroids therapy, underwent reassessment of airway responsiveness and
      asthmatic symptoms 3 and 6 months after.
    

Detailed description: 
      Airway hyperresponsiveness, the pivotal feature of asthma, can be assessed by bronchial
      provocation tests (BPTs), which may elicit bronchoconstriction via inhalation of stimuli.
      Histamine has been a direct stimulus for inducing bronchoconstriction via vasodilation,
      eosinophil chemotaxis and tissue edema. Clinically, histamine BPT (His-BPT) has gained
      extensive application for decades owing to the assay sensitivity and feasibility, but could
      not ideally predict anti-inflammatory treatment outcomes in practice. Additionally, mild
      adverse events (flushing and hoarseness) and insufficient capacity of identifying
      exercise-induced asthma have hampered further clinical applications.

      Adenosine monophosphate (AMP) is an inflammatory mediator that serves as an indirect
      bronchial stimulus for detecting airway hyperresponsiveness in asthma. Compared with
      histamine, AMP may be pathophysiologically more relevant to airway inflammation and
      hyperresponsiveness and has been linked to presence and magnitude of atopy. However,
      differences of response to AMP-BPT and His-BPT in different asthma control levels and their
      associations with asthmatic symptom scores have not been fully elucidated.

      We hypothesized that asthmatic patients, regardless of control levels, responded
      differentially to AMP-BPT and His-BPT, and that greater reduction in airway responsiveness to
      AMP (esp. responders of AMP-BPT) was associated with significant symptom alleviation.
      Henceforth, we sought to: 1) compare diagnostic performance and safety of AMP-BPT and His-BPT
      in different asthma control levels; 2) determine the association between airway
      responsiveness and asthmatic symptom scores.

      Currently, His-BPT is recommended by the Chinese guideline and shares considerable similarity
      with methacholine (another conventional stimulus) BPT, we therefore did not perform the
      latter in this study.
    

Intervention name(s): inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)
Intervention type(s): Drug
Intervention description(s): Patients with uncontrolled and partly controlled asthma, following accomplishment of study 1, were invited to participate in observational study (study 2), which sought to determine usefulness of both BPTs in reflecting improvement of asthmatic symptoms following 3 and 6 months of moderate-dose ICSs treatment (400~800μg budesonide or equivalent). Patient continued to administer their original ICS during follow-up. During two follow-up visits (3 months apart), AMP-BPT, His-BPT and Hogg's symptom scores were reassessed.
Intervention MeSH terms: Fluticasone; Budesonide; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: adenosine monophosphate; histamine; bronchial provocation test; asthma symptom score; asthma control