Clinical trial NCT02318043: AMP-BPT and His-BPT for Assessment of Asthma
Official title: Is Adenosine Monophosphate Superior to Histamine for Bronchial Provocation Test in Evaluation of Asthma?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: adenosine monophosphate
histamine
bronchial provocation test
asthma symptom score
asthma control
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
First posted: 2014-12-17
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. aged 18\~65 years;
2. nil respiratory infection within 3 weeks;
3. normal chest radiography;
4. baseline FEV1\>60% predicted;
5. withdrawn from, if any, oral leukotriene modifiers, corticosteroid or anti-histamine for 5 days, oral xanthenes or long-acting bronchodilators for 2 days, inhaled corticosteroids (ICSs) for 24 hours, and salbutamol for 6 hours

Exclusion Criteria:

1. FEV1 fall ≥20% following saline inhalation;
2. other chronic lower respiratory diseases (i.e. COPD);
3. severe systemic diseases (i.e. uncontrolled hypertension, malignancy);
4. limited understanding.

For healthy subjects, they had to be aged 18\~65 years and had nil respiratory infection within 3 weeks, systemic diseases and had normal lung function.

Primary outcomes:
measure: Cumulative dose eliciting 20% fall in FEV1 (PD20FEV1)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Asthma symptom score as proposed by Hoggs et al
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
Secondary outcomes:
measure: Baseline spirometry (FVC, FEV1, FEV1/FVC, MMEF, PEF)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Maximal decrease in FVC following bronchial provocation (expressed as percentage)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Maximal decrease in FEV1 following bronchial provocation (expressed as percentage)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Maximal decrease in MMEF following bronchial provocation (expressed as percentage)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Maximal decrease in PEF following bronchial provocation (expressed as percentage)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Assay positivity of AMP-BPT and His-BPT (expressed as percentage)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Diagnostic performance of AMP-BPT and His-BPT (area under the receiver operation characteristic curve, sensitivity, specificity, Youden index)
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Changes in post-treatment asthma symptom scores
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
measure: Changes in post-treatment PD20FEV1
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
Other outcomes:
measure: incidence of adverse events of both BPTs
timeFrame: up to 12 months (Jan 2007 to Dec 2007)
Locations:
Study officials:
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