Asthma
Conditions
Keywords
adenosine monophosphate, histamine, bronchial provocation test, asthma symptom score, asthma control
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.
Interventions
DRUGinhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)
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.
Sponsors
Guangzhou Institute of Respiratory Disease
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asthma symptom score as proposed by Hoggs et al | up to 12 months (Jan 2007 to Dec 2007) | Asthma symptom score recorded within 1 week, with the highest possible score of 42 for the whole week |
| Cumulative dose eliciting 20% fall in FEV1 (PD20FEV1) | up to 12 months (Jan 2007 to Dec 2007) | Cumulative dose eliciting 20% fall in FEV1 (PD20FEV1), reported as |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximal decrease in FVC following bronchial provocation (expressed as percentage) | up to 12 months (Jan 2007 to Dec 2007) | Maximal decrease in FVC following bronchial provocation, expressed as percentage as compared with baseline levels |
| Maximal decrease in FEV1 following bronchial provocation (expressed as percentage) | up to 12 months (Jan 2007 to Dec 2007) | Maximal decrease in FEV1 following bronchial provocation, expressed as percentage as compared with baseline levels |
| Maximal decrease in MMEF following bronchial provocation (expressed as percentage) | up to 12 months (Jan 2007 to Dec 2007) | Maximal decrease in MMEF following bronchial provocation, expressed as percentage as compared with baseline levels |
| Maximal decrease in PEF following bronchial provocation (expressed as percentage) | up to 12 months (Jan 2007 to Dec 2007) | Maximal decrease in PEF following bronchial provocation, expressed as percentage as compared with baseline levels |
| Diagnostic performance of AMP-BPT and His-BPT (area under the receiver operation characteristic curve, sensitivity, specificity, Youden index) | up to 12 months (Jan 2007 to Dec 2007) | area under the receiver operation characteristic curve, sensitivity, specificity, Youden index |
| Changes in post-treatment asthma symptom scores | up to 12 months (Jan 2007 to Dec 2007) | post-treatment minus pre-treatment asthma symptom score |
| Changes in post-treatment PD20FEV1 | up to 12 months (Jan 2007 to Dec 2007) | post-treatment minus pre-treatment PD20FEV1 |
| Assay positivity of AMP-BPT and His-BPT (expressed as percentage) | up to 12 months (Jan 2007 to Dec 2007) | Assay positivity of AMP-BPT and His-BPT, expressed as percentage |
| Baseline spirometry (FVC, FEV1, FEV1/FVC, MMEF, PEF) | up to 12 months (Jan 2007 to Dec 2007) | FVC, FEV1, FEV1/FVC, MMEF, PEF |
Other
| Measure | Time frame | Description |
|---|---|---|
| incidence of adverse events of both BPTs | up to 12 months (Jan 2007 to Dec 2007) | adverse events of AMP-BPT and His-BPT |
Outcome results
None listed