AMP-BPT and His-BPT for Assessment of Asthma

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.

Inclusion criteria

• aged 18~65 years;
• nil respiratory infection within 3 weeks;
• normal chest radiography;
• baseline FEV1>60% predicted;
• withdrawn from, if any, oral leukotriene modifiers, corticosteroid or anti-histamine for 5 days, oral xanthenes or long-acting bronchodilators for 2 days, inhaled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

• FEV1 fall ≥20% following saline inhalation;
• other chronic lower respiratory diseases (i.e. COPD);
• severe systemic diseases (i.e. uncontrolled hypertension, malignancy);
• 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.