AMP-BPT and His-BPT for Assessment of Asthma

NCT ID: NCT02318043

Last Updated: 2014-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2007-12-31

Brief Summary

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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

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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.

Conditions

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Asthma

Keywords

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adenosine monophosphate histamine bronchial provocation test asthma symptom score asthma control

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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AMP-BPT

Methods of AMP-BPT, by applying dosimeters, resembled that reported previously \[see references 21-25\]. Briefly, dilutions were delivered via nebulizers (output: 160 μl/min) using automated APS pro system (JAEGER, Hochburg, Germany). Inhalation challenge with normal saline served as control step. Challenge steps were proceeded if FEV1 fall \<15% and restored to \<10% within 1 minute. Subsequent inhalation challenges were performed at 1-minute intervals, and ceased when FEV1 fell by ≥20%. Salbutamol was administered via spacer (Volumatic, Allen \& Hanbury's, UK). Spirometry was reexamined at minutes 3, 5, 10 and thereafter, to ensure safety, before discharge.

Group Type ACTIVE_COMPARATOR

inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)

Intervention Type DRUG

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.

His-BPT

Methods of His-BPT, by applying dosimeters, resembled that reported previously \[see references 21-25\]. Briefly, dilutions were delivered via nebulizers (output: 160 μl/min) using automated APS pro system (JAEGER, Hochburg, Germany). Inhalation challenge with normal saline served as control step. Challenge steps were proceeded if FEV1 fall \<15% and restored to \<10% within 1 minute. Subsequent inhalation challenges were performed at 1-minute intervals, and ceased when FEV1 fell by ≥20%. Salbutamol was administered via spacer (Volumatic, Allen \& Hanbury's, UK). Spirometry was reexamined at minutes 3, 5, 10 and thereafter, to ensure safety, before discharge.

Group Type ACTIVE_COMPARATOR

inhaled corticosteroids (usually budesonide/fomorterol 160/4.5mcg; fluticasone/salmeterol 250/50mcg)

Intervention Type DRUG

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.

Interventions

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inhaled 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Guangzhou Institute of Respiratory Disease

OTHER

Sponsor Role lead

Responsible Party

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Jinping Zheng

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

References

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Other Identifiers

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GWJ

Identifier Type: -

Identifier Source: org_study_id