Bronchial Thermoplasty: Mechanism of Action and Defining Asthma Phenotype

National University Health System (NUHS)

Status

Unknown

Conditions

Asthma

Treatments

Procedure: Bronchial Thermoplasty

Study type

Interventional

Funder types

Other

Identifiers

NCT02075151

DSRB/2013/00144

Details and patient eligibility

About

According to World Health Organization (WHO) estimates, more than 200 million people suffer from asthma worldwide and in 2009, the disease had claimed 250,000 lives globally. Autopsy reports suggest 2 phenotypes of severe asthma: one that is characterized by intense airway inflammation with mucus plugging, and the other by severe bronchoconstriction causing respiratory failure in the absence of significant airway inflammation. However, it is not easy to stratify patients according to phenotypes without bronchoscopy. Although severe asthma comprises only 10% of affected individuals, it accounts for more than half of the total healthcare spending on asthma. Inhaled corticosteroids are effective by suppressing production of multiple pro-inflammatory mediators, unfortunately efficacy plateaus. Addition of long acting beta agonist and anti-cholinergic agent to inhaled corticosteroids offers some measure of relief but effective treatment of severe asthma remains an unmet goal, resulting in intensive utilization of healthcare resources. In 2010, the United States Food and Drug Administration (FDA) approved bronchial thermoplasty (BT) as an adjunctive therapy for severe asthma. BT is radiofrequency ablation of airway smooth muscle via bronchoscopy with each patient undergoing three procedures which targets different lobes of the lung 3 weeks apart. Studies have demonstrated improved symptom control allowing discontinuation of oral steroids in some patients as well as reductions in exacerbations, hospitalizations and use of rescue medications. No development of airway strictures or bronchiectasis, and regeneration of normal epithelium after BT has been observed. At present, it remains unclear if BT benefits all asthma phenotypes or if BT has any effect on airway inflammation and remodeling.

The hypothesis of this study is that bronchial thermoplasty is likely to benefit all severe asthma phenotypes, and achieves this by exerting an effect on airway inflammation and remodelling.

The specific aims of the study are: 1) to better define the asthma phenotype who will benefit from BT by microarray and gene expression profiling; 2) to study effects of BT on airway inflammation; 3) to define its role in the overall asthma management algorithm

Enrollment

50 estimated patients

Sex

All

Ages

21 to 64 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Males and females between 21-65 years of age
Poorly controlled severe persistent asthma (ACT score < 20) despite high-dose inhaled steroids (>500 mcg fluticasone/day or >800 mcg budesonide/day) in combination with inhaled long-acting Beta-2 agonist and/or anticholinergic agent. Other drugs include leukotriene modifiers, omalizumab (if used for at least 1 year prior), and oral corticosteroids 10mg/day or less
Stopped smoking for > 1 year and <10 pack-years
Stable maintenance asthma medications for 4 weeks
Pre-bronchodilator FEV1 >60% predicted

Exclusion criteria

Males and females <21 and >65 years of age
Presence of pacemaker, internal defibrillator, or other implantable electronic devices
Known sensitivity to medications required to perform bronchoscopy, including lignocaine and benzodiazepines
Patients previously treated with Bronchial Thermoplasty (BT)
Use of immunosuppressant (excluding oral steroids)
Increased risk of adverse events associated with bronchoscopy or anesthesia (including pregnancy, uncontrolled coronary artery disease, acute or chronic renal failure, and uncontrolled hypertension)
Inability to cease antiplatelet or anticoagulant therapy prior to procedure