Heart Rate Variability Biofeedback: It's Role in Asthma Therapeutics

The purpose of this study is to determine the role of Heart rate variability biofeedback
(HRV-BF) in asthma management as either a controller (alternative) or bronchodilator
(complementary) treatment, with respect to the current treatment of choice, inhaled
corticosteroid (ICS) therapy, using different methods from participants that demonstrated
clinically significant improvement in asthma outcomes in the investigator's previous research
(1), and adding a second site not involved in the investigator's previous work.

Inflammation of airways is viewed as the core pathophysiologic process in asthma. It is
thought to render airways more reactive, and therefore, more susceptible to
bronchoconstriction, leading to asthma exacerbations. Asthma is an episodic disease, where
the goal of therapy is to reduce susceptibility to exacerbations, which may cause severe,
even life-threatening illness. Anti-inflammatory medications reduce airways reactivity, while
bronchodilator medications primarily relieve symptoms once an asthma exacerbation is in
process, and may stop progressive constriction of airway smooth muscles (ASM). An
anti-inflammatory effect of HRV-BF would have important implications for asthma management
because adherence to ICS regimens is low due to a significant degree to feared side effects
of prolonged steroid medication. Even if HRV-BF is found to only allow partial reduction in
ICS requirements, this still would likely represent a major advance in asthma care.

Inclusion Criteria:

- Mild to moderate persistent asthma for at least the past one year

- Patients must not have taken oral or inhaled anti-inflammatory agents, including ICS
and leukotriene inhibitors, for at least one month prior to study entry; and anti-IgE
medications at least the past six months. Documented use of inhaled short-acting or
long-acting β2-agonists during the month prior to study entry is, however, required.
Xanthines, long-acting anticholinergics, and long-acting β2-agonists must be withdrawn
within 72 hours upon entering the screening phase; short acting anticholinergics must
be withdrawn within 48 hours before entering the screening phase. Patients will be
required to abstain from these medications for the duration of study participation.

- FEV1 values must be ≥60% of predicted normal values following a 6 hour albuterol
withhold, and reversibility of FEV1 of at least 12% (equal to or greater than 200 cc)
following up to four puffs of albuterol must occur; or asthma physician at study site
must state based on medical history, exam, and spirometry data that patient has
presumptive mild-moderate persistent asthma.

- Lack of current asthma control as evidenced by ACT ≤ 19, or rescue use of B2-agonist ≥
2/week within past 2 weeks, or waking due to asthma ≥ 1/week within past 2 weeks.

- Patients must be non-smokers for at least the past year and have less than a 15
pack-year smoking history. This will minimize the risk of co-occurring COPD

- Behavioral/linguistic competence: Ability to complete questionnaires and assessments
in English

- Patients must give informed consent prior to any study procedures.

Exclusion Criteria:

- Diagnosis of severe persistent asthma

- 2 or more inpatient hospitalizations in the past year for asthma exacerbations;

- History of only seasonal asthma

- Patients with serious concomitant disease

- Patients who have had a respiratory tract infection within 4 weeks of screening

- Patients with a history of chronic bronchitis, COPD, or emphysema

- Patients with a history of alcohol or drug abuse, or emotional or cognitive problems
requiring psychotropic medication or likely to interfere procedural and treatment
adherence

- Any other clinically relevant deviation from normal in general medical history,
physical examination, or laboratory parameters that would limit participation or
interfere with study procedures and/or data collection;

- Presence of exclusive extra-thoracic airway dysfunction

- Women who are pregnant

- Presence of a heart rhythm or other abnormality of heart rhythm on screening EKG that
could preclude ac-curate HRV assessment

- Chronically taking any medication likely to affect the autonomic or respiratory
systems

- Asthma therapy and concomitant medication

- Previous participation in an investigational drug trial within 30 days prior to
screening.

- Concurrent participation in any other clinical trial or observational study at any
time in the study.

- Planning to move away from the area within the next 4 months