Albuterol and Dynamic Hyperinflation in Idiopathic Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to determine if dynamic hyperinflation seen in patients with idiopathic pulmonary artery hypertension (iPAH) improves with albuterol therapy.

Detailed Description
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Only a few small studies have evaluated the relationship between iPAH, expiratory flow limitation, and exercise dyspnea. While not all patients with iPAH demonstrate airway involvement, those who demonstrate dynamic hyperinflation (DH), defined as a variable and temporary increase in end-expiratory lung volume, report increased dyspnea with exertion on maximal testing. There is a continued need for adjuvant therapy in iPAH, and bronchodilators have the potential to ameliorate dyspnea during exercise, which could lead to improved quality of life in this disabling condition. This study will investigate the presence of airway involvement in this population as measured by dynamic hyperinflation, and if there is any improvement in function with the use of inhaled albuterol.

Official Title
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Albuterol and Dynamic Hyperinflation in Idiopathic Pulmonary Arterial Hypertension

Conditions
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Idiopathic Pulmonary Arterial Hypertension.

Intervention / Treatment
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* Drug: Albuterol.
* Drug: Normal saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or greater. Idiopathic Pulmonary Arterial Hypertension, or Familial Pulmonary Arterial Hypertension. Forced expiratory flow 75% (FEF75%) of ≤ 65% of predicted. Exclusion Criteria: Clinical instability or change in medication therapy in preceding 3 months. Allergy or intolerance to inhaled albuterol. Body mass index > 30 Active tobacco use, or > 10 pack-year smoking history. Lung disease other than pulmonary hypertension Forced expiratory volume in 1 second (FEV1) ≤ 80% of predicted. Pregnancy Inability to perform pulmonary function testing. Inability to perform cardiopulmonary exercise testing. Supplemental oxygen requirement. Inability to read and understand English. Historical 6-minute walk distance <150 meters

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Albuterol<br>2.5 mg of albuterol inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET. | Drug: Albuterol.<br>* 2.5 mg of albuterol inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET.<br>|
| Placebo Comparator: Placebo<br>Normal saline placebo inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET. | Drug: Normal saline placebo<br>* Placebo inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End-expiratory lung volume:total lung capacity (EELV/TLC) ratio at matched metabolic isowork. | Determined by measuring inspiratory capacity every 2 minutes during cardiopulmonary exercise test (CPET) | up to 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in peak oxygen consumption with albuterol | Measured at the end of CPET | Study days 2 and 3 | 
| Change in O2 pulse with albuterol. | Measured throughout CPET and compared at matched metabolic isotimes | Study days 2 and 3 | 
| Exercise time | Total ramped exercise time | Study days 2 and 3 | 
| Borg dyspnea score | Measured every 2 minutes throughout CPET | Days 2 and 3 |