A Controlled Trial of Inhaled Bronchodilators in Familial Dysautonomia
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Chronic lung disease is a leading cause of premature death in patients with familial dysautonomia (FD). A significant number of patients have obstructive airway disease, yet it is not known whether this is pharmacologically reversible.
We conducted a double-blind, placebo-controlled, randomized clinical trial comparing the beta 2 agonist albuterol with the muscarinic blocker ipratropium bromide in patients homozygous for the IKBKAP founder mutation. Albuterol, ipratropium bromide, and placebo were administered on 3 separate days via nebulizer in the seated position. Airway responsiveness was evaluated using spirometry and impulse oscillometry 30 min post dose. Cardiovascular effects were evaluated by continuous monitoring of blood pressure, RR intervals, cardiac output, and systemic vascular resistance.
A total of 14 patients completed the trial. Neither active agent had significant detrimental effects on heart rate or rhythm or blood pressure. Albuterol and ipratropium were similar in their bronchodilator effectiveness causing significant improvement in forced expiratory volume in 1-s (FEV1, p = 0.002 and p = 0.030). Impulse oscillometry measures were consistent with a reduction in total airway resistance post nebulization (resistance at 5 Hz p < 0.006).
Airway obstruction is pharmacologically reversible in a number of patients with FD. In the short term, both albuterol and ipratropium were well tolerated and not associated with major cardiovascular adverse events.
KeywordsBronchodilators Familial dysautonomia/HSAN III Autonomic
We wish to thank staff at the Centers for their assistance including Cristina Fuente Mora, Ginny Devi Chou, Yehonatan Sharabi, Moran Lavie, Ifat Sarouk, Adi Dagan, Moshe Ashkenazi, and Daphna Vilozni. We acknowledge Kenneth Berger for his helpful discussions in developing the trial design.
LN-K, J-AP, and HK receive salary support from the National Institutes of Health (U54-NS065736) and the Food and Drug Administration. All authors receive salary support from the Dysautonomia Foundation, Inc.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interests.
Informed consent was obtained from all individual participants included in the study.
Research Involving with Human and Animal Rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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