Bat-El Bar-Aluma1,2, Ori Efrati3, Horacio Kaufmann4, Jose-Alberto Palma4, Lucy Norcliffe-Kaufmann4. 1. Pulmonary Unit and The National Center for Cystic Fibrosis, Edmond and Lily Safra Children's Pediatric Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel. BatEl.BarAluma@sheba.health.gov.il. 2. The Sackler Medical School, Tel Aviv University, Tel Aviv, Israel. BatEl.BarAluma@sheba.health.gov.il. 3. Pulmonary Unit and The National Center for Cystic Fibrosis, Edmond and Lily Safra Children's Pediatric Hospital, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel. 4. Dysautonomia Center, NYU Langone Medical Center, New York University School of Medicine, New York, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
RCT Entities:
BACKGROUND: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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Entities:
Keywords:
Autonomic; Bronchodilators; Familial dysautonomia/HSAN III
Authors: P A Finney; M G Belvisi; L E Donnelly; T T Chuang; J C Mak; C Scorer; P J Barnes; I M Adcock; M A Giembycz Journal: J Clin Invest Date: 2000-07 Impact factor: 14.808
Authors: Mikhail Kazachkov; Jose-Alberto Palma; Lucy Norcliffe-Kaufmann; Bat-El Bar-Aluma; Christy L Spalink; Erin P Barnes; Nancy E Amoroso; Stamatela M Balou; Shay Bess; Arun Chopra; Rany Condos; Ori Efrati; Kathryn Fitzgerald; David Fridman; Ronald M Goldenberg; Ayelet Goldhaber; David A Kaufman; Sanjeev V Kothare; Jeremiah Levine; Joseph Levy; Anthony S Lubinsky; Channa Maayan; Libia C Moy; Pedro J Rivera; Alcibiades J Rodriguez; Gil Sokol; Mark F Sloane; Tina Tan; Horacio Kaufmann Journal: Respir Med Date: 2018-06-21 Impact factor: 3.415