New study confirms the safety of asthma medications in the rare disease familial dysutonomia

Each inspiration moves fresh air into the lungs and every expiration expels stale air out. Normally, we breathe around 20,000 times a day and the air passes freely through the airways.

But, estimates suggest that around 15% of the population suffer from obstructive airway disease, in which the airways swell and constrict making it difficult to move air in and out. Breathing becomes noisy or wheezy and labored. Eventually, the smooth muscle lining the airways goes into spasm and mucus is secreted. Fortunately, doctors have options when it comes to managing obstructive airway disease. The smooth muscle lining the airway is filled with tiny autonomic receptors, which when activated with drugs relax the airways to ease breathing.

Airway obstruction in FD

Obstructive airway disease is very common in patients that suffer from the rare genetic disease familial dysautonomia (FD). In these patients, asthma-like exacerbations with coughing, wheezing and air-trapping account for over half of all emergency room visits. They can be an enormous source of untoward stress for the families. While many of them are treated with bronchodilators, the problem is that the medicines children with FD take for these asthmatic exacerbations have never been proved safe and effective for them.

Until now

A new study published this month now shows that 2 commonly used inhaled bronchodilators are effective and safe for FD patients. Using spirometry, a test that measures airflow, the investigators showed that albuterol and ipratroprium were not only successful in reversing airway obstruction, they were also safe, and did not have detrimental effects on the heart rate, rhythm or the circulation. “This is important”, explained the last author of the trial Dr. Lucy Norcliffe-Kaufmann. “Many of the medicines prescribed to patients with FD have not been tested in rigorous trials”.

Patients with FD are born without the nerves that regulate the autonomic (involuntary) functions of the body like breathing. This means that they can react unpredictably when given certain drugs. As Dr. Kaufmann explained, “The same safety assumptions that we make for the general population cannot always be directly translated to FD patients.”

Drugs that open the airways, by working on autonomic receptors in the smooth muscle are safe and effective in the short term for patients with FD

Good news

The good news is that the airway obstruction was pharmacologically reversible in around two-thirds of FD patients tested. 20 minutes after inhaling albuterol or ipratroprium (via a nebulizer mask), the team were able to measure relaxation of the airways. This means that we have medicines to prescribe that ease breathing in patients with FD and were not associated with side effects in the short term.

Checking in

One-third of the patients studied had little or no airway response to either drug. This means that doctors cannot just assume an inhaled bronchodilator is working. Patients with FD need to check back in with their pulmonologist (lung doctor) to test objectively whether the patient does indeed have a good airway relaxation response by repeating the spirometry tests after a bronchodilator challenge. If they don’t respond, it’s crucial to find out why.


The study was done in collaboration with Dr. Bat-et Bar and Dr. Ori Efrati at Sheba Medical Center in Israel and is the first international randomized controlled trial to be performed in patients with FD. As Dr. Horacio Kaufmann explained “While we understand that aggressive management of FD may be making a difference, it’s essential that we continue to question whether the choices we make in the clinic are the right ones”.

Designing clinical trials that help answer these pressing medical questions is an essential part of that process. Rather than rely on anecdotal reports, the team relies on objective data. It’s very easy to assume that a drug works or black list something as dangerous based on the experience of 1 or 2 cases. Well-designed double-blind placebo controlled studies of this nature help us decide which treatment to use because they provide objective data.

Read more here:

Bar-Aluma BE, Efrati O, Kaufmann H, Palma JA, Norcliffe-Kaufmann L. A Controlled Trial of Inhaled Bronchodilators in Familial Dysautonomia. Lung. 2017 Dec 12. doi: 10.1007/s00408-017-0073-7. PMID: 29234869

Albuterol is sold under brand names such as VENTOLIN or PROVENTIL. Ipratroprium us sold under the brand name ATROVENT. The study was sponsored by the Dysautonomia Foundation, Inc.