Medscape

Marcia Frellick

Gerry Gajadharsingh writes:

Short-acting beta-agonists (SABAs) are a class of prescription drugs used to quickly relieve shortness of breath and wheezing in people with asthma (and sometimes other respiratory conditions such as chronic obstructive pulmonary disease COPD), commonly a salbutamol inhaler (Ventolin). SABAs work by relaxing the smooth muscles of the airways leading to the lungs that become narrow during an asthma attack—allowing air to flow more freely and alleviating spasms.

When used as a rescue medication, a SABA can relieve dyspnoea (shortness of breath) and wheezing within minutes. After one or two puffs, the drug will remain active for around four to six hours.

SABAs belong to a class of drugs known as beta2 (β2)-adrenergic receptor agonists. By definition, agonists are drugs that bind to a cell receptor to trigger a specific reaction.

The receptor in this case is the beta2-adrenergic receptor, which relaxes smooth muscles. Smooth muscles are those in the walls of hollow organs that contract and relax involuntarily to, among other things, move food through the intestines, regulate blood pressure and circulation, or—as is relevant to asthma—open and close airways in the lungs.

The receptors are considered adrenergic because they respond to the hormone adrenaline that helps regulate smooth muscle function. By mimicking adrenaline, beta-agonists can bind to adrenergic receptors and trigger a chain reaction in which calcium is quickly released from channels within smooth muscles, causing them to relax.

SABAs are known to affect pulse rate, blood pressure, blood sugar, and thyroid hormone production and, on rare occasions, induce seizures.

I was diagnosed with an allergic asthma many years ago, to horses, cats and dogs, I have three dogs, don’t ask! Initially prescribed Ventolin by my GP I found it provoked a tachycardia (fast heart rate). I requested to be switched over to a combination drug Symbicort (which contains a low-dose steroid and a bronchodilator but not salbutamol). I take an absolute minimum dose 100mg maybe 2 to 3 times a week when I’m exposed to my allergens. Coupled with adopting good breathing behaviour and working out that there are co-allergens in my case chocolate and red wine, keeping these cofactors at bay means I have very good asthma control. By the way Symbicort has been approved as a COVID-19 medication. Asthma is yet another autoimmune problem (the body is attacking itself). I often find dietary change to lower inflammatory load also really helpful as well as keeping away from no or suspected triggers that provoke an inflammatory response.

The research below, looking at 1 million people in Europe, flags up the fact that one third of asthma patients are probably over using their SABA’s, ironically increasing the risk of us asthma attacks and mortality, with the UK having the incidence of highest overuse at 38%.

About one third of asthma patients have high use of short-acting beta agonists (SABAs) in Europe across all severity levels, said Santiago Quirce, MD, PhD, with Hospital Universitario in Madrid, Spain.

High use — defined as three or more canisters dispensed per year — “is a global public health issue,” and is associated with increased risk of asthma exacerbations and death, he said, along with increased healthcare costs.

Asthma patients tend to rely too heavily on SABAs and too little on inhaled corticosteroids (ICS), he said Saturday at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021, adding that SABA use continues to increase globally.

Quirce is a co-author on the SABINA study, the largest real-world study on SABA use. It included 1 million people with asthma across five European countries. Among the findings were that overuse varied greatly by country.

Overuse was 9% in Italy; 16% in Germany; 29% in Spain; 30% in Sweden; and 38% in the United Kingdom. In the UK, SABA overuse was greater for people with moderate-to-severe asthma compared with those who had mild asthma (58% vs 27%, respectively.)

Quirce also pointed to a 2012 study in the Annals of Allergy, Asthma & Immunology of more than 33,000 patients that identified values of SABA that predicted exacerbations in children in adults.

For adults, “use of 2 or more SABA canisters was found as the critical value with shorter optimal assessment periods of 3 and 6 months,” the 2012 study found. “Each additional SABA canister resulted in an 8% to 14%” increase in the risk for asthma-related exacerbation in children and “a 14% to 18%” increase in that risk in adults.

Patients become over reliant on the SABA inhalers, which have been in use for more than 50 years, for many reasons, Quirce said, despite the increased risk of exacerbations.

He noted that it’s difficult to increase awareness of the risks for SABA overuse among both patients and healthcare workers, partly because the inhalers offer fast relief, are easy to use, and are inexpensive.

However, the 2019 Global Initiative for Asthma (GINA) guidelines no longer recommend SABAs alone to treat asthma in adolescents and adults.

“[SABA overreliance] is one of the biggest problems we have in asthma management,” he said.

Quirce said that a better shared understanding of SABA overuse is needed, “so that specialists and GPs are totally aware of the problem.” Communicating that to patients is also important, he said.

Gaps in Understanding of Overuse are Wide

Researchers conducting a study published in NPJ Primary Care Respiratory Medicine interviewed asthma experts from hospital and primary care backgrounds to identify how SABA use is defined and perceived. They found providers’ definition of “acceptable SABA use” ranged from 0.5 SABA inhalers (100 doses per year) to 12 SABA inhalers (2400 doses/year).

Quirce suggests a “warning or red flag” from community pharmacists and efforts by scientific organizations to highlight the problem.

Additionally, restrictions on use vary widely worldwide.

Session moderator Stefano Del Giacco, MD, associate professor of allergy and clinical immunology at University of Cagliari, Cagliari, Italy, said, “In Italy we can take (SABA) without a prescription because it is considered an emergency medication. If you rush to the pharmacy and you ask for it, they will give it to you immediately.”

Lack of prescriptions, and thus lack of prescription data, may also help explain why overuse numbers in Italy are lower than in other European countries, Quirce said.

Del Giacco said he agreed that “red flags” at the pharmacy level should be instituted.

Stanley Szefler, MD, director of the Paedriatric Asthma Research Program and research medical director in the Breathing Institute at Children’s Hospital Colorado in Denver, told Medscape Medical News he suspects dependence on SABAs is similar in the US and Europe. He said it is also likely patients are driving the decisions to use SABA based on rapid relief and low cost.

“That is where close monitoring of prescription on a population basis could be helpful in identifying those patients and seeing what is going on,” he said.

He noted that, in the US, insurance provider Kaiser Permanente has set up a “SABA/ICS ration system” to detect patients who are over reliant on SABAs.

Quirce receives honoraria, serves on the speaker’s bureau, or is a consultant for ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Regeneron, Sanofi, and Teva. Szefler and Del Giacco have disclosed no relevant financial relationships.

European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2021: Plenary Session: New Frontiers in Asthma / Landscape of Short-Acting Beta Agonists in Europe. Presented July 10, 2021.