Prominent respiratory physician Sebastian Johnston has joined the call to ban the blue inhaler, saying beta agonists are probably responsible for asthma deaths.
Addressing an overflowing session on asthma management at the European Respiratory Society Congress in Madrid, the professor of respiratory medicine at Imperial College London’s National Heart and Lung Institute recalled his first publication: a case study of a 22-year-old woman who died from an asthma attack.
He said spates of asthma deaths had been linked to the beta agonist fenoterol and were thought to be due to cardiac events, but when that drug was withdrawn the number of exacerbations also went down, meaning the harm was respiratory.
There followed a procession of studies showing regular use of beta agonists was associated with worse airway hyperresponsiveness, worse asthma control, decline in lung function and longer-lasting attacks.
It had been shown that beta agonists induced inflammatory interleukins, brain derived neurotrophin factor, COX-2 and mucins in bronchial epithelial cells, but that corticosteroids such as fluticasone brought them down again.
Regular use of short and long-acting beta agonists had been repeatedly linked with asthma deaths, he said, but adding steroids made them safe and beneficial.
Therefore, he concluded, there should be no possibility of using one without the other.
“Using a LABA without ICS in asthma is clearly unsafe … overusing a SABA without ICS is also clearly unsafe, and I suspect that that kills people with asthma. I suspect that killed that 22-year-old I started my talk with.
“So I believe that blue inhalers for safety reasons should be banned and replaced with BA-ICS combination therapy in the same inhaler so that patients cannot take a beta agonist without at the same time taking an inhaled steroid to protect them from the adverse effects of beta agonists.
“That’s a very provocative couple of statements to end on, but I believe what I have presented supports those hypotheses, and putting these drugs in the same inhalers is essential to maintain our patients’ safety.”
An editorial in Lancet Respiratory Medicine by UK respiratory paediatrician Professor Andrew Bush in July caused a stir by calling the blue inhaler a “killer” and calling for it to be banned.
Professor Johnston was followed by Professor Helen Reddel, chair of the Global Initiative for Asthma (GINA) science committee and research leader at the Woolcock Institute of Medical Research in Sydney.
She described the pendulum swings of asthma management since the 1960s, when asthma was regarded as purely a disease of bronchoconstriction and treated with beta agonists, to the 1980s when oral corticosteroids were used, to high-dose inhaled corticosteroids in the 1990s, then back in the 2000s to beta agonists and lower-dose inhaled steroids.
She said GINA had taken 12 years to reach the conclusions expressed in its population-level strategy published this year, which recommends not using SABAs alone but instead using combined steroids and beta agonists either daily or as needed.
The big problem was convincing patients that the familiar, cheap, fast-acting, reliable medication that they’d used since childhood was in fact harmful, and should be replaced by a daily medication in the absence of symptoms.
Inhaled corticosteroids were currently underused and under-prescribed as they were perceived as risky, unnecessary and expensive.
When challenged by Professor Johnston from the audience to recommend banning the blue inhaler, Professor Reddel said GINA had considered it but there were not enough alternatives available.
This session did not cover the use of biologics, which are reserved for the most severe patients.
But a large Dutch study also presented at the conference found a third of severe asthma patients were taking harmful doses of oral steroids.
Dr Katrien Eger, a pulmonologist in training at Amsterdam University Medical Centre, said most of these patients needed to improve their adherence to their other asthma medication and their inhaler technique.
But of the rest, who would be eligible for treatment with biologic asthma drugs – which so far include omalizumab, mepolizumab, benralizumab, reslizumab and the newer dupilumab – only half were receiving them.
Oral steroids put patients at risk of diabetes, osteoporosis and adrenal insufficiency.