Aug 122018

When patients with asthma feel their symptoms worsening and fear a full-blown exacerbation is imminent, what should they do?

Doctors and researchers have never found a good answer to this question for most patients. The options are, generally: 1) continue current controller inhalers and observing; 2) increase the dose of inhaled steroid inhalers; or 3) start oral steroids while continuing the usual daily regimen.

Because of the short- and long-term toxicity of regular use of oral steroids, including obesity and diabetes, option 2 has been seen by many as the ideal theoretical approach -- but no one knows if it actually works.

It's been previously shown that doubling the dose of inhaled corticosteroids (ICS) is generally ineffective at preventing asthma exacerbations. Current guidelines from the Global Initiative for Asthma recommend quadrupling the ICS dose  when a patient feels an asthma attack is probable. However, any benefits of this were not well tested until recently, with two studies published in the New England Journal of Medicine.

Increased ICS Doses to Stop Asthma Exacerbations: Kids

In a U.S.-based multicenter study, 254 children with mild-to-moderate asthma who were taking low-dose ICS and had increased needs for albuterol were randomized to either quintuple their ICS dose from 88 μg fluticasone twice daily to 440 μg twice daily for 7 days, or to continue their current ICS doses (and seek other care if an asthma attack developed).

There were no differences in rates of exacerbations or asthma symptom scores between groups, after 48 weeks. The children assigned to the quintuple-dosing ICS group had measurable (though tiny) slower height growth (a quarter centimeter) on average, compared to the usual care group. Regular inhaled corticosteroid use in children is known to reduce their final attained height.

Increased ICS Doses to Stop Asthma Exacerbations: Adults

In the U.K., authors enrolled adults and adolescents with asthma who had recent past exacerbations and were taking inhaled steroids. They were all given a general self-management plan to refer to during threatened asthma exacerbations. In unblinded fashion they were randomized to also either quadruple their usual inhaled steroid dose for 7 to 14 days, or not, in response to lost asthma control.

Over one year, about 19% fewer severe exacerbations were observed in the group that quadrupled its ICS dose. As about half of patients experienced exacerbations overall, this translated to a number needed to treat of about 10 to prevent one severe exacerbation with quadrupled-dose ICS. The authors considered this a non-clinically meaningful result (having targeted a 30% reduction as clinically significant).

Further, more patients quadrupling steroids had side effects (lost voice, oral thrush), and experienced systemic absorption of steroids roughly equal to taking oral steroids for 5 days (authors estimated).


Treatment for asthma should be guideline-driven, but also tailored to the patient, health system factors, and the patient-physician relationship.  It seems unlikely that physicians will be encouraged to use increased doses of inhaled corticosteroids for periods of lost asthma control, based on these studies.

The most common self-management plan for threatened asthma exacerbations remains the prompt provision of oral corticosteroids. Since asthma control may worsen further while patients wait to hear back from their health care teams, many physicians provide reliable patients with a steroid pack to keep at home, to initiate based on their experience and judgment managing past asthma exacerbations.

Sources: NEJM (1), NEJM (2), NEJM (3)

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