Asthma

What the evidence shows

Long-acting beta agonists must never be given alone. Salmeterol added to usual therapy — which for many participants meant no inhaled steroid at all — produced 13 asthma deaths against 3 on placebo (SMART). That trial gave the class its black-box warning, and it is why every LABA now comes paired with a steroid in a single inhaler.

Short-acting reliever monotherapy is over. In mild asthma, as-needed budesonide-formoterol cut severe exacerbations by roughly two thirds compared with as-needed terbutaline (SYGMA 1) and matched daily inhaled steroid for exacerbation prevention on a quarter of the steroid dose (SYGMA 2). Be honest about the trade: daily inhaled steroid still gives better day-to-day symptom control. The same anti-inflammatory reliever principle extends to patients on separate maintenance therapy, and to salbutamol rather than formoterol (MANDALA).

Adding to inhaled steroid and LABA, a long-acting muscarinic antagonist gives modest bronchodilation and a 21% reduction in severe exacerbations (PrimoTinA-asthma) — cheap, tolerable, and worth trying before a biologic.

Inhaled steroids belong from diagnosis, not after failure. Low-dose daily budesonide nearly halved severe exacerbations in mild persistent asthma over three years (START) — though the lung function gains were small and shrank over time. It prevents attacks; it does not alter the trajectory.

Biologics work, and the interesting question is for whom. Tezepelumab acts upstream at TSLP and halved exacerbations regardless of eosinophil count, including in patients below 300 cells per microlitre (NAVIGATOR) — the group anti-IL-5 agents cannot help. Depemokimab achieved comparable exacerbation reduction with just two injections a year (SWIFT), though as with the other anti-IL-5 drugs quality of life did not follow. Benralizumab given at the time of an acute eosinophilic attack beat prednisolone (ABRA), which is a different idea altogether: treating the exacerbation rather than preventing it. The older anti-IL-5 and type-2 agents remain the workhorses: mepolizumab roughly halved exacerbations (MENSA), benralizumab did the same by depleting eosinophils outright (SIROCCO), and dupilumab added the largest bronchodilator effect of the class (QUEST).

For the patient no biologic will help — the neutrophilic, non-eosinophilic asthmatic — azithromycin remains one of the few options, reducing exacerbations by 41% and improving quality of life (AMAZES). Screen hearing and the QT interval first, as the trial did.

In the acute attack, bilevel positive pressure improved FEV1 and cut admissions from 62.5% to 17.6% (Soroksky 2003) — in 30 patients, never convincingly replicated, and still a selected-patient option rather than standard care.