Emerging evidence suggests that a single daily preventer dose of inhaled corticosteroid (beclomethasone), taken mid-afternoon may improve asthma control by better targeting the body’s natural rhythms.
Impact of dosing time on asthma outcomes
In a small clinical trial published in the journal Thorax, researchers investigated the impact of dosing time on asthma outcomes, using 400µg of beclomethasone administered at 3 different times:
- Once/day in the morning
- Once/day in the mid-afternoon
- Twice/day.
“Aligning the timing of drug treatment with the body clock, known as chronotherapy, can enhance the therapeutic effects of medicines,” say the researchers.
“This may be particularly important in asthma, which has a distinct daily rhythm, with the cardinal effects of airflow obstruction and airway inflammation peaking overnight, when 80% of fatal asthma attacks occur,” they explain.
The study
The study included 25 adults (18-65 years) with confirmed mild-moderate asthma lasting at least a year, and common respiratory allergies to cat hair, dust mites, or grass pollen.
Participants were randomly assigned to one of three dosing regimens for 28 days each.
At the end of each 28 day period, participants swapped their dosing regimen after a 14 to 21 day gap until all three trial arms had been completed.
Spirometry readings and blood biomarkers (inflammatory cells, levels of cortisol and salbutamol from reliever inhalers) were measured every 6 hours for 24 hours at the start and end of each of the 28 day periods.
21 people (84%), all of whom had similar sleep-wake cycles, completed all three of the trial arms.
Compared with baseline measurements, all the treatment arms improved night time lung function.
But the timing of the improvement differed according to the dosing regimen.
The largest Improvement, measured at 22:00 hours, was associated with the once daily mid afternoon dose (100ml more than the morning dose).
Similarly, all the dosing regimens suppressed airway inflammation compared with baseline levels. And this was significantly lower at 22.00 and 0400 hours with the once daily mid afternoon dose than it was with the twice daily dose.
There was no difference in cortisol levels between the three dosing regimens, compared with baseline levels, suggesting that there was no additional impairment in the body’s ability to produce the hormone — a potential side effect of inhaled steroid treatment.
Optimal timing of inhaled corticosteroid
“Our findings further support the hypothesis that the optimal timing of [inhaled corticosteroid] administration is at 16:00, coincident with enhanced glucocorticoid sensitivity at that time,” say the researchers.
“The notion that the onset of the inflammatory cascade begins mid-afternoon may also explain the findings we observed, and the attenuation of the predictable rhythmic recruitment of airway inflammatory cells at this time point may abolish the subsequent excessive nocturnal dip in lung function in asthma,” they suggest.
Potential benefits of chronotherapy
“This study offers promising insights into the potential benefits of using chronotherapy with inhaled corticosteroids for asthma patients.
“We believe that this is most likely to benefit those with more severe asthma, where marginal gains in lung function and a reduced eosinophil count are more likely to translate into better control and risk reduction,” say the researchers.
To read the study, visit: thorax.bmj.com/content/early/2025/04/10/thorax-2024-222073
