Timing crucial when measuring sputum eosinophils


By Nicola Garrett

11 Sep 2018

The time of day that a patient with severe asthma is seen in clinic could impact the ability to accurately diagnose and effectively treat the condition, new research suggests.

The most comprehensive circadian study of biomarkers in asthma to date has shown that time of day is crucial when measuring biomarkers in asthma, particularly if they are being used to inform management decisions.

Results showed that sputum eosinophil levels taken from an asthma patient in the morning were significantly higher than those taken from the same patient in the afternoon.

While the findings need to be confirmed in a prospective study, the implications are clinically important, say the researchers led by Dr Hannah Durrington, Senior Clinical Lecturer at the University of Manchester and Honorary Consultant in Respiratory Medicine, Wythenshawe Hospital, Manchester University NHS Foundation Trust.

“In severe asthma, having raised sputum eosinophils is an indicator for treatment escalation; we propose that based on our results different clinical decisions could be made based on whether the patient is allocated a morning or afternoon appointment,” they said.

The study, published in the American Journal of Respiratory and Critical Care Medicine, looked at circadian variation of blood and sputum eosinophils in 10 patients with mild/moderate atopic asthma compared to 10 controls, and then retrospectively compared sputum eosinophil counts from severe asthma patients attending either morning (131 patients) or afternoon clinic (193 patients).

Dr Durrington told the limbic: “We already know that airway obstruction in asthma varies by time of day and is worse around 4 am. This research demonstrates that sputum eosinophils vary by time of day in mild/moderate asthma and are highest at 4 am and lowest in the afternoon at 4 pm.

“However, sputum eosinophil counts are still significantly raised later in the morning (within the clinical working day) in severe asthma patients, compared to the in the afternoon – this is a new finding.”

Severe asthma patients attending morning clinic were almost twice as likely to have sputum eosinophilia (³3%) compared to patients attending afternoon clinic (37.4% vs 21.6%). There was no significant variation in sputum eosinophils in healthy volunteers.

The results also showed that blood eosinophils fluctuate over the course of the day in asthma, but in a similar manner to healthy individuals.

Dr Durrington said a further prospective study is needed to determine whether sputum eosinophils should be measured in the morning or afternoon to give the best management strategy for patients, adding that planning for this study is underway.

“The implications from our research are that biomarkers vary by time of day and we must determine when during the day is the ‘best’ time of day to measure biomarkers, not just in asthma but in other diseases also,” she said.

“More often than not biomarker studies do not take time of day into consideration, and more concerning implement clinical algorithms based on biomarker levels.

“Future studies must determine if it is better for clinical decision making if the biomarker is measured in the morning or afternoon,” she said.

Dr Durrington added: “By extension, if we understand more about how asthma varies by time of day then we may be able to identify a ‘window’ of time during the day when treatments might be most efficacious, and this might not be at a time when we traditionally take medications – after waking or on going to bed.”

“Our research did not evaluate the timing of inhaled corticosteroids, however, there are several small studies that show that steroids may be more effective if taken in the afternoon rather than in the morning,” she said.

A randomised controlled trial of chronotherapy in asthma, which will look at the best time of day to take inhaled corticosteroids, is due to start next year and will be carried out through the Manchester Biomedical Research Centre, she added.

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