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Matched cohort study of therapeutic strategies to prevent preschool wheezing/asthma attacks

Jonathan Grigg, Anjan Nibber, James Y Paton, et al. On behalf of the Respiratory Effectiveness Group.

J Asthma Allergy 2018;11:309–21.


Wheezing and asthma attacks affect as many as one-third to one-half of children in the US and Western Europe at least once in their first six years. Their prevention is an active area of study and debate, but asthma management guidelines offer little definitive guidance for recurrent attack prevention in this age group.

Clinical trials suggest that, for children at high risk of developing persistent asthma who are asymptomatic between wheezing episodes, therapy with daily low-dose or intermittent high-dose ICS reduces attack rates as well as symptom burden during attacks. A 2014 study reported no overall benefit of intermittent therapy with an LTRA in preschool wheeze. There is also speculation that administration of an EF-particle ICS could be more beneficial for the youngest children. Overall, the marked heterogeneity from all these studies indicate the need for further investigation.

The aim of this study was to assess the effectiveness of ICS or LTRA for preventing wheeze/asthma attacks in pre-schoolers with recurrent wheeze when added to a SABA. The study also tested the hypothesis that the use of EF-particle ICS would be associated with better outcomes than fine-particle ICS.

Electronic medical records from the Optimum Patient Care Research Database were used to set up a matched cohort analysis employing four two-way matched comparisons: (1) all ICSs by pMDI vs SABA; (2) LTRA vs SABA; (3) LTRA vs all ICSs by pMDI, and (4) EF-particle ICS vs fine-particle ICSs by pMDI. Children initiating ICS or LTRA were matched 1:4 to those prescribed only SABA. The primary study endpoint was a wheezing/asthma attack, defined according to the American Thoracic Society/European Respiratory Society criteria.

There was no significant difference in the odds of a wheezing/asthma attack during the outcome year between the matched cohorts in either of the two comparisons between controller therapy and SABA. Neither was there any significant difference in the odds of a wheezing/asthma attack during the outcome year between the matched cohorts in either of the two controller therapy comparisons. The authors highlighted three limitations of their study: (1) the study may represent children on the milder end of the spectrum; (2) they could not ascertain whether children had persistent symptoms or were symptom-free between wheezing/asthma attacks, and (3) the study authors could not assess medication adherence.

In conclusion, this study found no evidence that stepping up therapy, compared with as-needed SABA, reduces wheezing/asthma attacks in a diverse population of preschool children with at least two documented prior wheezing episodes. The fact that antibiotics are frequently prescribed for preschool wheeze (thought to be attributable to viral infections) suggests the need for further attention.

There is a need for better understanding of disease patterns and better targeting of existing therapies, and a ‘wait-and-see’ approach may be clinically prudent.

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