Predictors of response to medications for asthma in pediatric patients: A systematic review of the literature

Abstract

ObjectivesThere has been no systematic review of studies aimed to predict differential responses to medication regimens for asthma controller therapies in pediatric patients. The aim of the present study was to summarize those identifying biomarkers for the different asthma controller therapies.MethodsStudies published by June 2019 that report phenotypic or genotypic characteristics or biomarkers that could potentially serve as response predictors to asthma controller therapies in pediatric patients were included. The quality of studies was assessed using the Cochrane Risk of Bias tool and the Newcastle‐Ottawa Scale tool.ResultsOf 385 trials identified, 30 studies were included. Children with asthma and a positive family history of asthma, with more severe disease, of the white race, with allergy biomarkers, nonobese, with lower lung function, high bronchial hyperresponsiveness to methacholine, or having variants in the FCER2 and CRHR1 gene respond better to inhaled corticosteroids (ICS). Younger age (<10 years), short disease duration (<4 years), high cotinine and urinary leukotriene E4 (LTE4) levels, and 5/5 ALOX5 were associated with a better response to leukotriene receptor antagonist (LTRA). For patients that remain symptomatic, white Hispanics were more likely to respond to LTRA, blacks to ICS, white non‐Hispanics to LTRA or LABA, and children without a history of eczema, regardless of race or ethnicity to LABA set‐up therapy. In severe persistent asthma, those with atopy and body mass index greater than or equal 25 were more likely to benefit from omalizumab.ConclusionSeveral phenotypic characteristics, biomarkers, or pharmacogenomics markers could be useful for predicting the best drug for asthma treatment.

New Perspectives in the Management of Mild to Moderate Asthma in Children

“…3 Treatment options and studies on predictors of response to treatments in mild to moderate asthma are very limited. 5 Besides, mild asthma is no longer regarded as an easy condition to manage considering the severe exacerbation risk (0.12 and 0.77 severe exacerbations per patient per year). 6 Furthermore, compliance to regular controller medication is worse in mild, but also in the moderate spectrum of, asthma compared to severe asthma, that may be the main reason of severe exacerbations in these groups.…”

The pharmacoeconomics of the state-of-the-art drug treatments for asthma: a systematic review

“…In these cases, it is possible to resort to tiotropium and LTRAs as additional options, with good results in many patients, although generally inferior to ICS-LABAs. LTRAs should be used more selectively than it is currently done, as patients who respond best to them are preschool, female, high cotinine and urinary leukotriene E4 (LTE4) levels [ 73 ]. Most pharmacoeconomic studies about asthma therapies have several limitations and there is also a lack of headto- head studies not only among biologics, but also among asthma controller drugs that would allow a more effective comparison of results.…”

Sleep disorders in children with asthma

“…Over the past few decades it has become increasingly clear that asthma does not represent one disease but rather multiple different phenotypes leading to similar signs and symptoms but differing in many other aspects. 63 The same is likely true for sleep disorders, with growing evidence in adult SRBD of different phenotypes-some of which may overlap-and novel attempts at phenotype-directed approaches for precision medicine. 74 Much like one cannot (should not) study or treat wheeze in a preschool child and atopic asthma in a teenager in the same way, not all patients with asthma and SRBD will be the same, and therefore studies need to be carefully designed keeping disease heterogeneity in mind.…”

“…60 Asthma represents a heterogenous syndrome with multiple inflammatory mechanisms involved referred to as clinical phenotypes or endotypes separated according to such criteria as clinical, immunological, genetic and environmental features. 62,63 This shared inflammatory pathophysiological basis in SRBD and asthma is reflected in both diseases' response to similar medications such as the leukotriene receptor antagonists. Whether the same inflammatory processes lead to both diseases or inflammation at one site leads to inflammation at the other, according to the united airway theory, discussed below, remains unclear but there is likely a contribution of both.…”