Blood eosinophils in managing preschool wheeze: Lessons learnt from a proof-of-concept trial.

BACKGROUND: Management of preschool wheeze is based predominantly on symptom patterns. OBJECTIVE: To determine whether personalizing therapy using blood eosinophils or airway bacterial infection results in fewer attacks compared with standard care. METHODS: A proof-of-concept, randomized trial to investigate whether the prescription of inhaled corticosteroids (ICS) guided by blood eosinophils, or targeted antibiotics for airway bacterial infection, results in fewer unscheduled healthcare visits (UHCVs) compared with standard care. Children aged 1-5 years with ≥2 wheeze attacks in the previous year were categorized as episodic viral wheeze (EVW) or multiple trigger wheeze (MTW). The intervention group was prescribed ICS if blood eosinophils ≥3%, or targeted antibiotics if there is positive culture on induced sputum/cough swab. The control group received standard care. The primary outcome was UHCV at 4 months. RESULTS: 60 children, with a median age of 36.5 (range 14-61) months, were randomized. Median blood eosinophils were 5.2 (range 0-21)%, 27 of 60 (45%) children were atopic, and 8 of 60 (13%) had airway bacterial infection. There was no relationship between EVW, MTW and either blood eosinophils, atopic status or infection. 67% in each group were prescribed ICS. 15 of 30 control subjects and 16 of 30 patients in the intervention group had UHCV over 4 months (p = .8). The time to first UHCV was similar. 50% returned adherence monitors; in those, median ICS adherence was 67%. There were no differences in any parameter between those who did and did not have an UHCV. CONCLUSION: Clinical phenotype was unrelated to allergen sensitization or blood eosinophils. ICS treatment determined by blood eosinophils did not impact UHCV, but ICS adherence was poor.

Feasibility of lung clearance index in a clinical setting in pre-school children.

Lung function testing in pre-school children in the clinical setting is challenging. Most cannot perform spirometry and many infant lung function tests require sedation. Lung clearance index (LCI) derived from the multiple-breath washout (MBW) test has been shown to be sensitive to early disease changes but may be time consuming and so a shortened test (LCI0.5) may be more feasible in young children. We sought to establish feasibility of MBW in unsedated pre-school children in a clinic setting and hypothesised use of LCI0.5 would increase success rates.116 pre-school children (28 healthy controls and 88 with respiratory disease), median age 4.0 years (range 2-6 years), underwent MBW tests unsedated in a clinic setting, using sulfur hexafluoride as a tracer gas and an adapted photoacoustic gas analyser.81 (70%) out of 116 children completed LCI and 72% completed LCI0.5 measurement. Test success increased significantly in patients over 3 years (0% at <2.5 years, 33% at 2.5-3 years and 70% at >3 years, p<0.0001). LCI was elevated in those with respiratory disease compared with healthy controls.MBW is feasible in a clinic setting in unsedated pre-schoolers, particularly in those >3 years old, and LCI is raised in those with respiratory disease. Use of LCI0.5 did not increase success rate in pre-schoolers.

Electronic adherence monitoring identifies severe preschool wheezers who are steroid responsive.

Little is known about adherence to inhaled corticosteroids (ICS) in preschool children with troublesome wheeze. Children with aeroallergen senitization, or those reporting multiple trigger wheeze (MTW), are more likely to respond to ICS. We hypothesized that adherence to ICS and symptom control are only positively related in atopic children, or those reporting MTW. Patients aged 1 to 5 years with recurrent wheeze prescribed ICS were recruited from a tertiary respiratory clinic. Clinical phenotype and aeroallergen senitization were determined, and adherence assessed using an electronic monitoring device (Smartinhaler). Symptom control (test for respiratory and asthma control in kids [TRACK]), quality of life (PACQLQ), airway inflammation (offline exhaled nitric oxide) were assessed at baseline and follow-up. Forty-eight children (mean age 3.7 years; SD, 1.2) were monitored for a median of 112 (interquartile range [IQR], 91-126) days. At baseline n = 29 reported episodic viral wheeze and n = 19 reported MTW. Twenty-four out of 48 (50%) wheezers had suboptimal ICS adherence (<80%). Median adherence was 64% (IQR, 38-84). There was a significant increase in TRACK and PACQLQ in the group as a whole, unrelated to adherence. In subgroup analysis only atopic wheezers with moderate or good adherence ≥ 60% had a significant increase in TRACK. There was no relationship between clinical phenotype, and adherence or TRACK. In this pilot study, overall adherence to ICS was suboptimal and was positively related to symptom control in atopic wheezers only. Assessments of adherence are important in preschool troublesome wheezers before therapy escalation to help identify those with an ICS responsive phenotype.