Clinical and Lung Function Outcomes in a Cohort of Children With Severe Asthma

Patricia de Gouveia Belinelo; Aleisha Nielsen; Bernadette Goddard; Lauren Platt; Carla Rebeca Da Silva Sena; Paul D. Robinson; Bruce Whitehead; Jodi Hilton; Tanya Gulliver; Laurence Roddick; Kasey Pearce; Vanessa E. Murphy; Peter G. Gibson; Adam Collison; Joerg Mattes

Disclosures

BMC Pulm Med. 2020;20(66) 

In This Article

Results

Subject Characteristics

Twenty-five children were managed in the SAC between 2014 and 2019. Of those, two patients under the age of 4 years were excluded in this analysis due to the uncertainty of asthma diagnosis in this age. In regards to family history, 30% (n = 7) had a history of maternal asthma, 13% (n = 3) had a history of paternal asthma, 9% (n = 2) had a history of both maternal and paternal asthma, while 39% (n = 9) had no history of parental asthma. For two children, no information about parents' health status was available. The baseline characteristics were compared to 20 children from the GIA birth cohort study, of whom 7 children had mild to moderate asthma, and 13 were not diagnosed with asthma (Table 1).

While the median age was 10 to 12 years in all cohorts, the range was greater in the SAC cohort as expected, with the youngest child being 4 years of age and the oldest 16 years of age. The median ACT was 15 in the SAC cohort with some SAC patients (n = 6 out of 25) having had satisfactory asthma control (score > 19) in the past 4 weeks before their first SAC visit.

Further clinical characteristics of the SAC cohort are shown in Table 2. Median onset of asthma symptoms was at 1.5 years of age, and half of all SAC children were admitted to hospital for asthma in the past 12 months with a median number of three hospitalisations in the previous year. Two of those patients also had admissions to the Paediatric Intensive Care Unit (PICU) in the previous year.

The PAQLQ has 23 questions in 3 domains (symptoms, activity limitation, and emotional function), and children were asked to think about the previous week and respond to each of the 23 questions on a 7-point scale (7 = not bothered at all; 1 = extremely bothered). The median PAQLQ score was five and ranged from 3 to 7 (Table 2).

The median daily dose of inhaled corticosteroids was 2000mcg beclomethasone equivalents ranging between 640 and 4000mcg. Most children were atopic (n = 20 out of 23 positive in SPT or RAST) and had blood eosinophilia (n = 17 out of 23 with > 300 cells/mcl). A subpopulation of SAC children underwent bronchoscopy (n = 9) subsequent to the first visit with the main purpose to characterise their type of airways inflammation and to assess for pathogen growth (n = 8) and/or to exclude airway malformations (n = 1) (Table 2).

Lung Function at First SAC Visit

Lung function data at baseline are summarised in Table 3. FEV1% predicted, and FEV1/FVC% were significantly lower in SAC children both before and after bronchodilator inhalation as compared to children with doctor-diagnosed asthma and children without asthma even if BD response tended to be largest in the SAC children. In those children where N2 MBW was performed (n = 14, 61%), LCI was significantly higher in SAC children versus those with or without an asthma diagnosis (Table 3). The proportion of the cohort with an LCI outside of the normal range was higher than FEV1% (79% versus 52%, respectively, Table 3). Correlation between LCI and FEV1% (rs = − 0.699, p = 0.005, n = 14) showed to be significant, while correlation between LCI and residual volume to total lung capacity percentage ratio (RV/TLC%; "trapped air") was not significant (r = 0.402; p = 0.173; n = 13).

SAC Follow-up Visit

Nine SAC children were not followed-up; reasons included that they were unable to attend the follow-up (n = 1) and have not yet attended their appointment (n = 8). The follow-up assessment was performed after an average of 26 months from the first visit (median 32, range 4 to 56 months). In the 16 SAC children who had a follow-up SAC visit, a significant improvement in FEV1% predicted, FEV1/FVC %, and ACT score were observed while the reduction in LCI (11.0 to 9.5, p = 0.237) was not significant in the 6 subjects with N2 MBW at two occasions (Table 4).

Seven SAC children were commenced on biologics (n = 4 omalizumab; n = 3 benralizumab) before the follow-up SAC visit, while nine children received intervention without commencement of biologics (Table 5). Non-biologic treatment interventions were very diverse. They included nurse-led educational, behavioural and environmental interventions, and changes in medication (e.g., inhaler device, treatment of allergic rhinitis, azithromycin as needed[24]).

Improvements in lung function were significant for FVC % predicted before and after BD in the cohort of children treated with biologics (Table 5). In contrast, improvements in lung function were significant for FEV1% predicted and FEV1/FVC % but not FVC % predicted before and after BD in the cohort of children receiving intervention that did not include biologics (Table 5).

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