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


BMC Pulm Med. 2020;20(66) 

In This Article


Study Design and Participants

Data were collected retrospectively from March 2014 to March 2019 in the context of a clinical audit (Research ethics approval number AU201708–04). Patients were referred to the multidisciplinary SAC and seen on the basis of the clinical need. Referrals to the SAC were only accepted when made by a Paediatric Respiratory Specialist. Children were required to fulfil the European Respiratory Society (ERS) criteria for uncontrolled SA at the time of referral. Exceptions to those criteria included referrals of children who were not treated in accordance with GINA step 4 due to, for instance, prior side effects or lack of benefit with GINA step 4 treatment. No child was treated with biological agents before the first SAC visit because a comprehensive evaluation in the SAC was a prerequisite for the approval of prescribing biological agents in our department.

Nurse-led Home Visit

Prior to the first appointment in the SAC, a home visit was conducted to identify modifiable factors that could be addressed in order to improve the child's asthma control. The asthma clinical nurse consultant conducted an extensive assessment which included past medical history, inhaler check (technique and appropriateness of inhalers), adherence check, medication access, knowledge and understanding of asthma, indoor and outdoor allergen exposures, tobacco smoke exposure, allergic rhinitis, gastroesophageal reflux, child/family asthma management and the child's perspective on their home and school life. Paediatric asthma quality of life questionnaire (PAQLQ),[9] Asthma Control Test (ACT),[10,11] Asthma Control Questionnaire (ACQ-5),[12] Paediatric Index of Emotional Distress (PI-ED),[13] and Hospital Anxiety and Depression Scale (HADS)[14] were completed by the parent and child or nurse where appropriate.

SAC appointments (initial and follow-up) were attended by the asthma clinical nurse consultant, (a) paediatric respiratory specialist(s), and a general and adolescent paediatrician along with the parent(s)/carer(s) and the child. Future clinical management was determined after consideration of all available assessments by the multidisciplinary team in consultation with the family at the time of the visit.

Control Cohort

For some comparisons, data from the ongoing prospective birth cohort study Growing into Asthma (GIA)[15] were used. These children were born to asthmatic mothers who participated in the Management of Asthma in Pregnancy (MAP) study.[16] Children from the GIA cohort were followed-up at 10 years of age and stratified into children with and without doctor diagnosed asthma.

Pulmonary Function Testing

For the SAC patients, lung function testing was performed as clinically indicated and determined by the Paediatric Respiratory specialist in attendance at each appointment. Before each measurement, weight, length, and body mass index (BMI) were recorded.

For both cohorts, all lung function testing was performed according to ATS/ERS recommendations.[17,18] All measurements were carried out by qualified clinical respiratory scientists.


Spirometry was performed using the Medisoft Whole Body Plethysmograph System in SAC children (Medisoft, Sorinnes, Belgium) distributed by Ascencia. Melbourne, Australia. Three forced vital capacity (FVC) manoeuvres were performed, and the best value of FVC and FEV1 was recorded. This technique was repeated pre and post inhalation of 4 doses of a bronchodilator (BD, Salbutamol 0.1 mg per dose) via a Breath a Tech Spacer (Medical Developments International, Victoria, Australia).

Nitrogen Multiple Breath Washout (N2 MBW)

N2 MBW testing was performed using a commercially available device (Exhalyzer® D, Eco Medics AG, Duernten, Switzerland; Spiroware version 3.1), which measures N2 concentration indirectly using simultaneous assessment of O2 and CO2 concentrations. The test was performed in a seated position whilst watching a movie to encourage stable tidal breathing. A facemask interface was used for preschool children whilst a mouthpiece and nose clip was used in older children. A minimum of two (ideally three) technically acceptable trials were collected. Technically acceptable trials were determined using published quality control criteria,[19] based on consensus guideline recommendations.[20] A coefficient of variance (CoV) of within 10% for three trials and 5% for two trials was seen as reassuring of good data quality. Functional residual capacity (FRC) and the Lung Clearance Index (LCI) were reported as the mean of technically acceptable trials. The reference data within the software was used to define normality.[21]

Skin Prick Test

Skin prick testing (SPT) was conducted using the list of allergens (commonly requested Dermatophagoides pteronyssinus, Dermatophagoides farinae, grass and tree pollen mix, cat and dog dander, and Aspergillus fumigatus) requested by the Respiratory Specialist. A positive result was defined as 3 mm or greater than the negative saline control, determined by averaging maximal perpendicular wheal diameters 15 min after applying the lancet. The positive control was histamine base, 6 mg/ml (Stallergènes®, Antony, France), and had to be 3 mm or greater for a valid test. Patients were asked to withhold any antihistamines for 2 days prior to the test. GIA participants had their SPT standardised, and Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, dog, Aspergillus fumigatus, grass and tree pollen mix, and the standard food allergens (whole peanut extract, egg yolk, and egg white) were used.

Blood Tests

Blood tests such as total serum Immunoglobulin E (IgE), specific serum IgE (RAST), and blood eosinophils were requested if never done previously. Results were then checked and considered positive if higher than the normal range for each specific test.

Statistical Analysis

Categorical measures were summarised using counts and percentages, while continuous measures were summarised using means, median, standard deviations, and range. Statistical significance was determined using a nonparametric, two-tailed Mann-Whitney U-test or the parametric Student's t-test as appropriate. For the analysis of matched pair parameters, the paired t-test was performed.

Analysis of variance (ANOVA) was used to determine whether there were any statistically significant differences between the means of two or more independent (unrelated) groups, and when overall significance was discovered Post hoc testing was performed using a multiple comparison test.