The Development of Novel Clinical Tests to Diagnose and Monitor Asthma in Preschool Children
Condition: Asthma; Wheeze; Obstructive Sleep Apnea; Food Allergy; Virus
MeSH terms: Asthma; Sleep Apnea, Obstructive; Food Hypersensitivity
Study type: Observational

Summary: 
      The study will ascertain the ability of preschool lung function tests to distinguish healthy
      children from those with wheeze, and to differentiate phenotypes of wheezy children (high and
      low risk for asthma as defined by API) in order to predict response to therapy, and to
      explore the correlation between preschool lung function test results and symptoms, in order
      to develop objective methods for monitoring asthma.
    

Detailed description: 
      In Canada, the most common chronic disease of childhood is asthma. Childhood asthma places a
      significant burden on the health care system (refn). No objective preschool asthma diagnostic
      tools exist, and the current gold-standard, the Asthma Predictive Index, does not provide
      information about lung function and symptom management. In this study, it is hypothesized
      that the lung clearance index (LCI), a value derived from the multiple breath washout test,
      will be the most sensitive, responsive discriminative test for preschool asthma. If it proves
      useful in the monitoring and diagnosis of preschool asthma, LCI has the potential to improve
      the clinical management and thus potentially significantly reduce hospitalization rates for
      preschool children suffering with asthma. In this unique data set, the investigators will
      also compare the relative utility of the forced oscillation technique (FOT) and preschool
      spirometry with the LCI in order to detect abnormalities amongst those children at high risk
      for preschool asthma. In addition, the impact of sleep apnea as a risk factor for and
      modifier of asthma will be investigated in this study. Furthermore, changes to the
      composition of the nasal microbiome during and after a wheezing episodes and the role of
      viral infections in wheezing exacerbations will be explored. Finally, the utility of new
      methods of diagnosing food allergy, such as the basophil activation test, will be examined in
      this Canadian cohort.
    

Intervention name(s): Bronchodilator response; Allergy Skin Test; Multiple-Breath Washout; Forced Oscillation Technique; Spirometry; salbutamol; Nasal Brush; Blood sample; Basophil activation test; Nasal swab
Intervention type(s): Procedure; Procedure; Procedure; Procedure; Procedure; Drug; Procedure; Procedure; Procedure; Procedure
Intervention description(s): Bronchodilator (Salbutamol - dose dependent on participant prescription) to wheezing subjects. 15 minutes after bronchodilator, spirometry and FOT repeated.; Child will be tested for allergies to 17 different allergens, and positive (histamine) and negative (glycerin) controls, for a total of 19 allergens.; Facemask in children 3-5 yrs, Wash-in phase: medical air inhaled during tidal breathing until steady state. Bias flow switched to 100% oxygen. Wash-out phase: patient breathes in 100% oxygen until nitrogen levels reach ~2%. Each test in duplicate and average is calculated.; Sterile mouthpiece attached to FOT device. Patient is tested seated with noseclips and mouthpiece. FOT device produces oscillations at different frequencies (from that flow into lungs. Device measures resistance and reactance in lungs.; Forced exhale manoeuvre completed by participant into flow meter, measuring forced exhale volumes and speed.; Given during bronchodilator response.; Nasal brush of 1 inferior turbinate to collect epithelial cells. Collected on either nare, choice dependent on how clear the nare is (i.e. no mucous, no nasal mucosal edema, no major structural impediments).; 8mLs of venous blood collected using a butterfly needle of appropriate gauge. Blood sample used to collect CBC values, total IgE, serum, DNA, plasma, and whole blood.; Collect basophils from whole blood sample, and expose cells to food allergens in flow cytometry machine to measure allergic response, if any.; Gentle swabbing of both nasal openings to collect mucous sample for analysis of microbial contents (i.e. bacteria, virus, fungi).
Other intervention name(s): MBW; FOT; ventolin; BAT
Intervention MeSH terms: Albuterol; Bronchodilator Agents
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Wheezing preschool-aged subjects will be recruited within 5 days of their discharge from
        the Emergency Department at the Hospital for Sick Children.

        Healthy preschool-aged controls will be recruited from the community (concurrent
        observational studies being conducted by the PI at the Hospital for Sick Children, children
        of co-workers)
      
Biospecimen description: 
      Venous blood samples collected and divided into DNA pellet, plasma, serum, and whole blood.
      Small portion of sample sent for Total IgE and CBC. The eosinophil and IgE information will
      be used to assist with categorizing wheezy subjects into API categories. The DNA sample will
      be analyzed using genome-wide association studies (GWAS), and looking for single-nucleotide
      polymorphism (SNPs) that are known to be associated with asthma. The whole blood samples will
      be used for the basophil activation test; Urine samples; Nasal swab samples; Nasal brush
      samples;
    
Keywords: pediatric; lung ventilation inhomogeneity; preschool; asthma; wheeze