Scientific Community - Protocol

Eligibility Criteria

Asthma will be defined as a recurrent wheezing condition diagnosed as asthma by a consultant paediatrician with a respiratory interest. All asthmatic children attending a clinic under the care of SPRING members between March 2008 and November 2010 will be eligible. Children with coexisting respiratory morbidity, eg cystic fibrosis, will be excluded. Children aged under 5 years will be eligible, despite reduced likelihood of gaining spirometry and ENO, since questionnaire data and DNA will be valuable in what we plan will become a longitudinal study.

Study Design

We will recruit up to 1000 children We obtain basic demographics from clinic lists (gender, age and postcode) for all eligible children, including those not recruited, in order to study potential bias in recruitment. Parents are invited by post to enrol their children. Parents and children are given a number of options:

  1. Complete asthma questionnaire at home and return with DNA sample in the post
  2. 1 above plus complete quality of life and dietary questionnaires and return by post
  3. 2 above plus attend for clinical assessment including spirometry, bronchdilator response, exhaled nitric oxide, skin prick testing and salivary cotinine

Questionnaires

Asthma questionnare. This includes questions used in a community-based study of genes and asthma in Scottish children (the BREATHE study6), domestic details from the BioBank and the Children's Asthma Control Test.

Paediatric Asthma Quality of Life Questionnaire7

The Scottish Collaborative Group semi-quantitative food frequency questionnaire version C1 is used. This is 121-item food frequency questionnaire. Separate questionnaires are used for children aged >11 years and ≤11 years.

ENO Spirometry and Bronchodilator Response

These are measured in accordance with standard guidelines. Short acting beta agonists are withheld for 6 hours and long acting beta agonists for 12 hours prior to testing. Exhaled NO will be measured using a portable NO analyser (NIOX MINO®). Spirometry is measured using a portable spirometer (ML3500, MicroLab). The bronchodilator response will be determined as the change in FEV1 15 minutes after inhalation of 400 microg salbutamol, delivered from a metered dose inhaler via spacer device.

Skin Prick Reactivity

Standard methodology will be used to determine skin prick reactivity to house dust mite, cat dander, egg and grass (ALK, Northampton). Positive and negative controls will be used. A positive skin test will be defined as a weal ≥3mm in longest diameter or, in cases of dermatographism, greater than the negative control.

DNA Collection, Storage and Analysis

DNA will be extracted from saliva collected using Oragene sampling kits. This method produces a median yield of 110ug of high quality DNA which should be sufficient for all future studies and processes such as whole genome analysis by Affymetrix gene chip or Illumina bead array.

Ethical Considerations and Governance

We have approval for the study from the Plymouth and Cornwall Research Ethics Committee and also from Research and Development departments in each recruiting centre. The study has been adopted by the Scottish Medicines for Children Network. At a monthly meeting, the researchers discuss recruiting in each centre and standard operating procedures are applied across all centres.