Short summary

The main objective of this PhD study is to investigate whether elevated serum levels of Surfactant Protein D (SP-D), Microfibrillar-Associated Protein 4 (MFAP4) are associated with pediatric asthma, chronicity, and severity of asthma symptoms in a cohort of 1014 children, thoroughly investigated and diagnosed with asthma in 2003-2005. The subjects are invited to participate in a follow-up, including an extensive questionnaire-based interview, clinical examination, blood- and urine sampling, and lung function measurements, including mannitol provocation testing.

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Rationale

Childhood astma is the most prevalent chronic respiratory disease among children and adolescents, affecting approximately 110.000 in the age 0-17 years in Denmark. Asthma is associated with increased morbidity, reduced quality of life, and considerable expenditure estimated to 3-5,2 billion EUR in the European Union.

It is well-known that the disease is hard to diagnose because it is based on frequent airway symptoms, including cough, wheezing, and dyspnoea. Symptoms that are often interpreted differently among medical practitioners. Among toddlers, the diagnosis is mainly based on medical history and response to treatment, whereas the diagnosis among school children and adolescents is based on further examination including lung function measurement, bronchodilator test, provocation test, peak flow variability, and exhaled nitrogen oxid. Unfortunately, all these measurements are characterized by low sensitivity and specificity. Furthermore, children do not always present with classic symptoms of asthma, which implies that the condition is not diagnosed in some children. When the diagnosis has been established, a thorough prognostic evaluation is important to ensure adequate follow-up. Previous studies performed in Europe, USA and Asia have shown that 35-84% of individuals with asthma are not treated in accordance with international guidelines. The consequence of suboptimal treatment is poor asthma control and an increased risk of severe exacerbations. An optimal antiasthmatic treatment reduces risk of hospital admission and mortality whereas overuse of reliever medication is associated with severe exacerbations and increased asthma-related healthcare expenditure. Medical doctors lack valid tools to make correct asthma diagnoses and correct prognostic evaluation in children to ensure that the right medication is given to the right children at the right time.

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Description of the cohort

This study is a longitudinal investigation of all children from 0 to 15 yr diagnosed with asthma at the pediatric outpatient clinics at the hospitals in the region of Southern Denmark from October 1, 2003 to November 30, 2005 (Odense, Kolding, Sønderborg, and Esbjerg).

The children were primarily referred by their primary care practitioner, and all had at least one visit at a pediatric outpatient clinic. All visits included an extensive questionnaire-based interview (regarding atopic heredity, medical history, and environmental factors), clinical examination by a pediatrician, skin prick testing, and IgE measurements and lung function measurement when appropriate. Baseline serum was stored in a biobank for later analysis.

Data and biological material

The following examinations will be performed:

• Questionnaire-based interview
• Spirometri with reversibility test
• Mannitol provocation test (assessment of bronchial hyperreactivity)
• NO-measurement (degree of inflammation)
• Height, sitting height, parents height (estimation of final height)
• Weight and BMI
• Tanner staging and time of menarche
• Dual-Energy X-ray absorptiometry (DEXA)
• Assessment of quality of life ("Pediatric Asthma Quality of Life Questionnaire" and "Asthma Control Test")
• Blood and urine samples to biobank (Planned analysis: specific-IgE to a panel of inhalant allergens, SP-D, MFAP4 and cotinine)

Collaborating researchers and departments

H.C. Andersen Children's Hospital, Odense University Hospital

• Associate Professor Lone Agertoft, MD
• Professor Susanne Halken, MD, DMSc
• Head of Department Arne Høst, MD, DMSc

Institute for Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark

• Associate Professor Grith Lykke Sørensen, MSc, PhD

Institute of Public Health, Department of Environmental Medicine, University of Southern Denmark

• Professor Tina Kold Jensen, MD, PhD

Department of Pediatrics, Kolding Hospital

• Thomas Houmann, MD

Department of Pediatrics, Aabenraa Hospital

• Kirsten Arendt, MD

Department of Pediatrics, Esbjerg Hospital

• Jens Jakob Herche Petersen, MD

Publications associated with the project

Hoffmann-Petersen B, Suffolk R, Petersen JJH, Petersen TH, Brasch-Andersen C, Høst A, Halken S, Sorensen GL, Agertoft L. Association of serum surfactant protein D and SFTPD gene variants with asthma in Danish children, adolescents, and young adults. Immun Inflamm Dis. 2021 Nov 15. doi: 10.1002/iid3.560. Epub ahead of print. PMID: 34780682.