Title: Clinical utility and feasibility of a shortened multiple breath washout technique and offline exhaled nitric oxide in preschool children with wheezing disorders
Funder: Asthma UK

Abstract: <p>Although pulmonary function testing plays an important role in the diagnosis and management of asthma, assessments of lung function in preschool children with wheezing are not currently performed routinely as they are challenging in the clinical setting. The multiple breath washout technique provides a measure of function called the lung clearance index (LCI) and is recommended for lung function assessments in preschool children as it relies only on passive cooperation (tidal breathing). LCI measures the time to wash out either an inert gas such as sulphur hexafluoride or nitrogen washout by 100% oxygen; the longer the wash out time, the worse the peripheral airway gas mixing. Normal ranges have been established in young children. It is a very sensitive test of gas mixing in the distal airways, and may be abnormal in children with asthma despite them having normal spirometry. The technique allows bronchodilator responsiveness to be determined, as well as the identification of a group at high risk for asthma because of already impaired lung function. It has been shown to distinguish groups with different clinical phenotypes of preschool wheeze. It may also have utility in identifying those with a high risk for developing asthma, and to predict exacerbations, however, it is not used in routine clinical practice. We have found the duration of the test is the main factor that prevents reliable data from being obtained in the clinic. However, the duration for which gas is breathed in and out to obtain a value for LCI is arbitrary, and a shortened LCI has been shown to provide reliable data in older children, but has not been investigated in preschool children. A second non-invasive test that has been shown to distinguish preschool wheeze phenotypes is exhaled nitric oxide, which is a marker of airway inflammation. Our preliminary data suggests a positive relationship between LCI and exhaled nitric oxide. We therefore aim to determine the optimal shortest duration of LCI that can be used in preschool children to maximise successful tests and allow its use longitudinally in the clinic. In addition, we will confirm that shortening duration of washout does not sacrifice the relationship between exhaled nitric oxide and LCI, and the distinction between clinical wheeze phenotypes, as two quality control measures. Measurements of LCI and exhaled nitric oxide will be performed in preschool children aged 2-6 years with recurrent wheezing and compared to age matched healthy controls and disease controls (chronic cough and recurrent infections). This pilot study will allow us to determine the validity of a shortened LCI for preschool wheezers by assessing the ability to distinguish clinical wheeze phenotypes in a similar manner to the current gold standard full LCI. If successful, we will undertake a larger study that will compare the use of exhaled nitric oxide, shortened LCI and clinical wheeze phenotype to current clinical guidelines, that use clinical wheeze phenotype alone, to guide treatment of preschool wheeze.</p>


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY