Fractional exhaled nitric oxide concentration (FENO) increases in inflammatory airway diseases such as asthma. The standard FENO-measurement at 50 ml/s exhalation flow rate is used in clinic to assess the inflammatory type of asthma and to predict and monitor treatment response to inhaled corticosteroids. If FENO is measured at multiple flow rates, mathematical models of the lungs can be utilized to partition the central and peripheral sources of NO. Production of NO in conducting airways can be further divided to tissue concentration and diffusivity of NO, which allows estimating whether the elevated FENO results from elevated NO concentration or changes in diffusion properties of the airway wall.
— The extended FENO-measurement has several promising clinical applications in diagnosing different pulmonary diseases in addition to predicting and monitoring treatment responses. It can also be utilized in detecting inflammation in the small airways and on alveolar level, Pikkuaho tells.
However, inadequate technical standardizing and inconsistent measurement protocols hinder the development of the method. Different mathematical methods and flow rates produce different results, making inter-study comparison challenging. There is also inadequate knowledge on repeatability of the measurement and normal variation of the NO parameters in healthy subjects.
The normal variation and repeatability of the NO parameters were investigated for the first time in this thesis. Effects of different flow rates and mathematical methods on the NO parameters were investigated diversely in different patient and age groups. This thesis also investigated how quickly commencement of corticosteroid treatment effects the NO parameters in asthma.
The repeatability of the extended FENO-measurement was found to be good. Small but significant diurnal variation was detected, thus scheduling of repeated measurements to same time of day is recommended until more knowledge is gained. Practical recommendations were made regarding mathematical methods and flow rates that can be used in the later technical standards. Also, it was found that reduced FENO after corticosteroid treatment in asthma results from rapid decrease in NO-concentration in bronchial wall mucosa.
— Once the extended FENO-measurement becomes standardized, its additional clinical value can be tested in trials and, if found clinically useful, ultimately integrated into clinical applications, Pikkuaho states.
The doctoral dissertation of M.D. Tuomas Pikkuaho in the field of medicine titled Measurement of Nitric Oxide Dynamics in Central and Peripheral Airways will be publicly examined in the Faculty of Medicine and Health Technology at Tampere University at 12:00 on Friday 01.04.2022 in auditorium F114 of Arvo building Arvo Ylpön katu 34. The Opponent will be Professor Andrei Malinovschi from Uppsala University. The Custos will be Professor Lauri Lehtimäki from Tampere University.
The event can also be followed via remote connection
The dissertation is available online at:
https://urn.fi/URN:ISBN:978-952-03-2324-0
Photo: Mari Pikkuaho