Discussion
decline of lung function, lung diseases
INFLAMMATION, LUNG DISEASES
This proposed study has several strengths: (1) It is novel, because it includes subjects with mild (and potentially reversible) oral inflammation. (2) It is innovative, because it includes oral sanitization with lung function testing and measurements of the oral microbiome. (3) It has a high public health relevance, because this study examines the potential improvement of lung function in a period of maximum achieved lung function or at least before a major decline of lung function started and has the potential to develop a strategy to counteract against lung diseases in later life. (4) It might add a piece of causality, because of the interventional aspects and mediating effects by the changes of the microbiome. (5) It is a multidisciplinary research which combines expertise on lung physiology and lung function testing with oral health and oral microbiome and epidemiological skills and statistically modelling. (6) It is a cutting-edge project, because it brings together international experts in the field from Norway (PI: Randi J. Bertelsen), with the potential to extend this interventional study to other countries. (7) It goes beyond a simple observation and hypothesis generation, because this interventional study is a proof of principle.However, this study has also some limitations. The major limitation is related to the uncertainty about the results, because of the high novelty and the innovative characteristics of this proposed study. Due to the high methodological experience of the study group, the strong focus of an interventional study and the strong design, we believe to provide a sound answer to the underlying research question regardless of whether we could prove the primary hypothesis. (8) Finally, this trial also might have clinical implications, although the effect size of lung function changes may seem small. The power calculation of the study is based on assumed changes of 2% for FEV