THE RELEVANCE OF PHYSIOLOGICAL SMALL AIRWAYS FUNCTION IN DIAGNOSING ASTHMA AND ASSESSING BRONCHODILATOR RESPONSE

Abstract

Asthma is a common, chronic and heterogenous disease that is characterised by variable flow rate. Objectively assessing and diagnosing asthma can be difficult due to disease variability. Testing bronchodilator response (BDR) is one of the objective assessments for asthma, however, BDR can be found in other diseases such as chronic obstructive pulmonary disease (COPD) patients. Small airways dysfunction (SAD) is common in asthma and COPD, however the utility or standards of small airways function is new well described in asthma guidelines. The aim of this thesis was to evaluate the current evidence for the use of physiological small airways function in the diagnosis of asthma. Furthermore, the thesis aimed to evaluate the current evidence for small airways BDR compared to larger airways. It also aimed to understand the relationship between large and small airways indices using spirometry and the prevalence and risk factors of SAD. Firstly, a systematic review was conducted to review the current evidence for using physiological small airways tests in diagnosing asthma which includes spirometry (MMEF and FEF50) and Oscillometry (R5, R5-20, Ax, and X5). Ten studies were included in the review. Overall, studies were small, heterogeneous and were not standardised, however, differences were found in small airways measurements compared to healthy controls. Secondly, a retrospective analysis of real-world data assessed the physiological measurements of SAD, its prevalence in asthma and in those with airflow obstruction (AO), and risk factors for SAD. SAD was prevalent in asthma and although a strong relation was found between small and large airways indices, some patients had evidence of SAD without AO. This highlighted the potential importance of assessing the small airways, especially in smokers, which was found to be associated with SAD in asthma. Thirdly, a systematic review was conducted to assess the BDR in the small airways compared to large airways (forced expiratory volume in the 1st second (FEV1)) in asthmatics patients. The studies were small, with diverse methodologies used to conduct the BDR assessment. However, greater BDR was reported for small airways indices compared to FEV1 and approximately 25% of patients demonstrated BDR in the small airways tests but not in FEV1. Finally, a retrospective analysis of real-world data was conducted to assess the BDR for the large and the small airways and their relation to SAD. A greater improvement was found in small airways indices and SAD at baseline was found to be a predictor for a positive BDR for both FEV1 and MMEF, whereas AO was not. Overall, this thesis suggests there might be utility in assessing the small airways in asthma, but that standardisation is needed in order to enable definitive research studies.