Clinical implications of phenotyping in airway diseases : how blood eosinophil level affects disease prognosis and treatment of choice

Abstract

Phenotyping in airway diseases is one of the important research areas that has explosive development in recent years. Among different ways of phenotyping, blood eosinophil level is the most common one. Blood eosinophil level has been extensively studied as the biomarker for phenotyping of respiratory diseases. Yet, the current available evidence is still subject to debate and challenges. In this thesis, we present the research work we did related to phenotyping in airway diseases, focusing on the clinical implications from blood eosinophil level. We firstly presented how blood eosinophil level, as a single value, affects pulmonary and extra-pulmonary complications in airway diseases, followed by therapeutic implications, and lastly the role of blood eosinophil variability. In a retrospective study conducted to assess the association between baseline blood eosinophil count (BEC) and bronchiectasis exacerbation risks with subsequent validation with an independent patient cohort, patients with BEC < 250 cells/μL at clinical stable state were demonstrated to have increased risk of being hospitalised for bronchiectasis exacerbations. The relationship between asthma phenotyping and long-term renal outcome was assessed in a retrospective study, which demonstrated that non-eosinophilic asthma being an important risk factor for renal progression. We also conducted a territory-wide retrospective cohort study and demonstrated that chronic obstructive pulmonary disease (COPD) patients with BEC > 150 cells/μL upon admission, but not those with BEC < 150 cells/μL upon admission, had higher risks of developing respiratory and systemic complications from coronavirus disease 2019 (COVID-19), when compared with those without COPD. Next, we moved on and assess if blood eosinophil level affects the treatment of choices in bronchiectasis. A retrospective study was conducted among bronchiectasis patients, in which baseline BEC ≥3.5% was shown to be a potential indicator to predict the clinical benefits of ICS on preventing bronchiectasis exacerbation. While single value BEC is a well-established biomarker for phenotyping of airway diseases, challenges and criticisms do exist. In light of this, we conducted further studies on variability of baseline eosinophil level in airway diseases. A retrospective study among COPD patients demonstrated that baseline BEC variability at cut-off value of 50 cells/μL might predict COPD acute exacerbation (AECOPD) risks. Then we also conducted a prospective study. High variability of blood eosinophil level between baseline and upon AECOPD, as measured by absolute eosinophil variability with a cut-off at 105 cells/μL, was shown to be associated with shorter time to next AECOPD, as well as more episodes of subsequent AECOPD. This thesis presented how single value BEC impacts the prognosis and therapeutic options in airway diseases, in extra-pulmonary complications of airway diseases, as well as moving on assessing the role of variability of BEC in prognosticating airway diseases. The finding not only encored on what is known and reported, as well as bringing into insights on future research. What presented here is just the beginning of the endless journey in airway diseases research. Future research on airway disease phenotyping is on the pipeline, and we hope the research findings can benefit our patients.