Does Exhaled Nitric Oxide (FENO) Reflect Airway Inflammation In Mild To Moderate Asthma?

Abstract

Introduction: FENO is known to reflect eosinophilic airways inflammation in patients with moderate to severe asthma. Less is known about the relationship between FENO and other markers of airway inflammation and airway dysfunction in patients with a primary care diagnosis of asthma. This is important as in the UK up to 80% of asthma is managed purely in primary care and mild asthma may represent a different rather than simply less severe phenotype of asthma when compared to moderate to severe asthma. There is debate as to the role of monitoring FENO routinely in mild asthma. Methods: 200 non-smoking patients aged 18-75 with a GP diagnosis of mild to moderate asthma were recruited as part of a larger study. The inclusion criteria were; no need for oral steroids in the previous three months; no more than one exacerbation requiring oral steroids in the previous year; an ACQ score of less than 1.5; no hospitalisations with asthma exacerbation and less than ten pack years smoking history. All participants were asked to refrain from taking their ICS/LABA medications for 24-48hours prior to their appointment. Each participant performed a five flow exhaled nitric oxide test (FLEXFLOW, Aerocrine, Sweden) followed by spirometry (Vitallograph), blood tests for serum IgE level and serum eosinophil level, sputum induction for sputum eosinophil count, an ACQ questionnaire and methacholine challenge (PC20) using the Wright’s nebuliser technique. Data were analysed using STATA and Pearson’s correlation coefficient. Results: There was no significant correlation between baseline log (mean FENO 50ml) and log sputum eosinophil count (r= 0.1368, p=0.266). However there was a significant correlation between baseline log (mean FENO 50ml) and serum eosinophil level (r=0.3445, p<0.001), ACQ questionnaire (r=0.1625, p=0.035), log serum IgE level (r=0.2446, p=0.028), FEV1 % predicted (r=-0.1739, p=0.024), FVC % predicted (r=-0.1525, p=0.048) and FEV1/FVC ratio (r=-0.3015, p<0.001). Conclusion: Exhaled nitric oxide is thought to be a non-invasive biomarker of airway inflammation which could be used in place of more invasive techniques. However there appears to be no relationship between measures of airway inflammation in patients diagnosed with asthma in primary care. There is however a positive significant correlations between FENO at the 50ml profile and ACQ questionnaire, serum eosinophil level, log serum IgE level, FEV1 % predicted, FVC % predicted and FEV1/FVC ratio. FENO 50ml may reflect different aspects of airways disease and may not be suitable as an inflammometer in mild to moderate asthma.