Abstract Rationale Self-monitoring of peak expiratory flow (PEF) provides an objective means of assessing asthma control. However, international asthma management guidelines differ in their cutoff values for PEF variability (typically 10-20%), and the clinical relevance of PEF assessment in routine care remains uncertain. Furthermore, few studies have investigated PEF exclusively in patients with refractory asthma. Using longitudinal data from a well-characterized cohort, we aimed to identify novel PEF-derived indices predictive of future pulmonary function decline or asthma exacerbation. Objectives To investigate whether PEF fluctuation is associated with prognosis, specifically, decline in lung function or asthma exacerbation in patients with refractory asthma. Methods This study included 127 subjects with severe asthma, defined by the 2000 ATS criteria, enrolled in the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (UMIN ID: 000003254). Participants, including current and former smokers, recorded PEF twice daily (morning and afternoon) for 28 consecutive days in February, May, August, and November over a 3-year period, using an electronic PEF monitor (Piko-1®, nSpire Health, USA). To minimize inter-individual variability, we calculated the “monthly-normalized PEF (mPEF)” by normalized each PEF value by the individual’s monthly mean. Asthma exacerbation was defined as systemic corticosteroid use for ≥3 days. The annual change in FEV1 was estimated using a linear mixed-effects model among participants who had performed pulmonary function tests at least 3 times in 5-year follow-up as previously described (Kimura H, et al. Ann Allergy Asthma Immunol 2022). Results The standard deviation of mPEF showed a significant negative correlation with the annual change in FEV1, consistent across the 3-year observation period. Similar negative correlations were observed for both day-to-day and within-day differences in mPEF between morning and afternoon values, with stronger associations than when using raw PEF values. Participants with mPEF variation exceeding 9% exhibited a greater annual decline in FEV1 (Year1: 37.2 mL/year vs. 31.0mL/year; Year2 40.3 mL/year vs. 28.9 mL/year; Year3 39.6 mL/year vs. 30.3mL/year). In contrast, mPEF variability was not significantly associated with the frequency of asthma exacerbations during the study period. Conclusions Monthly normalization of PEF within individuals enhances the sensitivity of detecting clinically meaningful fluctuations in refractory asthma. Increased mPEF variability (9%) was associated with accelerated decline in lung function, suggesting that mPEF may serve as a practical prognostic marker for long-term respiratory deterioration in refractory asthma. This abstract is funded by: a scientific research grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (24249049 to M.N., 26461151 to S.K.) and a research grant from Japan Allergy Foundation, AstraZeneca K.K., and Kyorin Pharmaceutical Co., Ltd..
Kimura et al. (Fri,) studied this question.