Treatment of atopic asthma in primary health care guided by exhaled nitric oxide measurement

Abstract

Aims: The overall aims of this thesis were to increase knowledge about how patients with asthma rate their health and investigate if we can improve asthma management, with focus on asthma as a chronic inflammatory disease, by use of measurement of the fraction of exhaled nitric oxide (FENO) in monitoring of asthma in primary health care.

Methods: Study I included data from a public health questionnaire, which was sent to 8,200 persons (age > 18 years) randomly selected from the population register in Stockholm County. After two reminders, 5,355 persons had responded (67.5 %). Study II was a longitudinal, non-controlled study. Twenty patients with physician-diagnosed atopic asthma and perennial asthma symptoms (age 18 - 50 years) were consecutively recruited from Runby primary health care centre and examined four times during eight weeks (baseline, 2, 4 and 8 weeks). Data for study III and IV were collected in a randomised, controlled study, conducted at 17 primary health care centres in the middle and south of Sweden. A total of 187 non-smoking participants with physician-diagnosed asthma, verified perennial allergy and ongoing inhaled corticosteroid (ICS) treatment (age 18 – 64 years) were randomised to FENO-guided treatment or usual care and were followed up for five visits during one year.

Results: Respondents with asthma in study I had approximately three times higher odds of fair/poor self-rated health (SRH) than those in the corresponding sex and age groups who did not have asthma, excepting younger women (18 – 44 years). SRH was associated at least as strong as quality of life to asthma. Study II showed a significant correlation between FENO and IgE-antibody levels against perennial allergens at baseline (r = 0.47, p = 0.04), which disappeared after a step-up in ICS treatment. Nine patients had persistently elevated FENO at last visit (mean 35 ppb vs. 16 ppb). This group was more frequently exposed to relevant allergens or colds (89 % vs. 27 %, p < 0.05) and had higher perennial IgE levels compared with the normalised group (mean 28.9 vs. 10.7 kU/l, p < 0.05). Results from study III showed that total and specific IgE levels decreased 10 – 36 % (p < 0.05 all, except for mugwort) over one year. The changes were not related to any change in allergen exposure, and specific IgG4 levels remained unaltered. The decrease in IgE against perennial allergens related to mean ICS dose (p = 0.030), ii months on leukotriene-receptor antagonist (LTRA) (p = 0.013) and change in FENO (p = 0.003), and interestingly also to change in the Asthma Control Questionnaire (ACQ) score (p = 0.012) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) score (p = 0.009), as well as change in SRH rating (p = 0.041). In study IV, the change in mAQLQ score over one year (primary endpoint) did not differ between the groups (p = 0.197), whereas the mAQLQ symptom domain score (p = 0.041) and the ACQ score (p = 0.045) both improved significantly more in the FENO-guided group. Furthermore, the moderate exacerbation rate was reduced by almost 50 % in the FENO-guided group (p = 0.024). Mean overall ICS use was similar in the two groups (p = 0.95).

Conclusions: In Sweden, men > 18 years and women > 45 years with asthma score SRH worse compared with people in corresponding sex and age groups without asthma, which indicates that there is a need to improve asthma management. Exposure to relevant allergens, and type and degree of sensitisa-tion, are important factors to consider when assessing the FENO value. Optimised anti-inflammatory treatment with ICS and LTRA in asthma patients with ongoing treatment at baseline resulted in reduced total and specific IgE levels which were unrelated to the degree of allergen exposure. Using FENO to guide anti-inflammatory treatment within primary care significantly improved asthma symptom control and reduced exacerbation rate in adults with atopic asthma without increasing overall ICS use. FENO-guided anti-inflammatory treatment appears useful to improve the management of patients with atopic asthma.