Exhaled Nitric Oxide Monitoring Research Articles

Exhaled Nitric Oxide Daily Evaluation Is Effective in Monitoring Exposure to Relevant Allergens in Asthmatic Children

Though asthma is an airway inflammatory disease, the assessment of treatment efficacy is mainly based on symptom monitoring and the evaluation of lung function parameters. This study was aimed to evaluate the feasibility of exhaled nitric oxide monitoring in allergic asthmatic children who were exposed to relevant allergens in their homes. Twenty-two children allergic to mites underwent twice-daily fractional exhaled nitric oxide (FeNO) therapy using a portable device (NIOX MINO; Aerocrine AB; Stockholm, Sweden) and peak expiratory flow (PEF) measurements before, during, and after periods of natural exposure to mite allergens. The children were admitted to the study if they had lived in a mite-free environment for 3 months. They were observed in this environment for 10 days and then were moved to a site with natural mite exposure at sea level for 19 days. Finally, they were relocated to the mite-free environment for a period of 6 days for follow-up measurements. Significant differences were seen between the mite-free baseline FeNO level (26.4 parts per billion [ppb]; range, 19.3 to 36.2 ppb) and FeNO levels measured during natural mite exposure (37.3 ppb; 27.3 to 51 ppb) and after natural mite exposure (34.9 natural mite exposure; 25.2 to 48.2 ppb). Six children reported asthma symptoms during the mite exposure, and an increase in FeNO was observed in each case (p<0.031); PEF values showed no significant differences, whether between the different environments or between different periods. These data give further evidence for a possible role of frequent determinations of FeNO in order to promptly assess changes in the level of airway inflammation in asthmatic children.

Clinical studies of asthma phenotypes focusing on the role of leukotrienes

AbstractIntroduction: Inflammation in the airways in connection to asthma is complex and the mechanisms underlying the associated clinical symptoms involve the interaction of many different kinds of cells and mediators, giving rise to different phenotypes.Objective: The objective of the present thesis was to investigate the molecular and cellular mechanisms that result in two of these phenotypes, i.e. aspirin‐intolerant asthma (AIA) and allergic asthma. The main focus was on leukotrienes.Materials and Methods: (i) Thirty‐three subjects with diagnosed AIA were challenged with celecoxib, a selective inhibitor of cyclooxygenase (COX)‐2. (ii) With the ultimate objective of finding a marker that could be used to identify patients with leukotriene‐associated asthma, the capacity to produce leukotrienes and the responsiveness to inhaled leukotrienes were determined in 20 subjects with mild asthma and in 10 healthy control individuals. (iii) Eight individuals with mild allergic asthma were challenged repeatedly with low doses of allergen in an experimental model aimed at mimicking the natural exposure to allergen. Exhaled nitric oxide was measured throughout the study. (iv) Thirteen patients with allergic asthma were subjected to bronchial challenges with methacholine and leukotriene D4 (LTD4) prior to and after administration of 500‐µg fluticasone twice daily for 2 weeks, and their levels of exhaled nitric oxide and urinary leukotriene E4 (LTE4) were determined.Results: (i) Both escalating doses from 5–100 mg (administered in a blinded, placebo‐controlled study) and an open‐label challenge with 200 + 200 mg celecoxib were tolerated well by AIA individuals. (ii) Neither group exhibited a correlation between the formation of leukotriene B4 by their whole blood in response to ex vivo stimulation or urinary levels of LTE4 and airway responsiveness to LTD4. (iii) The level of nitric oxide in the air that they exhaled rose significantly. At the same time, these subjects did not report any symptoms of asthma, did not require rescue by bronchodilator medication, and did not display any change in the calibre of their airways. (iv) Inhalation of glucocorticoid attenuated the responsiveness to methacholine and reduced the level of exhaled nitric oxide, but neither the responsiveness to LTD4 nor urinary excretion of LTE4 was affected.Conclusions: (i) This finding indicates that the intolerance reaction leading to broncho‐constriction in patients with AIA is caused by inhibition of COX‐1 and, furthermore, provides a scientific basis for administration of selective inhibitors of COX‐2 to alleviate prostaglandin‐mediated pain and inflammation in these patients. (ii) In further attempts to predict which asthmatic patients will respond well to anti‐leukotriene treatment, investigations on the capacity for leukotriene synthesis, responsiveness to these agents and expression of their specific receptors in the lungs are being performed. (iii) Monitoring of exhaled nitric oxide on a daily basis may allow for early detection of exacerbation in subjects with allergic asthma. (iv) Neither the release nor the actions of leukotrienes appear to be sensitive to inhaled glucocorticoids, strengthening the rationale for using a combination of glucocorticosteroids and anti‐leukotrienes to treat allergic asthma.

Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years

Fractional exhaled nitric oxide (FE NO ) is used in monitoring of asthma. The aim of this multicenter study was to establish normal values of FE NO and assess feasibility in children with a standardized method and equipment approved for clinical use. FE NO was measured in healthy subjects of 4 to 17 years according to American Thoracic Society guidelines (single breath online, exhalation flow 50 mL/s) with a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden) in 3 European and 2 US centers. Each child performed 3 acceptable nitric oxide measurements within 6 attempts and completed an extended International Study of Asthma and Allergy in Children questionnaire. Measurement of FE NO was attempted in 522 children. Four hundred five children completed the study according to the protocol. Geometric mean FE NO in 405 children was 9.7 ppb, and the upper 95% confidence limit was 25.2 ppb. FE NO increased significantly with age, and higher FE NO was seen in children with self-reported rhinitis/conjunctivitis or hay fever. The success rate was age-dependent and improved from 40% in the children 4 years old to almost 100% from the age of 10 years. The repeatability of 3 approved measurements was 1.6 ppb (95% CI, 1.49-1.64 ppb). FE NO in healthy children is below 15 to 25 ppb depending on age and self-reported atopy. Measurement of FE NO by NIOX is simple and safe and has a good repeatability. Feasibility depends on age and may be difficult in the preschool child.

Exhaled nitric oxide levels correlate with measures of disease control in asthma

Background: Asthma guidelines emphasize maintaining disease control. However, objective measures of asthma disease control are lacking. Objective: We sought to examine the relationship between exhaled nitric oxide (NO) levels and measures of asthma disease control versus asthma disease severity. Methods: We performed a cross-sectional study of 100 patients (age range, 7-80 years) with asthma. We administered a questionnaire to identify characteristics of asthma, performed spirometric testing before and after administration of a bronchodilator, and measured exhaled NO levels in all participants. Results: Exhaled NO was significantly correlated with the following markers of asthma disease control: asthma symptoms within the past 2 weeks (P = .02), dyspnea score (P = .02), daily use of rescue medications (P = .01), and reversibility of airflow obstruction (P = .02). Exhaled NO levels were not correlated with the following markers of asthma disease severity: history of respiratory failure (P = .20), health care use (P = .08), fixed airflow obstruction (P = .91), or a validated asthma severity score (P = .19). Markers with relevance to both disease control and severity showed either a weak correlation (FEV1 and FEV1 percent predicted) or no correlation (controller drug use) with exhaled NO. Conclusion: We conclude that exhaled NO levels are correlated predominantly with markers of asthma control rather than asthma severity. Monitoring of exhaled NO may be useful in outpatient asthma management. (J Allergy Clin Immunol 2000;106:645-50.)