Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children

Robert C. Strunk, Stanley J. Szefler, Brenda R. Phillips, Robert S. Zeiger, Vernon M. Chinchilli, Gary Larsen, Kevin Hodgdon, Wayne J Morgan, Christine A. Sorkness, Robert F. Lemanske

Research output: Contribution to journalArticle

248 Citations (Scopus)

Abstract

Background: Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation. Insufficient information is available concerning correlations between eNO and biologic, physiologic, and clinical characteristics of asthma in children currently not taking controller medications. Objective: The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications. Methods: Children aged 6 to 17 years with mild to moderate persistent asthma, taking only albuterol as needed, were characterized during 2 visits 1 week apart before being randomly assigned into a clinical trial. At the screening visit, online measurements of eNO, spirometry before and after bronchodilator, and biomarkers of peripheral blood eosinophils, serum eosinophil cationic protein, total serum IgE, and urinary leukotriene E4 were obtained. During a week characterization period before randomization, symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device. At the randomization visit, eNO was repeated followed by a methacholine challenge and aeroallergen skin testing. Correlations and rank regression analyses between eNO and clinical characteristics, pulmonary function, and biomarkers were evaluated. Results: eNO was significantly correlated with peripheral blood eosinophils (r = .51, P < .0001), IgE (r = .48, P < .0001), and serum eosinophil cationic protein (r = .31, P = .0003) but not with urinary leukotriene E4 (r = .16, P = .08). A moderate correlation was found between eNO and the number of positive aeroallergen skin tests (r = .45, P < .0001). eNO did not correlate with FEV1 % predicted but was weakly correlated with FEV1/forced vital capacity (r = -.19, P = .032), bronchodilator response (r = .20, P = .023), and FEV1 PC 20 methacholine (r = -.31, P = .0005). No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements. The rank regression analysis demonstrated that 5 variables accounted for an R square of .52 (eosinophils [P < .0001], IgE [P = .0023], age [P < .0001], months of inhaled corticosteroid use in the year before study entry [P = .01], and FEV1 PC20 [P = .0061]). Conclusions: These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.

Original languageEnglish (US)
Pages (from-to)883-892
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume112
Issue number5
DOIs
StatePublished - Nov 2003

Fingerprint

Nitric Oxide
Asthma
Biomarkers
Eosinophils
Leukotriene E4
Immunoglobulin E
Eosinophil Cationic Protein
Methacholine Chloride
Bronchodilator Agents
Random Allocation
Regression Analysis
Inflammation
Albuterol
Spirometry
Vital Capacity
Skin Tests
Serum
Adrenal Cortex Hormones
Clinical Trials
Equipment and Supplies

Keywords

  • Biomarkers
  • Childhood asthma
  • Clinical characteristics
  • Eosinophils
  • Exhaled nitric oxide
  • IgE
  • Immediate hypersensitivity
  • Pulmonary function test measurements

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Strunk, R. C., Szefler, S. J., Phillips, B. R., Zeiger, R. S., Chinchilli, V. M., Larsen, G., ... Lemanske, R. F. (2003). Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. Journal of Allergy and Clinical Immunology, 112(5), 883-892. https://doi.org/10.1016/j.jaci.2003.08.014

Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. / Strunk, Robert C.; Szefler, Stanley J.; Phillips, Brenda R.; Zeiger, Robert S.; Chinchilli, Vernon M.; Larsen, Gary; Hodgdon, Kevin; Morgan, Wayne J; Sorkness, Christine A.; Lemanske, Robert F.

In: Journal of Allergy and Clinical Immunology, Vol. 112, No. 5, 11.2003, p. 883-892.

Research output: Contribution to journalArticle

Strunk, RC, Szefler, SJ, Phillips, BR, Zeiger, RS, Chinchilli, VM, Larsen, G, Hodgdon, K, Morgan, WJ, Sorkness, CA & Lemanske, RF 2003, 'Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children', Journal of Allergy and Clinical Immunology, vol. 112, no. 5, pp. 883-892. https://doi.org/10.1016/j.jaci.2003.08.014
Strunk, Robert C. ; Szefler, Stanley J. ; Phillips, Brenda R. ; Zeiger, Robert S. ; Chinchilli, Vernon M. ; Larsen, Gary ; Hodgdon, Kevin ; Morgan, Wayne J ; Sorkness, Christine A. ; Lemanske, Robert F. / Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children. In: Journal of Allergy and Clinical Immunology. 2003 ; Vol. 112, No. 5. pp. 883-892.
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abstract = "Background: Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation. Insufficient information is available concerning correlations between eNO and biologic, physiologic, and clinical characteristics of asthma in children currently not taking controller medications. Objective: The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications. Methods: Children aged 6 to 17 years with mild to moderate persistent asthma, taking only albuterol as needed, were characterized during 2 visits 1 week apart before being randomly assigned into a clinical trial. At the screening visit, online measurements of eNO, spirometry before and after bronchodilator, and biomarkers of peripheral blood eosinophils, serum eosinophil cationic protein, total serum IgE, and urinary leukotriene E4 were obtained. During a week characterization period before randomization, symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device. At the randomization visit, eNO was repeated followed by a methacholine challenge and aeroallergen skin testing. Correlations and rank regression analyses between eNO and clinical characteristics, pulmonary function, and biomarkers were evaluated. Results: eNO was significantly correlated with peripheral blood eosinophils (r = .51, P < .0001), IgE (r = .48, P < .0001), and serum eosinophil cationic protein (r = .31, P = .0003) but not with urinary leukotriene E4 (r = .16, P = .08). A moderate correlation was found between eNO and the number of positive aeroallergen skin tests (r = .45, P < .0001). eNO did not correlate with FEV1 {\%} predicted but was weakly correlated with FEV1/forced vital capacity (r = -.19, P = .032), bronchodilator response (r = .20, P = .023), and FEV1 PC 20 methacholine (r = -.31, P = .0005). No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements. The rank regression analysis demonstrated that 5 variables accounted for an R square of .52 (eosinophils [P < .0001], IgE [P = .0023], age [P < .0001], months of inhaled corticosteroid use in the year before study entry [P = .01], and FEV1 PC20 [P = .0061]). Conclusions: These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.",
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T1 - Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children

AU - Strunk, Robert C.

AU - Szefler, Stanley J.

AU - Phillips, Brenda R.

AU - Zeiger, Robert S.

AU - Chinchilli, Vernon M.

AU - Larsen, Gary

AU - Hodgdon, Kevin

AU - Morgan, Wayne J

AU - Sorkness, Christine A.

AU - Lemanske, Robert F.

PY - 2003/11

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N2 - Background: Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation. Insufficient information is available concerning correlations between eNO and biologic, physiologic, and clinical characteristics of asthma in children currently not taking controller medications. Objective: The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications. Methods: Children aged 6 to 17 years with mild to moderate persistent asthma, taking only albuterol as needed, were characterized during 2 visits 1 week apart before being randomly assigned into a clinical trial. At the screening visit, online measurements of eNO, spirometry before and after bronchodilator, and biomarkers of peripheral blood eosinophils, serum eosinophil cationic protein, total serum IgE, and urinary leukotriene E4 were obtained. During a week characterization period before randomization, symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device. At the randomization visit, eNO was repeated followed by a methacholine challenge and aeroallergen skin testing. Correlations and rank regression analyses between eNO and clinical characteristics, pulmonary function, and biomarkers were evaluated. Results: eNO was significantly correlated with peripheral blood eosinophils (r = .51, P < .0001), IgE (r = .48, P < .0001), and serum eosinophil cationic protein (r = .31, P = .0003) but not with urinary leukotriene E4 (r = .16, P = .08). A moderate correlation was found between eNO and the number of positive aeroallergen skin tests (r = .45, P < .0001). eNO did not correlate with FEV1 % predicted but was weakly correlated with FEV1/forced vital capacity (r = -.19, P = .032), bronchodilator response (r = .20, P = .023), and FEV1 PC 20 methacholine (r = -.31, P = .0005). No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements. The rank regression analysis demonstrated that 5 variables accounted for an R square of .52 (eosinophils [P < .0001], IgE [P = .0023], age [P < .0001], months of inhaled corticosteroid use in the year before study entry [P = .01], and FEV1 PC20 [P = .0061]). Conclusions: These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.

AB - Background: Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation. Insufficient information is available concerning correlations between eNO and biologic, physiologic, and clinical characteristics of asthma in children currently not taking controller medications. Objective: The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications. Methods: Children aged 6 to 17 years with mild to moderate persistent asthma, taking only albuterol as needed, were characterized during 2 visits 1 week apart before being randomly assigned into a clinical trial. At the screening visit, online measurements of eNO, spirometry before and after bronchodilator, and biomarkers of peripheral blood eosinophils, serum eosinophil cationic protein, total serum IgE, and urinary leukotriene E4 were obtained. During a week characterization period before randomization, symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device. At the randomization visit, eNO was repeated followed by a methacholine challenge and aeroallergen skin testing. Correlations and rank regression analyses between eNO and clinical characteristics, pulmonary function, and biomarkers were evaluated. Results: eNO was significantly correlated with peripheral blood eosinophils (r = .51, P < .0001), IgE (r = .48, P < .0001), and serum eosinophil cationic protein (r = .31, P = .0003) but not with urinary leukotriene E4 (r = .16, P = .08). A moderate correlation was found between eNO and the number of positive aeroallergen skin tests (r = .45, P < .0001). eNO did not correlate with FEV1 % predicted but was weakly correlated with FEV1/forced vital capacity (r = -.19, P = .032), bronchodilator response (r = .20, P = .023), and FEV1 PC 20 methacholine (r = -.31, P = .0005). No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements. The rank regression analysis demonstrated that 5 variables accounted for an R square of .52 (eosinophils [P < .0001], IgE [P = .0023], age [P < .0001], months of inhaled corticosteroid use in the year before study entry [P = .01], and FEV1 PC20 [P = .0061]). Conclusions: These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.

KW - Biomarkers

KW - Childhood asthma

KW - Clinical characteristics

KW - Eosinophils

KW - Exhaled nitric oxide

KW - IgE

KW - Immediate hypersensitivity

KW - Pulmonary function test measurements

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