Abstract
BACKGROUND—Increased fractional exhaled NO concentrations (FENO) and blood/tissue eosinophilia are frequently reported in allergic children with mild asthma and are thought to reflect the intensity of the inflammation characterising the disease. The aim of this study was to investigate possible differences in FENO levels or in the intensity of the blood eosinophilia in allergic and non-allergic asthmatic children. METHODS—112 children with stable, mild, intermittent asthma with a positive bronchial challenge to methacholine were consecutively enrolled in the study; 56 were skin prick test and RAST negative (non-sensitised) while 56 were sensitised to house dust mites (23 only to house dust mites (monosensitised) and 33 were sensitised to mites and at least another class of allergens (pollens, pet danders, or moulds)). Nineteen sex and age matched healthy children formed a control group. RESULTS—Compared with non-allergic patients, allergic children had a significantly higher rate of blood eosinophilia (p=0.0001) with no differences between mono- and polysensitised individuals. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% of vital capacity (FEF25-75%), and the degree of bronchial reactivity to methacholine were similar in non-atopic and atopic children, with no differences between mono- and polysensitised individuals. FENO levels measured by chemiluminescence analyser were higher in asthmatic children (15.9(14.3) ppb) than in the control group (7.6 (1.6) ppb, p=0.04) and higher in allergic patients (23.9 (2.1) ppb) than in non-allergic patients (7.9 (0.8) ppb, p=0.0001), but there were no differences between mono- and polysensitised individuals (p>0.1). Significant correlations between blood eosinophilia and FENO levels were seen only in allergic (r=0.35, p<0.01) and in polysensitised individuals (r=0.45, p<0.05). CONCLUSIONS—In children with mild asthma, a similar degree of functional disease severity may be associated with a higher inflammatory component in allergic than in non-allergic subjects.
Full Text
The Full Text of this article is available as a PDF (178.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Artlich A., Hagenah J. U., Jonas S., Ahrens P., Gortner L. Exhaled nitric oxide in childhood asthma. Eur J Pediatr. 1996 Aug;155(8):698–701. doi: 10.1007/BF01957156. [DOI] [PubMed] [Google Scholar]
- Baraldi E., Azzolin N. M., Zanconato S., Dario C., Zacchello F. Corticosteroids decrease exhaled nitric oxide in children with acute asthma. J Pediatr. 1997 Sep;131(3):381–385. doi: 10.1016/s0022-3476(97)80062-5. [DOI] [PubMed] [Google Scholar]
- Barnes P. J., Liew F. Y. Nitric oxide and asthmatic inflammation. Immunol Today. 1995 Mar;16(3):128–130. doi: 10.1016/0167-5699(95)80128-6. [DOI] [PubMed] [Google Scholar]
- Bentley A. M., Meng Q., Robinson D. S., Hamid Q., Kay A. B., Durham S. R. Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. Am J Respir Cell Mol Biol. 1993 Jan;8(1):35–42. doi: 10.1165/ajrcmb/8.1.35. [DOI] [PubMed] [Google Scholar]
- Bentley A. M., Menz G., Storz C., Robinson D. S., Bradley B., Jeffery P. K., Durham S. R., Kay A. B. Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis. 1992 Aug;146(2):500–506. doi: 10.1164/ajrccm/146.2.500. [DOI] [PubMed] [Google Scholar]
- Berlyne G. S., Parameswaran K., Kamada D., Efthimiadis A., Hargreave F. E. A comparison of exhaled nitric oxide and induced sputum as markers of airway inflammation. J Allergy Clin Immunol. 2000 Oct;106(4):638–644. doi: 10.1067/mai.2000.109622. [DOI] [PubMed] [Google Scholar]
- Bland J. M., Altman D. G. Measurement error. BMJ. 1996 Sep 21;313(7059):744–744. doi: 10.1136/bmj.313.7059.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crimi E., Spanevello A., Neri M., Ind P. W., Rossi G. A., Brusasco V. Dissociation between airway inflammation and airway hyperresponsiveness in allergic asthma. Am J Respir Crit Care Med. 1998 Jan;157(1):4–9. doi: 10.1164/ajrccm.157.1.9703002. [DOI] [PubMed] [Google Scholar]
- Folkard S. G., Westwick J., Millar A. B. Production of interleukin-8, RANTES and MCP-1 in intrinsic and extrinsic asthmatics. Eur Respir J. 1997 Sep;10(9):2097–2104. doi: 10.1183/09031936.97.10092097. [DOI] [PubMed] [Google Scholar]
- Frank T. L., Adisesh A., Pickering A. C., Morrison J. F., Wright T., Francis H., Fletcher A., Frank P. I., Hannaford P. Relationship between exhaled nitric oxide and childhood asthma. Am J Respir Crit Care Med. 1998 Oct;158(4):1032–1036. doi: 10.1164/ajrccm.158.4.9707143. [DOI] [PubMed] [Google Scholar]
- Gleich G. J. The eosinophil and bronchial asthma: current understanding. J Allergy Clin Immunol. 1990 Feb;85(2):422–436. doi: 10.1016/0091-6749(90)90151-s. [DOI] [PubMed] [Google Scholar]
- Gratziou C., Lignos M., Dassiou M., Roussos C. Influence of atopy on exhaled nitric oxide in patients with stable asthma and rhinitis. Eur Respir J. 1999 Oct;14(4):897–901. doi: 10.1034/j.1399-3003.1999.14d28.x. [DOI] [PubMed] [Google Scholar]
- Hoekstra M. O., Hovenga H., Gerritsen J., Kauffman H. F. Eosinophils and eosinophil-derived proteins in children with moderate asthma. Eur Respir J. 1996 Nov;9(11):2231–2235. doi: 10.1183/09031936.96.09112231. [DOI] [PubMed] [Google Scholar]
- Humbert M., Durham S. R., Ying S., Kimmitt P., Barkans J., Assoufi B., Pfister R., Menz G., Robinson D. S., Kay A. B. IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against "intrinsic" asthma being a distinct immunopathologic entity. Am J Respir Crit Care Med. 1996 Nov;154(5):1497–1504. doi: 10.1164/ajrccm.154.5.8912771. [DOI] [PubMed] [Google Scholar]
- Hunt J. F., Fang K., Malik R., Snyder A., Malhotra N., Platts-Mills T. A., Gaston B. Endogenous airway acidification. Implications for asthma pathophysiology. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):694–699. doi: 10.1164/ajrccm.161.3.9911005. [DOI] [PubMed] [Google Scholar]
- Jeffery P. K., Godfrey R. W., Adelroth E., Nelson F., Rogers A., Johansson S. A. Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma. A quantitative light and electron microscopic study. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):890–899. doi: 10.1164/ajrccm/145.4_Pt_1.890. [DOI] [PubMed] [Google Scholar]
- Kay A. B. Asthma and inflammation. J Allergy Clin Immunol. 1991 May;87(5):893–910. doi: 10.1016/0091-6749(91)90408-g. [DOI] [PubMed] [Google Scholar]
- Kobzik L., Bredt D. S., Lowenstein C. J., Drazen J., Gaston B., Sugarbaker D., Stamler J. S. Nitric oxide synthase in human and rat lung: immunocytochemical and histochemical localization. Am J Respir Cell Mol Biol. 1993 Oct;9(4):371–377. doi: 10.1165/ajrcmb/9.4.371. [DOI] [PubMed] [Google Scholar]
- Marshall H. E., Stamler J. S. NO waiting to exhale in asthma. Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):685–687. doi: 10.1164/ajrccm.161.3.16134. [DOI] [PubMed] [Google Scholar]
- Martin U., Bryden K., Devoy M., Howarth P. Increased levels of exhaled nitric oxide during nasal and oral breathing in subjects with seasonal rhinitis. J Allergy Clin Immunol. 1996 Mar;97(3):768–772. doi: 10.1016/s0091-6749(96)80154-0. [DOI] [PubMed] [Google Scholar]
- Nathan C., Xie Q. W. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994 Sep 23;78(6):915–918. doi: 10.1016/0092-8674(94)90266-6. [DOI] [PubMed] [Google Scholar]
- Nelson B. V., Sears S., Woods J., Ling C. Y., Hunt J., Clapper L. M., Gaston B. Expired nitric oxide as a marker for childhood asthma. J Pediatr. 1997 Mar;130(3):423–427. doi: 10.1016/s0022-3476(97)70204-x. [DOI] [PubMed] [Google Scholar]
- Oddera S., Silvestri M., Balbo A., Jovovich B. O., Penna R., Crimi E., Rossi G. A. Airway eosinophilic inflammation, epithelial damage, and bronchial hyperresponsiveness in patients with mild-moderate, stable asthma. Allergy. 1996 Feb;51(2):100–107. doi: 10.1111/j.1398-9995.1996.tb04565.x. [DOI] [PubMed] [Google Scholar]
- Ohashi Y., Motojima S., Fukuda T., Makino S. Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma. Am Rev Respir Dis. 1992 Jun;145(6):1469–1476. doi: 10.1164/ajrccm/145.6.1469. [DOI] [PubMed] [Google Scholar]
- Piacentini G. L., Bodini A., Costella S., Suzuki Y., Zerman L., Peterson C. G., Boner A. L. Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children. Eur Respir J. 2000 May;15(5):839–843. doi: 10.1034/j.1399-3003.2000.15e05.x. [DOI] [PubMed] [Google Scholar]
- Piacentini G. L., Bodini A., Costella S., Vicentini L., Mazzi P., Sperandio S., Boner A. L. Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children. Eur Respir J. 1999 Jun;13(6):1386–1390. doi: 10.1183/09031936.99.13613919. [DOI] [PubMed] [Google Scholar]
- Pizzichini E., Pizzichini M. M., Efthimiadis A., Evans S., Morris M. M., Squillace D., Gleich G. J., Dolovich J., Hargreave F. E. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308–317. doi: 10.1164/ajrccm.154.2.8756799. [DOI] [PubMed] [Google Scholar]
- Silvestri M., Oddera S., Crimi P., Rossi G. A. Frequency and specific sensitization to inhalant allergens within nuclear families of children with asthma and/or rhinitis. Ann Allergy Asthma Immunol. 1997 Dec;79(6):512–516. doi: 10.1016/S1081-1206(10)63058-X. [DOI] [PubMed] [Google Scholar]
- Silvestri M., Oddera S., Sacco O., Balbo A., Crimi E., Rossi G. A. Bronchial and bronchoalveolar inflammation in single early and dual responders after allergen inhalation challenge. Lung. 1997;175(4):277–285. doi: 10.1007/pl00007574. [DOI] [PubMed] [Google Scholar]
- Silvestri M., Spallarossa D., Battistini E., Brusasco V., Rossi G. A. Dissociation between exhaled nitric oxide and hyperresponsiveness in children with mild intermittent asthma. Thorax. 2000 Jun;55(6):484–488. doi: 10.1136/thorax.55.6.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silvestri M., Spallarossa D., Frangova Yourukova V., Battistini E., Fregonese B., Rossi G. A. Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma. Eur Respir J. 1999 Feb;13(2):321–326. doi: 10.1034/j.1399-3003.1999.13b17.x. [DOI] [PubMed] [Google Scholar]
- Smith D. L., Deshazo R. D. Bronchoalveolar lavage in asthma. An update and perspective. Am Rev Respir Dis. 1993 Aug;148(2):523–532. doi: 10.1164/ajrccm/148.2.523. [DOI] [PubMed] [Google Scholar]
- Tang C., Rolland J. M., Ward C., Quan B., Walters E. H. IL-5 production by bronchoalveolar lavage and peripheral blood mononuclear cells in asthma and atopy. Eur Respir J. 1997 Mar;10(3):624–632. [PubMed] [Google Scholar]
- Virchow J. C., Jr, Kroegel C., Walker C., Matthys H. Inflammatory determinants of asthma severity: mediator and cellular changes in bronchoalveolar lavage fluid of patients with severe asthma. J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S27–S40. [PubMed] [Google Scholar]
- Walker C., Bode E., Boer L., Hansel T. T., Blaser K., Virchow J. C., Jr Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis. 1992 Jul;146(1):109–115. doi: 10.1164/ajrccm/146.1.109. [DOI] [PubMed] [Google Scholar]
- Yates D. H., Kharitonov S. A., Barnes P. J. Effect of short- and long-acting inhaled beta2-agonists on exhaled nitric oxide in asthmatic patients. Eur Respir J. 1997 Jul;10(7):1483–1488. doi: 10.1183/09031936.97.10071483. [DOI] [PubMed] [Google Scholar]
- Ying S., Humbert M., Barkans J., Corrigan C. J., Pfister R., Menz G., Larché M., Robinson D. S., Durham S. R., Kay A. B. Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol. 1997 Apr 1;158(7):3539–3544. [PubMed] [Google Scholar]
- Youroukova V. F., Oddera S., Silvestri M., Spallarossa D., Rossi G. A. Blood eosinophilia and degree of sensitization to house dust mites in preschool and school children with asthma. J Asthma. 1998;35(6):489–496. doi: 10.3109/02770909809071002. [DOI] [PubMed] [Google Scholar]