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Published ahead of print on February 5, 2003, doi:10.1164/rccm.200206-549OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 11, June 2003, 1490-1495

A more recent version of this article appeared on June 1, 2003
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Submitted on June 12, 2002
Accepted on January 28, 2003

Clinical and biological heterogeneity in children with moderate asthma

Stefania La Grutta1, Rosalia Gagliardo2, Franco Mirabella2, Giovanni B Pajno3, Giovanni Bonsignore4, Jean Bousquet5, Vincenzo Bellia6, and Antonio M Vignola4*

1 Allergy Unit, Children Hospital-Azienda di Rilievo Nazionale e di Alta Specializzazione, Palermo, Italy, 2 Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale delle Ricerche, Palermo, Italy, 3 Istituto di Clinica Pediatrica, Universita di Messina, Messina, Italy, 4 Istituto di Medicina Generale e Pneumologia, Universita di Palermo, Palermo, Italy; Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale delle Ricerche, Palermo, Italy, 5 U454, Institut National de la Sante et de la Recherche Medicale, Montpellier, France, 6 Istituto di Medicina Generale e Pneumologia, Universita di Palermo, Palermo, Italy

* To whom correspondence should be addressed. E-mail: vignola.am{at}iol.it.

To evaluate the relationship between inflammatory markers and asthma severity in children, the amount of interleukin(IL)-8 and granulocyte-macrophage-colony-stimulating-factor (GM-CSF) released by peripheral-blood-mononuclear-cells (PBMC), exhaled nitric oxide (FENO)levels, p65 NF-{kappa}B subunit and phosphorylated I{kappa}B{alpha} (p-I{kappa}B{alpha}) expression by PBMC were assessed in 6 controls, 12 steroid naives intermittent and 17 moderate asthmatic children. To investigate their predictive value, biomarker levels were correlated with the number of exacerbations during a 18 months follow-up period. We found that GM-CSF release was higher in moderate and intermittent asthmatics than in controls, whereas IL-8 release was higher in moderate than in intermittent asthmatics and controls. FENO levels were similar among study groups. In moderate asthmatics, IL-8, GM-CSF and FENO significantly correlated with the exacerbation numbers. Moreover, p65 and p-I{kappa}B{alpha} levels were greater in moderate than in intermittent asthmatics and controls. According to GM-CSF, IL-8 and FENO levels, two distinct subgroups of moderate asthmatics (low- and high-producers) were identified. High producers experienced more exacerbations than low producers. This study shows ongoing inflammation associated with biological and clinical heterogeneity in moderate asthmatics in spite of regular treatment, and proposes that large prospective studies confirm the importance of biomarkers to assess inflammation and asthma control in asthmatic children.


Key words: asthma, inflammatory markers, fluticasone propionate




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