title: Sputum high mobility group box-1 in asthmatic children: a noninvasive sensitive biomarker reflecting disease status.
abstract: BACKGROUND
  The monitoring of asthma is based mainly on clinical history, physical examination, and lung function test evaluation. To improve knowledge of the disease, new biomarkers of airway inflammation, including high mobility group box-1 (HMGB1), are being developed.
  
  
  OBJECTIVE
  To evaluate sputum HMGB1 levels in children with stable, off-therapy, allergic asthma and to evaluate the relation between HMGB1 levels and lung function parameters.
  
  
  METHODS
  Fifty children with asthma (28 boys and 22 girls, median age 11.56 ± 1.41 years) and 44 healthy children (22 boys and 22 girls, median age 11.07 ± 2.12 years) were enrolled. Sputum HMGB1 was assessed in the cohort study. Lung function (predicted percentage of forced expiratory volume in 1 second [FEV1%] and forced expiratory flow between 25% and 75% [FEF25%-75%]), serum total IgE levels, and asthma severity by validated Global Initiative for Asthma criteria were recorded.
  
  
  RESULTS
  Sputum HMGB1 levels were higher in children with asthma than in healthy controls (100.68 ± 10.03 vs 9.60 ± 3.76 ng/mL, P < .0001). Sputum HMGB1 levels also were positively related to total IgE levels in children with asthma (r = 0.6567, P < .0001). An inverse and strict correlation between sputum HMGB1 levels and pulmonary function indices also were observed in children with mild (FEV1%, r = -0.86544, P < .0001; FEF25%-75%, r = -0.53948, P < .05), moderate (FEV1%, r = -0.99548, P < .0001; FEF25%-75%, r = -0.48668, P < .05), and severe (FEV1%, r = -0.90191, P < .0001; FEF25%-75%, r = -0.66777, P < .05) asthma.
  
  
  CONCLUSIONS
  The present study provides evidence that sputum HMGB1 is a sensitive biomarker of allergic asthma in children because it was increased and correlated directly with asthma severity and inversely with lung function indices.
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cuppari
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Manti
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Chirico
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Rosangela
authors.initials: R
authors.lastname: Caruso
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Salpietro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Giacchi
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Laganà
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Arrigo
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy. Electronic address: carmelo.salpietro@unime.it.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Salpietro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Leonardi
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D007073:Immunoglobulin E