title: Predictive value of lung function trend and FeNO for difficult asthma in children.
abstract: OBJECTIVE
  The aim of this study was to evaluate the predictive value of lung function and fraction of exhaled nitric oxide (FeNO) for difficult asthma in children.
  
  
  METHODS
  Children with asthma referred to an asthma clinic for uncontrolled persistent asthma on inhaled corticosteroids (ICSs) alone or in combination with a long-acting beta2-agonist and/or a leukotriene receptor antagonist were followed in a prospective 1-year study to identify difficult asthma. At the end of the study period, difficult asthma was considered for children with persistent asthma symptoms and/or frequent moderate/severe asthma exacerbations despite regular intake of ICSs (beclomethasone or equivalent) > 800 microg/d for at least 3 months, after correcting for adherence to treatment, inhalation technique, and comorbidities and after implementing an individualized treatment plan. The difficult asthma phenotype was characterized using a multidimensional approach combining clinical features and pathophysiologic features (lung function and inflammation). Unfavorable lung function trend (persistent airway obstruction and fluctuations in forced expiratory volume in the first second of alpha > 0.5) and persistently high FeNO levels (> 45 ppb despite increasing ICS doses) were analyzed as risk factors for difficult asthma in the logistic regression analysis together with male sex, atopy, concurrent severe rhinitis, obesity, psychopathology, exposure to tobacco smoke, low socioeconomic status, lack of adherence to treatment, and persistent bronchodilator response.
  
  
  RESULTS
  Forty-six asthmatic children (34 males, 74%) with a mean (SEM) age of 7.55 (3.04) years were enrolled. After 1 year, 24 children (52%) were labeled as having difficult asthma. Independent risk factors for difficult asthma were persistently high FeNO (P = .04), obesity (P = .04), and severe rhinitis (P = .03).
  
  
  CONCLUSIONS
  Persistently high FeNO predicts difficult asthma in children, while unfavorable lung function trend does not.
authors.affiliation: Department of Allergy and Clinical Immunology, Faculty of Medicine, Transylvania University, Brasov, Romania. ibrumaru@unitbv.ro
authors.forename: I
authors.initials: I
authors.lastname: Agache
authors.forename: C
authors.initials: C
authors.lastname: Ciobanu
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012129:Respiratory Function Tests; D012307:Risk Factors
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D009569:Nitric Oxide