title: Assessment of airflow limitation, airway inflammation, and symptoms during virus-induced wheezing episodes in 4- to 6-year-old children.
abstract: BACKGROUND
  It is disputed whether recurrent episodes of wheeze in preschool-aged children comprise a distinct asthma phenotype.
  
  
  OBJECTIVE
  We sought to prospectively assess airflow limitation and airway inflammation in children 4 to 6 years old with episodic virus-induced wheeze.
  
  
  METHODS
  Ninety-three children 4 to 6 years old with a history of mild, virus-induced episodes of wheeze who were able to perform acceptable fraction of exhaled nitric oxide (Feno) maneuvers and spirometry (with forced expiratory time ≥0.5 seconds) were followed prospectively. Lung function and Feno values were measured every 6 weeks (baseline) within the first 48 hours of an acute wheezing episode (day 0) and 10 and 30 days later. Symptom scores and peak flow measurement were recorded daily.
  
  
  RESULTS
  Forty-three children experienced a wheezing episode. At day 0, Feno values were significantly increased, whereas forced expiratory volume at 0.5 seconds (FEV(0.5)) significantly decreased compared with baseline (16 ppb [interquartile range {IQR}, 13-20 ppb] vs 9 ppb IQR, 7-11 ppb] and 0.84 L [IQR, 0.75-0.99 L] vs 0.99 L [IQR, 0.9-1.07 L], respectively; both P < .001). Airflow limitation at day 0 was reversible after bronchodilation. FEV(0.5) and Feno values were significantly associated with each other and with lower and upper respiratory tract symptoms when assessed longitudinally but not cross-sectionally at all time points independently of atopy. Feno and FEV(0.5) values returned to baseline levels within 10 days.
  
  
  CONCLUSIONS
  Mild episodes of wheeze in preschoolers are characterized by enhanced airway inflammation, reversible airflow limitation, and asthma-related symptoms. Feno values increase significantly during the first 48 hours and return to personal baseline within 10 days from the initiation of the episode. Longitudinal follow-up suggests that symptoms, inflammation, and lung function correlate well in this phenotype of asthma.
authors.affiliation: Department of Allergy and Clinical Immunology, 424 General Military Training Hospital, Thessaloniki, Greece. gnkonstantinou@gmail.com
authors.forename: George N
authors.initials: GN
authors.lastname: Konstantinou
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Xepapadaki
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Manousakis
authors.forename: Heidi
authors.initials: H
authors.lastname: Makrinioti
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Kouloufakou-Gratsia
authors.forename: Photini
authors.initials: P
authors.lastname: Saxoni-Papageorgiou
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Papadopoulos
mesh_terms: D002648:Child; D002675:Child, Preschool; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000503:physiopathology / Q000821:virology*; D008137:Longitudinal Studies; D008297:Male; D060737:Reproductive Tract Infections / Q000175:diagnosis* / Q000503:physiopathology / Q000821:virology*; D012135:Respiratory Sounds / Q000175:diagnosis* / Q000209:etiology*; D013147:Spirometry