title: Persistent airflow obstruction in patients with asthma: Characteristics of a distinct clinical phenotype.
abstract: BACKGROUND
  Some patients with asthma present persistent airflow limitation but their clinical and inflammatory characteristics have not been extensively described. In this study we aimed to identify differences in the clinical, functional and inflammatory characteristics between patients with asthma with and without persistent airflow obstruction.
  
  
  METHODS
  Patients (n = 170) were consecutively recruited from two tertiary Asthma Clinics. Patients' demographics, pulmonary function tests, inflammatory cells in induced sputum, bronchial hyperresponsiveness (BHR, PD15 to methacholine) and treatment regimens were recorded.
  
  
  RESULTS
  Sixty patients (35.3%) presented persistent airflow obstruction. Besides differences in lung function, patients with persistent obstruction presented, lower methacholine PD20, higher exhaled NO, and higher eosinophil and neutrophil counts in induced sputum. The majority (71.7%) of the patients with persistent obstruction fulfilled the ATS criteria for severe refractory asthma (SRA), in contrast to 4.5% in the group without persistent obstruction. A cluster analysis identified three clinically relevant clusters: Cluster 1 (n = 56, not related to persistent airflow obstruction) included non-atopic patients, who did not receive high-dose ICS without SRA; Cluster 2 (n = 53, related to persistent airflow obstruction) included atopic patients, receiving high-dose ICS and/or oral CS, fulfilling SRA criteria; Cluster 3 (n = 61, not related to persistent airflow obstruction) included atopic patients not receiving high-dose ICS, without SRA.
  
  
  CONCLUSIONS
  Asthma patients with persistent airflow obstruction present a distinct asthma phenotype, with significant differences in clinical, functional and inflammatory characteristics compared to patients without fixed airway obstruction. These patients present more often severe refractory asthma and require more intense treatment.
authors.affiliation: 1st Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Elissavet
authors.initials: E
authors.lastname: Konstantellou
authors.affiliation: 2nd Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Andriana I
authors.initials: AI
authors.lastname: Papaioannou
authors.affiliation: 2nd Respiratory Medicine Department, University of Athens Medical School, Athens, Greece. Electronic address: ssat@hol.gr.
authors.forename: Stelios
authors.initials: S
authors.lastname: Loukides
authors.affiliation: 1st Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Patentalakis
authors.affiliation: 1st Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Papaporfyriou
authors.affiliation: 1st Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Hillas
authors.affiliation: 2nd Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Papiris
authors.affiliation: 1st Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koulouris
authors.affiliation: 1st Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Bakakos
authors.affiliation: 2nd Respiratory Medicine Department, University of Athens Medical School, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kostikas
mesh_terms: D000328:Adult; D000368:Aged; D000402:Airway Obstruction / Q000209:etiology* / Q000503:physiopathology; D001249:Asthma / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D001944:Breath Tests / Q000379:methods; D001985:Bronchial Provocation Tests / Q000379:methods; D001993:Bronchodilator Agents / Q000627:therapeutic use; D016000:Cluster Analysis; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D010641:Phenotype; D013183:Sputum / Q000166:cytology; D014797:Vital Capacity / Q000502:physiology
chemical_list: D001993:Bronchodilator Agents; D005938:Glucocorticoids; D009569:Nitric Oxide
keywords: Airways inflammation; Asthma; Cluster analysis; Persistent airflow obstruction; Phenotype