title: Evaluation of the PPAR-γ Agonist Pioglitazone in Mild Asthma: A Double-Blind Randomized Controlled Trial.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial.
  
  
  METHODS
  Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency's reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis.
  
  
  RESULTS
  There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02).
  
  
  CONCLUSIONS
  We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01134835.
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: J R
authors: JR
authors: Anderson
authors: Liverpool School of Tropical Medicine, Liverpool, UK and Aintree University Hospital NHS Foundation Trust, Fazakerley, United Kingdom.
authors: K
authors: http://orcid.org/0000-0002-8118-8871
authors: K
authors: Mortimer
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: L
authors: L
authors: Pang
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: K M
authors: KM
authors: Smith
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: H
authors: H
authors: Bailey
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: D B
authors: DB
authors: Hodgson
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: D E
authors: DE
authors: Shaw
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: A J
authors: AJ
authors: Knox
authors: Nottingham Respiratory Research Unit, University of Nottingham, Clinical Sciences Building, City Hospital, Hucknall Road, Nottingham, NG5 1PB, United Kingdom.
authors: T W
authors: TW
authors: Harrison
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000032:analysis; D054357:Chemokine CXCL10 / Q000032:analysis; D004311:Double-Blind Method; D047150:Eosinophil Cationic Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D011788:Quality of Life; D012129:Respiratory Function Tests / Q000379:methods; D013183:Sputum / Q000378:metabolism; D011795:Surveys and Questionnaires; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D055815:Young Adult
chemical_list: C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D047150:Eosinophil Cationic Protein; D000077205:Pioglitazone