title: Objective approach for fending off the sublingual immunotherapy placebo effect in subjects with pollenosis: double-blinded, placebo-controlled trial.
abstract: BACKGROUND
  Symptom scoring for the assessment of allergen immunotherapy is associated with a substantial placebo effect.
  
  
  OBJECTIVE
  To assess the ability of exhaled breath temperature (EBT), a putative marker of airway inflammation, to evaluate objectively the efficacy of grass pollen sublingual immunotherapy in a proof-of-concept study.
  
  
  METHODS
  This was a double-blinded, placebo-controlled clinical trial in 56 subjects (mean ± SD 30 ± 12 years old, 33 men) sensitized to grass pollen. The objective measurements were EBT, spirometry, and periostin and high-sensitivity C-reactive protein in blood. Overall discomfort scored on a visual analog scale was used as a proxy for subjective symptoms. Evaluations were performed before, during, and after the grass pollen season.
  
  
  RESULTS
  Fifty-one subjects (25 and 26 in the active treatment and placebo groups, respectively) were assessed before and during the pollen season. The mean pre- vs in-season increase in EBT was significantly smaller (by 59.1%) in the active treatment than in the placebo group (P = .030). Of the other objective markers, only the blood periostin level increased significantly during the pollen season (P = .047), but without intergroup differences. Subjectively, the mean pre- vs in-season increase in the visual analog scale score was 32.3% smaller in the active treatment than in the placebo group, although this difference did not reach statistical significance (P = .116).
  
  
  CONCLUSIONS
  These results suggest that the efficacy of grass pollen sublingual immunotherapy can be assessed by EBT, a putative quantitative measurement of airway inflammation, which is superior in its power to discriminate between active and placebo treatment than a subjective assessment of symptoms assessed on a visual analog scale.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01785394.
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Tanya Z
authors.initials: TZ
authors.lastname: Kralimarkova
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria. Electronic address: ted.popov@gmail.com.
authors.forename: Todor A
authors.initials: TA
authors.lastname: Popov
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Maria
authors.initials: M
authors.lastname: Staevska
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mincheva
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Cvetelina
authors.initials: C
authors.lastname: Lazarova
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Rumyana
authors.initials: R
authors.lastname: Racheva
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Tihomir B
authors.initials: TB
authors.lastname: Mustakov
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Violina
authors.initials: V
authors.lastname: Filipova
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Margarita
authors.initials: M
authors.lastname: Koleva
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Kalina
authors.initials: K
authors.lastname: Bacheva
authors.affiliation: Clinic of Allergy & Asthma, Medical University Sofia, Sofia, Bulgaria.
authors.forename: Vasil D
authors.initials: VD
authors.lastname: Dimitrov
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D003233:Conjunctivitis, Allergic / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004311:Double-Blind Method; D045853:Exhalation; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D006109:Poaceae / Q000009:adverse effects; D011058:Pollen / Q000009:adverse effects*; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D063729:Sublingual Immunotherapy; D013696:Temperature
chemical_list: D000485:Allergens; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D010919:Placebos; D002097:C-Reactive Protein