title: Allergen-induced changes in airway responsiveness are not related to indices of airway edema.
abstract: BACKGROUND
  The mechanisms behind airway hyperresponsiveness in asthma are unknown. Airway wall edema has been proposed as one possible culprit of this phenomenon.
  
  
  OBJECTIVE
  To test the hypothesis that airway edema may be the cause of allergen-induced increases in airway responsiveness in asthma, this trial aimed at determining the relationship between allergen-induced changes in airway responsiveness to inhaled methacholine and indirect indices of edema, namely peripheral airway resistance and the levels of the plasma protein fibrinogen in bronchoalveolar lavage (BAL) fluids.
  
  
  METHODS
  Twenty-six atopic individuals with mild asthma were subjected to bronchoscopy at baseline and 28 hours after allergen inhalation. Before each bronchoscopy, methacholine bronchoprovocation was performed. During bronchoscopy, peripheral airway resistance measurements were obtained by wedged bronchoscopy. BAL fluids were analyzed for fibrinogen, as well as for eosinophilic cationic protein. Cytology was performed, and cytokine gene expression was assessed with competitive reverse transcriptase PCR from cell pellets.
  
  
  RESULTS
  A significant increase in airway responsiveness to methacholine was recorded after allergen, but this did not correlate with changes in peripheral airway resistance (which was not affected) or with BAL fibrinogen (which decreased after allergen). Other BAL outcomes confirmed that airway inflammation was produced and was characterized by a T(H)2 cytokine pattern.
  
  
  CONCLUSIONS
  Airway responsiveness in asthma increases after exposure to allergen in the absence of increased indirect indices of edema. The role of edema in this phenomenon should therefore be tested more vigorously.
authors.affiliation: Division of Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore 21224, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Peebles
authors.forename: E M
authors.initials: EM
authors.lastname: Wagner
authors.forename: M C
authors.initials: MC
authors.lastname: Liu
authors.forename: D
authors.initials: D
authors.lastname: Proud
authors.forename: R G
authors.initials: RG
authors.lastname: Hamilton
authors.forename: A
authors.initials: A
authors.lastname: Togias
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000009:adverse effects* / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001798:Blood Proteins / Q000032:analysis; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D001999:Bronchoscopy; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004487:Edema / Q000139:chemically induced*; D047091:Eosinophil Granule Proteins; D005340:Fibrinogen / Q000032:analysis; D020869:Gene Expression Profiling; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D016210:Methacholine Chloride; D012333:RNA, Messenger / Q000096:biosynthesis; D012140:Respiratory Tract Diseases / Q000139:chemically induced*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D001798:Blood Proteins; D016207:Cytokines; D047091:Eosinophil Granule Proteins; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D016210:Methacholine Chloride; D015847:Interleukin-4; D007371:Interferon-gamma; D005340:Fibrinogen; D012260:Ribonucleases