title: Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs.
abstract: BACKGROUND
  The systemic administration of theophylline is useful for asthma treatment. However its narrow therapeutic range makes it difficult to use. Little is known about its potential in inhalation therapy, particularly repeated inhalation.
  
  
  OBJECTIVE
  The purpose of this study is to investigate the therapeutic usefulness of inhaled aminophylline in an asthma model.
  
  
  METHODS
  The effects of pretreatment with inhaled aminophylline (25 mg/mL for 30 min/dose) on airway response and inflammation after an ovalbumin (OVA) challenge and airway hypersensitivity to acetylcholine (Ach) were evaluated using guinea pigs sensitized with OVA.
  
  
  RESULTS
  Aminophylline relaxed the ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Pretreatment with single-dose aminophylline inhalation suppressed OVA-induced airway constriction to the same extent as the intraperitoneal pretreatment with high-dose aminophylline (10-20 mg/kg). However, pretreatment with single-dose aminophylline inhalation did not suppress eosinophil infiltration into airways (neither bronchoalveolar lavage [BAL] fluid nor lung tissue) and did not suppress airway hyperreactivity to ACh, 24 h after OVA challenge. Repeated inhalation of aminophylline (twice daily for 7 days) suppressed the infiltration of eosinophils and suppressed airway hypersensitivity to ACh. In addition, high concentrations of aminophylline inhibited production of oxygen radicals by BAL cells.
  
  
  CONCLUSIONS
  Single-dose inhalation treatment with aminophylline has transient but relatively strong bronchodilating effects due to delivery of high doses into local airways. Repeated inhalation treatment suppressed airway inflammation and hypersensitivity induced by allergens. Therefore, inhaled aminophylline may be useful for asthma treatment.
authors.affiliation: Department of Respiratory Medicine and Allergology, Nara Hospital, Kinki University Faculty of Medicine , Ikoma , Japan and.
authors.forename: Masato
authors.initials: M
authors.lastname: Muraki
authors.forename: Shota
authors.initials: S
authors.lastname: Wada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohno
authors.forename: Souichirou
authors.initials: S
authors.lastname: Hanada
authors.forename: Hirochiyo
authors.initials: H
authors.lastname: Sawaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwanaga
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kume
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tohda
mesh_terms: D000280:Administration, Inhalation; D000628:Aminophylline / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016084:Bronchoconstriction / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D008168:Lung / Q000187:drug effects; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology*
chemical_list: D000628:Aminophylline; D010047:Ovalbumin
keywords: Airway hyperreactivity; airway inflammation; asthma; inhalation; theophylline