Bronchodilator actions of xanthine derivatives administered by inhalation in asthma

The airway response to the inhalation of four alkyl xanthines was studied in 17 subjects with moderately severe asthma (mean FEV1 1.19 litres, 42% predicted). Theophylline (10 mg/ml), glycine theophyllinate (50 mg/ml), theophylline ethylenediamine (aminophylline 50 mg/ml), and diprophylline (125 mg/ml) were administered by nebulisation and the airway response was measured as percentage change from baseline of specific airway conductance (sGaw). All xanthine derivatives had an unpleasant taste and produced coughing at the onset of nebulisation. All four xanthines produced a significant increase in sGaw by comparison with saline placebo, with a maximum mean increase from baseline of 35% for theophylline, 40% for glycine theophyllinate, 60% for aminophylline, and 32% for diprophylline. Inhalation of 200 micrograms salbutamol from a metered dose inhaler produced an additional increase in sGaw of 149%. Thus alkyl substituted xanthines administered by inhalation to patients with asthma cause significant short lived bronchodilatation, but this effect is small compared with that of a conventional dose of an inhaled beta 2 adrenoceptor agonist.