We examined the effect of aminophylline on air-flow-induced constriction in the canine lung periphery. A wedged bronchoscope technique was used to measure airway wall temperature (Taw) and collateral resistance (Rcs) before and after air flow was increased from a baseline flow of 200 to 500, 1,000, 1,500, or 2,000 ml/min for 2-min periods. When a sublobar segment was challenged with dry air, Taw fell during the challenge (p less than 0.05) and Rcs increased 5 min postchallenge (p less than 0.01). Pretreatment with aminophylline (20 mg/kg) reduced the fall in Taw by 31% and reduced the increase in Rcs by 53%. Aminophylline did not significantly affect either the concentrations of PGD2, TxB2, and histamine or the cell numbers and profiles obtained by bronchoalveolar lavage performed 5 min postchallenge. However, trends were consistent with the decreased physiologic responses observed. Finally, aminophylline proved ineffective in reducing the constrictor response of peripheral lung challenged directly with aerosolized histamine or PGD2. Because preaminophylline and postaminophylline peripheral lung sensitivity (as assessed by the ratio delta Rcs/delta Taw) were not significantly different, we conclude that aminophylline attenuates physiologic responses by reducing the strength of the stimulus. Aminophylline could do this by facilitating the replacement of heat and water removed during dry air challenge by increasing bronchial or pulmonary blood flow, or by reducing heat and water loss via changes in mucosal permeability.
In this study, cytological examination of nasal secretions of 17 patients with cystic fibrosis (CF) was combined with quantitative determination of common inflammatory mediators. Results showed a normal cytogram in these patients. However, obvious mucosal inflammation is evidenced by significantly higher concentrations of leukotriene C4 (LTC4) and eosinophil cationic protein (ECP). The activation of other common inflammatory cells such as mast cells (or basophils) and neutrophils could not be demonstrated since their mediators (histamine, tryptase and myeloperoxidase) are not raised. Increased concentrations of LTC4 and ECP indicate the active participation of eosinophils, and can contribute to the new concept of non-infectious inflammatory involvement of the nasal epithelium of patients with CF.
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