Acute respiratory response to prolonged, moderate levels of sidestream tobacco smoke.

Environmental tobacco smoke (ETS) is a significant component of indoor air pollution yet the acute upper respiratory response has not been well studied. The goal of this study was to determine the response of healthy subjects to moderate levels of sidestream tobacco smoke (SS). Twenty-three subjects were challenged on 2 separate days to clean air or SS (2 h, 15 ppm carbon monoxide, at rest). Subjects completed symptom questionnaires, posterior rhinomanometry, and body plethysmography. Average total and differential cell counts and albumin concentration were determined on nasal lavage samples. The urinary cotinine: creatinine ratio was used as a biomarker of exposure. Following SS exposure, irritant and rhinitis symptoms increased, nasal resistance rose from 4.9+/-0.4 to 6.3+/-0.6 cm H2O/L/s and specific airway conductance decreased from 0.14+/-0.01 to 0.13+/-0.01 cm H2O(-1) s(-1). Total cell counts, neutrophils, and albumin were unchanged. An increased nasal congestive response did not correlate with an increased cotinine: creatinine ratio. A history of ETS rhinitis did not predict an increased group response to smoke, but individuals with the largest physiologic and inflammatory response were historically ETS sensitive. In summary, healthy normal subjects demonstrate nasal congestion with exposure to moderate levels of SS without evidence of increased nasal vascular permeability.

Nasal inhalation challenge studies with sidestream tobacco smoke.

Environmental tobacco smoke (ETS) exposure is associated with rhinitis symptoms (i.e., runny nose and congestion) in some people. In an effort to better understand these symptoms, we recruited 18 historically ETS-sensitive subjects from the community and exposed them for 15 min to clean air and for 15 min to sidestream tobacco smoke (STS, 45 ppm carbon monoxide). Symptoms were recorded (0 = absent, 5 = severe), and posterior rhinomanometry was performed. There were significant changes in rhinitis symptoms (1.3 +/- 0.4 pre- versus 6.1 +/- 0.5 post-STS, p less than .05); nasal airway resistance (2.86 +/- 0.2 pre- versus 4.49 +/- 0.6 post-STS, p less than .05), and maximum inspiratory flow (2.74 +/- 0.3 pre- versus 2.14 +/- 0.3 post-STS, p less than .05). A spectrum of individual responsiveness to ETS was observed, and nasal resistance increased from 0% to 265%. Increased nasal resistance occurred primarily at the upstream or flow-limiting segment of the nasal airway.

Tolazoline pharmacokinetics in lambs.

Tolazoline has often been administered experimentally to lambs without consideration of its pharmacokinetics. We have used a chemically specific assay to determine tolazoline pharmacokinetic parameters in lambs after pulse and infusion doses: alpha = 0.184 +/- 0.046 (min-1), beta = 0.010 (pulse) and 0.0098 (infusion) +/- 0.0010 (min-1), Vdarea = 2534 +/- 688 ml/kg (pulse), and Vdss = 2890 +/- 342 ml/kg (infusion). The following doses can be used to reach steady-state plasma tolazoline concentrations: loading dose (microgram/kg) = 2890 X desired concentration (microgram/ml); infusion rate (microgram/kg X min) = 2890 (.010) X desired concentration (microgram/ml). These doses were used to produce 68 steady-state concentrations from 0.25 to 10.0 micrograms/ml. Clearances at steady state averaged 166 ml/min or 27.1 ml/min X kg at 2-17 days but increased markedly by 4 weeks of age. Using these doses, tolazoline-receptor interactions can be studied at constant plasma concentrations that approximate constant receptor concentrations.