Richard R. Martin

Lack of acute effects of ascorbic acid on spirometry and airway responsiveness to histamine in subjects with asthma

Sixteen adult subjects with asthma in a clinical steady state were studied. On day 1, after baseline spirometry, they underwent four histamine inhalation tests with functional recovery between each test. The provocative concentration causing a 20% fall in FEV1 (PC20) was obtained after each test. On days 2, 3, and 4, after baseline spirometry, active and placebo ascorbic acid (2 gm) was administered orally, double-blind, according to a 4.3.1 two-treatment crossover study design. One hour later, spirometry was performed, and PC20 was reassessed. We found no significant changes in FEV1 and FVC after ascorbic acid as compared with placebo administration. There was no difference between PC20 on days 2, 3, and 4 and by standardizing for the four PC20 results obtained on day 1. We conclude that ascorbic acid has no acute bronchodilator effect and does not alter bronchial responsiveness to histamine in subjects with asthma.

Theophylline partially inhibits bronchoconstriction caused by inhaled histamine in subjects with asthma

Sixteen adult subjects in a clinical steady state had four consecutive histamine inhalation tests on the same day when they were not receiving oral theophylline medication. The provocative concentration of histamine causing a 20% fall in FEV1 (PC20) was used to assess the response. They were then administered active or placebo sustained-release theophylline preparations according to a double-blind, randomized 4.4.1. two-treatment crossover design. Medication was administered for a minimum of 3 consecutive days, and PC20 was reassessed on 4 different days, 3 to 4 hours after receiving active or placebo medication (two visits for each medication). A significant but small bronchodilator and blocking effect on histamine excitability was demonstrated for the active medication. This latter effect was present even by adjusting for changes in baseline airway caliber and for the intraindividual variability of the four PC20 values obtained on day 1. We conclude that theophylline partially blocks bronchial responsiveness to inhaled histamine.

Effect of sodium cromoglycate on histamine inhalation tests

Sixteen adult asthmatic subjects in a clinical steady state were included in the study. On day 1, after baseline assessment of spirometry (FEV1, FEV1/FVC, FEF25-75), they underwent three to four consecutive inhalation tests using twofold increasing doses of histamine to measure the provocative concentration causing a fall in FEV1 of 20% (PC20). Baseline FEV1 was back to +/- 5% of the initial assessment before each histamine inhalation test (HIT). On days 2, 3, and 4, after baseline spirometry which confirmed that FEV1 was within 10% of initial day 1 assessment, placebo-lactose (P) or 40 mg of sodium cromoglycate (SCG) were nebulized in a double-blind randomized 4.3.1. two-treatment crossover study design. Ten minutes later, spirometry was repeated and followed by an HIT. Baseline spirometry was not significantly different on each day or after P and SCG. There was no statistical difference between the geometric means of the three or four PC20s done on day 1, indicating that there is no tachyphylaxis induced by repeated HIT. There was no statistical difference between mean PC20 after P (0.52 +/- 3.3 (SD) mg/ml), after SCG (0.50 +/- 3.2), and of the three to four HIT done on day 1 (0.40 +/- 3.6). We conclude that in asthmatic subjects SCG has no acute bronchodilator effect and does not alter the response to inhaled histamine.

Within- and between-day reproducibility of isocapnic cold air challenges in subjects with asthma☆

Eight adult subjects with asthma had isocapnic cold air challenges on 4 different days. Three consecutive tests were performed on each visit with functional recovery between tests. Subjects were asked to breathe dry cold air (-20 degrees C) for progressively increasing levels of minute ventilation (7.5, 15, 30, and 60 L/min and maximal voluntary ventilation) until a 20% fall in FEV1 had been reached or when maximal voluntary ventilation was done. FEV1 was assessed between each level. The doses of respiratory heat exchange and minute ventilation causing 10%, 15%, and 20% changes in FEV1 were interpolated from dose-response curves. The within- and between-day 95% confidence intervals based on a single determination on the loge scale varied from +/- 0.32 to 0.59 for the indices derived from respiratory heat exchange. Reproducibility of the between-day results was more satisfactory than for the corresponding within-day assessments. No significant within-day tachyphylaxis was demonstrated for these indices.