non-specific bronchial hyperresponsiveness

A double blind, crossover study was undertaken to determine whether non-specific hyperresponsiveness in subjects with asthma was reduced by long term treatment with sodium cromoglycate and, if so, whether this was related to change in lung function. Forty four adult asthmatic subjects (41 atopic, three non-atopic) entered the one year study at intervals staggered over six months. After a baseline period to ensure that asthma control was stable subjects entered the treatment period, during which they inhaled sodium cromoglycate 20 mg four times daily or matching placebo four times daily for 16 weeks each, in random order. Response was assessed at four weekly intervals by measurement of lung function and histamine inhalation tests, from which the provocative concentration of histamine causing a 20% fall in FEV, (PC20H) was calculated. The assessment included daily symptom score, morning and evening Airflometer readings and treatment; mean values for each treatment period and also for the final four weeks of each period were compared. There were no significant differences between placebo and sodium cromoglycate treatment for PC20H, FEV1, morning or evening flow meter readings, bronchodilator usage, or symptom scores for the group as a whole, for the 16 week period or for the final four weeks of each period. Thirteen subjects showed better morning and evening flow meter readings while taking sodium cromoglycate than while taking placebo and eight better readings with placebo than with sodium cromoglycate (p < 0-05). Improvement in lung function did not correlate with baseline lung function or baseline PC20H, or with features of atopy. These results suggest that long term sodium cromoglycate treatment does not alter non-specific bronchial responsiveness in adult asthmatic subjects. Many drugs used for the symptomatic treatment of asthma have been shown in short term or single dose studies to modify both specific and non-specific airway hyperresponsiveness.'" This effect is seen acutely with ,B2 adrenoceptor agonists,3 7, which nevertheless have not been shown to reduce airway responsiveness to histamine over a four week period.47 Two non-bronchodilator agents, inhaled sodium cromoglycate81l and inhaled corticosteroids,'2 have been reported to reduce non-specific airway hyperresponsiveness over longer periods of time. When the present study began no double blind, placebo controlled study examining the long term effect of sodium cromoglycate on airway hyperresponsiveness had been performed. While some Address for reprint requests: Dr C J Jenkins, Respiratory Unit, Concord Hospital, Concord, New South Wales 2139, Australia. Accepted 25 November 1986 circumstantial evidence, combined with a theoretical understanding of the drug's mode of action,13"5 suggested that sodium cromoglycate could reduce non-specific hyperresponsiveness, most of the data supported this hypothesis only indirectly.89 1618 Most single and multiple dose studies of the effect of sodium cromoglycate on histamine hyperresponsiveness have not shown any appreciable protection.' 19-21 Two more recent double blind, placebo controlled studies'°22 failed to find a significant change in bronchial responsiveness to methacholine or histamine after treatment with sodium cromoglycate for two weeks. Our study was undertaken to examine the hypothesis that long term administration of sodium cromoglycate could reduce non-specific bronchial hyperresponsiveness in subjects with chronic asthma. The relationship between change in airway obstruction and change in responsiveness was also examined to determine whether any observed effect was dependent on change in lung function. 664 group.bmj.com on May 1, 2017 Published by http://thorax.bmj.com/ Downloaded from