Effects ofnaftidrofuryl on breathlessness andexercise tolerance inchronic bronchitis

Naftidrofuryl enhances oxidative phosphorylation andmighttherefore beexpected to improve exercise tolerance andbreathlessness inadvanced chronic bronchitis. Thishypothesis was tested ina four-week placebo-controlled trial in11bronchitic patients. Sevenpatients completed thestudy. There was no evidence ofany benefit fromnaftidrofuryl either subjectively orafter a 12-minute walking test. Somepatients withchronic airflow limitation have distressing breathlessness andseverely limited exer- cise tolerance despite therapeutic efforts toimprove lungfunction. Attention hastherefore beenturned toalternative methods ofrelieving these symptoms. Physical training mayimprove exercise tolerance' in chronic bronchitics, andportable *oxygen also improves exercise tolerance andrelieves breathless- nessin"pink puffers."2 Promethazine mayalso be ofmarginal benefit.3 Reducing basal metabolic rate and thusoxygenrequirements by inducing hypothyroidism might beexpected toleave more oxygenavailable forexercise, butinacontrolled study using carbimazole noimprovement inexercise tolerance wasachieved.4 Naftidrofuryl (currently inuseforthetreatment ofperipheral vascular disease) hasnovel effects on cellular metabolism. Inmicethedrugproduces raised concentrations ofcerebral adenosine triphos- phate, phosphocreatine, andglucose, reduced lac- tateconcentrations, andprotection against the metabolic effect ofischaemia.5 Similar effects have beenshownintheaffected limbs ofpatients with peripheral vascular disease,6 andlowered lac- tate: pyruvate ratios after exercise inhealthy volun- teers given naftidrofuryl indirectly confirm that the drugenhances tissue oxidative metabolism.7 Because ofthese properties wethought that astudy oftheeffects ofnaftidrofuryl onexercise tolerance andbreathlessness inpatients withsevere chronic airflow limitation waswarranted. Methods