Chemotherapy for chronic bronchitis. Controversies

Abstract

Chronic bronchitis is a common inflammatory disease of the airways characterised by cough, sputum production and associated features such as dyspnoea and respiratory obstruction. It has a poor prognosis once fully developed and imposes a heavy financial burden on affected societies. Chronic bronchitis is subject to periodic exacerbations in which the role of bacterial infection and the rightful place of antibiotic therapy is only slowly emerging, largely due to the non-homogeneity of the populations under study. Haemophilus influenzae is implicated as the pathogen in more than half of all bacterial exacerbations, Streptococcus pneumoniae and Moraxella catarrhalis accounting for a further third. Viruses and mycoplasmas are also involved. Some 18-25% of patients receiving domiciliary therapy may fail to respond to initial treatment, calling into question the efficacy of antibiotics in acute exacerbations. In part this may relate to sub-optimal respiratory pharmacokinetics as most antibiotics are quite effective against sensitive respiratory pathogens in vitro. However, bacterial resistance rates against traditional agents are rising rapidly in Europe and new agents are needed to counter this threat. Paradoxically few such agents have been shown to improve on the results of amoxycillin and other standard drugs, probably because most trials include patients with exacerbations of only mild-to-moderate severity due to sensitive pathogens. Since recent large scale studies have demonstrated the efficacy of antibiotic therapy compared with placebo in defined exacerbations, use of these definitions has allowed more realistic assessment of new agents which, in terms of improved antibacterial potency and respiratory pharmacokinetics, should offer superior efficacy. Regression analysis of a large scale general practice survey in the UK has now shown the frequency of exacerbations and the presence of co-morbid conditions to correlate significantly with a poor therapeutic outcome and thus, by implication, with severity. Future trials of antibacterial chemotherapy for acute bacterial exacerbations of chronic bronchitis should incorporate such criteria so that real differences between existing and improved compounds can be assessed.