D.G. Downey

Forty-nine patients with atopic dermatitis entered a double blind placebo controlled cross-over study of mupirocin, a new topical antistaphylococcal antibiotic. Forty-five patients were evaluable. Quantitative bacteriological assessment before treatment showed that heavy colonization of the skin with Staphylococcus aureus was present in nearly all patients even in the absence of overt infection. However, the bacterial count was significantly reduced by 2 weeks' treatment with topical mupirocin, but not by the placebo. Moreover, a significant reduction of clinical severity was also observed after treatment with mupirocin, which was maintained over the following 4 weeks, although recolonization occurred during this period, with bacterial counts rising to pre-treatment levels. Despite recolonization, clinical deterioration was not observed during the trial period. No serious side-effects were observed. Phage typing showed that 50% of patients carried more than one bacterial phage type. Recolonization in eight patients (17%) was with a 'new' strain that had not previously been isolated.

Lung injury in cystic fibrosis is caused by recurrent airway infection and inflammation. Neutrophils are important in combating these infections but are also the predominate cells involved in the inflammatory process. This review of neutrophils in cystic fibrosis describes the cellular mechanisms involved in their migration into the airways and their role in bacterial phagocytosis. We discuss the inflammatory process and its resolution and ultimately how neutrophil function can be modulated.

We are currently witnessing transformative change for people with cystic fibrosis with the introduction of small molecule, mutation-specific drugs capable of restoring function of the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). However, despite being a single gene disorder, there are multiple cystic fibrosis-causing genetic variants; mutation-specific drugs are not suitable for all genetic variants and also do not correct all the multisystem clinical manifestations of the disease. For many, there will remain a need for improved treatments. Those patients with gene variants responsive to CFTR modulators may have found these therapies to be transformational; research is now focusing on safely reducing the burden of symptom-directed treatment. However, modulators are not available in all parts of the globe, an issue which is further widening existing health inequalities. For patients who are not suitable for- or do not have access to- modulator drugs, alternative approaches are progressing through the trials pipeline. There will be challenges encountered in design and implementation of these trials, for which the established global CF infrastructure is a major advantage. Here, the Cystic Fibrosis National Research Strategy Group of the UK NIHR Respiratory Translational Research Collaboration looks to the future of cystic fibrosis therapies and consider priorities for future research and development.