Chronic cough: a respiratory viewpoint.

PURPOSE OF REVIEW: This article reviews the common causes and investigation of chronic cough and explores unexplained cough and its relationship to cough hypersensitivity. RECENT FINDINGS: Cough plays a critical role in airway protection and clearance of secretions. Chronic cough, however, is a debilitating symptom that can significantly interfere with quality of life. Despite their limitations cough guidelines have raised the awareness of chronic cough as an important problem and provided a framework for a logical care pathway. The use of a systematic approach to diagnosis and management in a specialist clinic can result in successful identification as to the cause, with subsequent relief of symptoms. In a proportion of patients no diagnosis is reached or treatment fails. A common finding among these patients is cough reflex hypersensitivity and this is an important feature irrespective of the underlying diagnosis. The majority of patients referred to tertiary cough clinics are females. Women appear to have an intrinsically heightened cough response with augmented cough challenge and a high frequency of ACE-inhibitor cough. SUMMARY: The way in which we review cough has undergone radical change in the last decade. A distinct population of patients with chronic idiopathic cough is emerging in whom cough reflex hypersensitivity is a feature. Extended co-operation between clinicians, scientists and the pharmaceutical industry is required to better understand the pathophysiology of the enhanced cough reflex and the development of more effective antitussive therapies.

OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis infection claims approximately 2 million lives per year, and improved efficacy of the BCG vaccine remains a World Health Organization priority. Successful vaccination against M. tuberculosis requires the induction and maintenance of T cells. Targeting molecules that promote T-cell survival may therefore provide an alternative strategy to classic adjuvants. We show that the interaction between T-cell-expressed OX40 and OX40L on antigen-presenting cells is critical for effective immunity to BCG. However, because OX40L is lost rapidly from antigen-presenting cells following BCG vaccination, maintenance of OX40-expressing vaccine-activated T cells may not be optimal. Delivering an OX40L:Ig fusion protein simultaneously with BCG provided superior immunity to intravenous and aerosol M. tuberculosis challenge even 6 months after vaccination, an effect that depends on natural killer 1.1(+) cells. Attenuated vaccines may therefore lack sufficient innate stimulation to maintain vaccine-specific T cells, which can be replaced by reagents binding inducible T-cell costimulators.