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Published ahead of print on August 13, 2003, doi:10.1164/rccm.200304-597OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 8, October 2003, 995-1002

A more recent version of this article appeared on October 15, 2003
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Submitted on April 30, 2003
Accepted on July 31, 2003

A study of the cough reflex in idiopathic pulmonary fibrosis

Benjamin D M Hope-Gill1, Simon Hilldrup1, Christine Davies2, Russell P Newton3, and Nicholas K Harrison1*

1 Respiratory Unit, Morriston Hospital, Swansea, United Kingdom, 2 Pathology Department, Morriston Hospital, Swansea, United Kingdom, 3 Biological Sciences, University of Wales, Swansea, United Kingdom

* To whom correspondence should be addressed. E-mail: resp.unit{at}swansea-tr.wales.nhs.uk.

Little is known about the pathogenesis of cough in idiopathic pulmonary fibrosis. We hypothesised that abnormalities of respiratory tachykinin-containing sensory nerves may be implicated. We studied cough response to capsaicin, substance P and bradykinin in 10 healthy controls and 10 patients with idiopathic pulmonary fibrosis. Six patients were tested before and after steroid therapy. Induced sputum cell counts and neurotrophic factor levels were also measured in 13 patients and 13 controls. Results show cough sensitivity to capsaicin was greater in patients (p<0.01). Neither Substance P nor bradykinin induced cough in normals. Substance P and bradykinin induced cough in 7/10 patients (p<0.002) and 2/10 patients (NS) with idiopathic pulmonary fibrosis respectively. Prednisolone caused a reduction in cough sensitivity to capsaicin (p<0.05) and substance P (p<0.05) in all six patients treated. There were significantly more neutrophils (p=0.001) and higher levels of nerve growth factor (p<0.01) and brain-derived neurotrophic factor (p<0.01) in patient's sputa. These findings suggest functional upregulation of lung sensory neurones in idiopathic pulmonary fibrosis. The cough response to inhaled substance P in most patients may reflect disrupted respiratory epithelium. The response to corticosteroids demonstrates that the cough is amenable to therapy.
Key words: cough, idiopathic pulmonary fibrosis, neurotrophins




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