A study of the cough reflex in idiopathic pulmonary fibrosis

Am J Respir Crit Care Med. 2003 Oct 15;168(8):995-1002. doi: 10.1164/rccm.200304-597OC. Epub 2003 Aug 13.


Little is known about the pathogenesis of cough in idiopathic pulmonary fibrosis (IPF). We hypothesized that abnormalities of respiratory tract tachykinin-containing sensory nerves may be implicated. We studied cough response to capsaicin, substance P (SP), and bradykinin in 10 healthy control subjects and 10 patients with IPF. 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 control subjects. The results show that cough sensitivity to capsaicin was greater in patients (p < 0.01). Neither SP nor bradykinin induced cough in normal subjects. SP and bradykinin induced cough in 7/10 patients (p < 0.002) and 2/10 patients (not significant) with IPF, respectively. Prednisolone caused a reduction in cough sensitivity to capsaicin (p < 0.05) and SP (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 IPF. The cough response to inhaled SP in most patients may reflect disrupted respiratory epithelium. The response to corticosteroids demonstrates that the cough is amenable to therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Bradykinin
  • Brain-Derived Neurotrophic Factor / analysis
  • Bronchial Provocation Tests
  • Capsaicin
  • Case-Control Studies
  • Cough / diagnosis
  • Cough / drug therapy*
  • Cough / etiology*
  • Female
  • Forced Expiratory Volume
  • Humans
  • Inflammation
  • Leukocyte Count
  • Male
  • Nerve Growth Factor / analysis
  • Neutrophils / immunology
  • Prednisolone / pharmacology
  • Prednisolone / therapeutic use*
  • Pulmonary Fibrosis / complications*
  • Sputum / chemistry
  • Sputum / cytology
  • Substance P
  • Total Lung Capacity
  • Treatment Outcome


  • Anti-Inflammatory Agents
  • Brain-Derived Neurotrophic Factor
  • Substance P
  • Nerve Growth Factor
  • Prednisolone
  • Capsaicin
  • Bradykinin