Elevated substance P levels in nasal lavage fluids from patients with chronic nonproductive cough and increased cough sensitivity to inhaled capsaicin

J Allergy Clin Immunol. 2003 Oct;112(4):695-701. doi: 10.1016/s0091-6749(03)01784-6.


Background: The exact mechanism of a chronic nonproductive cough is sometimes unclear when patients who are without symptoms or signs indicating the major causes of chronic cough remain undiagnosed.

Objective: We hypothesized that some neurochemical alterations in the sensory nerves in the cough reflex may occur in the upper airway of chronic nonproductive cough patients.

Methods: We took nasal lavage fluid (NLF) specimens from 38 patients with a chronic nonproductive cough as the sole presenting symptom. All 38 had normal chest radiography, spirometry, and bronchial responsiveness. We likewise took NLF specimens from 14 healthy control subjects. We used a capsaicin cough provocation test to determine cough sensitivity and considered the value of C5 (the lowest capsaicin concentration inducing 5 consecutive coughs) as an index of cough sensitivity. We measured levels of substance P of NLF specimens by using ELISA. In addition, we evaluated the clinical response of each patient after subsequent therapeutic trials with an antihistamine and decongestant for 2 weeks.

Results: By using capsaicin cough sensitivity as the basis for grouping the study subjects, we divided the patients into 2 groups: an increased cough sensitivity group (ICS, C5 <32 mumol/L) and a normal cough sensitivity (NCS) group. Patients with ICS showed an elevated SP concentration in NLF (median value, 408 pg/mL) compared with that of the NCS group (237 pg/mL) and the control subjects (138 pg/mL) (P <.01). The median value of the percentage of remnant cough after therapeutic trial compared with the cough status before treatment was significantly higher in the ICS subgroup (70%) than that of NCS (25%) (P <.05).

Conclusions: Elevated substance P contents in NLF specimens were associated with ICS in patients with chronic nonproductive cough, suggesting a neurochemical abnormality in the upper airway.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Capsaicin / administration & dosage*
  • Case-Control Studies
  • Cetirizine / therapeutic use
  • Chronic Disease
  • Cough / diagnosis
  • Cough / drug therapy
  • Cough / etiology
  • Cough / metabolism*
  • Disease Susceptibility
  • Ephedrine / therapeutic use
  • Female
  • Histamine H1 Antagonists, Non-Sedating / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Nasal Decongestants / therapeutic use
  • Nasal Lavage Fluid / chemistry*
  • Nasal Provocation Tests
  • Osmolar Concentration
  • Substance P / analysis*


  • Histamine H1 Antagonists, Non-Sedating
  • Nasal Decongestants
  • Substance P
  • Ephedrine
  • Capsaicin
  • Cetirizine