The primary difference between patients with allergies/asthma and those with SHR is the absence of mucosal inflammation among the latter. Among allergy/asthma sufferers, this inflammation results in high levels of nerve growth factor (NGF), a protein that is essential for the survival and development of sensory neurons.

The authors hypothesised that a neurochemical alteration lay at the root of SHR. Although SHR patients do not experience mucosal inflammation, they have been shown to have an increased cough sensitivity to inhaled capsaicin (the hot ingredient in chili peppers). Capsaicin is known to stimulate sensory nerve endings and induce coughing when inhaled. The researchers therefore theorised that the NGF reaction in SHR patients "may be derived from hyperreactive nerve endings.”

The researchers studied 13 nonsmoking patients who had been referred to an asthma and allergy clinic due to symptoms suggestive of those conditions, but for whom allergy tests were negative and asthma medications ineffective. The subjects were given increasing levels of nebulised capsaicin. After this provocation, the subjects' coughs were counted and levels of NGF in nasal discharge measured.

The SHR group coughed significantly more than the control group. The SHR group also exhibited other symptoms from the capsaicin inhalation including throat irritation, heavy breathing, eye irritation, excess phlegm production, and runny nose, while the control group registered few or no additional symptoms. The authors observed a significant correlation between the number of coughs, change in NGF levels, and symptom scores for throat irritation, phlegm production, and runny nose.

The neurochemical imbalance causes SHR sufferers to react abnormally to chemicals and scents, even in "concentrations normally regarded as harmless,” the study says.; Source: Environmental Health Perspectives (NIEHS)