Sensory Hyperreactivity and Chemical Sensitivity, Tilia
About this website
På svenska
Auf Deutsch
Download books
Research group
Funding sources
Research abstracts

Latest update: 2011-02-27


Here we present the latest findings in SHR

1. Inhalation of ethanol may augment the airway symptoms in SHR
Fifteen patients with SHR and 15 control persons were provoked with inhalations of different concentrations of ethanol followed by a capsaicin inhalation provocation. The strongest concentration of ethanol increased the capsaicin cough sensitivity and the airway symptoms induced by capsaicin. Since perfumed products are believed to trigger the same nerve receptors as capsaicin do the conclusion is that ethanol; a common dissolvent for fragranced products may augment airway reactions like cough and “heavy breathing” in patients with SHR.

Inhaled ethanol potentiates the cough response to capsaicin in patients with airway sensory hyperreactivity

Authors: Millqvist E, Ternesten-Hasséus E, Bende M

Journal: Pulm Pharmacol Ther. 2008 Oct;21(5):794-7

A suggested explanation for airway symptoms induced by chemicals and scents is sensory hyperreactivity (SHR) of airway mucosal nerves. Patients with SHR have increased cough sensitivity to inhaled capsaicin, mediated by transient receptor potential (TRP) ion channels. In animal experiments, some TRP receptors are potentiated by ethanol, which is why in this study, the aim was to evaluate whether a pre-inhalation of ethanol could influence the capsaicin cough response in patients with SHR. Fifteen patients with SHR and 15 healthy controls were provoked on three occasions with two concentrations of inhaled capsaicin. Before each capsaicin provocation, a pre-inhalation of saline or one of two concentrations of ethanol was given in a double-blind, randomized fashion. The participants reacted in a dose-dependent way with cough on the capsaicin inhalations. Among the patients, but not in the control group, pre-inhalation of ethanol increased the cough response dose-dependently. The results suggest that the pathophysiology of SHR is related to airway mucosal TRP receptors in the sensory nerves. In scented products, the combination of ethanol as a solvent and perfume may augment an airway reaction in sensitive individuals.

PMID: 18621137 [PubMed - indexed for MEDLINE]
The full text is available at:

2. Exercise in cold air induces cough and airway symptoms in SHR
Patients with SHR who performed an exercise test in a cold chamber got symptoms from the airways like cough and “heavy breathing”, but with no bronchial obstruction. After the exercise the cough sensitivity to inhaled capsaicin was augmented. Healthy control persons had no airway symptoms and the cough sensitivity did not change.

Dyspnea from exercise in cold air is not always asthma

Authors: Ternesten-Hasseus E, Johansson EL, Bende M, Millqvist E

Journal: J Asthma 2008;45:705-9.

In the absence of other explanations, exercise-induced dyspnea is often labeled as a manifestation of asthma. The aim of this study was to use exercise provocation in cold air among patients with exercise-induced dyspnea, but without any bronchoconstriction, in order to study induced symptoms and different physiological parameters and to measure the possible influence of exercise in cold air on capsaicin cough sensitivity. Eleven patients with exercise-induced dyspnea but no asthma, along with 11 healthy controls, performed a capsaicin inhalation provocation on two occasions. One of these provocations was preceded by an exercise provocation in a cold chamber. Number of coughs, airway symptoms, spirometry, respiratory rate, pulse rate, end-tidal CO(2), and PSaO(2) were registered. During exercise, the patients coughed more than the controls and also had more airway symptoms. After exercise provocation, spirometry values remained unchanged, but capsaicin cough sensitivity was increased and end-tidal CO(2) decreased among the patients, both in comparison to the controls and in comparison to the patients themselves prior to exercise. Exercise-induced dyspnea may be associated with hypocapnia from hyperventilation and increased capsaicin cough sensitivity. The diagnosis of exercise-induced asthma should be questioned when the patient has no signs of bronchoconstriction.

PMID: 18951264 [PubMed - indexed for MEDLINE]
The full text is available at:

3. Hyperventilation with dry air decreased cough sensitivity to inhaled capsaicin in patients with SHR
Patients with chronic idiopathic cough and SHR coughed less from a capsaicin inhalation provocation when this was preceded by who a dry air hyperventilation. The findings may be of interest to understand basic mechanisms in chronic idiopathic cough and SHR.

Down-regulation of cough sensitivity after eucapnic dry air provocation in chronic idiopathic cough

Authors: Johansson EL, Ternesten-Hasséus E, Millqvist E

Journal: Pulm Pharmacol Ther. 2009 Dec;22(6):543-7

Down-regulation of cough sensitivity in humans is rarely discussed in terms other than pharmacological treatment of cough or hypersensitive cough reflex. Chronic cough and increased cough sensitivity could be due to a number of airway and other diseases. When such conditions are excluded, there still remains a group of patients with no evident medical explanation for persistent coughing; such patients are often described as having "chronic idiopathic cough". The aim of this study was to use a standardized eucapnic dry air provocation among patients with chronic idiopathic cough in order to study physiological parameters and measure their possible influence on capsaicin cough sensitivity. Fourteen female patients with chronic idiopathic cough and ten healthy controls underwent a capsaicin inhalation provocation on two occasions. In all patients, irritating environmental factors were known to induce cough and airway symptoms. One of the two capsaicin provocations was preceded by a eucapnic dry air provocation. Number of coughs, spirometry, respiratory rate, pulse rate, end-tidal CO(2), and oxygen saturation by pulse oximetry (PSaO(2)) were registered and compared. The patients showed increased capsaicin sensitivity compared with the control subjects. This sensitivity was decreased when the capsaicin test was preceded by a eucapnic dry air provocation. Before the dry air provocation and after the capsaicin provocations, end-tidal CO(2) was decreased among the patients in comparison with the controls. After dry air provocation, spirometry values remained unchanged. The results suggest that in patients with chronic idiopathic cough, physiological down-regulation of the cough sensitivity is possible with a eucapnic dry air provocation.

PMID: 19646543 [PubMed - indexed for MEDLINE]
The full text is available at:

4. Relationship between asthma and SHR
The aim of this study was to examine the relationship between asthma and SHR and to investigate whether patients with SHR show signs of increased psychiatric illness. Patients with well-documented asthma answered a questionnaire on self-reported reactions to chemicals and scents in the environment and also a questionnaire mirroring psychiatric problems like anxiety and depression. The patients were provoked with a standardized capsaicin inhalation cough test. In accordance with the strict guidelines to be diagnosed with SHR this syndrome was not more common among asthma patients compared with earlier results in the general population. However, asthma patients more often had airway symptoms induced by chemicals and scents and coughed more from capsaicin inhalation. There was no significant indication that SHR was related to either depression or anxiety.

Relationship of airway sensory hyperreactivity to asthma and psychiatric morbidity

Authors: Johansson A, Millqvist E, Bende M

Journal: Ann Allergy Asthma Immunol. 2010 Jul;105(1):20-3

BACKGROUND: Patients with airway symptoms induced by chemicals and odors are common in allergy clinics, but the problems cannot be explained by allergic or asthmatic reactions. Previous studies have shown that these patients often have increased sensitivity to inhaled capsaicin, which is known to reflect sensory reactivity; a diagnosis of airway sensory hyperreactivity (SHR) has been suggested for this condition.
OBJECTIVES: To examine the relationship between asthma and SHR and to investigate whether patients with SHR show signs of increased psychiatric morbidity.
METHODS: This study included 724 patients who were attending an allergy center because of suspected allergy or asthma. All the patients completed a quantitative questionnaire on self-reported affective reactions and behavioral disruptions caused by odorous/pungent substances. A standardized capsaicin inhalation test was performed and a questionnaire to assess psychiatric morbidity was administered in patients with pronounced chemical sensitivity to identify those with SHR.
RESULTS: The prevalence of SHR was approximately 6% in asthmatic patients in the allergy center population, which is in accordance with the prevalence in a general population. There was no significant indication that SHR was related to either depression or anxiety.
CONCLUSION: There is no strong relationship between SHR and either asthma or psychiatric morbidity.

PMID: 20642199 [PubMed - in process]
The full text is available at:

5. The cough hypersensitivity syndrome
A group of researchers in UK has recently postulated a new paradigm for what has former been called chronic idiopathic cough: The Cough Hypersensitivity Syndrome. This syndrome comprises patients with chronic cough induced by environmental irritants like SHR but also other groups of chronic coughers without evident explanation to the cough. Cough hypersensitivity syndrome: a distinct clinical entity

Authors: Morice AH, Faruqi S, Wright CE, Thompson R, Bland JM

Journal: Lung. 2011 Feb;189(1):73-9

We postulate that most patients with chronic cough have a single discrete clinical entity: Cough Hypersensitivity Syndrome. We constructed a questionnaire that elicits the major components of the syndrome. Here we describe the validation of this questionnaire. Following iterative development, the Hull Airway Reflux Questionnaire (HARQ) was administered to patients and normal volunteers. It is self-administered and comprises 14 items with a maximum score of 70. Unselected patients were recruited sequentially from the Hull Cough Clinic. Preclinic questionnaires were compared with those obtained at the clinic. Responsiveness was assessed 2 months after the clinic visit. One hundred eighty-five patients and 70 normal volunteers were included in this study. There was a marked difference in HARQ scores between patients with chronic cough and normal volunteers. The sensitivity (94%) and specificity (95%) of the HARQ was high, with an area under the ROC curve of 0.99. All items of the scale significantly correlated positively with others in the scale and with the total score. On repeatability testing using Cohen's kappa with quadratic weights, significant agreement was noted for all items. Good correlation was observed between the total scores (r = 0.78). The questionnaire was also responsive to treatment; the minimum clinically significant change was estimated to be 16 points. We have demonstrated the HARQ to have good construct and criterion validity. It is both reproducible and responsive to change. It can be used as a diagnostic instrument and demonstrates that chronic cough represents a single coherent entity: Cough Hypersensitivity Syndrome.

PMID: 21240613 [PubMed - in process]
The full text is available at: