Ewa Ternesten-Hasséus

Quality of Life and Capsaicin Sensitivity in Patients with Airway Symptoms Induced by Chemicals and Scents: A Longitudinal Study

Objective It is common in asthma and allergy clinics to see patients presenting with upper and lower airway symptoms that are induced by chemicals and scents and not explained by allergic or asthmatic reactions. Previous studies have shown that these patients often have increased cough sensitivity to inhaled capsaicin; such sensitivity is known to reflect the airway sensory reactivity. The aim of this study was to evaluate the duration of symptoms induced by chemicals and scents and to measure health-related quality of life (HRQL) in patients with chemically induced airway symptoms. We also wished to determine and compare repeatability of the cough response to capsaicin inhalation, and to evaluate the patients’ airway sensory reactivity in a long-term perspective. Participants Seventeen patients with a history of at least 12 months of airway symptoms induced by chemicals and scents were followed over 5 years with repeated questionnaires, measurements of HRQL, and capsaicin inhalation tests. Results The symptoms persisted and did not change significantly over time, and the patients had a reduced HRQL that did not change during the 5-year period. The capsaicin sensitivity was increased at the start of the study, the cough sensitivity was long-lasting, and the repeatability of the capsaicin inhalation test was considered to be good in a long-term perspective. Conclusions Upper and lower airway symptoms induced by chemicals and scents represent an entity of chronic diseases, different from asthma or chronic obstructive pulmonary disease, with persistent symptoms, a reduced HRQL, and unchanged sensory hyperreactivity.

Changes in levels of nerve growth factor in nasal secretions after capsaicin inhalation in patients with airway symptoms from scents and chemicals.

Patients complaining of upper and lower airway symptoms caused by scents and chemicals have previously been shown to have increased cough sensitivity to inhaled capsaicin, but the precise mechanisms behind this reaction are unknown. Hypothesizing that a neurochemical alteration related to sensory hyperreactivity (SHR) of the airway mucosa occurs, we measured levels of nerve growth factor (NGF) in nasal lavage fluid (NAL) before and after capsaicin inhalation provocations and related the capsaicin cough sensitivity to the NGF levels. Thirteen patients with SHR and 14 control subjects were provoked with capsaicin inhalation at three different doses. We measured NGF in NAL before and after provocation and recorded cough and capsaicin-induced symptoms. All subjects demonstrated a dose-dependent cough response to capsaicin inhalation, with a more pronounced effect in patients than in controls. Basal levels of NGF were significantly lower in the patient group than in the control subjects (p < 0.01). After capsaicin provocation, the patients showed a significant increase in NGF (p < 0.01), which was related to capsaicin cough sensitivity. The findings demonstrate that, in patients with airway symptoms induced by scents and chemicals, SHR is real and measurable, demonstrating a pathophysiology in the airways of these patients compared to healthy subjects.

Increased capsaicin cough sensitivity in patients with multiple chemical sensitivity.

Learning ObjectivesRecall the findings of past studies of lower respiratory function in persons having multiple chemical sensitivity (MCS).Identify criteria for participating in the present study, the grounds for exclusion, and how the trial was carried out.Explain the ways in which patients diagnosed as having MCS differed from control subjects in their reactions to inhaled capsaicin, and the possible implications of these findings. Multiple chemical sensitivity (MCS) is characterized by chemically induced symptoms from multiple organ systems. No consistent physical findings or laboratory abnormalities have been determined for the associated symptoms. Twelve patients with chemically induced airway symptoms, who satisfied Cullen’s criteria for MCS, were provoked double-blind, randomized with saline and three increments of inhaled capsaicin. The recordings were compared with those of a control group of healthy individuals. The results found that the patients coughed more than the control subjects at each dose of capsaicin (P < 0.05 for 0.4 &mgr;mol/L capsaicin and P < 0.005 for 2 &mgr;mol/L and 10 &mgr;mol/L). The capsaicin provocation also induced significantly more symptoms in patients with MCS. We conclude that airway sensory reactivity is increased in patients with MCS, a finding which suggests that neurogenic factors may be of importance in this condition.

Inhalation of menthol reduces capsaicin cough sensitivity and influences inspiratory flows in chronic cough

INTRODUCTIONnChronic cough is a common clinical problem and there is a shortage of effective treatments for it. Within the group of transient receptor potential ion channels a receptor for the cooling substance menthol has been identified. This study aimed to assess whether pre-inhalation of dissolved, nebulised menthol could increase capsaicin cough thresholds and influence spirometric values.nnnMETHODSnFourteen patients with chronic cough and airway sensitivity to environmental irritants and 15 control subjects were tested on three occasions. Each one inhaled a 1xa0mL of nebulised menthol solution of 0.5% or 1% or placebo (saline with 0.05% menthol) at each visit in a randomized and double-blind order. They were then provoked by capsaicin inhalation.nnnRESULTSnPatients cough thresholds differed significantly from the controls on all three provocations (Pxa0<xa00.0001). After inhalation of 1% menthol, the patients cough thresholds were significantly higher (Pxa0<xa00.02) compared to after placebo inhalation and to after 0.5% menthol inhalation (Pxa0<xa00.05). The patients peak inspiratory flows were significantly reduced after inhalation of the placebo (saline) (Pxa0<xa00.05) but not after inhalation of 0.5% or 1% menthol. Forced inspiratory flows 50% were lowered after inhalation of placebo and of 0.5% menthol (Pxa0<xa00.05) but not after 1% menthol. Among the controls, forced inspiratory flows 50% were lowered after only placebo inhalation (Pxa0<xa00.05).nnnCONCLUSIONSnIn patients with chronic cough, pre-inhalation of menthol reduces cough sensitivity to inhaled capsaicin and influences inspiratory flows. The findings may provide scientific support for the common practice of using menthol as a reliever for variant airway discomfort. The use of menthol in different cigarette brands could be questioned since it could conceal the natural irritation following smoking.

Symptoms induced by environmental irritants and health-related quality of life in patients with chronic cough - A cross-sectional study

BackgroundChronic cough is a common condition, but some patients have no evident medical explanation for their symptoms. A group of patients has been identified, characterized by upper and lower airway symptoms triggered by chemicals and scents, and heightened cough sensitivity to inhaled capsaicin. Chronic cough is usually a prominent symptom in these patients, and it has been suggested that they suffer from sensory hyperreactivity.Our main aim was to analyse, in a group of patients with chronic cough, the presence of symptoms induced by environmental factors such as chemicals, scents, and cold air, and to measure the social and emotional influences of these symptoms in relation to quality of life. A second aim was to pilot-test a Swedish translation of a cough-specific questionnaire.MethodsA total of 119 patients with chronic cough were asked to answer three different questionnaires: a local symptom questionnaire, the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR), and the Nottingham Health Profile (NHP). In addition, a Swedish version of the Hull Airway Reflux Questionnaire (HARQ) was developed and answered by a subgroup of patients and healthy controls.ResultsSixty-two patients (52%) with mean cough duration of 10.6 years answered the local symptom questionnaire, the CSS-SHR, and the NHP. Of these, 39 (63%) claimed to have cough and other symptoms induced by chemicals and scents. Compared to population-based findings, the patients scored higher on the CSS-SHR, and the CSS-SHR score was significantly higher among chemical-sensitive individuals (p < 0.001). The NHP showed that the patients had a significantly reduced quality of life, which was most pronounced among chemical-sensitive individuals. The 31 patients who answered the HARQ had significantly higher scores (p < 0.0001) than 59 healthy controls.ConclusionsAmong patients with chronic cough, a majority claimed that environmental factors induced coughing. Both the CSS-SHR and the HARQ score systems seem to be valuable instruments in the mapping of cough patients, supporting the novel paradigm of a cough hypersensitivity syndrome. Our results emphasize that cough is a substantial burden to the patient, influencing daily living and quality of life.

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

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.

Cough reduction using capsaicin.

UNLABELLEDnChronic unexplained cough triggered by environmental irritants is characterized by increased cough reflex sensitivity, which can be demonstrated by means of inhaled capsaicin. Topical capsaicin can be used to improve non-allergic rhinitis and intestinal hypersensitivity and to reduce neuropathic pain.nnnOBJECTIVESnWe established whether an oral intake of natural capsaicin (chilli) could desensitize the cough reflex and improve unexplained coughing.nnnMETHODSnTwenty-four patients with irritant-induced, unexplained chronic cough and 15 controls were included in the study. For 4 weeks, the participants took capsules with pure capsaicin, and for 4 weeks, they took placebo capsules. The protocol was crossover, randomized, and double blind. Cough sensitivity during the study was evaluated by a standardized capsaicin inhalation cough test that assessed the capsaicin concentration required to reach two coughs (C2) and five coughs (C5). Participants were also administered questionnaires on cough and cough-related symptoms.nnnRESULTSnThree patients withdrew before the study end, one during the active treatment period and two during the placebo period. After treatment with capsaicin, the thresholds for C2 were higher (improved) both in patients (pxa0<xa00.020) and in controls (pxa0<xa00.0061) compared to after the placebo period. Among patients, the concentration needed to reach C2 (pxa0<xa00.0004) and C5 (pxa0<xa00.0009) increased after the period with the active substance compared to cough thresholds at baseline. The cough symptom scores improved after 4 weeks of active treatment (pxa0<xa00.0030) compared to the baseline scores.nnnCONCLUSIONnCapsaicin powder taken orally decreased capsaicin cough sensitivity and cough symptoms. The findings suggest a desensitization of the cough-sensitive transient receptor potential vanilloid-1 (TRPV1).

Dyspnea from Exercise in Cold Air is Not Always Asthma

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 CO2, and PSaO2 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 CO2 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.

Capsaicin sensitivity in patients with chronic cough- results from a cross-sectional study

BackgroundA subgroup of patients with chronic cough is recognised as having airway symptoms resulting exposure to chemicals and scents related to enhanced cough sensitivity to inhaled capsaicin. Sensory hyperreactivity, which has an estimated prevalence of more than 6%, is one possible explanation for the symptoms experienced by these patients. We hypothesized that a number of patients diagnosed with chronic unexplained cough also have coughing provoked by chemical irritants associated with augmented capsaicin cough reaction, but the extent of such a relation is not known. One aim of the present study was to analyse cough sensitivity to inhaled capsaicin in patients with chronic unexplained cough. Another aim was to compare capsaicin sensitivity in individuals with chemically induced coughing (the chemical-sensitive group) to capsaicin sensitivity in those without such chemical sensitivity (non-sensitive group).MethodsFifty-six participants from an earlier cross-sectional study of 62 patients with chronic unexplained cough were asked to participate in this study: 33 were chemical-sensitive and 23 were non-sensitive. Each participant visited the clinic once and performed a capsaicin inhalation test with one of two inhalation devices. The number of coughs, induced airway symptoms, and spirometry results were recorded.ResultsThirty-nine of the invited patients participated in the study, with 32 in the chemical-sensitive group (21 women, 11 men), and 7 in the non-sensitive group (4 women, 3 men). The chemical-sensitive patients coughed significantly more on inhaling capsaicin, and had significantly more other airway symptoms compared to those in the non-sensitive group. Women coughed significantly more than men after receiving the higher concentration of capsaicin.ConclusionsEnvironmental irritants often trigger chronic unexplained cough. The current findings confirm that this sensitivity is related to enhanced capsaicin cough sensitivity and indicates more involvement of airway sensory nerves in the pathophysiology of the disease than in cough without evident trigger factors.

Respiratory movement and pain thresholds in airway environmental sensitivity, asthma and COPD

INTRODUCTIONnPatients with sensory hyperreactivity (SHR) have airway environmental sensitivity, chronic cough and dyspnoea. Cough, chest discomfort and sense of difficulties getting air are some of the symptoms these patients seek medical attendance for. The patients have increased cough sensitivity to inhaled capsaicin, mediated by ion channel receptors on sensory nerves also known to react to pain stimuli. Whether a link exists between capsaicin airway sensitivity and pain sensitivity has not yet been evaluated. The aim was to investigate chest mobility, respiratory movement and pain sensitivity in SHR patients compared with patients with asthma, chronic obstructive pulmonary disease (COPD) and alleged healthy control subjects.nnnMETHODSnThirty-five patients diagnosed with SHR, 19 with COPD, 32 with asthma and 28 control subjects were included. Chest expansion was measured with a measuring tape and thoracic and abdominal movement with light sensors. Pain sensitivity was assessed using a pressure algometer.nnnRESULTSnGroups differed significantly in lung function, respiratory rate and pain sensitivity but also in chest expansion and abdominal breathing movement. In comparison with the control and asthma groups but not the COPD patients, SHR patients had an increased respiratory rate and reduced abdominal movement during deep breathing. All patient groups showed lower pain thresholds than the controls.nnnCONCLUSIONnPatients with SHR have evident signs of dysfunctional breathing and appeared to be most similar to the COPD group except for lung function. Lower pain thresholds among the patients indicate a general up-regulation of the sensory nerve system.