Validity and reliability of the Swedish version of the Leicester Cough Questionnaire in unexplained chronic cough.

BACKGROUND: Cough is considered chronic when it lasts for >8 weeks. When no medical explanation can be found it is often called unexplained chronic cough (UCC), which may affect health-related quality of life (HRQOL). This study aimed to assesses the validity and reliability of the Swedish version of the Leicester Cough Questionnaire (LCQ-S) in patients with UCC. METHODS: Seventy-six consecutively selected patients with UCC replied to: a local questionnaire; the LCQ-S; a Visual Analog Scale (VAS) for cough; the Swedish version of the Hull Airway Reflux Questionnaire (HARQ-S); and the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR). To evaluate the reproducibility of the LCQ-S, the VAS and LCQ-S were answered again after two to four weeks. RESULTS: Seventy-four patients (17 men) answered the questionnaires at baseline. Concurrent validity for LCQ-S was regarded as moderate with the VAS for cough and HARQ-S. Internal consistency using Cronbach's alpha was high for the LCQ-S total score (0.92) and satisfactory for the LCQ-S domains (0.78-0.83). Reliability and reproducibility were analysed in 57 patients (14 men). Intra-class correlation for the LCQ-S total score and domains showed strong reliability (≥0.92), without any significant differences over time. The standard error of measurement and the smallest real difference were 1.26 and 3.49, respectively. The Bland-Altman plot showed no systematic change in the mean values. CONCLUSIONS: The LCQ-S has good validity and reliability and can be used in clinical settings to evaluate HRQOL in Swedish-speaking adult patients with UCC.

Small and large airways' reactions to inhaled capsaicin in patients with chronic idiopathic cough, or asthma and in healthy control subjects.

Aims: Cough is a common medical problem, and when it persists for more than 8 weeks it is arbitrarily defined as chronic. While spirometry assesses the large airways, impulse oscillometry system (IOS) measures peripheral airway function. The present study investigated whether provocation with inhaled capsaicin affects the large and small airways in patients with chronic idiopathic cough (CIC) or asthma and in healthy controls. Materials and methods: Twenty-one patients with CIC, 18 patients with asthma, and 22 healthy controls were subjected to a provocation with capsaicin, and lung function was assessed by IOS and spirometry. Results: At baseline, before the capsaicin provocation, the CIC group had significantly increased airway resistance compared to the controls. After capsaicin provocation, the CIC group exhibited a significant increase in total airway resistance. The asthma group showed a small but significant reduction in spirometry, increased airway resistance, and reactance after capsaicin provocation. Capsaicin inhalation affected neither the spirometry nor the IOS of the healthy controls. Conclusions: The present study demonstrates that inhaled capsaicin induces changes in lung function, both in patients with CIC and in patients with asthma, when IOS, which measures changes also in the peripheral airways, is used. IOS appears to be a more sensitive tool than spirometry for the detection of airway impairment in airway provocation studies. In patients with CIC, higher peripheral resistance at baseline may have clinical significance.

Small and large airway reactions to osmotic stimuli in asthma and chronic idiopathic cough.

BACKGROUND: Chronic cough is a common symptom and related to several pulmonary, airway and heart diseases. When all likely medical explanations for the coughing are excluded, there remains a large group of patients with chronic coughing, which is mostly a cough reflex easily triggered by environmental irritants and noxious stimuli. The main aim of this study was to improve the diagnostic ability to differentiate chronic idiopathic cough (CIC) from asthma. METHODS: Twenty-three patients with CIC, 16 patients with mild asthma and 21 control participants were included. The study consisted of three randomised bronchial provocations with osmotic stimuli: mannitol, eucapnic dry air and hypertonic saline. At each provocation lung function was assessed by spirometry and impulse oscillometry (IOS). RESULTS: In a comparison of the groups, while the FEV1 measurements did not differ, the CIC group had increased airway resistance and reactance after provocation with hypertonic saline compared to the control subjects. After mannitol provocation the patients with asthma had significantly increased airway resistance compared to the controls and from eucapnic dry air provocations these patients had a significant reduction in spirometry values and increased airway resistance compared to both the patients with CIC and the controls. CONCLUSION: The asthma group reacted in a predictable way with impaired lung function from osmotic provocations, whereas the patients with CIC demonstrated peripheral airway changes from hypertonic saline, also known to be a noxious stimulus. The IOS method uncovers differences between patients with CIC and control participants that contribute to our ability to provide a correct diagnosis.

Physical Therapy Treatment of Impaired Chest Mobility in Patients with Airway Sensory Hyperreactivity.

BACKGROUND AND PURPOSE: In sensory hyperreactivity (SHR), patients have symptoms from the airways and the chest induced by environmental irritants like scenting products and cigarette smoke. They are characterized by increased cough reaction to inhaled capsaicin compared with healthy controls. Lung function tests are normal, and asthma medications have no or little effect. In a recent published article, patients with SHR were found to have impaired chest mobility and increased pain sensitivity. The purpose of this study was to evaluate if a physiotherapeutic intervention can increase chest mobility in SHR, influence these patients' symptoms and reduce capsaicin cough sensitivity. METHODS: Forty-one SHR patients were initially randomized in to groups, one for training and one for symptom registration in this controlled training study. It consisted of a daily training programme containing simple movements to increase the flexibility of the chest, a breathing exercise and a relaxation session as well as symptom registration. Chest expansion was measured with a measuring tape and thoracic and abdominal movement with light sensors. Pain sensitivity was assessed using pressure algometry and a standardized capsaicin inhalation threshold provocation-evaluated cough sensitivity. RESULTS: Twenty seven patients were left for analyses after 12 weeks and 26 patients after 24 weeks. Chest mobility and upper thoracic respiratory movements improved (p < 0.01), feeling of chest pressure and the capsaicin cough sensitivity decreased (p < 0.01). The patients also showed of significantly lowered pain pressure thresholds measured with algometry, compared with healthy controls (p < 0.001). CONCLUSION: Improvement of chest mobility after physiotherapeutic intervention indicates that these patients may have acquired a dysfunctional breathing pattern. The regular use of a training programme and structural breathing instructions can be used to improve chest mobility, chest symptoms and capsaicin cough sensitivity in patients with SHR and signs of dysfunctional breathing. Copyright © 2016 John Wiley & Sons, Ltd.

Reliability and Validity of the Swedish Version of the Hull Airway Reflux Questionnaire (HARQ-S).

INTRODUCTION: Cough is a common symptom for which patients seek medical care and is defined as chronic if it has lasted for more than 8 weeks. The Hull Airway Reflux Questionnaire (HARQ) was developed with the aim of eliciting the major component of chronic cough. It comprises 14 items with a maximum total score of 70. A Swedish version (HARQ-S) has previously been developed but not yet formally validated. The aim of the present study was to validate the HARQ-S in terms of instrumental reliability and concurrent validity. METHODS: A total of 67 consecutively selected non-smoking patients with chronic cough and 91 non-smoking allegedly healthy controls were asked to answer two questionnaires, the HARQ-S and a local questionnaire, at two occasions about 3 weeks apart. RESULTS: The HARQ-S showed good psychometric properties. The patients had significantly higher total scores (p < 0.001) compared to the controls, and the questionnaire showed outstanding discrimination ability to distinguish between patients and controls, with an area under the receiver operating characteristic curve of 0.99. Fifty patients and 77 controls completed the HARQ-S twice, showing good test-retest agreement in all items as well as in the total scores in both groups, and without any significant differences over time. CONCLUSION: The Swedish version of the HARQ is a valid and reliable questionnaire with good agreement between the two measurements in both patients and controls. The HARQ-S has good reliability and validity and can be used as a diagnostic tool in Swedish-speaking patients with chronic cough.

Long-Term Follow-Up in Patients With Airway Chemical Intolerance.

OBJECTIVE: A 5-year follow-up study showed that a group of patients with airway symptoms from chemicals and scents had lasting symptoms, together with enduring increased capsaicin cough sensitivity. The aim was to follow up the same patients after another 5 years. METHODS: All previously participants were invited for an additional follow-up. They visited the clinic twice; at one opportunity, they undertook a capsaicin inhalation provocation, and at the other, a methacholine provocation, and answered various questionnaires. RESULTS: Sixteen patients attende the study after a median of 8 years. They reported unchanged symptoms from chemicals and scents; the capsaicin cough sensitivity was still increased, and the repeatability for the capsaicin inhalation was good. CONCLUSIONS: Airway symptoms induced by chemicals and scents constitute a chronic disease, with unchanged trigger factors, persistent symptoms, and unchanged, long-lasting sensory hyperreactivity.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.This study was supported by grants from the Herman Krefting Foundation Against Asthma/Allergy, the Swedish Heart and Lung Foundation, and the Swedish Cancer and Allergy Fund.

Cough reduction using capsaicin.

UNLABELLED: Chronic 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. OBJECTIVES: We established whether an oral intake of natural capsaicin (chilli) could desensitize the cough reflex and improve unexplained coughing. METHODS: Twenty-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. RESULTS: Three 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 (p < 0.020) and in controls (p < 0.0061) compared to after the placebo period. Among patients, the concentration needed to reach C2 (p < 0.0004) and C5 (p < 0.0009) 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 (p < 0.0030) compared to the baseline scores. CONCLUSION: Capsaicin 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).

Capsaicin cough threshold test in diagnostics.

BACKGROUND: Among patients with chronic unexplained cough, there is a recognized subgroup with respiratory symptoms induced by environmental irritants like chemicals and odours. The diagnosis of sensory hyperreactivity (SHR) has been suggested for this group of patients and can be made using a tidal breathing capsaicin inhalation test. The aim of the present study was to evaluate the ability of a single-breath, dose-response capsaicin threshold test to discriminate such patients from control subjects. METHODS: A total of 46 patients with chronic cough and SHR who had previously shown a positive reaction in accordance with limits set for a tidal breathing capsaicin test were tested once with a single-breath, dose-response capsaicin cough threshold test, assessing capsaicin concentrations to evoke 2 (C2), 5 (C5) or 10 (C10) coughs. Twenty-nine subjectively healthy control subjects were also included and tested with the threshold method. RESULTS: Patients had significantly lower C2, C5 and C10 in comparison to controls. From the results among patients and controls, sensitivity and specificity were calculated, and a receiver operating characteristic curve was constructed, showing excellent ability for C5 and C10 to discriminate patients from control subjects. CONCLUSIONS: For patients with SHR and chronic cough, capsaicin cough sensitivity was once again confirmed to be increased, in this case, using the single-breath dose-response method. Limits set for cough reactions regarded as more sensitive than normal can be useful in diagnostics and further research. C5 seems to be the best measure to use in research and differential diagnostics.

A study of two generic health-related quality of life questionnaires--Nottingham Health Profile and Short-Form 36 Health Survey--and of coping in patients with sensory hyperreactivity.

BACKGROUND: Sensory hyperreactivity (SHR) is one explanation for airway symptoms induced by chemicals and scents. Little is known about health-related quality of life (HRQOL) and coping, in this group of patients. A study was done in patients with SHR to (1) compare the Nottingham Health Profile (NHP) and the Short-Form 36 Health Survey (SF-36) in regard to their suitability, validity, reliability, and acceptability; (2) evaluate how the patients cope with the illness; (3) assess whether there are differences between women and men with respect to HRQOL and coping; and (4) assess whether there are differences between patients and normative data with respect to HRQOL and coping. METHODS: A total of 115 patients (91 women) with SHR were asked to answer five questionnaires: a study-specific questionnaire, the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR), the NHP, the SF-36, and the Jalowiec Coping Scale-60. RESULTS: Eighty-three patients (72%; 70 women) completed all questionnaires. The SF-36 scores were less skewed and more homogeneously distributed and showed fewer floor and ceiling effects than the NHP scores. The SF-36 was also discriminated better between patients with high and low CSS-SHR scores. The reliability standard for both questionnaires was satisfactory. There were no gender differences in HRQOL. Patients with SHR had significantly lower HRQOL scores than the normative data in comparable domains of the NHP and the SF-36: emotional reactions/mental health, energy/vitality, physical mobility/functioning, and pain/bodily pain. In social isolation/functioning, the results were different; the NHP scores were similar to the normative data and the SF-36 scores were lower. The most commonly used coping styles were optimistic, self-reliant, and confrontational. Women used optimistic coping more than men. Compared with the normative group, patients with SHR used confrontational and optimistic coping more and emotive coping less. CONCLUSIONS: The current findings showed that both the NHP and the SF-36 were reliable instruments; but the results suggest that the SF-36 is a more sensitive instrument than the NHP for elucidating HRQOL in patients with SHR. Patients with SHR experienced a poor HRQOL and they followed the Western tradition of preferring problem-focused coping strategies to palliative and emotive strategies.

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

BACKGROUND: A 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). METHODS: Fifty-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. RESULTS: Thirty-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. CONCLUSIONS: Environmental 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.

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

INTRODUCTION: Chronic 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. METHODS: Fourteen patients with chronic cough and airway sensitivity to environmental irritants and 15 control subjects were tested on three occasions. Each one inhaled a 1 mL 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. RESULTS: Patients' cough thresholds differed significantly from the controls' on all three provocations (P < 0.0001). After inhalation of 1% menthol, the patients' cough thresholds were significantly higher (P < 0.02) compared to after placebo inhalation and to after 0.5% menthol inhalation (P < 0.05). The patients' peak inspiratory flows were significantly reduced after inhalation of the placebo (saline) (P < 0.05) 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 (P < 0.05) but not after 1% menthol. Among the controls, forced inspiratory flows 50% were lowered after only placebo inhalation (P < 0.05). CONCLUSIONS: In 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.

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

INTRODUCTION: Patients 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. METHODS: Thirty-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. RESULTS: Groups 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. CONCLUSION: Patients 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.

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

BACKGROUND: Chronic 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. METHODS: A 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. RESULTS: Sixty-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. CONCLUSIONS: Among 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.

Sensitivity to environmental irritants and capsaicin cough reaction in patients with a positive methacholine provocation test before and after treatment with inhaled corticosteroids.

BACKGROUND: Increasing evidence points to a potential role for members of the transient receptor potential family of cation channels on several features of asthmatic disease. The cough sensitivity to inhaled capsaicin is known to reflect the reactivity of these airway sensory nerves. OBJECTIVE: The aim was to study, among patients having a positive methacholine provocation and diagnosed with asthma, capsaicin cough sensitivity, sensitivity to methacholine, and levels of exhaled nitric oxide before and after treatment with inhaled steroids, and further, to measure the self-reported impact from environmental irritants. METHODS: Eighteen steroid-naïve patients with a positive methacholine test underwent capsaicin inhalation provocation on two occasions, before and after regular use of inhaled steroids over at least 3 months. Comparisons were made to 21 healthy controls. Sensitivity to methacholine and levels of exhaled nitric oxide were measured before and after the treatment. The participants also answered a validated questionnaire regarding environmental irritants. RESULTS: The patients displayed higher capsaicin cough sensitivity than the controls before the treatment period, but not afterward. Before treatment, capsaicin cough answer correlated significantly with levels of exhaled nitric oxide, but not with methacholine sensitivity. After treatment with inhaled corticosteroids, the capsaicin cough sensitivity and the inflammatory parameters were normalized. In comparison to the control group, the patients reported more affective reactions to and behavioral disruptions induced by environmental irritants. CONCLUSIONS: In steroid-naïve patients with a positive methacholine test, there is a link between that part of the airway inflammation that is reflected by exhaled nitric oxide and that followed by an augmented reactivity of capsaicin-sensitive sensory nerves. This association disappears after steroid treatment.

Sensitivity to environmental irritants and quality of life in COPD.

It is a common clinical experience that patients with chronic obstructive pulmonary disease (COPD) complain of airway symptoms provoked by environmental irritants like chemicals and scents, although few studies can confirm such connections. The aim was to study the prevalence of airway symptoms induced by chemicals and scents in a group of patients with newly diagnosed CPOD and to analyze any relation to illness severity and quality of life. Eighty-one patients with COPD were recruited to the study. By mail they were asked to answer three questionnaires regarding symptoms, quality of life, and social and emotional influence of airway symptoms induced by environmental irritants. A majority (62%) of the COPD patients claimed to be hyperreactive to chemicals and scents. As a group they scored higher on a questionnaire measuring social and emotional influences of such environmental irritants compared to healthy control subjects. Further, high scores were more common among patients with a very severe form of COPD and among patients with regular use of ß(2)-stimulants. High scores were also associated with significantly more airway symptoms and, in some aspects, with impaired quality of life. In conclusion, the results of this study show that airway symptoms induced by environmental irritants are common in patients with COPD and that this increased airway sensitivity follows the impairment of lung capacity. The mechanisms behind this remain unclear.

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

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.

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 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.

Capsaicin provocation using two different inhalation devices.

BACKGROUND: Sensory hyperreactivity (SHR) has been suggested as one explanation for chemically induced airway symptoms; it can be diagnosed with a capsaicin inhalation test. Previous capsaicin inhalation studies of SHR have used a Pari Boy device. This model of inhalator device has become outdated, hence it is necessary to abandon it in favour of a new device. The aim of this study was to transfer the capsaicin inhalation test using the Pari Boy device to a corresponding model using the Maxin MA3 device. METHODS: Twenty-one patients with SHR and 44 healthy controls visited the clinic twice and underwent a randomised protocol. The participants were provoked with saline and capsaicin using one of two devices, Pari Boy and Maxin MA3. Eight patients also underwent two additional capsaicin provocations with Maxin MA3. A new series of capsaicin concentrations was chosen for Maxin MA3. The results from each device were analysed, the agreement between the two devices and the repeatability of the Maxin MA3 were evaluated. RESULTS: Among all participants, the mean number of coughs with the Pari Boy was 5.5 (95% CI: 2.7; 8.2) after inhalation of 0.4 micromol/L capsaicin and 20.0 (95% CI: 14.1; 25.9) after 2.0 micromol/L. With the Maxin MA3, the mean number of coughs was 3.6 (95% CI: 1.3; 4.0) after 0.06 micromol/L capsaicin, and 17.8 (95% CI: 12.0; 23.6) after 0.3 micromol/L. The Maxin MA3 showed good repeatability and the agreement between the devices with the capsaicin concentrations chosen for each device was considered to be good.

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.

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.