On the relation between capsaicin sensitivity and responsiveness to CO2: detection sensitivity and event-related brain potentials.

OBJECTIVE: Sensory hyperreactivity (SHR) with predominantly airway symptoms is a subgroup of chemical intolerance to various environmental substances with pungent/odorous properties. The hallmark of SHR is sensitivity to capsaicin inhalation, resulting in extensive coughing likely to be mediated by a C-fiber hyperreactivity of the airway sensory neurons. However, it is not clear whether capsaicin sensitivity implies a greater sensitivity to chemosomatosensory substances in general. Therefore, the present study tested the hypothesis of an association between capsaicin cough sensitivity and sensitivity to CO(2) with respect to detection sensitivity and electrophysiological brain response. METHODS: A correlational study was employed to investigate the relation between capsaicin cough sensitivity and detection thresholds and chemosomatosensory event-related potentials (ERPs) for CO(2) presented in the nasal cavity in 35 persons varying in capsaicin cough sensitivity. RESULTS: Number of coughs were found to correlate negatively with CO(2) threshold and tended to correlate negatively also with N1 and P2 latencies of the chemosomatosensory ERP for CO(2). No tendencies of correlations were found between number of coughs and latencies for olfactory and auditory ERPs, recorded for comparison, but, unexpectedly, were found between number of coughs and auditory N1 amplitude. CONCLUSIONS: The results imply that capsaicin cough sensitivity, such as in SHR, is related to higher detection sensitivity, and tends to be related to faster cortical processing of other chemosomatosensory substances, at least of CO(2).

A prospective study of allergy development in 158 children and 128 adults with new extensive exposure to furred animals.

BACKGROUND: There is still controversy over whether exposure to furred animals increases or decreases the risk of developing sensitization and allergic symptoms to such animals, and there is a need for further knowledge on this subject. OBJECTIVE: The aim of this study was to follow allergy development in relation to new extensive exposure to furred animals in adults and children. METHODS: A total of 286 individuals, 128 parents and 158 children, were recruited from 68 families who intended to buy a dog or a cat, or where one child of the family intended to start riding a horse. Subjects were examined before the new allergen exposure and once a year thereafter for 5 years, in all at six occasions, and they also completed questionnaires covering allergy symptoms. Serum IgE antibodies to cat, dog and horse were determined each year, and fur allergens from beds and living rooms were analysed. RESULTS: Two-hundred and fifty-six study subjects remained for evaluation, 37 of whom showed signs of allergic sensitization at the start of the study. Four children (11%) in this pre-sensitized group developed IgE antibodies to their new animal and six (16%) to another animal. Among the 219 participants who were not sensitized when entering the study, one male adult (0.4%) developed a sensitization to his new animal, and nobody developed sensitization to other animals. Pre-sensitized individuals had significantly more allergic symptoms at the study start, but the symptom scores did not change over time. CONCLUSIONS: When the first year of a human's life has passed, we have no strong evidence to recommend avoidance of a domestic animal in order to prevent new allergy development, even if there are known allergies in the family or if the individual is sensitized and has allergic symptoms to another allergen. Five years exposure to new fur allergens does not seem to influence sensitization to these animals in either sensitized or non-sensitized children and adults.

Prevalence and risk factors for self-reported odour intolerance: the Skövde population-based study.

OBJECTIVES: The present study was performed to determine the prevalence of odour intolerance in adults with respect to both self-reported general intolerance and affective and behavioural consequences. Furthermore, we aimed to relate odour intolerance to explanatory variables and risk factors. METHOD: This is a cross-sectional, population-based epidemiological study. A random sample of 1900 inhabitants from the age of 20, stratified for age and gender, were recruited. Subjects were invited for clinical examinations that included questions about general odour intolerance, respiratory symptoms and smoking habits, as well as a smell identification test. The chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) was used to quantify affective and behavioural consequences. RESULTS: In total 1387 volunteers (73% of the sample) were investigated. The overall prevalence of self-reported general odour intolerance was 33% (95% confidence interval (CI): 30-36%), with problems mainly from the upper respiratory tract. The prevalence of affective and behavioural consequences of odour intolerance (CSS-SHR score > or =43) was 19% (95% CI: 15-22%). The risk for the latter condition was increased in women compared with men (odds ratio = 2.3: 95% CI: 1.5-3.6), but no increased risk was found related to current smoking or impaired sense of smell. CONCLUSION: This study demonstrates that intolerance to odours is a widespread problem in society, and that it is about twice as common in women than in men.

Relationship of airway symptoms from chemicals to capsaicin cough sensitivity in atopic subjects.

BACKGROUND: It is well known that some patients with allergy complain of airway symptoms from chemicals (ASCs) and strong odours. However, the importance of such information for the treatment of allergic disease is not known. Such symptoms in non-allergic patients have previously been shown to be related to increased sensory nerve reactivity, which is expressed as increased cough sensitivity to inhaled capsaicin. OBJECTIVE: The aim of this study was to examine ASC in atopic patients and relate it to cough reaction to capsaicin inhalation. MATERIALS AND METHODS: Fifty-seven consecutively chosen, skin prick-positive patients with symptoms of the upper and/or lower airways completed a questionnaire concerning ASC. The patients were then divided into two groups, those with and those without such symptoms. Both groups were provoked with inhaled capsaicin in three increments and compared with 73 healthy control subjects. RESULTS: Out of 57 atopic patients, 34 reported ASC agents and 23 did not. The patients with ASC were older (P<0.01) and coughed significantly more on capsaicin provocation (P<0.001), but did not differ from them with respect to the allergic disease or its treatment or to smoking habits. Patients with atopy but without ASC did not differ from healthy controls with regard to sensitivity to capsaicin inhalation. The scored degree of ASC was directly related to the number of coughs during the capsaicin provocation. CONCLUSION: ASC in atopic patients are related to increased airway sensory nerve reactivity. There is still no explanation for this in certain patients with atopy, but age may be a confounding factor.

Capsaicin inhalation test for identification of sensory hyperreactivity.

BACKGROUND: Patients with upper and lower airway symptoms and with pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke, have been suggested to have sensory hyperreactivity (SHR). The symptoms have been difficult to identify with physiological measurements and the effects of various medications are doubtful. However, these patients have been found to be more sensitive to inhalation of capsaicin than healthy people. The aim of this study was to establish limit values with the capsaicin inhalation test in patients with SHR. METHODS: Ninety-five consecutive patients with upper and lower airway problems, who were admitted for allergy testing, underwent a capsaicin inhalation test with three different concentrations. The number of coughs was registered during each challenge. Score systems were used for symptoms and influence on social life of sensitivity to odours. In relation to scored symptoms, the patients were grouped as SHR or not, and compared with 73 healthy controls. RESULTS: All patients and controls coughed on capsaicin in a dose-dependent manner. Symptom score of odour sensitivity in patients was positively correlated to the response of the test. Out of 95 patients, 15 (16%) were scored to SHR. Patients with SHR reacted more to the capsaicin inhalation test than the other patients and the healthy controls. The limit values for a positive capsaicin inhalation test for the SHR were determined to be 10, 35 and 55 coughs at 0.4, 2.0 and 10 microM capsaicin, respectively. CONCLUSION: The capsaicin inhalation test well reflects the degree of airway sensitivity to chemicals and to what extent the social life is influenced. The cut-off values of the test can distinguish patients with pronounced sensitivity to odours.

Capsaicin cough sensitivity is decreased in smokers.

Although capsaicin provocation has been used to evaluate treatment against cough, which is one of the most common respiratory symptoms, there are still methodological considerations that are not fully known. Capsaicin stimulates the unmyelinated slow C-fibres of the sensory nervous system, which leads to coughing. Smoking often leads to respiratory symptoms with cough and phlegm. The aim of this study was to examine the effect of smoking on capsaicin provocation. Subjectively healthy smokers and non-smokers were challenged with capsaicin in increasing doses. The coughs were counted and irritation of the lower airways was graded on a symptom score. Smokers reacted to provocation with significantly fewer coughs, but there was no difference regarding other symptoms. These results are in agreement with the hypothesis that nicotine inhibits or blocks C-fibres of the sensory nervous system of the lower respiratory tract. Clinically, this may serve to explain increasing airway symptoms that are often seen after cessation of smoking.

Relationship between subjective nasal stuffiness and nasal patency measured by acoustic rhinometry.

Nasal geometry measured by acoustic rhinometry was compared with the subjective sensation of nasal stuffiness in healthy subjects before and after provocation with histamine. The correlation was poor at rest, but it was significant after histamine provocation in children and adults. It is easier to find a relationship between subjective and objective nasal obstruction afer inducing congestion. (American Journal of

Nasobronchial relationship after cold air provocation.

Provocation with cold air in the nose causes broncho-obstruction while warm air causes bronchodilation in patients with asthma, but not in healthy subjects. These findings have suggested the existence of a nasobronchial reflex. The present study aimed to block this effect and evaluate the mechanisms underlying the effect on lung function after cold stimulation of the nose. Lung function, as measured with specific conductance and forced expiratory flow, was reduced after cold stimulation of the nose, but this effect could not be blocked by anesthetizing the nose or by inhaling an anti-cholinergic drug before the provocation. These results confirm the presence of a nasobronchial relationship, but not of a nasobronchial reflex.

Combining a beta2-agonist with a face mask to prevent exercise-induced bronchoconstriction.

BACKGROUND: In this study, we aimed to test the effect of combining a P2-agonist with a heat- and moisture-exchanging cellulose face mask in patients with bronchoconstriction induced by exercise in cold air. METHODS: Nine allergic, asthmatic patients with a history of adverse reaction to exercise were tested on an ergometric bicycle at a temperature of approximately -10 degrees C. They were in turn given no treatment, given premedication with a beta2-agonist, allowed to breathe through a heat- and moisture-exchanging cellulose face mask, and given both premedication and the face mask. After each treatment regimen, they were subjected to provocation with exercise and cold air. RESULTS: The decrease in FEV, was greatest with no therapy (mean maximal change: 27%), and this diminished when the face mask was used (mean maximal change: 12%,) or premedication with a 32-agonist was given (mean maximal change: 7%); no decrease in FEV1 occurred with the combination of agonist and face mask. CONCLUSIONS: The results suggest that different mechanisms are involved in the pathophysiology of exercise-induced bronchoconstriction (EIB). This finding may be of importance for asthmatic athletes who train and compete in a cold climate and are affected by small changes in their lung function.

Quality of life and capsaicin sensitivity in patients with sensory airway hyperreactivity.

BACKGROUND: A group of patients with asthma-like symptoms and sensitivity to chemical irritants has shown an increased cough sensitivity to inhaled capsaicin compared to patients with asthma and to healthy controls. The condition is called sensory hyperreactivity (SHR), and the patients often feel that they are socially handicapped because of the risk of exposure to chemical irritants in daily life. METHODS: Twenty-six patients with asthma-like symptoms after exposure to nonspecific irritating stimuli, but without IgE-mediated allergy or demonstrable bronchial obstruction, were selected for a study of the response to a capsaicin test and measurement of quality of life by a general health profile (the Nottingham Health Profile [NHP]). We also investigated whether there was a correlation between quality of life and sensitivity to capsaicin. RESULTS: The patients demonstrated a dose-dependent response to the capsaicin provocation, with coughing and respiratory and other symptoms, that significantly differed from 12 healthy controls. The health profile showed that patients with SHR had a significantly reduced quality of life compared to reference values, and there was a significant correlation between the health profile and sensitivity to capsaicin. CONCLUSIONS: Patients with asthma-like symptoms verified by the capsaicin inhalation test for sensory hyperreactivity have a poor quality of life. The correlation between quality of life and sensitivity to capsaicin objectively demonstrates the validity of this general health profile study.

Cough provocation with capsaicin is an objective way to test sensory hyperreactivity in patients with asthma-like symptoms.

BACKGROUND: A group of patients with asthma-like symptoms and sensitivity to chemical irritants, but without bronchial obstruction, has been found among subjects referred for suspected asthma. They have no well-defined diagnosis, and no objective diagnostic method has previously been available. These patients are more sensitive to inhaled capsaicin than are patients with asthma or healthy controls. The aim was to study cough and other capsaicin-induced symptoms and to test the effect of a drug (lidocaine) that inhibits nerve transmission in sensory nerves. METHODS: Twelve patients were provoked with three different concentrations of inhaled capsaicin solutions in a randomized, double-blind order. They all had asthma-like symptoms and were sensitive to chemical irritants, but had no IgE-mediated allergy or demonstrable bronchial obstruction. Before the provocations, the patients inhaled lidocaine or placebo (saline), also in a double-blind, randomized order. The results were expressed as the number of coughs and scores of various symptoms. RESULTS: The patients reacted in a dose-dependent way with cough, airway, and eye symptoms, which were significantly reduced after preinhalation of lidocaine. CONCLUSIONS: A drug that inhibits transmission in sensory nerves successfully blocked the number of coughs and other symptoms provoked by inhalation of capsaicin. This indicates that the mechanisms underlying chemical sensitivity in these patients may originate in the sensory nervous system, and we call this condition "sensory hyperreactivity".

Effect of nasal air temperature on FEV1 and specific airways conductance.

We investigated whether changes in nasal air temperature affect specific airway conductance (SGaw) and one second forced expiratory volume (FEV1) in 10 asthmatic patients with a history of cold-sensitive asthma and eight healthy subjects. An air-stream (0.6 l s-1) of -15 degrees C, +22 degrees C or +37 degrees C was blown into both nostrils during a Valsalva manoeuvre. Each provocation consisted of 10 puffs of air, each of 15 s duration, at 1 min intervals. Before and at regular intervals after the provocations, SGaw and FEV1 were determined. In asthmatics, after cold air provocation, SGaw fell 23% (P<0.01) and FEV1 8% (P<0.01). After the warm air provocations, SGaw rose 15% (P<0.01) and FEV1 6% (P<0.01). After the ambient air provocations, no significant changes occurred in SGaw or FEV1. In the healthy subjects, the nasal provocations caused no significant changes in lung function. The present study shows that cold air in the nose causes a slight obstruction and warm air possibly a slight dilatation of the lower airways in patients with a history of cold-sensitive asthma but not in healthy subjects.

Provocations with perfume in the eyes induce airway symptoms in patients with sensory hyperreactivity.

BACKGROUND: In earlier studies, we have shown that patients with a history of sensory hyperreactivity develop asthma-like symptoms when exposed to strong scents, even if they cannot smell any scent. METHODS: For study of possible pathophysiologic mechanisms behind sensory hyperreactivity, the patients' airways and eyes were separately exposed to a common inducing factor, perfume. Eleven patients with a history of hyperreactivity to chemical trigger factors, such as perfume, were provoked single-blindly in a placebo-controlled, randomized study. During airway exposure, the eyes were covered and, during the eye exposure, the patients inhaled fresh air. A special face mask or a nose clip was used to avoid any smell. RESULTS: During the 30-min exposure to perfume, there was a gradual increase in three main symptoms; i.e., eye irritation, cough, and dyspnea, after both the airway and eye exposures. The increases were significant compared with placebo. CONCLUSIONS: Asthma-like and other symptoms, such as irritation of the eyes, may be induced by exposure of both the airways and the eyes in patients with sensory hyperreactivity. This points to the importance of studying the sensory nervous system, not only in the airways, but also in other organs.

Reference values for acoustic rhinometry in subjects without nasal symptoms.

Reference values for acoustic rhinometry are presented from 334 individuals without nasal symptoms between 4 years and 61 years old. There was a significant correlation between the minimal cross-sectional area (MCA) and nasal volume. Although the reproducibility of the method was good, the MCA varied widely. MCA correlated weakly to weight, height, age, and body mass index. Our data suggest that acoustic rhinometry is valuable for inter-individual comparisons.

Evaluation of side effects after nicotine nasal spray in patients with chronic rhinitis.

Thirty-three subjects with chronic rhinitis used nicotine nasal spray in an open study as an aid in smoking cessation. Thirty-eight percent of them were completely abstinent at 12 weeks, whereas 35% were completely abstinent at 20 weeks. The nasal spray was associated with irritant nasal side effects, which occurred most often in the early stages of treatment. Clinical nasal examinations could not observe any significant impairment in nasal conditions following spray use. In conclusion, this study confirms the short-term safety of the nicotine nasal spray as an aid in smoking cessation.

Methacholine provocations do not reveal sensitivity to strong scents.

BACKGROUND: It is common among patients with asthma to report sensitivity to strong scents. Provocations with methacholine are often used to verify this sensitivity. OBJECTIVE: To evaluate the significance of methacholine provocations in asthmatic patients complaining about sensitivity to strong scents, we compared sensitivity to methacholine and reactions to provocation with perfume. METHODS: Ten asthmatic patients having a PC20 less than 2 mg methacholine/mL were provoked with perfume or saline on four occasions. On two occasions, the patients wore a nose clip and underwent provocations with perfume for 5 and 30 minutes, respectively. On one occasion, the patients were provoked with perfume but without a nose clip for five minutes. All patients were also subjected to provocation with a placebo (saline). They were asked to estimate their sensitivity to strong scents in connections with symptoms of asthma. RESULTS: No changes in lung function occurred after any of the provocations with perfume compared with the baseline or with placebo. Although all patients were very sensitive to methacholine, no relationship was found to their reported sensitivity to strong scents in connection with asthmatic symptoms. CONCLUSION: In this study, asthmatic patients who were very sensitive to methacholine were not affected by provocations with perfume. One may therefore question the value of provocations with methacholine in patients complaining of symptoms after contact with strong scents.

Sensory hyperreactivity--a possible mechanism underlying cough and asthma-like symptoms.

BACKGROUND: Investigations of patients referred for suspected asthma have revealed a little-known group with symptoms suggesting hyperreactive airways in whom provocation with methacholine does not lead to bronchial obstruction. The underlying mechanisms are not known, and no objective diagnostic method has been available. METHODS: Provocations by inhalation of capsaicin solutions in stepwise increasing concentrations were used. Ten patients with asthma-like symptoms after exposure to nonspecific irritating stimuli, but without IgE-mediated allergy or demonstrable bronchial obstruction, were compared to 10 patients with verified bronchial asthma and 28 healthy controls. RESULTS: The patients with asthma-like symptoms reacted with cough in a dose-dependent way. The number of coughs was significantly greater than in asthmatic patients and healthy controls. The latter two groups did not differ significantly. CONCLUSIONS: The capsaicin provocation test may be a valuable method for showing not only a greater cough sensitivity, but also asthma-like symptoms. The pathophysiology underlying the symptoms may be related to increased sensitivity of free, overactive nerve endings in the respiratory mucosa. Therefore, we suggest that this overreaction in the lower airways be called "sensory hyperreactivity".