Eva Millqvist

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area. Cough hypersensitivity syndrome was clearly endorsed by opinion leaders as a valid and useful concept http://ow.ly/zxk83

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.

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.

A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response

Reports from individual centres suggest a preponderance of females with chronic cough. Females also have heightened cough reflex sensitivity. Here we have reviewed the age and sex of unselected referrals to 11 cough clinics. To investigate the cause of any observed sex dimorphism, functional magnetic resonance imaging of putative cough centres was analysed in normal volunteers. The demographic profile of consecutive patients presenting with chronic cough was evaluated. Cough challenge with capsaicin was undertaken in normal volunteers to construct a concentration-response curve. Subsequent functional magnetic resonance imaging during repeated inhalation of sub-tussive concentrations of capsaicin observed areas of activation within the brain and differences in the sexes identified. Of the 10 032 patients presenting with chronic cough, two-thirds (6591) were female (mean age 55 years). The patient profile was largely uniform across centres. The most common age for presentation was 60–69 years. The maximum tolerable dose of inhaled capsaicin was lower in females; however, a significantly greater activation of the somatosensory cortex was observed. Patients presenting with chronic cough from diverse racial and geographic backgrounds have a strikingly homogeneous demographic profile, suggesting a distinct clinical entity. The preponderance of females may be explained by sex-related differences in the central processing of cough sensation. Chronic cough in specialist clinics have homogenous demographic profiles, suggesting single clinical entity http://ow.ly/zrNAa

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.

The idiopathic environmental intolerance symptom inventory : development, evaluation, and application

Objective: To develop, evaluate, and apply a questionnaire-based instrument for investigation of specific symptoms in idiopathic environmental intolerance (IEI), called the Idiopathic Environmental Intolerance Symptom Inventory (IEISI). Methods: Participants with IEI to chemicals responded to 82 candidate symptoms and to three subscales of the Quick Environmental Exposure and Sensitivity Inventory (QEESI) at a test (n = 207) and retest (n = 193) occasion. Results: The 27 most commonly reported symptoms were selected and grouped into five symptom categories. Internal consistency, test–retest reliability, and concurrent validity were found to be satisfying. Cluster analysis identified two subgroups of IEI to chemicals. Conclusions: The results provide support for the IEISI being a reliable, valid, and fast tool for the study of specific symptom prevalence in IEI and encourage further study of subgroups.

The airway sensory hyperreactivity syndrome

After exclusion of diverse pulmonary illnesses, the remaining explanations for chronic cough include medication with angiotensin-converting enzyme (ACE) inhibitor, gastroesophageal reflux disease (GERD), and post-nasal drip. Different clinics report shifting frequencies for both the causes of chronic cough and the success of treatment. However, after all evaluations, differential diagnosis still leaves a group of patients with unexplained cough. This unexplained cough is also known as chronic idiopathic cough (CIC), though there are widely varying opinions as to its existence. Among patients previously diagnosed with CIC, a subgroup has been identified with both upper and lower airway symptoms, including cough induced by odours and chemicals, and with increased cough sensitivity to inhaled capsaicin, which is known to stimulate the airway sensory nerves. A suggested explanation for this condition is a hyperreactivity of the sensory nerves of the entire airways, and hence the condition is known as sensory hyperreactivity (SHR). SHR affects more than 6% of the adult population in Sweden. It is a longstanding condition, and is clearly associated with significant social and psychological impacts.

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 after inducing congestion.

Mechanisms of increased airway sensitivity to occupational chemicals and odors.

Purpose of reviewAirway symptoms induced by chemicals and odors are common problems that are also reported after contact with substances normally regarded as nontoxic. This article reviews current findings and opinions regarding mechanisms of increased airway sensitivity to occupational chemicals and odors. Recent findingsIndividuals exposed to organic solvents during work had more nasal irritation and lower threshold to pyridine odor compared with a nonexposed control group. Six percentage of a general population in Sweden had pronounced airway chemical sensitivity and augmented capsaicin cough sensitivity, known to reflect the sensory nerve reactivity of the airways. The cough sensitivity was associated with changed levels of nerve growth factor in nasal lavage and such patients had longstanding symptoms influencing their working capacity. Positron emission tomography activation studies with several different odorants showed in patients with odor-associated symptoms an odorant-related increase in activation of the anterior cingulate cortex and cuneus–precuneus in comparison with a control group. SummaryIn subgroups of individuals with airway symptoms induced by chemicals and odors, there seems to be a sustainable physiological mechanism behind the reactions. An increased vulnerability to stress cannot be neglected as a confounding factor in some sensitive individuals.