ERS guidelines on the diagnosis and treatment of chronic cough in adults and children.

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.

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.

Development and validation of the self-administered Falun health instrument (SAFHI) using data from health promoted workplaces in Sweden.

AIM: The aim of this study was to develop and to validate the self-administered Falun health instrument. An additional aim was to test its applicability in measuring people's lifestyles linked to health. METHODS: In 2002, an instrument was constructed containing questions regarding the hazardous use of alcohol, tobacco, unhealthy diets and insufficient physical activity. A pilot study using the instrument was assessed between 2002 and 2006. In Sweden, it was further expanded and tested during the years 2004-2014 among a total of 1295 people. RESULTS: Face validity was evaluated among colleagues and experts for clarity and completeness resulting in minor adjustments of some questions. With the test-retest method, the self-administered Falun health questionnaire showed a positive and high reproducibility and high compliance. Cronbach's alpha showed a high level of consistency (average 0.86). Factor analysis demonstrated the choice of questions correlated highly to the measured lifestyle. CONCLUSIONS: This study showed that the self-administered Falun health questionnaire is a valid and reliable instrument, useful for detecting individuals at risk of developing diseases that are related to individual choice of lifestyle.

Coping and social support in asthma and allergy: the Västerbotten Environmental Health Study.

OBJECTIVES: Asthma and allergy are stressful conditions that require coping strategies and social support to reduce stress and enhance health-promoting behavior. However, research is limited regarding coping and social support in asthma and allergy. The aim was to better understand the use of different coping strategies and perceived social support in low and high severity (exacerbation frequency) of asthma and allergy. METHODS: Population-based data were used to provide ratings of coping strategies (Study I) and social support (Study II) from 124 and 94 participants, respectively, with asthma and/or allergy, categorized as low or high in severity. Problem- and emotion-focused coping strategies were assessed as well as emotional, instrumental and informative social support from seven sources. RESULTS: Study I showed that avoiding certain environments (problem-based coping) and trying to accept one's situation (emotion-based) were the most commonly used coping strategies. These behaviors did not differ due to severity. Study II showed that more emotional than instrumental and informative support was perceived. The highest rated support sources were the partner, family members and the healthcare system. More social support was reported in low asthma/allergy severity compared to high asthma/allergy severity. CONCLUSION: The most commonly used coping strategies in the population of persons with these four types of asthma and allergy are avoiding certain environments and trying to accept one's situation. More emotional support than instrumental and informative is perceived to be received, and most of the support is received from one's partner and other family members and least from authorities and patient associations/support groups.

Heredity of nasal polyps.

BACKGROUND: Nasal polyps is a common disease but little is known about its` pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps. METHODOLOGY: Patients with nasal polyps who attended the clinic were recruited to the study and were asked whether they had any close adult relatives (siblings, parents or children). We intended to recruit two relatives per patient, one of each gender, for nasal endoscopy. The prevalence of nasal polyps in these relatives was compared with the prevalence of nasal polyps in a general population. RESULTS: During a 4-year period, 368 patients and 410 relatives were recruited to the study. Although we were unable to recruit two close relatives for every patient, we were able to calculate nasal polyp prevalence within families as being 19.2%. Compared with the prevalence of nasal polyps among individuals in a general Swedish population from the same geographical area, the relative risk for polyps among relatives was almost five times higher. CONCLUSION: This study strongly indicates that heredity is a factor of importance for development of nasal polyps.

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.

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.

Normative data for the chemical sensitivity scale for sensory hyperreactivity: the Västerbotten environmental health study.

OBJECTIVES: The chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) is used to quantify affective reactions to and behavioral disruptions by odorous/pungent substances in the environment and has documented good metric properties. However, normative data have not been available. The main objective of the present study was therefore to establish normative data for reference by means of a large-scale population-based study. MATERIALS AND METHODS: From a random sample of 8,520 reachable inhabitants in the county of Västerbotten in Sweden, aged 18-79 years, stratified for age and gender, 3,406 individuals agreed to participate. RESULTS: The results show fairly high internal consistency (Cronbach's α = 0.78-0.83) of the CSS-SHR and that it generates scores with approximately normal distributions (skewness: 0.045-0.454; kurtosis: -0.314 to 0.230), irrespective of age group and gender. Mean scores, standard deviations, confidence intervals, and proportions of individuals who met the diagnostic cutoff score for the CSS-SHR were obtained for reference of normality. CONCLUSIONS: CSS-SHR can be recommended for quantification of affective reactions to and behavioral disruptions by odorous/pungent environmental substances, and with the advantage of comparing scores with normality.

[New ICD-10 code for refractory and unexplained chronic cough]. / Refraktär och oförklarlig kronisk hosta har fått en egen ICD-10-kod.

Chronic cough is a common disease, causing distress and impaired quality of life [2]. In the Western world, cough is the most common reason for seeking medical attention [3]. The prevalence of chronic cough is about 10 percent in the adult population but of course hides several subgroups, and the numbers vary greatly [1]. A subgroup of chronic cough is Refractory Chronic Cough (RCC) or Unexplained Chronic Cough (UCC) where no ¼certain« underlying medical explanation can be found. Until January 2023, the diagnosis of chronic, refractory cough is not included in the ICD-10 codes applied in Sweden. In September 2022, an announcement came from the Swedish National Board of Health and Welfare that from January 1 2023 ¼Chronic Cough« including refractory and unexplained chronic cough will get its own code under R05 also in Sweden: R05.7.

Consensus goals and standards for specialist cough clinics: the NEUROCOUGH international Delphi study.

Background: Current guidelines on the management of chronic cough do not provide recommendations for the operation of specialist cough clinics. The objective of the present study was to develop expert consensus on goals and standard procedures for specialist cough clinics. Methods: We undertook a modified Delphi process, whereby initial statements proposed by experts were categorised and presented back to panellists over two ranking rounds using an 11-point Likert scale to identify consensus. Results: An international panel of 57 experts from 19 countries participated, with consensus reached on 15 out of 16 statements, covering the aims, roles and standard procedures of specialist cough clinics. Panellists agreed that specialist cough clinics offer optimal care for patients with chronic cough. They also agreed that history taking should enquire as to cough triggers, cough severity rating scales should be routinely used, and a minimum of chest radiography, spirometry and measurements of type 2 inflammatory markers should be undertaken in newly referred patients. The importance of specialist cough clinics in promoting clinical research and cough specialty training was acknowledged. Variability in healthcare resources and clinical needs between geographical regions was noted. Conclusions: The Delphi exercise provides a platform and guidance for both established cough clinics and those in planning stages.

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.

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.

The influence of personality traits and beliefs about medicines on adherence to asthma treatment.

AIM: To explore the influence of personality traits and beliefs about medicines on adherence to treatment with asthma medication. METHODS: Respondents were 35 asthmatic adults prescribed controller medication. They answered questionnaires about medication adherence, personality traits, and beliefs about medicines. RESULTS: In gender comparisons, the personality traits "Neuroticism" in men and "adherence to medication" were associated with lower adherent behaviour. Associations between personality traits and beliefs in the necessity of medication for controlling the illness were identified. Beliefs about the necessity of medication were positively associated with adherent behaviour in women. In the total sample, a positive "necessity-concern" differential predicted adherent behaviour. CONCLUSION: The results imply that personality and beliefs about medicines may influence how well adults with asthma adhere to treatment with asthma medication.

Objective cough frequency monitoring in real-world practice.

There are possibilities and obstacles to the use of objective cough monitoring in real-world practice. Advances in technology will overcome the difficulties and continuous real-time cough monitoring will then provide a valuable tool in cough management. https://bit.ly/3lu5cfk.

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.

Mechanisms of increased airway sensitivity to occupational chemicals and odors.

PURPOSE OF REVIEW: Airway 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 FINDINGS: Individuals 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. SUMMARY: In 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.