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.

Variations in respiratory and functional symptoms at four months after hospitalisation due to COVID-19: a cross-sectional study.

BACKGROUND: Much remains unknown about complex respiratory symptoms after COVID-19. Here we aimed to describe and analyse patients' various respiratory symptoms 4 months after discharge from hospitalisation for COVID-19, focusing on sex, previous pulmonary disease, and prolonged mechanical ventilation. METHODS: This cross-sectional study involved five hospitals and included 52 patients with self-assessed respiratory dysfunction at 4 months after discharge from hospitalisation for severe COVID-19. Their average age was 63 years, 38% were women, 15 had a previous diagnosed pulmonary disease, and 29 were current or previous smokers. Additionally, 31 had required intensive care-among whom 21 were intubated and 11 needed mechanical ventilation for ≥20 days. Respiratory function was tested concerning lung volumes, expiratory flow, muscle strength, physical capacity (including concurrent oxygen saturation), thoracic expansion, and respiratory movements. RESULTS: Among 52 patients, 47 (90%) had one or several objectively measured respiratory function abnormalities. Decreased thoracic expansion was observed in 32 patients (62%), abnormal respiratory movements in 30 (58%), decreased vital capacity in 21 (40%), low physical function in 13 (26%), and desaturation during the test in 9 (17%). Respiratory inspiratory muscle strength was more commonly diminished than expiratory strength (27% vs. 8%). We did not observe differences between men and women, or between patients with versus without diagnosed pulmonary disease, except that those with pulmonary disease had significantly lower physical capacity assessed with 6MWD (70% vs. 88% predicted, p = 0.013). Compared to those who did not, patients who required ≥20 days of mechanical ventilation performed similarly on most tests, except that all thoracic breathing movements were significantly smaller (p < 0.05). The numbers and combinations of abnormal findings varied widely, without clear patterns. CONCLUSION: Patients with remaining respiratory symptoms 4 months after discharge from hospitalization due to COVID-19 may suffer from various abnormal breathing functions, and dysfunctional breathing that is not detected using traditional measurements. These patients may benefit from multidimensional measuring of breathing movement, thoracic expansion, and respiratory muscle strength, along with traditional measurements, to assess their symptoms and enable prescription of optimal treatment interventions and rehabilitation. TRIAL REGISTRATION: FoU i Sverige (Research & Development in Sweden, Registration number: 274476, registered 2020-05-28).

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.

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.

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.

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.