Relationship between dyspnoea and related factors in patients with cancer: a cross-sectional study.

OBJECTIVES: Dyspnoea is a common and distressing symptom in patients with cancer. We aimed to analyse the association between dyspnoea and related factors and to estimate their causal relationship. METHODS: A cross-sectional study was conducted. Patients with cancer with dyspnoea and a mean Numerical Rating Scale (NRS) of ≥3 over 24 hours were enrolled at 10 institutions in Japan from December 2019 to February 2021. The outcomes included dyspnoea, cough and pain NRS over 24 hours, Eastern Cooperative Oncology Group Performance Status, Hospital Anxiety and Depression Scale, Somatosensory Amplification Scale, opioids for dyspnoea and respiratory failure. Path analyses were conducted to estimate the direct and indirect paths with reference to dyspnoea and related factors. RESULTS: A total of 209 patients were enrolled and 208 patients were included in the analysis. Cough worsened dyspnoea (ß=0.136), dyspnoea increased emotional distress (ß=1.104), emotional distress increased somatosensory amplification (ß=0.249) and somatosensory amplification worsened cough (ß=0.053) according to path analysis. CONCLUSION: There may be a vicious circle among dyspnoea and related factors: cough worsened dyspnoea, dyspnoea increased emotional distress, emotional distress increased somatosensory amplification and somatosensory amplification worsened cough. When treating dyspnoea in patients with cancer, managing these factors aimed at interrupting this vicious circle may be useful. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000038820).

Effect of intravenous and topical laryngeal lidocaine on sore throat after extubation: a prospective randomized controlled study.

OBJECTIVE: The present study aimed to compare the effect of topical laryngeal lidocaine with intravenous lidocaine before endotracheal intubation on the incidence and severity of postoperative sore throat, hoarseness, and cough. PATIENTS AND METHODS: This prospective randomized controlled study enrolled 144 patients undergoing laparoscopic cholecystectomy with endotracheal intubation. The patients were randomized to three groups and received 2% lidocaine by topical laryngeal spray (group T), intravenous 2% lidocaine (group I), and the equivalent volume of intravenous saline (group C) before intubation. The incidence and severity of sore throat, hoarseness, and cough reaction at 0.5, 1, 6, and 24 h after extubation were collected. RESULTS: The incidence of sore throat was significantly lower in group T than in groups I and C (6.4% vs. 37.2% and 86.7%, p < 0.001), respectively at 0.5 h after extubation, and it was significantly lower in group I than that in group C (37.2% vs. 86.7%, p < 0.001). Both the incidence of hoarseness and cough were significantly lower in group T than in group I and in group C (14.9% vs. 97.7% and 97.8%, p < 0.001, and 19.1% vs. 72.0% and 93.3%, p < 0.001), respectively. The severity of sore throat, hoarseness and cough in group T was significantly lower than that in group I and that in group C (p < 0.05), and it was significantly lower in group I than in group C (p < 0.05). CONCLUSIONS: Both topical laryngeal lidocaine and intravenous lidocaine before intubation have positive effects on preventing sore throat. Topical laryngeal route was superior to intravenous route. Chictr.org.cn ID: ChiCTR2100042442.

Characteristics of adults with potential refractory chronic cough identified using an algorithm designed for administrative claims databases: A descriptive study.

Objective As population-based studies describing the characteristics of patients with refractory chronic cough (RCC) are sparse, the objective of this descriptive study was to identify and describe such patients using an algorithm developed for administrative claims databases and requiring validation in future. Methods We identified adults with chronic cough (N = 782,121) from Optum Clinformatics™ Data Mart as individuals with a 'cough event' (primary cough event; based on ICD codes/relevant prescriptions) and ≥2 cough events in the 56-180 preceding days. We applied several exclusion criteria to identify potential RCC cases and stratified them into probable, possible, and unlikely RCC cohorts by the number of cough events during 1-year follow up (≥3, 1-2 or 0 events, respectively). Patient characteristics were described during the year before the primary cough event and follow up. Results 16.8% (n = 131,772) of patients with chronic cough were potential RCC cases: 25.8% probable, 35.9% possible and 38.3% unlikely. The majority were female (66.4-70.5%); median age was 53-60 years. The most common comorbidities and cough-associated complications at baseline were: allergic rhinitis (30.7-39.1%), hypertension (37.3-47.7%), gastro-oesophageal reflux disease (23.7-34.3%), asthma (18.1-27.3%), insomnia (6.3-8.3%) and stress incontinence (2.5-3.9%). Among probable RCC cases, use of several medications was higher during follow up versus baseline: 52.7% versus 49.0% (cough treatments), 73.3% versus 69.0% (respiratory drugs), 40.5% versus 34.2% (gastrointestinal drugs) and 58.8% versus 56.1% (psychotherapeutics). Conclusion Our algorithm requires validation but provides a starting point to identify patients with RCC in claims databases in future studies.

Factors Influencing Early Diagnosis and Poor Prognosis of Dysphagia After Senile Ischemic Stroke.

Dysphagia is often a long-term problem after ischemic stroke, which are often accompanied by complications and results in poor outcome. This study aimed to investigate the influencing factors associated with the prognosis of dysphagia after senile ischemic stroke and evaluate the diagnostic performance of crucial factors. A total of 192 elderly ischemic stroke patients (96 patients without dysphagia with average age of 69.81 ± 4.61 years and 96 patients with dysphagia with average of 70.00 ± 6.66 years) were enrolled in the retrospective study. The clinical factors of the patients were collected and recorded for chi-square analysis and logistic analysis. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of international normalized ratio (INR) and homocysteine (Hcy) in senile ischemic stroke patients. The age, cough reflex, history of stroke, mechanical ventilation, eating posture, insufficient elevation of the larynx, standard swallowing assessment (SSA) score, Hcy value, and INR were closely related to endpoint events of patients with dysphagia. The joint model (combined INR and Hcy value) can increase the area under the curve (AUC) value (0.948) with higher sensitivity and specificity for predicting patients with dysphagia occurred endpoint events. The influencing factors for older ischemic stroke patients with dysphagia include age, cough reflex, history of stroke, mechanical ventilation, eating posture, insufficient elevation of the larynx, SSA score, Hcy value, and INR. INR and Hcy were independent risk factors for prognosis and diagnostic markers for patients with dysphagia after senile ischemic stroke.

Achalasia-associated megaoesophagus presenting with dyspnoea and cough.

We present an unusual case of achalasia presenting with dyspnoea and persistent cough. These symptoms persisted for months, leading to the patient undergoing a chest X-ray by her general practitioner which showed right basal consolidation and a density extending along the right mediastinum. CT scan was done which revealed megaoesophagus with a diameter of 7 cm causing tracheal compression, as well as right basal consolidation, consistent with aspiration. Further history revealed 6-month history of progressive swallowing difficulty, retrosternal chest pain and shortness of breath which worsened when eating solid foods. After thorough workup, a diagnosis of idiopathic achalasia (type II) was made. She was treated with laparoscopic Heller cardiomyotomy and Dor fundoplication with significant improvement at follow-up. Dyspnoea and respiratory symptoms are unusual presenting symptoms, suggesting a need to consider achalasia in a wider range of presentations. Successful treatment of achalasia depends on timely diagnosis and intervention prior to oesophageal failure.

Cough Correlates of Functional Swallow Outcomes in Atypical Parkinsonism.

BACKGROUND: Swallow and cough impairments lead to aspiration and reduced clearance of aspirate material. Both behaviors are impaired in Parkinson's disease, but it is unknown whether a similar relationship of dysfunction exists in forms of atypical Parkinsonism (APD). Elucidating this association in APD may lead to early, comprehensive airway protection treatment. OBJECTIVES: We tested the hypotheses that swallow deficits in APD are associated with impaired cough and that airway protective dysfunction is associated with longer disease duration. METHODS: Swallowing difficulty was described by 11 participants with APD. Penetration-Aspiration Scale (PAS) and DIGEST scores for thin liquid trials were extracted from medical records of videofluoroscopic swallow study reports. Voluntary and capsaicin induced-reflex cough measures of flow, volume, and timing were analyzed. RESULTS: While most participants did not have post-swallow residue, ~80% received abnormal PAS scores and reported swallowing difficulty. Those with abnormal PAS scores had lower voluntary cough expired volume (P = 0.037; mean rank difference = 5.0); lower reflex inspiratory flow rate (P = 0.034; mean rank difference = 5.5); and longer reflex expiratory flow rise time (P = 0.034; mean rank difference = 5.5). Higher PAS scores and reduced reflex cough volume acceleration were significantly correlated (r = -0.63; P = 0.04) and longer disease duration predicted larger voluntary cough expired volume (R2 = 0.72) and longer flow rise times (R2 = 0.47). CONCLUSIONS: As swallow safety worsens, so might the ability to clear the airways with effective cough in in APD; particularly with longer disease duration. Assessing cough in conjunction with swallowing is important for informing airway protection treatment plans in APD.

Management of mixed urinary incontinence: IUGA committee opinion.

INTRODUCTION AND HYPOTHESIS: Mixed urinary incontinence (MUI) is defined by the International Urogynecology Association (IUGA) and International Continence Society as the complaint of involuntary leakage of urine associated with urgency and also with exertion, effort, sneezing or coughing. It therefore implies the coexistence of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). MUI is a heterogeneous diagnosis that requires an assessment of its individual components of SUI and UUI. Management requires an individualised approach to the symptom components. The aim of this review is to identify the assessment/investigations and management options for MUI. METHODS: A working subcommittee from the IUGA Research & Development (R&D) Committee was created and volunteers invited from the IUGA membership. A literature review was performed to provide guidance focused on the recommended assessment and management of MUI. The document was then evaluated by the entire IUGA R&D Committee and IUGA Board of Directors and revisions made. The final document represents the IUGA R&D Committee Opinion. RESULTS: The R&D Committee MUI opinion paper provides guidance on the assessment and management of women with MUI and summarises the evidence-based recommendations. CONCLUSIONS: Mixed urinary incontinence is a complex problem and successful management requires alleviation of both the stress and urge components. Care should be individualised based on patient preferences. Further research is needed to guide patients in setting goals and to determine which component of MUI to treat first. The evidence for many of the surgical/procedural treatment options for MUI are limited and needs to be explored in more detail.

Environmental risk factors for respiratory infection and wheeze in young children: A multicentre birth cohort study.

INTRODUCTION: Respiratory infections and wheeze have a considerable impact on the health of young children and consume significant healthcare resources. We aimed to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood. METHODS: Environmental risk factors including: daycare attendance; breastfeeding; siblings; damp within the home; environmental tobacco smoke (ETS); child's bedroom flooring; animal exposure; road traffic density around child's home; and solid fuel pollution within home were assessed in children recruited to the GO-CHILD multicentre prospective birth cohort study. Follow-up information on respiratory infections (bronchiolitis, pneumonia, otitis media and cold or flu), wheeze and cough symptoms, healthcare utilisation and medication prescription was collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data. RESULTS: Follow-up was obtained on 1344 children. Daycare was associated with increased odds of pneumonia (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.04-5.49), bronchiolitis (OR = 1.40, 1.02-1.90), otitis media (OR = 1.68, 1.32-2.14) and emergency department attendance for wheeze (RR = 1.81, 1.17-2.80). Breastfeeding beyond 6 months was associated with a reduced odds of bronchiolitis (OR = 0.55, 0.39-0.77) and otitis media (OR = 0.75, 0.59-0.99). Siblings at home was associated with an increased odds of bronchiolitis (OR = 1.65, 1.18-2.32) and risk of reliever inhaler prescription (RR = 1.37, 1.02-1.85). Visible damp was associated with an increased odds of wheeze (OR = 1.85, 1.11-3.19), and risk of reliever inhaler (RR = 1.73, 1.04-2.89) and inhaled corticosteroid prescription (RR = 2.61, 1.03-6.59). ETS exposure was associated with an increased odds of primary care attendance for cough or wheeze (OR = 1.52, 1.11-2.08). Dense traffic around the child's home was associated with an increased odds of bronchiolitis (OR = 1.32, 1.08-2.29). CONCLUSION: Environmental factors likely influence the wide variation in infection frequency and symptoms observed in early childhood. Larger population studies are necessary to further inform and guide public health policy to decrease the burden of respiratory infections and wheeze in young children.

Long-term outcome after surgical management of symptomatic non-union rib fractures.

INTRODUCTION: Traumatic chest wall injuries are common however the incidence of non-union rib fractures is unknown. Previous studies have suggested that surgical management of symptomatic non-union rib fractures could be beneficial in selected patients, although many experience persisting pain despite surgery. The aim of this study is to investigate the long-term outcome after surgical management of symptomatic non-union rib fractures. METHODS: This is a cross-sectional study including adults (≥18 years) managed surgically for symptomatic non-union rib fractures with plate fixation during the period 2010-2020 at Sahlgrenska University Hospital. Patients operated for acute chest wall injury or injury due to cardiopulmonary resuscitation were excluded. Patients answered standardized questionnaires concerning remaining symptoms and satisfaction with surgery, quality of life (QoL, EQ-5D-5 L) and disability (Disability Rating Index, DRI). Lung function, movement of chest wall and thoracic spine, and shoulder function (Boström index) were assessed. RESULTS: Sixteen patients, 12 men and four women, with mean age 61.6± 11.1 were included in the study. The mechanism of injury was trauma in 10 patients and cough-induced injuries in five patients. Lung disease was significantly more prevalent in cough-induced injuries compared to traumatic injuries, 5 vs 1 (p = 0.008). The mean follow-up time was 3.5 years. Ninety-four percent were satisfied with the surgery and reported that their symptoms had decreased, although 69 % had remaining symptoms, especially pain, from the chest wall. Quality of Life was decreased with EQ-5D-5 L index 0.819 (0.477-0.976) and EQ-VAS 69 (10-100). Disability Rating Index was 31.5 (1.3-76.7) with problems running, lifting heavy objects, and performing heavy work. Predicted lung function was decreased with Forced Vital Capacity (FVC) 86.2 ± 14.2 %, Forced Expiratory Volume in 1 second (FEV1) 79.1 ± 10.7 % and Peak Expiratory Flow (PEF) 89.7 ± 14.5 %. Patients with cough-induced injuries had full shoulder mobility. CONCLUSIONS: Chest wall surgery for symptomatic non-union rib fractures results in decreased symptoms and patient satisfaction in most cases despite remaining symptoms, reduced lung function, chest wall movement, and QoL and persistent disability.

Prolonged cough and dyspnea following a single episode of intense silica exposure.

Long term exposure to silica at worksites can cause silicosis. This typically has two radiographic forms, simple silicosis and complicated or conglomerate silicosis. Patients with acute silicosis have rapid progression of disease with fulminant respiratory failure over months rather than years. The patient described in this case report had a one-time 4 to 5-h exposure to silica and sand dust at work when his mask malfunctioned. He developed cough and shortness of breath. During his initial clinic visit he had significant cough. His chest examination was clear without crackles or wheezes. His pulmonary function tests were within normal limits. His chest x-ray was clear. Both symptoms, especially the cough, persisted over the next 6+ months even after treatment with oral corticosteroids and inhaled corticosteroids and long-acting beta agonists. Consequently, this patient developed severe cough following a one-time exposure to silica particulates. Laboratory studies have demonstrated that silica exposure can cause reactive oxygen species which potentially could have activated transient receptor potential vanilloid 1 channels in the afferent sensory nerves in his bronchial epithelium. This could cause sustained cough for more than 6 months. His symptoms improved but did not resolve with corticosteroid treatment. Therefore, this case demonstrates that acute silica exposure can cause sustained airway symptoms in healthy workers.

An 85-Year-Old Man with Fever, Dyspnea, and Dry Cough Diagnosed with Idiopathic Hypereosinophilic Syndrome, Successfully Treated with High-Dose Corticosteroids.

BACKGROUND Idiopathic hypereosinophilic syndrome (I-HES) is a rare disease diagnosed as absolute eosinophil count >1500 cells/µl and end-organ involvement attributable to tissue eosinophilia with no secondary cause of underlying eosinophilia. The mean age of presentation for I-HES is 44 years. The skin, lungs, and gastrointestinal (GI) system are most common sites of presenting manifestations, including fatigue, cough, dyspnea, myalgias, angioedema, rash, fever, nausea, and diarrhea. Although cardiac and neurologic symptoms are less common at presentation, they can be life-threatening. CASE REPORT We report the case of an 85-year-old man who presented with fever, malaise, and loss of appetite for 3 weeks, followed by dyspnea and dry cough for 2 weeks. His absolute eosinophil count was 9000 cells/µl, which was not responding to empirical antibiotic therapy, with worsening of symptoms, suggesting a non-infective origin. He was then extensively evaluated to establish underlying an etiology for specific treatment, which was negative for common causes like atypical infections, malignancy, and autoimmune disorders. He was then started on corticosteroid therapy to overcome an exaggerated immune response and reduce inflammation-related injury, to which he responded well. On follow-up, hypereosinophilia was fully cured, with reversal of end-organ involvement including myocarditis and pneumonitis. CONCLUSIONS This report shows that idiopathic HES can present with various clinical features and that accurate diagnosis, excluding known causes of eosinophilia, and early management are essential to prevent long-term organ damage. Our patient responded to prompt treatment with high-dose corticosteroids.

Different Endotracheal Intubations for Non-Small Cell Lung Cancer Surgery: A Retrospective-Case-Matched Study on Postoperative Complications and Quality of Life.

BACKGROUND: Lung isolation and separation is still controversial in thoracic surgery. Preferences of the surgeon can drive the decision to use single- vs. double-lumen endotracheal intubation. We aimed to compare complications and quality of life (QOL) after radical lung cancer resection with a single-lumen tube (ST) and a double-lumen tube (DT) for patients with non-small cell lung cancer (NSCLC). METHODS: A total of 309 patients who underwent radical lung cancer resection with video-assisted thoracoscopy-lobectomy were subsequently included in the study. Based on the type of endotracheal intubation tube used during surgery, we divided all the patients into a single-lumen tube group (ST-G) and double-lumen tube group (DT-G). Then, we applied propensity score matching (1:1) to balance the baseline characteristics between the two groups. The Analysis of Variance (ANOVA) of two-factor repeated measures data was performed to compare postoperative complications at three and six months after surgery and postsurgical QOL at baseline at one month, three months, six months, and twelve months. RESULTS: Within three months after surgery, patients in the ST-G presented less cough symptoms in Lung Cancer Symptom Scale (LCSS), lower cough symptom scores (CSS) (one month and three months, p < 0.05) and better performance of Leicester Cough Questionnaire (LCQ) scores in physical part (one month, three months and six months, p < 0.05) with better overall QOL (one month and three months, p < 0.05) than those in the DT-G. CONCLUSIONS: Patients with STs displayed less postoperative cough symptoms and higher overall QOL than those with DTs. Although DT is the gold standard for thoracic surgeries, we suggest that postoperative cough symptoms should be given sufficient attention by surgeons.

¿Se puede utilizar la determinación del pico flujo de tos para valorar la capacidad tusígena en enfermedades respiratorias obstructivas graves? / Can cough peak flow be used to assess cough capacity in severe obstructive respiratory diseases?

Introducción: La valoración de la capacidad tusígena se realiza con la medición del flujo espiratorio máximo durante la tos (peak-flow tos [PFT]). Sin embargo, esta valoración podría alterarse por enfermedades con obstrucción espiratoria de la vía aérea. El objetivo fue valorar la medición de la capacidad tusígena mediante PFT en pacientes con enfermedad pulmonar obstructiva crónica (EPOC), así como las correlaciones con la función pulmonar, muscular respiratoria y orofaríngea. Métodos: Se seleccionaron los pacientes con EPOC y con enfermedad neuromuscular, así como los sujetos sanos a los que se había realizado una medición de la fuerza de los músculos respiratorios de forma asistencial. De esta población, se analizaron los valores de la función respiratoria, así como la fuerza muscular orofaríngea. En un subgrupo de pacientes con EPOC se realizó el estudio de deglución por videofluoroscopia. Resultados: Se incluyeron 307 sujetos (59,3% EPOC, 38,4% enfermedades neuromusculares y 2,3% sanos). En el grupo EPOC, el PFT se encontraba disminuido de forma estadísticamente significativa comparado tanto con el grupo de los sanos como con los enfermos neuromusculares. El 70% de los EPOC tenían una disminución patológica del PFT. Solamente, existía una correlación directa entre el PFT con el grado de obstrucción bronquial y la fuerza de los músculos espiratorios. No se encontró alteración de la función de los músculos inspiratorios ni orofaríngeos. Conclusiones: La utilización del PFT en los pacientes con EPOC no refleja la capacidad tusígena ya que se ve influenciada por el grado de obstrucción bronquial. Por tanto, se deberían valorar nuevas pruebas diagnósticas para la medición de la capacidad tusígena, fundamentalmente, en los pacientes que coexistan enfermedades neuromusculares y patología obstructiva bronquial grave.(AU)

Introduction: Cough capacity is assessed by measuring cough peak flow (CPF). However, this assessment could be altered by obstructive airway diseases. The aim was to assess measurement of cough capacity by CPF in patients with chronic obstructive pulmonary disease (COPD), as well as correlations with pulmonary, respiratory muscle, and oropharyngeal function. Methods: Patients with COPD, and with neuromuscular disease, were selected as well as healthy subjects who had undergone respiratory muscle strength measurement in a healthcare setting. From this population, respiratory function values and lung and oropharyngeal muscle function were analysed. A subgroup of COPD patients underwent a videofluoroscopic swallow study. Results: Three hundred and seven subjects were included (59.3% COPD, 38.4% neuromuscular diseases, and 2.3% healthy). CPF was found to be statistically significantly decreased in the COPD group compared to both the healthy and neuromuscular disease groups. Of the COPD patients, 70% had a pathological decrease in CPF. There was only a direct correlation between CPF with the degree of bronchial obstruction and expiratory muscle strength. No alteration of inspiratory or oropharyngeal muscle function was found. Conclusions: The use of CPF in COPD patients does not reflect cough capacity as it is influenced by the degree of bronchial obstruction. Therefore, new diagnostic tests to measure cough capacity should be considered, especially in patients with coexisting neuromuscular diseases and severe bronchial obstructive disease.(AU)

Patient experiences with SARS-CoV-2: Associations between patient experience of disease and coping profiles.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2,) caused an influx of patients with acute disease characterized by a variety of symptoms termed COVID-19 disease, with some patients going on to develop post-acute COVID-19 syndrome. Individual factors like sex or coping styles are associated with a person's disease experience and quality of life. Individual differences in coping styles used to manage COVID-19 related stress correlate with physical and mental health outcomes. Our study sought to understand the relationship between COVID-19 symptoms, severity of acute disease, and coping profiles. METHODS: An online survey to assess symptoms, functional status, and recovery in a large group of patients was nationally distributed online. The survey asked about symptoms, course of illness, and included the Brief-COPE and the adapted Social Relationship Inventory. We used descriptive and cluster analyses to characterize patterns of survey responses. RESULTS: 976 patients were included in the analysis. The most common symptoms reported by the patients were fatigue (72%), cough (71%), body aches/joint pain (66%), headache (62%), and fever/chills (62%). 284 participants reported PACS. We described three different coping profiles: outward, inward, and dynamic copers. DISCUSSION: Fatigue, cough, and body aches/joint pains were the most frequently reported symptoms. PACS patients were sicker, more likely to have been hospitalized. Of the three coping profiles, outward copers were more likely to be admitted to the hospital and had the healthiest coping strategies. Dynamic copers activated several coping strategies both positive and negative; they were also younger and more likely to report PACS. CONCLUSION: Cough, fatigue, and body aches/joint pain are common and most important to patients with acute COVID-19, while shortness of breath defined the experience for patients with PACS. Of the three coping profiles, dynamic copers were more likely to report PACS. Additional investigations into coping profiles in general, and the experience of COVID-19 and PACS is needed.

Chronic Cough as a Genetic Neurological Disorder? Insights from Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS).

Chronic cough is common, and in many cases unexplained or refractory to otherwise effective treatment of associated medical conditions. Cough hypersensitivity has developed as a paradigm that helps to explain clinical and research observations that frequently point towards chronic cough as a neuropathic disorder. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described neurological condition whose clinical features include gait ataxia, unsteadiness, peripheral neuropathy, and autonomic dysfunction. Chronic cough is also a common feature of the syndrome, with features of hypersensitivity, often preceding core neurological symptoms by up to 30 years or more. The genetic basis in a majority of cases of CANVAS appears to be biallelic variable repeat intron expansion sequences within RFC1, a gene normally involved in the regulation of DNA replication and repair. The same polymorphism has now been identified at an increased frequency in patients with unexplained or refractory chronic cough in the absence of defining clinical features of CANVAS. This review expands on these points, aiming to increase the awareness of CANVAS amongst clinicians and researchers working with chronic cough. We discuss the implications of a link between RFC1 disease and cough. Improved understanding of CANVAS may lead to an enhanced grasp of the pathophysiology of chronic cough, and new approaches to antitussive treatments.

Characterization of changes in the intestinal microbiome following combination therapy with zinc preparation and conventional treatment for children with rotavirus enteritis.

Background: Rotavirus (RV) is one of the most common pathogens causing diarrhea in infants and young children worldwide. Routinely, antiviral therapy, intestinal mucosa protection, and fluid supplementation are used in clinic, however this is not efficacious in some severe cases. Zinc supplementation has previously been shown to improve resolution of symptoms from infectious diarrhea. Methods: In this study differences in response rate, duration of hyperthermia, vomiting, and diarrhea, and the persistence time of cough and lung rales in groups were compared. 16SrDNA gene sequencing technology was used to analyze and compare changes in the intestinal microflora of children with RV enteritis who received the conventional treatment with or without the zinc preparation. In addition, the correlations between the differential bacterial species and the related inflammatory factors were determined. Results: Conventional therapy combined with the zinc preparation significantly shortened the duration of hyperthermia, vomiting, and diarrhea compared with the conventional treatment alone. In addition, the time to symptom relief showed that the absorption time of cough and lung rales was significantly shorter in the combination treatment group than that in the conventional treatment group in the children with pneumonia. Further, compared with the conventional treatment, the combined treatment significantly increased the diversity and abundances of florae as compared with the conventional treatment. This combination therapy containing zinc preparation markedly increased the abundances of Faecalibacterium, Bacteroidales, Ruminoccoccoccus, and Lachnospiraceae at the genus level. The LEfSe analysis suggested that Clostridiumbolteae were most significantly altered after the combination therapy. In addition, a correlation analysis revealed significantly negative correlations between the inflammatory factors especially IL-6, TNF-a, CRP and some intestinal florae such as Bacteroides, Faecalibacterium, Blautia, Parabacteroides, Subdoligranulum, and Flavonifractor. Conclusion: Compared with the conventional therapy alone, the combined therapy with the zinc preparation significantly improves symptoms caused by RV. The combination therapy containing the zinc preparation significantly increases the diversity and abundances of some beneficial groups of bacteria. Further, The presence of these groups was further negatively correlated with relevant inflammatory factors. More importantly, this combination therapy containing the zinc preparation provides a reference for the clinical management of children with RV enteritis.

[Investigation of diagnostic methods and criteria for gastroesophageal reflux-related cough].

Gastroesophageal reflux-related cough is a multidisciplinary disease that cannot be diagnosed solely based on typical reflux-related symptoms. Its current diagnostic methods and criteria are largely derived from those used for gastroesophageal reflux disease, with slight differences. Esophageal reflux monitoring can provide objective evidence for the diagnosis of gastroesophageal reflux-related cough and is therefore the first-choice of laboratory tests recommended by the guidelines for cough management. Acid exposure time and syndrome association probability have been accepted as the diagnostic criteria, while esophageal motility assessment also has some certain auxiliary diagnostic value. Based on the existing evidence, we have reviewed how to improve the diagnostic methods and criteria for gastroesophageal reflux-related cough, as well as the issues that need to be addressed in the future.

Predictors of treatment response to pregabalin in unexplained or refractory chronic cough.

BACKGROUND: Patients with chronic cough (>8 weeks) often remain symptomatic after appropriate investigations and therapeutic trials. Prior research has shown a benefit in certain individuals from pregabalin, but clinical improvement is quite unpredictable and variable. OBJECTIVE: The main objective of this study was to identify the demographic and clinical characteristics associated with a higher likelihood of cough improvement with a trial of pregabalin therapy. METHODS: 50 consecutive patients with chronic cough were enrolled in this prospective cohort study. Subjects were prescribed pregabalin 75 mg oral qhs for 4 weeks followed by 75 mg oral bid. Leicester Cough Questionnaire (LCQ) was completed at treatment initiation and after 3 months of therapy. A comparison was performed between treatment responders (LCQ total score improvement ≥1.3) and non-responders. RESULTS: 56% of patients reported a LCQ total score improvement ≥1.3 (minimal clinically important difference). Responders to pregabalin therapy were more likely to have refractory (with underlying pulmonary disease) versus unexplained chronic cough (p = 0.01). Patients with significant improvement were also on average more symptomatic at baseline (mean LCQ total score 10.2 versus 13.0, p < 0.01). No significant relationship was identified with age, gender, body mass index, history of anxiety and/or depression, cigarette smoking history, or cough duration (p > 0.05). The unexplained chronic cough group had a strong female predominance (85.7% versus 40.9% for refractory cough, p < 0.01). CONCLUSION: This is the first study that has investigated clinical predictors of treatment response to pregabalin in chronic cough patients. Further research is needed to develop therapies for subjects who do not improve with currently available neuromodulating medications.

Phenotypic characteristics, healthcare use, and treatment in children with night cough compared with children with wheeze.

OBJECTIVES: Population-based studies of children with dry night cough alone compared with those who also wheeze are few and inconclusive. We compared how children with dry night cough differ from those who wheeze. METHODS: LuftiBus in the school is a population-based study of schoolchildren conducted between 2013 and 2016 in Zurich, Switzerland. We divided children into four mutually exclusive groups based on reported dry night cough (henceforth referred as "cough") and wheeze and compared parent-reported symptoms, comorbidities, exposures, FeNO, spirometry, and healthcare use and treatment. RESULTS: Among 3457 schoolchildren aged 6-17 years, 294 (9%) reported "cough," 181 (5%) reported "wheeze," 100 (3%) reported "wheeze and cough," and 2882 (83%) were "asymptomatic." Adjusting for confounders in a multinomial regression, children with "cough" reported more frequent colds, rhinitis, and snoring than "asymptomatic" children; children with "wheeze" or "wheeze and cough" more often reported hay fever, eczema, and parental histories of asthma. FeNO and spirometry were similar among "asymptomatic" and children with "cough," while children with "wheeze" or "wheeze and cough" had higher FeNO and evidence of bronchial obstruction. Children with "cough" used healthcare less often than those with "wheeze," and they attended mainly primary care. Twenty-two children (7% of those with "cough") reported a physician diagnosis of asthma and used inhalers. These had similar characteristics as children with wheeze. CONCLUSION: Our representative population-based study confirms that children with dry night cough without wheeze clearly differed from those with wheeze. This suggests asthma is unlikely, and they should be investigated for alternative aetiologies, particularly upper airway disease.

Prevalence, clinical presentation and factors associated with chronic lung disease among children and adolescents living with HIV in Kenya.

INTRODUCTION: Children and adolescents with HIV (CAHIV) may experience recurrent and severe respiratory disease and are at risk of residual lung sequelae, and long-term morbidity from chronically damaged lungs. With improved survival due to increased access to effective antiretroviral therapy there is an increasing population of CAHIV who require optimal life-long care. Chronic lung disease in CAHIV is an under-recognised problem in African settings. We sought to determine the prevalence, clinical presentation and factors associated with chronic lung disease (CLD) among CAHIV in Kenya. METHODS: CAHIV aged ≤19 years in care at a public hospital in Nairobi were enrolled into a longitudinal cohort study. Sociodemographic and clinical information were obtained through interview, medical record review, physical examination and six-minute walk test. CD4 counts and viral load were determined. Enrolment data was analysed to determine baseline sociodemographic and clinical characteristics. Prevalence of CLD defined as presence of ≥2 respiratory symptoms or signs at enrolment was computed. Logistic regression analysis was performed to evaluate for association between various factors and presence or absence of CLD. RESULTS: We enrolled 320 CAHIV of median age 13 (IQR 10-16) years, 80 (25%) were <10 years, 46% were female, 31% lived in a one-room house and 51% used polluting cooking fuel. Antiretroviral therapy (ART) was initiated after age five years in 56%, 43% had prior pneumonia or tuberculosis, 11% had low CD4 count and 79% were virologically suppressed. Common respiratory symptoms and signs were exertional breathlessness (40%), chronic cough (23%), chest problems in the preceding year (24%), tachypnoea (52%), finger clubbing (6%), exercise limitation (59%) and oxygen desaturation during exercise (7%). CLD was present in 82 (26%) participants, and adding the six-minute walk distance <70% of predicted (exercise limitation) identified an additional 28 (9%) CAHIV with CLD. CLD was more common among older teenagers (odds ratio (OR) 1.95), those who had prior TB or pneumonia (OR 2.04), delayed initiation of ART (OR 2.60), cotrimoxazole prophylaxis (OR 3.35) or TB preventive therapy (OR 2.81). CLD was associated with viraemia (OR 2.7), lower quality of life (OR 12.7), small houses (OR 2.05), caregiver having fewer years of education (OR 2.46), outdoor pollution exposure (OR 3.31) and lower use of polluting cooking fuel indoors (OR 0.26). Adjusted analysis revealed CLD to be associated with prior tuberculosis or pneumonia (adjusted OR (aOR) [95%CI] 2.15 [1.18-3.91]), small house (aOR 1.95 [1.02-3.73]), lower use of polluting cooking fuel (aOR 0.35 [0.13-0.94]) and negative impact on health-related quality of life (aOR 6.91 [3.66-13.03]). CONCLUSIONS: CLD is highly prevalent across the age spectrum of CAHIV, and most are symptomatic with cough or exertional breathlessness. CLD is associated with prior tuberculosis or pneumonia, socio-environmental factors, and lower quality of life. Structured interventions are needed to provide optimal care specific to their needs.