Cough Hypersensitivity Syndrome Research Articles

Postoperative exacerbated cough hypersensitivity syndrome induces dramatic respiratory alkalosis, lactatemia, and electrolyte imbalance

BackgroundThe perioperative management of patients with chronic cough or cough hypersensitivity syndrome and its sometimes severe effects is currently under-researched and under-reported.Case presentationA 46-year-old female patient with a history of chronic cough and Cough Hypersensitivity Syndrome. After laparoscopic hiatoplasty and anterior fundoplication under general anesthesia, experienced a pronounced exacerbation of coughing symptoms. Despite prompt and extensive treatment involving antitussives, inhalants, anxiolytics, and sedatives, the symptoms remained uncontrollable. Within a few hours, the patient developed a respiratory alkalosis with severe and life-threatening electrolyte shift (pH 7.705, pCO2 1.72 kPa, K+ 2.1 mmol/l). Lactatemia lasted for more than 12 hours with values up to 6.6 mmol/l. Acute bleeding, pneumothorax, and an acute cardiac event were ruled out. Deep analgosedation and inhalation of high-percentage local anesthetics were necessary to manage the clinical symptoms.ConclusionsThis case highlights the challenging nature of chronic cough and hypersensitivity syndrome perioperatively. A tailored anesthesiologic approach, exclusion of other provoking medical problems, and knowledge of possible management and treatment options are key.

Eosinophilic Cationic Protein and Immunoglobulin E: Unraveling Biomarkers in Chronic Pediatric Cough

Although the cough reflex is one of the essential protective mechanisms in the respiratory tract, it is considered a considerable health problem in adults and children when it becomes chronic and hypersensitive. However, the need for biomarkers for chronic cough in children and adults is critical. The problem with cough is also a severe symptom in hypersensitivity children. Respiratory infections are a considerable challenge for pediatricians, especially in allergic children. The term cough hypersensitivity syndrome, although introduced in adults, was questioned for children. Eosinophil cationic protein (ECP) is a promising marker for chronic cough but still needs to be validated and proved in clinical settings. In this review article, we aimed to discuss the possible role of ECP in connection to IgE for chronic cough in children.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype.

Chronic cough is a frequent disorder that is defined by cough of more than 8 weeks duration. Despite extensive investigation, some patients exhibit no aetiology and others do not respond to specific treatments directed against apparent causes of cough. Such patients are identified as having unexplained or refractory chronic cough. Recently, a high proportion of patients with chronic cough in the context of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) was highlighted. CANVAS is a rare neurological disorder with a biallelic variation in the replication factor C subunit 1 (RFC1) gene corresponding mostly to an intronic AAGGG repeat expansion. Chronic cough in patients with CANVAS shares similar characteristics with cough hypersensitivity syndrome. The high prevalence of chronic cough in CANVAS gives the opportunity to better understand the neurogenic mechanism of chronic cough. In this review, we will describe the characteristics and mechanisms of CANVAS. We will also address the potential mechanisms responsible for chronic cough in CANVAS. Finally, we will address chronic cough management in the context of CANVAS.

Chronic cough and refractory chronic cough: An important distinction

Cough is the most common concern for which patients in the United States seek medical attention. Cough is typically classified according to its duration: acute cough (<3 weeks), subacute cough (3‐8 weeks), and chronic cough (>8 weeks). The vast majority of cases of acute cough in patients are due to an acute viral upper respiratory tract infection (common cold) and are self limited. Subacute cough is often due to a prolonged postviral cough. Once a cough meets the definition of chronic, it becomes likely that the cough is due to one or more treatable underlying etiologies: upper airway cough syndrome (formerly, postnasal drip syndrome), asthma and non-asthmatic eosinophilic bronchitis, and gastroesophageal reflux disease. Refractory chronic cough (RCC) refers to chronic cough that persists despite adequate therapeutic trials aimed at the known causes of chronic cough. The term cough hypersensitivity syndrome has recently been introduced to stress the concept that RCC is a distinct disease entity due to vagal hyperactivity causing hypersensitivity of the cough reflex. No medications have ever been approved for chronic cough or RCC in the United States and most of the world. Thus, physicians are limited to the use of off-label medications for their patients with this chronic and often debilitating condition. However, recent insights into the mechanisms of cough have resulted in multiple molecules currently being evaluated as potential antitussives. Among these, furthest along in the drug development pipeline are the P2X3-antagonists, of which, gefapixant has completed phase III trials, and camlipixant is currently in phase III studies.

A randomized, double-blinded, placebo-controlled clinical trial of duloxetine hydrochloride enteric-coated tablets in the treatment of refractory chronic cough

IntroductionRefractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and lowering the patient's quality of life. Cough hypersensitivity syndrome (CHS) is proposed as a potential cause, and reducing sensory nerve hyperresponsiveness is suggested as an effective treatment. However, current drugs have low efficacy and benefit rates and numerous side effects. This trail proposes using duloxetine, a selective 5-HT and norepinephrine reuptake inhibitor, as a potential treatment for refractory cough, which has shown promise in treating pain and depression. Duloxetine may inhibit pain conduction and oxidative stress in peripheral nerves by inhibiting the activity of TRPV1 channels, which play an important role in the peripheral afferent pathway of refractory cough. Meanwhile, the antidepressant effects of duloxetine may also play a role in the treatment of refractory cough.Methods and analysisThis is a single-center, prospective, randomized, double-blind, and controlled trial. A total of 98 individuals will be randomized in a 1:1 ratio to duloxetine group and placebo control group (starting with 20 mg QD, increasing 20 mg daily until 20 mg TID). After a screening period, the second stage runs from baseline to the 42nd (last) day of treatment, with follow-up visits on the 3rd, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days. The main end-stage observation indicators include objective cough frequency, cough visual analog scale (VAS), cough symptom score, Leicester Cough Questionnaire (LCQ), and cough evaluation test (CET); the secondary end-stage observation indicators include capsaicin cough sensitivity, Patient Health Questionnaire-9 (PHQ-9), Major Depression Inventory (MDI), the Generalized Anxiety Disorder-7 scale (GAD-7), Life Events Scale (LES-32), induced sputum supernatant. The safety measures will be AEs/SAEs, vital signs, liver and kidney function, fecal occult blood test.DiscussionThis study is the first randomized, double-blind, and controlled clinical trial investigating the use of duloxetine in the treatment of refractory coughs. The study aims to provide a high-quality basis for evaluating the efficacy and safety of duloxetine for this condition.Trial registrationOur study was registered in the Chinese Clinical Trials Register (www.chictr.org.cn/) (ChiCTR2000037429) in 28/08/2020.

Cough Hypersensitivity Syndrome: Why Its Use Is Inappropriate in Children.

In children and adults, chronic cough is a common symptom presenting to health professionals worldwide. It is internationally accepted that children with chronic cough should be managed with pediatric specific management guidelines. The newly proposed clinical entity of 'cough hypersensitivity syndrome' has gained significant attention in adult literature. Given the significant differences between childhood and adult chronic cough, including in respiratory physiology and anatomy, and cough sensitivity, we address the suitability of the use of cough hypersensitivity syndrome in children. We explore these differences between childhood and adult chronic cough, explain what cough hypersensitivity is and highlight why the term cough hypersensitivity syndrome should not be used in children.

Epidemiology of unexplained chronic cough in adults: a population-based study.

Unexplained chronic cough accounts for a significant proportion of chronic cough cases in adults, and its persistent phenotype shows female preponderance that is demographically similar to individuals with cough hypersensitivity https://bit.ly/3EwjWVo.

Repeat Expansions of RFC1 in Refractory Chronic Cough: A Missing Piece of the Puzzle?

Over the last decade, the concept of cough hypersensitivity syndrome (CHS) has emerged in adults.1 CHS is defined as a clinical syndrome characterized by troublesome coughing, often triggered by low levels of thermal, mechanical, or chemical exposure. A neurologic dysfunction is now appreciated as the main mechanism of chronic cough and also of refractory chronic cough (RCC). Patients with RCC experience not only a reduction in quality of life but also a lack of explanation regarding the origin of their cough.

Cough Hypersensitivity Syndrome Following Whooping Cough Showing Persistent Hypercytokinemia with Autoimmune Feature in Relation to Genetic Hypohaptoglobinemia: a Case Report

Cough Hypersensitivity Syndrome Following Whooping Cough Showing Persistent Hypercytokinemia with Autoimmune Feature in Relation to Genetic Hypohaptoglobinemia: a Case Report

Un asma sine asma: la SIRT

The paper describes the case of a girl with recurrent cough attributable to the so-called Cough Hypersensitivity Syndrome (CHS). The cough was misdiagnosed as drug resistant asthma for long time. CHS should be considered in all cases where recurrent, spasmodic cough, more than wheezing, predominates in the clinical picture.

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition)

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.

Understanding the foundations of chronic cough.

Despite chronic cough being one of the most frequent reasons for both primary care and specialty physician visits, its diagnosis and treatment remain challenging. The most common causes are upper airway cough syndrome, asthma, and gastroesophageal reflux disease; however, new research has implicated a cough hypersensitivity syndrome that may link many underlying etiologies. To accurately diagnose and treat patients with chronic cough, a thorough understanding of the various definitions, epidemiology, and pathophysiology is crucial. This article reviews these factors as well as the healthcare and socioeconomic burden of chronic cough.

Novel approach to chronic cough

Cough is the most common symptom for which people seek medical advice. A multitude of reasons can cause it. In clinical practice, a new term “Cough hypersensitivity syndrome“ was proposed, which defines unaccountable reasons forcough and different groups of patients with chronic cough. Adenosine triphosphate (ATP) as a driver of chronic cough is the most important target in nowadays clinical trials. Extracellular ATP activates P2X purinoreceptor 3 (P2X3) receptor channels, which are expressed in sensory neurons. New treatment methods that block P2X3 receptors are being developed.

Peripheral and central mechanisms of cough hypersensitivity.

Chronic cough is a difficult to treat symptom of many respiratory and some non-respiratory diseases, indicating that varied pathologies can underpin the development of chronic cough. However, clinically and experimentally it has been useful to collate these different pathological processes into the single unifying concept of cough hypersensitivity. Cough hypersensitivity syndrome is reflected by troublesome cough often precipitated by levels of stimuli that ordinarily don’t cause cough in healthy people, and this appears to be a hallmark feature in many patients with chronic cough. Accordingly, a strong argument has emerged that changes in the excitability and/or normal regulation of the peripheral and central neural circuits responsible for cough are instrumental in establishing cough hypersensitivity and for causing excessive cough in disease. In this review, we explore the current peripheral and central neural mechanisms that are believed to be involved in altered cough sensitivity and present possible links to the mechanism of action of novel therapies that are currently undergoing clinical trials for chronic cough.

Recent progress in the management of chronic cough.

Chronic cough is a common clinical condition with significant impact on quality of life and for which effective therapy remains an unmet clinical need. Over the past decade, there has been a major shift in how we approach this problem, driven by better appreciation of the clinical manifestation of chronic cough and an improved understanding of the associated neurobiology. “Cough hypersensitivity syndrome” has been proposed as a new diagnostic term for chronic cough, encompassing different phenotypes of the condition. Accumulating evidence suggests that this new concept is clinically relevant. However, while it is gaining widespread endorsement within the allergy and respiratory community, raising its profile in routine clinical practice is a priority. Thus, the present paper reviews recent progress in our understanding and management of chronic cough, with focus on mechanistic and clinical studies. It also provides detail on knowledge gaps and future research directions.

Diagnoses and management of adult cough: An Indian Environmental Medical Association (EMA) position paper.

Cough is a common yet distressing symptom that results in significant health care costs from outpatient visits and related consultations. The understanding of the pathobiology of cough in recent times has undergone an evolution with Cough hypersensitivity syndrome (CHS) being suggested in most cases of dry cough. However, in the case of productive cough, ancillary mechanisms including impaired Mucociliary clearance, in addition to hypermucosecretory bronchospastic conditions of Smoker's cough, asthma-COPD overlap, bronchiectasis, and allergic bronchopulmonary aspergillosis, need to be critically addressed while optimizing patient care with symptomatic therapy in outpatient settings of India. In this review, evidence-based graded recommendations on use of antitussives - & protussives as a Position Paper were developed based on the Level and Quality of Scientific evidence as per Agency for Health Care and Quality (AHRQ) criteria listing and Expert opinions offered by a multidisciplinary EMA panel in India. Management of acute or chronic cough involves addressing common issues of environmental exposures and patient concerns before instituting supportive therapy with antitussives or bronchodilatory cough formulations containing mucoactives, anti-inflammatory, or short-acting beta-2 agonist agents. The analyses provides a real world approach to the management of acute or chronic cough in various clinical conditions with pro- or antitussive agents while avoiding their misuse in empirical settings.

The role of ATP in cough hypersensitivity syndrome: new targets for treatment.

Clinically, chronic cough can be effectively controlled in most patients by etiological treatment; however, there remain a small number of patients whose cough has unidentifiable etiology or where treatment efficacy is poor following etiology identification, whose condition is described as unexplained chronic cough or refractory chronic cough. Patients with refractory chronic or unexplained chronic cough commonly have increased cough reflex sensitivity, which has been described as cough hypersensitivity syndrome. The adenosine triphosphate (ATP)-gated P2X3 receptor may be a key link in the activation of sensory neurons that regulate cough reflexes and has recently draw attention as a potential target for the treatment of refractory chronic cough, with a number of clinical studies validating the therapeutic effects of P2X3 receptor antagonists in patients with this condition. As the energy source for various cells in vivo, ATP localizes within cells under normal physiological conditions, and has physiological functions, including in metabolism; however, under some pathological circumstances, ATP can act as a neuromodulator and is released into the extracellular space in large quantities as a signal transduction molecule. In addition, ATP is involved in regulation of airway inflammation and the cough reflex. Here, we review the generation, release, and regulation of ATP during airway inflammation and its role in the etiology of cough hypersensitivity syndrome, including the potential underlying mechanism.

Cough Desensitization Therapy for Cough Hypersensitivity Syndrome

Cough Desensitization Therapy for Cough Hypersensitivity Syndrome

New Approach to Chronic Cough: An Introductory Guide Based on Recent Clinical Practice Guidelines

The cough reflex is a vital protective mechanism for the lower airways against aspiration, but when dysregulated, it becomes a clinical problem. Indeed, chronic cough is an important clinical issue as it is common in the general population and causes considerable morbidity. Anatomic diagnostic protocols were the first breakthrough in the management of patients with chronic cough; however, as systematic approaches are not always successful, a new paradigm of cough hypersensitivity syndrome has been proposed. The introduction of this paradigm has provided new opportunities for managing chronic cough, including development of new cough assessment tools and effective cough control therapies. However, it also warranted re-appraisal of existing clinical evidence and refinement of our clinical pathways. Against this background, international and domestic evidence-based practice guidelines based on a strict methodology have been published recently. In this review, we introduce clinical approaches based on the concept of cough hypersensitivity syndrome and discuss key aspects of recently published guidelines for chronic cough in adults. Keywords: Cough; Guideline 중심 단어: 기침; 가이드라인

Chronic cough. Cough reflex hypersensitivity syndrome

The cough reflex is a protective mechanism of the airway; it avoids bronchoaspiration and its complications and, when it is altered, it can appear as a hypersensitivity syndrome; cough per se is the most common symptom for which medical consultation is sought. Chronic cough represents a public health problem with a high degree of morbidity; It represents a syndrome by itself, regardless of the underlying condition. Recent evidence suggests an abnormal and altered neurophysiologic process. Recent literature and new therapeutic mechanisms were reviewed. We are in the process of understanding the cough syndrome.