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Nature Reviews. Disease Primers Jun 2022Chronic cough is globally prevalent across all age groups. This disorder is challenging to treat because many pulmonary and extrapulmonary conditions can present with... (Review)
Review
Chronic cough is globally prevalent across all age groups. This disorder is challenging to treat because many pulmonary and extrapulmonary conditions can present with chronic cough, and cough can also be present without any identifiable underlying cause or be refractory to therapies that improve associated conditions. Most patients with chronic cough have cough hypersensitivity, which is characterized by increased neural responsivity to a range of stimuli that affect the airways and lungs, and other tissues innervated by common nerve supplies. Cough hypersensitivity presents as excessive coughing often in response to relatively innocuous stimuli, causing significant psychophysical morbidity and affecting patients' quality of life. Understanding of the mechanisms that contribute to cough hypersensitivity and excessive coughing in different patient populations and across the lifespan is advancing and has contributed to the development of new therapies for chronic cough in adults. Owing to differences in the pathology, the organs involved and individual patient factors, treatment of chronic cough is progressing towards a personalized approach, and, in the future, novel ways to endotype patients with cough may prove valuable in management.
Topics: Adult; Chronic Disease; Cough; Humans; Hypersensitivity; Lung; Quality of Life
PubMed: 35773287
DOI: 10.1038/s41572-022-00370-w -
European Respiratory Review : An... Dec 2021Chronic cough is defined in adults as a cough that lasts for ≥8 weeks. When it proves intractable to standard-of-care treatment, it can be referred to as refractory... (Review)
Review
Chronic cough is defined in adults as a cough that lasts for ≥8 weeks. When it proves intractable to standard-of-care treatment, it can be referred to as refractory chronic cough (RCC). Chronic cough is now understood to be a condition of neural dysregulation. Chronic cough and RCC result in a serious, often unrecognized, disease burden, which forms the focus of the current review.The estimated global prevalence of chronic cough is 2-18%. Patients with chronic cough and RCC report many physical and psychological effects, which impair their quality of life. Chronic cough also has a significant economic burden for the patient and healthcare systems. RCC diagnosis and treatment are often delayed for many years as potential treatable triggers must be excluded first and a stepwise empirical therapeutic regimen is recommended.Evidence supporting most currently recommended treatments is limited. Many treatments do not address the underlying pathology, are used off-label, have limited efficacy and produce significant side-effects. There is therefore a significant unmet need for alternative therapies for RCC that target the underlying disease mechanisms. Early clinical data suggest that antagonists of the purinergic P2X3 receptor, an important mediator of RCC, are promising, though more evidence is needed.
Topics: Adult; Chronic Disease; Cough; Humans; Quality of Life
PubMed: 34853095
DOI: 10.1183/16000617.0127-2021 -
Chest Jan 2016Unexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC. (Review)
Review
BACKGROUND
Unexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC.
METHODS
This systematic review of randomized controlled trials (RCTs) asked: What is the efficacy of treatment compared with usual care for cough severity, cough frequency, and cough-related quality of life in patients with UCC? Studies of adults and adolescents aged > 12 years with a chronic cough of > 8 weeks' duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the American College of Chest Physicians organization methodology.
RESULTS
Eleven RCTs and five systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used an assortment of descriptors and assessments to identify UCC. Although gabapentin and morphine exhibited positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) were affected by intervention fidelity bias; when this factor was addressed, ICS were found to be ineffective for UCC. Esomeprazole was ineffective for UCC without features of gastroesophageal acid reflux. Studies addressing nonacid gastroesophageal reflux disease were not identified. A multimodality speech pathology intervention improved cough severity.
CONCLUSIONS
The evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology-based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and identifies gaps in our knowledge as well as areas for future research.
Topics: Adolescent; Adult; Algorithms; Child; Chronic Disease; Cough; Decision Trees; Humans; Practice Guidelines as Topic
PubMed: 26426314
DOI: 10.1378/chest.15-1496 -
Deutsches Arzteblatt International Feb 2022Chronic cough, i.e., cough lasting longer than eight weeks, affects approximately 10% of the population and is a common reason for outpatient medical consultation. Its...
BACKGROUND
Chronic cough, i.e., cough lasting longer than eight weeks, affects approximately 10% of the population and is a common reason for outpatient medical consultation. Its differential diagnosis is extensive, and it is generally evaluated in poorly structured fashion with a variety of diagnostic techniques. The German Clinical Practice Guideline on Acute and Chronic Cough was updated in 2021 and contains a description of the recommended stepwise, patient-centered, and evidencebased procedure for the management of chronic cough.
METHODS
The guideline has been updated in accordance with the findings of a systematic search of the literature for international guidelines and systematic reviews. All recommendations were developed in an interdisciplinary manner and agreed upon by formal consensus. The target group consists of adult patients with cough.
RESULTS
History-taking, after the exclusion of red flags, should include questioning about smoking status, medications, and relevant present and past illnesses (COPD, asthma). Subsequent diagnostic testing should include a chest x-ray and pulmonary function tests. If the patient is taking an ACE inhibitor, a test of drug discontinuation can be carried out first. Radiologically detected pulmonary masses or evidence of rare diseases (interstitial lung diseases, bronchiectasis) are an indication for chest CT or for direct referral to an appropriate specialist. If the imaging studies and pulmonary function tests are normal, the patient is most likely suffering from a disease entity that can be treated empirically, such as upper airway cough syndrome or cough variant asthma. Any patient with an unexplained or refractory cough must receive proper patient education; individual therapeutic trials of physiotherapeutic or speech-therapeutic methods are possible, as is the off-label use of gabapentin or morphine.
CONCLUSION
Chronic cough should be evaluated according to an established diagnostic algorithm in collaboration with specialists. Treatments such as inhaled corticosteroids should be tested exhaustively in accordance with the guidelines, and the possibility of multiple causes as well as the role of patient compliance should be kept in mind before a diagnosis of unexplained or intractable cough is assigned.
Topics: Adrenal Cortex Hormones; Adult; Asthma; Bronchiectasis; Chronic Disease; Cough; Humans; Practice Guidelines as Topic
PubMed: 34918623
DOI: 10.3238/arztebl.m2021.0396 -
Clinical Pharmacology and Therapeutics Mar 2021Chronic cough, defined as a cough lasting > 8 weeks, is a common medical condition that exerts a substantial physical, mental, and social burden on patients. A subset... (Review)
Review
Chronic cough, defined as a cough lasting > 8 weeks, is a common medical condition that exerts a substantial physical, mental, and social burden on patients. A subset of patients with chronic cough are troubled with a cough that persists despite optimal treatment of presumed associated common and uncommon conditions (refractory chronic cough; RCC) or in which no diagnosable cause for cough can be identified despite extensive assessment (unexplained chronic cough; UCC). Many of these patients exhibit clinical features of cough hypersensitivity, including laryngeal paresthesia, hypertussia, and allotussia. Over-the-counter cough remedies are ineffective and can lead to intolerable side effects when used for RCC/UCC, and the lack of approved treatments indicated for these conditions reflects a major unmet need. An increased understanding of the anatomy and neurophysiology of protective and pathologic cough has fostered a robust clinical development pipeline of several targeted therapies for RCC/UCC. This manuscript reviews the mechanisms presumed to underly RCC/UCC together with the rationale and clinical evidence for several targeted therapies currently under clinical investigation, including transient receptor potential channel antagonists, P2X3-receptor antagonists, voltage-gated sodium channel blockers, neuromodulators, and neurokinin-1-receptor antagonists. Finally, we provide an overview of targets that have been investigated in preclinical models of cough and other airway diseases that may hold future promise for clinical studies in RCC/UCC. Development of targeted therapies with different sites of action may foster a precision medicine approach to treat this heterogeneous, underserved patient population.
Topics: Animals; Antitussive Agents; Chronic Disease; Cough; Drug Design; Humans; Molecular Targeted Therapy; Signal Transduction
PubMed: 32748976
DOI: 10.1002/cpt.2003 -
Chest Jan 2021The purpose of this state-of-the-art review is to update the American College of Chest Physicians 2006 guideline on global physiology and pathophysiology of cough. A... (Review)
Review
The purpose of this state-of-the-art review is to update the American College of Chest Physicians 2006 guideline on global physiology and pathophysiology of cough. A review of the literature was conducted using PubMed and MEDLINE databases from 1951 to 2019 and using prespecified search terms. We describe the basic phenomenology of cough patterns, behaviors, and morphological features. We update the understanding of mechanical and physiological characteristics of cough, adding a contemporary view of the types of cough and their associated behaviors and sensations. New information about acoustic characteristics is presented, and recent insights into cough triggers and the patient cough hypersensitivity phenotype are explored. Lastly, because the clinical assessment of patients largely focuses on the duration rather than morphological features of cough, we review the morphological features of cough that can be measured in the clinic. This is the first of a two-part update to the American College of Chest Physicians 2006 cough guideline; it provides a more global consideration of cough phenomenology, beyond simply the mechanical aspects of a cough. A greater understanding of the typical features of cough, and their variations, may allow a more informed interpretation of cough measurements and the clinical relevance for patients.
Topics: Cough; Humans
PubMed: 32888932
DOI: 10.1016/j.chest.2020.08.2086 -
Respiratory Medicine Feb 2014Loss of consciousness following cough was first described in 1876 as "laryngeal vertigo" Since then, several hundred cases of what is now most commonly termed cough... (Review)
Review
Loss of consciousness following cough was first described in 1876 as "laryngeal vertigo" Since then, several hundred cases of what is now most commonly termed cough syncope have been reported, often in association with various medical conditions. Some early authors assumed this entity to be a form of epilepsy, but by the mid-20th century, general consensus reflected that post-tussive syncope was a consequence of markedly elevated intrathoracic pressures induced by coughing. A typical profile of the cough syncope patient emerging from the literature is that of a middle-aged, large-framed or overweight male with obstructive airways disease. Presumably, such an individual would be more likely to generate the extremely high intrathoracic pressures associated with cough-induced fainting. The precise mechanism of cough syncope remains a matter of debate. Theories proposed include various consequences of the marked elevation of intrathoracic pressures induced by coughing: diminished cardiac output causing decreased systemic blood pressure and, consequently, cerebral hypoperfusion; increased cerebrospinal fluid (CSF) pressure causing increased extravascular pressure around cranial vessels, resulting in diminished brain perfusion; or, a cerebral concussion-like effect from a rapid rise in CSF pressure. More recent mechanistic studies suggest a neurally mediated reflex vasodepressor-bradycardia response to cough. Since loss of consciousness is a direct and immediate result of cough, elimination of cough will eliminate the resultant syncopal episodes. Thus, the approach to the patient with cough syncope requires thorough evaluation and treatment of potential underlying causes of cough, as summarized in several recently published cough management guidelines.
Topics: Acute Disease; Chronic Disease; Cough; Female; Humans; Male; Syncope
PubMed: 24238768
DOI: 10.1016/j.rmed.2013.10.020 -
Physiological Research Mar 2020Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review... (Review)
Review
Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review presents recent knowledge on drug-induced coughs in patients with chronic cough. The focus is placed on ACEIs, for which there are a multitude of studies documenting their associations with cough. Additional drugs are discussed for which there are reports of cough as a side effect of treatment, and the potential mechanisms of these effects are discussed.
Topics: Analgesics, Opioid; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Chronic Disease; Cough; Fentanyl; Humans; Reflex
PubMed: 32228014
DOI: 10.33549/physiolres.934406 -
Therapeutic Advances in Respiratory... 2021Patients with chronic cough experience considerable burden. The cough severity visual analog scale (VAS) records patients' assessment of cough severity on a 100-mm... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Patients with chronic cough experience considerable burden. The cough severity visual analog scale (VAS) records patients' assessment of cough severity on a 100-mm linear scale ranging from "no cough" (0 mm) to "worst cough" (100 mm). Although cough severity scales are widely used in clinical practice and research, their use in patients with refractory or unexplained chronic cough has not been formally validated.
METHODS
This analysis includes data from a phase 2b randomized controlled trial of the P2X3-receptor antagonist gefapixant for treatment of refractory or unexplained chronic cough (NCT02612610). Cough severity VAS scores were assessed at baseline and Weeks 4, 8, and 12. The cough severity VAS was validated using several outcomes, including the Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), patient global impression of change (PGIC) scale, and objective cough frequency. Validation metrics included test-retest reliability, convergent and known-groups validity, responsiveness, and score interpretation (i.e., clinically meaningful change threshold).
RESULTS
The analysis included 253 patients (median age, 61.0 years; females, 76%). Test-retest reliability of the cough severity VAS was moderate (intraclass correlation coefficient, 0.51). The cough severity VAS had acceptable convergent validity with other related measures (Pearson of 0.53 and -0.41 for CSD and LCQ total scores, respectively; < 0.0001 for each). Known-groups validity was supported by significant differences in mean cough severity VAS scores across severity groups defined using CSD, LCQ, and cough frequency tertiles. A large effect size was observed in patients with the greatest improvements in PGIC (Cohen = -1.8). A ⩾ 30-mm reduction in the cough severity VAS was estimated as a clinically meaningful change threshold for clinical trials in chronic cough.
CONCLUSIONS
The cough severity VAS is a valid and responsive measure. A cough severity VAS reduction of ⩾ 30 mm can discriminate clinically meaningful changes in chronic cough severity in clinical studies.
Topics: Chronic Disease; Cough; Female; Humans; Middle Aged; Quality of Life; Reproducibility of Results; Surveys and Questionnaires; Visual Analog Scale
PubMed: 34697975
DOI: 10.1177/17534666211049743 -
Chest Jan 2006
Topics: Adolescent; Adult; Child; Child, Preschool; Cough; Evidence-Based Medicine; Humans
PubMed: 16428686
DOI: 10.1378/chest.129.1_suppl.1S