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Study Points
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- Describe the background and terminology related to chronic cough.
- Compare and contrast available cough severity measures.
- Outline the epidemiology of chronic cough and underlying etiologies.
- Evaluate the impact of chronic cough on various dimensions of patients' lives.
- Discuss the natural history and course of chronic cough.
- Describe the pathophysiology of chronic cough.
- Outline components of the initial evaluation of patients with chronic cough.
- Identify potential underlying etiologies of chronic cough as well as appropriate management approaches for these conditions.
- Analyze available treatment modalities for chronic cough of various underlying causes, including upper respiratory, lower respiratory, and reflux-associated cough.
- Identify appropriate modalities for the treatment of refractory chronic cough, including pharmacotherapy, nonpharmacologic approaches, and investigational agents.
A cough lasting seven weeks is categorized as
Click to ReviewCHRONIC COUGH TERMINOLOGY
Term Definition Acute cough Cough lasting less than 3 weeks Subacute cough Cough lasting 3 to 8 weeks Chronic cough Cough lasting more than 8 weeks Refractory chronic cough Cough that persists despite guideline-based treatment of the presumed underlying cause(s) Unexplained chronic cough No diagnosable cause of cough is found despite extensive investigation for common and uncommon causes Allotussia Cough triggered by innocuous stimuli (e.g., laughing, talking, changes in ambient temperature) Hypertussia Exaggerated coughing triggered by mildly tussive stimuli (e.g., strong odors, second-hand cigarette smoke) Urge to cough (laryngeal paresthesia) A distinct, often debilitating sensation of irritation or "itch" in the throat or chest that precede cough and is not satiated by coughing Cough reflex hypersensitivity The cardinal feature of cough hypersensitivity syndrome Cough hypersensitivity syndrome Disorder characterized by cough triggered by mildly tussive or innocuous stimuli, with features of allotussia, hypertussia, and/or laryngeal paresthesia Cough hypersensitivity syndrome is
Click to ReviewCHRONIC COUGH TERMINOLOGY
Term Definition Acute cough Cough lasting less than 3 weeks Subacute cough Cough lasting 3 to 8 weeks Chronic cough Cough lasting more than 8 weeks Refractory chronic cough Cough that persists despite guideline-based treatment of the presumed underlying cause(s) Unexplained chronic cough No diagnosable cause of cough is found despite extensive investigation for common and uncommon causes Allotussia Cough triggered by innocuous stimuli (e.g., laughing, talking, changes in ambient temperature) Hypertussia Exaggerated coughing triggered by mildly tussive stimuli (e.g., strong odors, second-hand cigarette smoke) Urge to cough (laryngeal paresthesia) A distinct, often debilitating sensation of irritation or "itch" in the throat or chest that precede cough and is not satiated by coughing Cough reflex hypersensitivity The cardinal feature of cough hypersensitivity syndrome Cough hypersensitivity syndrome Disorder characterized by cough triggered by mildly tussive or innocuous stimuli, with features of allotussia, hypertussia, and/or laryngeal paresthesia Which of the following is an objective tool for cough measurement?
Click to ReviewCOUGH MEASURES
Name Domains/Items, Rating and Minimal Clinically Importance Difference (MCID) Comments Health-related quality of life patient-reported outcome tools Leicester Cough Questionnaire (LCQ) Seven-point Likert scale (1=all of the time; 7=none of the time); 19 items in 3 domains: physical, psychological, and social. Total score range: 3 (maximal impairment) to 21 (no quality-of-life impairment). MCID: 1.5 to 2.5 increase The most widely used tool for assessing quality of life impact of chronic cough Cough Quality of Life Questionnaire (CQLQ) Four-point Likert scale (1=strongly disagree; 4=strongly agree); 28 items over 6 domains: physical and extreme physical complaints, psychosocial issues, emotional well-being, safety fears, and functional abilities. Total score range: 28 (no adverse effect of cough) to 112 (worst possible impact). MCID: 10.6 to 21.9 Contains more items on physical impact of chronic cough (e.g., fractured ribs, headaches, immune deficiency, tuberculosis) Hull Airway Reflux Questionnaire (HARQ) Six-point scale (0=no symptoms; 5=most severe) of 14 items that measure airway hypersensitivity in chronic cough. Total score range: 0 to 70 Normal is <14 MCID: 16 Also used as a diagnostic tool for airway reflux, and to assess unexplained respiratory symptoms Cough Severity Diary (CSD) 11-point scale (0=never; 10=constantly) of 7 items on frequency; intensity; disruptiveness MCID ≥1.3 total score, −1.4 to −1.1 domain scores Captures the severity and impact of chronic cough. Developed in response to patient feedback. Objective assessment tools VitaloJAK Cough Monitor Electronic cough recording monitors worn by patients to measure cough frequency, typically as coughs per hour over 24 hours MCID: ≥20% to 30% decrease Does not capture the episodic nature of chronic cough, a primary factor in patients' disease burden Leicester Cough Monitor (LCM) Subjective tools Visual Analogue Scale (VAS) Score range 0 (no cough) to 100 mm (worst cough ever) MCID: 30-mm reduction on the 100-mm cough severity VAS — Numerical Rating Scale (NRS) Score range 0 (no cough) to 10 (worst cough ever) What is the approximate prevalence of chronic cough among U.S. adults?
Click to ReviewChronic cough has a prevalence among U.S. adults of roughly 10%, of whom 92% visited healthcare clinicians in the past six months [32]. Chronic cough is estimated to cost $6.8 billion annually in the United States, and an estimated $3.6 billion is spent annually on over-the-counter therapies [33]. The economic implications of chronic cough include the cost of outpatient visits, plus diagnostic workups, prescription medications to treat cough, and lost work and lost school productivity [1]. While inconsistent definitions prohibit direct comparisons of chronic cough prevalence between different countries or ethnicities, chronic cough appears to be more common in Europe, North America, and Australia than in Asian countries [32,34].
Which of the following is a risk factor for the development of chronic cough?
Click to ReviewRisk factors of chronic cough include smoking, female sex, older age, obesity, asthma, allergic rhinitis, rhinosinusitis, and angiotensin-converting enzyme (ACE) inhibitor use for hypertension treatment [34,39].
Cough-induced rib fractures, a painful and potentially serious complication of chronic cough, often involve ribs
Click to ReviewCough-induced rib fractures, another painful and potentially serious complication of chronic cough, often involve multiple ribs, particularly ribs 5 through 7. The number of ribs fractured is associated with higher mortality rates, particularly in older patients who often have decreased bone density due to osteoporosis (also an adverse effect of long-term corticosteroid treatment). However, rib fractures can also occur in patients with normal bone density [44,46].
Studies of patients with chronic cough have reported high rates of
Click to ReviewThe psychological effects associated with chronic cough are highly prevalent, with an impact on mental health comparable to that of stroke or Parkinson disease. Studies of patients with chronic cough have reported high rates of anxiety (33% to 52%) and depression (16% to 91%) [28].
Which of the following statements regarding the natural history and clinical course of chronic Cough is TRUE?
Click to ReviewLittle is known about the natural history of cough hypersensitivity, but the available evidence suggests that patients often suffer from it for many years [4]. In a longitudinal study of patients with unexplained chronic cough, cough severity worsened (36%) or was unchanged (23%) over 7 to 10 years. Predictors of cough persistence or improvement could not be identified. Unexpectedly, longitudinal spirometry data showed declines in forced expiratory volumes over one second (FEV1) that were well above population norms for similarly aged nonsmokers. The striking magnitude of decline argued against a chance finding. Around 10% of patients developed spirometric features of COPD [52].
In summary, chronic cough is related to an accelerated FEV1 decline over time, regardless of smoking history or COPD diagnosis, but the relationship between chronic cough and worse clinical outcomes lacks a clear pathophysiological explanation [55].
What are the phases of cough?
Click to ReviewCough occurs in three phases [31,56]. The first is inspiratory, during which the glottis opens widely followed by rapid inhalation sufficient for generating enough air movement to be productive. The second phase is compression. This phase is characterized by the rapid closure of the glottic apparatus and contraction of abdominal and other respiratory muscles compresses the alveoli and bronchiole, increasing intrathoracic pressure to greater than 300 mm Hg. The final phase is expiration, or the sudden opening of the epiglottis and vocal cords results in rapid, high-volume expiratory airflow that may exceed 500 mph in velocity. The force of this process loosens and expels mucous secretions from the airway wall, while the rapid airflow vibrates the larynx and pharynx, inducing the characteristic sounds of cough.
Excessive coughing is a consequence of increased activation of neuronal cough-mediating pathways due to
Click to ReviewChronic cough, unlike protective cough, is a pathologic state that no longer serves a physiologic role [60]. Excessive coughing is a consequence of increased activation of neuronal cough-mediating pathways due to [62,63]:
Excessive activation of airway vagal afferent terminals by chemical or mechanical irritants
Neuroplastic changes in vagal afferent fibers
Neuroplastic changes in the CNS
Which of the following statements best describes the concept of cough hypersensitivity syndrome as it relates to chronic cough and chronic pain?
Click to ReviewCough hypersensitivity syndrome frames chronic cough as a hypersensitivity disorder, akin to chronic pain. Sensitization of vagal afferents by upper or lower airway inflammation leads to increased cough sensitivity to normally anodyne stimuli, the cardinal feature of cough hypersensitivity syndrome [22,58].
In chronic cough, as in chronic pain, peripheral sensitization is necessary but probably insufficient without central sensitization, which alters the efficacy of neurotransmission in the brainstem and regulation of cough reflex-mediating brain pathways [21]. Patients with cough hypersensitivity or chronic pain have shown abnormal activity in the same midbrain areas that amplify incoming cough (or pain) signals [58,67,68].
Chronic pain research substantially informs the conceptual transformation in how chronic cough and refractory chronic cough are understood. Both disorders involve abnormal sensory processing. Taking inspiration from chronic pain, hypertussia describes abnormal excessive coughing in response to airway irritation. Allotussia describes coughing in response to innocuous stimuli. Laryngeal paresthesia describes noxious sensations in the throat or chest associated with an "urge to cough." Peripheral and central sensitization describe processes that alter cough pathway function [62,63].
The first step in evaluating cough is to
Click to ReviewThus, the first step in evaluating cough is to determine its duration. This also helps to narrow the differential diagnosis based on the most common underlying causes [10,100]:
Acute (<3 weeks) cough:
Infectious etiologies, especially with viral causes
Exacerbations of chronic diseases (e.g., asthma, COPD)
Pneumonia
Environmental exposures
Subacute (3 to 8 weeks) cough:
Postinfectious cough
Exacerbations of chronic diseases (e.g., asthma, COPD)
Upper airway cough syndrome
Chronic (>8 weeks) cough:
Upper airway cough syndrome
Asthma
Nonasthmatic eosinophilic bronchitis
GERD
All of the following are "red flag" signs/symptoms in patients with chronic cough that warrant further evaluation, EXCEPT:
Click to ReviewIn cough of any duration, the initial evaluation should identify any danger signs that may indicate a diagnosis requiring urgent attention. Important danger signs that will need further evaluation with chest x-ray and possibly laboratory testing and computed tomography (CT) include [44,100]:
Systemic symptoms (raises suspicion for chronic infection or rheumatic disease):
Fever
Night sweats
Weight loss
Peripheral edema with weight gain
Hemoptysis, an indicator of infection (e.g., bronchiectasis, lung abscess, tuberculosis), cancer (e.g., lung, bronchus, or larynx), rheumatologic diseases, heart failure, or foreign body inhalation
Prominent dyspnea, especially at rest or at night, a possible clue to airway obstruction or lung parenchymal disease
Possible foreign-body inhalation (requires urgent bronchoscopy)
Smoker older than 45 years of age with a new cough, change in cough, or co-occurring voice disturbance
Hoarseness
Trouble swallowing when eating or drinking
Vomiting
Recurrent pneumonia
Abnormal respiratory exam and/or abnormal chest radiograph coinciding with duration of cough
Which of the following diagnostic tests is recommended for patients with chronic cough suspected to be related to gastroesophageal reflux disease (GERD)?
Click to ReviewEVALUATION OF COMMON CAUSES OF CHRONIC COUGH
Evaluation Common Causes Asthma NAEB UACS GERD Spirometry X Bronchodilator reversibility X Bronchoprovocation challenge X Allergy evaluation X X X Sputum eosinophilia X Blood eosinophilia X Fractional exhaled nitric oxide (FeNO) X Sinus imaging X Nasopharyngoscopy X Empiric treatment trialsa X X X X aDiagnostic-Therapeutic Trials UACS First-generation oral antihistamines Inhaled corticosteroids Inhaled ipratropium Asthma or NAEB Inhaled corticosteroids Systemic (oral) corticosteroids Leukotriene receptor antagonist GERD High-dose proton pump inhibitor (PPI) acid-suppression therapy Anti-reflux lifestyle measures Pro-kinetic agent: metoclopramide GERD = gastroesophageal reflux disease; NAEB = nonasthmatic eosinophilic bronchitis; UACS = upper airway cough syndrome. Which of the following statements accurately reflects the diagnostic approach for differentiating between classic asthma, cough-variant asthma, and nonasthmatic eosinophilic bronchitis?
Click to ReviewClassic asthma, cough-variant asthma, and nonasthmatic eosinophilic bronchitis are clinical diagnoses with no clear-cut, absolute diagnostic test available to either rule asthma in or out as the cause of a patient's chronic cough [10]. In a stepwise diagnostic approach, initial abnormal lung function testing suggests classic asthma or COPD; normal testing is inclusive of cough-variant asthma, nonasthmatic eosinophilic bronchitis, or chronic bronchitis. Absence of bronchial hyperreactivity to methacholine challenge in patients with normal physical exam and spirometry findings suggests nonasthmatic eosinophilic bronchitis. Negative airway responsiveness can exclude cough-variant asthma. Abnormal spirometry contraindicates bronchial challenge testing [104].
In patients with negative physical examination and spirometry findings, what testing should be performed to confirm airway hyper-reactivity consistent with symptomatic asthma?
Click to ReviewIn patients with negative physical examination and spirometry findings, bronchial challenge testing (e.g., methacholine) should be performed to confirm airway hyper-reactivity consistent with symptomatic asthma [84]. Bronchial challenge testing is recommended in patients with reactive airway diseases to help diagnosis of asthma and nonasthmatic eosinophilic bronchitis as a cause of chronic cough. A negative bronchial challenge test (defined as an FEV1 decrease of <20% at the highest methacholine challenge dose [10 mg/mL]) has a high negative predictive value of asthma as an etiological diagnosis in chronic cough [104].
Which of the following statements best describes the treatable traits approach in managing airway disease?
Click to ReviewA trait is defined as clinically relevant, measurable, and treatable. These traits can be identified by their phenotypes and/or endotypes in pulmonary, extrapulmonary, and behavioral/environmental domains, and can coexist, interact, and change over time in the same patient. The treatable traits approach is agnostic to the traditional diagnostic labels of asthma or COPD and can be used in any patient with airway disease. The treatable traits approach often extends beyond the diagnostic label itself to find more treatment targets, especially in complex patients with suboptimal response to conventional guideline-based treatment [87,88]. In other words, the treatable traits approach represents a transdiagnostic model.
In patients with chronic cough in asthma, the first-line treatment is
Click to ReviewIn patients with chronic cough in asthma, the first-line treatment is inhaled corticosteroid with or without long-acting beta-agonist [6]. A leukotriene receptor antagonist or long-acting muscarinic antagonist may be added in for those who do not fully respond to initial treatment. Whether biologics can treat chronic cough related to asthma has not been studied.
Which of the following best describes the systematic approach for empiric treatment of chronic cough according to the ACCP guidelines?
Click to ReviewEmpiric treatment of chronic cough is systematically directed at the four most common causes of cough, starting with upper airway cough syndrome. In its 2006 guideline, the ACCP states that therapy should be given in sequential and additive steps, because more than one cause of cough may be present [82]. Initial empiric treatment should begin with an oral first-generation antihistamine/decongestant.
If chronic cough persists after treatment for upper airway cough syndrome, asthma as the possible cause should be worked up next. If spirometry does not indicate reversible airflow obstruction, bronchoprovocation testing is performed in the evaluation for asthma.
With the diagnoses of upper airway cough syndrome and asthma ruled out or treated without the elimination of cough, nonasthmatic eosinophilic bronchitis should be considered next, with a properly performed induced sputum test for eosinophils. In most patients with suspected cough due to asthma, a bronchoprovocation challenge should be performed and, if the result is positive, some combination of inhaled corticosteroids, inhaled beta-agonists, and/or oral leukotriene inhibitors should be administered.
In patients whose cough responds only partially or not at all to interventions for upper airway cough syndrome and asthma or nonasthmatic eosinophilic bronchitis, treatment for GERD should be instituted next. In patients with cough whose condition remains undiagnosed after all of these conditions has been worked up, referral to a cough specialist is indicated.
Chronic cough in idiopathic pulmonary fibrosis
Click to ReviewChronic cough in idiopathic pulmonary fibrosis predicts disease progression and mortality, is as distressing as breathlessness for patients, and remains one of the most difficult symptoms to control [64,125]. Among 1,447 patients with idiopathic pulmonary fibrosis cough, every 1-point decrease in LCQ score increased the risk of respiratory-related hospitalization by 6.5%, death by 7.4%, and lung transplantation by 8.7% over 12 months. Worse cough-specific quality of life independently associated with increased risk of respiratory hospitalization, death, and lung transplantation [126].
Wheezing and NSAID hypersensitivity are features of which rhinitis phenotype?
Click to ReviewDISTINGUISHING CHARACTERISTICS OF RHINITIS PHENOTYPES
Rhinitis Phenotype Primary Symptoms Associated Features More Responsive to Less Responsive to Allergic Sneezing, nasal pruritis, clear rhinitis Ocular itching, wheezing, atopic dermatitis INCS, INAH, FGAH, SGAH, SCS, AIT Decongestants, ABX Nonallergic noninfectious Intermittent congestion, clear rhinitis Physical triggers (temperature changes, food, irritants) INCA, INAH, INAC FGAH, SGAH, SCS, AIT, ABX GERD-associated Postnasal drip, throat clearing Epigastric pain, heartburn, dysphagia GERD diet and lifestyle changes, INAC FGAH, SGAH, INCS, INAH, SCS, ABX, AIT Chronic rhinosinusitis with or without nasal polyposis Anosmia/hyposmia, unremitting congestion, facial pain/pressure Wheezing, NSAID hypersensitivity SCS, biologics, intermittent INCS FGAH, SGAH, INAH Infectious Acute onset, sinus pressure, nasal congestion with purulent discharge Viral prodrome, episodic nature lasting <2 weeks Saline nasal lavage, INAH, decongestants, INAC FGAH, SGAH, INCS, SCS, ABX, AIT ABX = antibiotics; AIT = allergen immunotherapy; FGAH = first-generation oral antihistamines; GERD = gastroesophageal reflux disease; INAC = intranasal anticholinergics; INAH = intranasal antihistamines; INCS = intranasal corticosteroids, SCS = systemic corticosteroids; SGAH = second-generation oral antihistamines. According to the 2016 ACCP clinical practice guideline for reflux-associated chronic cough, when should esophageal manometry and pH-metry be performed?
Click to ReviewThe 2016 ACCP clinical practice guideline for reflux-associated chronic cough suggests that esophageal manometry and pH-metry be performed in patients with suspected reflux cough refractory to a three-month antireflux trial and being evaluated for surgical management (antireflux or bariatric); or with strong clinical suspicion warranting diagnostic testing for gastroesophageal reflux (Table 6). Esophageal manometry assesses for major motility disorder. It involves placing the pH electrode 5 cm above the lower esophageal sphincter in the pH monitoring study after the patient is off PPIs for seven days and histamine H2-receptor antagonists for three days [83].
Which of the following is a common pitfall in the management of chronic cough associated with upper airway cough syndrome?
Click to ReviewPITFALLS IN THE MANAGEMENT OF CHRONIC COUGH
Upper Airway Cough Syndrome Failing to recognize that upper airway cough syndrome (also asthma or GERD) can present as a cough-phlegm syndrome, misdiagnosed as chronic bronchitis. Assuming that all histamine H1 receptor antagonists (H1RAs) are the same. H1RAs without anticholinergic activity do not help nonallergic rhinitis conditions. Further, anticholinergic H1RAs may adversely affect memory, glaucoma, and prostate problems. Instead, consider ipratropium bromide nasal therapy. Failing to consider: "Silent" upper airway cough syndrome when a patient does not sense a postnasal drip or realize their frequent throat clearing
Allergic rhinitis and recommend the avoidance of allergens because symptoms are perennial
Sinusitis because it is nonobvious
NSAID-exacerbated disease
The potentially beneficial role of upper respiratory endoscopy
Asthma Failing to recognize that: Asthma can present as cough alone (i.e., cough-variant asthma) Inhaled medications may exacerbate cough Positive methacholine challenge alone is not diagnostic of asthma Nonasthmatic Eosinophilic Bronchitis Failing to consider the diagnosis, occupational/environmental causes, or order the correct test GERD Failing to recognize that:
"Silent" reflux disease can be causal and that it may take two to three months of intensive treatment before cough starts to improve and five to six months to resolve
GERD can be worsened by comorbidities (e.g., obstructive sleep apnea) or their treatment (e.g., nitrates or calcium channel blockers for coronary artery disease, progesterone for hormone replacement)
Assuming that:
Cough cannot be due to GERD because cough remains unchanged when gastrointestinal symptoms improve
Vocal cords' appearance can diagnose GERD, when inflammatory changes from coughing can mimic those of reflux
Being unaware that acid suppression alone will not improve cough
Failing to consider:
Non-acid reflux disease
The role of diet, intense exercise, and prokinetic therapy
Adequately treat co-existing causes of cough that perpetuate the cycle of cough and reflux because cough can provoke reflux
Triad of Upper Airway Cough Syndrome, Asthma, and GERD Failing to consider that more than one condition may be contributing simultaneously to cough, or failing to consider additional contributing conditions because of another "obvious" cause (e.g., COPD) Failing to appreciate: These chronic disorders cannot be cured and will periodically flare, especially with viral illness
When cough flares after a period of remission, re-evaluate as if a new problem
Asthma may become a problem when it was not before
Unsuspected Airway Diseases Failing to perform bronchoscopy when chest x-ray and CT are normal. Transnasal route allows inspection of both upper and lower respiratory tracts. Failing to appreciate that prolonged IV therapy for suppurative airway disease may succeed when the same drug given orally failed Which of the following agents is recommended by the American College of Chest Physicians for neuromodulator treatment of refractory/unexplained chronic cough?
Click to ReviewGUIDELINE RECOMMENDATIONS FOR NEUROMODULATOR TREATMENT OF REFRACTORY/UNEXPLAINED CHRONIC COUGH
Drug Guideline Organization (Year) ACCP (2016) ERS (2020) GRS (2020)a FRS (2023) BTS (2023) NEURO-COUGH (2023) Low-dose morphine slow-release Not reportedb Strong recommendation Strong recommendation Recommended: Grade B Recommended Recommended, very high consensus Codeine Not reported Not recommended Not reported Not reported Recommended against Not reported Gabapentin Recommended Conditional recommendation Can be used Recommended: Grade B Recommended Recommended, high consensus Pregabalin Not reported Conditional recommendation Can be used Recommended: Grade B Recommended Not reported Amitriptyline Not reported Not reported Can be used Recommended: Grade C Not reported Recommended, high consensus Baclofen Not reported Not reported Not reported Not reported Not reported Not reported a"Can be used" is a weaker endorsement than "recommendation" (i.e., "should be used"). b75% of expert panelists endorsed a recommendation of morphine, falling short of 80% required for inclusion; thus, morphine is neither recommended for nor against. ACCP = American College of Chest Physicians; BTS = British Thoracic Society; ERS = European Respiratory Society; FRS = French-Speaking Society of Respiratory Diseases; GRS = German Respiratory Society; NEURO-COUGH = New Understanding in the treatment Of COUGH Clinical Research Collaboration; SR = sustained-release. The usual starting dose of pregabalin for chronic cough is
Click to ReviewGabapentin should be started at a low dose (e.g., 100 mg three times per day) and titrated up to a maximum dose (600 mg three times per day), depending on clinical effects and tolerability. The usual starting dose of pregabalin for chronic cough is 25 mg twice daily, with increases in increments to a maximum 75 mg twice daily. Patients should be reassessed during dose titration and therapy stopped if there are significant side effects or inadequate response to treatment [5].
In clinical trials, what is the most common side effect of nalbuphine extended-release?
Click to ReviewNalbuphine extended-release (ER) is an opioid agonist-antagonist. In a double-blind randomized controlled trial of patients with idiopathic pulmonary fibrosis and chronic cough, nalbuphine ER tablets (titrated up to 162 mg twice daily) led to 75.1% reduction in daytime objective cough frequency, compared with 22.6% with placebo, a 50.8% placebo-adjusted reduction in 24-hour cough frequency, and similar improvements in patient reported outcomes [162]. Nalbuphine ER was the first therapy to show robust effects on chronic cough in idiopathic pulmonary fibrosis [25]. However, nalbuphine side effects of nausea (42.1%), fatigue (31.6%), constipation (28.9%), and dizziness (26.3%) led to a 24% dropout during the drug initiation phase, partially attributed to the inflexible forced-titration study design [162].
Which of the following statements accurately describes the role and findings related to gefapixant, a P2X3 receptor antagonist, in the treatment of refractory chronic cough?
Click to ReviewA breakthrough occurred when gefapixant, a P2X3 receptor antagonist, demonstrated a dramatic reduction in chronic cough. Other P2X3 antagonists confirmed the efficacy of this drug class in refractory chronic cough. The endogenous ligand for P2X3 is ATP. Epithelial damage is believed to release ATP. Evidence suggests that ATP largely mediates peripheral hypersensitivity; therefore, gefapixant is peripherally acting in refractory chronic cough [166].
P2X3 receptors are ion channels found on sensory afferent nerve fibers, activated by ATP. In preclinical studies, vagal C fibers, including those thought to be important in mediating cough, have been shown to express P2X3 and P2X2. At present, it is unclear whether ATP concentrations are elevated or P2X3 receptor expression increased in the airways of patients with refractory chronic cough, or how antagonism of P2X3 plays a role in reducing coughing to a range of chemical irritants, temperature changes, and mechanical stimuli. Nonetheless, in clinical trials, P2X3 receptor antagonism has provided robust reductions in cough frequency and patient-reported outcomes [25].
Which of the following accurately describes the use of lidocaine in the context of treating chronic cough?
Click to ReviewLidocaine non-selectively blocks voltage-gated sodium channels important in the initiation of action potentials and their conduction and is a local anesthetic agent in routine topical use to reduce coughing during bronchoscopy. Case reports and case series have also described the use of nebulized lidocaine as an antitussive to treat refractory chronic cough [169].
Which of the following statements best describes the challenges and considerations associated with speech and language therapy for chronic cough?
Click to ReviewSpeech and language therapy is a complex intervention, comprising components of education, cough suppression techniques, vocal hygiene, and psychoeducational counseling. Thus, it is difficult to standardize the intervention, and it is not clear whether all or just some of the components are essential for efficacy. In practice, the therapy seems to be most effective when delivered by experienced therapists, who may not be widely available. There is also a question about the durability of the effects over longer timescales when patients may not continue to practice the techniques [25].
What vocal hygiene approaches are recommended in the treatment of refractory/unexplained chronic cough?
Click to ReviewVocal and laryngeal hygiene and hydration are advised with a reduction in caffeine and alcohol intake. Nasal breathing with nasal douching may be recommended with nasal steam inhalation [19].
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- Review the course material online or in print.
- Complete the course evaluation.
- Review your Transcript to view and print your Certificate of Completion. Your date of completion will be the date (Pacific Time) the course was electronically submitted for credit, with no exceptions. Partial credit is not available.