|
| A) | acute. | ||
| B) | subacute. | ||
| C) | chronic. | ||
| D) | post-chronic. |
CHRONIC 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 |
| A) | cough that persists despite guideline-based treatment of the presumed underlying cause(s). | ||
| B) | cough triggered by innocuous stimuli (e.g., laughing, talking, changes in ambient temperature). | ||
| C) | a distinct, often debilitating sensation of irritation or "itch" in the throat or chest that precede cough and is not satiated by coughing. | ||
| D) | a disorder characterized by cough triggered by mildly tussive or innocuous stimuli, with features of allotussia, hypertussia, and/or laryngeal paresthesia. |
CHRONIC 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 |
| A) | Visual Analog Scale (VAS) | ||
| B) | Cough Severity Diary (CSD) | ||
| C) | Leicester Cough Monitor (LCM) | ||
| D) | Cough Quality of Life Questionnaire (CQLQ) |
COUGH 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) |
| The most widely used tool for assessing quality of life impact of chronic cough | |||
| Cough Quality of Life Questionnaire (CQLQ) |
| Contains more items on physical impact of chronic cough (e.g., fractured ribs, headaches, immune deficiency, tuberculosis) | |||
| Hull Airway Reflux Questionnaire (HARQ) |
| Also used as a diagnostic tool for airway reflux, and to assess unexplained respiratory symptoms | |||
| Cough Severity Diary (CSD) |
| Captures the severity and impact of chronic cough. Developed in response to patient feedback. | |||
| Objective assessment tools | |||||
| VitaloJAK Cough Monitor |
| 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) |
| — | |||
| Numerical Rating Scale (NRS) | Score range 0 (no cough) to 10 (worst cough ever) | ||||
| A) | 1% | ||
| B) | 10% | ||
| C) | 25% | ||
| D) | 50% |
Chronic 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].
| A) | Frailty | ||
| B) | Male sex | ||
| C) | Younger age | ||
| D) | Angiotensin-converting enzyme (ACE) inhibitor use |
Risk 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].
| A) | 1 and 2. | ||
| B) | 3 through 5. | ||
| C) | 5 through 7. | ||
| D) | 7 through 9. |
Cough-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].
| A) | bipolar disorder. | ||
| B) | anxiety and depression. | ||
| C) | substance use disorders. | ||
| D) | ADHD and obsessive-compulsive disorder. |
The 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].
| A) | The natural history of cough hypersensitivity is clearly established. | ||
| B) | Most patients with chronic Cough are diagnosed and effectively treated within months. | ||
| C) | Chronic cough is related to an accelerated FEV1 decline over time, regardless of smoking history or COPD diagnosis. | ||
| D) | The relationship between chronic cough and worse clinical outcomes has a clear pathophysiological explanation. |
Little 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].
| A) | Diastole and systole | ||
| B) | Waxing, full, and waning | ||
| C) | Inspiration, compression, and expiration | ||
| D) | Latent period, contraction, and relaxation |
Cough 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.
| A) | Neuroplastic changes in the CNS | ||
| B) | Neuroplastic changes in vagal afferent fibers | ||
| C) | Excessive activation of airway vagal afferent terminals by chemical or mechanical irritants | ||
| D) | All of the above |
Chronic 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
| A) | Cough hypersensitivity syndrome is primarily characterized by a direct infection of the vagal afferent fibers. | ||
| B) | The primary feature of cough hypersensitivity syndrome is a lack of sensitivity to normally non-irritating stimuli. | ||
| C) | Cough hypersensitivity syndrome and chronic pain both involve a direct inflammation of the brainstem's cough reflex pathways, leading to excessive coughing. | ||
| D) | Chronic cough in cough hypersensitivity syndrome is similar to chronic pain in that both involve peripheral and central sensitization, which alters sensory processing in the brain. |
Cough 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].
| A) | identify its etiology. | ||
| B) | determine its duration. | ||
| C) | start empirical/diagnostic therapy. | ||
| D) | evaluate impact on patient quality of life. |
Thus, 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
| A) | Hoarseness | ||
| B) | Hemoptysis | ||
| C) | History of asthma | ||
| D) | Systemic symptoms (e.g., fever, weight loss) |
In 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
| A) | Spirometry | ||
| B) | Nasopharyngoscopy | ||
| C) | Empiric treatment trial | ||
| D) | Bronchoprovocation challenge |
EVALUATION 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 |
| ||||||
| Asthma or NAEB |
| ||||||
| GERD |
| ||||||
| GERD = gastroesophageal reflux disease; NAEB = nonasthmatic eosinophilic bronchitis; UACS = upper airway cough syndrome. | |||||||
| A) | Abnormal spirometry findings are used to diagnose nonasthmatic eosinophilic bronchitis and contraindicate further bronchial challenge testing. | ||
| B) | Classic asthma can be definitively diagnosed with a single methacholine challenge test, while cough-variant asthma is ruled out by normal spirometry findings. | ||
| C) | Normal lung function testing rules out classic asthma and confirms nonasthmatic eosinophilic bronchitis, while abnormal spirometry indicates the need for further bronchial challenge testing. | ||
| D) | The absence of bronchial hyperreactivity to methacholine challenge in patients with normal physical exams and spirometry suggests nonasthmatic eosinophilic bronchitis, while a negative airway responsiveness can exclude cough-variant asthma. |
Classic 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].
| A) | Laryngoscopy (fiberoptic) | ||
| B) | Chest computed tomography (CT) | ||
| C) | Peripheral blood eosinophil count | ||
| D) | Bronchial challenge testing (e.g., methacholine) |
In 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].
| A) | Traits in the treatable traits approach are defined as clinically relevant, measurable, and treatable. | ||
| B) | The treatable traits approach focuses solely on traditional diagnostic labels such as asthma and COPD to determine treatment plans. | ||
| C) | In the treatable traits approach, only phenotypes are considered for treatment, while endotypes are not relevant in identifying treatment targets. | ||
| D) | The treatable traits approach is limited to identifying and treating only those traits that are associated with conventional asthma and COPD diagnoses. |
A 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.
| A) | biologics. | ||
| B) | allergy medications. | ||
| C) | inhaled corticosteroid with or without long-acting beta-agonist | ||
| D) | a leukotriene receptor antagonist or long-acting muscarinic antagonist. |
In 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.
| A) | Empiric treatment begins with the use of oral leukotriene inhibitors and only moves to other treatments if there is no response. | ||
| B) | Initial empiric treatment involves directly starting bronchoprovocation testing and, if positive, initiating inhaled corticosteroids without first addressing upper airway cough syndrome. | ||
| C) | In cases where cough persists despite treatment, the guidelines recommend immediate referral to a cough specialist before evaluating for nonasthmatic eosinophilic bronchitis or GERD. | ||
| D) | The treatment approach starts with a sequential and additive focus on upper airway cough syndrome, followed by evaluation for asthma, nonasthmatic eosinophilic bronchitis, and then GERD if needed. |
Empiric 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.
| A) | is relatively rare. | ||
| B) | is one of the easier symptoms to control. | ||
| C) | predicts disease progression and mortality. | ||
| D) | is less distressing than breathlessness for patients. |
Chronic 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].
| A) | Allergic | ||
| B) | GERD-associated | ||
| C) | Nonallergic noninfectious | ||
| D) | Chronic rhinosinusitis with or without nasal polyposis |
DISTINGUISHING 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. | ||||
| A) | As a first-line diagnostic test for all patients with chronic cough, regardless of response to antireflux therapy | ||
| B) | Only in patients who have not responded to a six-month antireflux trial, regardless of their surgical management plans | ||
| C) | In patients who have responded partially to antireflux medication but do not have a clear diagnosis of gastroesophageal reflux | ||
| D) | In patients with suspected reflux cough who are refractory to a three-month antireflux trial and are being considered for surgical management, or in those with strong clinical suspicion warranting diagnostic testing for gastroesophageal reflux |
The 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].
| A) | Failing to consider NSAID-exacerbated disease | ||
| B) | Failing to consider "silent" upper airway cough syndrome when a patient does not sense a postnasal drip or realize their frequent throat clearing | ||
| C) | Failing to recognize that upper airway cough syndrome (also asthma or GERD) can present as a cough-phlegm syndrome, misdiagnosed as chronic bronchitis | ||
| D) | All of the above |
PITFALLS IN THE MANAGEMENT OF CHRONIC COUGH
| Upper Airway Cough Syndrome | |||||
| |||||
| Asthma | |||||
| |||||
| Nonasthmatic Eosinophilic Bronchitis | |||||
| Failing to consider the diagnosis, occupational/environmental causes, or order the correct test | |||||
| GERD | |||||
|
Failing to recognize that:
Assuming that:
Being unaware that acid suppression alone will not improve cough Failing to consider:
| |||||
| Triad of Upper Airway Cough Syndrome, Asthma, and GERD | |||||
| |||||
| Unsuspected Airway Diseases | |||||
| |||||
| A) | Baclofen | ||
| B) | Gabapentin | ||
| C) | Amitriptyline | ||
| D) | Low-dose morphine slow-release |
GUIDELINE 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) | 25 mg twice daily. | ||
| B) | 75 mg twice daily. | ||
| C) | 250 mg twice daily. | ||
| D) | 100 mg three times daily. |
Gabapentin 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].
| A) | Nausea | ||
| B) | Fatigue | ||
| C) | Dizziness | ||
| D) | Constipation |
Nalbuphine 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].
| A) | Gefapixant, a P2X3 receptor antagonist, has been shown to provide only modest reductions in chronic cough and does not address peripheral hypersensitivity. | ||
| B) | The endogenous ligand ATP is not involved in the action of gefapixant, and the efficacy of P2X3 antagonists in refractory chronic cough remains unproven. | ||
| C) | Gefapixant primarily acts centrally to reduce cough and is not effective against cough induced by chemical irritants, temperature changes, or mechanical stimuli. | ||
| D) | P2X3 receptors, activated by ATP, are found on sensory afferent nerve fibers and play a key role in peripheral hypersensitivity; gefapixant has demonstrated dramatic reductions in cough frequency in clinical trials. |
A 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].
| A) | Lidocaine primarily functions as a systemic analgesic and is not effective for treating coughs associated with bronchoscopy or chronic cough. | ||
| B) | Lidocaine selectively blocks specific types of sodium channels to reduce coughing during bronchoscopy, and it is not used for chronic cough. | ||
| C) | Lidocaine's main role in treating chronic cough is through its action as a central nervous system depressant rather than its local anesthetic properties. | ||
| D) | Lidocaine is a local anesthetic that non-selectively blocks voltage-gated sodium channels, which helps in reducing coughing during bronchoscopy and has been used in nebulized form to treat refractory chronic cough. |
Lidocaine 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].
| A) | Speech and language therapy is most effective when delivered by novice therapists and does not require continued practice by patients to maintain its effects. | ||
| B) | Speech and language therapy for chronic cough involves a complex, multifaceted approach, making it difficult to standardize and assess the necessity of each component. | ||
| C) | The intervention is typically standardized and easy to implement, with clear evidence of its long-term effectiveness regardless of the therapist's experience or patient adherence. | ||
| D) | Speech and language therapy is a straightforward intervention with standardized components, including education and vocal hygiene, and has clearly defined long-term efficacy. |
Speech 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].
| A) | Optimal hydration | ||
| B) | Nasal breathing with nasal douching | ||
| C) | Reduction in caffeine and alcohol intake | ||
| D) | All of the above |
Vocal 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].