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Flashcards in 73 Cough Deck (26):
1

How does the definition of chronic cough differ from acute cough and subacute cough?

How does the definition of chronic cough differ from acute cough and subacute cough?

The American College of Chest Physicians (ACCP) current guidelines define:

  • Acute as symptoms lasting < 3 weeks,
  • Subacute as symptoms lasting 3 - 8 weeks,
  • Chronic cough as symptoms lasting > 8 weeks.

2

What is meant by the terms “unexplained cough” and “neuropathic cough”?

What is meant by the terms “unexplained cough” and “neuropathic cough”?

“Unexplained cough” describes a cough that persists despite a comprehensive diagnostic evaluation, exclusion of common causes, and appropriate therapeutic trials for common causes of cough. The term unexplained cough was chosen over idiopathic cough because it implies that there may be as yet unidentified causes for the cough or that it may be multifactorial. Cough hypersensitivity syndrome has been applied to individuals that appear to have common causes for cough and despite appropriate therapy have a persistent cough response. The underlying pathophysiology for this remains undefined but has been proposed to follow mechanisms similar to those for chronic pain (lower threshold for stimulation of afferent pain receptors). This has also led to the term neuropathic cough being applied to this group of patients.

3

What is the burden of illness related to chronic cough?

What is the burden of illness related to chronic cough?

It has been estimated that annually in the United States approximately 40% of the 30 million outpatient pulmonary clinic visits are for chronic cough. Approximately 3.6 billion dollars are spent annually on over-the-counter (OTC) medications for chronic cough in the United States.

4

What are the different types of afferent cough receptors?

What are the different types of afferent cough receptors?

Chemoreceptors react to things such as water, ammonia, carbon dioxide, sulfur dioxide, cigarette smoke, milk, gastric contents, and capsaicin.

Mechanoreceptors respond to pressure (touch), flow, proprioception, and laryngeal muscle contraction.

Laryngeal irritant receptors include nociceptive C fibers and G-protein coupled receptors (GPCR) plus the ion channel receptors Transient receptor potential vanilloid (TRPV-1) and Transient receptor potential ankyrin 1 (TRPA-1). These latter two are actually ion channels in the membrane (Figure 73-1).

5

Where are these cough receptors distributed?

Where are these cough receptors distributed?

There is a network of afferent sensory receptors found in the subepithelial layer throughout the respiratory tract as well as the GI tract and cardiovascular system that are all capable of triggering cough with appropriate and sufficient stimulus.

The larynx, trachea, and lower airways have a rich network of cough reflex afferent nerves that are capable of inducing cough. The main inputs are from the cough receptors themselves:

  • Slowly adapting pulmonary stretch receptors (SAR)
  • Rapidly adapting pulmonary stretch receptors (RAR)
  • Bronchial and pulmonary fibers (C-fibers)
  • Aδ fibers.

6

Describe the physiology of the cough reflex.

Describe the physiology of the cough reflex.

When an intense stimulus depolarizes the afferent receptor nerve terminal over the threshold, voltage gated sodium and potassium channels (Kv) are opened and trigger action potentials. Activation of C-fibers can cause mast cell degranulation and release of histamine and bradykinin leading to airway edema and activation of mechanoreceptors and neuropeptides with resultant neurogenic inflammation. The afferent input is relayed to the brainstem where the information can be centrally processed and modulated further before the efferent output leads to the elicitation of a cough. The increased sensitivity of the cough reflex seems to be driven by a complex interaction between

  • C-fiber receptors
  • rapidly adapting receptors
  • peripheral and central nervous system that remains poorly understood.

The nucleus tractus solitarius seems to be a central area for modifying cough through both long-term and short-term neuroplasticity (see Figure 73-1).

7

What role does the nose play in the pathophysiology of chronic cough?

What role does the nose play in the pathophysiology of chronic cough?

Allergies, infections, and irritants are capable of inducing inflammation in the nose that can lead to symptoms of sneezing, nasal itching, rhinorrhea, and nasal blockage. These responses are likely mediated by trigeminal sensory nerves.

Interestingly, it has been shown that intranasal administration of histamine or capsaicin does not cause coughing, but does increase the sensitivity to various tussigenic aerosols.

8

What are the neurologic connections between the gastrointestinal tract and the respiratory tract that contribute to the cough reflex?

What are the neurologic connections between the gastrointestinal tract and the respiratory tract that contribute to the cough reflex?

Vagal afferents from the esophagus and respiratory tract converge in the brainstem. Esophageal afferents may be triggered simply by significant acid secretion into the esophagus, thus triggering a cough response. Previous studies have demonstrated that acid infusion into the esophagus induces bronchoconstriction, presumably through a vagally mediated esophageal-tracheobronchial reflex, and dual channel pH monitoring correlated with cough both in terms of proximal and distal acid reflux. Further, acid infused into the distal esophagus of patients with chronic cough increased the frequency of coughing and cough reflex sensitivity, a phenomenon that can be blocked with topical lidocaine.

9

What are the common causes of chronic cough?

What are the common causes of chronic cough?

  • Upper airway cough syndrome (previously referred to as postnasal drip)
  • Lower airway conditions including
    • bronchial asthma
    • cough variant asthma
    • eosinophilic bronchitis
    • atopic cough
  • Gastroesophageal reflux disease 

Atopic cough is defined as a cough that manifests in atopic individuals without bronchial hyper-responsiveness that responds well to antihistamines alone without inhaled steroids, whereas the other lower airway conditions typically require inhaled steroids. These conditions often coexist in various combinations and failure to address and treat all concurrently may be one of the major impediments to successful amelioration of chronic cough.

10

What are less common causes of chronic cough?

What are less common causes of chronic cough?

  • Lower Airway
    • chronic bronchitis
    • chronic infection
    • interstitial lung disease
  • Medications: ACE-I
  • Cardiac diseases
    • CHF
    • Mitral valve disorders
  • Stimulation of hairs in the external auditory canal (Arnold’s nerve reflex).
  • There have been several occupational and environmental exposures also associated with chronic cough (Box 73-2).

11

What distinguishes upper airway cough syndrome from postnasal drip?

What distinguishes upper airway cough syndrome from postnasal drip?

What previously was referred to as chronic postnasal drip has more recently been labeled as upper airway cough syndrome (UACS) in recognition of the fact that posterior nasal drainage may result from several conditions of the sinuses and nasal passages (Box 73-3). Inflammatory signaling and possible neurogenic mechanisms originating in the upper airway may contribute to development of cough in addition to the physical and possible chemical irritation of posterior nasal drainage. While allergic rhinitis is often a culprit, other common causes include chronic rhinosinusitis, nasal polyposis, chronic bacterial overgrowth, fungal disease, anatomic anomalies, and postsurgical changes.

Secondly, the “unified airway” hypothesis proposes that processes that cause upper airway congestion and postnasal drainage induce inflammation in the lower airways. Such changes may lead to increased sensitivity of the cough receptors in the lower airways independent of direct stimulation by the postnasal drainage itself. Further, there is evidence that intense irritant exposures to the nose may cause the release of cytokines and various other mediators into the systemic circulation that induce changes in the lower respiratory tract that may enhance lower airway cough reflex sensitivity.

Findings such as these form the basis for the adoption of the term upper airway cough syndrome in place of postnasal drip, to reinforce that cough may be triggered by immune/inflammatory signaling and neuroplastic changes increasing cough receptor sensitivity rather than simply being the result of mechanical and/or irritant receptor triggering by postnasal secretions collecting in the larynx and or lower respiratory tract.

12

What is cough variant asthma?

What is cough variant asthma?

Cough variant asthma is diagnosed in individuals without wheezing, shortness of breath, or chest tightness who report coughing as their sole symptom when exposed to strong odors, exercise, or other triggers and who have a positive methacholine challenge. Spirometry testing is commonly normal and there may be no bronchodilator response.

13

What is nonasthmatic eosinophilic bronchitis?

What is nonasthmatic eosinophilic bronchitis?

Individuals with eosinophilic bronchitis report symptoms very similar to asthma and are often initially diagnosed with asthma but exhibit a negative methacholine challenge. Studies of sputum reveal that they have eosinophils and typically respond well to inhaled corticosteroids.

14

What are the mechanisms by which reflux from the gastrointestinal tract contributes to chronic cough?

What are the mechanisms by which reflux from the gastrointestinal tract contributes to chronic cough?

There are several different mechanisms by which gastrointestinal reflux may contribute to chronic cough. This is supported by the observation that PPI therapy alone rarely resolves GERD-related cough. First there is a convergence of vagal afferents from the esophagus and respiratory tract in the brainstem as outlined earlier (see Questions 5 and 6). Esophageal dysmotility may lead to esophageal reflux to the larynx that may be aspirated into the lungs or simply irritate the laryngeal mucosa.

Aspiration of gastric contents may or may not be associated with typical symptoms of GERD such as heartburn, regurgitation, water-brash, sour taste, chest pain, globus sensation or pharyngeal symptoms such as dysphonia, hoarseness, and sore throat depending on whether it is predominantly acid or nonacid reflux. Individuals with nonacid reflux often report no significant reflux symptoms but demonstrate signs of aspiration on bronchoscopic lavage with increased lymphocytes or neutrophils and possibly endobronchial signs of squamous metaplasia.

15

What is the prevalence of cough related to ACE inhibitors?

What is the prevalence of cough related to ACE inhibitors?

Cough induced by ACE inhibitors is estimated to occur in 5% to 35% of users and is reported to be more common in women and nonsmokers. It has also been noted to be more common in patients on ACE inhibitors for congestive heart failure compared to those taking it for other cardiovascular diseases such as hypertension. It may cause cough with the first dose or after months of use.

16

Is there any difference in incidence of chronic cough with ACE inhibitors and angiotensin receptor blockers?

Is there any difference in incidence of chronic cough with ACE inhibitors and angiotensin receptor blockers?

Studies suggest that the incidence of cough with ARBs is less than that with ACE inhibitors and there is no contraindication to trying ARBs if a patient develops a cough related to ACE inhibitor use. They should be aware of the possibility that the cough may return with ARB use and inform their physician if this occurs.

17

Discuss an initial diagnostic approach to chronic cough.

Discuss an initial diagnostic approach to chronic cough.

The ACCP guidelines recommend that if there are signs and symptoms suggestive of upper airway cough syndrome, asthma, nonasthmatic eosinophilic bronchitis, or GERD (which accounts for 80% of all causes of chronic cough) all disorders suspected should be treated empirically at the same time to see if there is a resolution or significant reduction of the cough. Patients who smoke should be encouraged to stop smoking (Figure 73-2).

If there are any symptoms or physical signs suggestive of cardiopulmonary disease or any suspicion for lung cancer, interstitial lung disease, or bronchiectasis, a chest radiograph should be performed. If there is partial resolution of the cough related to treating any of these entities, the treatment should be continued. It must be emphasized that more than one process may contributing to the chronic cough and all must be treated at the same time.

18

What other tests are useful in evaluation of reflux-associated cough?

What other tests are useful in evaluation of reflux-associated cough?

  • Barium esophogram is useful to assess for hiatal hernia, gastroesophageal reflux, and esophago-laryngeal reflux. It is also useful to evaluate other esophageal anomalies.
  • Impedance probe testing allows for evaluation of both acid and nonacid reflux in addition to distal versus proximal events and whether there is any correlation between cough, throat clearing, hoarseness, chest pain, and reflux events. Studies have been varied in showing good correlation between cough events and reflux events. If the cough is being triggered solely by acid events in the lower esophagus then there may very well be a strong correlation between cough events and reflux events. However, if the mechanism is related to laryngopharyngeal reflux with or without aspiration, this may lead to a general increased sensitivity to a variety of irritant exposures.
  • EGD is helpful to look for esophageal changes related to reflux or significant damage indicating Barrett’s esophagitis.
  • Esophageal manometry can be useful to assess if there are significant motility issues that may be contributing to reflux issues and/or determine whether a patient may be a candidate for a gastric fundoplication.

19

What should be the next step(s) if empiric treatment for the common causes of chronic cough fails?

What should be the next step(s) if empiric treatment for the common causes of chronic cough fails?

It is imperative that all causes of cough are treated concurrently and optimally. If the cough continues to be present, depending on the clinical history, a number of further tests may be considered.

A CT scan of the chest can be helpful to rule out cough caused by things that may be missed by plain chest radiograph such as interstitial lung diseases, bronchiectasis, chronic infections such as atypical mycobacterial infections, lung cancer, aspiration, or mitral valve disease.

A CT scan of the sinuses can identify anatomic anomalies, polyps, persistent inflammation, and ostial obstruction.

Skin testing can be used to evaluate for significant environmental allergens that may be contributing to UACS. Identifying pet, dust mite, cockroach, or mold allergies can lead to remediation that may significantly reduce upper airway congestion and inflammation.

20

When should bronchoscopy be considered in evaluation of chronic cough?

When should bronchoscopy be considered in evaluation of chronic cough?

The current ACCP guidelines suggest there is not enough evidence for the routine use of bronchoscopy as part of an evaluation of patients with chronic cough. If a thorough pulmonary workup has been performed without identifying a cause, or there is concern for reflux-associated cough or a cough from a chronic low-grade infection such as mycobacteria or mycoplasma, then bronchoscopy may be helpful. BAL may show evidence of high neutrophils and/or lymphocytes which have previously been associated with aspiration and cultures will reveal the presence of noncommensal microbes that may indicate chronic infection/colonization. Biopsies may show changes of squamous metaplasia that are associated with aspiration.

21

What are useful tests to rule out a cardiac cause of chronic cough?

What are useful tests to rule out a cardiac cause of chronic cough?

Chest radiographs to look for signs of congestive heart failure and mitral valve calcification are useful but a CT scan of the chest may be more sensitive in this regard. An echocardiogram is helpful to rule out mitral valve disease and cardiac wall motion abnormalities.

22

What are treatment options for UACS?

What are treatment options for UACS?

First-generation antihistamines such as bromopheniramine, chlorpheneramine, and promethazine have been shown to have central cough suppressive properties while newer generation nonsedating antihistamines do not have this property. Decongestants can be combined with first-generation antihistamines and are offered in several combinations. Some studies have suggested that for patients with significant nasal and/or sinus congestion saline nasal rinses can be helpful, although evidence is limited.

23

When should one consider discontinuing ACE inhibitors to see if they are the cause of the cough?

When should one consider discontinuing ACE inhibitors to see if they are the cause of the cough?

If there are not signs or symptoms suggestive of more common causes of cough, then discontinuation of ACE inhibitors and appropriate replacement therapy should be attempted right away. A cough caused by ACE inhibitor use will generally subside within 2 to 4 weeks. If there are other factors present that may explain a chronic cough but 4 weeks of an empiric treatment fails to lead to substantial resolution, then discontinuation of an ACE inhibitor is indicated.

If the cough persists despite being off the ACE inhibitor for 4 weeks, it is unlikely to be the cause and it can be restarted.

If the cough does stop, the ACE inhibitor can be tried again after 2 to 3 months but discontinued permanently if the cough returns.

24

What if substitution of an ACE inhibitor is not an option?

What if substitution of an ACE inhibitor is not an option?

Medication commonly used to suppress cough can be tried, including sodium cromoglycate, theophylline, sulindac, indomethacin, amlodipine, ferrous sulfate, and picotamide.

25

What are medication options for treating unexplained cough?

What are medication options for treating unexplained cough?

Persistent cough may be related to cough habituation and also neuropathic changes (peripheral and central) created by the cough itself. Central cough suppressants such as dextromethorphan or codeine containing products are effective for some but there are concerns about long-term use of narcotics.

Benzonatate is reported to reduce stretch receptor sensitivity in the lungs. Some patients respond to baclofen, transdermal lidocaine patches, or nebulized lidocaine. Peripheral afferent cough suppressants are proposed to block sensory receptors peripherally, and have been shown to suppress cough in randomized controlled trials, but these are not available in the United States (e.g., moguisteine and levodropropizine).

Given the theories that chronic cough is somewhat akin to chronic pain syndrome, it is not surprising that there are recommendations for use of such agents as tricyclic antidepressants and gabapentin, but data are limited as far as their efficacy for neuropathic cough.

26

What is the role of speech therapy in treatment of chronic cough?

What is the role of speech therapy in treatment of chronic cough?

Speech therapy techniques for cough suppression, throat clearing suppression, and throat relaxation play a vital role in breaking the viscious cycle of chronic cough. Techniques used to treat paradoxical vocal fold motion disorder (commonly referred to as vocal cord dysfunction (VCD)) may be helpful in this group as a number of patients exhibit both chronic cough and VCD.

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