The role of the family doctor is emphasized through the following approach identifying the role that a pulmonary doctor and Otolaryngologist as well as gastroenterologist may play in assisting them in an evaluation. This multi-disciplinary approach to evaluation and management of chronic cough may be useful in the care of patients with cough refractory to management of initial treatment of the most common causes (upper airway cough syndrome, asthma, and gastroesophageal reflux).

See Chronic Cough Management Options Including Medications (under construction) for information on management of chronic cough.

A. HISTORY:

When evaluating a chronic cough the patient history can provide information that can help to create a differential diagnosis.

• When did the cough start?
  • A chronic cough has been defined by some investigators as persisting for greater than 3 months (Kavitt 2015) although others have used a cut-off of 8 weeks (Poe 1989). 
  • After the start of a new medication?
  • At the start of allergy season?
  • After an acute illness?
• How long has the cough been present?
  • Years vs months vs weeks can rule in and out different diagnoses
• Intermittent vs constant?
  • If the cough is intermittent think about what could be triggering coughing spells.
• Productive vs Non-productive cough?
  • dry, clear, yellow, green or bloody sputum
• Are there associated triggers?
  • Cold weather, exercise, allergies, acid reflux
• Is the patient a smoker?
  • There is a high correlation with smoking and many of the cuases of chronic cough listed below.
• Start of new medications?
  • There are many different medications that can cause cough as an adverse effect.
• Are there associated symptoms?
  • This can help to narrow, which organ system might be causing the cough.
• Does anything help to relieve the cough?
  • Medications, activities, position
• Is there associated shortness of breath?
  • It can be useful to distinguish the onset of SOB if this is a positive finding.
• History of autoimmune/granulomatous disease?
  •  There are both granulomatous, autoimmune, and vascular causes of cough that can be assocaited with autoimmune diseases.
• Questions specific to the most common causes of chronic cough
  • Symptoms of GERD?
  • Symptoms of asthma?
  • Symptoms of allergies?

REVIEW OF SYSTEMS:

There are different primary sources of chronic cough and it is it can be useful to ask the patient about their areodigestive tract as well as the head and neck.

FAMILY HISTORY:

Some causes of chronic cough may be related to family history

• Asthma has been reported to have a genetic association. (Palmer 2000)
• The rare Goodpasture syndrome (autoimmune disorder) has been reported with a cough associated with kidney disease. (Lazor 2007)

PAST MEDICAL HISTORY:

The patient’s past medical history may also to help to reveal a cause of the chronic cough.

• History of acid reflux.
• History of allergies
• History of immune suppression
• History of heart failure
• History of asthma

B. PHYSICAL EXAM:

The physical examination for evaluation of a chronic cough may be guided by findings in the patient’s history

LUNGS

An examination of the lungs can be done for suspected pulmonary pathology; not all pulmonary causes of cough may be evident on physical exam.

• Exam of the lungs may include:
  • Auscultation 
  • Percussion can be useful for pulmonary edema
  • Special Tests can also be used
    • (Repeated 99’s with tactile fremitus, egophony)

Evaluate for:

• Wheezing 
• Rales 
• Rhonchi 
• Absent or decreased breath sounds
• Stidor - see: The Evaluation of Stridor in Pediatric Patients

HEAD AND NECK

• Exam of the head and neck may include:
  • Inspection of the oral cavity and nasal cavity.
  • Palpation for cervical lymph nodes
  • Laryngoscopy to evaluate the anatomy of the pharynx and larynx

Look for evidence of:

• Interarytenoid edema - link 
• “Cobblestoning” of the posterior pharynx- link
• Post cricoid edema
• Drainage of the nasopharynx
• stenosis/stricture of the subglottic/laryngeal anatomy

HEART

An evaluation of the cardiovascular system may be warranted is there is a suspected cardiac cause of the chronic cough.

• Exam of the cardiac system may include:
  • Auscultation of the heart
  • Palpation of the point of maximal impulse
  • Evaluation for Jugular Venous Distension
• Look for evidence of:
  • S3/S4 - link
  • Cardiac Murmurs

MUSCULOSKELETAL

Evaluation of the peripheral musculoskeletal system can in certain instances provide useful diagnostic clues.

Examples would be:

• Digital clubbing (highly associated with pulmonary pathology) - 
• Chronic inflammatory arthritis of the hands and feet specifically PIP and MCP joints in rheumatoid arthritis, which has associated lung pathology. 

C. DIFFERENTIAL DIAGNOSIS

The first three disorders listed (upper airway cough syndrome, asthma, and gastroesophageal reflux) alone or in combination, have been reported to be responsible for greater than 90 percent of cases of  nonproductive chronic cough. (Mello 1996)

1. Upper Airway Cough Syndrome 

• Cough reported to be related to stimulation of the cough receptors in the larynx from post nasal drip has been termed 'upper airway cough syndrome'.
• Underlying reasons for postnasal drip include but are not limited to allergic, perennial nonallergic, and vasomotor rhinitis; acute nasopharyngitis; and sinusitis. (Patrick 1995)
• Common Symptoms reported among patients with upper airway cough syndrome:
  • frequent nasal discharge,
  • a sensation of liquid dripping into the back of the throat
  • frequent throat clearing 
  • postnasal drip may also be "silent," so that the absence of these symptoms does not necessarily exclude the diagnosis (Pratter 1993) 
• Clues on physical examination:
  • cobblestone appearance to the nasopharyngeal mucosa
  • the presence of secretions in the nasopharynx.
• Diagnosis:
  • Upper Airway Cough Syndrome is a clinically based diagnosis based on signs and symptoms.
  • Successful relief of the cough with treatment of the source of post nasal drip may help to establish the diagnosis.
• Useful links:
  • Medical Management of Sinusitis

2. Asthma

• Asthma has been reported to be the second leading cause of persistent cough in adults, and the most common cause in children. (Honlinger 1991)
• Cough due to asthma is reported to be commonly accompanied by episodic wheezing and dyspnea
• Cough can also be the sole manifestation of a form of asthma called "cough variant asthma" (Johnson 1991)
• Common Symptoms:
  • Cough, wheezing or dyspnea related to allergic exmposure
  • Worsening of cough with cold weather or exrecise
  • Worsening of cough after starting a beta blocker
  • Allergy to Aspirin
• Clues on Physical Exam:
  • Wheezing on physical exam (absense of wheezing does not necessarily exclude asthma as a diagnosis)
  • Eczema
  • Less commonly - nasal polyps
• Diagnosis:
  • Spirometry/Pulmonary Function Testing
    • FEV1 should improve by ≥12 percent with addition of bronchodilators (Galant 2007)
  • Trial of bronchodilator medication (such as Albuterol inhaler)
  • Allergy testing
  • Chest X-ray (if there is not intial response to Bonchodilators)
    • this can show hyperinflation

3. Gastroesophageal Reflux (GERD)

• GERD is frequently sited as one of the top three most common causes of chronic cough. (Irwin 2006)
• Gastoesophageal reflux is very common disorder with up to 10 to 20 percent of people in the Western world having symptoms ascribed to GERD. (Dent 2005)
• GERD may be related to an incompetent lower esophageal sphincter.
• Common Symptoms:
  • Heartburn - a burning sensation in the retrosternal area, most commonly experienced in the postprandial period. (Vakil 2006)
    • This can be absent in as many as forty percent of patients with cough related to GERD. (Irwin 1990)
  • Sense of stomach contents into the back of the throat.
  • globus sensation (fullness in throat)
  • chronic cough, hoarseness, wheezing
  • dysphagia
  • chest pain
• Clues on Physical Exam:
  • Diagnosis of GERD is usually clinical, however there are findings assocaited with upper endoscopic exam
    • Incompetent Lower esophageal sphincter
    • Lower Esophagus Esophogitis
    • Barretts changes in the lower esophagus - this is a metaplasia characterized by replacement of normal esophagus with glandular tissue more commonly seen later in the GI tract.
    • Evidence of laryngeal/hypopharyngeal irritation and inflammation
• Diagnosis:
  • A trial of anti-reflux medication such as PPI or H2 blocker may be offered.
    • despite symptomatic improvement, success on anti-reflux medication does not always correlate with results of pH monitoring. (Newmans 2004)
  • pH monitoring - pH changes within the esophagus can help identify acid reflux episodes.
  • If a patient presents with atypical symptoms such as chest pain it may be necessary to rule out possible more dangerous cardiac etiologies.
• Useful Links:
  • Esophagoscopy with narrow band imaging (NBI) for Reflux Esophagitis
  • Handout: Esophageal Reflux Precautions
  • Reflux Symptom Index (RSI)
  • Phlegm and Its Management

4. Laryngopharyngeal reflux (LPR)

• LPR - is the retrograde movement of gastric contents (including acid and enzymes such as pepsin) into the laryngopharynx leading to symptoms referable to the larynx/hypopharynx (Koufman 2002)
• As per Koufman, only 35 percent of people with LPR will report heartburn as a symptom (Koufman 2002)
• Whereas GERD and LPR may share similarity in etiology (reflux) they are considered by some to be distinct entities.  GERD is felt to be a problem of the lower esophageal sphincter and mainly occurs in a recumbent position. By contrast, LPR is thought to possibly represent  primarily an upper esophageal sphincter problem that mainly occurs in the upright position intermittently compromised during periods of physical exertion (eg, bending over, Valsalva, exercise). (Koufman 2002)
• Koufman relates the majority of GERD patients have signs of esophagitis on biopsy, while only 25 percent of LPR patients do. (Koufman 2002)
• Common Symptoms of LPR: (Percentages are those reported from Koufman 1991)
  • Dysphonia or hoarseness (71 percent)
  • Cough (51 percent)
  • Globus Sensation (47 percent)
  • Throat clearing (42 percent)
  • Dysphagia (35 percent)
• Clues on Physical Exam
  • laryngoscopic exam may show:
    • arytenoid erythema and edema and pharyngeal inflammation
• Diagnosis
  • Clinical History
  • 24-hour dual sensor pH probe
  • Trial of Anti-reflux Medication such as PPI or H2 blocker
• Useful Links:
  • Extraesophageal reflux disease
  • Hoarseness

5. Respiratory Tract Infection

• Cough following viral or other upper respiratory tract infection can persist for more than eight weeks after the acute infection. (Poe 1989)
• Others have defined chronic cough as one persisting for more than 3 months (Kavitt 2015)
• The cause of the chronic cough can be related to increased secretions in the pharynx and nasopharynx leading to post nasal drip, inflammation from the infection leading to a hyperresponsive cough reflex, or enhanced sensitivity of the nerves within the airway.
• Chronic cough can in some instances be caused by a chronic infection such as in Bordetella pertussis infection (Whooping cough).
• Common Symptoms:
  • Symptoms most likely will be related to whatever infectious process is causing the cough.
  • There will likely be a history of some upper respiratory infection followed by a chronic dry cough.
  • Pertussis - this specifically has a distinct symptom set:
    • Catarrhal phase - nonspecific symptoms including generalized malaise, rhinorrhea, and mild cough.
    • Paroxysmal phase - paroxysmal cough which are series of severe, vigorous coughs that occur during a single expiration. This is the "whooping cough"
      •  Untreated, the paroxysmal phase generally lasts two to three months then gradually transitions to the convalescent phase. (Mattoo 2005)
    • Convalescent phase -  gradual reduction in the frequency and severity of cough.
• Clue on Physical Exam:
  • In cases of upper airway infections causing chronic cough there may or may not be physical exam findings related to the infection. Diagnosis is mainly based on patient history.
• Diagnosis:
  • Chronic cough from a previuos viral illness does not necessarily require additional workup.
  • If an underlying chronic infection is suspected then serology/culture for certain viruses and bacteria can be done.

6. Medication Induced Chronic Cough

• There a few medications that can induce pathologic and nonpathologic chronic cough. (Amiodarone, Bleomycin, Aspirin - in the setting of an allergy)
• One of the more common causes of a dry persistent cough is the use of ACE inhibitors.
  • A nonproductive cough is a recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, and has been reported to occur in up to 15 percent of patients treated with these agents. (Morris 2003)
  • It is hypothesized that accumulation of bradykinin, which is normally degraded in part by Angiotensin converting enzyme, may stimulate afferent C-fibers in the airway. (Dykewicz 2004)
  • Common Symptoms:
    • Cough usually begins early after starting therapy, but the onset can be delayed up to six months.
    • Patients may experience a tickling, scratchy, or itchy sensation in the throat.
    • The cough typically resolves within one to four days of discontinuing therapy, but can take up to four weeks.
    • The cough generally recurs with rechallenge, either with the same or a different ACE inhibitor. (Irwin 2006)
    • It usually does not cause airway obstruction
      • Life threatening angioedema has been reported in association with ACE inhibitor use
      • History of ACE inhibitor-induced cough was found to be an independent risk factor for developing ACE inhibitor-related angioedema in one retrospective cohort study. (Dykewicz 2004)
  • Clues on Physical Exam:
    • Dry cough without any significant physical exam findings related to the cough.
  • Diagnosis:
    • Diagnosis is supported by eradication of cough through trial of discontinuation of medication.
  • It is noteworthy that treatment with angiotensin-converting enzyme inhibitors has been advocated in the treatment of pateints with heart failure and COPD (Horodinschi 2019)

7. Chronic Bronchitis

• This is defined as a cough and sputum production on most days over at least a three-month period for more than two consecutive years in a patient without other explanations for cough. Almost all of these patients will have a postive smoking history. (Irwin 1990)
• This will be a productive "wet" cough compared to the others on our list
• This can be associated with exacerbations and subsequent bacterial infections causing worsening shortness of breath and purulent cough.
• Common Symptoms:
  • Chronic cough productive of clear/whitish sputum
  • Dyspnea
  • Wheezing
• Clues on Physical Exam
  • Wheezing can be present on auscultation of the lungs
  • Later on in the disease there may be lung hyperinflation and evidence of increased work of breathing such as posturing and pursed lips.
• Diagnosis
  • Pulmonary function testing can be a useful tool in diagnosing chronic bronchitis.
    • This can show an obstructive pattern that won't fully correct with bronchodilator therpay.
    • GOLD guidelines support using the traditional postbronchodilator FEV1/FVC ratio less than 0.7 as the threshold that indicates airflow limitation.
  • Chest radiogaphy
    • This may show changes related to COPD such as flattening of the diaphragm or increased radiolucency of the lung

8. Bronchiectasis

• Bronchiectasis is damage to the airway caused from severe repeated inflammation.
• Because of damage there is poor mucocilliary clearance. This predisposes the airway to further inflmmation and infection.
• Common Symptoms:
  • Cough is the most common symptom. This can be dry or mucopurulent.
• Clues on Physical Exam:
  • Usually physical exam will be normal however there can be scattered changes such as wheezing and rhonchi.
• Diagnosis:
  • Diagnosis is typically first done radiographically:
    • Chest X-ray may show some thickening of the proximal airways
    • CT scan is a better modality to visualize the airways and secure a diagnosis
  • Bronchoscopy
    • This can be done to directly visualize the airway and to take microbiologic samples that can be cultured and help to formulate a treatment. (Schaefer 2003)

9. Lung Cancer

• Lung cancer is the etiology in less than 2 percent of the cases of chronic cough. (Irwin 2006) However, if there are other warning signs, then this is a diagnosis that can be considered.
• Look for a history of smoking or of some other chronic lung exposure (asbestos, asbestos, radon, arsenic, chromium, nickel, ionizing radiation) as this would support a diagnosis. (Alberg 2003)
• Symptoms:
  • Cough is present in 50 to 75 percent of lung cancer patients at presentation and occurs most frequently in patients with squamous cell and small cell carcinomas because of their tendency to involve central airways. (Kocher 2015)
    • This cough can be dry, mucoid, or bloody
    • Hemoptysis is only present in 20- 50 percent of people with lung cancer. (Kocher 2015)
  • Chest pain
  • Dyspnea
  • Fatigue
  • Weight loss
  • Pancoast tumor
  • Hoarseness - unilateral vocal cord paralysis
  • Paraneoplastic processes
• Clues on Physical Exam
  • There may be decreased breath sounds or findings related to an obstructive lung process
• Diagnosis
  • Typically diagnosis will be intially through radiographic imaging, with a high resolution CT scan being the a good modality to evaluate the lesion. Low dose CTs are used for screening purposes in patients with a smoking history.
  • PET CT scan can be useful in identifying local and metistatic spread
  • Definitive diagnosis through tumor biopsy can be done. The method by which this is performed is dependent on tumor location.
• Useful Links:
  • Unilateral Laryngeal Paralysis or Vocal Cord Paralysis

10. More Rare Causes of Chronic Cough

• Chronic granulomatous processes such as TB, fungal infections or Sarcoidosis
• Pulmonary Fibrosis - Idiopathic pulmonary fibrosis, bronchiolitis obliterans organizing pneumonia, Hypersensitivity pneumonitis
• Pneumoconiosis - such as silicosis, coal miners lung, and asbestosis
• Cardiac Causes of cough - heart failure causing pulmonary edema, premature ventricular contractions
• Lesions that compress the upper airway, including arteriovenous malformations (McLaughlin 1999) and retrotracheal masses, may present with chronic cough. (Gülmez 1999)
• Cough also can be a symptom of tracheobronchomalacia. This is from loss of the rigid support of the airways, which causes inspiratory collapse. This is more commonly seen in smokers. (Thorton 2001)
• Laryngeal sensory neuropathy has been reported as a casue of chronic cough and can be associated with laryngospasm or throat clearing. Laryngeal electromyography (of questioned value) has been supported to aid in the diagnosis in the past as has videostroboscop. (Lee 2005) Dysfunction of the vagus nerve was reported as a possible cause of cough. Termed a 'hypersensitivity syndrome' by Bowen et al (Bowen 2018), the pathophysiology was proposed to parallel plastic changes in the peripheral and central nervous system similar to the neuropathic pain of allodynia. Treatment by 'neuromodulation' with tricyclic antidepressnats (amitriptyline, nortriptyline, or desipramine), gabpentin, and tramadol have been reported. Variable response to this treatment has been reported (Bastian 2015)
  • Dicpinigaitis et al. (2019) identified testing for 'Arnold nerve reflex'
    • Testing: stimulation of the external auditory canal of each ear with a cotton-tipped applicator - cough occurring within 10 seconds of stimulation considered as induced by the intervention
    • Arnold's never reflex present in 23.3% of adults with chronic cough and in 2% in healthy adults and children
    • Authors interpret this data as support for the concept of "Cough Hypersensititivy Syndrome"
  • Gefipixant (Lyfnua®) is a medication under study for 'refractory cough' or 'unexplained chronic cough' that was reported by Markham (2022) as being approved for marketing in Japan as of Jan 20, 2022.
    • this orally administered medication - blocks the P2X3 receptors (P2X3 receptor antagonist) with the most common side effect (63.1%) being taste disturbance in a dose dependent fashion 
• Irritation of the external auditory canal can be an unusual cause of a chronic cough. This is caused by the Arnold's nerve cough reflex. (Jegoux 1993)
• Psychogenic cough, or a tic disorder with cough are other possible causes.
• Autoimmune processes affecting the lungs - Rhuematoid arthritis, Wegners Granulomatosis, Goodpasture Syndrome

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