The causes of cough are numerous and can be multifactorial. The etiology of a cough can be sought out by a careful history, diagnostic tests, and response to treatment. The most common causes of cough are upper airway cough syndrome, previously known as postnasal drip syndrome, asthma, and gastroe-sophageal reflux disease.
The American College of Chest Physicians’ Evidence-Based Clinical Practice Guidelines concluded from four prospective studies that these three etiologies comprised greater than 92% of patients with cough (who had normal chest radiographs, were nonsmokers and not on angiotensin-converting enzyme inhibitors).
Upper Airway Cough Syndrome (Postnasal Drip Cough)
Upper airway cough syndrome, or postnasal drip syndrome, is the most common cause of cough. The physical drainage of nasal mucus down the posterior pharynx to the larynx and upper airway induces cough. Upper airway cough syndrome includes allergic, nonallergic, and infectious rhinitis. Note that the cough may be due to more than one of these etiologies. The strategy is to discern the primary and secondary causes. The history that suggests upper airway cough syndrome includes tickling of the throat, hoarseness, throat clearing, and congestion of the throat. This type of postnasal drip cough is often alleviated by drinking or eating. The action of swallowing causes the reflexive closure of the epiglottis. A closed epiglottis shunts the postnasal drip to the esophagus bypassing the posterior pharynx and larynx. This may be the main reason why taking a cough drop and drinking water both help relieve symptoms of cough.
Allergic rhinitis affects as many as 20% to 25% of the population. It is defined as an inflammatory response of the nasal mucosa to airborne antigens. This action is mediated by an IgE antibody. Allergic rhinitis often presents as postnasal drip, nasal congestion, rhinorrhea, and eustachian tube dysfunction. Postnasal drip causes both mechanical and inflammatory mediators to trigger the cough reflex in the larynx and trachea.
Table. Respiratory innervations.
| Location |
Innervations |
| Pharynx |
Glossopharyngeal nerve and branch of superior laryngeal nerve |
| Larynx |
Superior and recurrent laryngeal nerves |
| Trachea and Bronchi |
Rapid adapting receptor
(rapid adapting receptor) Slowly adapting stretch
receptors (SARs) C Fibers |
Table. Causes of cough.
| Upper airway cough syndrome (upper airway cough syndrome)
(postnasal drip cough) |
| Allergic rhinitis |
| Nonallergic rhinitis |
| Vasomotor rhinitis |
| Nonallergic rhinitis with eosinophilia syndrome
(nonallergic rhinitis with eosinophilia syndrome) |
| Rhinitis medicamentosa |
| Gustatory rhinitis |
| Infectious rhinitis/sinusitis |
| Pertussis |
| Mycoplasma |
| Chlamydia |
| Irritant inhalation (e.g., tobacco smoke, noxious fumes) |
| Angiotensin-converting enzyme inhibitor (angiotensin-converting enzyme inhibitors)
cough |
| Asthma |
| Cough variant asthma (Cough variant asthma) |
| Nonasthmatic eosinophilic bronchitis |
| Gastroesophageal reflux disease (gastroe-sophageal reflux disease) |
| Pulmonary infection |
| Bronchitis |
| Pneumonia |
| Tuberculosis |
| Chronic obstructive pulmonary disease
(COPD)/emphysema |
| Aspiration/foreign body obstruction |
| Congestive heart failure |
| Pulmonary embolism |
| Interstitial lung disease |
| Bronchiectasis |
| Cystic fibrosis |
| Sarcoidosis |
| Vasculitis |
| Respiratory tumors |
| Anatomic abnormality of the larynx/trachea |
| Psychogenic cough |
The history attained from the patient can usually be subdivided into seasonal versus perennial symptoms. Patients who suffer from these symptoms in spring are affected by grass and tree pollen. Symptoms occurring during the fall are typically caused by weed pollen. The perennial symptoms are usually triggered by dust mites, animal proteins, and mold spores. Itching of the nose and eyes is the key symptom that distinguishes allergic rhinitis from other causes. Although sneezing is an associated symptom, it is not unique to allergic rhinitis. Sneezing can be due to infectious, mechanical, or chemical nasal irritation.
Physical examination findings that may help in ascertaining allergic rhinitis include the appearance of posterior pharynx “cobblestoning” and/or observation of mucus draining down the posterior pharynx. Tests such as allergy skin tests and the radioallergosorbent test (radioallergosorbent test) can help establish or rule out allergic causes. However, allergy testing alone without a clinically significant history will lead to an inaccurate diagnosis. Ultimately, the use of a daily intranasal corticosteroid for 2 weeks is the most practical solution for discerning allergic rhinitis from other causes. If symptoms improve, then the likely cause is allergic rhinitis. Asking the patient to assign a percentage of improvement with this therapy is helpful in modifying the treatment plan. If the patient is still symptomatic after using the intranasal corticosteroid, adjunctive therapy with a daily leukotriene receptor antagonist for an additional 2 weeks may be beneficial.
Nonallergic Rhinitis and Cough
A significant etiology of chronic cough that is often overlooked is nonallergic rhinitis with postnasal drip. It encompasses vasomotor rhinitis, nonallergic rhinitis with eosinophilia syndrome, rhinitis medicamentosa, and gustatory rhinitis. Nonallergic rhinitis is usually perennial, triggered by irritants, and has negative IgE allergy skin tests or radioallergosorbent test.
Vasomotor Rhinitis
Vasomotor rhinitis is defined as rhinorrhea, nasal congestion, and postnasal drip cough caused by nasal mucosal autonomic nerve instability or dysfunction. The autonomic nerve instability causes vasodilation and vascular leakage leading to mucosal edema as well as triggering an overproduction of mucus. The stimuli for vasomotor rhinitis usually consist of physical and chemical irritants. These common irritants include odors, smoke, fumes, changes in temperature, and changes in barometric pressure/humidity. A positive correlation between the patient’s history and exposure to the irritants is the key to diagnosing this entity. Avoidance of the offending agent, if possible, is the first course of action. However, if this is not possible, medications can serve as a diagnostic tool as well as a treatment option.
If nasal congestion is elicited in the patient’s history, the use of azelastine nasal spray two puffs per nostril twice a day for a 2-week trial would be in order. If the nonallergic rhinitis symptom is mostly rhinorrhea, then a 2-week trial of nasal ipratropium bromide, 0.03% or 0.06% one to two puffs per nostril up to four times a day, would reduce mucus production.
Nonallergic rhinitis with eosinophilia syndrome
Nonallergic rhinitis with eosinophilia syndrome occurs when eosinophils are found in the nasal mucosa. This syndrome has all of the symptoms of vaso-motor rhinitis with the addition of itching of the nose and eyes. The IgE allergy skin test or radioallergosorbent test is negative in nonallergic rhinitis with eosinophilia syndrome. A nasal swab for eosinophils is conducted with Hansel’s stain to help make the diagnosis. nonallergic rhinitis with eosinophilia syndrome is treated with an intranasal corticosteroid to inhibit the eosinophils and inflammatory mediators.
Rhinitis Medicamentosa
Rhinitis medicamentosa is defined as paradoxical nasal congestion due to the overuse of topical nasal vasoconstrictors (e.g., oxymetazoline). The long-term use of topical vasoconstrictors (typically alpha agonists) can cause tachyphylaxis or a need for more of the drug to maintain the effect that was initially attained with the medication. Withdrawal of the topical vasoconstrictor causes a rebound vasodilatory effect, which leads to nasal congestion. Associated with this phenomenon is a postnasal drip cough due to overproduction of mucus. The treatment is cessation of the topical nasal vasoconstrictor. It may take up to 2 weeks before the congestion resolves completely.
Gustatory Rhinitis
Gustatory rhinitis is rhinorrhea, nasal congestion, and/or postnasal drip caused by the act of eating or drinking. This is a vagal reflex that causes vasodilation of the nasal mucosa and an increase in mucus production. Rhinorrhea is the most common symptom, and ipratropium bromide nasal spray is the drug of choice. Again, if there is a nasal congestion component, azelastine may be helpful.
Infectious Rhinitis and Cough
Infectious postnasal drip cough can occur with viral infection, sinusitis, and/or from a postinfectious cause. Patients who have viral infections experience malaise, clear mucus drainage, nasal congestion, postnasal drip cough, myalgia, and sometimes fevers. Treatment using saline rinses, decongestants and mucolytics usually help resolve symptoms of cough in a couple of weeks. If coughing persists, bacterial sinusitis needs to be considered.
Bacterial sinusitis can be diagnosed with a history of purulent drainage that persists for longer than 10 days and sometimes with symptoms of maxillary tooth pain. Sinus radiographs or computed tomography scans tend to be the studies of choice. The common bac-terias associated with sinusitis are Streptococcus pneumonia, Haemophilus influenzae, and Moraxella catarrhalis in children. In chronic sinusitis, anaerobic bacteria may play a role. The treatment method should consist of a three-step approach:
1. Decrease nasal mucosa swelling with intranasal corticosteroid with or without a short burst of oral steroids to allow for proper mucus drainage.
2. Loosen up thick mucus with a mucolytic (e.g., guaifenesin).
3. Neutralize the bacteria with the appropriate antibiotic (e.g., amoxicillin or penicillin alternative).
Acute sinusitis requires 2 weeks of treatment; chronic sinusitis requires 4 to 6 weeks of treatment. If a sinus radiograph or computed tomography sinus is positive, and the patient does not respond to antibiotics, fungal sinusitis needs to be considered. Fungal sinusitis requires surgical resection.
Postinfectious cough can comprise 11% to 15% of upper respiratory tract infections. This is the type of cough that lingers for longer than 3 weeks. It usually resolves before the eighth week of symptoms. The two organisms of interest are Bordetella pertussis and Mycoplasma pneumoniae. Although culturing or antibody titers can be attempted, a trial of an oral macrolide for 2 weeks would be the most practical course of action.
Angiotensin-Converting Enzyme Inhibitor Cough
With the rise of diabetes and hypertension in the general population, the use of angiotensin-converting enzyme inhibitors has become more prevalent. It can cause a persistent cough in up to 35% of its users. The mechanism is believed to be the inhibition of ACE, which normally degrades bradykinin and substance P. These mediators induce upper airway cough. This class of medications is unusual because the cough can occur much later after the initial use of the medication. The cough may take up to 3 months to resolve after discontinuation of the angiotensin-converting enzyme inhibitors.
Asthma and Cough
Cough is one of many symptoms associated with asthma. However, there tends to be an overdiagnosis of asthma as the cause of chronic cough. The definition of asthma can be elusive. Its most basic definition is hyperresponsive airway disease that is reversible. This hyperresponsive airway is driven most of the time by chronic inflammation of the bronchioles triggered by atopic, physical, or chemical irritation. The chronic inflammatory mediators then cause bronchial smooth muscle constriction and an overproduction of mucus that necessitates clearing the airway with coughing.
Although symptoms of cough, dyspnea, and wheezing may suggest asthma, the need for allergy skin tests/radioallergosorbent test, pulmonary function tests, and response to treatment are important. Spirometry with pre- and post-short-acting bronchodilator agents (e.g., albuterol) showing a forced expiratory volume in 1 second (FEV,) increase of greater than 12% and 200 mL is a practical approach to showing reversible airway disease. However, if the patient is not actively having bronchospasm, the spirometry may yield a normal result. A better and more definitive test is a methacholine challenge. This test induces airway reactivity if the patient has underlying asthma. Patients are given increasing sequential doses of methacholine, and spirometry is administered after every dilution. A provocative concentration that causes a 20% reduction from the baseline forced expiratory volume in the first second (PC20FEV,) or a decrease in specific conductance of 35% to 45% from the baseline at less than 16 mg/mL of methacholine is considered a positive methacholine challenge.
An adequate trial of asthma medications is the last step to diagnosing asthma, after having considered and treated upper airway cough syndrome and other potential causes of cough. An inhaled corticosteroid used on a daily maintenance schedule with or without a long-acting beta agonist is the drug of choice depending on severity. If the patient has a severe cough or shortness of breath, using a trial of pred-nisone, 40 mg once a day for 7 days, will help control the inflammation more efficiently. Leukotriene receptor antagonists can also be added later, if symptoms persist.
Cough Variant Asthma
Cough variant asthma is a subset of asthma that can present as cough alone with a normal physical examination and a normal spirometry. Patients with Cough variant asthma tend to have a more sensitive cough reflex but less bronchial reactivity when compared to classic asthmatics. A methacholine challenge may assist in confirming bronchial reactivity, but it does not necessarily establish the diagnosis of Cough variant asthma. The definitive diagnosis depends on resolution of symptoms after being treated with asthma medications.
Nonasthmatic Eosinophilic Bronchitis
Nonasthmatic eosinophilic bronchitis is a steroid responsive chronic cough found in nonsmokers who have sputum eosinophils without variable airflow obstruction. The sputum should contain a nonsquamous cell sputum eosinophil count of greater than 3%. Methacholine challenges in patients with no asthmatic eosinophilic bronchitis usually yield a normal result. It can be associated with occupational exposures as well as allergens. The treatment is avoiding offending agents and using asthma anti-inflammatory medications.
Gastroesophageal Reflux Disease and Cough
Gastroesophageal reflux disease frequently causes a persistent cough. It is defined as a retrograde movement of gastric material from the stomach to the esophagus. Common symptoms of gastroe-sophageal reflux disease include heartburn, regurgitation, sour taste in the back of the mouth, and coughing. In a normal individual, it can occur 50 times a day. Some studies suggest that the patient may not detect symptoms of gastroesophageal reflux disease 75% of the time.
Gastroesophageal reflux disease causes cough in two ways. Gastric material (frequently acid) can make its way up the esophagus to the larynx and cause direct irritation. However, this is not always necessary. Acid or other caustic agents (e.g., pancreatic enzymes or bile) can irritate the distal esophagus. This stimulation of the vagal reflexes can cause bronchoconstriction or cough. The diagnostic procedures that may be helpful are 24-hour esophageal pH monitoring and barium esophagography. The 24-hour esophageal pH monitoring is the most sensitive and specific test for measuring acid in the esophagus. However, by itself this test does not establish causation. Barium esophagography helps determine if there is an esophageal lesion from nonacid gastroe-sophageal reflux disease. Perhaps the most helpful information for diagnosing gastroe-sophageal reflux disease is a significant resolution of the persistent cough after a 1- to 3-month trial of antireflux treatment. The preferential choice of antireflux treatment is a proton pump inhibitor. This therapy would then be followed by changes in diet and lifestyle modifications to reduce acid production.