TOC | Pulm

Chronic Cough                          See:  Chronic_cough.htm  

Common causes of Chronic Cough:    (Negative chest x-ray or Chest CT scan)
  • Post nasal drip
  • Asthma (cough-variant) ,  Bronchospasm  , Bronchial hyperreactivity  
  • GE reflux
  • Post-viral infection bronchial hyperreactivity  
  • Angiotensin converting enzyme inhibitors
  • Rhinitis - perennial, vasomotor rhinitis, allergic rhinitis, post viral rhinitis
  • Occupational/environmental irritants
  • Chronic sinusitis
  • Chronic bronchitis (history of smoking)
  • Bronchiectasis
  • One or more of the above in combination                                         

Less common causes of cough: (less than 6% of all cases)

  • pertussis
  • aspiration/ aspiration secondary to a Zenker's diverticulum
  • occult pulmonary infection
  • industrial bronchitis
  • intraluminal or extraluminal mass affecting the trachea and bronchi
  • interstitial lung disease (sarcoidosis); lymphangitic carcinomatosis (breast)
  • occult congestive heart failure
  • disorders of external auditory canals, diaphragms, the pleura or pericardium
  • disorders of the esophagus or stomach, nasal polyps
  • esophageal cyst, endobronchial sutures, rhinoliths, hair touching eardrum
  • Tourette's Syndrome, Sjogren's syndrome (xerotrachea)
  • neurolemma of vagus nerve
  • uvular or tonsilar enlargement
  • thyroid disorders
  • psychogenic cough

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REF: the Virtual Hospital Home Page - U. of Iowa

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Ref: Bope: Conn's Current Therapy 2010

Cough is among the most common presenting complaints of outpatients in the United States. It serves as a protective reflex against foreign material and as a method to clear secretions from the airway. The cough center is located in the medulla, and the cough reflex is mediated by way of multiple nervous system pathways including the trigeminal, glossopharyngeal, vagus, and phrenic nerves.

Angiotensin-converting enzyme (ACE) inhibitors increase cough reflex sensitivity and have been shown to decrease the risk of pneumonia in patients with cerebrovascular accidents.

Cough can be subcategorized into acute and chronic cough, and post-upper respiratory infection persistent cough.
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Acute Cough

Acute cough may be defined as cough that has been present for less than 8 weeks. Because all causes of chronic coughs initially cause acute symptoms, patients with acute cough may actually have cough caused by one of the etiologies discussed later in this section; however, acute cough more commonly is the result of a less indolent process.

Causes of Acute Cough  < 8 weeks.

  • Upper respiratory infections: most commonly viral etiology (the common cold) ;  
    - Infectious etiologies are a frequent cause of acute cough. Most acute cough is the result of viral infections, specifically the common cold. Most cough resulting from the common cold is self-limited and lasts less than 3 weeks.  
    Bronchitis or pneumonitis

  • Acute sinusitis (usually viral, occasionally bacterial)

  • Exacerbation of chronic obstructive pulmonary disease  

  • Allergic rhinitis

  • Bordetella Pertussis infection
    - In subjects with cough and vomiting, known exposure to a case of B. pertussis, or in the presence of a B. pertussis epidemic in the community, empiric therapy for this illness should be pursued.

  • Noninfectious processes that lead to acute cough include allergic rhinitis, congestive heart failure, asthma, and aspiration.

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Postinfectious Cough
Postinfectious cough begins with an acute upper respiratory tract infection but persists following the resolution of the other acute symptoms. Postnasal drip syndrome may present following the common cold or sinusitis. Bronchospasm may lead to postinfectious cough either as a result of a single episode of postinfectious wheezing or an exacerbation of underlying asthma. Postinfectious cough may be the initial presentation of asthma.

Causes of Postinfectious Cough

  • Postnasal drip syndrome

  • Bronchospasm

  • Bordetella pertussis infection

  • Bacterial sinusitis

  • Mycoplasma pneumoniae/Chlamydia pneumoniae infection

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Causes of Chronic Cough
- Most non-smoker patients with problematic, persistent cough have multiple etiologies
  • 1. Postnasal drip syndrome

  • 2. Asthma

  • 3. Gastroesophageal reflux disease (GERD)  
    - These top three etiologies are the most common cause of chronic cough regardless of patient age. In nonsmokers with a normal chest radiograph who are not taking an ACE inhibitor, these three etiologies alone or in combination are the cause of more than 85% of chronic cough .

  • 4. Post-infectious Cough

  • 5. Angiotensin-converting enzyme inhibitors

  • 6. COPD, Chronic bronchitis, Eosinophilic bronchitis  

  • 7. Eosinophilic bronchitis   

Occasionally, chronic cough may be the result of:

  • Bronchogenic carcinoma

  • Metastatic carcinoma

  • Bronchiectasis

  • Sarcoidosis

  • Pulmonary fibrosis

  • Pneumoconiosis

  • Hypersensitivity pneumonitis

  • Congestive heart failure

  • Chronic infection, such as tuberculosis or Mycobacterium avium complex

  • Recurrent aspiration because of pharyngeal or esophageal abnormalities

* Habit cough and psychogenic cough
are diagnoses of exclusion (Grade III). The character of the cough ( eg, honking or barking) is not diagnostically helpful in adults (Grade II-2). However, the pediatric literature suggests that honking and barking coughs are consistent with psychogenic cough (Grade III). After exclusion of other causes, psychological counseling and short-term antitussive therapy may be appropriate for psychogenic cough (Grade III).

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Approach to Chronic Cough Patients:                chronic_cough_approach.htm  

All Patients Presenting With Cough

  • Perform thorough history and physical examination.

  • Review timing and nature of cough along with exacerbating or mitigating factors.

  • Review prior history of cough, allergies, asthma, or gastroesophageal reflux.

  • Take medication history, particularly use of ACE inhibitors.

  • Focus physical examination on head, neck, and thorax.

Patients With Postinfectious or Chronic Cough  

  • Obtain chest radiograph, particularly in patients with an abnormal respiratory examination.

  • Evaluate airflow obstruction with spirometry.

  • Stop ACE inhibitors and assess for improvement.

  • Administer empiric therapy for postnasal drip, asthma, or gastroesophageal reflux.

  • Consider methacholine challenge testing to evaluate for airway hyperreactivity.

  • Induce sputum for eosinophils or empiric trial of corticosteroids for eosinophilic bronchitis.

  • If cough persists, consider esophagoscopy, 24-hour pH probe monitoring, high-resolution chest CT, or bronchoscopy.

  • Abbreviations: ACE = angiotensin-converting enzyme; CT = computed tomography.

Common Diagnostic Tests for Chronic Cough:

  • Chest xray

  • Pulmonary Function Test

  • Chest CT scan

  • Sinus CT scan  

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Treatment of Acute Cough
  • Common cold: Supportive care with dexbrompheniramine, 6mg, and pseudoephedrine, 120mg (Drixoral Cold and Allergy Tablets); or ipratropium nasal spray (Atrovent, 0.06%), two 42-mcg sprays in each nostril 3 times daily for 4 to 7d depending on duration of symptoms.

  • Acute sinusitis: Treat as a common cold. Add oxymetazoline (Afrin), two sprays twice daily for three days. If symptoms persist, consider antibiotic therapy directed against Haemophilus influenzae and Streptococcus pneumoniae such as azithromycin (Zithromax), 500mg daily for 3d.

  • Exacerbation of chronic obstructive pulmonary disease: Antibiotics directed against H. influenzae and S. pneumoniae for 3 to 7d such as clarithromycin (Biaxin), 500mg twice daily for 7d; systemic corticosteroids such as prednisone (Deltasone), 40mg tapered over 10d; inhaled anticholinergics such as tiotropium (Spiriva), one inhalation daily; and short-acting ß-agonists such as albuterol (Proventil), two inhalations every 4h as needed; smoking cessation.

  • Allergic rhinitis: Nasal corticosteroids such as mometasone (Nasonex), two sprays in each nostril daily; nonsedating antihistamines such as fexofenadine (Allegra), 180mg daily; allergen avoidance if possible.

  • Bordetella pertussis: Erythromycin 500mg four times daily for 14d or trimethoprim 160mg/sulfamethoxazole (Bactrim DS),[1] 800mg twice daily for 14d. Other macrolide antibiotics such as azithromycin (Zithromax)[1] or clarithromycin (Biaxin)[1] are likely effective and may be better tolerated.


Treatment of Postinfectious Cough

  • Postnasal drip syndrome: Dexbrompheniramine, 6mg, and pseudoephedrine (Drixoral Cold and Allergy Tablets), 120mg for up to 3wk; ipratropium (Atrovent), 0.06% nasal spray for up to 3wk; azelastine (Astelin) nasal spray (137mcg), two sprays each nostril twice daily for up to 3wk.

  • Bronchospasm: Inhaled corticosteroid such as budesonide (Pulmicort),[1] two inhalations daily with or without inhaled long-acting ß-agonist such as formoterol (Foradil), two inhalations twice daily; short-acting ß-agonist such as albuterol (Ventolin), two puffs every 4h as needed. Oral steroids such as prednisone (Deltasone), 40mg tapered over 10d.

  • Bordetella pertussis: Erythromycin, 500mg four times daily for 14d, or trimethoprim 160mg/sulfamethoxazole, 800mg (Bactrim DS)[1] twice daily for 14d. Other macrolide antibiotics such as azithromycin (Zithromax)[1] or clarithromycin (Biaxin)[1] are likely effective and may be better tolerated.

  • Bacterial sinusitis: Dexbrompheniramine, 6mg, and pseudoephedrine (Drixoral Cold and Allergy Tablets), 120mg for up to 3wk; oxymetazoline (Afrin), two sprays twice daily for 3d; azithromycin (Zithromax), 500mg daily for 3d.

  • Chlamydia/mycoplasma: Clarithromycin (Biaxin), 500mg twice daily for 14d.


Treatment of Chronic Cough

  • Postnasal drip syndrome

    • Nonallergic: Dexbrompheniramine, 6mg, and pseudoephedrine (Drixoral Cold and Allergy Tablets), 120mg for up to 3wk; ipratropium (Atrovent), 0.06% nasal spray for up to 3wk; azelastine (Astelin) nasal spray (137mcg), two sprays each nostril twice daily for up to 3wk.

    • Allergic: Fluticasone (Flonase) (50mcg), two sprays each nostril daily; fexofenadine (Allegra), 180mg daily; allergen avoidance.

  • Asthma: Albuterol (Proventil), two puffs every 4 hours as needed; inhaled corticosteroid such as budesonide (Pulmicort), two inhalations daily with or without inhaled long-acting ß-agonist such as formoterol (Foradil), two inhalations twice daily; combination of long-acting ß-agonist and inhaled steroid such as fluticasone/salmeterol (Advair) (100/50mcg), inhaled twice daily; montelukast (Singulair), 10mg daily; prednisone (Deltasone), 40mg daily with tapering dose over 10d.

  • Gastroesophageal reflux: Dietary and lifestyle modifications, lansoprazole (Prevacid), 30mg daily for up to 3mo; metoclopramide (Reglan), 10mg before meals and sleep.

  • Eosinophilic bronchitis: Fluticasone (Flovent)[1] (110mcg), two inhalations twice daily; prednisone (Deltasone), 30mg daily for 3wk.
    1 Not FDA approved for this indication.

  • ACE inhibitor: Discontinue medication.

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Postnasal Drip Syndrome (PNDS),
either singly or in combination with other conditions, is the single most common cause of chronic cough for which patients seek medical attention (Grade II-2). The symptoms and signs of PNDS are nonspecific (Grade II-2); therefore, a definitive diagnosis of PNDS-induced cough cannot be made from history and physical examination alone. A favorable response to specific therapy for PNDS, with resolution of cough, is a crucial step in confirming that PNDS is present and is the etiology of cough. The combination of a first-generation antihistamine and a decongestant is considered to be the most consistently effective sole form of therapy in treating most patients with PNDS-induced cough not due to sinusitis (Grade II-2). In most patients, some improvement in cough will be seen within 1 week of initiation of therapy. Newer-generation, relatively nonsedating antihistamines have been found ineffective in treating acute cough associated with the common cold (Grade I) and are not as effective as first-generation antihistamines in treating PNDS secondary to nonallergic conditions. The first-generation antihistamines should be used preferentially to treat PNDS-induced cough that is nonhistamine-mediated (Grade I, II-2).

Asthma
is a common cause of chronic cough. A diagnosis of cough-variant asthma is suggested by the presence of airway hyperresponsiveness, and confirmed only when the cough resolves with asthma medications. The treatment of cough-variant asthma is the same as for asthma presenting with other symptoms. Inhaled medications prescribed for asthma may worsen the cough.

GERD
can cause cough by aspiration, but it most likely causes chronic cough in patients with normal radiographs by a vagally mediated reflex mechanism (Grade II, II-2). When GERD is the cause of chronic cough, GI symptoms are often absent (Grade II-2). Twenty-four-hour esophageal pH monitoring is the most sensitive and specific test for GERD. In interpreting the test, it is important to assess the duration and frequency of reflux episodes, and the temporal relationship between reflux and cough episodes. Patients with normal standard reflux parameters may still have reflux as a cause of cough if a temporal relationship exists (Grade II-2). When 24-h esophageal pH monitoring cannot be done, an empiric trial of antireflux medication is appropriate when GERD is suspected as a cause of cough. However, if empiric treatment fails, GERD cannot be ruled out until objective studies are conducted (Grade III) because the empiric therapy may not have been intensive enough or medical therapy may have failed. Because minimum consistently effective therapy for GERD-induced chronic cough is not known, initial treatment should include diet and lifestyle changes in addition to drugs. Cough due to GERD has been reported to resolve with medical therapy in 70 to 100% of patients; mean time to recovery may take as long as 169 to 179 days (Grade II-2). Antireflux surgery may be considered after intensive medical therapy has been documented to have failed.

Chronic bronchitis
Cough is a principal feature of chronic bronchitis (CB) and its treatment should chiefly be directed to reduction of sputum production and airway inflammation ( eg, by smoking cessation and removal of environmental irritants) (Grade II-2). While CB is among the most frequent causes of chronic cough in the community, it is the cause in only about 5% in series of patients who seek medical attention for cough. Ipratropium can decrease sputum production and cough (Grade I). Nonspecific cough suppressants should be avoided, and mucolytics are of uncertain benefit. Although the effectiveness of systemic corticosteroids and antibiotics on cough have not been specifically studied, they are likely to be helpful in decreasing cough during exacerbations of COPD (Grade III).

Bronchiectasis
is a cause of chronic cough in a relatively small number of patients; the diagnosis is established by clinical history, chest radiograph, high-resolution CT scan of the thorax, and cough disappearance with specific therapy. Cough associated with flares of the disease can be treated with a combination of chest physiotherapy, drugs to stimulate mucociliary clearance, and systemic antibiotics (Grade II-2). Inhaled antibiotics are recommended only in cystic fibrosis (CF) patients with bronchiectasis (Grade I).

Postinfectious cough
is a diagnosis of exclusion; it should be considered when a patient complains only of cough after a respiratory tract infection and has a normal chest radiograph. Postinfectious cough ultimately resolves over time; oral corticosteroids (Grade II-3), inhaled corticosteroids (Grade III), or ipratropium bromide (Grade I) may attenuate the cough.

Bronchogenic carcinoma
Coughs that develop for the first time and last for months in susceptible groups are suggestive of bronchogenic carcinoma. Bronchogenic carcinoma is not a common cause of chronic cough (Grade II-2), and is very unlikely in never-smokers (Grade II-2). Present or prior cigarette smoking or occupational exposures increase the risk. Chest radiographs, sputum cytology, and flexible bronchoscopy are the most important initial tests for evaluating bronchogenic carcinoma as a cause of chronic cough.

ACE-Inhibitors
Cough due to ACE-Inhibitors   is a class effect of these drugs and is not dose-related. The cough is typically nonproductive and is associated with an irritating, tickling, or scratchy sensation in the throat. ACEI-induced cough may appear hours to weeks or months after ACEI is started (Grade II). Because no laboratory test predicts who will have ACEI-induced cough, the diagnosis should be considered in any patient who has a cough while taking an ACEI (Grade III). Cough due to ACEIs will disappear or substantially improve within 4 weeks of discontinuing the drug (Grade I); definitive treatment of ACEI-induced cough is discontinuation of the drug.

Habit cough and psychogenic cough
are diagnoses of exclusion (Grade III). The character of the cough ( eg, honking or barking) is not diagnostically helpful in adults (Grade II-2). However, the pediatric literature suggests that honking and barking coughs are consistent with psychogenic cough (Grade III). After exclusion of other causes, psychological counseling and short-term antitussive therapy may be appropriate for psychogenic cough (Grade III).

Chronic interstitial pulmonary disease
is an uncommon cause of cough; treatment of such cough is based on treatment of the underlying condition. If this treatment fails to resolve the cough, the cough may still be treatable with specific therapy for other comorbid conditions. The most common causes of chronic cough should be investigated before antitussives are prescribed (Grade III).

In children, asthma, upper and lower respiratory tract infections, and GERD are the most common causes of acute and chronic cough. Less common causes of cough in children are congenital anomalies, aspiration and environmental exposures. The approach to managing chronic cough in children is similar to the approach in adults (Grade III). Diagnostic testing may be limited because many children are unable to cooperate in testing, and positive tests do not necessarily establish diagnosis or predict a favorable response to specific therapy (Grade III). A chest radiograph should be obtained in nearly all children with chronic cough to rule out lower respiratory tract and cardiac pathology (Grade III). A sweat test for CF may be considered when no clear etiology for cough is established. The recommended diagnostic approach to cough in children is history, physical examination, and determination of a most likely etiology (Grade III).

The cause of chronic cough can be determined in most patients; specific therapy will be successful in the majority of patients when chronic cough is evaluated in a systematic manner. Guidelines and algorithms for evaluating acute and chronic cough in immunocompetent and immunocompromised adults, and children, with diagnostic caveats, are presented in the body of this report.

Pharmacologic treatment of cough is either

Antitussive therapy is indicated when cough serves no useful function such as clearing the airways. Specific antitussive therapy is directed at the etiology or mechanism causing cough ( eg, cigarette smoking, postnasal drip). Nonspecific antitussive therapy is directed at the symptom rather than the etiology or mechanism. Because of the high probability of being able to determine the causes of cough and prescribe specific treatment that can be successful, there is a limited role for nonspecific antitussive treatment (Grade II-2, II-3). It is indicated (Grade III) when specific therapy has not had a chance to work or will not work ( eg, inoperable lung cancer).

Protussive therapy is indicated when cough performs a useful function and needs to be encouraged ( eg, in bronchiectasis, CF). Although hypertonic saline, amiloride, and terbutaline by aerosol following chest physiotherapy have been shown to increase cough clearance (Grade I), or cough clearability in the case of amiloride, their clinical utility remains to be determined in future studies that assess short-term and long-term effects of these agents on the patient’s condition. Hypertonic saline in CF appears promising.


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