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Chronic Cough

para>Children with chronic cough not responsive to an inhaled β-agonist and without overt stressors should undergo spirometry (if age-appropriate) and foreign body evaluation (CXR).  
Initial Tests (lab, imaging)
  • Evaluation will be dictated by findings in the comprehensive history and physical.
  • Evaluation of peak flow may be indicated.
  • If considering neoplasm, heart failure, or infectious etiologies, CXR or B-type natriuretic peptide (BNP) may be indicated.
  • In cases of failure to respond to initial trial of empiric therapy, CXR may also be beneficial.

Follow-Up Tests & Special Considerations
  • Examples:
    • If considering chronic obstructive pulmonary disease (COPD), asthma, or restrictive lung disease: spirometry
    • If suspicious of cystic fibrosis: sweat chloride testing
    • If suspicious of hypereosinophilic syndrome, tuberculosis, or malignancy: sputum for eosinophils and cytology
  • If abnormal CXR, suspected neoplasm, or underlying pulmonary disorder, consider a chest CT.
  • Consider pulmonary consultation.
  • Refer to gastroenterologist for endoscopy.

Diagnostic Procedures/Other
If diagnosis suggested and inadequate response to initial measures, other procedures can be considered:  
  • Pulmonary function testing
  • Purified protein derivative (PPD) skin testing
  • Allergen testing
  • 24-hour esophageal pH monitor
  • Bronchoscopy, if history of hemoptysis or smoking with normal CXR
  • Endoscopic or video fluoroscopic swallow evaluation or barium esophagram
  • Sinus CT
  • Ambulatory cough monitoring and cough challenge with citric acid, capsaicin, or other bronchodilator (at specialized cough clinic)
  • Echocardiogram

Test Interpretation
Specific to underlying cause  

TREATMENT


  • With chronic cough, empiric treatment should be directed at the most common causes as clinically indicated (UACS, asthma, GERD) (2)[C].
  • Oral antihistamine/decongestant therapy with a 1st-generation antihistamine or nasal steroid spray can be used as initial empiric treatment (2)[C].
  • In patients with cough associated with the common cold, nonsedating antihistamines were not found to be effective in reducing cough (2)[C].
  • In stable patients with chronic bronchitis, therapy with ipratropium bromide may reduce chronic cough (3)[C].
  • Centrally acting antitussive drugs (dextromethorphan, hydrocodone) may be used for short-term symptomatic relief of coughing in patients with chronic bronchitis but have limited efficacy in cough due to upper respiratory infections (3)[C].
  • For cough associated with lung cancer, narcotic cough suppressants are recommended (3)[C].
  • The American Academy of Pediatrics does not recommend central cough suppressants for treating any kind of cough (2)[B].
  • In children <14 years, when pediatric recommendations are not available, adult recommendations should be used with caution (2)[C].
  • Some children with recurrent cough and no evidence of airway obstruction may benefit from an inhaled β-agonist (4)[C].
  • In infants and children with nonspecific chronic cough, trials of empiric PPI therapy were not effective (5)[C].

GENERAL MEASURES


  • In patients with chronic cough, considerations for potential etiology should include asthma (2)[B] or UACS (2)[C].
  • With concomitant complaints of heartburn and regurgitation, GERD should be considered as a potential etiology (2)[C].
  • 90% of patients will have resolution of cough after smoking cessation (2)[A].
  • When indicated, ACE inhibitor therapy should be switched in patients in whom intolerable cough occurs (3)[A]. It may take several days or weeks for cough to resolve after stopping ACE inhibitor therapy.
  • Empirically treat postnasal drip and GERD.
  • Consider nonpharmacologic options, such as warm fluids, hard candy, or nasal drops. In infants and children, try clearing secretions with a bulb syringe.
  • Attempt maximal therapy for single most likely cause for several weeks, then search for coexistent etiologies.

MEDICATION


  • Treatments (nasal steroids, classic antihistamines, antacids, bronchodilators, inhaled corticosteroids, PPIs, antibiotics) should be directed at the specific cause of cough.
  • If history and physical exam suggest GERD, may want to trial H2 blocker or PPI therapy prior to further diagnostic testing.
  • A comparative effectiveness review of 49 studies with common opioid and nonanesthetic antitussives stated there is some efficiency for treating cough in adults, but evidence is limited (6)[C].
  • The FDA issued a public health advisory stating that OTC cough and cold medicines, including antitussives, expectorants, nasal decongestants, antihistamines, or combinations, should not be given to children <2 years. Subsequently, manufacturers have changed labeling to state "do not use" in children <4 years. National estimates have shown a decline in emergency department visits in children <2 years related to adverse events from cough and cold medicine ingestion (7).
  • Routine empiric treatment of children with chronic cough with leukotriene receptor antagonists lacks evidence and cannot be recommended (8)[C]. A small pilot study with montelukast in adults demonstrated some symptom relief after 2 weeks of treatment (9)[A].

First Line
  • In adults, oral antihistamine/decongestant therapy can be empiric treatment. Multiple formulations are available OTC in combination with other ingredients. Advise patients to review labels carefully or consult pharmacist:
    • Chlorpheniramine 2 mg/phenylephrine 5 mg/acetaminophen 325 mg (Tylenol Allergy Multi-Symptom) 2 caplets or gel caps PO q4h (maximum 12 caplets or gel caps in 24 hours; for patients >12 years)
    • Nasal steroids: fluticasone, budesonide, others, 1 spray BID
  • Central cough suppressants for short-term symptomatic relief of nonproductive cough
    • Dextromethorphan 10 to 20 mg PO q4h for patients >12 years; use 5 to 10 mg PO q4h for patients 6 to 12 years
      • Concomitant use of dextromethorphan and agents with serotonergic activity (e.g., SSRIs) should be avoided due to risk of serotonin syndrome.
    • Narcotics: codeine 15 to 30 mg PO q6h; hydrocodone/acetaminophen (Vicodin) 5 mg PO q6h; hydrocodone/chlorpheniramine (Tussionex Pennkinetic) 10 mg (5 mL) PO q12h for patients ≥12 years (no benefit in children; no good efficacy data in adults)

Second Line
  • A peripherally acting antitussive agent has been used:
    • In patients >10 years, benzonatate (Tessalon Perles) 100 to 200 mg PO TID as needed (maximum 600 mg/day)
  • Results from a small randomized placebo-controlled trial (n = 27) demonstrated subjective cough score improvement in patients using slow-release morphine sulfate. Patients had failed with other antitussive therapies. Side effects included constipation and drowsiness, and there were no discontinuations due to adverse events (10)[A].
    • Morphine was administered 5 to 10 mg PO BID.
  • An analysis of studies evaluating inhaled corticosteroid use in chronic cough for patients without additional indication such as asthma did not show consistent benefits (11)[C].

ISSUES FOR REFERRAL


Patients with chronic cough may benefit from evaluation by pulmonary, gastroenterology, ear-nose-and-throat (ENT), and/or allergy specialists.  

SURGERY/OTHER PROCEDURES


Fundoplication may be effective for cough secondary to refractory GERD.  

ONGOING CARE


FOLLOW-UP RECOMMENDATIONS


Consider stepwise withdrawal of medications after resolution of cough.  
Patient Monitoring
Frequent follow-up is necessary to assess the effectiveness of treatment  

DIET


Dietary modification: Patients with GERD may benefit by avoiding ethanol, caffeine, nicotine, citrus, tomatoes, chocolate, and fatty foods.  

PATIENT EDUCATION


  • Reassure patient that most cases of chronic cough are not life-threatening and that the condition can usually be managed effectively.
  • Counsel that several weeks to a month may be needed for significant reduction or elimination of cough
  • Prepare the patient for the possibility of multiple diagnostic tests and therapeutic regimens because the treatment is very often empiric.

PROGNOSIS


  • >80% of patients can be effectively diagnosed and treated using a systematic approach.
  • Cough from any cause may take weeks to months until resolution, and resolution depends greatly on efficacy of treatment directed at underlying etiology.

COMPLICATIONS


  • Cardiovascular: arrhythmias, syncope
  • Stress urinary incontinence
  • Abdominal and intercostal muscle strain
  • GI: emesis, hemorrhage, herniation
  • Neurologic: dizziness, headache, seizures
  • Respiratory: pneumothorax, laryngeal, or tracheobronchial trauma
  • Skin: petechiae, purpura, disruption of surgical wounds
  • Medication side effects
  • Other: negative impact on quality of life

REFERENCES


11 Morice  AH, Millqvist  E, Belvisi  MG, et al. Expert opinion on the cough hypersensitivity syndrome in respiratory medicine. Eur Respir J.  2014; 44(5):1132-1148.22 Irwin  RS, Baumann  MH, Bolser  DC, et al. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest.  2006;129(1)(Suppl):1S-23S.33 Bolser  DC. Cough suppressant and pharmacologic protussive therapy: ACCP evidence-based clinical practice guidelines. Chest.  2006;129(1)(Suppl):238S-249S.44 Gupta  A, McKean  M, Chang  AB. Management of chronic non-specific cough in childhood: an evidence-based review. Arch Dis Child Educ Pract Ed.  2007;92(2):33-39.55 Chang  AB, Lasserson  TJ, Gaffney  J, et al. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev.  2011;(1):CD004823.66 Yancy  WSJr, McCrory  DC, Coeytaux  RR, et al. Efficacy and tolerability of treatments for chronic cough: a systematic review and meta-analysis. Chest.  2013;144(6):1827-1838.77 Hampton  LM, Nguyen  DB, Edwards  JR, et al. Cough and cold medication adverse events after market withdrawal and labeling revision. Pediatrics.  2013;132(6):1047-1054.88 Chang  AB, Winter  D, Acworth  JP. Leukotriene receptor antagonist for prolonged non-specific cough in children. Cochrane Database Syst Rev.  2006;(2):CD005602.99 Mincheva  RK, Kralimarkova  TZ, Rasheva  M, et al. A real-life observational pilot study to evaluate the effects of two-week treatment with montelukast in patients with chronic cough. Cough.  2014;10(1):2.1010 Morice  AH, Menon  MS, Mulrennan  SA, et al. Opiate therapy in chronic cough. Am J Respir Crit Care Med.  2007;175(4):312-315.1111 Johnstone  KJ, Chang  AB, Fong  KM, et al. Inhaled corticosteroids for subacute and chronic cough in adults. Cochrane Database Syst Rev.  2013;(3):CD009305.

ADDITIONAL READING


Dicpinigaitis  PV, Morice  AH, Birring  SS, et al. Antitussive drugs-past, present, and future. Pharmacol Rev.  2014;66(2):468-512.  

SEE ALSO


  • Asthma; Bronchiectasis; Congestive Heart Failure; Eosinophilic Pneumonias; Gastroesophageal Reflux Disease; Laryngeal Cancer; Lung, Primary Malignancies; Pertussis; Pulmonary Edema; Rhinitis, Allergic; Sinusitis; Tuberculosis
  • Algorithm: Cough, Chronic

CODES


ICD10


  • R05 Cough
  • J44.9 Chronic obstructive pulmonary disease, unspecified
  • J41.0 Simple chronic bronchitis

ICD9


  • 786.2 Cough
  • 496 Chronic airway obstruction, not elsewhere classified
  • 491.0 Simple chronic bronchitis

SNOMED


  • 68154008 Chronic cough (finding)
  • 13645005 Chronic obstructive lung disease (disorder)
  • 46802002 smokers cough (disorder)

CLINICAL PEARLS


  • Chronic cough is defined as a cough that persists for >8 weeks in adults.
  • In patients with chronic cough, most frequent etiologies include a history of smoking, asthma, UACS, and GERD.
  • The FDA issued a public health advisory stating that OTC cough and cold medicines should not be given to children <2 years. OTC cough expectorant and suppressant product labels state "do not use" in children <4 years.
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