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A. Viruses Causing Common Cold [4]

  1. Rhinoviruses ~40%
  2. Coronaviruses ~12% (also cause SARS)
  3. Influenza viruses Types A and B ~8%
  4. Respiratory Syncytial Virus (RSV) 5%
  5. Parainfluenza viruses 5%
  6. Adenoviruses <5%
  7. Enteroviruses <5%
  8. Metapneumovirus (unknown frequency)
  9. Unknown causes ~25%
  10. Cold viruses are the major cause of acute bronchitis
  11. Cold virus infection can precipitate severe asthma and chronic bronchitis attacks [19]

B. Symptoms

  1. Rhinorrhea
  2. Nasal Congestion
  3. Headache
  4. Fatigue
  5. Sinusitis
  6. Fever
  7. Sore throat
  8. Cough
  9. Bronchitis [4]
  10. Asthma (exacerbation or trigger) [2]
  11. Purulent secretions from nose or throat do not distinguish viral from bacterial cause [3]
  12. Aircraft cabin recirculated air (compared with fresh air) does not increase risk of cold symptoms after ~2 hour airplane flights [15]
  13. Viral Infection versus Inhalational Anthrax [18]
    1. High suspicion for anthrax required even with symptoms consistent with viral infection
    2. Fever and cough do not distinguish viral respiratory infection from anthrax
    3. Nonheadache neurolgoic symptoms, dyspnea, nausea/vomiting more common in anthrax
    4. Rhinorrhea and sore throat more common in viral respiratory infection
    5. Finding any abnormality on lung auscultation associated much more with anthrax

C. Pathophysiology [2]

  1. Different viruses produce somewhat different syndromes
  2. However, all cold viruses have many mechanisms in common
  3. Cold viruses attach to upper airway, bronchial, or bronchiolar epithelial cells
  4. Infection of epithelium stimulates inflammatory mediators
    1. Cytokines
    2. Chemokines
    3. Growth factors
    4. Adhesion molecules - ICAM1 is receptor for 90% of rhinoviruses
    5. Reactive oxygen species
    6. Inducible nitric oxide synthetase (iNOS)
    7. 5-lipoxygenase (leads to increased leukotrienes)
  5. Macrophages, T cells, B cells, and sometimes eosinophils are recruited to airways
  6. Systemic symptoms occur when large amounts of cytokines (mainly IL-6) are released
  7. Airway epithelium may also undergo cell death and slough (depends on virus)
  8. Mucus consisting of neutrophils, monocytes, and dead epithelium can be produced
  9. SARS coronavirus uniquely causes marked apoptosis in airway cells [17]
  10. Bronchoconstriction may occur in susceptible individuals
  11. Cold viruses can provoke frank and severe asthma attacks

D. Treatment

  1. Symptomatic treatment is central focus at present time EXCEPT for:
    1. RSV
    2. Influenza
  2. Nonsteroidal antiinflammatory agents (NSAIDS) reduce symptoms
    1. Frequent dosing of over the counter (OTC) NSAIDS is required
    2. Acetaminophen (Tylenol®) probably less effective than NSAIDs
  3. Ipatroprium bromide (Atrovent®) Nasal spray
    1. Topical anticholinergic agent with little systemic absorption
    2. Safe and effective in reducing rhinorrhea
  4. Decongestants
    1. These are primarily alpha1-adrenergic agonists
    2. Topical - including oxymetazoline (Afrin®, others), phenylephrine (NeoSynephrine®)
    3. Oral - pseudoephedrine (Sudafed®), others
    4. Phenylpropanoloamine has been withdrawn from the over-the-counter market due to increased risk of stroke in women but not men [5]
    5. Combination of nasal glucocorticoids and topical decongestants reduces "rebound" and provides improved relief
    6. For use of topical decongestants for >2 days, recommend short course concommitant nasal glucocorticoids
  5. Antihistamines - oral agents improve sneezing and rhinorrhea
  6. Saline nasal spray may improve dryness from anticholinergic agents
  7. Pleconaril [1]
    1. Novel rhinoviral and enteroviral capsid binder with oral activity
    2. When instituted within 36 hours of symptoms, reduces duration 1-1.5 days
  8. Zinc Losenges [1,6]
    1. Losenges shown to reduce symptom duration from 7.6 to 4.4 days [7]
    2. However, meta-analysis failed to show a benefit of zinc salts losenges on colds [8]
    3. Zinc acetate losenges slightly reduced cytokine levels and appeared to reduce cough [9]
    4. A prospective, randomized study failed to show benefits in children [10]
    5. Generally well tolerated; unclear if any long term safety issues
    6. Zinc may have some benefit, but efficacy is not clear and some trials are negative
  9. Sodium cromoglicate of no benefit in children with suspected viral URI [11]
  10. Tremacamra (Soluble ICAM-1, BIRR 4) [12]
    1. ICAM-1 (intercellular adhesion molecule 1) is the receptor for cold rhinoviruses
    2. Normally, ICAM-1 binds to integrins (CD11a,b/CD18) on lymphocytes
    3. Rhinovirus blockade of ICAM-1 leads to increased IL-8 levels
    4. Tremacamra is a soluble form of ICAM-1
    5. Inhaled or powdered formulations of tremacamra significantly reduced cold symptoms
  11. Antibiotics (Antibacterial Agents)
    1. Not indicated for URI unless chronic obstructive pulmonary disease (COPD) is present
    2. Antibiotics should not be used for nonspecific URI in previously healthy adults [3,13]
    3. Clarithromycin had no benefit in experimental rhinovirus 16 induced colds [14]
  12. Ruprintrivir - human rhinolvirus 3C protease inhibitor in development [1]
  13. Echinacea has no beneficial effect on early common cold symptoms or duration in adults [16] or children [20] or experimental infection [21]
  14. Airborne® Herbal Supplement [22]
    1. 7 herbal extracts
    2. 3 vitamins
    3. 2 amino acids
    4. Selenium
    5. Zinc
    6. Other ingredients
    7. Being promoted for prevention or treatment of colds
    8. No efficacy has been demonstrated for any of the ingredients
    9. Safey has not been established

References

  1. Heikkinen T and Jarvinen A. 2003. Lancet. 361(9351):51 abstract
  2. Jacoby DB. 2002. JAMA. 287(6):755 abstract
  3. Gonzales R, Bartlett JG, Besser RE, et al. 2001. Ann Intern Med. 134(6):490 abstract
  4. Wenzel RPO and Fowlder AA. 2006. NEJM. 355(20):2125 abstract
  5. Phenylpropanolamine. 2000. Med Let. 42(1094):113 abstract
  6. Zinc Losenges. 1997. Med Let. 39(993):9
  7. Mossad SB, Macknin ML, Medendorp SV, Mason P. 1996. Ann Intern Med. 125(2):81 abstract
  8. Jackson JL, Peterson C, Lesho E. 1997. Arch Intern Med. 157(20):2373 abstract
  9. Prasad AS, Fitzgerald JT, Bao B, et al. 2000. Ann Intern Med. 133(4):247
  10. Macknin ML, Piedmonte M, Calendine C, et al. 1998. JAMA. 279(24):1962 abstract
  11. Butler CC, Robling M, Prout H, et al. 2002. Lancet. 359(9324):2153 abstract
  12. Turner RB, Wecker MT, Phol G, et al. 1999. JAMA. 281(19):1797 abstract
  13. Snow V, Mottur-Pilson C, Gonzales R. 2001. Ann Intern Med. 134(6):487 abstract
  14. Abisheganaden JA, Avila PC, Kishiyama JL, et al. 2000. Am J Med. 108(6):453 abstract
  15. Zitter JN, Mazonson PD, Miller DP, et al. 2002. JAMA. 288(4):483 abstract
  16. Barrett BP, Brown RL, Locken K, et al. 2002. Ann Intern Med. 137(12):939 abstract
  17. Kuiken T, Fouchier RAM, Schutten M, et al. 2003. Lancet. 362(9380):263 abstract
  18. Hupert N, Bearman GML, Mushlin AI, Callahan MA. 2003. Ann Intern Med. 139(5):337 abstract
  19. Tan WC, Xiang X, Qiu D, et al. 2003. Am J Med. 115(4):272 abstract
  20. Taylor JA, Weber W, Standish L, et al. 2003. JAMA. 290(21):2824 abstract
  21. Turner RB, Bauer R, Woelkart K, et al. 2005. NEJM. 353(4):341 abstract
  22. Airborne. 2005. Med Let. 47(1199):1 abstract