eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Nasal & Sinus Diseases

Cystic Fibrosis

Author: Nicole Murray, MD, Assistant Professor, Department of Pediatric Otolaryngology, Connecticut Children's Medical center
Contributor Information and Disclosures

Updated: Jul 3, 2008

Introduction

Background

Cystic fibrosis (CF) is a chronic multisystem disorder characterized by recurrent endobronchial infections, progressive obstructive pulmonary disease, and pancreatic insufficiency with intestinal malabsorption.

Most patients with CF present to an otolaryngologist for sinonasal disease. Studies suggest that other head and neck problems, such as otitis media and adenotonsillar disease, appear to be similar in prevalence and pathophysiology to those in patients without CF.1,2 Otitis media actually appears to be less prevalent in patients with CF than in patients without CF, for reasons that remain unclear.3 This article, therefore, focuses on the sinonasal manifestations of CF.

Pathophysiology

The CF gene product is a cyclic-AMP mediated chloride channel called the cystic fibrosis transmembrane conductance regulator (CFTR). Malfunction causes abnormal chloride ion transport on the apical surface of epithelial cells in exocrine gland tissues, leading to abnormally viscid secretions. Recently, 6 classes of defects in the CFTR gene have been described and are as follows: complete absence of protein synthesis, defective protein maturation and early degradation (caused by the most common mutation, D F508), disordered regulation, defective chloride conductance or channel gating, diminished transcription, and accelerated channel turnover from the cell surface.4

Patients most commonly have severe chronic lung disease and exocrine pancreatic insufficiency, but they may also have nasal polyposis, pansinusitis, rectal prolapse, chronic diarrhea, pancreatitis, cholelithiasis, cirrhosis, or other forms of hepatic dysfunction.

The exact mechanism by which a malfunctioning CFTR causes sinus disease is not completely understood. Chloride ions cannot be excreted, sodium is excessively absorbed, and water passively follows. This desiccates the mucosal surface and alters the viscosity of the normal mucus blanket, which alone can lead to obstruction of sinus ostia.5 Additional abnormalities exist in these patients, including ciliary dysfunction, increased inflammatory mediators, and increased colonization with Pseudomonas aeruginosa, that further impair normal sinus clearance and aeration.6 Chronic sinus infection and inflammation are the net result.

Frequency

United States

In whites, CF occurs in 1 per 3500 live births. In African Americans, CF occurs in 1 per 17,000 live births.

International

Worldwide incidence varies from 1 per 377 live births in parts of England to 1 per 90,000 Asian live births in Hawaii.

Mortality/Morbidity

Median survival age varies from country to country and is highest in the United States and Canada, at 28 and 32 years, respectively. Median survival age in Latin America is 6 years. Cause of death is generally respiratory failure and cor pulmonale.

Medical and surgical treatment options are changing these statistics, and an individual with CF born in the United States today is expected to survive longer than 40 years.7

Race

Whites, as indicated above, are most often affected, at a rate of about 1 per 3500 births. Incidence is also high for Hispanics, at a rate of 1 per 9500 live births. CF is quite rare in native Asians and Africans (<1 per 15,000 births), but it occurs somewhat more frequently in Asian American or African American populations, reflecting white admixture.8

Sex

No sex predilection has been identified, although for reasons that are unclear, male sex may be associated with a slower rate of pulmonary function decline.9

Age

Median age at diagnosis is 6-8 months. CF is diagnosed in two thirds of patients by 1 year of age.

Clinical

History

  • Elicit a thorough history of sinonasal symptoms from patients with cystic fibrosis (CF). A complete history is critical because most clinical decisions are based on this information.
    • While 90-100% of patients have radiologic evidence of sinus disease,10,11,12 the frequency of nasal polyposis is quite variable and may be found in 6-67% of patients.2 Clinically symptomatic sinusitis, as evidenced by pain, discharge, fever, or postnasal drip, is found in only about 10% of patients with CF.10 Most patients with radiologically evident disease, therefore, do not report symptoms. This phenomenon may represent a truly asymptomatic disease state, or it may suggest that patients with this chronic disease have psychologically adapted to their symptoms.13
    • Given the above facts, clinical history is often weighed more heavily than radiographic evaluation when treatment decisions are made.
  • Symptoms to inquire about include the following:14
    • Nasal obstruction
    • Worsening nasal discharge
    • Facial pain
    • Worsening cough
    • Fever
  • Question patients regarding recent pulmonary status.
    • Chronic sinusitis seems closely associated with endobronchial bacterial infections and also appears to impact pulmonary reactivity and chronicity of disease within the sinobronchial tract.15,16
    • Decreasing exercise tolerance also correlates with acute sinus exacerbations or worsening chronic disease.

Physical

  • Most patients already have a CF diagnosis upon presentation to the otolaryngologist and are being referred for consideration of sinus surgery. Perform a thorough physical examination to evaluate the nose and sinuses as well as to uncover other conditions that may exacerbate sinus disease.
    • Facial evaluation may reveal a widened nasal bridge due to chronic polyposis. Sometimes polyps may even protrude from the nares.
    • Swollen turbinates, purulent nasal discharge, and nasal polyps may be visible on anterior rhinoscopy.
    • Endoscopy may reveal polyps obstructing both the airway and the sinus ostia in the middle meatus. Purulent discharge may also be found on endoscopy. Patients also often have a bulging uncinate process that obstructs the nasal airway.
    • The nasopharynx must also be evaluated. Adenoid hypertrophy may be present in younger patients and may play a role in nasal obstruction. Address this problem prior to surgical intervention in the sinuses of these patients, as with patients without CF.
  • A CF diagnosis may occasionally be made by the otolaryngologist based on the presence of nasal polyposis in an otherwise healthy child. Patients sometimes tolerate mild forms of CF, thereby escaping early diagnosis. Nasal polyposis is otherwise quite rare in children. Evaluate any child found to have nasal polyps with a sweat chloride test.

Causes

CF is inherited as an autosomal recessive trait.

  • The gene responsible was identified in 1989 as a transmembrane conductance regulator glycoprotein (CFTR gene) localized to the long arm of chromosome 7.17
  • To date, at least 1500 different mutations in the gene have been identified.
  • Half of affected individuals of northern European descent are homozygous for the D F508 mutation, which is the deletion of a single phenylalanine residue at amino acid 508 of the CFTR gene (a class II defect).
  • Genotype does not always predict phenotype, which suggests either an environmental component of organ dysfunction or modifying genes that are only recently being characterized.18

More on Cystic Fibrosis

Overview: Cystic Fibrosis
Differential Diagnoses & Workup: Cystic Fibrosis
Treatment & Medication: Cystic Fibrosis
Follow-up: Cystic Fibrosis
Multimedia: Cystic Fibrosis
References
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References

  1. Cipolli M, Canciani M, Cavazzani M, et al. Ear disease is not a common complication in cystic fibrosis. Eur J Pediatr. Mar 1993;152(3):265-6. [Medline].

  2. Halvorson DJ. Cystic fibrosis: an update for the otolaryngologist. Otolaryngol Head Neck Surg. Apr 1999;120(4):502-6. [Medline].

  3. Haddad J Jr, Gonzalez C, Kurland G, et al. Ear disease in children with cystic fibrosis. Arch Otolaryngol Head Neck Surg. May 1994;120(5):491-3. [Medline].

  4. Rowe SM, Clancy JP. Advances in cystic fibrosis therapies. Curr Opin Pediatr. Dec 2006;18(6):604-13. [Medline].

  5. Rutland J, Cole PJ. Nasal mucociliary clearance and ciliary beat frequency in cystic fibrosis compared with sinusitis and bronchiectasis. Thorax. 1981;36:654-658.

  6. Hauber HP, Manoukian JJ, Nguyen LHP. Increased expression of interleukin-9, interleukin-9 receptor, and the calcium-activated chloride channel hCLCA1 in the upper airways of patients with cystic fibrosis. Laryngoscope. 2003;113:1037-1042.

  7. Elborn JS, Shale DJ, Britton JR. Cystic fibrosis: current survival and population estimates to the year 2000. Thorax. Dec 1991;46(12):881-5. [Medline].

  8. National Institutes of Health Consensus. Genetic testing for cystic fibrosis. National Institutes of Health Consensus Development Conference Statement on genetic testing for cystic fibrosis. Arch Intern Med. Jul 26 1999;159(14):1529-39. [Medline].

  9. Boat TF. Cystic fibrosis. In: Nelson Textbook of Pediatrics. Philadelphia, Pa:. WB Saunders Co;2000:1315-1327.

  10. Cepero R, Smith RJ, Catlin FI, et al. Cystic fibrosis--an otolaryngologic perspective. Otolaryngol Head Neck Surg. Oct 1987;97(4):356-60. [Medline].

  11. Neely JG, Harrison GM, Jerger JF, et al. The otolaryngologic aspects of cystic fibrosis. Trans Am Acad Ophthalmol Otolaryngol. Mar-Apr 1972;76(2):313-24. [Medline].

  12. Shwachman H, Kulcycki LL, Mueller HL. Nasal polyposis in patients with cystic fibrosis. Pediatrics. 1962;30:389-401.

  13. Nishioka GJ, Cook PR. Paranasal sinus disease in patients with cystic fibrosis. Otolaryngol Clin North Am. Feb 1996;29(1):193-205. [Medline].

  14. Brihaye P, Clement PA, Dab I, Desprechin B. Pathological changes of the lateral nasal wall in patients with cystic fibrosis (mucoviscidosis). Int J Pediatr Otorhinolaryngol. Jan 1994;28(2-3):141-7. [Medline].

  15. Ramsey B, Richardson MA. Impact of sinusitis in cystic fibrosis. J Allergy Clin Immunol. Sep 1992;90(3 Pt 2):547-52. [Medline].

  16. Nishioka GJ, Barbero GJ, Konig P, et al. Symptom outcome after functional endoscopic sinus surgery in patients with cystic fibrosis: a prospective study. Otolaryngol Head Neck Surg. Oct 1995;113(4):440-5. [Medline].

  17. Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. Sep 8 1989;245(4922):1059-65. [Medline].

  18. Gambardella S, Biancolella M, D'Apice MR, Amati F, Sangiuolo F, Farcomeni A. Gene expression profile study in CFTR mutated bronchial cell lines. Clin Exp Med. Dec 2006;6(4):157-65. [Medline].

  19. Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics. Apr 1996;97(4):524-8. [Medline].

  20. April MM, Zinreich SJ, Baroody FM, Naclerio RM. Coronal CT scan abnormalities in children with chronic sinusitis. Laryngoscope. Sep 1993;103(9):985-90. [Medline].

  21. Ledesma-Medina J, Osman MZ, Girdany BR. Abnormal paranasal sinuses in patients with cystic fibrosis of the pancreas. Radiological findings. Pediatr Radiol. Feb 1980;9(2):61-4. [Medline].

  22. Shapiro ED, Milmoe GJ, Wald ER, et al. Bacteriology of the maxillary sinuses in patients with cystic fibrosis. J Infect Dis. Nov 1982;146(5):589-93. [Medline].

  23. Muhlebach MS, Miller MB, Moore C, Wedd JP, Drake AF, Leigh MW. Are lower airway or throat cultures predictive of sinus bacteriology in cystic fibrosis?. Pediatr Pulmonol. May 2006;41(5):445-51. [Medline].

  24. Brook I. Discrepancies in the recovery of bacteria from multiple sinuses in acute and chronic sinusitis. J Med Microbiol. Sep 2004;53(Pt 9):879-85. [Medline].

  25. Wald ER. Rhinitis and acute and chronic sinusitis. Pediatr Otolaryngol. 1996;2:843-858.

  26. Desrosiers MY, Salas-Prato M. Treatment of chronic rhinosinusitis refractory to other treatments with topical antibiotic therapy delivered by means of a large-particle nebulizer: results of a controlled trial. Otolaryngol Head Neck Surg. Sep 2001;125(3):265-9. [Medline].

  27. Moss RB, King VV. Management of sinusitis in cystic fibrosis by endoscopic surgery and serial antimicrobial lavage. Reduction in recurrence requiring surgery. Arch Otolaryngol Head Neck Surg. May 1995;121(5):566-72. [Medline].

  28. Raynor EM, Butler A, Guill M, Bent JP 3rd. Nasally inhaled dornase alfa in the postoperative management of chronic sinusitis due to cystic fibrosis. Arch Otolaryngol Head Neck Surg. May 2000;126(5):581-3. [Medline].

  29. Cimmino M, Nardone M, Cavaliere M, Plantulli A, Sepe A, Esposito V. Dornase alfa as postoperative therapy in cystic fibrosis sinonasal disease. Arch Otolaryngol Head Neck Surg. Dec 2005;131(12):1097-101. [Medline].

  30. Rashid M, Durie P, Andrew M, et al. Prevalence of vitamin K deficiency in cystic fibrosis. Am J Clin Nutr. Sep 1999;70(3):378-82. [Medline].

  31. Mendelsohn MG, Gross CW. Soft-tissue shavers in pediatric sinus surgery. Otolaryngol Clin North Am. Jun 1997;30(3):443-9. [Medline].

  32. Crockett DM, McGill TJ, Healy GB, et al. Nasal and paranasal sinus surgery in children with cystic fibrosis. Ann Otol Rhinol Laryngol. Jul-Aug 1987;96(4):367-72. [Medline].

  33. Davidson TM, Murphy C, Mitchell M, et al. Management of chronic sinusitis in cystic fibrosis. Laryngoscope. Apr 1995;105(4 Pt 1):354-8. [Medline].

  34. Albritton FD, Kingdom TT. Endoscopic sinus surgery in patients with cystic fibrosis: an analysis of complications. American Journal of Rhinology. 2000;14:379-385.

  35. Duplechain JK, White JA, Miller RH. Pediatric sinusitis. The role of endoscopic sinus surgery in cystic fibrosis and other forms of sinonasal disease. Arch Otolaryngol Head Neck Surg. Apr 1991;117(4):422-6. [Medline].

  36. Cuyler JP. Follow-up of endoscopic sinus surgery on children with cystic fibrosis. Arch Otolaryngol Head Neck Surg. May 1992;118(5):505-6. [Medline].

  37. Friedman EM, Stewart M. An assessment of sinus quality of life and pulmonary function in children with cystic fibrosis. Am J Rhinol. Nov-Dec 2006;20(6):568-72. [Medline].

  38. Halvorson DJ, Dupree JR, Porubsky ES. Management of chronic sinusitis in the adult cystic fibrosis patient. Ann Otol Rhinol Laryngol. Nov 1998;107(11 Pt 1):946-52. [Medline].

  39. Madonna D, Isaacson G, Rosenfeld RM, Panitch H. Effect of sinus surgery on pulmonary function in patients with cystic fibrosis. Laryngoscope. Mar 1997;107(3):328-31. [Medline].

  40. Umetsu DT, Moss RB, King VV, Lewiston NJ. Sinus disease in patients with severe cystic fibrosis: relation to pulmonary exacerbation. Lancet. May 5 1990;335(8697):1077-8. [Medline].

  41. Garey KW, Alwani A, Danziger LH, Rubinstein I. Tissue reparative effects of macrolide antibiotics in chronic inflammatory sinopulmonary diseases. Chest. Jan 2003;123(1):261-5. [Medline].

  42. Murray TS, Egan M, Kazmierczak BI. Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients. Curr Opin Pediatr. Feb 2007;19(1):83-8. [Medline].

  43. Rubin BK. Emerging therapies for cystic fibrosis lung disease. Chest. Apr 1999;115(4):1120-6. [Medline].

  44. Medical Economics Company. Flonase. Physicians' Desk Reference. 2001;Available at: http://www.pdr.net/HomePage_template.jsp.

  45. Medical Economics Company. Nasonex. Physicians' Desk Reference. 2001;Available at: http://www.pdr.net/HomePage_template.jsp.

  46. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. Sep 8 1989;245(4922):1066-73. [Medline].

  47. Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med. May 12 2005;352(19):1992-2001. [Medline].

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Further Reading

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Keywords

cystic fibrosis, CF, mucoviscidosis, endobronchial infection, obstructive pulmonary disease, sinonasal disease, severe chronic lung disease, nasal polyposis, pansinusitis, chronic sinusitis

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Contributor Information and Disclosures

Author

Nicole Murray, MD, Assistant Professor, Department of Pediatric Otolaryngology, Connecticut Children's Medical center
Nicole Murray, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery
Disclosure: Nothing to disclose.

Medical Editor

Todd Schneiderman, MD, Consulting Surgeon, Atlanta Ear Nose and Throat Associates
Todd Schneiderman, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery and American Rhinologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Gregory C Allen, MD, Assistant Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Gregory C Allen, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Academy of Pediatrics, American Cleft Palate/Craniofacial Association, American College of Surgeons, American Laryngological Rhinological and Otological Society, American Medical Association, Christian Medical & Dental Society, and Colorado Medical Society
Disclosure: Nothing to disclose.

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: Advanced Headache Intervention Consulting fee Consulting; Covidien Corp Consulting fee Consulting

 
 
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