Surfactant and its Role in the Upper Respiratory System and Eustachian Tube
Surfactant research was originally directed toward lung mechanics, however, with growing information on the biology of the surfactant system it has expanded beyond the borders of basic physiology. The research has become interdisciplinary, not only considering aspects of lungs biology relevant for breathing, but also those aspects relevant for airway defence.
Surfactant consists mainly of phospholipids that lower the alveolar surface tension to prevent lung collapse at expiration. They also support mechanical elimination of inhaled pathogens by reducing the viscosity of airway mucus. Approximately 8-10% of surfactant is made up of proteins. Among them, specific proteins SP-A and SP-D play a crucial role in the innate defence system. They belong to collectins family and serve as the first step in immune response to inhaled pathogens. In limited extent, SP-B and SP-C are also involved in immunomodulation.
Although numerous studies have focused on the physiological function of surfactant in the lower airways, relatively little is known about its role in the upper respiratory system. Identification of lamellar bodies in ciliated epithelium of the upper airways indicates that surfactant may have a role in normal sinonasal function and pathology. Decreased levels of the main component of surfactant, phospholipids, have been implicated in atrophic rhinitis and altered levels of surfactant proteins have been observed in a number of respiratory tract diseases. The pattern of inflammation in the upper respiratory tract generally appears to parallel that in the lower airways and nowadays upper respiratory disease and lower airway disease are considered as two manifestations of one pathological process. Therefore, surfactant proteins may play a significant role in the upper respiratory tract diseases.
In addition, surfactant has been identified in the Eustachian tube where it helps to lower the opening pressure between nasopharynx and middle ear. The alterations in surfactant levels may adversely affect Eustachian tube function and contribute to chronic ear infection.
The review summarizes the current knowledge on the presence and the role of surfactant in the upper respiratory system and Eustachian tube.
If the inline PDF is not rendering correctly, you can download the PDF file here.
Halliday HL. Surfactants: Past present and future. J Perinatol 2008; 28 (Suppl 1): S47-56.
Madsen J Tornoe I Nielsen O Koch C Steinhilber W Holmskov U. Expression and localization of lung surfactant protein A in human tissues. Am J Respir Cell Mol Biol 2003; 29(5): 591-597.
Lin Z deMello D Phelps DS Koltun WA Page M Floros J. Both human SP-A1 and SP-A2 genes are expressed in small and large intestine. Pediatr Pathol Mol Med 2001; 20(5): 367-386.
Madsen J Klien A Torneo I Skjodt K Koch C Holmskov U. Localization of surfactant protein D on mucosal surfaces in human tissues. J Immunol 2000; 164 (11): 5866-5870.
Woodwort BA Smythe N Spicer SS Schulte BA Schlosser RJ. Presence of surfactant lamellar bodies in normal and diseased sinus mucosa. ORL J Otorhinolaryngol Relat Spec 2005; 67(4): 199-202.
Svane-Knudsen V Rasmussen G Clausen PP. Surfactant-like lamellar bodies in the mucosa of the human nose. Acta Otolaryngol 1990; 109(3-4): 307-313.
Dutton JM Goss K Khubchandani KR Shah ChD Smith RJH Snyder JM. Surfactant protein A in rabbit sinus and middle ear mucosa. Ann Otol Rhinol Laryngol 1999; 108(10): 915-924.
Wright JR Clemets JA. Metabolism and turnover of lung surfactant. Am Rev Respir Dis 1987; 136(2): 426-444.
Pastva AM Wright JR Williams KL. Immunomodulatory roles of surfactant proteins A and D. Implication in lung disease. Proc Am Thorac Soc 2007; 4(3): 252-257.
Johansson J Curstedt T Robertson B. The proteins of the surfactant system. Eur Respir J 1994; 7(2): 372-391.
Wright JR Dobbs LG. Regulation of pulmonary surfactant secretion and clearance. Annu Rev Physiol 1991; 53: 395-414.
Gehr P Green FHY Geiser M Hof V Lee MM Schurch S. Airway surfactant a primary defense barrier: Mechanical and immunological aspects. J Aerosol Med 1996; 9(2): 163-181.
Schlosser RJ. Surfactant and its role in chronic sinusitis. Ann Otol Rhinol Laryngol 2006 196: 40-44.
Nogee LM Garnier G Dietz HC Singer L Murphy AM deMello DE Colten HR. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kinders. J Clin Invest 1994; 93(4): 1860-1863.
Miles PR Bowman L Rao KM Baatz JE Huffman L. Pulmonary surfactant inhibits LPS-induced nitric oxide production by alveolar macrophages. Am J Physiol 1999; 276(1): L186-196.
Ikegami M Whitsett JA Martis PC Weaver TE. Reversibility of lung inflammation caused by SP-B deficiency. Am J Physiol Lung Cell Mol Physiol 2005; 289(6): L962-970.
Glasser SW Senft AP Whitsett JA Maxfield MD Ross GF Richardson TR Prows DR Xu Y Korfhagen TR. Macrophage dysfunction and susceptibility to pulmonary pseudomonas aeruginosa infection in surfactant protein c-deficient mice. J Immunol 2008; 181(1): 621-628.
De Sanctis GT Tomkiewicz RP Rubin BK Schurch S King M. Exogenous surfactant enhances mucociliary clearance in the anesthetized dog. Eur Respir J 1994; 7(9): 1616-1621.
Kakuta Y Sasaki H Takishima T. Effect of artificial surfactant on ciliary beat frequency in guinea pig trachea. Respir Physiol 1991; 83(3): 313-321.
Chroneos ZC Sever-Chroneos Z Shepherd VL. Pulmonary surfactant: An immunological perspective. Cell Physiol Biochem 2010; 25(1): 13-26.
Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 2005; 5(1): 58-68.
Kishor U Madan T Sarma PU Singh M Urban BC Reid KB. Protective roles of pulmonary surfactant proteins SP-A and SP-D against lung allergy and infection caused by Aspergillus fumigatus. Immunobiology 2002; 205(4-5): 610-618.
Pikaar JC Voorhout WF van Golde LM Verhoef J Van Strijp JA van Iwaarden JF. Opsonic activities of surfactant proteins A and D in phagocytosis of gram negative bacteria by alveolar macrophages. J Infect Dis 1995; 172(2): 481-489.
Williams MC Hawgood S Hamilton RL. Changes in lipid structure produced by surfactant proteins SP-A SP-B and SP-C. Am J Respir Cell Mol Biol 1991; 5(1): 41-50.
Korfhagen TR Bruno MD Ross GF Huelsman KM Ikegami M Jobe AH Wert SE Stripp BR Morris RB Glasser SW Bachurski CJ Iwamoto HS Whitsett JA. Altered surfactant function and structure in SP-A gene targeted mice. Proc Natl Acad Sci USA 1996; 93(18): 9594-9599.
Sun B Curstedt T Lindgren G Franzén B Alaiya AA Calkovska A Robertson B. Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A. Eur Respir J 1997; 10(9): 1967-1974.
Hens G Hellings PW. The nose: gatekeeper and trigger of bronchial disease. Rhinology 2006; 44(3): 179-187.
Calkovska A Engler I Mokra D Drgova A Kmetova M Tatarkova Z Calkovsky V Brozmanova M Tatar M. Differences in oxidative status lung function and pulmonary surfactant during long-term inhalation of medical oxygen and partially ionized oxygen in guinea pigs. J Physiol Pharmacol 2008; 59 (Suppl. 6): 173-181.
Calkovsky V Hajtman A. Functional aspects of upper and lower airways. Head and Neck Diseases 2003; 12(3/4): 23-27 (in Slovak).
Passalacqua G Ciprandi G Canonica GW. The nose-lung interaction in allergic rhinitis and asthma: united airways disease. Curr Opin Allergy Clin Immunol 2001; 1(1): 7-13.
Bachert C Patou J Van Cauwenberge P. The role of sinus disease in asthma. Curr Opin Allergy Clin Immunol 2006; 6(1): 29-36.
Farooque SP Lee TH. Aspirin-sensitive respiratory disease. Annu Rev Physiol 2009; 71(1): 465-487.
Pakdaman MN Corry DB Luong A. Fungi linking the pathophysiology of chronic rhinosinusitis with nasal polyps and allergic asthma. Immunol Invest 2011; 40(7): 767-785.
Boari L de Castro Júnior NP. Diagnosis of chronic rhinosinusitis in patients with cystic fibrosis: correlation between anamnesis nasal endoscopy and computed tomography. Braz J Otorhinolaryngol 2005; 71(6): 705-710.
Roberts NJ Llyod-Owen SJ Rapado F Patel IS Wilkinson TM Donaldson GC Wedzicha JA. Relationship between chronic nasal and respiratory symptoms in patients with COPD. Respir Med 2003; 97(8): 909-914.
Kim HY So YK Dhong HJ Chung SK Choi DCh Kwon NH Oh MJ. Prevalence of lower airway diseases in patients with chronic rhinosinusitis. Acta Oto-Laryngologica 2007; 127(Suppl. 558): 110-114.
Sayed RH Abou-Elhamd KE Abdel-Kader M Saleem TH. Study of surfactant level in cases of primary atrophic rhinits. J Laryngol Otol 2000; 114(4): 254-259.
King RJ Clements JA. Surface active materials from dog lung. II. Composition and physiological correlation. Am J Physiol 1972; 223(3): 715-726.
Hills BA. Analysis of eustachian surfactant and its function as a release agent. Arch Otolaryngol 1984; 110(1): 3-9.
Günther A Siebert C Schmidt R Ziegler S Grimminger F Yabut M Temmesfeld B Walmrath D Morr H Seeger W. Surfactant alterations in severe pneumonia acute respiratory distress syndrome and cardiogenic lung oedema. Am J Respir Crit Care Med 1996; 153(1): 176-184.
Gregory TJ Longmore WJ Moxley MA Whitsett JA Reed CR Fowler AA 3rd Hudson LD Maunder RJ Crim C Hyers TM. Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest 1991; 88(6): 1976-1981.
Woodworth BA Wood R Baatz JE Schlosser RJ. Sinonasal surfactant protein A1 A2 and D gene expression in cystic fibrosis: A preliminary report. Otolaryngol Head Neck Surg 2007; 137(1): 34-38.
Woodworth BA Neal JG Newton D Joseph K Kaplan AP Baatz JE Schlosser RJ. Surfactant protein A and D in human sinus mucosa: a preliminary report. ORL J Otorhinolaryngol Relat Spec 2007; 69(1): 57-60.
Woodworth BA Lathers D Neal JG Skinner M Richardson M Young MR Schlosser RJ. Immunolocalization of surfactant protein A and D in sinonasal mucosa. Am J Rhinol 2006 20(2): 461-465.
Kim JK Kim SS Rha KW Kim ChH Cho JH Lee ChH Lee JG Yoon JH. Expression and localization of surfactant proteins in human nasal epithelium. Am J Physiol Lung Cell Mol Physiol 2007; 292(4): L879-L884.
Woodworth BA Wood R Bhargave G Cohen NA Baatz JE Schlosser RJ. Surfactant protein B detection and gene expression in chronic rhinosinusitis. Laryngoscope 2007; 117(7): 1296-1301.
Beatty AL Malloy JL Wright JR. Pseudomonas aeruginosa degrades pulmonary surfactant and increases conversion in vitro. Am J Respir Cell Mol Biol 2005; 32(2): 128-134.
Noah TL Murphy PC Alink JJ Leigh MW Hull WM Stahlman MT Whitsett JA. Bronchoalveolar lavage fluid surfactant protein A and surfactant protein D are inversely related to inflammation in early cystic fibrosis. Am J Respir Crit Care Med 2003; 168(6): 685-691.
Lee HM Kang J Woo JS Chae SW Lee SH Hwang SJ. Upregulation of surfactant protein A in chronic rhinosinusitis. Laryngoscope 2006; 116(2): 328-330.
Wooten CT Labadie RF Chen A Lane KF. Differential expression of surfactant protein A in the nasal mucosa of patients with allergy symptoms. Arch Otolaryngol Head Neck Surg 2006; 132(9): 1001-1007.
Bluestone CD Klein JO. Physiology pathophysiology and pathogenesis. In: Donley SS editor. Otitis media in infants and children. 3rd ed. Philadelphia PA: Saunders; 2001 p. 34-57.
Teele DW Klein JO Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective cohort study. J Infect Dis 1989; 160(1): 83-94.
Teele DW Klein JO Chase C Menyuk P Rosner BA. Otitis media in infancy and intellectual ability school achievement speech and language at age of 7 years. Greater Boston Otitis Media Study Group. Pediatr Infect Dis J 1990; 162(3): 685-694.
Flisberg K Ingelstedt S Ortegren U. On middle ear pressure. Acta Otolaryngol (Stockh) 1963; 182: 43-56.
Grace A Kwok P Hawke M. Surfactant in middle ear effusions. Otolaryngol Head Neck Surg 1984; 96(4): 336-340.
Karchev T Watanabe N Fujiyoshi T Mogi G Kato S. Surfactant-producing epithelium in the dorsal part of the cartilaginous eustachian tube of mice. Light transmission and scanning electron microscopic observations. Acta Otolaryngol (Stockh) 1994; 114(1): 64-69.
Paananen R Glumhoff V Hallman M. Surfactant protein A and D expression in the porcine eustachian tube. FEBS Lett 1999; 452(3): 141-144.
Hills BA. Analysis of eustachian surfactant and its function as a release agent. Arch Otolaryngol 1984; 110(1): 3-9.
Svane-Knudsen V Larsen HF Brask T. Secretory otitis media - A question of surface activity in eustachian tube? Acta Otolaryngol (Stockh) 1988; 105(1-2): 114-119.
Heerbeek N Tonnaer E Ingels K Curfs J Cremers C. Effect of exogenous surfactant on ventilatory and clearance function of rat's eustachian tube. Otol Neurootol 2003; 24(1): 6-10.
Calkovsky V Hajtman A. The importance of surface-active material in Eustachian tube and the relation to otitis media. Otorinol a foniatr 2007; 56(3): 160-163 (in Slovak).
Koten M Uzun C Yazig R Adali MK Karasalihoglu AR Tatman-Otkun M Altaner S. Nebulized surfactant as a treatment choice for otitis media with effusion: an experimental study in the rabbit. J Laryngol Otol 2001; 115(5): 363-368.
De Sanctis GT Tomkiewicz RP Rubin BK Schück S King M. Exogenous surfactant enhances mucociliary clearance in the anesthetized dog. Eur Respir J 1994; 7(9): 1616-1621.
Calkovska A Some M Linderholm B Curstedt T Robertson B. Therapeutic effects of exogenous surfactant enriched with dextran in newborn rabbits with respiratory failure induced by airway instillation of albumin. Pulm Pharmacol Ther 2008; 21(2): 393-400.
Calkovska A Some M Linderholm B Johansson J Curstedt T Robertson B. Biophysical and physiological properties of porcine surfactant enriched with polymyxin B. Biol Neonate 2005; 88(2): 101-108.