Skip to main content
SpringerLink
Log in

The Genetics and Epidemiology of Asthma

  • Chapter
Bronchial Asthma

  • 128 Accesses

Abstract

What roles do genes and the environment play in the development and expression of asthma? This question has intrigued scientists since Cooke and Vander Veer (1) conducted the first twin studies of atopy more than 75 years ago. Since then, our understanding of human genetics has advanced enormously, although our knowledge of the role of hereditary factors in the etiology of IgE-mediated disease has accumulated at a slower pace (2,3). This chapter will review the genetics and epidemiology of asthma and illustrate recent advances in the quantitative genetic modeling of asthma liability. We first distinguish asthma from other respiratory disorders and symptoms—wheezy breathing, bronchial hyperreactivity, and bronchitis—and then review asthma prevalence, incidence, mortality rates, and genetic aspects. The environmental risk factors for asthma are also briefly reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cooke RA and Van der Veer, A Jr. Human sensitization. J. Immunol. 1916; 1:201–305.

    CAS  Google Scholar 

  2. Cookson WOCM and Hopkin JM. Dominant inheritance of atopic immunoglobulin-E responsiveness. Lancet 1988; 1:86–88.

    Article  PubMed  CAS  Google Scholar 

  3. Cookson WOCM, Faux JA, Sharp PA, and Hopkin JM. Linkage between immunoglobulin E responses underlying asthma and rhinitis and chromosome 11q. Lancet 1989; 1:1292–1294.

    Article  PubMed  CAS  Google Scholar 

  4. Busse WW. Respiratory infections and bronchial hyperreactivity. J. Allergy Clin. Immunol. 1988; 81:770–775.

    Article  PubMed  CAS  Google Scholar 

  5. Levitt RC, Mitzner W, and Kleeberger SR. A genetic approach to the study of lung physiology: understanding biological variability in airway responsiveness. Am. J. Physiol. 1990; 258:L157–L164.

    PubMed  CAS  Google Scholar 

  6. Sheppard D. Mechanisms of acute increases in airway responsiveness caused by environmental chemicals. J. Allergy Clin. Immunol. 1988; 81:128–132.

    Article  PubMed  CAS  Google Scholar 

  7. Elwood W, Lotvall JO, Barnes PJ, and Chung KF. Characterization of allergen-induced bronchial hyperesponsiveness and airway inflammation in actively sensitized Brown-Norway rats. J. Allergy Clin. Immunol. 1991; 88:951–960.

    Article  PubMed  CAS  Google Scholar 

  8. Barnes PJ. New concepts in the pathogenesis of bronchial hyperesponsiveness and asthma. J. Allergy Clin. Immunol. 1989; 122:1013–1026.

    Article  Google Scholar 

  9. Dodge RR and Burrows B. The prevalence and incidence of asthma and asthma-like symptoms in a general population sample. Am. Rev. Resp. Dis. 1980; 122:567.

    PubMed  CAS  Google Scholar 

  10. Burr ML, Butland BK, King S, and Vaughan-Williams E. Changes in asthma prevalence: two surveys 15 years apart. Arch. Dis. Child. 1989; 64:1452–1456.

    Article  PubMed  CAS  Google Scholar 

  11. Weitzman M, Gortmaker S, and Sobol A. Racial, social and environmental risks for childhood asthma. Am. J. Dis. Child. 1990; 144:1189–1194.

    PubMed  CAS  Google Scholar 

  12. Gergen PJ and Weiss KB. Changing patterns of asthma hospitalization among children: 1979-1987. JAMA 1990; 264:1688–1692.

    Article  PubMed  CAS  Google Scholar 

  13. Turkeltaub PC and Gergen PJ. Prevalence of upper and lower respiratory conditions in the US population by social and environmental factors: data from the second National Health and Nutrition Examination Survey, 1976 to 1980 (NHANES II). Ann. Allergy 1991; 67:147–154.

    PubMed  CAS  Google Scholar 

  14. Voy RO. The US Olympic Committee experience with exercise-induced bronchospasm. 1984. Med. Sci. Sports Exerc. 1986; 18:328–330.

    Article  PubMed  CAS  Google Scholar 

  15. Evans R, Wilson RW, Rosenberg HM, and Chevarley FM. National trends in the morbidity and mortality of asthma in the US. Prevalence, hospitalization and death from asthma over two decades: 1965-1984. Chest 1987; 91(Suppl.): 65S–74S.

    Google Scholar 

  16. Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, Boivin JF, McNutt M, Buist AS, and Rebuck AS. The use of beta agonists and the risk of death and near death from asthma. N. Eng. J. Med. 1992; 326: 501–506.

    Article  CAS  Google Scholar 

  17. Jackson R, Sears MR, Beaglehole R, and Rea HH. International trends in asthma mortality: 1970 to 1985. Chest 1988; 94:914–918.

    Article  PubMed  CAS  Google Scholar 

  18. Mitchell EA. Is current treatment increasing asthma mortality and morbidity? Thorax 1989; 44:81–84.

    Article  PubMed  CAS  Google Scholar 

  19. Buist AS and Vollmer WM. Reflections on the rise in asthma morbidity and mortality. JAMA 1990; 264:1719–1720.

    Article  PubMed  CAS  Google Scholar 

  20. Paulozzi LJ, Coleman JJ, and Buist AS. A recent increase in asthma mortality in the Northwestern United States. Ann. Allergy 1986; 56:392–395.

    PubMed  CAS  Google Scholar 

  21. Weiss KB. Seasonal trends in US asthma hospitalizations and mortality. JAMA 1990; 263:2323–2328.

    Article  PubMed  CAS  Google Scholar 

  22. NationalAsthma Education Program Expert Panel Report. Guidelines for the Diagnosis and Management of Asthma. 3. Asthma mortality. US Department of Health and Human Services, 1991. Pub No 91–3042, pp. 29–31.

    Google Scholar 

  23. Weiss KB and Wagener DK. Changing patterns of asthma mortality. Identifying target populations at high risk. JAMA 1990; 264:1683–1687.

    Article  PubMed  CAS  Google Scholar 

  24. Burney PGJ. Asthma mortality: England and Wales. J. Allergy Clin. Immunol. 1987; 80:379–382.

    Article  PubMed  CAS  Google Scholar 

  25. Anderson HR and Strachan DP. Asthma mortality in England and Wales, 1979-89. Lancet 1991; 337:1357.

    Article  PubMed  CAS  Google Scholar 

  26. Dawson KP and Mitchell EA. Asthma in New Zealand children. J. Asthma 1990; 27:291–297.

    Article  PubMed  CAS  Google Scholar 

  27. Mitchell EA, Anderson HR, Freeling P, and White PT. Why are hospital admissions and mortality rates for childhood asthma higher in New Zealand than in the United Kingdom? Thorax 1990; 45:176–185.

    Article  PubMed  CAS  Google Scholar 

  28. Sears MR and Beaglehole R. Asthma morbidity and mortality: New Zealand. J. Allergy Clin. Immunol. 1987; 80:383–388.

    Article  PubMed  CAS  Google Scholar 

  29. Bousquet J, Hatton F, Godard P, and Michel FB. Asthma mortality in France. J. Allergy Clin. Immunol. 1989; 80:389–394.

    Article  Google Scholar 

  30. Wever-Hess J, Wever AMJ, and Yntema JL. Mortality and morbidity from respiratory diseases in childhood in the Netherlands, 1980-1987. Eur. Resp. J. 1991; 4:429–433.

    CAS  Google Scholar 

  31. So SY, Ng MMT, Ip SM, and Lam WK. Rising asthma mortality in young males in Hong Kong, 1976-1985. Resp. Med. 1990; 84:457–461.

    Article  CAS  Google Scholar 

  32. Stolley PD and Schinnar R. Association between asthma mortality and isoproterenol aerosols: a review. Brev. Med. 1978; 7:319–338.

    Google Scholar 

  33. Woolcock AJ. Beta-agonists and asthma mortality. What have we learned, what questions remain? Drugs 1990; 40:653–656.

    Article  PubMed  CAS  Google Scholar 

  34. Pearce J, Grainger J, Atkinson M, Crane J, Brugess C, Culling C, Windom H, and Beasley R. Case-control study of prescribed fenoterol and death from asthma in New Zealand, 1977-81. Thorax 1990; 45:170–175.

    Article  PubMed  CAS  Google Scholar 

  35. Grainger J, Woodman K, Pearce N, Crane J, Burgess C, Keane A, and Beasley R. Prescribed fenoterol and death from asthma in New Zealand, 1981–7: a further case-control study. Thorax 1991; 46:105–111.

    Article  PubMed  CAS  Google Scholar 

  36. Falconer DS. Quantitative Genetics. Oliver and Boyd, Edinburgh, Scotland, 1960.

    Google Scholar 

  37. Holzinger KJ. The relative effect of nature and nurture influences on twin differences. J. Educ. Psych. 1929; 20:245–248.

    Google Scholar 

  38. Jinks JL and Fulker DW. Comparison of the biometrical genetical, MAVA, and classical approaches to the analysis of human behavior. Psych. Bull. 1970; 73:311–349.

    Article  CAS  Google Scholar 

  39. Marsh DG and Blumenthal MN, eds. Genetics and Environmental Factors in Clinical Allergy. University of Minnesota, Minneapolis, MN, 1990.

    Google Scholar 

  40. Eaves LJ, Eysenck HJ, and Martin NG. Genes, Culture and Personality. Academic, London, 1989; p. 23.

    Google Scholar 

  41. Edfors-Lubs ML. Allergy in 7,000 twin pairs. Acta Allergol. 1971; 26:249–285.

    Article  PubMed  CAS  Google Scholar 

  42. Gottesman I and Carey G. Extracting meaning and direction from twin data. Psych. Devel. 1983; 1:35–50.

    CAS  Google Scholar 

  43. Smith, C. Concordance in twins: methods and interpretation. Am. J. Hum. Genet. 1974; 26:454–466.

    PubMed  CAS  Google Scholar 

  44. Edfors-Lubs, ML. Allergy in 7,000 twin pairs. Acta Allergol. 1971; 26:273.

    Article  Google Scholar 

  45. Jöreskog KG and Sörbom D. PRELIS: A Preprocessor for LISREL. Scientific Software, Mooresville, IN, 1986.

    Google Scholar 

  46. Jöreskog KG and Sörbom D. LISREL VII. Scientific Software, Mooresville, IN, 1988.

    Google Scholar 

  47. Niemininen MM, Kaprio J, and Koskenvuo MD. A population-based study of bronchial asthma in adult twin pairs. Chest 1991; 100:70–75.

    Article  Google Scholar 

  48. Niemininen MM, Kaprio J, and Koskenvuo MD. A population-based study of bronchial asthma in adult twin pairs. Chest 1991; 100:72.

    Article  Google Scholar 

  49. Duffy D. Letter to the editor, Chest 1992; 102:654.

    Article  PubMed  CAS  Google Scholar 

  50. Duffy D, Martin NG, Battistutta D, Hopper JL, and Mathews JD. Genetics of asthma and hay fever in Australian twins. Am. Rev. Resp. Dis. 1990; 142:1351–1358.

    Article  PubMed  CAS  Google Scholar 

  51. Heath AC, Neale MC, Hewitt JK, Eaves LJ, and Fulker DW. Testing structural equation models for twin data using LISREL. Behav. Genet. 1989; 19:9–35.

    Article  PubMed  CAS  Google Scholar 

  52. Muthén BO. LISCOMP. Analysis of Linear Structural Equations with a Comprehensive Measurement Model, User’s Guide. Scientific Software, Mooresville, IN, 1987.

    Google Scholar 

  53. Waller NG and Muthén BO. Genetic Tobit Factor Analysis: quantitative genetic modeling with censored data. Behav. Genet. 1992; 22:265–292.

    Article  PubMed  CAS  Google Scholar 

  54. Sporik R, Holgate ST, Platts-Mills TAE, and Cogswell JJ. Exposure to house dust mite allergen (Der p I) and the development of asthma in childhood: a prospective study. N. Eng. J. Med. 1990; 323:502–507.

    Article  CAS  Google Scholar 

  55. Sporik R, Holgate ST, and Cosgswell JJ. The natural history of asthma in childhood. A birth cohort study. Arch. Dis. Child. 1991; 66:1050–1053.

    Article  PubMed  CAS  Google Scholar 

  56. Dekker H. Asthma und Milben. Munchener Medizinische Wochenschrift. 1928; 515–516. (Translated by Deaner, WC. J. Allergy Clin. Immunol. 1971; 48:251-252.)

    Google Scholar 

  57. Platts-Mills TAE, Thomas WR, Aalberse RC, Vervloet D, and Chapman MD. Dust mite allergens and asthma: report of a second international workshop. J. Allergy Clin. Immunol. 1992; 89:1046–1060.

    Article  PubMed  CAS  Google Scholar 

  58. Korsgaard J. Mite asthma and residency. A case-control study on the impact of exposure to house-dust mites in dwellings. Am. Rev. Resp. Dis. 1983; 128:231–235.

    PubMed  CAS  Google Scholar 

  59. Welliver RC, Wong DT, Sun M, Middleton E Jr., Vaughan RS, and Ogra PL. The development of respiratory syncytial virus specific IgE and the release of histamine in nasopharyngeal secretions after infection. N. Engl. J. Med. 1981; 305:841–846.

    Article  PubMed  CAS  Google Scholar 

  60. McIntosh K, Ellis EF, Hoffman LS, Lybass TG, Eller JJ, and Fulginiti VA. The association of viral and bacterial respiratory infections with exacerbations of wheezing in young asthmatic children. J. Pediatr. 1973; 82:578–590.

    Article  PubMed  CAS  Google Scholar 

  61. Lemanske RF Jr, Dick EC, Swenson CA, Vrtis RF, and Busse WW. Rhinovirus upper respiratory infection increases airway reactivity in late asthmatic reactions. J. Clin. Invest. 1989; 83:1–10.

    Article  PubMed  Google Scholar 

  62. Hudgel DW, Langsten E Jr, Seiner JC, and Mclntosh K. Viral and bacterial infections in adults with chronic asthma. Am. Rev. Resp. Dis. 1979; 120:393–397.

    PubMed  CAS  Google Scholar 

  63. Minor TE, Dick EC, Backer JW, Ouellette JJ, Cohen M, and Reed CE. Rhinovirus and influenza A infections as precipitants of asthma. Am. Rev. Resp. Dis. 1976; 113:149–153.

    PubMed  CAS  Google Scholar 

  64. Richards W. Effects of air pollution on asthma. Ann. Asthma 1990; 65:345–347.

    CAS  Google Scholar 

  65. Imai M, Yoshida K, and Kitabatake M. Mortality from asthma and chronic bronchitis associated with changes in sulfur oxides air pollution. Arch. Environ. Health 1986; 41:29–35.

    Article  PubMed  CAS  Google Scholar 

  66. Koenig JQ, Covert DS, Marshall SG, van Belle G, and Pierson WE. The effects of ozone and nitrogen dioxide on pulmonary function in healthy and in asthmatic adolescents. Am. Rev. Resp. Dis. 1987; 136:1152–1157.

    Article  PubMed  CAS  Google Scholar 

  67. Holtzman MJ, Fabbri LM, O’Byrne PM, Bold BD, Aizawa H, Walters EH, Albert SE, and Nadel JA. Importance of airway inflammation for hyperresponsiveness induced by ozone in dogs. Am. Rev. Resp. Dis. 1983; 127:686–690.

    PubMed  CAS  Google Scholar 

  68. O’Byrne PM, Walters EH, Gold BK, Aizawa HA, Fabbri LM, Alpert SE, Nadel JA, and Holtzman MJ. Neutrophil depletion inhibits airway hyperresponsiveness induced by ozone exposure. Am. Rev. Resp. Dis. 1984; 130:214–219.

    PubMed  Google Scholar 

  69. Murlas CG and Roum JH. Sequence of pathologic changes in the airway mucosa of guinea pigs during ozone-induced bronchial hyperreactivity. Am. Rev. Resp. Dis. 1985; 131:314–320.

    PubMed  CAS  Google Scholar 

  70. Lee HK and Murlas C. Ozone-induced bronchial hyperreactivity in guinea pigs is abolished by BW755c or FPL55712 but not by indomethacin. Am. Rev. Resp. Dis. 1985; 132:1005–1009.

    PubMed  CAS  Google Scholar 

  71. Graham DE and Koren HS. Biomarkers of inflammation in ozone-exposed humans: comparison of the nasal and bronchoalveolar lavage. Am. Rev. Resp. Dis. 1990; 142:152–156.

    Article  PubMed  CAS  Google Scholar 

  72. Kreit JW, Gross KB, Moore TB, Lorenzen TJ, D’Arcy J, and Eschenbacher WL. Ozone-induced changes in pulmonary function and bronchial responsiveness in asthmatics. J. Appl. Physiol. 1989; 66:217–222.

    PubMed  CAS  Google Scholar 

  73. Lippmann M. Health effects of ozone. A critical review. J. Air Pollut. Control Assoc. 1989; 39:672–695.

    CAS  Google Scholar 

  74. Koenig JQ, Pierson WE, Horike M, and Frank R. Effects of SO2 plus NaCl aerosol combined with moderate exercise on pulmonary function in asthmatic adolescents. Environ. Res. 1981; 25:340–348.

    Article  PubMed  CAS  Google Scholar 

  75. Sandström T, Stjernberg N, Andersson M-C, Kolomodin-Hedman B, Lundgren R, Rosenhall L, and Angström T. Cell response in broncholalveolar lavage fluid after exposure to sulfur dioxide: a time-response study. Am. Rev. Resp. Dis. 1989; 140:1828–1831.

    Article  PubMed  Google Scholar 

  76. Koenig JQ, Pierson WE, and Horike M. The effects of inhaled sulfuric acid on pulmonary function in adolescent asthmatics. Am. Rev. Resp. Dis. 1983; 128:221–225.

    PubMed  CAS  Google Scholar 

  77. Utell, MJ, Morrow PE, and Hyde RW. Airway reactivity to sulfate and sulfuric acid aerosols in normal and asthmatic subjects. J. Air Pollut. Control Assoc. 1984; 34:931–935.

    Article  PubMed  CAS  Google Scholar 

  78. Burrows B, Halonen-Barbee RA, and Lebowitz MD. The relationship of serum immunoglobulin E to cigarette smoking. Am. Rev. Resp. Dis. 1981; 124:523–525.

    PubMed  CAS  Google Scholar 

  79. Warren CPW, Holford-Strevens V, Wong C, and Manfreda J. The relationship between smoking and total immunoglobulin E levels. J. Allergy Clin. Immunol. 1982; 69:370–375.

    Article  PubMed  CAS  Google Scholar 

  80. Cockcroft D. Cigarette smoking, airway hyperresponsiveness, and asthma. Chest 1988; 94:675–676.

    Article  PubMed  CAS  Google Scholar 

  81. Gortmaker SL, Walker DK, Jacobs FH, and Ruch-Ross H. Parental smoking and the risk of childhood asthma. Am. J. Public Health 1982; 72:574–579.

    Article  PubMed  CAS  Google Scholar 

  82. Martinez FD, Antognini G, Macri F, Bonci E, Midulla F, De Castro G, and Ronchetti R. Parental smoking enhances bronchial responsiveness in nine year old children. Am. Rev. Resp. Dis. 1988; 138:518–523.

    Article  PubMed  CAS  Google Scholar 

  83. Willers S, Svenoniou E, and Skarping G. Passive smoking in childhood asthma: urinary cotinine levels in children with asthma and in referents. Allergy 1991; 46:330–334.

    Article  PubMed  CAS  Google Scholar 

  84. Dekker C, Dales R, Bartlett S, Brunekreef B, and Zwanenburg H. Childhood asthma and the indoor environment. Chest 1991; 100:922–926.

    Article  PubMed  CAS  Google Scholar 

  85. Spector SL. Common triggers of asthma. Postgrad. Med. 1991; 90:50–59.

    PubMed  CAS  Google Scholar 

  86. Mendis AH, Venaille TJ, and Robinson BW. Study of human epithelial cell detachment and damage: effects of proteases and oxidants. Immunol. Cell Biol. 1990;68:95–105.

    Article  PubMed  CAS  Google Scholar 

  87. Meltzer S, Goldberg B, Lad P, and Easton J. Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma. J. Allergy Clin. Immunol. 1989; 83:960–966.

    Article  PubMed  CAS  Google Scholar 

  88. Chanez P, Dent G, Yukawa T, Barnes PJ, and Chung KF. Generation of oxygen free radicals from blood eosinophils from asthma patients after stimulation with PAF or phorbol ester. Eur. Resp. J. 1990; 3:1002–1007.

    CAS  Google Scholar 

  89. Cluzel M, Damon M, Chanez P, Bousquet J, Crastes de Paulet A, Michel FB, and Godard P. Enhanced alveolar cell luminol-dependent chemiluminescence in asthma. J. Allergy Clin. Immunol. 1987; 80:195–201.

    Article  PubMed  CAS  Google Scholar 

  90. Doelman CJ and Bast A. Oxygen radicals in lung pathology. Free Radical Biol. Med. 1990; 9:381–400.

    Article  CAS  Google Scholar 

  91. Barnes PJ. Reactive oxygen species and airway inflammation. Free Radical Biol. Med. 1990; 9:235–243.

    Article  CAS  Google Scholar 

  92. Nijkamp FP and Henricks PA. Receptors in airway disease. Beta-adrenoceptors in lung inflammation. Am. Rev. Resp. Dis. 1990; 141:S145–S150.

    Article  PubMed  CAS  Google Scholar 

  93. Chilvers ER, Garratt H, Whyte MK, Fink R, and Ind PW. Absence of circulating products of oxygen derived free radicals in acute severe asthma. Eur. Resp. J. 1989; 2:950–954.

    CAS  Google Scholar 

  94. Stone J, Hinks LJ, Beasley R, Holgate ST, and Clayton BA. Reduced selenium status of patients with asthma. Clin. Sci. 1989; 77:495–500.

    PubMed  CAS  Google Scholar 

  95. De Lucia F, Bonavia M, Crimi E, Scaricabarozzi I, and Brucasco V. Antiinflammatory-antioxidant treatment with a methane sulfonalide in allergen-induced asthma. Ann. Allergy 1991; 66:424–429.

    Google Scholar 

  96. Busse W, Randley B, and Sedgwick J. The effect of azelastine on neutrophil and eosinophil generation of Superoxide. J Allergy Clin. Immunol. 1989; 83:400–405.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of California School of Medicine, Davis, CA, USA

    Niels G. Waller

  2. University of California School of Medicine, Davis, CA, USA

    Suzanne S. Teuber

  3. University of California School of Medicine, Davis, CA, USA

    M. Eric Gershwin

Authors
  1. Niels G. Waller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suzanne S. Teuber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Eric Gershwin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California School of Medicine, Davis, CA, USA

    M. Eric Gershwin  & Georges M. Halpern  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Waller, N.G., Teuber, S.S., Gershwin, M.E. (1994). The Genetics and Epidemiology of Asthma. In: Gershwin, M.E., Halpern, G.M. (eds) Bronchial Asthma. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-0297-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-0297-4_1

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-6697-6

  • Online ISBN: 978-1-4612-0297-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation