Export file:

Format

  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text

Content

  • Citation Only
  • Citation and Abstract

Immunological and toxicological effects of bad indoor air to cause Dampness and Mold Hypersensitivity Syndrome

1 Medicum, Department of Bacteriology and Immunology, University of Helsinki, Finland. P.O. Box 21, 00014 University of Helsinki, Finland
2 Medical Center Kruunuhaka Oy, Kaisanimenkatu 8Ba, Helsinki, Finland
3 Medicum, Department of Pathology, P.O. Box 21, 00014 University of Helsinki, Finland

Water damage in buildings is a universe problem. Long-lasting or cumulative stay in water damaged buildings is a serious health hazard. Exposure to fungal and bacterial toxins, nanoparticles from dampness microbiota as well as decay products from construction materials together with biocides used for cleaning will first cause irritation of the mucosa and later chronic inflammation with stimulation or inhibition of the compartments of the innate and/or adaptive immunity. Mold-related disease has been called Dampness and Mold Hypersensitive Syndrome (DMHS) because hypersensitivity is the cornerstone feature of the disease. The background of hypersensitivity is both immunologic processes and hyperactivation of sensory receptors, neurogenic inflammation and central sensitisation. Immunologic hypersensitivity can occur either through the production of mold specific IgE-class antibodies, which is rare, or through sensitisation and proliferation of T and B specific lymphocyte clones. Immunological switch to Th2/Th17 arm of adaptive immunity often occurs. DMHS is a systemic and multi-organ disease where involvement of mucosa of pulmonary or gastrointestinal tract is central to the pathology. Symptoms include recurrent infections, chronic rhinosinusitis, swelling of the sinuses, irritation of the eyes and skin, voice problems, chronic non-productive cough, neurological symptoms, joint and muscle symptoms, irritable bowel syndrome and cognitive problems. Underdiagnosed or neglected continuous insidious inflammation may lead to Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS) especially when trigged by new infections or even vaccination. Multiple Chemical Sensitivity (MCS) may also develop, however in the later stages of the disease. Chronic cough is sometimes diagnosed as asthma if the criteria for asthma are met. Non-productive cough may also manifest allergic alveolitis, which is often overlooked. Avoidance of new exposure to dampness microbiota is crucial for recovery. We review the underlying toxicological and immunological mechanisms that are central in the pathology of DMHS.
  Figure/Table
  Supplementary
  Article Metrics

References

1. Environmental health/indoor air/mold house and water damage. From the National Institute of Health and Welfare. Available from: https://thl.fi/fi/web/ymparistoterveys/sisailma/hometalo-ja-kosteusvaurio Assessed 12.10.2018.

2. Reijula K (1996) Health risks and diagnostics of diseases caused by moisture and mold damage buildings. Kosteus-ja homevauriorakennuksien aiheuttamat terveysriskit ja sairauksien diagnostiikka. Duodecim 112: 1390–1397.

3. Becher R, Høie AH, Bakke JV, et al. (2017) Dampness and moisture problems in Norwegian homes. Int J Environ Res Public Health 14: 1241.    

4. WHO (2009) WHO guidelines for indoor air quality: Dampness and mould. World Health Organization 2009. Copenhagen, Denmark. ISBN-13: 978-92-890-4168-3.

5. Reponen T, Levin L, Zheng S, et al. (2013) Family and home characteristics correlate with mold in homes. Environ Res 124: 67–70.    

6. Available from: http://www.sisailmayhdistys.fi/Terveellisettilat/Kosteusvauriot/Mikrobit/ Microbial growth conditions. Assessed 23.7.2018 (Finnsh).

7. Finnish Broadcasting from YLE. Available from: https://yle.fi/uutiset/3-9885382. Assessed 23.7.2018 (Finnish).

8. Kuhn DM, Ghannoum MA (2003) Indoor mold, toxigenic fungi, and Stachybotrys chartum: Infectious disease perspective. Clin Microbiol Rev 16: 144–172.    

9. Miller CS (2001) The compelling anomaly of chemical intolerance. Ann N Y Acad Sci 933: 1–23.

10. Global Indoor Health Network (GIHN) Diagnosis and Treatment of Illness Caused by Contaminants in Water-Damaged Buildings. "Working Together for Healthy Indoor Environments" PO Box 777308 Henderson, NV 89077-7308, Available from: https://www.globalindoorhealthnetwork.com/.

11. Valtonen V (2017) Clinical diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the literature and suggested diagnostic criteria. Front Immunol 8: 951.    

12. Park JH, Cox-Ganser JM (2011) Mold exposure and respiratory health in damp indoor environments. Front Biosci (Elite Ed) 3: 757–771.

13. Fisk WJ, Lei-Gomez Q, Mendell MJU (2007) Meta-analyses of the associations of respiratory health effects with dampness and mold in homes. Indoor Air 17: 284–296.    

14. Fisk WJ, Elisevaara A, Mendel MJ (2010) Association of residential dampness and mold with respiratory tract infections and bronchitis: A meta-analysis. Environ Health 15: 1–11.

15. Hurraβ J, Heinzow B, Aurbach U, et al. (2017) Medical diagnostics for indoor mold exposure. Int J Hyg Envir Health 220: 305–328.    

16. Mendell MJ, Mirer AG, Cheung K, et al. (2011) Respiratory and allergic health effects of dampness, mold, and dampness-related agents: A review of the epidemiologic evidence. Environ Health Persp 119: 748–756.    

17. Alenius H, Haahtela T, Hakulinen A, et al. (2007) Recommendations of Majvik II-Identifying symptoms related to moisture damage microbes. Majvik II-suositus: Kosteusvauriomikrobeihin liittyvien oireiden selvittely SLL 7: 655–664.

18. Park JH, Cho SJ, White SK, et al. (2018) Changes in respiratory and nonrespiratory symptoms in occupants of a large office building over a period of moisture damage remediation attempts. PLoS One 13: e0191165.    

19. Aggarwald AN, Chakrabarti A (2013) Does climate mould influence of mold on asthma? Lung India 30: 273–276.    

20. Empting LD (2009) Neurologic and neuropsychiatric syndrome features of mold and mycotoxin exposure. Toxicol Int Health 25: 577–581.    

21. Tuuminen T, Rinne KS (2017) Severe sequelae to mold-related illness as demonstrated in two finnish cohorts. Front Immunol 8: 382.

22. Tuuminen T, Jääskeläinen T, Vaali K, et al. (2018) Dampness and mold hypersensitivity syndrome and vaccination as risk factors for chronic fatigue syndrome. Autoimmun Rev 5: S1568–S9972.

23. Thrasher JD, Gray MR, Kilburn KH, et al. (2012) A water-damaged home and health of occupants: A case study. J Environ Public Health 2012: 10.

24. Pitkäranta A, Hytönen M, Näin hoidan (2006) Pitkittynyt nuha. Duodecim 122: 827.

25. Shaaban R, Zureik M, Soussan D, et al. (2008) Rhinitis and onset of asthma: A longitudinal population-based study. Lancet 372: 1049–1057.    

26. Brewer JH, Thrasher JD, Hooper D (2013) Chronic illness associated with mold and mycotoxins: Is naso-sinus fungal biofilm the culprit? Toxins 24: 66–80.

27. Kwon JW, Kim TW, Kim KM, et al. (2012) Differences in airway inflammation according to atopic status in patients with chronic rhinitis. Asia Pac Allergy 2: 248–255.    

28. Lanthier-Veilleux M, Baron G, Généreux M (2016) Respiratory diseases in university students associated with exposure to residential dampness or mold. Int J Environ Res Public Health 13: 1154.    

29. Jalanko H (2017) Infections in child. Infektiokierre lapsella. Duodecim Terveyskirjasto. Available from: https://www.terveyskirjasto.fi/kotisivut/tk.koti?p_artikkeli=dlk00131.

30. Löwhagen O (2015) Diagnosis of asthma-new theories. J Asthma 52: 538–544.    

31. Hasegawa T, Uga H, Mori A, et al. (2017) Increased serum IL-17A and Th2 cytokine levels in patients with severe uncontrolled asthma. Eur Cytokine Netw 28: 8–18.

32. Reponen T, Vesper S, Levin L, et al. (2011) High environmental relative moldiness index during infancy as a predictor of asthma at 7 years of age. Ann Allerg Asthma Im 107: 120–126.    

33. Hsu J, Chen J, Mirabelli MC (2018) Asthma morbidity, comorbidities, and modifiable factors among older adults. J Allergy Clin Immun 6: 236–243.    

34. Kanchongkittiphon W, Mendell MJ, Gaffin JM, et al. (2015) Indoor environmental exposures and exacerbation of asthma: An update to the 2000 review by the institute of medicine. Environ Health Persp 123: 6–20.    

35. Bush RK, Portnoy JM, Saxon A, et al. (2006) The medical effects of mold exposure. J Allergy Clin Immun 117: 326–333.    

36. Eerikäinen J, Nynäs P, Uitti J (2013) Subacute allergic alveolitis caused by work-related moisture damage microbes. Työperäinen kosteusvauriomikrobien aiheuttama subakuutti allerginen alveoliitti. Duodecim 129: 972–975.

37. Selman M, Pardo A, King Jr TE (2012) Hypersensitivity pneumonitis: Insights in diagnosis and pathobiology. Am J Resp Crit Care 186: 314–324.

38. Thörn Å, Lewene M, Belin L (1996) Allergic alveolitis in a school environment. Scand J Work Environ Health 22: 311–314.    

39. Reijula K, Sutinen S (1986) Ultrastructure of extrinsic allergic bronchiolo-alveolitis. Pathol Res Pract 181: 418–429.    

40. Galeazzo G, Sforza R, Marinou A (2017) Hypersensitivity pneumonitis: A complex lung disease. Clin Mol Allergy 15: 1–8.    

41. Kumar V, Aster JC, Fausto N, et al. (2014) Robbins and cotran pathologic basis of disease, Professional Edition. Elsevier LTD, Oxford.

42. Agarwal R, Chakrabarti A, Shah A, et al. (2013) Allergic bronchopulmonary aspergillosis: Review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy 43: 850–873.    

43. Greenberger PA, Bush RK, Demain JG, et al. (2014) Allergic bronchopulmonary aspergillosis. J Allergy Clin Immun 2: 703–708.    

44. Chowdhary A1, Agarwal K, Kathuria S, et al. (2014) Allergic bronchopulmonary mycosis due to fungi other than aspergillus: A global overview. Crit Rev Microbiol 40: 30–48.    

45. Nordman H, Uitti J, Toskala-Hannikainen E, et al. (2007) Kosteusvauriomikrobien aiheuttamien sairauksien tutkiminen. SLL 9: 911–918.

46. Kankkunen P, Teirilä L, Rintahaka J, et al. (2010) (1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. J Immunol 184: 6335–6342.    

47. Korkalainen M, Täubel M, Naarala J, et al. (2017) Synergistic proinflammatory interactions of microbial toxins and structural components characteristic to moisture-damaged buildings. Indoor Air 27: 13–23.    

48. Gray MR, Thrasher JD, Crago R, et al. (2003) Mixed mold mycotoxicosis: Immunological changes in humans following exposure in water-damaged buildings. Arch Environ Health 58: 410–420.    

49. Trasher JD (2016) Fungi, bacteria, nanoparticulates, mycotoxins and human health in water damaged indoor environments. J Comm Pub Health Nurs. researchgate.net.

50. Pestka JJ, Yike I, Dearborn DG, et al. (2008) Stachybotrys chartarum, trichothecene mycotoxins, and damp building-related illness: new insights into a public health enigma. Toxicol Sci 104: 4–26.    

51. Edmondson DA, Barrios CS, Brasel TL, et al. (2009) Immune response among patients exposed to molds. Int J Mol Sci 10: 5471–5484.    

52. Ammann HM (2002) Indoor mold contamination-a threat to health? J Environ Health 64: 43.

53. Ammann HM (2003) Indoor mold contamination-a threat to health? Part two. J Environ Health 66: 47.

54. Ammann HM (2016) Inhalation exposure and toxic effects of mycotoxins. Biol Microfungi 495–523.

55. Mikkola R, Andersson MA, Grigoriev P, et al. (2017) The mitochondrial toxin produced by Streptomyces griseus strains isolated from an indoor environment is valinomycin. J Appl Microbiol 123: 436–449.    

56. Islam Z, Harkema JR, Pestka JJ (2006) Satratoxin G from the black mold stachybotrys chartarum evokes olfactory sensory neuron loss and inflammation in the murine nose and brain. Environ Health Persp 114: 1099–1107.    

57. Jarvis BB (2003) Analysis for mycotoxins: The chemist's perspective. Arch Environ Health 58: 479–483.    

58. Kankkunen P, Välimäki E, Rintahaka J, et al. (2014) Trichothecene mycotoxins activate NLRP3 inflammasome through a P2X7 receptor and Src tyrosine kinase dependent pathway. Hum Immunol 75: 134–140.

59. Wong J, Magun BE, Wood LJ (2016) Lung inflammation caused by inhaled toxicants: A review. Int J Chron Obstruct Pulmon Dis 11: 1391–1401.

60. Huttunen K, Hyvärinen A, Nevalainen A, et al. (2003) Production of proinflammatory mediators by indoor air bacteria and fungal spores in mouse and human cell lines. Environ Health Persp 111: 85–92.    

61. Li M, Harkema JR, Islam Z, et al. (2006) T-2 toxin impairs murine immune response to respiratory retrovirus and exacerbates viral bronchiolitis. Toxicol Appl Pharm 217: 76–85.    

62. Wang H, Yadav JS (2006) DNA damage, redox changes, and associated stress-inducible signaling events underlying the apoptosis and cytotoxicity in murine alveolar macrophage cell line MH-S by methanol-extracted Stachybotrys chartarum toxins. Toxicol Appl Pharm 214: 297–308.    

63. Penttinen P, Tampio M, Mäki-Paakkanen J, et al. (2007) DNA damage and p53 in RAW264.7 cells induced by the spores of co-cultivated Streptomyces californicus and Stachybotrys chartarum. Toxicol 235: 92–102.

64. Penttinen P, Pelkonen J, Huttunen K, et al. (2005) Interactions between streptomyces californicus and Stachybotrys chartarum can induce apoptosis and cell cycle arrest in mouse RAW264.7 macrophages. Toxicol Appl Pharm 202: 278–288.    

65. Ndika J, Suojalehto H, Täubel M, et al. (2018) Nasal mucosa and blood cell transcriptome profiles do not reflect respiratory symptoms associated with moisture-damage. Indoor Air, May 4. doi: 10.1111/ina.12472.

66. Hellgren UM, Leino M, Aarnisalo AA, et al. (2009) Low tumor necrosis factor alpha levels and neutrophil counts in nasal lavage after mold exposure. Ann Allergy Asthma Im 102: 210–215.    

67. Schütze N, Lehmann I, Bönisch U, et al. (2010) Exposure to mycotoxins increases the allergic immune response in a murine asthma model. Am J Resp Crit Care 181: 1188–1199.

68. Bhan U, Newstead MJ, Zeng X, et al. (2011) Stachybotrys chartarum-induced hypersensitivity pneumonitis is TLR9 dependent. Am J Pathol 179: 2779–2787.    

69. Vincent M, Percier P, De Prins S, et al. (2017) Investigation of inflammatory and allergic responses to common mold species: Result from in vitro experiments, from a mouse model of asthma, and from a group of asthmatic patients. Indoor Air 27: 933–945.    

70. Taskinen T. Moisture and mould problem in school children. Väitöskirja. Kuopio KTL. A9/2001. (Academic dissertation).

71. Flamant-Hulin M, Anniesi-Maesano I, Caillaud D (2013) Relationships between molds and asthma suggesting non-allergic mechanisms. A rural-urban comparison. Pediatr Allergy Immu 24: 345–352.    

72. Weinmayr G, Gehring U, Genuneit J, et al. (2013) Dampness and moulds in relation to respiratory and allergic symptoms in children: A result from Phase two of the international study of asthma and allergies in childhood (ISAAC phase two). Clin Exp Allergy 43: 762–774.    

73. Andersson MA, Mikkola R, Helin J, et al. (1998) A novel sensitive bioassay for detection of Bacillus cereus emetic toxin and related depsipeptide ionophores. Appl Environ Microb 64: 1338–1343.

74. Andersson MA, Mikkola R, Kroppenstedt RM, et al. (1998) The mitochondrial toxin produced by Streptomyces griseus strains isolated from an indoor environment is valinomycin. Appl Environ Microb 64: 4767–4773.

75. Korppi M, Dunder T, Remes S, et al. (2011) Congenital dysfunction of ciliary cells in children Värekarvojen synnynnäiset toimintahäiriöt lapsilla. Duodecim 127: 2294–2302.

76. Piecková E (2003) In vitro toxicity of indoor Chaetomium Kunze ex Fr. Ann Agr Env Med 10: 9–14.

77. Piecková E, Wilkins K (2004) Airway toxicity of house dust and its fungal composition. Ann Agr Env Med 11: 67–73.

78. Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140: 805–820.    

79. Zhang Z, Myers JMB, Brandt EB, et al. (2017) β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses. J Allerg Clin Immun 139: 54–65.    

80. Martin TR, Frevert CW (2005) Innate immunity in the lungs. P Am Thorac Soc 2: 403–411.    

81. Rasimus-Sahari S, Teplova VV, Andersson MA, et al. (2015) The peptide toxin amylosin of Bacillus amyloliquefaciens from moisture-damaged buildings is immunotoxic, induces potassium efflux from mammalian cells, and has antimicrobial activity. Appl Environ Microb 81: 2939–2949.    

82. van de Veerdonk FL, Gresnigt MS, Romani L, et al. (2017) Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol 15: 661–674.    

83. Kankkunen P, Rintahaka J, Aalto A, et al. (2009) Trichothecene mycotoxins activate inflammatory response in human macrophages. J Immunol 182: 6418–6425.    

84. Peltonen S, Kari O, Jarva H, et al. (2008) Complement activation in tear fluid during occupational mold challenge. Ocul Immunol Inflamm 16: 224–229.    

85. Lam K, Schleimer R, Kern RC (2015) The etiology and pathogenesis of chronic rhinosinusitis: A review of current hypotheses. Curr Allergy Asthma Rep 15: 41.    

86. Veldhoen M (2017) Interleukin 17 is a chief orchestrator of immunity. Nat Immunol 18: 612–621.    

87. Lichtenstein JHR, Hsu YI, Gavin IM, et al. (2015) Environmental mold and mycotoxin exposures elicit specific cytocine and chemocine responses. PLoS One 10: e0126926.    

88. Nikulin M, Reijula K, Jarvis BB, et al. (1997) Effects of intranasal exposure to spores of Stachybotrys atria in mice. Fund Appl Toxicol 35: 182–188.    

89. Leino M, Mäkelä M, Reijula K, et al. (2003) Intranasal exposure to a damp building mould, Stachybotrys chartum, induces lung inflammation in mice by satratoxin-indipendent mechanisms. Clin Exp Allergy 33: 1603–1610.    

90. King J, Richardson M, Quinn AM, et al. (2017) Bagpipe lung; a new type of interstitial lung disease? Thorax 72: 380–382.    

91. Wolff H, Mussalo-Rauhamaa H, Raitio H, et al. (2009) Patients referred to an indoor air health clinic: Exposure to water-damaged buildings causes an increase of lymphocytes in bronchoalveolar lavage and a decrease of CD19 leucocytes in peripheral blood. Scand J Clin Lab Inv 69: 537–544.    

92. Tuuminen T, Lohi J (2018) Revising the criteria for occupational mold-related disease: Arguments, misconceptions and facts. EMJ Allergy Immunol 1: 128–135.

© 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Article outline

Show full outline
Copyright © AIMS Press All Rights Reserved