Newer Molecular Methods Bring New Insights into Human- And Building-Health Risk Assessments from Water-Damaged Buildings: Defining Exposure and Reactivity, the Two Sides of Causation of CIRS-WDB Illness

Main Article Content

R. Shoemaker Neil V Heyman A van der Westhuizen M McMahon S Lark D

Abstract

Scientific disciplines dependent on accurate analytics invariably evolve due to advances in technical aspects of measurement. In disciplines in which adequate measurement is not available for applications to public health policy, the impact of new paradigms in measurement can extend far beyond scientific thought. Both of these concepts apply to the effect of exposure to water-damaged buildings (WDB) on human health. What causes the putative illness and what government should do to make buildings safe for use, have been impacted by development of molecular methods, particularly Next Generation Sequencing (NGS) and transcriptomics.


The impact of human exposure to Actinobacteria, for example, and identification of immune reactivity specific to these bacteria are now revolutionizing: (i) both detection and quantitation of newly recognized pathogenic organisms; and (ii) the approach to the genomic basis of diagnosis and treatment of disease as manifested by differential gene activation. NGS permits quantitation of exposure and confirmation of risk associated with the threshold of exposure, using defined human health biomarkers, that in turn has led to advances in the metabolic and inflammatory issues in WDB illness, called CIRS, both from molecular hypometabolism and activation of TGF beta-1 signaling that defines immunoreactivity to Actinobacteria.


Current recommendations for assessment of exposure/reactivity to fungi and methods of remediation based on fungi alone do not support continued use, now that endotoxins and Actinobacteria are found to be the major causes of human illness from exposure to WDB.

Keywords: transcriptomics, molecular hypometabolism, Next-Generation Sequencing, Actinobacteria, endotoxins, Gram-negative rods

Article Details

How to Cite
SHOEMAKER, R. et al. Newer Molecular Methods Bring New Insights into Human- And Building-Health Risk Assessments from Water-Damaged Buildings: Defining Exposure and Reactivity, the Two Sides of Causation of CIRS-WDB Illness. Medical Research Archives, [S.l.], v. 9, n. 3, mar. 2021. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2358>. Date accessed: 08 may 2024. doi: https://doi.org/10.18103/mra.v9i3.2358.
Section
Research Articles

References

1. Shoemaker R, Johnson K, Jim L, Berry Y, Dooley M, Ryan J, McMahon S. Diagnostic process for Chronic Inflammatory response Syndrome (CIRS): A consensus statement report of the Consensus Committee of Surviving Mold. Int. Med Rev. 2018, 4(5): 1-47.
2. Shoemaker R. Metabolism, molecular hypometabolism and inflammation: Complications of proliferative physiology include metabolic acidosis, pulmonary hypertension, T reg cell deficiency, insulin resistance and neuronal injury. Trends Diabetes Metab 2020; 3: 1-15.
3. Ryan J, Shoemaker R. RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal polypeptide (VIP) shows a shift in metabolic state and innate immune functions that coincide with healing. Med Res Arch 2016; 4(7): 1-11.
4. Geffcken v. D’Andrea. 2006 California 2d Civil No. B176232.
5. Clark, N., Ammann, H., Brennan, T., Brunekreef, B., Douwes, J., Eggleston, P., Fisk, W., Fullilove, R., Guernsey, J., Nevalainen, A., Essen, S. (2004). Damp Indoor Spaces and Health., The National Academies Press.
6. Storey N, Dangman K, Hodgson, et al. 2004 Guidance for clinicians on the recognition of health effects related to mold exposure and moisture indoors. US EPA.
7. Shoemaker R. 2006 A report to St. Bernard’s Parish on Parish residents temporarily housed on the Scotia Prince compared to a control group of ship employees. Symptoms, visually reported exposures and Visual Contrast Sensitivity. wwwsurvivingmold.com, accessed 1/5/2021.
8. Thomas G, Burton N, Mueller C, Page E, Vesper S. Comparison of work-related symptoms and visual contrast sensitivity between employees of a severely water-damaged school and a school without water-damage. AJIM 2012; 55: 844-854
9. Dooley M, McMahon S. A comprehensive review of mold research literature from 2011-2018. IMR 2020; 6:1-39
10. US GAO 2008 Indoor mold: Better coordination of research on health effects and more consistent guidance would improve Federal efforts.
11. Shoemaker R, House D. SBS and exposure to water damaged buildings: time series study, clinical trial and mechanisms; Neurotoxicology and Teratology 2006; 28: 573-588.
12. Shoemaker, R IAQA, Las Vegas, Nevada. 10/14/07 Sequential activation of innate immune elements: a health index for people re-exposed to water-damaged buildings.
13. Afshari A, Anderson HR, Cohen A, de Oliveira Fernandes E, Douwes J, Gorny R, Hirvonen M-R, Jaakola J, Levin H, Mendell M, Molhave L, Morwska L, Nevalainen A, Richardson M, Rudnai P, Schleibinger HW, Schwarze PE, Seifert B, Sigsgaard T, Song W, Spengler J, Szewzyk R, Panchatcharam S, Gallo G, Giersig M, Nolokke J, Cheung K, Mirer AG, Meyer HW, Roponen M. (2009). World Health Organization guidelines for indoor air quality: dampness and mould. WHO guidelines for indoor air quality.
14. Vesper S, McKinstry R, Yang C, Haugland R, Dearborn D, et al. Specific molds associated with asthma in water-damaged homes. JOEM 2006; 48:852-858.
15. Shoemaker R, Mark L, McMahon S, Thrasher J, Grimes C. 2010. Policyholders of America. Research Committee Report on diagnosis and treatment of chronic inflammatory response syndrome caused by exposure to the interior environment of water-damaged buildings.
16. Shoemaker R, Lark D - 2016, HERTSMI-2 and ERMI: “Correlating Human Health Risk with Mold Specific qPCR in Water-Damaged Buildings”, #658 in Proceedings of the 14th International Conference on Indoor Air Quality and Climate, International Society for Indoor Air Quality and Climate, Ghent, Belgium.
17. Shoemaker R, Lark D, Ryan J. Healthy Buildings Europe 2017. Exposure to buildings with elevated MSQPCR reduces health benefits from VIP treatment of CIRS-WDB.
18. Shoemaker R, Heyman A. NeuroQuant, Lyme and Mold: Implications for enhanced Diagnostic Accuracy. NorVect, Oslo, Norway 5/15/15.
19. Shoemaker R, House D. SBS and exposure to water damaged buildings: time series study, clinical trial and mechanisms; Neurotoxicology and Teratology 2006; 28: 573-588.
20. Ryan J, Wu Q, Shoemaker R. Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin. BMC Med Genomics 2015; 8, 2015.
21. Shoemaker R, House D, Ryan J. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health 2013; 5(3): 396-401.
22. Chew G, Wilson J, Rabito F, Grimsley F, Iqbal S, Reponen T, Mullendberg M, Thorne P, Dearborn D, Morley R. 2006 Mold and endotoxin levels in the aftermath of hurricane Katrina: a pilot project of homes in New Orleans undergoing renovation. EHP 114:1883-89.
23. Rao C, Riggs M, Chew G, Muilenberg M, Thorne P, Van Sickle D, Dunn K, Brown C. Characterization of airborne molds, endotoxins, and glucans in homes in New Orleans after Hurricanes Katrina and Rita. Appld Env Micro. 2007 Mar; 73(5): 1630-4.
24. Brandt M, Burkhart J, Burton N, Cox-Ganser J, Damon S, Falk H, Fridkin S, Garbe P, Kreiss K, McGeehin M, Morgan J, Page E, Rao C, Redd S, Sinks T, Trout D, Wallingford K, Warnock D, Weissman D. Mold Prevention strategies and possible health effects in the aftermath of Hurricanes Katrina and Rita. CDC October 2005.
25. Jones S, Pham C, Zambri M, McKillip J, Carlsson e, Elliott M. Streptomyces volatile compounds influence exploration and microbial community dynamics by altering iron availability. mBio 2019; 10: e00171-19.
26. Marr N, Novikov A, Hajjar A, Caroff, M, Fernandez R. Variability in the lipooligosaccharide structure and endotoxicity among Bordetella pertussis strains. JID 2010; 202:1897-906.
27. Medically sound investigation and remediation of water-damaged buildings in cases of CIRS-WDB. Part 1. Berndtson K, McMahon S, Ackerley M, Rapaport S, Gupta S, Shoemaker R. 10/15. www.survivingmold.com.
28. ANSI/IICRC S520 Standard and reference Guide for Professional Water Damage Restoration 2015, 4th Edition.
29. Schrantz M, Banta J, Charlton J, Heiblum J, Schwartz L, Weatherman G, Weber B, Shoemaker R. Indoor Environmental Professional Panel of Surviving Mold Consensus Statement for Microbial Remediation 2020. Medical Review Archives 2021: 9:1-30.
30. Shoemaker R, Johnson K, Jim L, Berry Y, Dooley M, Ryan J, McMahon S. Diagnostic process for Chronic Inflammatory response Syndrome (CIRS): A consensus statement report of the Consensus Committee of Surviving Mold. Int. Med Rev. 2018, 4(5): 1-47.
31. Adams R, Sylvain I, Spilak M, Taylor J, Waring M, Mendell M. Fungal signature of moisture damage in buildings: Identification by targeted and untargeted approaches with
mycobiome data. Applied and Environmental Microbiology 2020; 86: 17: e01047-20.
32. Adams R, Bateman A, Bik H, Meadow J. Microbiota of the indoor environment: a meta-analysis. Microbiome 2014; 3:49.
33. Adams R, Miletto M, Lindow S, Taylor J, Bruns T. Airborne bacterial communities in residences: similarities and differences with fungi. PLoS One 2014; 9: 3-e91283.
34. Adams R, Bhangar S, Pasut W, Arens E, Taylor J, Lindow S, Nazaroff W, Bruns T. Chamber bioaerosol study: outdoor air and human occupants as sources of indoor airborne microbes. PLoS One 2015; 10: e0128022.
35. Adams R, Miletto M, Taylor J, Bruns T. The diversity and distribution of fungi on residential surfaces. PLoS One 2013; 11: 8-e78866
36. Jayaprakash B, Adams R, Kirjavainen P, Karvonen A, Vepsalainen A, Valkonen M, Jarvi K, Sulyok M, Pekkanen J, Hyvarinen A, Taubel M. Indoor microbiota in severely moisture damaged homes and the impact of interventions. Microbiome 2017; 5: 138.
37. Patovirta R, Haverinen U, Vahteristo M, Uitti A, Tukiainen H, Nevalainen A. The remediation of mold damaged school- - a three- year follow-up study on teachers’ health. Cen Eur J Public Health 2004; 12: 36-42.
38. Reponen T, Singh U, Schaffer C, Vesper S, Johansson E, Adhikari A, Grinshpun S, Indugula R, Ryan P, Levin L, LeMasters G. Visually observed mold and moldy odor versus quantitatively measured microbial exposed in homes. Sci Total Environ 2010; 408: 5565-5574.
39. Pitkaranta M, Meklin T, Hyvarinen A, Nevalainen A, Paulin L, Auvinen P, Lignell U, Rintala H. Molecular profiling of fungal communities in moisture damaged buildings before and after remediation a comparison of culture-dependent and culture independent methods. BMC Microbiology 2011; 11:235.
40. Park J, Sulyok M, Lemons A, Green B, Cox-Ganser J. Characterization of fungi in office dust: Comparing results of microbial secondary metabolites, fungal internal transcribed spacer region sequencing, viable culture and other microbial indices. Indoor Air 2018; 28: 708-720.
41. Huttunen K, Tirkkonen J, Taubel M, Krop E, Mikkonen S, Pekkanan J, Heederik D, Zock P, Hyvarinen A, Hirvonen M. Inflammatory potential in relation to the microbial content of settled dust samples collected from moisture-damaged and reference schools: results of HITEA study. Indoor Air 2016; 26: 380-90.
42. Choi H, Schmidbauer N, Spengler J, Bornehag C. Sources of propylene glycol and glycol ethers in air at home. Int. J. Environ Res. Public Health 2010; 7: 4213-4237.
43. Pitkaranta M, Meklin T, Hyvarinen A, Nevalainen A, Paulin L, Auvinen P, Lignell U, Rintala H. Molecular profiling of fungal communities in moisture damaged buildings before and after remediation – a comparison of culture-dependent and culture-independent methods. BMC Microbiology 2011; 11: 235
44. Vesper S, Cox-Ganser J, Wymer L, Park J. Quantification of mold contamination in multi-level buildings using the Environmental Relative Moldiness Index. J Occup Environ Hyg 2018; 15: 38-43.
45. Sylvain I, Adams R, Taylor J. A different suite: The assemblage of distinct fungal communities in water-damaged units of a poorly-maintained public housing building. PLoS One 2019; 14: e0213355.
46. Park J, Cox-Ganser M, White S, Laney A, Caulfield S, Turner W, Sumner A, Kreiss K. Bacteria in a water-damaged building: associations of Actinobacteria and non-tuberculous mycobacteria with respiratory health in occupants. Indoor Air 2017; 27: 24-33.
47. Suutari M, Ronka E, Lignell U, Rintala H, Nevalainen A. Characterisation of Streptomyces spp. isolated from water-damaged buildings. FEMS Microbiol Ecol 2001; 39: 77-84.
48. Park J, Cox-Ganser M, White S, Laney A, Caulfield S, Turner W, Sumner A, Kreiss K. Bacteria in a water-damaged building: associations of Actinobacteria and non-tuberculous mycobacteria with respiratory health in occupants. Indoor Air 2017; 27: 24-33.
49. Rintala H, Nevalainen A, Suutari M. Diversity of Streptomycetes in water-damaged building materials based on 16S rDNA sequences. Letters in Applied Microbiology 2002; 34: 1-11.
50. Roponen M, Toivola M, Ruotsalainen M, Nevalainen A, Hirvonen M. Differences in inflammatory responses and cytotoxicity in RAW264.7 macrophages induced by Streptomyces anulatus grown on different building materials. Indoor Air 2001; 11: 179-84.
51. Taubel M, Sulyok M, Vishwanath V, Bloom E, Turunen M, Jarvi K, Kauhanen E, Krska R, Hyvarinen A, Larsson L, Nevalainen A. Co-occurrence of toxic bacterial and fungal secondary metabolites in moisture-damaged indoor environments. Indoor Air 2011; 21: 368-375.
52. Jarvi K, Hyvarinen A, Taubel M, Karvonen A, Turunen M, Jalkanen K, Patovirta R, Syrjanen T, Pirinen J, Salonen H, Nevalainen A, Pikkanen J. Microbial growth in building material samples and occupants’ health in severely moisture-damaged homes. Indoor Air 2018; 28: 287-297.
53. Kazemian N, Pakpour S, Milani A, Klironomos J. Environmental factors influencing fungal growth on gypsum boards and their structural biodeterioration: A university campus case study. PLoS One 2019; 14: e0220556.
54. Kontro M, Hirvonen M, Nevalainen A. pH effects on 10 Streptomyces spp. Growth and sporulation depend on nutrients. Lett Appl Microbiol 2005; 41: 32-8.
55. Adhikari A, Kettleson E, Vesper S, Kumar S, Popham D, Schaffer C, Indugula R, Chatterjee K, Allam K, Grinshpun S, Reponen T. Dustborne and airborne gram-positive and gram-negative bacteria in high versus low ERMI homes. Sci Total Environ 2014; 0*: 92-99.
56. Hyvarinen A, Roponen M, Tittanen P, Laitinen S, Nevalainen A, Pekkanen J. Dust sampling methods for endotoxin-an essential but under-estimated issue. Indoor Air 2006; 16: 20-7.
57. Kirjavainen P, Taubel M, Karvonen A, Sulyok M, Tittanen P, Krska R, Hyvarinen A, Pekkanen J. Microbial secondary metabolites in homes in association with moisture damage and asthma. Indoor Air 2016; 26: 448-56.
58. Ndika J, Suojalehto H, Taubel M, Lehto M, Karvala K, Pallasaho P, Sund J, Auvinen P, Jarvi K, Pekkanen J, Kinaret P, Greco D, Hyvarinen A, Alenius H. Nasal mucosa and blood cell transcriptome profiles do not reflect respiratory symptoms associated with moisture damage. Indoor Air 2018; doi: 10.1111/ina.12472.
59. Korkalainen M, Taubel M, Naarala J, Kirjavainen P, Koistinen A, Hyvarinen A, Komulainen H, Viluksela M. Synergistic proinflammatory interactions of microbial toxins and structural components characteristic to moisture-damaged buildings. Indoor Air 2017; 27: 13-23.
60. Park J, Schleiff P, Attfield D, Cox-Ganser J, Kreiss K. Building-related respiratory symptoms can be predicted with semi-quantitative indices of exposure to dampness and mold. Indoor Air 2004; 14: 425-33.
61. Huttunen K, Rintala H, Hirvonen M, Vepsalainen A, Hyvarinen A, Meklin T, Toivola M, Nevalainen A. Indoor air particles and bioaerosols before and after renovation of moisture-damaged buildings: the effect on biological activity and microbial flora. Environ Res 2008; 107: 291-8.
62. Haverinen-Shaughnessy U, Hyvarinen A, Putus T, Nevalainen A. Monitoring success of remediation: seven case studies of moisture and mold damaged buildings. Sci Total Environ 2008; 399: 19-27.
63. Cho S, Park J, Kreiss K, Cox-Ganser J. Levels of microbial agents in floor dust during remediation of a water-damaged office building. Indoor Air 2011; 21: 417-26.
64. Cho S, Cox-Ganser J, Kreiss K, Park J. Evaluation of individual-based and group-based exposure estimation of microbial agents in health effects associated with a damp building. J Expo Sci Epidemiol 2013; 23: 409-15.
65. Murtoniemi T, Penttinen P, Nevalainen A, Hirvonen M. Effects of microbial cocultivation on inflammatory and cytotoxic potential of spores. Inhal Toxicol 2005; 17: 681-93.
66. Toivola M, Alm S, Nevalainen A. Viable fungi and bacteria in personal exposure samples in relation to microenvironments. J Environ Monit 2004; 6: 113-20.
67. Toivola M, Alm S, Nevalainen A. Viable fungi and bacteria in personal exposure samples in relation to microenvironments. J Environ Monit 2004; 6: 113-20.
68. Wu M, Xiao H, Ren W, Yin J, Tan B, Liu G, Li L, Nyachoti C, Xiong X, Wu G. Thereutic effects of glutamic acid in piglets challenged with deoxynivalenol. PLoS One 2014; 9: e100591
69. Duan J, Yin J, Wu M, Liao P, Deng D, Liu G, Wen Q, Wang Y, Qiu W, Liu Y, Wu X, Ren W, Tan B, Chen M, Xiao H, Wu L, Li T, Nyachoti C, Adeloa O, Yin Y. Dietary glutamate supplementation ameliorates mycotoxin-induced abnormalities in the intestinal structure and expression of amino acid transporters in young pigs. PLoS One 2014; 9: e112357.
70. Wu M, Xiao H, Ren W, Yin J, hu J, Duan J, Liu G, Tan B, Xiong X, Oso A, Adeola O, Yao K, Yin Y, Li T. An NMR-based metabolomic approach to investigate the effects of supplementation with glutamic acid in piglets challenged with deoxynivalenol. PLoS One 2014; 9: e113687. doi: 10.371/journal.pone.0133687
71. Sarkanj B, Ezekiel C, Turner P, Abia W, Rychlik M, Krska R, Sulyok M, Warth B. Ultra-sensitive, stable isotope assisted quantification of multiple urinary mycotoxin exposure biomarkers. Anal Chim Acta 2018; 1019: 84-92.
72. Heyndrickx E, Sioen I, Huybrechts B, Callebaut A, De Henauw S, De Saeger S. Human biomonitoring of multiple mycotoxins in the Belgian population: Results of the BIOMYCO study. Environ Int 2015; 84: 82-9.
73. Gambacorta L, Olsen M, Solfrizzo M. Pig urinary concentration of mycotoxins and metabolites reflects regional differences, mycotoxin intake and feed contaminations. Toxins 2019; 11: 378.
74. Fan K, Xu J, Jiang K, Liu X, Meng J, Di Mavungu J, Guo W, Zhang Z, Jing J, Li H, Yao B, Li H, Zhao Z, Han Z. Determination of multiple mycotoxins in paired plasma and urine samples to assess human exposure in Nanjing, China. Environ Pollut 2019; 248: 865-873.
75. Wallin S, Gambacorta L, Notova N, Lemming E, Nalsen C, Solfrizzo M, Olsen M. Biomonitoring of concurrent mycotoxin exposure among adults in Sweden through urinary multi-biomarker analysis. Food Chem Toxicol 2015; 83: 133-9.
76. Vettorazzi A, Delft J, Cerain A. A review on ochratoxin A transcriptomic studies. Food Chem Toxicol 2013; 59: 766-83.
77. Vidal A, Claeys L, Mengelers M, Vanhoorne V, Vervaet C, Huybrechts B, De Saeger S, De Boevre M. Humans significantly metabolize and excrete the mycotoxin deoxynivalenol and its modified form deoxynivalenol-3-glucoside within 24 hours. Scientific Reports 2018; 8: 5255.
78. Osteresch B, Viegas S, Cramer B, Humpf H. Multi-mycotoxin analysis using dried blood spots and dried serum spots. Anal Bioanal Chem 2017; 409: 3369-3382.
79. Derynck R, Zhang Y. Smad-dependent and Smad-independent pathways in TGF-beta family signaling. Nature 2003; 425: 577-84.
80. Verrecchia F, Vindevoghel L, Lechleider J, Uitto J, Mauviel A. Smad3/Ap-2 interactions control transcriptional responses to TGF-beta in a promoter-specific manner. Oncogene 2001; 26:3332-3340.
81. Tsunematsu Y, Nishimura S, Hattori A, Oishi S, Fuji N, Kakeya H. Isolation, structure elucidation, and total synthesis of tryptopeptins A and B, new TGF-B signaling modulators from Streptomyces spp. Org Letter 2015; 17:258-261.