Co-morditities of environmental diseases: A common cause

Open access


The global pandemic of non-vector borne environmental diseases may, in large part, be attributed to chronic exposures to ever increasing levels of exogenous lipophilic chemicals. These chemicals include persistent organic pollutants, semi-volatile compounds and low molecular weight hydrocarbons. Such chemicals facilitate the sequential absorption of otherwise not absorbed more toxic hydrophilic species that attack numerous body organs and systems, leading to environmental disease. Co-morbidities of noncommunicable environmental diseases are alarmingly high, with as many as half of all individuals chronically ill with two or more diseases. Co-morbidity is to be anticipated, since all of the causative chemicals identified have independently been shown to trigger the individual diseases.

Aaron LA, Burke MM, Buchwald MD. (2012). Overlapping conditions among patients with chronic fatigue syndrome, fi bromyalgia, and temporomandibular disorder. Arch Intern Med 160: 221-227.

Aaron LA., Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J et al. (2001). Comorbid clinical conditions in chronic fatigue. J Gen Intern Med 16: 24-31.

Agarwal S, Zaman T, Tuzcu EM, Kapadia SR. (2011). Heavy metals and cardiovascular disease: results from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Angiology 62(5): 422-29.

Al-Bishri J, Attar SM, BAssuni N, Al-Yofaiey, Qutbuddeen H, Al-Harthi S et al. (2013). Comorbidity profi le among patients with rheumatoid arthritis and the impact on prescription trend. Clin Med Insights: Arthritis and Musculoskeletal Disorders 6: 11-18.

Antshel KM, Zhang-James Y, Faraone SV. (2013). The comorbidity of ADHD and autism spectrum disorder. Expert Rev Neurother 13(10): 1117-28.

Baccarelli A, Bollati V. (2009). Epigenetics and environmental chemicals. Curr Opin Pediatr 21(2): 243-51.

Bauer UE, Briss PA, Goodman RA, Bowman BA. (2014). Prevention of chronic disease in the 21st century: elimination of the leading preventable causes of premature death and disability in the USA. Lancet 384(9937): 45-52.

Blackman JA, Conaway MR. (2013). Developmental, emotional and behavioral co-morbidities across the chronic health condition spectrum. J Pediatr Rehabil Med 6(2): 63-71.

Bolanos JP, Moro MA, Lizasoain I, Almeida A. (2009). Adv Drug Deliv Rev 61(14): 1299-1315.

Boyle JP, Thompson TJ, Gregg EW, Barker LE, Williamson DF. (2010). Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality and prediabetes prevalence. Popul Health Metr 8: 29-41.

Caciari T, Sancini A, Fioravanti M, Capozzella A, Casale T, Montuori L. et al. (2013). Cadmium and hypertension in exposed workers: a meta-analysis. Int J Occup Med Environ Health 26(3): 440-56.

Caress SM, Steinemann AC. (2005). National prevalence of asthma and chemical hypersensitivity: an examination of potential overlap. JOEM 47(5): 518-22.

Carocci A, Rovito N, Sinicropi MS, Genchi G. (2014). Mercury toxicity and neurodegenerative eff ects. Rev Environ Contam Toxicol 229: 1-18.

Carpenter DO. (2008). Environmental contaminants as risk factors for developing diabetes. Rev Environ Health 23(1): 59-74.

Cazzola M, Segreti A, Calzetta L, Rogliani P. (2013). Comorbidities of asthma: current knowledge and future research needs. Curr Opin Pulm Med 19(1): 36-41.

Chatila WM, Thomashow BM, Minai OA, Criner GJ, Make BJ. (2008). Comorbidities in chronic obstructive pulmonary disease. Proc Am Thorac Soc 5: 549-55.

Choi J, Eom J, Kim J, Lee S, Kim Y. (2014). Association between some endocrine- disrupting chemicals and childhood obesity in biological samples of young girls: a cross-sectional study. Environ Toxicol Pharmacol 38(1): 51-57.

Ciccone DS, Natelson BH. (2003). Comorbid ilness in women with chronic fatigue syndrome: a test of the single syndrome hypothesis. Psychosomatic Med 65: 268-75.

Colborn T, Dumanoski D, Myers JP. (1997). Our stolen future. Penguin Books, New York.

Colosia AD, Palencia R, Khan S. (2013). Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review. Diabetes Metal Syndr Obes 6: 327-38.

Cordu N, Schymura MJ, Nogotia S, Rej R, Carpenter DO. (2007). Diabetes in relation to serum levels of polychlorinated biphenyls and chlorinated pesticides in adult native Americans. Environ Health Perspect 115(10): 1442-47.

Crespi B. (2011). Autism and cancer risk. Autism Research 4: 302-10.

Cristino AS, Williams SM, Hawi Z, An JY, Bellgrove MA, Schwartz CE et al. (2013). Neurodevelopment and neuropsychiatric disorders represent an interconnected molecular system. Mol Psychiatry 19(3): 294-301.

Dirinck EL. Dirtu AC, Govidian M, Covaci A, Van Gaal LF, Jorens PG. (2014). Exposure to persistent organic pollutants: relationship with abnormal glucose metabolism and visceral adiposity. Diabetes Care 37(7): 1951-58.

Duthie A, Chew D, Soiza RL. (2011). Non-psychiatric comorbidity associated with Alzheimer’s disease. Q J Med 104: 913-20.

Fasmer OB, Riise T, Eagan TM, Lund A, Dilsaver SC Hundal O et al. (2011): Comorbidity of asthma with ADHD. J Atten Disord 15(7): 564-71.

Fortin M, Bravo G, Hudon C, Vanasse A, Lapointe MA. (2005). Prevalence of multimorbidity among adults seen in family practice. Ann Family Med 3(3): 223-28.

Gage H, Hendricks A, Zhang S, Kazis L. (2003). The relative health related quality of life of veterans with Parkinson’s Disease. J Neurol Neurosurg Psychiatry 74: 163-69.

Gallo MV, Schell LM, DeCaprio AP, Jacobs A. (2011). Levels of persistent organic pollutant and their predictors among young adults. Chemosphere 83: 1374-82.

Habib SL. Rojna M. (2013). Diabetes and risk of cancer. ISRN Oncology 2013: Article ID 583786, 16 pages.

Hidalgo CA, Blumm N, Barabasi AL, Christakis NA. (2009). A dynamic network approach for the study of human phenotypes. PLoS Computational Biol 5(4): e1000353.

Hudon C, Fortin M, Soubhi H. (2008). Chronic musculoskeletal conditions and comorbidities in primary care settings. Canadian Family Physician 54: 74-5.

Jakovcevski M, Akbarian S. Epigenetic mechanisms in neurological disease. Nat Med 18(8): 1194-1204.

Jakovljevic M, Ostojic L. (2013). Comorbidity and multimorbidity in medicine today: challenges and opportunities for bringing separated branches of medicine closer to each other. Psychiatr Danub 25(Suppl 1): 18-28.

Jason LA, Taylor RR, Kennedy CL. (2000). Chronic fatigue syndrome, fi bromyalgia, and multiple chemical sensitivities in a community-based sample of persons with chronic fatigue-like symptoms. Psychosomatic Med 62: 655-63.

Jensen CM, Steinhausen HC. (2014). Cormorbid mental disorders in children and adolescents with attention-defi cit/hyperactivity disorder in a large nationwide study. Atten Defi c Hyperact Discord June 19, [Epub ahead of print].

Jung KH, Perzanowski M, Rundle A, Moors K, Yan B, Chillrud SN et al. (2014).

Polycyclic aromatic hydrocarbon exposure, obesity and childhood asthma in an urban cohort. Environ Res 128: 35-41.

Karlstad O, Nafstad P, Tverdal A, Skurtveit S, Furu K. (2012). Comorbidities in an asthma population 8-29 years old: a study from the Norwegian prescription database. Pharmacoepidemiol 21(10): 1045-52.

Katon WJ. (2008). The comorbidity of diabetes mellitus and depression. Am J Med 121(11 Suppl 2): S8-15.

Khan AR, Awan FR. (2014). Metals in the pathogenesis of type 2 diabetes. J Diabetes Metabolic Disorders 13: 16. doi: 10.1186/2251-6581-13-16.

Khaodhiar L, McCowen KC, Blackburn GL. (1999). Obesity and its comorbid conditions. Clin Cornerstone 2(3): 17-31.

Kohane IS, McMurry A, Weber G, McFadden D, Rappaport L, Kunkel L et al. (2012). The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS ONE 7(4): e33224.

Kreatsoulas C, Anand SS, Subramarian SV. (2014). An emerging double burden of disease: the prevalence of individuals with cardiovascular disease and cancer. J Intern Med 275(5): 494-505.

Kuo CC, Moon K, Thayer KA, Navas-Acien A. (2013). Environmental chemicals and type 2 diabetes: an updated systematic review of the epidemiologic evidence. Curr Diab Rep 13(6): 831-49.

Langer P, Ukropec J, Kocan A, Drobna B, Radikova Z, Huckova M et al. (2014).

Obesogenic and diabetogenic impact of high organochlorine levels (HCB, p,p-DDE, PCBs) on inhabitants in the highly polluted Eastern Slovakia. Endocr Regul 48(1): 17-24.

Larsen BA, Christenfeld NJS. (2009). Cardiovascular disease and psychiatric comorbodity: the potential role of perservative cognition. Cardiovascular Psychiatry Neurology 2009: Article ID 791017, 8 pages, doi: 10.1155/2d009/791017.

Lee, DH, Porta M, Jacobs DR Jr, Vandenberg LN. (2014). Chlorinated persistent organic pollutants, obesity, and type 2 diabetes. Endocr Rev 35(4): 557-601.

Lee DH, Lind PM, Jacobs, Jr. DR, Salihovic S, van Bavel B, Lind L (2011). Polychlorinated biphenyls and organochlorine pesticides in plasma predict development of type 2 diabetes in the elderly: the prospective investigation of the vasculature in Uppsala seniors (PIVUS) study. Diabetes Care 34(8): 1778-84.

Lee, DH, Steff es MW, Sjoden A, Jones RS, Needham LL, Jacobs DR Jr. (2011a).

Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes. PLoS One 26(6): e15977.

Lee DS, Park J, Kay KA, Christakis NA, Oltavi ZN, Barabasi AL. The implications of human metabolic network topology for disease comorbidity. (2008). PNAS 105(29): 9880-85.

Lee DH, Steff es MW, Sjoden A, Jones RS, Needham LL, Jacobs, Jr. DR. (2010).

Low dose of some persistent organic pollutants predicts type 2 diabetes: A nested case-control study. Environ Health Perspect 118(9): 1235-42.

Lee DH, Jacobs, Jr., DR, Steff es M. (2008). Association of organochlorine pesticides with peripheral neuropathy in patients with diabetes or impaired fasting glucose. Diabetes 57: 3108-11.

Lee DH, Lee IK, Porta M, Steff es M, Jacobs, Jr. DR. (2007). Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002. Diabetologia 50: 1841-51.

Lee DH, Lee IK, Song K, Steff es M, Toscano W Baker BA, Jacobs, Jr. DR (2006). A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes. Diabetes Care 29(7): 1638-44.

Leonhard BE, Myint A. (2006). Inflammation and depression: is there a causal conection with dementia? Neurotox Res 10: 149-60. Lugtenberg M, Burgers JS, Clancy C, Westert GP, Schneider EC. (2011). Current guidelines have limited applicability to patients with comorbid conditions: a systematic analysis of evidence-based guidelines. PLos ONE 6(10): e25978.

Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers Penninx BWJH et al. Overweight, obesity, and depression. Arch Gen Psychiatry 67(3): 220-29.

Mannino DM, Thorn D, Swensen A, Holguin F. (2008). Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. European Resp J 32(4): 962-69.

Marie RA, Hanwell H. (2013). General health issues in multiple sclerosis: comorbidities, secondary conditions and health behaviors. Continuum (Minneap Minn) 19(4): 1046-57.

Mates JM, Segura JA, Alonso FJ, Marquez J. (2010). Roles of dioxins and heavy metals in cancer and neurological diseases using ROS-mediated mechanisms. Free Rad Biol Med 49(9): 1328-41.

Matson JL, Rieske RD, Williams LW. (2013). The relationship between autism spectrum disorders and attention-defi cit/hyperactivity disorder: an overview. Res Dev Disabil 34(9): 2475-84.

McIntyre RS, Nguyen HT, Soczynska JK, Lourenco MTC, Woldeyohannes HO, Konarski JZ. (2008). Medical and substance-related comorbidity in bipolar disorder: translational research and treatment opportunities. Dialogues Clin Neurosci 10: 203-13.

Miller AH, Ancoli-Israel S, Bower JE, Capuron L, Irwin MR. (2008). Neuroendocrine- immune mchanisms of behavioral comorbidities in patients with cancer. J Clin Oncol 26: 971-82.

Mostafalou S, Abdollahi M. (2013). Pesticides and human chronic diseases: evidences, mechanisms and perspectives. Toxicol Appl Pharmacol 268(2): 157-77.

Murray DJL, Vos T, Lozano R, Naghavi M, Flaxman AD et al. (2012). Disability adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: 2197-2223.

Nousen EK, Franco JG, Sullivan EL. (2013). Unraveling the mechanisms responsible for the comorbidity between metabolic syndrome and mental health disorders. Neuroendocrinology 98(4): 254-66.

O’Dwyer L, Tanner C, van Dongen EV, Greven CU, Bralten J, Zwiers MP et al. (2014). Brain volumetric correlates of autism spectrum disorder symptoms in attention defi cit/hyperactivity disorder. PLoS ONE 9(6): e101130.

Perju-Dumbrava L, Muntean ML, Muresanu DF. (2014). Cerebrovascular profi le assessment in Parkinson’s Disease patients. CNS Neurol Discord Drug Targets 13(4): 712-17.

Philibert A, Schwartz H, Mergler D. (2009). An exploratory study of diabetes in First Nation community with respect to the serum concentrations of p,p’-DDE and PCBs and fi sh consumption. In J Environ Res Public Health 6(12): 3179-89.

Pinart M, Benet M, Annesi-Maesano I, von Berg A, Berdel D, Carlsen KC et al. (2014). Comorbidity of eczema, rhinitis, and asthma in IgE-sensitised and non-IgE-sensitised children in MeDALL: a population-based cohort study. Lancet Respir Med 2(2): 131-40.

Ramakrishnan J, Majgi SM, Premarajan KC, Lakshminarayanan S, Thangaraj S, Chinnakali P. (2013). High prevalence of cardiovascular risk factors among policemen in Puducherry South India. J Cardiovasc Disease Res 4: 112-15.

Simmons AL, Schlezinger JJ, Corkey BE. (2014): What are we putting in our food that is making us fat? Food additives, contaminants, and other putative contributors to obesity. Curr Obes Res 3(2): 273-85.

Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. (2008). Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in population-derived sample. J Am Acad Child Adolesc Psychiatry 47(8): 921-29.

Slater M, Perruccio AV, Badley EM. (2011). Musculoskeletal comorbidities in cardiovascujlar disease, diabetes and respiratory disease: the impact on activity limitations; a representative population-based study. BMC Public Health 11: 77. doi: 10.1186/1471-2458-11-77.

Somers EC, Thomas SL, Smeeth L, Hall AJ. (2009): Are individuals with an autoimmune disease at higher risk of a second autoimmune disorder? Am J Epidemiol 169: 749-55.

Sorensen HT. (2013). Multimorbidity and cancer outcomes: a need for more research. Clin Epidemiol 5(Suppl 1): 1-2.

Sowers JR, Epstein M. (1995). Diabetes mellitus and associated hypertension, vascular disease, and nephropathy. Hypertension 26: 869-79.

Sowers JR, Epstein M, Frolich ED. (2001). Diabetes, hypertension, and cardiovascular disease an update. Hypertension 37: 1053-59.

Strujis JN, Baan CA, Schellevis FG, Westert GP, van den Bos GAM. (2006). Comorbidity in patients with diabetes mellitus: impact on medical health care utilization. BMC Health Serv Res 6: 84-93.

Suren P, Gunnes N, Roth C, Bresnahan M, Hornig M, Hirtz D et al. (2014). Parental obesity and risk of autism spectrum disorder. Pediatrics 133(5): 1128-38.

Tyler CV, Schramm SC, Karafa M, TAng AS, Jain AK. (2011). Chronic disease risks in young adults with autism spectrum disorder: forewarned is forearmed. Am J Intell Dev Disabil 116(5): 371-80.

Urdinguio RG, Sanchez-Mut JV, Esteller M. (2009). Epignetic mechanisms in neurological diseases: genes, syndromes, and therapies. The Lancet Neurology 8: (11): 1056-72.

Uttara B, Singh AV, Zamboni P, Mahajan RT. (2009). Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant theropeutic options. Curr Neuropharmacol 7(1): 65-74.

Uzun S, Kozumplik O, Topic R, Jakovljevik M. (2009). Depressive disorders and comorbidity: somatic illness vs. side eff ect. Psychiatria Danub 21(3): 391-98.

Vaclavik E, Tjonneland A, Stripp C, Overvad K, Philippe-Weber J, Raaschou- Nielsen O. (2006). Organochlorines in Danish women: predictors of adipose tissue concentrations. Environ Res 100(3): 362-70.

Valera MVL, de Oca MM, Halbert R, Muino A, Talamo D, Perez-Padilla R et al. (2013). Comorbidities and health status in individuals with and without COPD in five Latin American cities: the PLATINO study. Arch Bronconeumol 49(11): 468-74.

van Baal PH, Engelfriet PM, Boshuizen HC, van de Kassteele, Schellevis FG, Hoogenveen RT. (2011). Co-occurrence of diabetes, myocardial infarction, stroke and cancer: quantifying age patterns in the Dutch population using health survey data. Population Health Metrics 9: 51. doi: 10.1186/1478-7954-9-51/

van der Molen T. (2010). Co-morbidities of COPD in primary care: frequency, relation to COPD, and treatment consequences. Primary Care Resp J 19(4): 326-34.

van Oostrom SH, Picavet HSJ, van Gelder BM, Lemmens LC, Hoeymans N, van Dijk CE et al. (2012). Multimorbidity and comorbidity in te Dutch population - data from general practices. BMC Public Health 12: 715. doi: 10.1186/1471-2458-12-715/

Vos T. Flaxman AD Naghavi M, Lorenzo R, Michaud C et al. (2012). Years lived with disability(YLDs) for 1160 sequalae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380: 2163-96.

Wang RY, Needham LL. (2007). Environmental chemicals: from the environment to food, to breast milk, to the infant. J Toxicol Environ Health B Crit Rev 10(8): 597-609.

Weiss B. (2012). The intersection of neurotoxicology and endrocrine disruption. Neurotoxicology 33(6): 1410-19.

WrightA, Charlesworth B, Rudan I, Carothers A, Campbell H. (2003). A polygenic basis for late-onset disease. Trends in Genetics 19(2): 97-106.

Zamrini E, Parrish JA, Parsons D, Harrell LE. (2004). Medical comorbidity in black and white patients with Alzheimer’s Disease. Southern Med J 97(1): 2-16.

Zeliger HI, Pan Y, Rea WJ. (2012). Predicting co-morbidities in chemically sensitive individuals from exhaled breath analysis. Interdiscp Toxicol 5(3): 123-6.

Zeliger HI. (2013). Lipophilic chemical exposure as a cause of type 2 diabetes (T2D). Rev Environ Health 28(1): 9-20.

Zeliger HI. (2013a). Lipophlic chemical exposure as a cause of cardiovascular disease. Interdiscip Toxicol 6(2): 55-62.

Zeliger HI. (2013b). Exposure to lipophilic chemicals as a cause of neurological impairments, neurodevelopmental disorders and neurodegenerative diseases. Interdiscip Toxicol 6(3): 103-10.

Zeliger HI. Human toxicology of chemical mixtures, 2nd ed., (2012). Elsevier, London, pp 40-41.

Zeliger HI. (2003). Toxic eff ects of chemical mixtures. Arch Environ Health 58(1): 23-29.

Zhang Y, De S, Garner JR, Smith K, Wang SA, Becker KG. (2010). Systematic analysis, comparison, and integration of disease based human genetic association data and mouse genetic phenotype information. BMC Med Genomics 3: 1. doi: 10.1186/1755-8794-3-1.

Ziem G, Donnay A. (1995). Chronic fatigue, fi bromyalgia, and chemical sensitivity: overlapping disorders. Arch Int Med 155(17): 1913.

Interdisciplinary Toxicology

The Journal of Institute of Experimental Pharmacology of Slovak Academy of Sciences

Journal Information

CiteScore 2018: 1.78

SCImago Journal Rank (SJR) 2018: 0.274
Source Normalized Impact per Paper (SNIP) 2018: 0.671

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 204 128 7
PDF Downloads 100 76 9