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A Meta-analysis of Arsenic Exposure and Lung Function: Is There Evidence of Restrictive or Obstructive Lung Disease?

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Abstract

Purpose of Review

Hundreds of millions of people worldwide are exposed to arsenic via contaminated water. The goal of this study was to identify whether arsenic-associated lung function deficits resemble obstructive- or restrictive-like lung disease, in order to help illuminate a mechanistic pathway and identify at-risk populations.

Recent Findings

We recently published a qualitative systematic review outlining the body of research on arsenic and non-malignant respiratory outcomes. Evidence from several populations, at different life stages, and at different levels of exposure showed consistent associations of arsenic exposure with chronic lung disease mortality, respiratory symptoms, and lower lung function levels. The published review, however, only conducted a broad qualitative description of the published studies without considering specific spirometry patterns, without conducting a meta-analysis, and without evaluating the dose-response relationship.

Summary

We searched PubMed and Embase for studies on environmental arsenic exposure and lung function. We performed a meta-analysis using inverse-variance-weighted random effects models to summarize adjusted effect estimates for arsenic and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Across nine studies, median water arsenic levels ranged from 23 to 860 μg/L. The pooled estimated mean difference (MD) comparing the highest category of arsenic exposure (ranging from > 11 to > 800 μg/L) versus the lowest (ranging from < 10 to < 100 μg/L) for each study for FEV1 was – 42 mL (95% confidence interval (CI) − 70, − 16) and for FVC was – 50 mL (95% CI − 63, − 37). Three studies reported effect estimates for FEV1/FVC, for which there was no evidence of an association; the pooled estimated MD was 0.01 (95% CI − 0.005, 0.024). This review supports that arsenic is associated with restrictive impairments based on inverse associations between arsenic and FEV1 and FVC, but not with FEV1/FVC. Future studies should confirm whether low-level arsenic exposure is a restrictive lung disease risk factor in order to identify at-risk populations in the USA.

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Abbreviations

ATS:

American Thoracic Society

CFTR:

Cystic fibrosis transmembrane conductance

ERS:

European Respiratory Society

FEV1/FVC:

Ratio of FEV1 to FVC

FEV1 :

Forced expiratory volume in one second

FVC:

Forced vital capacity

PFT:

Pulmonary function test

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. World Health Organization. Exposure to arsenic: a major public health concern. http://www.who.int/ipcs/features/arsenic.pdf. Published 2010. Accessed November 15, 2016.

  2. National Research Council. Critical aspects of EPA’s IRIS assessment of inorganic arsenic: interim report. Washington, DC: The National Academies Press; 2014.

    Google Scholar 

  3. Straif K, Benbrahim-Tallaa L, Baan R, Grosse Y, Secretan B, el Ghissassi F, et al. A review of human carcinogens—part C: metals, arsenic, dusts, and fibres. Lancet Oncol. 2009;10(5):453–4. https://doi.org/10.1016/S1470-2045(09)70134-2.

    Article  PubMed  Google Scholar 

  4. Sanchez TR, Perzanowski M, Graziano JH. Inorganic arsenic and respiratory health, from early life exposure to sex-specific effects: a systematic review. Environ Res. 2016;147:537–55. https://doi.org/10.1016/j.envres.2016.02.009.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Smith AH, Marshall G, Yuan Y, Liaw J, Ferreccio C, Steinmaus C. Evidence from Chile that arsenic in drinking water may increase mortality from pulmonary tuberculosis. Am J Epidemiol. 2011;173(4):414–20. https://doi.org/10.1093/aje/kwq383.

    Article  PubMed  Google Scholar 

  6. Smith AH, Marshall G, Yuan Y, Ferreccio C, Liaw J, von Ehrenstein O, et al. Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood. Environ Health Perspect. 2006;114(8):1293–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Tsai SM, Wang TN, Ko YC. Mortality for certain diseases in areas with high levels of arsenic in drinking water. Arch Environ Health. 1999;54(3):186–93. https://doi.org/10.1080/00039899909602258.

    Article  PubMed  CAS  Google Scholar 

  8. Argos M, Parvez F, Rahman M, Rakibuz-Zaman M, Ahmed A, Hore SK, et al. Arsenic and lung disease mortality in Bangladeshi adults. Epidemiology. 2014;25(4):536–43. https://doi.org/10.1097/EDE.0000000000000106.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Pesola GR, Parvez F, Chen Y, Ahmed A, Hasan R, Ahsan H. Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study. Eur Respir J. 2012;39(5):1076–83. https://doi.org/10.1183/09031936.00042611.

    Article  PubMed  CAS  Google Scholar 

  10. Rahman A, Vahter M, Ekstrom EC, Persson LA. Arsenic exposure in pregnancy increases the risk of lower respiratory tract infection and diarrhea during infancy in Bangladesh. Environ Health Perspect. 2011;119(5):719–24. https://doi.org/10.1289/ehp.1002265.

    Article  PubMed  CAS  Google Scholar 

  11. Parvez F, Chen Y, Yunus M, Olopade C, Segers S, Slavkovich V, et al. Arsenic exposure and impaired lung function. Findings from a large population-based prospective cohort study. Am J Respir Crit Care Med. 2013;188(7):813–9. https://doi.org/10.1164/rccm.201212-2282OC.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dauphine DC, Ferreccio C, Guntur S, et al. Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings. Int Arch Occup Environ Health. 2011;84(6):591–600. https://doi.org/10.1007/s00420-010-0591-6.

    Article  PubMed  CAS  Google Scholar 

  13. Recio-Vega R, Gonzalez-Cortes T, Olivas-Calderon E, Lantz RC, Gandolfi AJ, De Alba CG. In utero and early childhood exposure to arsenic decreases lung function in children. J Appl Toxicol. 2015;35(4):358–66. https://doi.org/10.1002/jat.3023.

    Article  PubMed  CAS  Google Scholar 

  14. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948–68. https://doi.org/10.1183/09031936.05.00035205.

    Article  PubMed  CAS  Google Scholar 

  15. Steele MP, Schwartz DA. Molecular mechanisms in progressive idiopathic pulmonary fibrosis. Annu Rev Med. 2012;64(1):120928131129008–276. https://doi.org/10.1146/annurev-med-042711-142004.

    Article  CAS  Google Scholar 

  16. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology a proposal for reporting. JAMA. 2000;283(15):2008–12. https://doi.org/10.1001/jama.283.15.2008.

  17. Navas-Acien A, Francesconi KA, Silbergeld EK, Guallar E. Seafood intake and urine concentrations of total arsenic, dimethylarsinate and arsenobetaine in the US population. Environ Res. 2011;111(1):110–8. https://doi.org/10.1016/j.envres.2010.10.009.

    Article  PubMed  CAS  Google Scholar 

  18. Ho JC, Au WY, Han L, Kwong YL, Ip MS. Effect of therapeutic arsenic exposure on pulmonary function. Respir Med. 2013;107(9):1423–30. https://doi.org/10.1016/j.rmed.2013.06.012.

    Article  PubMed  Google Scholar 

  19. Navas-Acien A, Sharrett AR, Silbergeld EK, Schwartz BS, Nachman KE, Burke TA, et al. Arsenic exposure and cardiovascular disease: a systematic review of the epidemiologic evidence. Am J Epidemiol. 2005;162(11):1037–49. https://doi.org/10.1093/aje/kwi330.

    Article  PubMed  Google Scholar 

  20. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987;9:1–30.

    Article  PubMed  CAS  Google Scholar 

  21. Das D, Bindhani B, Mukherjee B, Saha H, Biswas P, Dutta K, et al. Chronic low-level arsenic exposure reduces lung function in male population without skin lesions. Int J Public Health. 2014;59(4):655–63. https://doi.org/10.1007/s00038-014-0567-5.

    Article  PubMed  Google Scholar 

  22. von Ehrenstein OS, Mazumder DNG, Yuan Y, Samanta S, Balmes J, Sil A, et al. Decrements in lung function related to arsenic in drinking water in West Bengal, India. Am J Epidemiol. 2005;162(6):533–41. https://doi.org/10.1093/aje/kwi236.

    Article  Google Scholar 

  23. Steinmaus C, Ferreccio C, Acevedo J, Balmes JR, Liaw J, Troncoso P, et al. High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile. Toxicol Appl Pharmacol. 2016;313:10–5. https://doi.org/10.1016/j.taap.2016.10.006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Egger M, Davey-Smith G, Altman D (eds). Systematic reviews in health care: meta-analysis in context, 2nd edition. London: BMJ Publishing Group; 2001. https://doi.org/10.1002/9780470693926.

  25. Smith AH, Yunus M, Khan AF, Ercumen A, Yuan Y, Smith MH, et al. Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh. Int J Epidemiol. 2013;42(4):1077–86. https://doi.org/10.1093/ije/dyt120.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ahmed S, Akhtar E, Roy A, von Ehrenstein OS, Vahter M, Wagatsuma Y, et al. Arsenic exposure alters lung function and airway inflammation in children: a cohort study in rural Bangladesh. Environ Int. 2017;101:108–16. https://doi.org/10.1016/j.envint.2017.01.014.

    Article  PubMed  CAS  Google Scholar 

  27. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997;315(7109):629–34. https://doi.org/10.1136/bmj.315.7109.629.

  28. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.

    Article  PubMed  CAS  Google Scholar 

  29. Crippa A, Orsini N. Dose-response meta-analysis of differences in means. BMC Med Res Methodol. 2016;16:91. https://doi.org/10.1186/s12874-016-0189-0.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Harbord RM, Higgins JPT. Meta-regression in Stata. Stata J. 2008;8(4):493–519.

    Google Scholar 

  31. Nafees AA, Kazi A, Fatmi Z, Irfan M, Ali A, Kayama F. Lung function decrement with arsenic exposure to drinking groundwater along River Indus: a comparative cross-sectional study. Environ Geochem Health. 2011;33(2):203–16. https://doi.org/10.1007/s10653-010-9333-7.

    Article  PubMed  CAS  Google Scholar 

  32. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–38. https://doi.org/10.1183/09031936.05.00034805.

    Article  PubMed  CAS  Google Scholar 

  33. Feng W, Huang X, Zhang C, et al. The dose–response association of urinary metals with altered pulmonary function and risks of restrictive and obstructive lung diseases: a population-based study in China. BMJ Open. 2015;1(5):1–24. https://doi.org/10.1017/CBO9781107415324.004.

    Article  Google Scholar 

  34. De BK, Majumdar D, Sen S, Guru S, Kundu S. Pulmonary involvement in chronic arsenic poisoning from drinking contaminated ground-water. J Assoc Physicians India. 2004;52:395–400.

    PubMed  CAS  Google Scholar 

  35. Selman M, Pardo A. Alveolar epithelial cell disintegrity and subsequent activation. Am J Respir Crit Care Med. 2012;186(2):119–21. https://doi.org/10.1164/rccm.201206-0997ED.

    Article  PubMed  CAS  Google Scholar 

  36. Olsen CE, Liguori AE, Zong Y, Lantz RC, Burgess JL, Boitano S. Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2008;295(2):L293–302. https://doi.org/10.1152/ajplung.00134.2007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Lantz RC, Chau B, Sarihan P, Witten ML, Pivniouk VI, Chen GJ. In utero and postnatal exposure to arsenic alters pulmonary structure and function. Toxicol Appl Pharmacol. 2009;235(1):105–13. https://doi.org/10.1016/j.taap.2008.11.012.

    Article  PubMed  CAS  Google Scholar 

  38. Choudhury S, Gupta P, Ghosh S, Mukherjee S, Chakraborty P, Chatterji U, et al. Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses. Toxicology. 2016;357-358:85–96. https://doi.org/10.1016/j.tox.2016.06.005.

    Article  PubMed  CAS  Google Scholar 

  39. Mazumder DN, Steinmaus C, Bhattacharya P, et al. Bronchiectasis in persons with skin lesions resulting from arsenic in drinking water. Epidemiology. 2005;16(6):760–5.

    Article  PubMed  Google Scholar 

  40. •• Mazumdar M, Christiani DC, Biswas SK, Ibne-Hasan OS, Kapur K, Hug C. Elevated sweat chloride levels due to arsenic toxicity. N Engl J Med. 2015;372(6):582–3. https://doi.org/10.1056/NEJMc1413312. This study shows evidence that arsenic is associated with elevated sweat chloride levels among persons exposed to arsenic in the absence of a genetic diagnosis of cystic fibrosis.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Bomberger JM, Coutermarsh BA, Barnaby RL, Stanton BA. Arsenic promotes ubiquitinylation and lysosomal degradation of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in human airway epithelial cells. J Biol Chem. 2012;287(21):17130–9. https://doi.org/10.1074/jbc.M111.338855.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Han SG, Castranova V, Vallyathan V. Heat shock protein 70 as an indicator of early lung injury caused by exposure to arsenic. Mol Cell Biochem. 2005;277(1–2):153–64. https://doi.org/10.1007/s11010-005-5874-y.

    Article  PubMed  CAS  Google Scholar 

  43. Cohen DS, Palmer E, Welch WJ, Sheppard D. The response of guinea pig airway epithelial cells and alveolar macrophages to environmental stress. Am J Respir Cell Mol Biol. 1991;5(2):133–43.

    Article  PubMed  CAS  Google Scholar 

  44. Broeckaert F, Clippe A, Knoops B, Hermans C, Bernard A. Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Ann N Y Acad Sci. 2000;923:68–77. https://doi.org/10.1111/j.1749-6632.2000.tb05520.x.

    Article  PubMed  CAS  Google Scholar 

  45. Parvez F, Chen Y, Brandt-Rauf PW, Bernard A, Dumont X, Slavkovich V, et al. Nonmalignant respiratory effects of chronic arsenic exposure from drinking water among never-smokers in Bangladesh. Environ Health Perspect. 2008;116(2):190–5. https://doi.org/10.1289/ehp.9507.

    Article  PubMed  CAS  Google Scholar 

  46. Olivas-Calderon E, Recio-Vega R, Gandolfi AJ, et al. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic. Toxicol Appl Pharmacol. 2015;287:161–7. https://doi.org/10.1016/j.taap.2015.06.001.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Atkinson JJ, Senior RM. Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol. 2003;28(1):12–24. https://doi.org/10.1165/rcmb.2002-0166TR.

    Article  PubMed  CAS  Google Scholar 

  48. Lederer DJ, Enright PL, Kawut SM, Hoffman EA, Hunninghake G, van Beek EJR, et al. Cigarette smoking is associated with subclinical parenchymal lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA)-lung study. Am J Respir Crit Care Med. 2009;180(5):407–14. https://doi.org/10.1164/rccm.200812-1966OC.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ferreccio C, Gonzalez C, Milosavjlevic V, Marshall G, Sancha AM, Smith AH. Lung cancer and arsenic concentrations in drinking water in Chile. Epidemiology. 2000;11(6):673–9. https://doi.org/10.1097/00001648-200011000-00010.

    Article  PubMed  CAS  Google Scholar 

  50. Hertz-Picciotto I, Smith AH, Holtzman D, Lipsett M, Alexeeff G. Synergism between occupational arsenic exposure and smoking in the induction of lung cancer. Epidemiology. 1992;3(1):23–31.

    Article  PubMed  CAS  Google Scholar 

  51. IHME. Epi visualization. http://ghdx.healthdata.org/gbd-results-tool?params=querytool-permalink/fc7c45515025010a96c2a7dd49ed751f. Published 2016. Accessed October 27, 2016.

  52. Carlin DJ, Naujokas MF, Bradham KD, Cowden J, Heacock M, Henry HF, et al. Arsenic and environmental health: state of the science and future research opportunities. Environ Health Perspect. 2015;124:890–9. https://doi.org/10.1289/ehp.1510209.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Farzan SF, Korrick S, Li Z, Enelow R, Gandolfi AJ, Madan J, et al. In utero arsenic exposure and infant infection in a United States cohort: a prospective study. Environ Res. 2013;126:24–30. https://doi.org/10.1016/j.envres.2013.05.001.

    Article  PubMed  CAS  Google Scholar 

  54. Araujo BB, Dolhnikoff M, Silva LFF, Elliot J, Lindeman JHN, Ferreira DS, et al. Extracellular matrix components and regulators in the airway smooth muscle in asthma. Eur Respir J. 2008;32(1):61–9. https://doi.org/10.1183/09031936.00147807.

    Article  PubMed  CAS  Google Scholar 

  55. • Sherwood CL, Lantz RC. Lung cancer and other pulmonary disease. In: States JC, ed. Arsenic: exposure sources, health risks, and mechanisms of toxicity. John Wiley & Sons, Inc.; 2015:137–162. https://doi.org/10.1002/9781118876992.ch7. This chapter reviews possible mechanisms for arsenic-associated lung disease, both malignant and non-malignant.

  56. Ramsey KA, Larcombe AN, Sly PD, Zosky GR. In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice. BMC Pharmacol Toxicol. 2013;14:13. https://doi.org/10.1186/2050-6511-14-13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Funding

This work was supported by the National Institute of Environmental Health Sciences at the National Institutes of Health (grant numbers R01ES021367, 1R01ES025216, 5P30ES009089, and P42ES010349).

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Correspondence to Tiffany R. Sanchez.

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Sanchez, T.R., Powers, M., Perzanowski, M. et al. A Meta-analysis of Arsenic Exposure and Lung Function: Is There Evidence of Restrictive or Obstructive Lung Disease?. Curr Envir Health Rpt 5, 244–254 (2018). https://doi.org/10.1007/s40572-018-0192-1

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