Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital

Michael J Coffey, Isabelle R McKay, Michael Doumit, Sandra Chuang, Susan Adams, Sacha Stelzer-Braid, Shafagh A Waters, Nadine A Kasparian, Torsten Thomas, Adam Jaffe, Tamarah Katz, Chee Y Ooi, Michael J Coffey, Isabelle R McKay, Michael Doumit, Sandra Chuang, Susan Adams, Sacha Stelzer-Braid, Shafagh A Waters, Nadine A Kasparian, Torsten Thomas, Adam Jaffe, Tamarah Katz, Chee Y Ooi

Abstract

Introduction: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the 'Evaluating the Alimentary and Respiratory Tracts in Health and disease' (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions.

Methods and analysis: The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor.

Ethics and dissemination: Ethics approval: Sydney Children's Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals.

Trial registration number: NCT04071314.

Keywords: gastroenterology; nutrition & dietetics; paediatrics; respiratory medicine (see Thoracic Medicine).

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Burns KH, Casey PH, Lyle RE, et al. . Increasing prevalence of medically complex children in US hospitals. Pediatrics 2010;126:638–46. 10.1542/peds.2009-1658
    1. Satterwhite BB. Impact of chronic illness on child and family: an overview based on five surveys with implications for management. Int J Rehabil Res 1978;1:7–17. 10.1097/00004356-197801000-00002
    1. Wijlaars LPMM, Gilbert R, Hardelid P. Chronic conditions in children and young people: learning from administrative data. Arch Dis Child 2016;101:881–5. 10.1136/archdischild-2016-310716
    1. , Peterson J, Garges S, et al. , NIH HMP Working Group . The NIH human microbiome project. Genome Res 2009;19:2317–23. 10.1101/gr.096651.109
    1. Pinquart M, Shen Y. Depressive symptoms in children and adolescents with chronic physical illness: an updated meta-analysis. J Pediatr Psychol 2011;36:375–84. 10.1093/jpepsy/jsq104
    1. Conviser JH, Fisher SD, McColley SA. Are children with chronic illnesses requiring dietary therapy at risk for disordered eating or eating disorders? A systematic review. Int J Eat Disord 2018;51:187–213. 10.1002/eat.22831
    1. Saxby N, Painter C, Kench A. Nutrition guidelines for cystic fibrosis in Australia and New Zealand. Sydney: Thoracic Society of Australia and New Zealand, 2017.
    1. Statovci D, Aguilera M, MacSharry J, et al. . The impact of Western diet and nutrients on the microbiota and immune response at mucosal interfaces. Front Immunol 2017;8:838. 10.3389/fimmu.2017.00838
    1. Valdes AM, Walter J, Segal E, et al. . Role of the gut microbiota in nutrition and health. BMJ 2018;361:k2179. 10.1136/bmj.k2179
    1. Farrell PM, Rosenstein BJ, White TB, et al. . Guidelines for diagnosis of cystic fibrosis in newborns through older adults: cystic fibrosis Foundation consensus report. J Pediatr 2008;153:S4–14. 10.1016/j.jpeds.2008.05.005
    1. Massie RJ, Olsen M, Glazner J, Robertson CF, et al. . Newborn screening for cystic fibrosis in Victoria: 10 years' experience (1989-1998). Med J Aust 2000;172:584–7. 10.5694/j.1326-5377.2000.tb124123.x
    1. Sutherland R, Katz T, Liu V, et al. . Dietary intake of energy-dense, nutrient-poor and nutrient-dense food sources in children with cystic fibrosis. J Cyst Fibros 2018;17:804–10. 10.1016/j.jcf.2018.03.011
    1. Nielsen S, Needham B, Leach ST, et al. . Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis. Sci Rep 2016;6:24857. 10.1038/srep24857
    1. Dhaliwal J, Leach S, Katz T, et al. . Intestinal inflammation and impact on growth in children with cystic fibrosis. J Pediatr Gastroenterol Nutr 2015;60:521–6. 10.1097/MPG.0000000000000683
    1. Pang T, Leach ST, Katz T, et al. . Elevated fecal M2-pyruvate kinase in children with cystic fibrosis: a clue to the increased risk of intestinal malignancy in adulthood? J Gastroenterol Hepatol 2015;30:866–71. 10.1111/jgh.12842
    1. Ooi CY, Pang T, Leach ST, et al. . Fecal human β-defensin 2 in children with cystic fibrosis: is there a diminished intestinal innate immune response? Dig Dis Sci 2015;60:2946–52. 10.1007/s10620-015-3842-2
    1. Lee JM, Leach ST, Katz T, et al. . Update of faecal markers of inflammation in children with cystic fibrosis. Mediators Inflamm 2012;2012:1–6. 10.1155/2012/948367
    1. Coffey MJ, Nightingale S, Ooi CY. Predicting a biliary aetiology in paediatric acute pancreatitis. Arch Dis Child 2013;98:965–9. 10.1136/archdischild-2013-304462
    1. Coffey MJ, Nightingale S, Ooi CY. Serum lipase as an early predictor of severity in pediatric acute pancreatitis. J Pediatr Gastroenterol Nutr 2013;56:602–8. 10.1097/MPG.0b013e31828b36d8
    1. Kaakoush NO, Pickford R, Jaffe A, et al. . Is there a role for stool metabolomics in cystic fibrosis? Pediatr Int 2016;58:808–11. 10.1111/ped.13063
    1. Debyser G, Mesuere B, Clement L, et al. . Faecal proteomics: a tool to investigate dysbiosis and inflammation in patients with cystic fibrosis. J Cyst Fibros 2016;15:242–50. 10.1016/j.jcf.2015.08.003
    1. Kosorok MR, Zeng L, West SE, et al. . Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition. Pediatr Pulmonol 2001;32:277–87. 10.1002/ppul.2009.abs
    1. Nixon GM, Davey M. Sleep apnoea in the child. Aust Fam Physician 2015;44:352–5.
    1. Moreno-Indias I, Torres M, Montserrat JM, et al. . Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J 2015;45:1055–65. 10.1183/09031936.00184314
    1. Poroyko VA, Carreras A, Khalyfa A, et al. . Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice. Sci Rep 2016;6:35405. 10.1038/srep35405
    1. Xue J, Zhou D, Poulsen O, et al. . Intermittent hypoxia and hypercapnia accelerate atherosclerosis, partially via Trimethylamine-Oxide. Am J Respir Cell Mol Biol 2017;57:581–8. 10.1165/rcmb.2017-0086OC
    1. Tripathi A, Melnik AV, Xue J, et al. . Intermittent hypoxia and hypercapnia, a hallmark of obstructive sleep apnea, alters the gut microbiome and metabolome. mSystems 2018;3. 10.1128/mSystems.00020-18
    1. Durgan DJ, Ganesh BP, Cope JL, et al. . Role of the gut microbiome in obstructive sleep Apnea-Induced hypertension. Hypertension 2016;67:469–74. 10.1161/HYPERTENSIONAHA.115.06672
    1. Barceló A, Esquinas C, Robles J, et al. . Gut epithelial barrier markers in patients with obstructive sleep apnea. Sleep Med 2016;26:12–15. 10.1016/j.sleep.2016.01.019
    1. Wu BG, Sulaiman I, Wang J, et al. . Severe obstructive sleep apnea is associated with alterations in the nasal microbiome and an increase in inflammation. Am J Respir Crit Care Med 2019;199:99–109. 10.1164/rccm.201801-0119OC
    1. Frykman PK, Nordenskjöld A, Kawaguchi A, et al. . Characterization of bacterial and fungal microbiome in children with Hirschsprung disease with and without a history of enterocolitis: a multicenter study. PLoS One 2015;10:e0124172. 10.1371/journal.pone.0124172
    1. Demehri FR, Frykman PK, Cheng Z, et al. . Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis. J Pediatr Surg 2016;51:81–6. 10.1016/j.jpedsurg.2015.10.012
    1. Barr JJ, Auro R, Furlan M, et al. . Bacteriophage adhering to mucus provide a non-host-derived immunity. Proc Natl Acad Sci U S A 2013;110:10771–6. 10.1073/pnas.1305923110
    1. Zuo T, Lu X-J, Zhang Y, et al. . Gut mucosal virome alterations in ulcerative colitis. Gut 2019;68:1169–79. 10.1136/gutjnl-2018-318131
    1. Minot S, Sinha R, Chen J, et al. . The human gut virome: inter-individual variation and dynamic response to diet. Genome Res 2011;21:1616–25. 10.1101/gr.122705.111
    1. Rodriguez-Brito B, Li L, Wegley L, et al. . Viral and microbial community dynamics in four aquatic environments. Isme J 2010;4:739–51. 10.1038/ismej.2010.1
    1. Kan JM, Cowan CSM, Ooi CY, et al. . What can the gut microbiome teach us about the connections between child physical and mental health? A systematic review. Dev Psychobiol 2019;61:700–13. 10.1002/dev.21819
    1. Dinan TG, Cryan JF. The microbiome-gut-brain axis in health and disease. Gastroenterol Clin North Am 2017;46:77–89. 10.1016/j.gtc.2016.09.007
    1. He Y, Wen Q, Yao F, et al. . Gut-lung axis: the microbial contributions and clinical implications. Crit Rev Microbiol 2017;43:81–95. 10.1080/1040841X.2016.1176988
    1. Callaghan BL, Fields A, Gee DG, et al. . Mind and gut: associations between mood and gastrointestinal distress in children exposed to adversity. Dev Psychopathol 2020;32:309–28. 10.1017/S0954579419000087
    1. Barfod KK, Roggenbuck M, Hansen LH, et al. . The murine lung microbiome in relation to the intestinal and vaginal bacterial communities. BMC Microbiol 2013;13:303. 10.1186/1471-2180-13-303
    1. Chan A-W, Tetzlaff JM, Altman DG, et al. . Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. Wheeler R. Gillick or Fraser? a plea for consistency over competence in children. BMJ 2006;332:807. 10.1136/bmj.332.7545.807
    1. Whittaker RH. Evolution and measurement of species diversity. Taxon 1972;21:213–51. 10.2307/1218190
    1. Shannon CE. A mathematical theory of communication. Bell System Technical Journal 1948;27:379–423. 10.1002/j.1538-7305.1948.tb01338.x
    1. Lozupone CA, Hamady M, Kelley ST, et al. . Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities. Appl Environ Microbiol 2007;73:1576–85. 10.1128/AEM.01996-06
    1. Bray JR, Curtis JT. An Ordination of the upland forest communities of southern Wisconsin. Ecol Monogr 1957;27:325–49. 10.2307/1942268
    1. Hubbell SP. The unified neutral theory of biodiversity and biogeography. Princeton, N.J: Princeton University Press, 2001.
    1. Conceição-Neto N, Zeller M, Lefrère H, et al. . Modular approach to customise sample preparation procedures for viral metagenomics: a reproducible protocol for virome analysis. Sci Rep 2015;5:16532. 10.1038/srep16532
    1. Watson JF, Collins CE, Sibbritt DW, et al. . Reproducibility and comparative validity of a food frequency questionnaire for Australian children and adolescents. Int J Behav Nutr Phys Act 2009;6:62. 10.1186/1479-5868-6-62
    1. Burrows T, Berthon B, Garg ML, et al. . A comparative validation of a child food frequency questionnaire using red blood cell membrane fatty acids. Eur J Clin Nutr 2012;66:825–9. 10.1038/ejcn.2012.26
    1. Burrows TL, Warren JM, Colyvas K, et al. . Validation of overweight children's fruit and vegetable intake using plasma carotenoids. Obesity 2009;17:162–8. 10.1038/oby.2008.495
    1. Collins CE, Burrows TL, Truby H, et al. . Comparison of energy intake in toddlers assessed by food frequency questionnaire and total energy expenditure measured by the doubly labeled water method. J Acad Nutr Diet 2013;113:459–63. 10.1016/j.jand.2012.09.021
    1. Varni JW, Bendo CB, Denham J, et al. . PedsQL gastrointestinal symptoms module: feasibility, reliability, and validity. J Pediatr Gastroenterol Nutr 2014;59:347–55. 10.1097/MPG.0000000000000414
    1. Varni JW, Kay MT, Limbers CA, et al. . PedsQL gastrointestinal symptoms module item development: qualitative methods. J Pediatr Gastroenterol Nutr 2012;54:664–71. 10.1097/MPG.0b013e31823c9b88
    1. Varni JW, Limbers CA, Neighbors K, et al. . The PedsQL™ infant scales: feasibility, internal consistency reliability, and validity in healthy and ill infants. Qual Life Res 2011;20:45–55. 10.1007/s11136-010-9730-5
    1. Benninga MA, Faure C, Hyman PE, et al. . Childhood functional gastrointestinal disorders: Neonate/Toddler. Gastroenterology 2016;150:1443–55. 10.1053/j.gastro.2016.02.016
    1. Hyams JS, Di Lorenzo C, Saps M, et al. . Functional disorders: children and adolescents. Gastroenterology 2016.
    1. Nauta MH, Scholing A, Rapee RM, et al. . A parent-report measure of children's anxiety: psychometric properties and comparison with child-report in a clinic and normal sample. Behav Res Ther 2004;42:813–39. 10.1016/S0005-7967(03)00200-6
    1. Spence SH. Structure of anxiety symptoms among children: a confirmatory factor-analytic study. J Abnorm Psychol 1997;106:280–97. 10.1037/0021-843X.106.2.280
    1. Angold A, Costello EJ, Messer SC, et al. . The development of a short questionnaire for use in epidemiological studies of depression in children and adolescents. Int J Methods Psychiatr Res 1995;5:237–49.
    1. Messer SC, Angold A, Costello EJ, et al. . Development of a short questionnaire for use in epidemiological studies of depression in children and adolescents: factor composition and structure across development. Int J Methods Psychiatr Res 1995;5:251–62.
    1. Australian Bureau of statistics Socio-Economic indexes for areas (SEIFA) technical paper 2016. Canberra: ABS, 2016.
    1. Edgar RC. Search and clustering orders of magnitude faster than blast. Bioinformatics 2010;26:2460–1. 10.1093/bioinformatics/btq461
    1. Lin J, Kramna L, Autio R, et al. . Vipie: web pipeline for parallel characterization of viral populations from multiple NGS samples. BMC Genomics 2017;18:378. 10.1186/s12864-017-3721-7
    1. Roux S, Enault F, Hurwitz BL, et al. . VirSorter: mining viral signal from microbial genomic data. PeerJ 2015;3:e985. 10.7717/peerj.985
    1. Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 2008;26:1367–72. 10.1038/nbt.1511
    1. Yatsunenko T, Rey FE, Manary MJ, et al. . Human gut microbiome viewed across age and geography. Nature 2012;486:222–7. 10.1038/nature11053
    1. Derrien M, Alvarez A-S, de Vos WM. The gut microbiota in the first decade of life. Trends Microbiol 2019;27:997–1010. 10.1016/j.tim.2019.08.001
    1. Milani C, Duranti S, Bottacini F, et al. . The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev 2017;81. 10.1128/MMBR.00036-17. [Epub ahead of print: 08 Nov 2017].
    1. Simon WL, Salk HM, Ovsyannikova IG, et al. . Cytokine production associated with smallpox vaccine responses. Immunotherapy 2014;6:1097–112. 10.2217/imt.14.72
    1. Talaat KR, Halsey NA, Cox AB, et al. . Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination. Influenza Other Respir Viruses 2018;12:202–10. 10.1111/irv.12509
    1. Anderson JL, Miles C, Tierney AC. Effect of probiotics on respiratory, gastrointestinal and nutritional outcomes in patients with cystic fibrosis: a systematic review. J Cyst Fibros 2017;16:186–97. 10.1016/j.jcf.2016.09.004
    1. Mandal S, Van Treuren W, White RA, et al. . Analysis of composition of microbiomes: a novel method for studying microbial composition. Microb Ecol Health Dis 2015;26:27663. 10.3402/mehd.v26.27663
    1. Daviss WB, Birmaher B, Melhem NA, et al. . Criterion validity of the mood and feelings questionnaire for depressive episodes in clinic and non-clinic subjects. J Child Psychol Psychiatry 2006;47:927–34. 10.1111/j.1469-7610.2006.01646.x
    1. Chervin RD, Hedger K, Dillon JE, et al. . Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Med 2000;1:21–32. 10.1016/S1389-9457(99)00009-X

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