A modern approach to identifying and characterizing child asthma and wheeze phenotypes based on clinical data
Autoři:
Bronwyn K. Brew aff001; Flaminia Chiesa aff001; Cecilia Lundholm aff001; Anne Örtqvist aff001; Catarina Almqvist aff001
Působiště autorů:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
aff001; National Perinatal Epidemiology and Statistics Unit, Centre for Big Data Research in Health and the School of Women and Children’s Health, University of New South Wales, Sydney, Australia
aff002; IQVIA Nordics, Stockholm, Sweden
aff003; Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
aff004; Department of Obstetrics and Gynecology, Visby Lasarett, Gotland, Sweden
aff005; Pediatric Allergy and Pulmonology Unit, Karolinska University Hospital, Stockholm, Sweden
aff006
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0227091
Souhrn
‘Asthma’ is a complex disease that encapsulates a heterogeneous group of phenotypes and endotypes. Research to understand these phenotypes has previously been based on longitudinal wheeze patterns or hypothesis-driven observational criteria. The aim of this study was to use data-driven machine learning to identify asthma and wheeze phenotypes in children based on symptom and symptom history data, and, to further characterize these phenotypes. The study population included an asthma-rich population of twins in Sweden aged 9–15 years (n = 752). Latent class analysis using current and historical clinical symptom data generated asthma and wheeze phenotypes. Characterization was then performed with regression analyses using diagnostic data: lung function and immunological biomarkers, parent-reported medication use and risk-factors. The latent class analysis identified four asthma/wheeze phenotypes: early transient wheeze (15%); current wheeze/asthma (5%); mild asthma (9%), moderate asthma (10%) and a healthy phenotype (61%). All wheeze and asthma phenotypes were associated with reduced lung function and risk of hayfever compared to healthy. Children with mild and moderate asthma phenotypes were also more likely to have eczema, allergic sensitization and a family history of asthma. Furthermore, those with moderate asthma phenotype had a higher eosinophil concentration (β 0.21, 95%CI 0.12, 0.30) compared to healthy and used short-term relievers at a higher rate than children with mild asthma phenotype (RR 2.4, 95%CI 1.2–4.9). In conclusion, using a data driven approach we identified four wheeze/asthma phenotypes which were validated with further characterization as unique from one another and which can be adapted for use by the clinician or researcher.
Klíčová slova:
Allergies – Asthma – Child health – Children – Medical risk factors – Pediatrics – Pulmonary function – Twins
Zdroje
1. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2016 [2017-01-22]. www.ginasthma.org.
2. Deliu M, Belgrave D, Sperrin M, Buchan I, Custovic A. Asthma phenotypes in childhood. Expert Rev Clin Immunol. 2017;13(7):705–13. Epub 2016/11/08. doi: 10.1080/1744666X.2017.1257940 27817211.
3. Deliu M, Yavuz TS, Sperrin M, Belgrave D, Sahiner UM, Sackesen C, et al. Features of asthma which provide meaningful insights for understanding the disease heterogeneity. Clin Exp Allergy. 2018;48(1):39–47. Epub 2017/08/24. doi: 10.1111/cea.13014 28833810.
4. Hose AJ, Depner M, Illi S, Lau S, Keil T, Wahn U, et al. Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts. J Allergy Clin Immunol. 2017;139(6):1935–45 e12. Epub 2016/10/25. doi: 10.1016/j.jaci.2016.08.046 27771325.
5. Depner M, Fuchs O, Genuneit J, Karvonen AM, Hyvarinen A, Kaulek V, et al. Clinical and epidemiologic phenotypes of childhood asthma. Am J Respir Crit Care Med. 2014;189(2):129–38. Epub 2013/11/29. doi: 10.1164/rccm.201307-1198OC 24283801.
6. Henderson J, Granell R, Heron J, Sherriff A, Simpson A, Woodcock A, et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax. 2008;63(11):974–80. Epub 2008/08/06. doi: 10.1136/thx.2007.093187 18678704.
7. Granell R, Henderson AJ, Sterne JA. Associations of wheezing phenotypes with late asthma outcomes in the Avon Longitudinal Study of Parents and Children: A population-based birth cohort. J Allergy Clin Immunol. 2016;138(4):1060–70 e11. Epub 2016/04/24. doi: 10.1016/j.jaci.2016.01.046 27106203.
8. Savenije OE, Granell R, Caudri D, Koppelman GH, Smit HA, Wijga A, et al. Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA. J Allergy Clin Immunol. 2011;127(6):1505–12 e14. Epub 2011/03/18. doi: 10.1016/j.jaci.2011.02.002 21411131.
9. Deliu M, Sperrin M, Belgrave D, Custovic A. Identification of Asthma Subtypes Using Clustering Methodologies. Pulm Ther. 2016;2:19–41. Epub 2016/08/12. doi: 10.1007/s41030-016-0017-z 27512723.
10. Howard R, Rattray M, Prosperi M, Custovic A. Distinguishing Asthma Phenotypes Using Machine Learning Approaches. Curr Allergy Asthma Rep. 2015;15(7):38. Epub 2015/07/06. doi: 10.1007/s11882-015-0542-0 26143394.
11. Belgrave DCM, Simpson A, Semic-Jusufagic A, Murray CS, Buchan I, Pickles A, et al. Joint modeling of parentally reported and physician-confirmed wheeze identifies children with persistent troublesome wheezing. J Allergy Clin Immunol. 2013;132(3):575–83 e12. Epub 2013/08/03. doi: 10.1016/j.jaci.2013.05.041 23906378.
12. Rzehak P, Wijga AH, Keil T, Eller E, Bindslev-Jensen C, Smit HA, et al. Body mass index trajectory classes and incident asthma in childhood: results from 8 European Birth Cohorts—a Global Allergy and Asthma European Network initiative. J Allergy Clin Immunol. 2013;131(6):1528–36. Epub 2013/02/14. doi: 10.1016/j.jaci.2013.01.001 23403049.
13. Garden F, Simpson JM, Mellis CM, Marks GB. Change in the manifestations of asthma and asthma-related traits in childhood: a latent transition analysis. Eur Respir J. 2016;47:362–65. doi: 10.1183/13993003.02011-2015 26828043
14. Herr M, Just J, Nikasinovic L, Foucault C, Le Marec AM, Giordanella JP, et al. Risk factors and characteristics of respiratory and allergic phenotypes in early childhood. J Allergy Clin Immunol. 2012;130(2):389–96 e4. Epub 2012/08/01. doi: 10.1016/j.jaci.2012.05.054 22846748.
15. Lazic N, Roberts G, Custovic A, Belgrave D, Bishop C, Winn J, et al. Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts. Allergy. 2013;68:764–70. doi: 10.1111/all.12134 23621120
16. Spycher BD, Silverman M, Brooke AM, Minder CE, Kuehni CE. Distinguishing phenotypes of childhood wheeze and cough using latent class analysis. Eur Respir J. 2008;31(5):974–81. Epub 2008/01/25. doi: 10.1183/09031936.00153507 18216047.
17. Spycher BD, Silverman M, Pescatore AM, Beardsmore CS, Kuehni CE. Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts. J Allergy Clin Immunol. 2013;132(5):1058–67. Epub 2013/10/01. doi: 10.1016/j.jaci.2013.08.002 24075230.
18. Anckarsäter H, Lundström S, Kollberg L, Kerekes N, Palm C, Carlström E, et al. The Child and Adolescent Twin Study in Sweden (CATSS). Twin Res Hum Gen. 2012;14(06):495–508. doi: 10.1375/twin.14.6.495 22506305
19. Almqvist C, Ortqvist AK, Ullemar V, Lundholm C, Lichtenstein P, Magnusson PK. Cohort Profile: Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA). Twin Res Hum Genet. 2015;18(3):273–80. doi: 10.1017/thg.2015.17 25900604.
20. Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, et al. International study of asthma and allergies in childhood (ISAAC): rationale and methods. Eur Resp J. 1995;8(3):483–91. doi: 10.1183/09031936.95.08030483 7789502
21. Ludvigsson JF, Almqvist C, Bonamy AE, Ljung R, Michaelsson K, Neovius M, et al. Registers of the Swedish total population and their use in medical research. Eur J Epidemiol. 2016;31:125–36. doi: 10.1007/s10654-016-0117-y 26769609.
22. Lindemalm C, Nordlund B, Ortqvist AK, Lundholm C, van Hage M, Gong T, et al. Associations Between Asthma and Sensitization to Pet or Pollen Allergens in Young Swedish Twins—The STOPPA Study. Twin Res Hum Genet. 2017;20(5):380–8. doi: 10.1017/thg.2017.48 28975873.
23. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;40(6):1324–43. doi: 10.1183/09031936.00080312 22743675.
24. Martinez F, Morgan WJ, Wright A, Holberg CJ, Taussig LM. Diminised lung function as a predisposing factor for wheezing respiratory illness in infants. NEJM. 1988;319:1112–7. doi: 10.1056/NEJM198810273191702 3173442
25. Stern DA, Morgan WJ, Wright AL, Guerra S, Martinez FD. Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007;370(9589):758–64. doi: 10.1016/S0140-6736(07)61379-8 17765525
26. Owens L, Laing IA, Zhang G, Le Souef PN. Infant lung function predicts asthma persistence and remission in young adults. Respirology. 2016;22:2.
27. Raza A, Kurukulaaratchy RJ, Grundy JD, Clayton CB, Mitchell FA, Roberts G, et al. What does adolescent undiagnosed wheeze represent? Findings from the Isle of Wight Cohort. Eur Respir J. 2012;40(3):580–8. Epub 2012/01/24. doi: 10.1183/09031936.00085111 22267759.
28. Ullemar V, Lundholm C, Almqvist C. Twins’ risk of childhood asthma mediated by gestational age and birthweight. Clin Exp Allergy. 2015;45(8):1328–36. doi: 10.1111/cea.12547 25845700.
Článek vyšel v časopise
PLOS One
2019 Číslo 12
- Jak a kdy u celiakie začíná reakce na lepek? Možnou odpověď poodkryla čerstvá kanadská studie
- Pomůže v budoucnu s triáží na pohotovostech umělá inteligence?
- Spermie, vajíčka a mozky – „jednohubky“ z výzkumu 2024/38
- Infekce se v Americe po příjezdu Kolumba šířily nesrovnatelně déle, než se traduje
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
Nejčtenější v tomto čísle
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells
- Oregano powder reduces Streptococcus and increases SCFA concentration in a mixed bacterial culture assay
- The characteristic of patulous eustachian tube patients diagnosed by the JOS diagnostic criteria
- Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts
Zvyšte si kvalifikaci online z pohodlí domova
Všechny kurzy