Abstract
Pediatric severe asthma is actually considered a rare disease with a heterogeneous nature. Recent cohort studies focusing on children with severe asthma identified different clinical presentations (phenotypes) and underlying pathophysiological mechanisms (endotypes). Phenotyping and endotyping asthma represent the current approach to patients with severe asthma and consist in characterizing objectively measurable and non-invasive indicators (biomarkers) capable of orienting diagnosis, management and personalized treatment, as advocated by the Precision Medicine approach. The aim of this review is to provide a practical overview of current and emerging biomarkers in pediatric severe asthma.
Keywords: Biomarkers, eosinophils, fractional exhaled nitric oxide, IgE, neutrophils, pediatric, periostin, severe asthma.
Graphical Abstract
[http://dx.doi.org/10.1183/09031936.00202013] [PMID: 24337046]
[http://dx.doi.org/10.1111/resp.13085] [PMID: 28543931]
[http://dx.doi.org/10.1002/ppul.23152] [PMID: 25604054]
[http://dx.doi.org/10.3389/fped.2017.00044] [PMID: 28316969]
[http://dx.doi.org/10.1080/17476348.2017.1381564] [PMID: 28918658]
[http://dx.doi.org/10.1177/039463201402700405] [PMID: 25572729]
[http://dx.doi.org/10.3389/fped.2018.00170] [PMID: 29971223]
[http://dx.doi.org/10.1007/s11882-017-0688-z] [PMID: 28353215]
[http://dx.doi.org/10.1016/j.jaip.2017.04.031] [PMID: 28689839]
[http://dx.doi.org/10.1016/j.jaip.2017.05.027] [PMID: 28803186]
[http://dx.doi.org/10.1183/13993003.congress-2018.PA4674]
[http://dx.doi.org/10.1136/thoraxjnl-2013-204815] [PMID: 24646659]
[http://dx.doi.org/10.1016/j.jaip.2015.10.008] [PMID: 26772923]
[http://dx.doi.org/10.1183/13993003.00780-2015] [PMID: 26405287]
[http://dx.doi.org/10.1089/ped.2018.0886] [PMID: 30069422]
[http://dx.doi.org/10.1080/17460441.2018.1396315] [PMID: 29077521]
[http://dx.doi.org/10.1097/MCP.0000000000000342] [PMID: 27798418]
[http://dx.doi.org/10.1080/03007995.2018.1439463] [PMID: 29421950]
[http://dx.doi.org/10.1111/cea.12939] [PMID: 28422351]
[http://dx.doi.org/10.1016/j.jaip.2017.05.032] [PMID: 28866107]
[http://dx.doi.org/10.1111/cea.12880] [PMID: 28036144]
[http://dx.doi.org/10.1111/imr.12540] [PMID: 28658544]
[http://dx.doi.org/10.1038/ni.3049] [PMID: 25521684]
[http://dx.doi.org/10.4168/aair.2017.9.6.466] [PMID: 28913985]
[http://dx.doi.org/10.1016/j.jaci.2012.01.059] [PMID: 22385633]
[http://dx.doi.org/10.1097/ACI.0000000000000045] [PMID: 24500296]
[http://dx.doi.org/10.1016/j.jaci.2013.05.007] [PMID: 23727039]
[http://dx.doi.org/10.1016/S0140-6736(12)60988-X] [PMID: 22901886]
[http://dx.doi.org/10.1186/1471-2466-13-11] [PMID: 23442497]
[http://dx.doi.org/10.1038/nm.3300] [PMID: 23921745]
[http://dx.doi.org/10.1186/s12890-016-0271-8] [PMID: 27473851]
[PMID: 26793004]
[http://dx.doi.org/10.1016/j.jaci.2014.10.026] [PMID: 25488689]
[http://dx.doi.org/10.1016/j.jaci.2016.09.028] [PMID: 27777180]
[http://dx.doi.org/10.2174/1573398X13666170616110738] [PMID: 29290750]
[http://dx.doi.org/10.2174/1872213X12666180430161351] [PMID: 29714140]
[http://dx.doi.org/10.1016/j.rmed.2009.09.011] [PMID: 19846286]
[http://dx.doi.org/10.1016/j.jaci.2013.02.032] [PMID: 23591271]
[http://dx.doi.org/10.1164/rccm.201208-1414OC] [PMID: 23471469]
[http://dx.doi.org/10.1016/S2213-2600(16)30031-5] [PMID: 27177493]
[http://dx.doi.org/10.1016/j.jaci.2017.10.005] [PMID: 29221581]
[http://dx.doi.org/10.1164/rccm.201707-1323OC] [PMID: 28915080]
[http://dx.doi.org/10.1111/all.12101] [PMID: 23347007]
[http://dx.doi.org/10.1136/thoraxjnl-2014-205634] [PMID: 25422384]
[http://dx.doi.org/10.1002/ppul.22769] [PMID: 23401467]
[http://dx.doi.org/10.1002/ppul.22810] [PMID: 23798479]
[http://dx.doi.org/10.1067/mai.2001.119411] [PMID: 11692100]
[http://dx.doi.org/10.1016/j.jaci.2010.02.008] [PMID: 20398920]
[http://dx.doi.org/10.1164/ajrccm.161.1.9809100] [PMID: 10619799]
[http://dx.doi.org/10.1111/cea.12935] [PMID: 28390083]
[http://dx.doi.org/10.1136/thx.54.5.403] [PMID: 10212103]
[http://dx.doi.org/10.1164/ajrccm.155.5.9154849] [PMID: 9154849]
[http://dx.doi.org/10.1136/thx.2010.156836] [PMID: 21825081]
[http://dx.doi.org/10.1002/14651858.CD005603.pub3] [PMID: 28837221]
[http://dx.doi.org/10.1586/1744666X.2015.1086645] [PMID: 26358006]
[http://dx.doi.org/10.1034/j.1399-3038.13.s.15.8.x] [PMID: 12688623]
[http://dx.doi.org/10.1016/j.jaci.2011.12.979] [PMID: 22386512]
[http://dx.doi.org/10.1007/s40272-014-0107-z] [PMID: 25404353]
[http://dx.doi.org/10.1517/17460441.2015.1048220] [PMID: 25979110]
[http://dx.doi.org/10.2174/1573398X13666170426094536] [PMID: 29213221]
[http://dx.doi.org/10.1093/rheumatology/kev410] [PMID: 26790456]
[http://dx.doi.org/10.1111/all.12580] [PMID: 25631525]
[http://dx.doi.org/10.1016/j.jaci.2012.06.025] [PMID: 22857879]
[http://dx.doi.org/10.1073/pnas.1009426107] [PMID: 20660732]
[http://dx.doi.org/10.1056/NEJMoa1804092] [PMID: 29782217]
[http://dx.doi.org/10.1016/j.anai.2018.07.033]
[http://dx.doi.org/10.1177/0194599817737967] [PMID: 29040053]
[http://dx.doi.org/10.1111/pai.12744] [PMID: 28631851]
[http://dx.doi.org/10.1007/s40521-016-0106-0] [PMID: 27942431]
[http://dx.doi.org/10.1111/all.12599] [PMID: 25703927]
[http://dx.doi.org/10.1111/pai.12575] [PMID: 27062336]
[http://dx.doi.org/10.1183/09031936.02.00293102] [PMID: 12166573]
[http://dx.doi.org/10.1186/s40733-018-0045-6] [PMID: 30094051]
[http://dx.doi.org/10.1164/ajrccm.162.5.2002014] [PMID: 11069821]
[http://dx.doi.org/10.1164/rccm.9120-11ST] [PMID: 21885636]
[http://dx.doi.org/10.1111/j.1365-2222.2007.02897.x] [PMID: 18076708]
[http://dx.doi.org/10.1183/09031936.00151010] [PMID: 21920894]
[http://dx.doi.org/10.1183/09031936.00019811] [PMID: 22743669]
[http://dx.doi.org/10.12932/AP-270717-0126] [PMID: 29223148]
[http://dx.doi.org/10.1016/j.jaci.2016.09.002] [PMID: 27664377]
[http://dx.doi.org/10.1002/ppul.23371] [PMID: 26829581]
[http://dx.doi.org/10.1002/14651858.CD011439.pub2] [PMID: 27825189]
[http://dx.doi.org/10.1088/1752-7155/2/3/037003] [PMID: 21386164]
[http://dx.doi.org/10.1183/13993003.00965-2016] [PMID: 28446552]
[http://dx.doi.org/10.1016/j.iac.2018.06.002]
[http://dx.doi.org/10.1002/ppul.22615] [PMID: 22782807]
[http://dx.doi.org/10.1183/09031936.02.00101202] [PMID: 11936527]
[http://dx.doi.org/10.1016/j.jaci.2003.10.046] [PMID: 14767439]
[http://dx.doi.org/10.1016/j.rmed.2008.11.009] [PMID: 19110408]
[http://dx.doi.org/10.3389/fped.2018.00196] [PMID: 30035104]
[PMID: 26100359]
[http://dx.doi.org/10.1002/ppul.23785] [PMID: 29082668]
[http://dx.doi.org/10.1111/all.12793] [PMID: 26476125]
[http://dx.doi.org/10.1183/13993003.01817-2017] [PMID: 29326334]
[http://dx.doi.org/10.1111/cea.12052] [PMID: 23786277]
[http://dx.doi.org/10.1183/09031936.00010712] [PMID: 23645402]
[http://dx.doi.org/10.1164/ajrccm.160.3.9812110] [PMID: 10471631]
[http://dx.doi.org/10.1183/09031936.03.00261903] [PMID: 14516137]
[http://dx.doi.org/10.1016/j.rmed.2014.10.007] [PMID: 25456708]
[http://dx.doi.org/10.1016/j.jaci.2013.10.011] [PMID: 24332216]
[http://dx.doi.org/10.1164/ajrccm.161.1.9802048] [PMID: 10619791]
[http://dx.doi.org/10.3389/fped.2019.00289]
[http://dx.doi.org/10.1016/j.jaci.2007.02.042] [PMID: 17472810]
[http://dx.doi.org/10.1136/thorax.57.10.875] [PMID: 12324674]
[http://dx.doi.org/10.1002/ppul.20159] [PMID: 15678506]
[http://dx.doi.org/10.1164/ajrccm.161.4.9812061] [PMID: 10764310]
[http://dx.doi.org/10.1002/ppul.23366] [PMID: 26678320]
[http://dx.doi.org/10.1016/j.jaci.2017.02.004] [PMID: 28390574]
[http://dx.doi.org/10.1378/chest.119.5.1329] [PMID: 11348936]
[http://dx.doi.org/10.1016/j.it.2011.06.008] [PMID: 21839682]
[http://dx.doi.org/10.1378/chest.11-1838] [PMID: 22345378]
[http://dx.doi.org/10.1164/ajrccm.160.5.9806170] [PMID: 10556116]