1,335
Views
19
CrossRef citations to date
0
Altmetric
Review

Approaches to the assessment of severe asthma: barriers and strategies

, , , &
Pages 235-251 | Published online: 23 Aug 2019

References

  • Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, [Updated 2018]. Available from: https://ginasthma.org/wp-content/uploads/2018/04/wms-GINA-2018-report-V1.3-002.pdf. Accessed 12 2, 2018.
  • McDonald VM, Hiles SA, Jones KA, Clark VL, Yorke J. Health-related quality of life burden in severe asthma. Med J Aust. 2018;209(2 Suppl):S28–S33.30453870
  • Cordova-Rivera L, Gibson PG, Gardiner PA, Powell H, McDonald VM. Physical activity and exercise capacity in severe asthma: key clinical associations. J Allergy Clin Immunol Pract. 2018;6(3):814–822. doi:10.1016/j.jaip.2017.09.02229133222
  • Foster JM, McDonald VM, Guo M, Reddel HK. “I have lost in every facet of my life”: the hidden burden of severe asthma. Eur Respir J. 2017;50:3. doi:10.1183/13993003.00711-2017
  • Reddel HK, Bateman ED, Becker A, et al. A summary of the new GINA strategy: a roadmap to asthma control. Eur Respir J. 2015;46(3):622–639. doi:10.1183/13993003.00853-201526206872
  • Hekking PP, Wener RR, Amelink M, et al. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135(4):896–902. doi:10.1016/j.jaci.2014.08.04225441637
  • Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343–373. doi:10.1183/09031936.0020201324337046
  • Hiles SA, Harvey ES, McDonald VM, et al. Working while unwell: workplace impairment in people with severe asthma. Clin Exp Allergy. 2018;48(6):650–662. doi:10.1111/cea.1315329676834
  • Wark PA, Hew M, Maltby S, McDonald VM, Gibson PG. Diagnosis and investigation in the severe asthma clinic. Expert Rev Respir Med. 2016;10(5):491–503. doi:10.1586/17476348.2016.116509626967545
  • McDonald VM, Maltby S, Reddel HK, et al. Severe asthma: current management, targeted therapies and future directions-A roundtable report. Respirology. 2017;22(1):53–60. doi:10.1111/resp.1295727905186
  • National AE. Prevention P. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol. 2007;120(5 Suppl):S94. doi:10.1016/j.jaci.2007.09.02917983880
  • Upham JW, Chung LP. Optimising treatment for severe asthma. Med J Aust. 2018;209(S2):S22–S27.30453869
  • Chung LP, Hew M, Bardin P, McDonald VM, Upham JW. Managing patients with severe asthma in Australia: current challenges with the existing models of care. Intern Med J. 2018;48(12):1536–1541. doi:10.1111/imj.1410330517993
  • Carr TF, Bleecker E. Asthma heterogeneity and severity. World Allergy Organ J. 2016;9(1):41. doi:10.1186/s40413-016-0118-z27980705
  • Papaioannou AI, Kostikas K, Zervas E, et al. Control of asthma in real life: still a valuable goal? Eur Respir Rev. 2015;24(136):361. doi:10.1183/16000617.0000221526028647
  • Gibson P, McDonald VM. Management of severe asthma: targeting the airways, comorbidities and risk factors. Intern Med J. 2017;47(6):623–631. doi:10.1111/imj.1344128580744
  • Tay TR, Lee JW-Y, Hew M. Diagnosis of severe asthma. Med J Aust. 2018;209(2 Suppl):S3–S10.
  • Moore VC. Spirometry: step by step. Breathe. 2012;8(3):232. doi:10.1183/20734735.0021711
  • Ayuk AC, Uwaezuoke SN, Ndukwu CI, et al. Spirometry in asthma care: a review of the trends and challenges in pediatric practice. Clin Med Insights Pediatr. 2017;11:1179556517720675. doi:10.1177/117955651772067528781518
  • Brannan JD, Lougheed MD. Airway hyperresponsiveness in asthma: mechanisms, clinical significance, and treatment. Front Physiol. 2012;3:460. doi:10.3389/fphys.2012.0046023233839
  • Sanguinetti CM. When to perform a bronchial challenge with mannitol? Multidiscip Respir Med. 2011;6(2):76–78. doi:10.1186/2049-6958-6-2-7622958857
  • Taylor DR, Pijnenburg MW, Smith AD, De Jongste JC. Exhaled nitric oxide measurements: clinical application and interpretation. Thorax. 2006;61(9):817–827. doi:10.1136/thx.2005.05609316936238
  • Pijnenburg MW. The role of FeNO in predicting asthma. Front Pediatr. 2019;7:41. doi:10.3389/fped.2019.0004130847334
  • Ruppel GL. What is the clinical value of lung volumes? Respir Care. 2012;57(1):26–38. doi:10.4187/respcare.0137422222123
  • Ritz T, Dahme B, Dubois AB, et al. Guidelines for mechanical lung function measurements in psychophysiology. Psychophysiology. 2002;39(5):546–567.12236321
  • Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J. 2017;49(1):1600016. doi:10.1183/13993003.00016-201628049168
  • Bailey KL. The importance of the assessment of pulmonary function in COPD. Med Clin North Am. 2012;96(4):745–752. doi:10.1016/j.mcna.2012.04.01122793942
  • McDonald VM, Fingleton J, Agusti A. et al. Treatable traits: a new paradigm for 21st century management of chronic airway diseases: treatable traits down under international workshop report. Eur Respir J. 2019;1802058. doi:10.1183/13993003.02058-201830846468
  • Fricker M, Heaney LG, Upham JW. Can biomarkers help us hit targets in difficult-to-treat asthma? Respirology. 2017;22(3):430–442. doi:10.1111/resp.1301428248008
  • Centre of Excellence in Severe Asthma. The severe asthma toolkit. Available from: https://toolkit.severeasthma.org.au/. Accessed 715, 2019.
  • McDonald VM, Vertigan AE, Gibson PG. How to set up a severe asthma service. Respirology. 2011;16(6):900–911. doi:10.1111/j.1440-1843.2011.02012.x21692918
  • Chung LP, Johnson P, Summers Q. Models of care for severe asthma: the role of primary care. Med J Aust. 2018;209(2 Suppl):S34–S40.30453871
  • McDonald VM, Yorke J. Adherence in severe asthma: time to get it right. Eur Respir J. 2017;50:6. doi:10.1183/13993003.00711-2017
  • Chuenjit W, Engchuan V, Yuenyongviwat A, Sangsupawanich P. Achieving good adherence to inhaled corticosteroids after weighing canisters of asthmatic children. F1000Res. 2017;6:266. doi:10.12688/f1000research.10710.128868133
  • McNicholl DM, Stevenson M, McGarvey LP, Heaney LG. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2012;186(11):1102–1108. doi:10.1164/rccm.201204-0587OC23024023
  • Lindsay JT, Heaney LG. Nonadherence in difficult asthma - facts, myths, and a time to act. Patient Prefer Adherence. 2013;7:329–336. doi:10.2147/PPA.S3820823723690
  • Taylor TE, Zigel Y, Egan C, et al. Objective assessment of patient inhaler user technique using an audio-based classification approach. Sci Rep. 2018;8(1):2164. doi:10.1038/s41598-018-20523-w29391489
  • Lavorini F, Fontana GA, Usmani OS. New inhaler devices-the good, the bad and the ugly. Respiration. 2014;88(1):3–15. doi:10.1159/00036339024902629
  • Faruqi S, Thompson J, Robinson T, et al. Fractional exhaled nitric oxide (FeNO) suppression with directly observed inhaled corticosteroid therapy: does it make a difference to patient outcomes? Eur Respir J. 2018;52(suppl62):PA4453. doi:10.1183/13993003.01675-2018
  • Gamble J, Stevenson M, McClean E, Heaney LG. The prevalence of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2009;180(9):817–822. doi:10.1164/rccm.200902-0166OC19644048
  • Murphy AC, Proeschal A, Brightling CE, et al. The relationship between clinical outcomes and medication adherence in difficult-to-control asthma. Thorax. 2012;67(8):751–753. doi:10.1136/thoraxjnl-2011-20109622436168
  • Gibson PG, McDonald VM, Marks GB. Asthma in older adults. Lancet. 2010;376(9743):803–813. doi:10.1016/S0140-6736(10)61087-220816547
  • Clark VL, Gibson PG, Genn G, et al. Multidimensional assessment of severe asthma: a systematic review and meta-analysis. Respirology. 2017;22(7):1262–1275. doi:10.1111/resp.1313428776330
  • Gibson P, McDonald V. Phenotyping asthma and COPD. BRN Rev. 2016;2:239–252.
  • McDonald V, Clark V, Wark P, Baines K, Gibson P. Multidimensional assessment and targeted therapy of severe asthma: a randomised controlled trial (RCT). Eur Respir J. 2017;50(suppl 61):OA1482. doi:10.1183/13993003.00711-2017
  • Hudon C, Chouinard M-C, Lambert M, Dufour I, Krieg C. Effectiveness of case management interventions for frequent users of healthcare services: a scoping review. BMJ Open. 2016;6(9):e012353. doi:10.1136/bmjopen-2016-012353
  • McDonald VM, Higgins I, Wood LG, Gibson PG. Multidimensional assessment and tailored interventions for COPD: respiratory utopia or common sense? Thorax. 2013;68(7):691–694. doi:10.1136/thoraxjnl-2012-20264623503624
  • Orozco-Beltrán D, Carratalá-Munuera C, Arriero JM, et al. Management and referral of patients with severe and poorly controlled asthma in primary care. Fam Pract. 2016;33(6):678–683. doi:10.1093/fampra/cmw08127543792
  • Braido F, Baiardini I, Stagi E, et al. Unsatisfactory asthma control: astonishing evidence from general practitioners and respiratory medicine specialists. J Investig Allergol Clin Immunol. 2010;20(1):9–12.
  • Cousins JL, Wark PA, McDonald VM. Acute oxygen therapy: a review of prescribing and delivery practices. Int J Chron Obstruct Pulmon Dis. 2016;11:1067–1075. doi:10.2147/COPD.S10360727307722
  • Morrow S, Daines L, Wiener-Ogilvie S, et al. Exploring the perspectives of clinical professionals and support staff on implementing supported self-management for asthma in UK general practice: an IMP(2)ART qualitative study. NPJ Prim Care Respir Med. 2017;27(1):45. doi:10.1038/s41533-017-0041-y28720751
  • Price D, Bjermer L, Bergin DA, Martinez R. Asthma referrals: a key component of asthma management that needs to be addressed. J Asthma Allergy. 2017;10:209–223. doi:10.2147/JAA.S13430028794645
  • Baiardini I, Braido F, Bonini M, Compalati E, Canonica GW. Why do doctors and patients not follow guidelines? Curr Opin Allergy Clin Immunol. 2009;9(3):228–233. doi:10.1097/ACI.0b013e32832b465119390434
  • Lugtenberg M, Zegers-van Schaick JM, Westert GP, Burgers JS. Why don’t physicians adhere to guideline recommendations in practice? An analysis of barriers among Dutch general practitioners. Implement Sci. 2009;4:54. doi:10.1186/1748-5908-4-5419674440
  • Lenney W, Bush A, Fitzgerald DA, et al. Improving the global diagnosis and management of asthma in children. Thorax. 2018;73(7):662. doi:10.1136/thoraxjnl-2018-211626
  • Moffat M, Cleland J, van der Molen T, Price D. Poor communication may impair optimal asthma care: a qualitative study. Fam Pract. 2007;24(1):65–70. doi:10.1093/fampra/cml06217158184
  • Dombkowski KJ, Hassan F, Wasilevich EA, Clark SJ. Spirometry use among pediatric primary care physicians. Pediatrics. 2010;126(4):682–687. doi:10.1542/peds.2010-036220819894
  • Mazrou SHA. Expected benefits of clinical practice guidelines: factors affecting their adherence and methods of implementation and dissemination. JHS. 2013;1(3):141.
  • McDonald VM, Gibson PG. The severe asthma toolkit: a new online resource for clinicians. Respir Med Today. 2018;3(1):26–27.
  • McDonald V, Kennington E, Hyland M. Understanding the experience of people living with severe asthma In: Chung KF, Israel E, Gibson P, editors. Severe Asthma (ERS Monograph). Sheffield: European Respiratory Society; 2019:16–29.
  • Aaron SD, Boulet LP, Reddel HK, Gershon AS. Underdiagnosis and overdiagnosis of asthma. Am J Respir Crit Care Med. 2018;198(8):1012–1020. doi:10.1164/rccm.201804-0682CI29756989
  • Menzies-Gow A, Canonica GW, Winders TA, et al. A charter to improve patient care in severe asthma. Adv Ther. 2018;35(10):1485–1496. doi:10.1007/s12325-018-0777-y30182174
  • Ryan D, Murphy A, Stallberg B, Baxter N, Heaney LG. ‘SIMPLES’: a structured primary care approach to adults with difficult asthma. Prim Care Respir J. 2013;22(3):365–373. doi:10.4104/pcrj.2013.0007523974674
  • Laforest L, Van Ganse E, Devouassoux G, et al. Management of asthma in patients supervised by primary care physicians or by specialists. Eur Respir J. 2006;27(1):42–50. doi:10.1183/09031936.06.0003580516387934
  • Dennis SM, Zwar NA, Marks GB. Diagnosing asthma in adults in primary care: a qualitative study of Australian GPs’ experiences. Prim Care Respir J. 2010;19(1):52–56. doi:10.4104/pcrj.2009.0004619623470
  • Young HN, Len-Rios ME, Brown R, Moreno MM, Cox E. How does patient-provider communication influence adherence to asthma medications? Patient Educ Couns. 2017;100(4):696–702. doi:10.1016/j.pec.2016.11.02227916463
  • Crespo-Lessmann A, Plaza V, González-Barcala F-J, Fernández-Sánchez T, Sastre J. Concordance of opinions between patients and physicians and their relationship with symptomatic control and future risk in patients with moderate–severe asthma. BMJ Open Respir Res. 2017;4(1):e000189. doi:10.1136/bmjresp-2017-000189
  • Eassey D, Reddel HK, Foster JM, et al. “…I've said I wish I was dead, you'd be better off without me”: A systematic review of people's experiences of living with severe asthma. J Asthma 2019;56(3):311-322.
  • Moffat M, Cleland J, van der Molen T, Price D. Sub-optimal patient and physician communication in primary care consultations: its relation to severe and difficult asthma. Prim Care Respir J. 2006;15(3):159–165. doi:10.1016/j.pcrj.2006.02.00616757396
  • Taylor DR, Bateman ED, Boulet LP, et al. A new perspective on concepts of asthma severity and control. Eur Respir J. 2008;32(3):545–554. doi:10.1183/09031936.0015530718757695
  • Bidad N, Barnes N, Griffiths C, Horne R. Understanding patients’ perceptions of asthma control: a qualitative study. Eur Respir J. 2018;51(6):1701346. doi:10.1183/13993003.01346-201729773688
  • Lingner H, Burger B, Kardos P, et al. What patients really think about asthma guidelines: barriers to guideline implementation from the patients’ perspective. BMC Pulm Med. 2017;17(1):13. doi:10.1186/s12890-016-0346-628077097
  • Fitzpatrick AM. Biomarkers of asthma and allergic airway diseases. Ann Allergy Asthma Immunol. 2015;115(5):335–340. doi:10.1016/j.anai.2015.09.00326505931
  • Ward PR, Rokkas P, Cenko C, et al. ‘Waiting for’ and ‘waiting in’ public and private hospitals: a qualitative study of patient trust in South Australia. BMC Health Serv Res. 2017;17(1):333. doi:10.1186/s12913-017-2281-528476130
  • Normansell R, Welsh E. “Asthma can take over your life but having the right support makes that easier to deal with.” Informing research priorities by exploring the barriers and facilitators to asthma control: a qualitative analysis of survey data. Asthma Res Pract. 2015;1(1):11. doi:10.1186/s40733-015-0011-527965765
  • Fielden JM, Cumming JM, Horne JG, et al. Waiting for hip arthroplasty: economic costs and health outcomes. J Arthroplasty. 2005;20(8):990–997. doi:10.1016/j.arth.2004.12.06016376253
  • Eguiluz-Gracia I, Tay TR, Hew M, et al. Recent developments and highlights in biomarkers in allergic diseases and asthma. Allergy. 2018;73(12):2290–2305. doi:10.1111/all.1362830289997
  • Berry M, Morgan A, Shaw DE, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007;62(12):1043–1049. doi:10.1136/thx.2006.07342917356056
  • Green RH, Brightling CE, McKenna S, et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;360(9347):1715–1721. doi:10.1016/S0140-6736(02)11679-512480423
  • Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360(10):973–984. doi:10.1056/NEJMoa080899119264686
  • Pavlidis S, Takahashi K, Ng Kee Kwong F, et al. “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin. Eur Respir J. 2019;53:1. doi:10.1183/13993003.01184-2018
  • Zhang XY, Simpson JL, Powell H, et al. Full blood count parameters for the detection of asthma inflammatory phenotypes. Clin Exp Allergy. 2014;44(9):1137–1145. doi:10.1111/cea.1234524849076
  • Smith AD, Cowan JO, Brassett KP, Herbison GP, Taylor DR. Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. N Engl J Med. 2005;352(21):2163–2173. doi:10.1056/NEJMoa04359615914548
  • Schleich FN, Seidel L, Sele J, et al. Exhaled nitric oxide thresholds associated with a sputum eosinophil count ≥3% in a cohort of unselected patients with asthma. Thorax. 2010;65(12):1039–1044. doi:10.1136/thx.2009.12492520671307
  • Jia G, Erickson RW, Choy DF, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol 2012;130(3):647-654.e10.
  • Simpson JL, Yang IA, Upham JW, et al. Periostin levels and eosinophilic inflammation in poorly-controlled asthma. BMC Pulm Med. 2016;16(1):67. doi:10.1186/s12890-016-0276-327130294
  • Wagener AH, de Nijs SB, Lutter R, et al. External validation of blood eosinophils, FENO and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70(2):115–120. doi:10.1136/thoraxjnl-2014-20563425422384
  • Medrek SK, Parulekar AD, Hanania NA. Predictive biomarkers for asthma therapy. Curr Allergy Asthma Rep. 2017;17(10):69. doi:10.1007/s11882-017-0739-528929293
  • Gibson PG. Variability of blood eosinophils as a biomarker in asthma and COPD. Respirology. 2018;23(1):12–13. doi:10.1111/resp.1320029052302
  • Schleich FN, Manise M, Sele J, et al. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC Pulm Med. 2013;13:11. doi:10.1186/1471-2466-13-1123442497
  • Hastie AT, Moore WC, Li H, et al. Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects. J Allergy Clin Immunol. 2013;132(1):72–80. doi:10.1016/j.jaci.2013.03.04423706399
  • Gibson PG. Inflammatory phenotypes in adult asthma: clinical applications. Clin Respir J. 2009;3(4):198–206. doi:10.1111/j.1752-699X.2009.00162.x20298405
  • Wadsworth S, Sin D, Dorscheid D. Clinical update on the use of biomarkers of airway inflammation in the management of asthma. J Asthma Allergy. 2011;4:77–86. doi:10.2147/JAA.S1508121792321
  • Korevaar DA, Westerhof GA, Wang J, et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med. 2015;3(4):290–300. doi:10.1016/S2213-2600(15)00050-825801413
  • Trevor JL, Chipps BE. Severe asthma in primary care: identification and management. Am J Med. 2018;131(5):484–491. doi:10.1016/j.amjmed.2017.12.03429355509
  • Mcdonald VM, Maltby S, Clark VL, et al. Development of the Severe Asthma Toolkit: A Clinical Website Resource for the Management of Severe Treatment-refractory Asthma. Respirology 2018;23(S2):28-28.
  • Alexandrine JL, Sandra P, Roland G, et al. Facilitators and solutions for practicing optimal guided asthma self-management: the physician perspective. Can Respir J. 2013;20(4):285. doi:10.1155/2013/56210423936888
  • Cabana MD, Slish KK, Evans D, et al. Impact of physician asthma care education on patient outcomes. Pediatrics. 2006;117(6):2149–2157. doi:10.1542/peds.2005-105516740859
  • Clark NM, Cabana MD, Nan B, et al. The clinician-patient partnership paradigm: outcomes associated with physician communication behavior. Clin Pediatr (Phila). 2008;47(1):49–57. doi:10.1177/000992280730565017901215
  • Wolf A, Moore L, Lydahl D, et al. The realities of partnership in person-centred care: a qualitative interview study with patients and professionals. BMJ Open. 2017;7(7):e016491. doi:10.1136/bmjopen-2017-016491
  • Apter AJ, Morales KH, Han X, et al. A patient advocate to facilitate access and improve communication, care, and outcomes in adults with moderate or severe asthma: rationale, design, and methods of a randomized controlled trial. Contemp Clin Trials. 2017;56:34–45. doi:10.1016/j.cct.2017.03.00428315481
  • Kane B, Cramb S, Hudson V, et al. Specialised commissioning for severe asthma: oxymoron or opportunity? Thorax. 2016;71(2):196–198. doi:10.1136/thoraxjnl-2015-20738026609007
  • Loscalzo J, Kohane I, Barabasi AL. Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol Syst Biol. 2007;3:124. doi:10.1038/msb410016317625512
  • Ritchie MD, de Andrade M, Kuivaniemi H. The foundation of precision medicine: integration of electronic health records with genomics through basic, clinical, and translational research. Front Genet. 2015;6:104. doi:10.3389/fgene.2015.0010425852745
  • Verrills NM, Irwin JA, He XY, et al. Identification of novel diagnostic biomarkers for asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;183(12):1633–1643. doi:10.1164/rccm.201010-1623OC21471098
  • Baines KJ, Simpson JL, Wood LG, et al. Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes. J Allergy Clin Immunol. 2014;133(4):997–1007. doi:10.1016/j.jaci.2013.12.109124582314
  • Kim S, Oesterreich S, Kim S, Park Y, Tseng GC. Integrative clustering of multi-level omics data for disease subtype discovery using sequential double regularization. Biostatistics. 2017;18(1):165–179. doi:10.1093/biostatistics/kxw03927549122
  • Dallinga JW, Robroeks CM, van Berkel JJ, et al. Volatile organic compounds in exhaled breath as a diagnostic tool for asthma in children. Clin Exp Allergy. 2010;40(1):68–76. doi:10.1111/j.1365-2222.2009.03343.x19793086
  • Thwaites RS, Jarvis HC, Singh N, et al. Absorption of nasal and bronchial fluids: precision sampling of the human respiratory mucosa and laboratory processing of samples. J Vis Exp 2018(131):e56413.
  • Melo JT Jr., Tunstall T, Pizzichini MMM, et al. IL-5 levels in nasosorption and sputosorption correlate with sputum eosinophilia in allergic asthma. Am J Respir Crit Care Med. 2019;199(2):240–243. doi:10.1164/rccm.201807-1279LE30335470
  • Restifo LL, Phelan GR. The cultural divide: exploring communication barriers between scientists and clinicians. Dis Model Mech. 2011;4(4):423–426. doi:10.1242/dmm.00817721708897
  • St John A. The evidence to support point-of-care testing. Clin Biochem Rev. 2010;31(3):111–119.24150515
  • Ferguson BS, Hoggarth DA, Maliniak D, et al. Real-time, aptamer-based tracking of circulating therapeutic agents in living animals. Sci Transl Med. 2013;5(213):213ra165–213ra165. doi:10.1126/scitranslmed.3007095