Obese, non-eosinophilic asthma: frequent exacerbators in a real-world setting

References

• Asthma UK. The great asthma divide: the annual asthma survey 2019. London: The Asthma UK And British Lung Foundation Partnership; 2020 May.
   Google Scholar
• Rennard SI. Exacerbations and progression of disease in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2004;1(2):88–92.
   PubMedGoogle Scholar
• O’Byrne PM, Pedersen S, Lamm CJ, Tan WC, Busse WW. Severe exacerbations and decline in lung function in asthma. Am J Respir Crit Care Med. 2009;179(1):19–24. doi:10.1164/rccm.200807-1126OC.
   PubMed Web of Science ®Google Scholar
• Miller MK, Lee JH, Miller DP, Wenzel SE. Recent asthma exacerbations: a key predictor of future exacerbations. Respir Med. 2007;101(3):481–489.
   PubMed Web of Science ®Google Scholar
• Ivanova JI, Bergman R, Birnbaum HG, Colice GL, Silverman RA, McLaurin K. Effect of asthma exacerbations on health care costs among asthmatic patients with moderate and severe persistent asthma. J Allergy Clin Immunol. 2012;129(5):1229–1235.
   PubMed Web of Science ®Google Scholar
• Kuruvilla ME, Lee FE-H, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219–233.
   PubMed Web of Science ®Google Scholar
• Denlinger LC, Phillips BR, Ramratnam S, Ross K, Bhakta NR, Cardet JC, Castro M, Peters SP, Phipatanakul W, Aujla S, et al. Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations. Am J Respir Crit Care Med. 2017;195(3):302–313. doi:10.1164/rccm.201602-0419OC.
   PubMed Web of Science ®Google Scholar
• Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D’Agostino R, Castro M, Curran-Everett D, Fitzpatrick AM, et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med. 2010;181(4):315–323. doi:10.1164/rccm.200906-0896OC.
   PubMed Web of Science ®Google Scholar
• FitzGerald JM, Barnes PJ, Chipps BE, Jenkins CR, O’Byrne PM, Pavord ID, Reddel HK. The burden of exacerbations in mild asthma: a systematic review. ERJ Open Res. 2020;6(3):00359-2019. doi:10.1183/23120541.00359-2019.
   PubMedGoogle Scholar
• ten Brinke A. Risk factors of frequent exacerbations in difficult-to-treat asthma. Eur Respir J. 2005;26(5):812–818.
   PubMed Web of Science ®Google Scholar
• Kupczyk M, ten Brinke A, Sterk PJ, Bel EH, Papi A, Chanez P, Nizankowska-Mogilnicka E, Gjomarkaj M, Gaga M, Brusselle G, the BIOAIR investigators, et al. Frequent exacerbators—a distinct phenotype of severe asthma. Clin Exp Allergy. 2014;44(2):212–221. doi:10.1111/cea.12179.
   PubMed Web of Science ®Google Scholar
• Janson C, Lisspers K, Ställberg B, Johansson G, Thuresson M, Telg G, Larsson K. Prevalence, characteristics and management of frequently exacerbating asthma patients: an observational study in Sweden (PACEHR). Eur Respir J. 2018;52(2):1701927. doi:10.1183/13993003.01927-2017.
   PubMed Web of Science ®Google Scholar
• Boulay M-È, Pruneau-Pomerleau C, Villeneuve H, Deschesnes F, Ringuette L, Boulet L-P. Comparative features of Asthma with frequent or infrequent exacerbations: a longitudinal study of retrospective and prospective events. J Asthma. 2018;55(3):231–243. doi:10.1080/02770903.2017.1323918.
   PubMed Web of Science ®Google Scholar
• Exarchos KP, Beltsiou M, Votti C-A, Kostikas K. Artificial intelligence techniques in asthma: a systematic review and critical appraisal of the existing literature. Eur Respir J. 2020;56(3):2000521. doi:10.1183/13993003.00521-2020.
   PubMed Web of Science ®Google Scholar
• Zeiger RS, Heller S, Mellon MH, Wald J, Falkoff R, Schatz M. Facilitated referral to asthma specialist reduces relapses in asthma emergency room visits. J Allergy Clin Immunol. 1991;87(6):1160–1168. doi:10.1016/0091-6749(91)92162-T.
   PubMed Web of Science ®Google Scholar
• Mayo PH, Richman J, Harris HW. Results of a program to reduce admissions for adult asthma. Ann Intern Med. 1990;112(11):864–871. doi:10.7326/0003-4819-112-11-864.
   PubMed Web of Science ®Google Scholar
• Park HJ, Byun MK, Kim HJ, Ahn CM, Rhee CK, Kim K, Kim BY, Bae HW, Yoo K-H. Regular follow-up visits reduce the risk for asthma exacerbation requiring admission in Korean adults with asthma. Allergy Asthma Clin Immunol. 2018;14(1):29. doi:10.1186/s13223-018-0250-0.
   PubMed Web of Science ®Google Scholar
• British Thoracic Society/Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. [Internet]. London: British Thoracic Society; 2019. p. 1–204. https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/.
   Google Scholar
• Reddel HK, Taylor DR, Bateman ED, Boulet L-P, Boushey HA, Busse WW, Casale TB, Chanez P, Enright PL, Gibson PG, American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59–99. doi:10.1164/rccm.200801-060ST.
   PubMed Web of Science ®Google Scholar
• Bel EH, Sousa A, Fleming L, Bush A, Chung KF, Versnel J, Wagener AH, Wagers SS, Sterk PJ, Compton CH, Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome (U-BIOPRED) Consortium, Consensus Generation, et al. Diagnosis and definition of severe refractory asthma: an international consensus statement from the innovative medicine initiative (IMI). Thorax. 2011;66(10):910–917. doi:10.1136/thx.2010.153643.
   PubMed Web of Science ®Google Scholar
• Bjerrum OW, Siersma V, Hasselbalch HC, Lind B, Andersen CL. Association of the blood eosinophil count with end-organ symptoms. Ann Med Surg (Lond). 2019;45:11–18. doi:10.1016/j.amsu.2019.06.015.
   PubMed Web of Science ®Google Scholar
• Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, et al. Standardization of spirometry 2019 update. an official American Thoracic Society and European Respiratory Society technical statement. Am J Respir Crit Care Med. 2019;200(8):e70–e88. doi:10.1164/rccm.201908-1590ST.
   PubMed Web of Science ®Google Scholar
• Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin A-C, Plummer AL, Taylor DR, American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602–615. doi:10.1164/rccm.9120-11ST.
   PubMed Web of Science ®Google Scholar
• National Institute for Health and Care Excellence. Asthma: diagnosis, monitoring and chronic asthma management [Internet]. London: National Institute for Health and Care Excellence; 2017. https://www.nice.org.uk/guidance/ng80.
   Google Scholar
• Ash SY, Diaz AA. The role of imaging in the assessment of severe asthma. Curr Opin Pulm Med. 2017;23(1):97–102. doi:10.1097/MCP.0000000000000341.
   PubMed Web of Science ®Google Scholar
• National Institute for Health and Care Excellence. Inhaled corticosteroid doses for NICE’s asthma guideline [Internet]. National Institute for Health and Care Excellence; 2018. p. 1–3. https://www.nice.org.uk/guidance/ng80/resources/inhaled-corticosteroid-doses-pdf-4731528781.
   Google Scholar
• Global Initiative for Asthma. Asthma management and prevention for adults and children older than 5 years [Internet]. Global Initiative for Asthma; 2019. p. 16. https://ginasthma.org/wp-content/uploads/2019/04/GINA-2019-main-Pocket-Guide-wms.pdf.
   Google Scholar
• Sperber C, Samarasinghe SR, Lomax GP. An upper and lower bound of the medication possession ratio. PPA. 2017;11:1469–1478. doi:10.2147/PPA.S136890.
   Google Scholar
• d’Ancona G, Kavanagh J, Roxas C, Green L, Fernandes M, Thomson L, Dhariwal J, Nanzer AM, Jackson DJ, Kent BD, et al. Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma. Eur Respir J. 2020;55(5):1902259. doi:10.1183/13993003.02259-2019.
   PubMed Web of Science ®Google Scholar
• Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, Bateman ED, Bel EH, Bleecker ER, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343–373. doi:10.1183/09031936.00202013.
   PubMed Web of Science ®Google Scholar
• Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, Wardlaw AJ, Green RH. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218–224. doi:10.1164/rccm.200711-1754OC.
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhang L, Wang G, Feng M, Liang R, McDonald VM, Zhang HP, Yu H, Liang ZA, Wang L, et al. Clinical phenotypes of patients hospitalized for an asthma exacerbation: prognostic implications. J Allergy Clin Immunol Pract. 2021;9(2):830–841.e14. doi:10.1016/j.jaip.2020.09.031.
   PubMed Web of Science ®Google Scholar
• Peters MC, Mauger D, Ross KR, Phillips B, Gaston B, Cardet JC, Israel E, Levy BD, Phipatanakul W, Jarjour NN, et al. Evidence for exacerbation-prone asthma and predictive biomarkers of exacerbation frequency. Am J Respir Crit Care Med. 2020;202(7):973–982. doi:10.1164/rccm.201909-1813OC.
   PubMed Web of Science ®Google Scholar
• Mosen DM, Schatz M, Magid DJ, Camargo CA. The relationship between obesity and asthma severity and control in adults. J Allergy Clin Immunol. 2008;122(3):507–511.e6. doi:10.1016/j.jaci.2008.06.024.
   PubMed Web of Science ®Google Scholar
• Cockcroft DW, Ford GT. Obesity and airway hyper-responsiveness. Can J Respir Crit Care. Sleep Med. 2019;3(2):112–116. doi:10.1080/24745332.2018.1517622.
   Web of Science ®Google Scholar
• Jones RL, Nzekwu M-MU. The effects of body mass index on lung volumes. Chest. 2006;130(3):827–833. doi:10.1378/chest.130.3.827.
   PubMed Web of Science ®Google Scholar
• Zeng Z, Wang L, Ma W, Zheng R, Zhang H, Zeng X, Zhang H, Zhang W. Inhibiting the notch signaling pathway suppresses Th17-associated airway hyperresponsiveness in obese asthmatic mice. Lab Invest. 2019;99(12):1784–1794. doi:10.1038/s41374-019-0294-x.
   PubMed Web of Science ®Google Scholar
• Hudey SN, Ledford DK, Cardet JC. Mechanisms of non-type 2 asthma. Curr Opin Immunol. 2020;66:123–128. doi:10.1016/j.coi.2020.10.002.
   PubMed Web of Science ®Google Scholar
• Boulet L-P, Franssen E. Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma. Respir Med. 2007;101(11):2240–2247. doi:10.1016/j.rmed.2007.06.031.
   PubMed Web of Science ®Google Scholar
• Sutherland ER, Goleva E, Strand M, Beuther DA, Leung DYM. Body mass and glucocorticoid response in asthma. Am J Respir Crit Care Med. 2008;178(7):682–687. doi:10.1164/rccm.200801-076OC.
   PubMed Web of Science ®Google Scholar
• Ma J, Strub P, Xiao L, Lavori PW, Camargo CA, Wilson SR, Gardner CD, Buist AS, Haskell WL, Lv N, et al. Behavioral weight loss and physical activity intervention in obese adults with asthma. a randomized trial. Annals Ats. 2015;12(1):1–11. doi:10.1513/AnnalsATS.201406-271OC.
   Google Scholar
• Freitas PD, Ferreira PG, Silva AG, Stelmach R, Carvalho-Pinto RM, Fernandes FLA, Mancini MC, Sato MN, Martins MA, Carvalho CRF, et al. The role of exercise in a weight-loss program on clinical control in obese adults with asthma. a randomized controlled trial. Am J Respir Crit Care Med. 2017;195(1):32–42. doi:10.1164/rccm.201603-0446OC.
   PubMed Web of Science ®Google Scholar
• Willeboordse M, Kant K. D G v d, Tan FES, Mulkens S, Schellings J, Crijns Y, Ploeg L. v d, van Schayck CP, Dompeling E. A multifactorial weight reduction programme for children with overweight and asthma: a randomized controlled trial. PLoS One. 2016;11(6):e0157158. doi:10.1371/journal.pone.0157158.
   PubMed Web of Science ®Google Scholar
• Hasegawa K, Tsugawa Y, Chang Y, Camargo CA. Risk of an asthma exacerbation after bariatric surgery in adults. J Allergy Clin Immunol. 2015;136(2):288–294.e8. doi:10.1016/j.jaci.2014.12.1931.
   PubMed Web of Science ®Google Scholar
• Littner MR, Leung FW, Ballard ED, Huang B, Samra NK, Lansoprazole Asthma Study Group. Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms. Chest. 2005;128(3):1128–1135. doi:10.1378/chest.128.3.1128.
   PubMed Web of Science ®Google Scholar
• Kiljander TO, Junghard O, Beckman O, Lind T. Effect of esomeprazole 40 mg once or twice daily on asthma. Am J Respir Crit Care Med. 2010;181(10):1042–1048. doi:10.1164/rccm.200910-1537OC.
   PubMed Web of Science ®Google Scholar
• Hiles S, Mcdonald V, Guilhermino M, Brusselle G, Gibson P. Does long-term macrolide treatment reduce asthma exacerbations? An individual patient data meta-analysis. In: Airway pharmacology and treatment. European Respiratory Society; 2019. p. PA2536. doi:10.1183/13993003.congress-2019.PA2536.
   Google Scholar
• Goto T, Camargo CA, Faridi MK, Yun BJ, Hasegawa K. Machine learning approaches for predicting disposition of asthma and COPD exacerbations in the ED. Am J Emerg Med. 2018;36(9):1650–1654.
   PubMed Web of Science ®Google Scholar
• Zein JG, Wu C-P, Attaway AH, Zhang P, Nazha A. Novel machine learning can predict acute asthma exacerbation. Chest. 2021;159(5):1747–1757. doi:10.1016/j.chest.2020.12.051.
   PubMed Web of Science ®Google Scholar
• Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44–56. doi:10.1038/s41591-018-0300-7.
   PubMed Web of Science ®Google Scholar
• Stanford RH, Shah MB, D’Souza AO, Dhamane AD, Schatz M. Short-acting β-agonist use and its ability to predict future asthma-related outcomes. Ann Allergy Asthma Immunol. 2012;109(6):403–407. doi:10.1016/j.anai.2012.08.014.
   PubMed Web of Science ®Google Scholar
• Nwaru BI, Ekström M, Hasvold P, Wiklund F, Telg G, Janson C. Overuse of short-acting β 2 -agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020;55(4):1901872. doi:10.1183/13993003.01872-2019.
   PubMed Web of Science ®Google Scholar
• Gupta S, Price C, Agarwal G, Chan D, Goel S, Boulet L-P, Kaplan AG, Lebovic G, Mamdani M, Straus SE. The electronic asthma management system (eAMS) improves primary care asthma management. Eur Respir J. 2019;53(4):1802241. doi:10.1183/13993003.02241-2018.
   PubMed Web of Science ®Google Scholar
• Mattke S, Martorell F, Hong SY, Sharma P, Cuellar A, Lurie N. Anti-inflammatory medication adherence and cost and utilization of asthma care in a commercially insured population. J Asthma. 2010;47(3):323–329. doi:10.3109/02770900903497196.
   PubMed Web of Science ®Google Scholar
• Vähätalo I, Ilmarinen P, Tuomisto LE, Tommola M, Niemelä O, Lehtimäki L, Nieminen P, Kankaanranta H. 12-year adherence to inhaled corticosteroids in adult-onset asthma. ERJ Open Res. 2020;6(1):00324-2019. doi:10.1183/23120541.00324-2019.
   PubMedGoogle Scholar
• Engelkes M, Janssens HM, de Jongste JC, Sturkenboom MCJM, Verhamme KMC. Medication adherence and the risk of severe asthma exacerbations: a systematic review. Eur Respir J. 2015;45(2):396–407. doi:10.1183/09031936.00075614.
   PubMed Web of Science ®Google Scholar
• Bender BG, Bender SE. Patient-identified barriers to asthma treatment adherence: responses to interviews, focus groups, and questionnaires. Immunol Allergy Clin North Am. 2005;25(1):107–130. doi:10.1016/j.iac.2004.09.005.
   PubMed Web of Science ®Google Scholar
• Jamal S, Menon B, Yousoof M, Vardhan H. Reason for non-compliance to inhaled medications among adult patients of asthma and COPD attending outpatient department in a tertiary care hospital. In: 16 General Practice and Primary Care [Internet]. Brussels:European Respiratory Society; 2016. p. PA852. doi:10.1183/13993003.congress-2016.PA852.
   Google Scholar
• Backman H, Jansson S-A, Stridsman C, Eriksson B, Hedman L, Eklund B-M. Severe asthma among adults: prevalence and clinical characteristics. In: Epidemiology [Internet]. Brussels:European Respiratory Society; 2018. p. PA3918. doi:10.1183/13993003.congress-2018.PA3918.
   Google Scholar
• Corren J, Du E, Gubbi A, Vanlandingham R. Variability in blood eosinophil counts in patients with eosinophilic asthma. J Allergy Clin Immunol Pract. 2020;9(3):1224–1231.
   PubMed Web of Science ®Google Scholar