Investigations of a combination of atopic status and age of asthma onset identify asthma subphenotypes

References

• Miranda C, Busacker A, Balzar S, Trudeau J, Wenzel SE. Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol. 2004;113:101–108.
   PubMed Web of Science ®Google Scholar
• Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405–413.
   PubMed Web of Science ®Google Scholar
• Tan DJ, Walters EH, Perret JL, Lodge CJ, Lowe AJ, Matheson MC, et al. Age-of-asthma onset as a determinant of different asthma phenotypes in adults: a systematic review and meta-analysis of the literature. Expert Rev Respir Med. 2015;9:109–123.
   PubMed Web of Science ®Google Scholar
• Fuchs O, Bahmer T, Rabe KF, von Mutius E. Asthma transition from childhood into adulthood. Lancet Respir Med. 2017;5:224–234.
   PubMed Web of Science ®Google Scholar
• Azim A, Freeman A, Lavenu A, Mistry H, Haitchi HM, Newell C, et al. New perspectives on difficult asthma; sex and age of asthma-onset based phenotypes. J Allergy Clin Immunol Pract. 2020;8:3396–3406.
   PubMed Web of Science ®Google Scholar
• Zureik M, Neukirch C, Leynaert B, Liard R, Bousquet J, Neukirch F, European Community Respiratory Health Survey Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. BMJ. 2002;325(7361):411–414.
   PubMed Web of Science ®Google Scholar
• Neukirch C, Henry C, Leynaert B, Liard R, Bousquet J, Neukirch F. Is sensitization to Alternaria alternata a risk factor for severe asthma? A population-based study. J Allergy Clin Immunol. 1999;103:709–711.
   PubMed Web of Science ®Google Scholar
• Parthasarathi A, Padukudru S, Krishna MT, Mahesh PA. Clinical characterization of asthma with fungal sensitization in a South Indian paediatric cohort. Clin Exp Allergy. 2022;52:456–460.
   PubMed Web of Science ®Google Scholar
• O'Hollaren MT, Yunginger JW, Offord KP, Somers MJ, O'Connell EJ, Ballard DJ, et al. Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma. N Engl J Med. 1991;324:359–363.
   PubMed Web of Science ®Google Scholar
• Black PN, Udy AA, Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy. 2000;55(5):501–504.
   PubMed Web of Science ®Google Scholar
• Medrek SK, Kao CC, Yang DH, Hanania NA, Parulekar AD. Fungal sensitization is associated with increased risk of life-threatening asthma. J Allergy Clin Immunol Pract. 2017;5:1025–1031.
   PubMed Web of Science ®Google Scholar
• Ross MA, Curtis L, Scheff PA, Hryhorczuk DO, Ramakrishnan V, Wadden RA, Persky VW. Association of asthma symptoms and severity with indoor bioaerosols. Allergy. 2000;55(8):705–711.
   PubMed Web of Science ®Google Scholar
• Dales RE, Cakmak S, Burnett RT, Judek S, Coates F, Brook JR. Influence of ambient fungal spores on emergency visits for asthma to a regional children’s hospital. Am J Respir Crit Care Med. 2000;162(6):2087–2090. doi:10.1164/ajrccm.162.6.2001020.
   PubMed Web of Science ®Google Scholar
• Tham R, Vicendese D, Dharmage SC, Hyndman RJ, Newbigin E, Lewis E, et al. Associations between outdoor fungal spores and childhood and adolescent asthma hospitalizations. J Allergy Clin Immunol. 2017;139:1140–1147.
   PubMed Web of Science ®Google Scholar
• O'Driscoll BR, Hopkinson LC, Denning DW. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions. BMC Pulm Med. 2005;5:4.
   PubMedGoogle Scholar
• Goh KJ, Yii ACA, Lapperre TS, Chan AK, Chew FT, Chotirmall SH, et al. Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma. J Asthma Allergy. 2017;10:131–140.
   PubMed Web of Science ®Google Scholar
• Targonski PV, Persky VW, Ramekrishnan V. Effect of environmental molds on risk of death from asthma during the pollen season. J Allergy Clin Immunol. 1995;95:955–961.
   PubMed Web of Science ®Google Scholar
• Lehmann S, Sprünken A, Wagner N, Tenbrock K, Ott H. Clinical relevance of IgE-mediated sensitization against the mould Alternaria alternata in children with asthma. Ther Adv Respir Dis. 2017;11:30–39.
   PubMed Web of Science ®Google Scholar
• Sullivan A, Hunt EB, Ward C, Lapthorne S, Eustace JA, Fanning LJ, Plant BJ, O'Byrne PM, MacSharry JA, Murphy DM, et al. The presence of Aspergillus fumigatus in asthmatic airways is not clearly related to clinical disease severity. Allergy. 2020;75(5):1146–1154. doi:10.1111/all.14087.
   PubMed Web of Science ®Google Scholar
• Bush A. Kids, difficult asthma and fungus. J Fungi (Basel). 2020;6:55.
   PubMedGoogle Scholar
• Pividori M, Schoettler N, Nicolae DL, Ober C, Im HK. Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies. Lancet Respir Med. 2019;7:509–522.
   PubMed Web of Science ®Google Scholar
• Ferreira MAR, Mathur R, Vonk JM, Szwajda A, Brumpton B, Granell R, et al. Genetic architectures of childhood- and adult-onset asthma are partly distinct. Am J Hum Genet. 2019;104:665–684.
   PubMed Web of Science ®Google Scholar
• Schoettler N, Rodríguez E, Weidinger S, Ober C. Advances in asthma and allergic disease genetics: Is bigger always better? J Allergy Clin Immunol. 2019;144:1495–1506.
   PubMed Web of Science ®Google Scholar
• Kao CC, Hanania NA, Parulekar AD. The impact of fungal allergic sensitization on asthma. Curr Opin Pulm Med. 2021;27:3–8.
   PubMed Web of Science ®Google Scholar
• van Tilburg Bernardes E, Gutierrez MW, Arrieta MC. The fungal microbiome and asthma. Front Cell Infect Microbiol. 2020;10:583418.
   PubMed Web of Science ®Google Scholar
• Castanhinha S, Sherburn R, Walker S, Gupta A, Bossley CJ, Buckley J, et al. Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33. J Allergy Clin Immunol. 2015;136:312–322.
   PubMed Web of Science ®Google Scholar
• Godwin MS, Reeder KM, Garth JM, Blackburn JP, Jones M, Yu Z, et al. IL-1RA regulates immunopathogenesis during fungal-associated allergic airway inflammation. JCI Insight. 2019;4:e129055.
   PubMed Web of Science ®Google Scholar
• Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 2019;47:D1005–D1012.
   PubMed Web of Science ®Google Scholar
• Overton NL, Simpson A, Bowyer P, Denning DW. Genetic susceptibility to severe asthma with fungal sensitization. Int J Immunogenet. 2017;44:93–106.
   PubMed Web of Science ®Google Scholar
• Li X, Ampleford EJ, Howard TD, Moore WC, Torgerson DG, Li H, et al. Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases. J Allergy Clin Immunol. 2012;130:861–868.
   PubMed Web of Science ®Google Scholar
• Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–373.
   PubMed Web of Science ®Google Scholar
• Denlinger LC, Phillips BR, Ramratnam S, Ross K, Bhakta NR, Cardet JC, et al. Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations. Am J Respir Crit Care Med. 2017;195:302–313.
   PubMed Web of Science ®Google Scholar
• Teague WG, Phillips BR, Fahy JV, Wenzel SE, Fitzpatrick AM, Moore WC, et al. Baseline Features of the Severe Asthma Research Program (SARP III) Cohort: differences with age. J Allergy Clin Immunol Pract. 2018;6:545–554.
   PubMed Web of Science ®Google Scholar
• Li X, Christenson SA, Modena B, Li H, Busse WW, Castro M, et al. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. J Allergy Clin Immunol. 2021;147:894–909.
   PubMed Web of Science ®Google Scholar
• Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010;181:315–323.
   PubMed Web of Science ®Google Scholar
• Jarjour NN, Erzurum SC, Bleecker ER, Calhoun WJ, Castro M, Comhair SA, et al. Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. Am J Respir Crit Care Med. 2012;185:356–362.
   PubMed Web of Science ®Google Scholar
• Li X, Hastie AT, Peters MC, Hawkins GA, Phipatanakul W, Li H, et al. Investigation of the relationship between IL-6 and type 2 biomarkers in patients with severe asthma. J Allergy Clin Immunol. 2020;145:430–433.
   PubMed Web of Science ®Google Scholar
• Peters MC, McGrath KW, Hawkins GA, Hastie AT, Levy BD, Israel E, et al. Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts. Lancet Respir Med. 2016;4:574–584.
   PubMed Web of Science ®Google Scholar
• Hawkins GA, Robinson MB, Hastie AT, Li X, Li H, Moore WC, et al. The IL6R variation Asp(358)Ala is a potential modifier of lung function in subjects with asthma. J Allergy Clin Immunol. 2012;130:510–515.
   PubMed Web of Science ®Google Scholar
• Hastie AT, Moore WC, Li H, Rector BM, Ortega VE, Pascual RM, Peters SP, Meyers DA, Bleecker ER, National Heart, Lung, and Blood Institute’s Severe Asthma Research Program 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.2013.03.044.
   PubMed Web of Science ®Google Scholar
• Hastie AT, Mauger DT, Denlinger LC, Coverstone A, Castro M, Erzurum S, et al. Baseline sputum eosinophil + neutrophil subgroups’ clinical characteristics and longitudinal trajectories for NHLBI Severe Asthma Research Program (SARP 3) cohort. J Allergy Clin Immunol. 2020;146:222–226.
   PubMed Web of Science ®Google Scholar
• Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–575. doi:10.1086/519795.
   PubMed Web of Science ®Google Scholar
• Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven RM. The link between fungi and severe asthma: a summary of the evidence. Eur Respir J. 2006;27(3):615–626. doi:10.1183/09031936.06.00074705.
   PubMed Web of Science ®Google Scholar
• Panettieri RA, Jr, Covar R, Grant E, Hillyer EV, Bacharier L. Natural history of asthma: persistence versus progression-does the beginning predict the end? J Allergy Clin Immunol. 2008;121(3):607–613. doi:10.1016/j.jaci.2008.01.006.
   PubMed Web of Science ®Google Scholar
• Ross KR, Gupta R, DeBoer MD, Zein J, Phillips BR, Mauger DT, Li C, Myers RE, Phipatanakul W, Fitzpatrick AM, et al. Severe asthma during childhood and adolescence: A longitudinal study. J Allergy Clin Immunol. 2020;145(1):140–146.e9. doi:10.1016/j.jaci.2019.09.030.
   PubMed Web of Science ®Google Scholar
• Vink NM, Postma DS, Schouten JP, Rosmalen JG, Boezen HM. Gender differences in asthma development and remission during transition through puberty: the TRacking Adolescents’ Individual Lives Survey (TRAILS) Study. J Allergy Clin Immunol. 2010;126(3):498–504. doi:10.1016/j.jaci.2010.06.018.
   PubMed Web of Science ®Google Scholar
• Masaki K, Fukunaga K, Matsusaka M, Kabata H, Tanosaki T, Mochimaru T, Kamatani T, Ohtsuka K, Baba R, Ueda S, et al. Characteristics of severe asthma with fungal sensitization. Ann Allergy Asthma Immunol. 2017;119(3):253–257. doi:10.1016/j.anai.2017.07.008.
   PubMed Web of Science ®Google Scholar
• Li X, Hawkins GA, Ampleford EJ, Moore WC, Li H, Hastie AT, Howard TD, Boushey HA, Busse WW, Calhoun WJ, et al. Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients. J Allergy Clin Immunol. 2013;132(2):313–320.e15. doi:10.1016/j.jaci.2013.01.051.
   PubMed Web of Science ®Google Scholar