The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.

Allergy Royal Brompton Hospital London United Kingdom

Centre of Academic Primary Care Division of Applied Health Sciences University of Aberdeen Aberdeen United Kingdom

Department Clinical Pharmacy and Pharmacology University of Groningen University Medical Center Groningen Groningen Netherlands

Department for Pediatric Pneumology and Immunology Charite University Medicine Berlin Germany

Department of Allergy and Rhinology Royal National ENT Hospital London United Kingdom

Department of Allergy Inflammation Center Helsinki University Hospital and University of Helsinki Helsinki Finland

Department of Allergy La Paz University Hospital IdiPAZ Madrid Spain

Department of Clinical Immunology and Allergology University Teaching Hospital in Martin Martin Slovak Republic

Department of Dermatology Bispebjerg Hospital University of Copenhagen Copenhagen Denmark

Department of Dermatology University Hospital of Zurich Zurich Switzerland

Department of Dermatology University of Zurich Zurich Switzerland

Department of Microbiology Immunology and Transplantation KU Leuven Catholic University of Leuven Leuven Belgium

Department of Otolaryngology Head and Neck Surgery University of North Carolina at Chapel Hill Chapel Hill NC United States

Department of Otorhinolaryngology Head and Neck Surgery and Audiology Rigshospitalet Copenhagen University Copenhagen Denmark

Department of Otorhinolaryngology Head and Neck Surgery University Hospitals Leuven Belgium

Department of Otorhinolaryngology Kuopio University Hospital and University of Eastern Finland Kuopio Finland

Department of Otorhinolarynogology and Head Neck Surgery Amsterdam University Medical Centres University of Amsterdam Amsterdam Netherlands

Department of Paediatrics Jessenius Faculty of Medicine in Martin Comenius University in Bratislava University Teaching Hospital in Martin Martin Slovak Republic

Department of Pulmonology and Phthisiology Jessenius Faculty of Medicine in Martin Comenius University in Bratislava University Teaching Hospital in Martin Martin Slovak Republic

Department of Pulmonology STZ Centre of Excellence for Asthma COPD and Respiratory Allergy Franciscus Gasthuis and Vlietland Rotterdam Netherlands

Department of Respiratory Medicine 1st Faculty of Medicine Charles University and Thomayer Hospital Prague Czech Republic

Department of Respiratory Medicine and Allergology Institute for Clinical Science Skane University Hospital Lund University Lund Sweden

Department of Rhinology and Skull Base Surgery Guy's and St Thomas' Hospital NHS Foundation Trust London United Kingdom

Division of Immunity and Infection University College London United Kingdom

Escuela de Doctorado UAM Centro de Estudios de Posgrado Universidad Autónoma de Madrid Calle Francisco Tomás y Valiente no 2 Ciudad Universitaria de Cantoblanco Madrid Spain

Kidsallergy Centre Cape Town South Africa

Laboratory of Allergy and Clinical Immunology University Hospitals Leuven Leuven Belgium

Observational and Pragmatic Research Institute Singapore Singapore

Otolaryngology Department Clinic Barcelona Barcelona Spain

Otolaryngology Department University of Barcelona Barcelona Spain

Otolaryngology Head and Neck Surgery A Gemelli University Hospital Foundation IRCCS Rome Italy

Paediatric Allergist Red Cross Children's Hospital and University of Cape Town Cape Town South Africa

Rhinology Unit and Smell Clinic ENT Department Hospital Clínic FRCB IDIBAPS Universitat de Barcelona CIBERES Barcelona Spain

The Allergy Clinic Blairgowrie Randburg South Africa

The European Forum for Research and Education in Allergy and Airway Diseases Scientific Expert Team Members Brussels Belgium

Upper Airways Research Laboratory Department of Head and Skin Ghent University Ghent Belgium

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Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Diabetes prevention program research group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. (2002) 346(6):393–403. 10.1056/NEJMoa012512 PubMed DOI PMC

Scadding GK, McDonald M, Backer V, Scadding G, Bernal-Sprekelsen M, Conti DM, et al. Pre-asthma: a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1—allergic asthma. Front. Allergy. (2024) 4:1291185. 10.3389/falgy.2023.1291185 PubMed DOI PMC

Turan N, van der Veen TA, Draijer C, Fattahi F, Ten Hacken NH, Timens W, et al. Neutrophilic asthma is associated with smoking, high numbers of IRF5+, and low numbers of IL10+ macrophages. Front Allergy. (2021) 2:676930. 10.3389/falgy.2021.676930 PubMed DOI PMC

Alviani C, Roberts G, Mitchell F, Martin J, Zolkipli Z, Michaelis LJ, et al. Primary prevention of asthma in high-risk children using HDM SLIT: assessment at age 6 years. J Allergy Clin Immunol. (2020) 145(6):1711–3. 10.1016/j.jaci.2020.01.048 PubMed DOI PMC

Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol. (2014) 133(6):1557–63.e5. 10.1016/j.jaci.2013.10.011 PubMed DOI PMC

Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. (2008) 178(3):218–24. 10.1164/rccm.200711-1754OC PubMed DOI PMC

Pearce N, Douwes J, Beasley R. Is allergen exposure the major primary cause of asthma? Thorax. (2000) 55(5):424–31. 10.1136/thorax.55.5.424 PubMed DOI PMC

Douwes J, Gibson P, Pekkanen J, Pearce N. Non-eosinophilic asthma: importance and possible mechanisms. Thorax. (2002) 57(7):643–8. 10.1136/thorax.57.7.643 PubMed DOI PMC

Bachert C, Luong AU, Gevaert P, Mullol J, Smith SG, Silver J, et al. The unified airway hypothesis: evidence from specific intervention with anti-IL-5 biologic therapy. J Allergy Clin Immunol Pract. (2023) 11(9):2630–41. 10.1016/j.jaip.2023.05.011 PubMed DOI

Ying S, Humbert M, Meng Q, Pfister R, Menz G, Gould HJ, et al. Local expression of epsilon germline gene transcripts and RNA for the epsilon heavy chain of IgE in the bronchial mucosa in atopic and nonatopic asthma. J Allergy Clin Immunol. (2001) 107(4):686–92. 10.1067/mai.2001.114339 PubMed DOI

Wilson DR, Merrett TG, Varga EM, Smurthwaite L, Gould HJ, Kemp M, et al. Increases in allergen-specific IgE in BAL after segmental allergen challenge in atopic asthmatics. Am J Respir Crit Care Med. (2002) 165(1):22–6. 10.1164/ajrccm.165.1.2010112 PubMed DOI

Quirce S, Heffler E, Nenasheva N, Demoly P, Menzies-Gow A, Moreira-Jorge A, et al. Revisiting late-onset asthma: clinical characteristics and association with allergy. J Asthma Allergy. (2020) 13:743–52. 10.2147/JAA.S282205 PubMed DOI PMC

Mukherjee M, Nair P. Autoimmune responses in severe asthma. Allergy Asthma Immunol Res. (2018) 10(5):428–47. 10.4168/aair.2018.10.5.428 PubMed DOI PMC

Gevaert P, Han JK, Smith SG, Sousa AR, Howarth PH, Yancey SW, et al. The roles of eosinophils and interleukin-5 in the pathophysiology of chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. (2022) 12(11):1413–23. 10.1002/alr.22994 PubMed DOI PMC

Castillo JA, Plaza V, Rodrigo G, Juliá B, Picado C, Fernández C, et al. Chronic rhinosinusitis with nasal polyps and allergic rhinitis as different multimorbid treatable traits in asthma. J Allergy Clin Immunol Glob. (2023) 2(4):100134. 10.1016/j.jacig.2023.100134 PubMed DOI PMC

Hellings PW, Klimek L, Cingi C, Agache I, Akdis C, Bachert C, et al. Non-allergic rhinitis: position paper of the European academy of allergy and clinical immunology. Allergy. (2017) 72(11):1657–65. 10.1111/all.13200 PubMed DOI

Shaaban R, Zureik M, Soussan D, Neukirch C, Heinrich J, Sunyer J, et al. Rhinitis and onset of asthma: a longitudinal population-based study. Lancet. (2008) 372(9643):1049–57. 10.1016/S0140-6736(08)61446-4 PubMed DOI

Shin YS, Tse K, Lee YJ. The association between non-allergic rhinitis and asthma exacerbations: a systematic review and meta-analysis. J Asthma. (2018) 55(12):1292–302. 10.1080/02770903.2017.1421197 DOI

Rondón C, Bogas G, Barrionuevo E, Blanca M, Torres MJ, Campo P. Nonallergic rhinitis and lower airway disease. Allergy. (2017) 72(1):24–34. 10.1111/all.12988 PubMed DOI

De Corso E, Seccia V, Ottaviano G, Cantone E, Lucidi D, Settimi S, et al. Clinical evidence of type 2 inflammation in non-allergic rhinitis with eosinophilia syndrome: a systematic review. Curr Allergy Asthma Rep. (2022) 22(4):29–42. 10.1007/s11882-022-01027-0 PubMed DOI

Gelardi M, Maselli del Giudice A, Fiorella ML, Fiorella R, Russo C, Soleti P, et al. Non-allergic rhinitis with eosinophils and mast cells constitutes a new severe nasal disorder. Int J Immunopathol Pharmacol. (2008) 21(2):325–31. 10.1177/039463200802100209 PubMed DOI

Khan A, Vandeplas G, Huynh TMT, Joish VN, Mannent L, Tomassen P, et al. The global allergy and asthma European network (GALEN rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps. Rhinology. (2019) 57(1):32–42. 10.4193/Rhin17.255 PubMed DOI

ten Brinke A, Grootendorst DC, Schmidt JT, de Bruïne FT, van Buchem MA, Sterk PJ, et al. Chronic sinusitis in severe asthma is related to sputum eosinophilia. J Allergy Clin Immunol. (2002) 109(4):621–6. ISSN 0091-6749. 10.1067/mai.2002.122458 PubMed DOI

Khalid AN, Hunt JG, Hamilos DL. Inflammatory endotypes in chronic rhinosinusitis with nasal polyps and asthma. Ann Am Thorac Soc. (2011) 8(4):347–55. 10.1513/AnnalsATS.201011-173OC DOI

Wang X, Sima Y, Zhao Y, Zhang N, Zheng M, Du K, et al. Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors. J Allergy Clin Immunol. (2023) 151(2):458–68. 10.1016/j.jaci.2022.10.010 PubMed DOI

Philpott CM, Erskine S, Hopkins C, Kumar N, Anari S, Kara N, et al. Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: data from the UK national chronic rhinosinusitis epidemiology study. Respir Res. (2018) 19(1):129. 10.1186/s12931-018-0823-y PubMed DOI PMC

De Corso E, Pasquini E, Trimarchi M, La Mantia I, Pagella F, Ottaviano G, et al. Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): a multicentric observational phase IV real-life study (DUPIREAL). Allergy. (2023) 78(10):2669–83. 10.1111/all.15772 PubMed DOI

Chuang CC, Guillemin I, Bachert C, Lee SE, Hellings PW, Fokkens WJ, et al. Two-year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months. Allergy. (2023) 78(10):2684–97. 10.1111/all.15796 PubMed DOI

Haxel BR, Hummel T, Fruth K, Lorenz K, Gunder N, Nahrath P, et al. Real-world-effectiveness of biological treatment for severe chronic rhinosinusitis with nasal polyps. Rhinology. (2022) 60(6):435–43. 10.4193/Rhin22.129 PubMed DOI

Szczeklik A, Nizankowska E. Clinical features and diagnosis of aspirin induced asthma. Thorax. (2000) 55:S42–4. 10.1136/thorax.55.suppl_2.S42 PubMed DOI PMC

Szczeklik A, Nizankowska E, Duplaga M. Natural history of aspirin-induced asthma. AIANE investigators. European network on aspirin-induced asthma. Eur Respir J. (2000) 16:432–6. 10.1034/j.1399-3003.2000.016003432.x PubMed DOI

Dages KN, Sofola-James O, Sehanobish E, Regula P, Chen C-C, Chiarella SE, et al. Sex, ethnicity, BMI, and environmental exposures associated with NSAID-exacerbated respiratory disease symptom sequence. J Allergy Clin Immunol Pract. (2023). 10.1016/j.jaip.2023.07.035 PubMed DOI PMC

Mullol J, Boyce J, Dahlén SE, Dahlén B, Picado C, Bobolea I. Eicosanoid dysregulation and type 2 inflammation in AERD. J Allergy Clin Immunol. (2021) 148(5):1157–60. 10.1016/j.jaci.2021.08.015 PubMed DOI

Schwartz BS, Pollak JS, Bandeen-Roche K, Hirsch AG, Lehmann AE, Kern RC, et al. Sinus inflammation and chronic rhinosinusitis are associated with a diagnosis of new onset asthma in the following year. Allergy. (2023). 10.1111/all.15771 PubMed DOI PMC

Cohen NA, Widelitz JS, Chiu AG, Palmer JN, Kennedy DW. Familial aggregation of sinonasal polyps correlates with severity of disease. Otolaryngol Head Neck Surg. (2006) 134(4):601–4. 10.1016/j.otohns.2005.11.042 PubMed DOI

Greisner WA, 3rd, Settipane GA. Hereditary factor for nasal polyps. Allergy Asthma Proc. (1996) 17(5):283–6. 10.2500/108854196778662192 PubMed DOI

Martin MJ, Garcia-Sanchez A, Estravis M, Gil-Melcón M, Isidoro-Garcia M, Sanz C, et al. Genetics and epigenetics of nasal polyposis: a systematic review. J Investig Allergol Clin Immunol. (2021) 31(3):196–211. 10.18176/jiaci.0673 PubMed DOI

Jerschow E, Dubin R, Chen CC, iAkushev A, Sehanobish E, Asad M, et al. Aspirin-exacerbated respiratory disease is associated with variants in filaggrin, epithelial integrity, and cellular interactions. J Allergy Clin Immunol Glob. (2024) 3(2):100205. 10.1016/j.jacig.2024.100205 PubMed DOI PMC

Park BL, Kim TH, Kim JH, Bae JS, Pasaje CF, Cheong HS, et al. Genome-wide association study of aspirin-exacerbated respiratory disease in a Korean population. Hum Genet. (2013) 132:313–21. 10.1007/s00439-012-1247-2 PubMed DOI

Dahlin A, Weiss ST. Genetic and epigenetic components of aspirin-exacerbated respiratory disease. Immunol Allergy Clin North Am. (2016) 36(4):765–89. 10.1016/j.iac.2016.06.010 PubMed DOI PMC

Stevens WW, Staudacher AG, Hulse KE, Carter RG, Winter DR, Abdala-Valencia H, et al. Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. (2021) 147:600–12. 10.1016/j.jaci.2020.04.031 PubMed DOI PMC

Imoto Y, Takabayashi T, Sakashita M, Kato Y, Yoshida K, Kidoguchi M, et al. Enhanced 15-lipoxygenase 1 production is related to periostin expression and eosinophil recruitment in eosinophilic chronic rhinosinusitis. Biomolecules. (2020) 10:1–13. 10.3390/biom10111568 PubMed DOI PMC

Kristjansson RP, Benonisdottir S, Davidsson OB, Oddsson A, Tragante V, Sigurdsson JK, et al. A loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis. Nat Genet. (2019) 51:267–76. 10.1038/s41588-018-0314-6 PubMed DOI

Muluk NB, Altın F, Cingi C. Role of superantigens in allergic inflammation: their relationship to allergic rhinitis, chronic rhinosinusitis, asthma, and atopic dermatitis. Am J Rhinol Allergy. (2018) 32(6):502–17. 10.1177/1945892418801083 PubMed DOI

Zock JP, Jarvis D, Luczynska C, Sunyer J, Burney P, European Community Respiratory Health Survey (ECRHS). Housing characteristics, reported mold exposure, and asthma in the European community respiratory health survey. J Asthma. (2007) 44(4):257–64. 10.1080/02770900701203427 PubMed DOI

Schleich F, Maury E, Bachert C, Hanon S, Michel O, Jansen M, et al. Epidemiology of sensitization to perennial aeroallergens in adults with severe asthma in Belgium. The BEIgE study. Allergy. (2023) 78(10):2774–7. 10.1111/all.15785 PubMed DOI

Kogevinas M, Zock JP, Jarvis D, Kromhout H, Lillienberg L, Plana E, et al. Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II). Lancet. (2007) 370(9584):336–41. 10.1016/S0140-6736(07)61164-7 PubMed DOI

Bakke PS, Baste V, Hanoa R, Gulsvik A. Prevalence of obstructive lung disease in a general population: relation to occupational title and exposure to some airborne agents. Thorax. (1991) 46(12):863–70. 10.1136/thx.46.12.863 PubMed DOI PMC

Sit G, Letellier N, Iwatsubo Y, Goldberg M, Leynaert B, Nadif R, et al. Occupational exposures to organic solvents and asthma symptoms in the CONSTANCES cohort. Int J Environ Res Public Health. (2021) 18(17):9258. 10.3390/ijerph18179258 PubMed DOI PMC

Sit G, Orsi L, Iwatsubo Y, Brigitte Dananché, Florence Orsi, Marcel Goldberg, et al. Chronic occupational exposures to irritants and asthma in the CONSTANCES cohort. Occup Environ Med. (2024). 10.1136/oemed-2023-109100 PubMed DOI

Klein DK, Silberbrandt A, Frøssing L, Hvidtfeldt M, von Bülow A, Nair P, et al. Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma. Eur Respir J. (2022) 60(4):2102446. 10.1183/13993003.02446-2021 PubMed DOI

Lajunen TK, Jaakkola JJK, Jaakkola MS. Different effects of smoking on atopic and non-atopic adult-onset asthma. Clin Transl Allergy. (2021) 11(8):e12072. 10.1002/clt2.12072 PubMed DOI PMC

Chalermwatanachai T, Vilchez-Vargas R, Holtappels G, Lacoere T, Jáuregui R, Kerckhof FM, et al. Chronic rhinosinusitis with nasal polyps is characterized by dysbacteriosis of the nasal microbiota. Sci Rep. (2018) 8(1):7926. 10.1038/s41598-018-26327-2 PubMed DOI PMC

Choi S, Sohn KH, Jung JW, Kang MG, Yang MS, Kim S, et al. Lung virome: new potential biomarkers for asthma severity and exacerbation. J Allergy Clin Immunol. (2021) 148(4):1007–1015.e9. 10.1016/j.jaci.2021.03.017 PubMed DOI

Bachert C, van Steen K, Zhang N, Holtappels G, Cattaert T, Maus B, et al. Specific IgE against Staphylococcus aureus enterotoxins: an independent risk factor for asthma. J Allergy Clin Immunol. (2012) 130(2):376–81.e8. 10.1016/j.jaci.2012.05.012 PubMed DOI

Pastacaldi C, Lewis P, Howarth P. Staphylococci and staphylococcal superantigens in asthma and rhinitis: a systematic review and meta-analysis. Allergy. (2011) 66(4):549–55. 10.1111/j.1398-9995.2010.02502.x PubMed DOI

Song WJ, Chang YS, Lim MK, Yun EH, Kim SH, Kang HR, et al. Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma. Clin Exp Allergy. (2014) 44(4):553–62. 10.1111/cea.12239 PubMed DOI

Kim YC, Won HK, Lee JW, Sohn KH, Kim MH, Kim TB, et al. Staphylococcus aureus nasal colonization and asthma in adults: systematic review and meta-analysis. J Allergy Clin Immunol Pract. (2019) 7(2):606–615.e9. 10.1016/j.jaip.2018.08.020 PubMed DOI

Shaghayegh G, Cooksley C, Bouras GS, Panchatcharam BS, Idrizi R, Jana M, et al. Chronic rhinosinusitis patients display an aberrant immune cell localization with enhanced S aureus biofilm metabolic activity and biomass. J Allergy Clin Immunol. (2023) 151(3):723–736.e16. ISSN 0091-6749. 10.1016/j.jaci.2022.08.031 DOI

Shaghayegh G, Cooksley C, Bouras G, Nepal R, Houtak G, Panchatcharam BS, et al. Staphylococcus aureus biofilm properties and chronic rhinosinusitis severity scores correlate positively with total CD4+ T-cell frequencies and inversely with its Th1, Th17 and regulatory cell frequencies. Immunology. (2023) 170(1):120–33. 10.1111/imm.13655 PubMed DOI

Bachert C, van Zele T, Gevaert P, De Schrijver L, Van Cauwenberge P. Superantigens and nasal polyps. Curr Allergy Asthma Rep. (2003) 3(6):523–31. 10.1007/s11882-003-0065-y PubMed DOI

Heaton T, Mallon D, Venaille T, Holt P. Staphylococcal enterotoxin induced IL-5 stimulation as a cofactor in the pathogenesis of atopic disease: the hygiene hypothesis in reverse? Allergy. (2003) 58(3):252–6. 10.1034/j.1398-9995.2003.00088.x PubMed DOI

Ou LS, Goleva E, Hall C, Leung DY. T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. J Allergy Clin Immunol. (2004) 113(4):756–63. 10.1016/j.jaci.2004.01.772 PubMed DOI

Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med. (2007) 175(7):661–6. 10.1164/rccm.200611-1717OC PubMed DOI PMC

Arismendi E, Bantulà M, Picado C. Obese asthma syndrome: much work to do. Arch Bronconeumol. (2023) 59(8):473–5. (English, Spanish). 10.1016/j.arbres.2023.02.012 PubMed DOI

Bantulà M, Arismendi E, Tubita V, Roca-Ferrer J, Mullol J, de Hollanda A, et al. Effect of obesity on the expression of genes associated with severe asthma-a pilot study. J Clin Med. (2023) 12(13):4398. 10.3390/jcm12134398 PubMed DOI PMC

Holguin F, Bleecker ER, Busse WW, Calhoun WJ, Castro M, Erzurum SC, et al. Obesity and asthma: an association modified by age of asthma onset. J Allergy Clin Immunol. (2011) 127(6):1486–93.e2. 10.1016/j.jaci.2011.03.036 PubMed DOI PMC

Dixon AE, Pratley RE, Forgione PM, Kaminsky DA, Whittaker-Leclair LA, Griffes LA, et al. Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation. J Allergy Clin Immunol. (2011) 128(3):508–15.e1–2. 10.1016/j.jaci.2011.06.009 PubMed DOI PMC

Sutherland ER, Goleva E, King TS, Lehman E, Stevens AD, Jackson LP, et al. Cluster analysis of obesity and asthma phenotypes. PLoS One. (2012) 7(5):e36631. 10.1371/journal.pone.0036631 PubMed DOI PMC

Carr TF, Kraft M. Use of biomarkers to identify phenotypes and endotypes of severeasthma. Ann Allergy Asthma Immunol. (2018) 121(4):414–20. 10.1016/j.anai.2018.07.029 PubMed DOI

Nwaru BI, Pillinger R, Tibble H, Shah SA, Ryan D, Critchley H, et al. Hormonal contraceptives and onset of asthma in reproductive-age women: population-based cohort study. J Allergy Clin Immunol. (2020) 146(2):438–46. 10.1016/j.jaci.2020.02.027 PubMed DOI

Shah SA, Tibble H, Pillinger R, McLean S, Ryan D, Critchley H, et al. Hormone replacement therapy and asthma onset in menopausal women: national cohort study. J Allergy Clin Immunol. (2021) 147(5):1662–70. 10.1016/j.jaci.2020.11.024 PubMed DOI

Lemmetyinen R, Karjalainen J, But A, Renkonen R, Pekkanen J, Haukka J, et al. Diseases with oral manifestations among adult asthmatics in Finland: a population-based matched cohort study. BMJ Open. (2021) 11(12):e053133. 10.1136/bmjopen-2021-053133 PubMed DOI PMC

Ilmarinen P, Tuomisto LE, Phenotypes KH, Factors R. And mechanisms of adult-onset asthma. Mediators Inflamm. (2015) 2015:514868. 10.1155/2015/514868 PubMed DOI PMC

Xiang B, Hu M, Yu H. Highlighting the importance of healthy sleep patterns in the risk of adult asthma under the combined effects of genetic susceptibility: a large-scale prospective cohort study of 455 405 participants. BMJ Open Respir Res. (2023) 10:e001535. 10.1136/bmjresp-2022-001535 PubMed DOI PMC

Cullinan P, Muñoz X, Suojalehto H, Agius R, Jindal S, Sigsgaard T, et al. Occupational lung diseases: from old and novel exposures to effective preventive strategies. Lancet Respir Med. (2017) 5(5):445–55. 10.1016/S2213-2600(16)30424-6 PubMed DOI

Farraia M, Paciência I, Castro Mendes F, Cavaleiro Rufo J, Shamji M, Agache I, et al. Allergen immunotherapy for asthma prevention: a systematic review and meta-analysis of randomized and non-randomized controlled studies. Allergy. (2022) 77(6):1719–35. 10.1111/all.15295 PubMed DOI

Polosa R, Al-Delaimy WK, Russo C, Piccillo G, Sarvà M. Greater risk of incident asthma cases in adults with allergic rhinitis and effect of allergen immunotherapy: a retrospective cohort study. Respir Res. (2005) 6(1):153. 10.1186/1465-9921-6-153 PubMed DOI PMC

Jayes L, Haslam PL, Gratziou CG, Powell P, Britton J, Vardavas C, et al. Smokehaz: systematic reviews and meta-analyses of the effects of smoking on respiratory health. Chest. (2016) 150(1):164–79. 10.1016/j.chest.2016.03.060 PubMed DOI

Bantulà M, Tubita V, Roca-Ferrer J, Mullol J, Valero A, Bobolea I, et al. Weight loss and vitamin D improve hyporesponsiveness to corticosteroids in obese asthma. J Investig Allergol Clin Immunol. (2023) 33(6):464–73. 10.18176/jiaci.0861 PubMed DOI

Lenharo M. Obesity drugs have another superpower: taming inflammation. Nature. Available online at: https://www.nature.com/articles/d41586-024-00118-4 (Accessed January 26, 2024). PubMed

Menezes-Martins LF, Vianna P, Viegas-Júnior OA, et al. Intranasal corticosteroids and the prevention of asthma onset in non-allergic rhinitis patients: a pilot randomized controlled trial. J Asthma. (2019) 56(9):954–62. 10.1080/02770903.2018.1506672 DOI

Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. Executive summary of EPOS 2020 including integrated care pathways. Rhinology. (2020) 58(2):82–111. 10.4193/Rhin20.601 PubMed DOI

Rimmer J, Fokkens W, Chong LY, Hopkins C. Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps. Cochrane Database Syst Rev. (2014) 12:CD006991. 10.1002/14651858.CD006991.pub2 PubMed DOI PMC

Ragab S, Parikh A, Darby YC, Scadding GK. An open audit of montelukast, a leukotriene receptor antagonist, in nasal polyposis associated with asthma. Clin Exp Allergy. (2001) 31(9):1385–91. 10.1046/j.1365-2222.2001.01160.x PubMed DOI

De Corso E, Anzivino R, Galli J, Baroni S, Di Nardo W, De Vita C, et al. Antileukotrienes improve naso-ocular symptoms and biomarkers in patients with NARES and asthma. Laryngoscope. (2019) 129(3):551–7. 10.1002/lary.27576 PubMed DOI

Hopkins C, Rimmer J, Lund VJ. Does time to endoscopic sinus surgery impact outcomes in chronic rhinosinusitis? Prospective findings from the national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis. Rhinology. (2015) 53(1):10–7. 10.4193/Rhino13.217 PubMed DOI

Plaza V, del Cuvillo A, Soto-Retes L. Functional endoscopic Sinus surgery for nasal polyposis in asthma patients: impact on bronchial inflammation. Arch Bronconeumol:56(6):403–5. 10.1016/j.arbres.2019.12.029 PubMed DOI

Jerschow E, Edin ML, Chi Y, Hurst B, Abuzeid WM, Akbar NA, et al. Sinus surgery is associated with a decrease in aspirin-induced reaction severity in patients with aspirin exacerbated respiratory disease. J Allergy Clin Immunol Pract. (2019) 7(5):1580–8. 10.1016/j.jaip.2018.12.014 PubMed DOI PMC

Divekar R, Hagan J, Rank M, Park M, Volcheck G, O'Brien E, et al. Diagnostic utility of urinary LTE4 in asthma, allergic rhinitis, chronic rhinosinusitis, nasal polyps, and aspirin sensitivity. J Allergy Clin Immunol Pract. (2016) 4(4):665–70. 10.1016/j.jaip.2016.03.004 PubMed DOI PMC

Huang CC, Wang CH, Fu CH, Huang CC, Chang PH, Chen IW, et al. The link between chronic rhinosinusitis and asthma: a questionnaire-based study. Medicine (Baltimore). (2016) 95(31):e4294. 10.1097/MD.0000000000004294 PubMed DOI PMC

Makowska JS, Burney P, Jarvis D, Keil T, Tomassen P, Bislimovska J, et al. Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey. Allergy. (2016) 71(11):1603–11. 10.1111/all.12941 PubMed DOI

Schatz M, Hsu JW, Zeiger RS, Chen W, Dorenbaum A, Chipps BE, et al. Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J Allergy Clin Immunol. (2014) 133(6):1549–56. 10.1016/j.jaci.2013.10.006 PubMed DOI

Eraso I, Sangiovanni S, Morales EI, Fernández-Trujillo L. Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: a systematic review of the literature and meta-analysis. PLoS One. (2021) 16(3):e0247871. 10.1371/journal.pone.0247871 PubMed DOI PMC

Atanasio A, Orengo JM, Sleeman MA, Stahl N. Biologics as novel therapeutics for the treatment of allergy: challenges and opportunities. Front Allergy. (2022) 3:1019255. 10.3389/falgy.2022.1019255 PubMed DOI PMC

Striz I, Golebski K, Strizova Z, Loukides S, Bakakos P, Hanania NA, et al. New insights into the pathophysiology and therapeutic targets of asthma and comorbid chronic rhinosinusitis with or without nasal polyposis. Clin Sci (Lond). (2023) 137(9):727–53. 10.1042/CS20190281 PubMed DOI PMC

Kolkhir P, Akdis CA, Akdis M, Bachert C, Bieber T, Canonica GW, et al. Type 2 chronic inflammatory diseases: targets, therapies and unmet needs. Nat Rev Drug Discov. (2023) 22(9):743–67. 10.1038/s41573-023-00750-1 PubMed DOI

Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. (2014) 371(13):1189–97. 10.1056/NEJMoa1403291 PubMed DOI

Rabe KF, Nair P, Brusselle G, Maspero JF, Castro M, Sher L, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. (2018) 378(26):2475–85. 10.1056/NEJMoa1804093 PubMed DOI

Canonica GW, Rottoli P, Bucca C, Zappa MC, Michetti G, Macciocchi B, et al. Improvement of patient-reported outcomes in severe allergic asthma by omalizumab treatment: the real life observational PROXIMA study. World Allergy Organ J. (2018) 11(1):33. 10.1186/s40413-018-0214-3 PubMed DOI PMC

Barroso B, Valverde-Monge M, Alobid I, Olaguibel JM, Rial MJ, Quirce S, et al. Improvement in olfaction in patients with CRSwNP and severe asthma taking anti-IgE and anti-IL-5 biologics: a real-life study. J Investig Allergol Clin Immunol. (2023) 33(1):37–44. 10.18176/jiaci.0812 PubMed DOI

Wechsler ME, Scelo G, Larenas-Linnemann DES, Torres-Duque CA, Maspero J, Tran TN, et al. Association between T2-related comorbidities and effectiveness of biologics in severe asthma. Am J Respir Crit Care Med. (2024) 209(3):262–72. 10.1164/rccm.202305-0808OC PubMed DOI

Oykhman P, Paramo FA, Bousquet J, Kennedy DW, Brignardello-Petersen R, Chu DK. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis. J Allergy Clin Immunol. (2022) 149(4):1286–95. 10.1016/j.jaci.2021.09.009 PubMed DOI

Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. (2019) 394(10209):1638–50. 10.1016/S0140-6736(19)31881-1 PubMed DOI

Schneider S, Poglitsch K, Morgenstern C, Quint T, Gangl K, Sinz C, et al. Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease. Eur Respir J. (2023) 61(3):2201335. 10.1183/13993003.01335-2022 PubMed DOI PMC

Ahmad-Mansour N, Loubet P, Pouget C, Dunyach-Remy C, Sotto A, Lavigne JP, et al. Staphylococcus aureus toxins: an update on their pathogenic properties and potential treatments. Toxins (Basel). (2021) 13(10):677. 10.3390/toxins13100677 PubMed DOI PMC

Schmidt F, Meyer T, Sundaramoorthy N, Michalik S, Surmann K, Depke M, et al. Characterization of human and Staphylococcus aureus proteins in respiratory mucosa by in vivo- and immunoproteomics. J Proteomics. (2017) 155:31–9. 10.1016/j.jprot.2017.01.008 PubMed DOI

Ragab S, Scadding GK, Lund VJ, Saleh H. Treatment of chronic rhinosinusitis and its effects on asthma. Eur Respir J. (2006) 28(1):68–74. 10.1183/09031936.06.00043305 PubMed DOI

Van Zele T, Gevaert P, Holtappels G, Beule A, Wormald PJ, Mayr S, et al. Oral steroids and doxycycline: two different approaches to treat nasal polyps. J Allergy Clin Immunol. (2010) 125(5):1069–1076.e4. ISSN 1874-3919. 10.1016/j.jaci.2010.02.020 PubMed DOI

Davis MF, McCormack MC, Matsui EC. Growing concerns with Staphylococcus aureus and asthma: new territory for an old foe? J Allergy Clin Immunol Pract. (2019) 7(2):616–7. 10.1016/j.jaip.2018.10.003 PubMed DOI PMC

Tzani-Tzanopoulou P, Skliros D, Megremis S, Xepapadaki P, Andreakos E, Chanishvili N, et al. Interactions of bacteriophages and bacteria at the airway mucosa: new insights into the pathophysiology of asthma. Front Allergy. (2021) 1:617240. 10.3389/falgy.2020.617240 PubMed DOI PMC

Hartert TV, Deng X, Hartman TJ, Wen W, Yang G, Gao YT, et al. The Shanghai women’s asthma and allergy study: objectives, design, and recruitment results. Am J Epidemiol. (2008) 167(11):1387–96. 10.1093/aje/kwn057 PubMed DOI PMC

Zhu LY, Ni ZH, Luo XM, Wang XB. Advance of antioxidants in asthma treatment. World J Respirol. (2017) 7(1):17–28. 10.5320/wjr.v7.i1.17 DOI

Zhu XD, Lei XP, Dong WB. Resveratrol as a potential therapeutic drug for respiratory system diseases. Drug Des Devel Ther. (2017) 11:3591–8. 10.2147/DDDT.S148868 PubMed DOI PMC

Alharris E, Alghetaa H, Seth R, Chatterjee S, Singh NP, Nagarkatti M, et al. Resveratrol attenuates allergic asthma and associated inflammation in the lungs through regulation of miRNA-34a that targets FoxP3 in mice. Front Immunol. (2018) 9:2992. 10.3389/fimmu.2018.02992 PubMed DOI PMC

Ediger D, Günaydın FE, Erbay M, Pekbak G. Can omalizumab be an alternative treatment for non-atopic severe asthma? A real-life experience with omalizumab. Tuberk Toraks. (2023) 71(1):24–33. (English). 10.5578/tt.20239904 PubMed DOI PMC

Bohman A, Oscarsson M, Holmberg K, Johansson L, Millqvist E, Nasic S, et al. Heredity of nasal polyps. Rhinology. (2015) 53(1):25–8. 10.4193/Rhino14.032 PubMed DOI