Gene expression of cytokines IL-17 and IL-33 in plasma and nasal lavage fluid of patients with allergic rhinitis and bronchial asthma

Gene expression of cytokines IL-17 and IL-33 in plasma and nasal lavage fluid of patients with allergic rhinitis and bronchial asthma* Sjoerd Miedema1, Dimitrina Georgieva2,3 , Kremena Naydenova4, Vasil Dimitrov5, Tsvetelina Velikova3 1 Faculty of Biology, Sofia University “St. Kliment Ohridski”, Bul. Dragan Tsankov 8, 1164 Sofia, Bulgaria 2 Department of Genetics, Faculty of Biology, Sofia University “St. Kliment Ohridski”, 8 Dragan Tzankov Str., 1164 Sofia, Bulgaria 3 Medical Faculty, Sofia University “St. Kliment Ohridski”, 1 Kozyak str, 1407 Sofia, Bulgaria 4 Clinical Center of Allergology, University Hospital Alexandrovska, Medical University of Sofia, Georgi Sofyiski 1 Str., 1431 Sofia, Bulgaria 5 Clinic of Pulmonology and Allergology at the Medical Institute of the Ministry of Interior, General Mihail Skobelev blvd 79, 1606 Sofia, Bulgaria Corresponding author: Sjoerd Miedema ([email protected]) Received 15 July 2025♦ Accepted 10 October 2025♦ Published 3 November 2025 Citation: Miedema S, Georgieva D, Naydenova K, Dimitrov V, Velikova T (2025) Gene expression of cytokines IL-17 and IL-33 in plasma and nasal lavage fluid of patients with allergic rhinitis and bronchial asthma. Pharmacia 72: 1–10. https://doi.org/10.3897/ pharmacia.72.e165215 Abstract The research presented in this article determined the systemic (blood plasma) and local (nasal lavage fluid) levels of interleukin-17 (IL17) and interleukin-33 (IL-33) in healthy volunteers, patients with allergic rhinitis (AR), and patients with both allergic rhinitis and recently diagnosed bronchial asthma (AR+BA). IL-17 and IL-33 levels were consistent between AR and AR+BA patients but diverged when comparing either patient group or the combined group of all patients with healthy volunteers. These results indicate that AR and AR+BA patients represent a homogeneous group and suggest a role for IL-17 and/or IL-33 in the progression of AR to AR+BA. In conclusion, our data show that patients with AR only and those who progress to AR+BA from AR alone have elevated IL-17 levels in both nasal lavage fluid (NLF) and serum. This finding is consistent with recent studies and identifies a novel population of AR+BA patients with elevated IL-17 levels. The possibility of novel IL-33 regulatory mechanisms in these patients warrants further research. Keywords allergic rhinitis, bronchial asthma, cytokines, IL-17, IL-33, nasal lavage, therapy * This article is part of: “Bridging Science and Innovation: Advances in Diagnosis, Therapy, and Translational Medicine: Insights from the Second SUMMIT Conference”, edited by Georgi Momekov, Ivan Padjen, Naim Mahroum. Introduction One airway disease Allergic rhinitis (AR) and bronchial asthma (BA) are inflammatory diseases of the upper and lower respiratory systems, respectively, and represent a significant burden on healthcare systems worldwide (Cardell et al. 2016; Nurmagambetov et al. 2018; Avdeeva et al. 2020; Roland et al. 2021; Håkansson et al. 2023). Estimates of the prevalence of AR vary from 5 to 50%, depending on the methodology and population studied (Oliveira et al. 2020; Alqahtani 2020). Copyright Miedema S et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Pharmacia 72: 1–10 DOI 10.3897/pharmacia.72.e165215 Research Article Miedema S et al.: IL-17 and IL-33 in allergic rhinitis and bronchial asthma2 Epidemiological studies with a more restrictive definition of AR, incorporating IgE plasma levels to confirm the presence of atopic immune responses, report prevalences of 10–12% (Tschopp et al. 1998; Salo et al. 2011). The reported prevalence of BA ranges from 5.4 to 17.9% (Song et al. 2022). Available data indicate that the pathogeneses of AR and BA are linked. In 1997, J. Grossman published the “one airway, one disease” theory, which states that asthma and allergic rhinitis are “described better as a continuum of inflammation involving one common airway” than as distinct and separate entities (Grossman 1997). Data from the SAPALDIA cohort study published the following year show that 60% of patients with BA also suffer from AR (Tschopp et al. 1998). In 1999, data from the ECRHS showed that patients with BA are likely to be co-diagnosed with AR (Leynaert et al. 1999), and updated data from the same study confirmed AR as a risk factor for BA (Shaaban et al. 2008). More recent studies show a similar connection (Jacob et al. 2016; Acevedo-Prado et al. 2022). Additional evidence for the one airway theory of AR and BA lies in the morphology and cytology of the respiratory epithelium, a key tissue in the inflammatory processes of the upper and lower respiratory tracts. The major component of the respiratory epithelium throughout the airways is the ciliated columnar epithelial cells, which make up 50–80% of the tissue by cell count. Additional major cell types include goblet cells, which produce mucus (Jaramillo et al. 2018); basal cells, which are the major population of stem cells in this tissue (Cumplido-Laso et al. 2023); and chemosensory cells, which serve as initiators of physiological responses to external stimuli by interfacing with the immune and nervous systems (Hollenhorst and Krasteva-Christ 2023). Evidence for the interplay between AR and BA has also been found in the clinical setting. A 3-year, randomized, open-label trial of immunotherapy in 205 children with AR showed that those receiving immunotherapy were less likely than the control group to develop BA (Möller et al. 2002). Follow-up studies showed that the protective effect was maintained for up to 10 years after therapy (Niggemann et al. 2006; Jacobsen et al. 2007). Omalizumab is an anti-IgE antibody that received marketing authorization for use in asthma in 2005. Results from the pivotal clinical trial showed a statistically significant reduction in clinically relevant symptoms after 28 weeks of treatment in patients with severe persistent asthma (Humbert et al. 2005). Subsequent meta-analyses show that the use of omalizumab is also associated with a meaningful improvement in AR symptoms, overall quality of life, and a reduction in medication use for AR (Tsabouri et al. 2014; Yu et al. 2020). Dupilumab is an anti-interleukin-4 (IL-4) receptor alpha (IL-4Rα) antibody, which reduces Th2-type inflammation by decreasing the availability of the receptor for proinflammatory cytokines IL-4 and IL-13. In a randomized, double-blind, placebo-controlled study, dupilumab was shown to reduce corticosteroid use by 70% compared to a 42% reduction in the placebo group. Patients treated with dupilumab experienced 59% fewer asthma exacerbations compared to those receiving placebo (Rabe et al. 2018). Two post hoc analyses of the clinical data for dupilumab showed that patients with AR receiving dupilumab experienced a statistically significant reduction in symptoms (Wenzel et al. 2016; Busse et al. 2020). Interleukins 33 and 17A Innate and adaptive immune responses are broadly classified into three types, which are induced and characterized by the presence of specific cytokines (Fig. 1). Each type of immune response is tailored to defend against different types of pathogens, but when dysregulated, it may give rise to inflammatory, autoimmune, or atopic diseases. In the case of asthma, it is known that dysregulated immune responses of different types can result in very similar symptoms. Endotypes of asthma include type 2-high asthma, which is characterized by high blood and sputum eosinophil counts (Ogulur et al. 2021). Type 2-low asthma is characterized by the absence of type 2 biomarkers and is often associated with the presence of sputum neutrophils (Sze et al. 2020). Efforts to understand the pathways behind type 2-low asthma are important, as this endotype represents 30–50% of patients with refractory asthma, and there are few specific therapy options available (Hinkset al. 2021). Mutations affecting the IL17A gene have been found to be associated with both asthma and AR (Wang et al. 2012; Du et al. 2016; Lee and Song 2023). In addition, IL17A protein levels have been found to be consistently elevated in patients with asthma compared to healthy volunteers (Wong et al. 2001; Chien et al. 2013; Tao et al. 2015; Chen et al. 2016; Lv et al. 2016; Hatta et al. 2017), while IL17A is also elevated in the plasma of patients with acute or refractory asthma compared to patients with mild asthma (Chien et al. 2013; Tao et al. 2015). The same correlations hold for IL17A in AR patients compared to healthy volunteers and when comparing relatively more severe AR with milder AR (Ciprandi et al. 2008; Tang et al. 2014; Degirmenci et al. 2018; Erkan et al. 2020). IL17A is expressed in several immune cell types upon activation, including innate lymphoid cells (ILC), natural killer (NK) cells, CD8⁺ T cells, γδ T cells, and, importantly, Th17 cells. It performs its intercellular signaling function as a homodimer or as a heterodimer with IL17F (Liu et al. 2013a; Goepfert et al. 2017). Receptors for the IL17A homoor heterodimer are found in diverse tissues and organs; however, the best-characterized response to IL17A signaling occurs in epithelial cells, endothelial cells, and fibroblasts (Gaffen 2009; Nirula et al. 2016), where IL17A signaling precipitates expression of chemokines CXCL1 and CXCL8, cytokines IL1β, IL6, and TNF, and metalloproteases with direct antimicrobial functions (Rex et al. 2023). The chemokines and cytokines induced by IL17A attract and activate macrophages and neutrophils, which affect the removal of harmful pathogens in a protective immune response and contribute to the pathology of autoimmune or atopic diseases when dysregulated (Mills 2023). Pharmacia 72: 1–10 3 Genome-wide association studies (GWAS) have identified 128 mutations associated with asthma, including many that affect IL33, its receptor IL1RL1, or its downstream effectors (El-Husseini et al. 2020). IL33 is constitutively expressed in many tissues throughout the body, including the respiratory system (Moussion et al. 2008; Fagerberg et al. 2014). IL33 is released into the intercellular space in response to tissue or cell damage, where it induces an immune response, the specifics of which depend on the types of immune cells present and the cytokine milieu (Funakoshi-Tago et al. 2008; Salmond et al. 2012). IL33 is subject to several post-translational regulatory mechanisms, including nuclear localization during homeostasis (Carriere et al. 2007); activating proteolysis in the intercellular space (Lefrançais et al. 2014; Scott et al. 2018); deactivating proteolysis during apoptosis (Lingel et al. 2009; Liu et al. 2013b); deactivating oxidation in the intercellular space (Lingel et al. 2009; Liu et al. 2013b); and sequestration by circulating dummy receptors (Hayakawa et al. 2007). These mechanisms suggest IL33’s key role as a highly localized but generalized activating signal to the immune system in cases of tissue damage. A series of experiments published in 2014 (Mizutani et al. 2014) suggests a mechanism for the interaction between IL33 and IL17A in BA. Both anti-IL33 and anti-IL17A antibodies decrease neutrophilic inflammation in mice; however, the administration of anti-IL33 antibodies does not affect IL17A levels. Further, mice begin to express elevated levels of IL17A after repeated intrabronchial exposure to IL33. After sensitization by intrabronchial IL33 administration, the combined administration of IL33 and IL17A results in higher levels of neutrophilic inflammation than the administration of IL33 or IL17A alone. These results suggest an interaction in which repeated stresses expose the respiratory microenvironment to IL33, ultimately leading to activation of an IL17A-driven immune response that exacerbates inflammation triggered by future IL33-mediated responses to external stimuli. Subsequent publications appear to support this proposed interaction (Vocca et al. 2015; Cheng et al. 2022). This hypothesis contends that, since AR and BA are manifestations of the same inflammatory process, investigation of the expression levels of IL17A and IL33 in patients with AR and BA may provide valuable insights into their interactions and help assess their value as biomarkers for different endotypes of the disease. Materials and methods Subjects Five subjects were enrolled in each of the following three groups: five patients with AR, five patients with both AR and BA, and five healthy controls. The mean age of patients with AR was 29.6 ± 6.7 years, the mean age of patients with AR+BA was 36.8 ± 11.6 years, and the mean age of healthy controls was 30.6 ± 9.76 years. Each group included three males and two females. Inclusion criteria included age ≥ 18 years, moderate or severe seasonal or perennial AR, and mild, newly diagnosed BA with long-standing AR. Subjects were selected from the existing database of Figure 1. Cell lineages, inductor and effector cytokines, and key transcription factors of the three major types of innate and adaptive cell-mediated effector immunity. Adapted from Annunziato et al. (2014). Miedema S et al.: IL-17 and IL-33 in allergic rhinitis and bronchial asthma4 an ongoing national study conducted at the Allergology Clinic of the “Aleksandrovska” University Hospital in Sofia, where they provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and approved by the local Ethics Committee. Subjects were selected using a stratified random sampling approach to ensure that the sample was representative of the overall study population. Samples Serum and nasal lavage fluid (NLF) samples were collected as part of the national study. Serum samples were obtained from venous blood, allowed to settle for 20 minutes, and then centrifuged at 1,200 rpm for 15 minutes. The samples were subsequently frozen at –70 °C. NLF was obtained by instilling 10 mL of sterile saline solution into each nostril. After 10 seconds in a reclined position, subjects were asked to blow their nose into sample containers. Samples were centrifuged at 1,200 rpm for 15 minutes and frozen at –20 °C. Both serum and NLF samples were collected outside the pollen season and in the absence of active symptoms for each subject. Methods ELISA For the quantitative measurement of IL17A and IL33 protein levels in serum and NLF, enzyme-linked immunosorbent assay (ELISA) tests were performed using two commercially available ELISA kits (Human IL-17A ELISA Kit, Gene Probe, Diaclone, France; and Human IL-33 ELISA Kit, R&D Systems, USA). Results were measured using an ELISA reader (Tecan Spark 2100) at 450/630 nm. RT-PCR RNA from serum and NLF was isolated using the commercially available QIAamp RNA Blood Mini Kit (QIAGEN). Isolated RNA concentrations and purity were measured using a Harvard Bioscience™ BioDrop DUO UV/Vis Spectrophotometer. Reverse-transcriptase polymerase chain reaction (RTPCR) was used to amplify the isolated mRNA for IL17A and IL33. The commercially available kit KiCqStart® SYBR® Green qPCR ReadyMix™ (Sigma-Aldrich, MERCK) was used with a Rotor-Gene Q 2plex machine and HPLC primers for IL17A (F-ACCGATCCACCTCACCTTGG, R-AGTCCACGTTCCCATCAGCG), IL33 (F-AGCCTTCTTTTTCAAGCTGG, R-TCATAAGGCCAGAGCGGAGC), and the reference gene GAPDH (F-TCCTGTTCGACAGTCAGCCG, R-GTGACCAGGCGCCCAATACG). Statistical analysis Shapiro–Wilk tests were performed on the results to confirm normality. Because not all results were normally distributed, Mann–Whitney U tests were performed to determine the statistical significance of differences observed between groups. Results Protein levels of the cytokines measured by ELISA Protein levels of IL17A and IL33 measured by ELISA are presented in Tables 1, 2 below. Comparison of protein levels at different anatomical sites within patient groups revealed no significant difference in protein levels between serum and NLF in healthy volunteers (see Tables 1, 2). In contrast, patients with AR+BA showed significantly higher IL17A levels in serum than in NLF (p = 0.003) and higher IL33 levels in NLF than in serum (p = 0.005). Patients with AR only did not show statistically significant differences in IL17A (p = 0.051) or IL33 levels (p = 0.742) between serum and NLF. Comparison of protein levels between patient groups showed significantly increased IL17A in NLF compared to healthy volunteers in both AR patients (p < 0.001) and AR+BA patients (p < 0.001), and significantly decreased IL33 in NLF compared to healthy volunteers for both AR patients (p = 0.042) and AR+BA patients (p = 0.033). Serum protein levels compared with those of healthy volunteers showed a significant elevation of IL-17A in AR+BA patients only (p = 0.002). A comparison of protein levels between AR-only and AR+BA patients revealed no significant differences. Figs 2–5 show graphical representations of these and additional selected comparisons. IL17 and IL33 mRNA levels quantified by RT-PCR RT-PCR of total RNA from serum and nasal lavage fluid (NLF) of patients with allergic rhinitis (AR) or allergic rhinitis with bronchial asthma (AR+BA) showed a 2–2.5fold increase in the expression of IL17A in both patient groups and both sample types, compared to a 1–1.5-fold increase in healthy volunteers (p < 0.01 for AR serum; p < 0.01 for AR NLF; p < 0.001 for AR+BA serum; p < 0.001 for NLF) (see Fig. 6). RT-PCR of total RNA from serum and NLF of patients with AR or AR+BA showed a 2.2–2.8-fold increase in the expression of IL33 in both patient groups and both sample types, compared to an approximately 1.5-fold increase in healthy volunteers (p < 0.01 for AR serum; p < 0.01 for AR NLF; p < 0.001 for AR+BA serum; p < 0.01 for NLF) (see Fig. 7). Discussion Our results suggest that patients with allergic rhinitis (AR) and those with allergic rhinitis and bronchial asthma (AR+BA) form a homogeneous patient population characterized by increased IL-17A levels in both local (nasal lavage fluid; NLF) and systemic (serum) samples compared to healthy volunteers and decreased IL-33 levels Pharmacia 72: 1–10 5 Table 1. IL-17A protein levels in the tested subjects. IL-17A pg/ml - serum IL-17А pg/ml – NLF Healthy AR AR+BA Healthy AR AR+BA 0.21 216.27 77.70 0.10 8.46 7.39 0.10 35.98 55.12 0.20 7.74 8.84 0.20 44.51 61.36 0.10 10.15 10.03 0.11 50.10 45.01 1.36 9.10 8.51 0.03 56.80 49.77 0.21 9.36 9.36 Table 2. IL-33 protein levels in the tested subjects. IL-33 pg/ml - serum IL-33 pg/ml – NLF Healthy AR AR+BA Healthy AR AR+BA 0.10 0.37 0.45 7.70 0.40 0.65 0.30 0.61 0.12 6.80 0.57 1.17 2.50 0.17 0.31 6.40 0.90 0.67 6.40 1.20 0.03 3.70 0.02 0.90 7.30 0.34 0.35 0.10 0.73 0.92 Figure 2. Comparison of protein levels of IL-17A and IL-33 in serum and nasal lavage fluid (NLF) between healthy volunteers and all patients. Figure 3. Comparison of protein levels of IL-17A and IL-33 in healthy volunteers and all patients between serum and nasal lavage fluid (NLF). Figure 4. Comparison of protein levels of IL-17A and IL-33 in healthy volunteers and patients with allergic rhinitis (AR) or allergic rhinitis with bronchial asthma (AR+BA). Miedema S et al.: IL-17 and IL-33 in allergic rhinitis and bronchial asthma6 in both NLF and serum compared to healthy volunteers. Notably, there were no statistically significant differences between the two patient populations. An additional difference between healthy volunteers and AR or AR+BA patients was the increased IL-33 levels in NLF compared to serum, which was not observed in healthy volunteers. Limitations of this study include the small sample size and the fact that the observed numerical difference between AR serum IL-17A levels and healthy serum IL-17A levels was not statistically significant (p = 0.062). Additional research with a larger sample size is needed to improve the statistical power of these observations. Gene expression data from three European birth cohorts show that rhinitis without additional atopic disease in patients aged 10–20 years has an identifiable and distinct pattern of gene expression clustered around IL17A and Toll-like receptor (TLR) overexpression, which does not overlap with the expression profile of patients with combined asthma, rhinitis, and/or atopic dermatitis (Lemonnier et al. 2020). Based on this information, our data may be interpreted as consistent with an IL-17–driven etiology for allergic rhinitis in the patients included in this study. Interestingly, the age of AR and AR+BA patients in our study was higher than that reported by Lemonnier et al. (AR patients: 29.6 ± 6.7; AR+BA patients: 36.8 ± 11.6). Our findings suggest that IL-17–driven AR may progress to AR+BA through as-yet-unknown mechanisms. Further research will be needed to determine the risk factors and biomarkers for the progression of IL17A-driven AR to AR+BA. IL33 mRNA was elevated compared to healthy volunteers in both AR and AR+BA patients. The decreased protein levels of IL-33 in both patient groups compared to healthy volunteers therefore suggest the involvement of posttranscriptional regulatory mechanisms. Tang et al. (2018) reported that IL-33 regulation by miR-200b and miR-200c is reduced in asthma patients and that the degree of this regulation is inversely correlated with asthma severity. As the patients in our study had mild or no asthma, it would be consistent to find that these microRNAs regulate IL-33 expression. Another major posttranscriptional regulatory mechanism affecting IL33 is the presence of soluble decoy receptors in the extracellular space. These decoy receptors, known as soluble suppressor of tumorigenicity 2 (sST2), consist of the extracellular domain of IL1RL1, excluding the transmembrane and intracellular portions of the full protein. sST2 recognizes and binds to IL-33 at the same site as the active receptor IL1RL1, thereby blocking the formation of the IL33/IL1RL1 receptor complex. It may, therefore, be the case that AR and AR+BA patients included in this study have increased sST2 levels compared to healthy volunteers. Zhu et al. (2021) reported that sST2 is elevated in patients with AR (19.8 ± 7.5 ng/mL). In addition, Mai et al. (2021) reported that the IL-33 ELISA kit used in our experiments is tolerant to only 1 ng/mL of sST2. It is, therefore, likely that the ELISA results were affected by the presence of sST2 and that the IL33 protein levels in all samples were underestimated. The apparent lack of posttranscriptional IL33 regulation in healthy volunteers may be due to differential sST2 levels between the healthy and patient populations. Follow-up research should determine sST2 levels to control for this confounding factor. If it is confirmed that IL33 levels are subject to greater regulation in the AR and AR+BA patients enrolled in this study compared to healthy volunteers, this Figure 5. Comparison of protein levels of IL-17A and IL-33 in serum and nasal lavage fluid (NLF) for patients with allergic rhinitis (AR) or allergic rhinitis with bronchial asthma (AR+BA). Figure 6. Relative gene expression of IL17A in serum (white bars) and nasal lavage fluid (NLF; gray bars). ** p <0.01; ***p< 0.001. Figure 7. Relative gene expression of IL33 in serum (white bars) and nasal lavage fluid (NLF; gray bars).** p < 0.01; *** p < 0.001. Pharmacia 72: 1–10 7 would raise the interesting possibility that these regulatory pathways are either instrumental in or a consequence of the etiology of IL17A-driven AR. The existence of a population of patients who progress from AR alone to AR combined with BA raises immediate interest in therapeutic options to prevent this progression. It may be the case that the pathological burden caused by AR is either causative for the progression to BA or a necessary upstream factor in the process. Conventional therapies for AR, such as antihistamines or corticosteroids, would then likely prove effective in preventing progression to BA in patients with AR who have elevated IL-17 and IL-33. Progression of AR patients to AR+BA in this population may also rely on a mechanism that does not respond to symptomatic treatment of AR. Marketed biologicals targeting IL-17 pathway components – including secukinumab, ixekizumab, and brodalumab – may be effective in preventing progression to AR+BA. Precise epidemiological data will be necessary to assess whether the risk– benefit ratio of these medicines is favorable for an indication such as AR. Conclusion Our data show that patients with AR only and those who progress to AR+BA from AR alone have elevated IL-17 levels in both NLF and serum. This finding is consistent with recent studies and reveals a novel population of AR+BA patients with elevated IL-17 levels. The possibility of novel IL-33 regulatory mechanisms in these patients warrants further research. Additional information Conflict of interest The authors have declared that no competing interests exist. Ethical statements Informed consent from the humans, donors or donors’ representatives: Allergology clinic of the “Aleksandrovska” University Hospital in Sofia. The authors declared that no experiments on animals were performed for the present study. The authors declared that no commercially available immortalised human and animal cell lines were used in the present study. Use of AI No AI was used by the authors in the performance of the described research nor in the preparation of this article. Funding This study was financed by the European Union–NextGenerationEU through the National Recovery and Resilience Plan of the Republic of Bulgaria, project No. BG-RRP-2.004-0008. Author contributions Conceptualization, D.M. and T.V.; methodology, D.M., K.N.; software, T.V.; validation, T.V., D.M. and V.D.; formal analysis, S.M.; investigation, S.M.; resources, D.M., K.N.; data curation, S.M.; writing – original draft preparation, S.M.; writing – review and editing, D.M., T.V.; visualization, S.M.; supervision, D.M.; project administration, T.V.; funding acquisition, T.V. All authors have read and agreed to the published version of the manuscript. Author ORCIDs Sjoerd Miedema https://orcid.org/0009-0002-6125-9908 Dimitrina Georgieva https://orcid.org/0000-0002-5931-2426 Kremena Naydenova https://orcid.org/0000-0002-6805-2590 Vasil Dimitrov https://orcid.org/0000-0001-7704-4202 Tsvetelina Velikova https://orcid.org/0000-0002-0593-1272 Data availability Quantitative RT-PCR data reflected in Figs 6 and 7 is available to the authors and may be shared upon request. All other data that support the findings of this study are available in the main text. References Acevedo-Prado A, Seoane-Pillado T, Lopez-Silvarrey-Varela A, Salgado F, Cruz M, Faraldo-Garcia A, Nieto-Fontarigo J, Pertega-Diaz S, Sanchez-Lastres J, San-Jose-Gonzalez M, Bamonde-Rodriguez L, Garnelo-Suarez L, Perez-Castro T, Sampedro-Campos M, Gonzalez-Barcala F (2022) Association of rhinitis with asthma prevalence and severity. 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