IL-1β and iNOS May Contribute to Asthmatic Comorbidities and Decreased Lung Function in Children with Perennial Allergic Rhinitis

doi:10.21203/rs.3.rs-3094750/v1

Download PDF

Research Article

IL-1β and iNOS May Contribute to Asthmatic Comorbidities and Decreased Lung Function in Children with Perennial Allergic Rhinitis

https://doi.org/10.21203/rs.3.rs-3094750/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 02 Jan, 2024

Read the published version in Allergy, Asthma & Clinical Immunology →

You are reading this latest preprint version

Background: Asthma and Allergic Rhinitis (AR) often coexist, with a significant number of AR patients eventually developing asthma. Early detection and treatment of AR can prevent disease progression and enhance the quality of life.

Objectives and Methods: This study explores the roles of Interleukin-1β (IL-1β), a pro-inflammatory cytokine, and inducible Nitric Oxide Synthase (iNOS) in the comorbidity of AR and asthma, as well as their impact on lung function in Korean children with perennial AR. A cohort of 240 subjects (aged 6-10 years old) with AR and comorbid asthma were assessed for various biomarkers, including IL-1β, iNOS, and Epithelial-Mesenchymal Transition (EMT) markers. We examined the blood levels of eosinophils and Immunoglobulin E (IgE). IL-1β, CCL-24, E-cadherin, and vimentin were measured using Enzyme-Linked Immunosorbent Assay (ELISA), while epithelial iNOS was evaluated with the NOS kit.

Results: Our observations revealed that elevated serum levels of IL-1β, iNOS, and vimentin emerged as significant risk factors for the development of AR and asthma comorbidity. Additionally, IL-1β, iNOS, and vimentin were identified as significant risk factors for decreased lung function in children with perennial AR. Moreover, IL-1β expression was found to correlate with the expression of E-cadherin, vimentin, and CCL-24. iNOS expression correlated with the expression of CCL-24 in children with AR. However, there was no observed correlation between IL-1β and iNOS.

Conclusions: This study underscores the significance of IL-1β and iNOS in the progression of AR and asthma comorbidity, suggesting them as potential targets for early intervention and treatment.

Allergic rhinitis

asthma

Comorbidity

IL-1β

iNOS

Epithelial-mesenchymal transition

E-cadherin

Vimentin

Asthma and Allergic Rhinitis (AR) are epidemiologically and biologically interconnected, with 30% of AR patients developing asthma, and 80% of patients with perennial asthma exhibiting AR. Many children with AR also have asthma, and several studies have corroborated that AR is a risk factor for developing asthma. Early and aggressive treatment of AR can prevent the progression to asthma, improving disease control and overall quality of life [1–3]. Therefore, early identification of signs of AR and asthma comorbidity can lead to timely treatment and prevention of disease progression. Moreover, appropriate management of AR enhances asthma control. Despite ongoing studies by Allergic Rhinitis and its Impact on Asthma (ARIA) report to identify risk or protective factors in patients with multimorbidity, conclusive evidence is yet to be obtained [3].

Nitric Oxide (NO) plays a crucial role in regulating various physiological functions of the respiratory epithelium. NO is synthesized from arginine by the action of NO Synthase (NOS), comprising constitutive Neuronal NOS (nNOS), inducible NOS (iNOS), and constitutive Endothelial or Epithelial NOS (eNOS). Specifically, pro-inflammatory stimuli and cytokines induce epithelial iNOS expression, increasing NO. IL-1β and TNF-α are involved in synthesizing tetrahydrobiopterin (BH4), an essential cofactor for iNOS activity [4]. A dysregulated increase in NO concentration by iNOS activity induces chronic inflammatory responses and nitration of proteins, triggering bronchial epithelial tissue injury, leading to various pulmonary diseases such as asthma [4].

Airway remodeling plays a crucial role in increased airway hyperresponsiveness, airflow obstruction, and irreversible decrease in lung function in asthma. It is regarded as a result of repetitive injury caused by chronic airway inflammation. Recently, the Epithelial-Mesenchymal Transition (EMT), in which epithelial cells lose their characteristics and gain mesenchymal traits, has been recognized as pivotal in the airway remodeling of asthma [5, 6]. EMT is a pathophysiological process induced by multiple signaling pathways, including a decrease in E-cadherin and an increase in N-cadherin or vimentin expression. Previous studies have indicated that various inflammatory factors, including innate immune cytokines and type 2 cytokines, are involved in EMT, potentially contributing to airway remodeling and leading to poor asthma control [7–9].

In previous studies, we reported that the activation of IL-1β, a pro-inflammatory cytokine, might be a risk factor for moderate perennial AR and worsening of AR symptoms [10]. Therefore, this study investigated the role of IL-1β, previously established as a significant marker [10], in the progression of comorbid disease and decline in lung function. And this study was carried out alongside the expression of various biomarkers in Korean children with perennial AR.

Study subjects

This study included children enrolled in the Elementary School Student Cohort (2009–2016) to identify various factors of allergic disease at Environmental Health Center of Ulsan University Hospital (Ulsan, Korea) [11]. This study was approved by the institutional ethics review committee of the Ulsan University Hospital (approval number 2009-09-061-011). A total of 240 subjects (6 to 10 years old) with perennial AR (AR alone: 113 children, Comorbidity of AR and asthma: 127 children) were recruited in a nested case-control study. The comorbidity group of AR and asthma was defined as children with asthmatic symptoms for one year. Subjects received a detailed questionnaire at enrollment and laboratory tests were performed. All students responded to the questionnaire and underwent routine medical checks, including a skin prick test, a blood test for total IgE levels and eosinophil counts, and a lung function test. The questionnaires used in this study included survey questions from the International Society Asthma and Allergy of Children [12] and questions regarding the socioeconomic status of the patients and hazardous environmental factors. Parents or guardians of all participants provided their written informed consent. We assembled a cohort of patients diagnosed with perennial AR to conduct a nested case-control study. We identified all children who were diagnosed with AR based on clinical symptoms and objective IgE-mediated skin prick tests.

Diagnosis of AR

We used the clinical definition of AR for diagnosis, which includes AR symptoms such as rhinorrhea, nasal obstruction, nasal itching, and sneezing, which are reversible spontaneously or with treatment, and objective tests of IgE-mediated allergies, such as the skin prick test. As part of the study, the skin prick test was performed during the medical examination to measure responses to 18 allergens, compared with the positive and negative control. Positive reactions for each allergen were defined as a wheal diameter at least 3 mm greater than that of the negative control.

Pulmonary function test (PFT)

Spirometry (Microspiro HI-801, Tokyo, Japan) was used to measure lung function. Before measurement, the child was fully instructed how to perform the test, stabilized, and then asked to bite the mouthpiece in a standing position, inhale as deeply as possible, and exhale as hard and fast as possible for at least 6 s to obtain a flow-volume curve. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced expiratory flow at 25–75% of FVC (FEF 25–75%) were measured in triplicate and the highest measurement was taken. The test was performed according to the American Thoracic Society standard test and the determination of decreased lung function was based on the study by Park et al. (Normalized spirometric values in Korean children) [13].

Measurement and analysis of serum biomarkers

To determine the expression of inflammatory or airway remodeling related biomarkers in children with perennial AR, expression level of several biomarkers was measured in the serum. Blood levels of eosinophils and immunoglobulin E (IgE) were examined. IL-1β (which represents the activation of inflammasomes), CCL-24 (chemokines that induce eosinophils in allergic diseases) and the EMT marker (E-cadherin, vimentin) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, epithelial iNOS data were measured by a NOS kit (Cat. No. ELH-ENOS). The details of each of the ELISA kits used in the study are as follows: IL-1β (catalog No. DLB50), CCL-24 (catalog No. DCC240B), E-cadherin (ab233611), and vimentin (KA3127, Abnova). Kits were obtained from R & D Systems (Minneapolis, MN), Abcam (Cambridge, MA), and Novus Biologicals (Centennial, CO).

Statistical analysis

Independent t-tests and chi-square tests were used to analyze baseline differences. Furthermore, univariate and multivariate analyzes were performed to determine possible relationships between variables and the development of comorbidity and decreased lung function. Multiple logistic regression analyzes were performed using significant variables in the univariate analysis and were reported to be associated with the development of severe AR. A P-value less than 0.05 was considered statistically significant in all analyzes. Analyses of the receiver operating characteristic [14] curve and the differences in the area under curves [15] were used to estimate the diagnostic precision of each test.

Characteristics of participants and comparison of AR and comorbidity group

The characteristics of 113 subjects with AR (perennial AR) and 127 subjects with comorbidities (perennial AR and asthma) in this study are summarized in Table 1. There were no significant differences between the AR and control groups in sex, age, total IgE, and eosinophil count. However, IL-1β and CCL-24 were significantly higher in the comorbidity group than in the AR group (p = 0.027 and p = 0.044, respectively). Furthermore, iNOS were considerably higher in the comorbidity group than in the AR group (p = 0.04). However, E-cadherin expression was significantly lower in the comorbidity groups than in the AR alone group (p = 0.034). However, the vimentin expression did not differ significantly between the two groups.

Table 1

Demographic characteristics of children with AR and comorbidity (N = 240)
	Allergic rhinitis (N = 113)	Comorbidity (N = 127)	p-value
Sex, Male (%)	63 (55.7)	70 (55.1)	0.658
Mean age (year)	7.60	7.81	0.415
Total IgE (IU/mL)	210.40 ± 35.93	189.06 ± 28.80	0.592
Eosinophils (%)	2.85 ± 0.19	2.98 ± 0.20	0.766
IL-1ß (pg/ml)	10.81 ± 3.22	20.65 ± 4.30	0.027
CCL24 (pg/ml)	337.73 ± 20.92	285.56 ± 20.41	0.044
iNOS (ng/ml)	58.95 ± 5.70	74.89 ± 5.56	0.049
E-cadherin(pg/ml)	112.93 ± 71.41	101.70 ± 34.28	0.034
Vimentin (pg/ml)	489.61 ± 24.15	508.27 ± 28.89	0.415
IL interleukin, CCL C–C motif chemokine ligand, iNOS inducible nitric oxide synthase

Independent risk factors for the development of comorbidity of AR and asthma

Table 2 presents the univariate analysis of factors, including clinical factors and biomarker expression, regarding the presence of comorbidity of AR and asthma. We also determined whether IL-1β, CCL24, iNOS, E-cadherin and vimentin could be used diagnostically in children with comorbidity with classification according to the cut-off value in the ROC curves. In the univariate analysis, the history of AR in siblings, IL-1β (> 10.84 pg/ml), iNOS (> 43.63 pg/ml) and vimentin (> 486.0 pg/ml) were associated with the development of comorbidity (p = 0.040, 0.003, 0.038 and 0.005, respectively). And the history of allergic disease of the parents or other clinical records, such as birth type and a history of general anesthesia, did not contribute to the comorbidity.

Table 2

Univariate analysis to determine factors related to comorbidity (N = 240)
Variables	AR (N = 113)	Comorbidity (N = 127)	P-value
No paternal history of AR	91	90	0.056
Paternal history of AR	22	37	0.056
No Maternal history of AR	88	88	0.087
Maternal history of AR	25	39	0.087
IL-1β (≤ 10.84 pg/ml)	71	55	0.003
IL-1β (> 10.84 pg/ml)	42	72	0.003
CCL24 (≤ 308.0 pg/ml)	59	71	0.329
CCL24 (> 308.0 pg/ml)	54	56	0.329
iNOS (≤ 43.63 pg/ml)	61	3	0.038
iNOS (> 43.63 pg/ml)	52	74	0.038
E-cadherin (≤ 93.39 pg/ml)	61	57	0.101
E-cadherin (> 93.39 pg/ml)	52	70	0.101
Vimentin (≤ 486.0 pg/ml)	45	73	0.005
Vimentin (> 486.0 pg/ml)	68	54	0.005
IL interleukin, CCL C–C motif chemokine ligand, iNOS inducible nitric oxide synthase

Multivariate analysis revealed that elevated IL-1β (5.6-fold increase in risk) and high expression of iNOS and vimentin (6.3 and 7.9-fold increase in risk) were significant risk factors for the development of comorbidity (Table 3).

Table 3

Multivariate analysis to determine factors related to comorbidity.
pg/ml	95% CI		OR	P-value
IL-1β > 10.84	.649	.275	5.595	0.012
iNOS > 43.63	.700	.279	6.287	0.026
Vimentin > 486	.615	.279	4.891	0.027
IL interleukin, iNOS inducible nitric oxide synthase, CI confidence interval, OR odds ratio

Independent risk factors for decreased lung function in perennial AR

In addition, we investigated the risk factors for decreased lung function and the results of chronic airway inflammation or remodeling. In the normal PFT (n = 126) and decreased PFT (n = 113) groups, there were no significant differences in total levels of IgE, eosinophil, CCL24 and E-cadherin (Table 4). However, IL-1β, iNOS and vimentin were significantly higher in subjects with the decreased PFT group than in the normal PFT group (P < 0.001, < 0.001 and 0.008, respectively). Table 5 presents a univariate analysis of risk factors, including clinical factors and biomarker expression for decreased lung function. In univariate analysis, IL-1β (> 10.84 pg/ml), iNOS (> 43.63 pg/ml), and vimentin (> 486.0 pg/ml) were associated with decreased lung function (p = 0.027, < 0.001 and 0.020, respectively).

Table 4

Expression of biomarkers in the groups of normal lung function and decreased lung function (n = 239)
	Normal PFT (N = 126)	Decreased PFT (N = 113)	p-value
Total IgE (IU/mL)	214.61 ± 28.21	183.56 ± 36.656	0.596
Eosinophils (%)	3.02 ± 0.19	2.82 ± 0.19	0.137
IL-1ß (pg/ml)	11.10 ± 1.86	20.84 ± 4.37	< 0.001
CCL24 (pg/ml)	307.24 ± 24.89	321.72 ± 20.18	0.110
iNOS(ng/ml)	49.18 ± 5.97	87.74 ± 5.66	< 0.001
E-cadherin(pg/ml)	114.15 ± 61.58	106.86 ± 67.99	0.350
Vimentin (pg/ml)	437.80 ± 33.23	532.12 ± 23.07	0.008
PFT pulmonary function test, IL interleukin, CCL C–C motif chemokine ligand, iNOS inducible nitric oxide synthase

Table 5

**Univariate analysis to determine factors related to decreased lung function (n = 239)**
Variables	AR (N = 126)	Comorbidity (N = 113)	P-value
No paternal history of AR	95	85	0.100
Paternal history of AR	31	28	0.100
No Maternal history of AR	92	84	0.087
Maternal history of AR	34	29	0.087
IL-1β (≤ 10.84 pg/ml)	57	68	0.027
IL-1β (> 10.84 pg/ml)	68	45	0.027
CCL24 (≤ 308.0 pg/ml)	67	62	0.797
CCL24 (> 308.0 pg/ml)	59	51	0.797
iNOS (≤ 43.63 pg/ml)	74	31	< 0.001
iNOS (> 43.63 pg/ml)	52	82	< 0.001
E-cadherin (≤ 93.39 pg/ml)	67	50	0.195
E-cadherin (> 93.39 pg/ml)	59	63	0.195
Vimentin (≤ 486.0 pg/ml)	53	65	0.020
Vimentin (> 486.0 pg/ml)	73	48	0.020

IL interleukin, CCL C–C motif chemokine ligand, iNOS inducible nitric oxide synthase

Multivariate analysis revealed that elevated IL-1β (7.8-fold increase in risk) and high expression of iNOS and vimentin (22.3 and 6.7- fold increase in risk) were significant risk factors for the development of decreased lung function (Table 6). Furthermore, elevated iNOS was the strongest risk factor for comorbidity and decreased lung function.

Table 6

Multivariate analysis to determine factors related to decreased lung function.
pg/ml	95% CI		OR	P-value
IL-1β > 10.84	−.933	.289	7.845	0.005
iNOS > 43.63	.288	1.359	22.333	< 0.001
Vimentin > 486	−.707	.287	6.742	0.009
IL interleukin, iNOS inducible nitric oxide synthase, CI confidence interval, OR odds ratio

Relationship between IL-1β and other biomarkers

To further investigate the mechanism of IL-1β inducing iNOS and EMT, correlation analysis was used to detect the expression of candidate signaling pathway-related proteins. A regression analysis showed that the IL-1β was associated with increased vimentin and CCL-24 expression and decreased E-cadherin in children with AR (p = 0.001) (Table 7). However, IL-1β did not correlate with iNOS (p = 0.094). Therefore, we analyzed the correlation of iNOS and other inflammatory biomarkers and found that the expression of iNOS was correlated with the expression of CCL-24 (Table 8). Thus, IL-1β or iNOS can independently induce comorbidity or decrease of lung function in AR through activation of CCL-24 or vimentin.

Table 7

Multiple linear regression between IL-1β and inflammatory markers
Variables	Standardized coefficient (95% CI)	Adjusted R2	P-value
iNOS	0.108 (− 0.001–0.946)	0.008	0.094
CCL24	0.005 (0.002–0.195)	0.045	0.001
Vimentin	0.005 (-0.651–0.998)	0.096	< 0.001
E-cadherin	−0.001(− 0.015–2.062)	0.019	0.018
IL interleukin, iNOS inducible nitric oxide synthase, CI confidence interval, CCL C–C motif chemokine ligand

Table 8

Multiple linear regression between iNOS and inflammatory markers
Variables	Standardized coefficient (95% CI)	Adjusted R2	P-value
CCL24	0.241 (0.032–0.100)	0.058	< 0.001
Vimentin	0.011(− 0.025–0.029)	−0.004	0.866
E-cadherin	−0.105 (− 0.129–0.116)	−0.004	0.917
iNOS inducible nitric oxide synthase, CI confidence interval, CCL C–C motif chemokine ligand

Previously, IL-1β level in the baseline sputum was reported to be a predicting marker for poor improvement in lung function in neutrophilic asthmatics. The potential mechanism may be related to IL-1β augmenting TGF-β1-induced steroid-resistant EMT pathways [11]. In this study, we observed that children with higher IL-1β levels faced increased risks of AR and asthma comorbidity, as well as decreased lung function. And vimentin, a marker of airway remodeling, was identified as a risk factor for both comorbidity and decreased lung function. Furthermore, elevated IL-1β was associated with increased vimentin expression in children with perennial AR, suggesting that IL-1β can trigger airway remodeling as comorbidity develops through vimentin activation. Yet, most inhibitors targeting IL-1β lack specificity and efficacy, indicating a potential need for site-specific therapies to more effectively suppress inflammation and airway remodeling. [16, 17]. Thus, the development of targeted site-specific therapies may be more beneficial in suppressing inflammation and airway remodeling.

Biologically, NO is derived from L arginine and oxygen in a reaction catalyzed by NO synthases. The iNOS makes the most significant amount of NO, and iNOS is usually induced by inflammatory or immunological stimuli such as cytokines. And iNOS is expressed in airway epithelial cells in asthmatic patients and is predominantly expressed in macrophages and epithelial cells during airway inflammation [18]. NO levels increase in FENO in asthmatic patients is mainly induced by increase of expression and activity of the iNOS enzyme [19]. However, the pathophysiological role of increased iNOS in AR, particularly in children, remains unclear. Our findings reveal that iNOS plays a crucial role in inducing comorbidity and decreasing lung function, evidenced by its correlation with CCL-24. We demonstrated that iNOS is essential in inducing comorbidity and decreasing lung function through correlation with CCL-24.

Interestingly, the IL-1β was not directly correlated with iNOS. These results suggest that IL-1β and iNOS can independently induce comorbidity or decrease lung function in children with perennial AR through association with airway remodeling biomarkers. Although these results provide valuable insights, our study did not include experimental data, leaving room for further exploration of the candidates studied. The identified potential biomarkers shift the focus towards discovering diagnostic and therapeutic tools for allergic disease comorbidity. Despite these limitations, our findings are significant, demonstrating oxidative and inflammatory changes in children with allergic comorbidity.

This study identified several factors associated with comorbidity and decreased lung function in children with perennial AR. Our findings add new information to identify children with AR at an increased risk for comorbidity.

This study indicates that oxidative stress and inflammation biomarkers may contribute to the co-morbidity of asthma and Allergic Rhinitis (AR) in children. Alongside IL-1β, increased serum iNOS levels could serve as early markers for the progression of comorbidity and decreased lung function due to airway remodeling and chronic inflammation. Furthermore, our identification of these biomarkers provides an opportunity to uncover previously unknown mechanisms and to design effective treatments for the comorbidity of asthma and AR, as well as severe asthma.

IL, interleukin; iNOS, inducible nitric oxide synthase; CCL, C–C motif chemokine ligand; OR, odds ratios;

CI, confidence intervals

Acknowledgements: None

Authors’ contributions

MH and JL designed the study. MH, SK, IO, and JL coordinated the overall undertaking of the study. MH and JL performed statistical analyses. MH and JL wrote the manuscript. All authors contributed to the revision. All authors read and approved the final manuscript.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This work received a grant from the Environmental Health Center funded by the Ministry of Environment, Republic of Korea, and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health &Welfare, the Republic of Korea (Grant HC15C1335).

Ethics approval and consent to participate

This study was approved by the institutional ethics review committee of Ulsan University Hospital (approval number 2009-09-061-011). The parents or legal guardians of all participants provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Author details

¹ Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan‑doro, Dong‑gu, Ulsan 44033, Republic of Korea. ² Environmental Health Center, University of Ulsan College of Medicine, Ulsan, Republic of Korea. ³ Department of Occupational and Environmental Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunhwan‑doro, Dong‑gu, Ulsan 44033, Republic of Korea.

Corren J, Adinoff AD, Buchmeier AD, Irvin CG. Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma. J Allergy Clin Immunol. 1992;90:250-6.
Incorvaia C, Masieri S, Cavaliere C, Makri E, Sposato B, Frati F. Asthma associated to rhinitis. J Biol Regul Homeost Agents. 2018;32:67-71.
Bousquet J, Schünemann HJ, Togias A, Bachert C, Erhola M, Hellings PW, et al. Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence. J Allergy Clin Immunol. 2020;145:70-80.e3.
Yalcin AD, Gumuslu S, Parlak GE, Bisgin A, Yildiz M, Kargi A, et al. Systemic levels of ceruloplasmin oxidase activity in allergic asthma and allergic rhinitis. Immunopharmacol Immunotoxicol. 2012;34:1047-53.
Boonpiyathad T, Sözener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol. 2019;46:101333.
Knight DA, Grainge CL, Stick SM, Kicic A, Schuliga M. Epithelial Mesenchymal Transition in Respiratory Disease: Fact or Fiction. Chest. 2020;157:1591-6.
Sohal SS, Ward C, Walters EH. Importance of epithelial mesenchymal transition (EMT) in COPD and asthma. Thorax. 2014;69:768.
Sun Z, Ji N, Ma Q, Zhu R, Chen Z, Wang Z, et al. Epithelial-Mesenchymal Transition in Asthma Airway Remodeling Is Regulated by the IL-33/CD146 Axis. Front Immunol. 2020;11:1598.
Han L, Luo H, Huang W, Zhang J, Wu D, Wang J, et al. Modulation of the EMT/MET Process by E-Cadherin in Airway Epithelia Stress Injury. Biomolecules. 2021;11.
Han MW, Kim SH, Oh I, Kim YH, Lee J. Serum IL-1beta can be a biomarker in children with severe persistent allergic rhinitis. Allergy Asthma Clin Immunol. 2019;15:58.
Abuelezz SA. Nebivolol attenuates oxidative stress and inflammation in a guinea pig model of ovalbumin-induced asthma: a possible mechanism for its favorable respiratory effects. Can J Physiol Pharmacol. 2018;96:258-65.
Asher MI, Keil U, Anderson HR, Beasley R, Crane J, Martinez F, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8:483-91.
Chul Hyue Park, Hyo-Bin Kim, Young Ho Jung, Eun Lee, Song I Yang, Ju-Hee Seo, et al. Predicted normal values of pulmonary function tests in normal Korean children: Allergy Asthma & Respiratory Diseases. 2014;2:187-93.
Dai C, Yao X, Gordon EM, Barochia A, Cuento RA, Kaler M, et al. A CCL24-dependent pathway augments eosinophilic airway inflammation in house dust mite-challenged Cd163(-/-) mice. Mucosal Immunol. 2016;9:702-17.
Madouri F, Guillou N, Fauconnier L, Marchiol T, Rouxel N, Chenuet P, et al. Caspase-1 activation by NLRP3 inflammasome dampens IL-33-dependent house dust mite-induced allergic lung inflammation. J Mol Cell Biol. 2015;7:351-65.
Theofani E, Semitekolou M, Morianos I, Samitas K, Xanthou G. Targeting NLRP3 Inflammasome Activation in Severe Asthma. J Clin Med. 2019;8.
Wei-xu H, Qin X, Zhu W, Yuan-yi C, Li-feng Z, Zhi-yong L, et al. Therapeutic potential of anti-IL-1β IgY in guinea pigs with allergic asthma induced by ovalbumin. Mol Immunol. 2014;58:139-49.
Ricciardolo FL, Nijkamp FP, Folkerts G. Nitric oxide synthase (NOS) as therapeutic target for asthma and chronic obstructive pulmonary disease. Curr Drug Targets. 2006;7:721-35.
Bayarri MA, Milara J, Estornut C, Cortijo J. Nitric Oxide System and Bronchial Epithelium: More Than a Barrier. Front Physiol. 2021;12:687381.

Download PDF

Journal Publication

published 02 Jan, 2024

Read the published version in Allergy, Asthma & Clinical Immunology →

Editorial decision: Major revision
17 Jul, 2023
Reviewers agreed at journal
03 Jul, 2023
Reviewers invited by journal
03 Jul, 2023
Editor assigned by journal
01 Jul, 2023
First submitted to journal
25 Jun, 2023

You are reading this latest preprint version

IL-1β and iNOS May Contribute to Asthmatic Comorbidities and Decreased Lung Function in Children with Perennial Allergic Rhinitis

Status:

Journal Publication

Version 1

Abstract

Introduction

Patients and methods

Study subjects

Diagnosis of AR

Pulmonary function test (PFT)

Measurement and analysis of serum biomarkers

Statistical analysis

Results

Characteristics of participants and comparison of AR and comorbidity group

Independent risk factors for the development of comorbidity of AR and asthma

Independent risk factors for decreased lung function in perennial AR

Relationship between IL-1β and other biomarkers

Discussion

Conclusions

Abbreviations

Declarations

References

Status:

Journal Publication

Version 1