Analysis of Multimorbidity of Moderate to Severe Allergic Rhinitis in Children: A Real-World Study.

INTRODUCTION: Allergic rhinitis (AR) in children is associated with various comorbidities, posing challenges for treatment and management. There have been few investigations of these multimorbidities in Chinese children with AR. Here, we investigated the prevalence of multimorbidities in children with moderate to severe AR and analyzed the influencing factors using real-world data. METHODS: In total, 600 children who visited the outpatient clinic of our hospital and were diagnosed with moderate-severe AR were prospectively enrolled. All children underwent allergen detection and electronic nasopharyngoscopy. Parents or guardians completed a questionnaire that included age, sex, mode of delivery, feeding pattern, and familial history of allergy. The multimorbidities investigated included atopic dermatitis (AD), asthma, allergic conjunctivitis (AC), chronic rhinosinusitis (CRS), adenoid hypertrophy (AH), tonsil hypertrophy (TH), recurrent epistaxis, and recurrent respiratory tract infections (RRTIs). RESULTS: The AR multimorbidities reported in children were as follows: recurrent epistaxis (46.5%), AC (46.3%), AD (40.7%), asthma (22.5%), RRIs (21.3%), CRS (20.5%), AH (19.7%), and TH (12.5%). In univariate logistic regression analysis, age (<6 years), birth mode, familial history of allergy, and single dust mite allergy were associated with AR multimorbidity (p < 0.05). Multivariate logistic regression revealed that a familial history of allergy was an independent risk factor for AC (odds ratio [OR] = 1.539, 95% confidence interval [CI]: 1.104-2.145) and AH (OR = 1.506, 95% CI: 1.000-2.267) (p < 0.05). Age (<6 years) was independently associated with the risk of AD (OR = 1.405, 95% CI: 1.003-1.969) and RRTIs (OR = 1.869, 95% CI: 1.250-2.793) (p < 0.05), cesarean section with AR and CRS risk (OR = 1.678, 95% CI: 1.100-2.561), and single dust mite allergy with asthma (OR = 1.590, 95% CI: 1.040-2.432) and CRS (OR = 1.600, 95% CI: 1.018-2.515) risk (p < 0.05). Further, non-dust mite allergy was independently associated with AR and CRS (OR = 2.056, 95% CI: 1.084-3.899). CONCLUSION: AR was found to be accompanied by different comorbidities, including both allergic and non-allergic comorbidities, complicating disease treatment. These findings demonstrated that age (<6 years), familial history of allergy, types of allergens, and cesarean section were risk factors for different multimorbidities associated with AR.

Genetic risk of FCRL3 and FCRL5 polymorphisms in children with asthma and allergic rhinitis in a Chinese Han population.

OBJECTIVES: Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the FCRL3 and FCRL5 genes have recently been shown to be associated with various immune-related disorders. This study evaluated the association of FCRL3 and FCRL5 polymorphisms with asthma and allergic rhinitis (AR) in a Han Chinese population. METHODS: Seven single nucleotide polymorphisms (SNPs) of the FCRL3 and FCRL5 were genotyped in 300 asthmatic children, and 206 healthy unrelated individuals using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Genotyping was validated by direct sequencing. RESULTS: Our results showed that the frequencies of the rs6692977 CT genotype and T allele within FCRL5 were significantly higher in asthma with comorbid AR compared to healthy controls (Bonferroni-corrected p (Pc) = 3.75 × 10-6; Pc = 0.006, respectively), whereas these of the CC genotype and C allele were significantly lower (Pc = 4.15 × 10-5; Pc = 0.006, respectively). The frequencies of the rs7528684 A allele (Pc = 1.80 × 10-3) and the rs10489678 G allele (Pc = 0.04) within FCRL3 were higher in asthma with comorbid AR than in controls. However, no differences in the tested genetic polymorphisms were detected between asthma and healthy individuals. CONCLUSION: This study identified novel SNPs in FCRL3 and FCRL5 significantly associated with the risk for asthma with comorbid AR in the Chinese population. The genetic variants may play role in the development of the asthma phenotype in children with asthma.

Allergen induced Treg response in the peripheral blood mononuclear cells (PBMCs) of patients with nasal polyposis.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses regulated by T cells. Regulatory T (Treg) cells are involved in controlling immune responses and inhibiting the allergen-specific effector cell response. The aim of this study was to evaluate whether NP patients had defects in Treg cells after specific allergen exposure and the possible correlation between atopy and Treg cells. METHODS: Peripheral blood mononuclear cells (PBMCs), isolated from NP patients and controls, were cultured with allergen+phytohemagglutinin (PHA) or PHA stimulation for 48h. The frequency of CD4+CD25+Foxp3+ cells was measured by flow cytometry. The level of Foxp3 was measured by Real-time PCR. Concentrations of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Interleukin-5 (IL-5), Interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) in culture supernatants were determined by ELISA. RESULTS: Both atopic and non-atopic NP patients had a significantly decreased frequency of Treg cells and Foxp3 level in allergen stimulated PBMCs, also significantly decreased TGF-ß level in culture supernatants. The decrease was even more striking in the atopic group. Also, there were significantly negative correlations between Treg cells and IFN-γ, IL-4, IL-5. Moreover, inthe atopic group, allergen stimulation downregulated Treg cells and increased IFN-γ, IL-4, IL-5 levels, while upregulating Treg cells and decreasing IFN-γ, IL-4, IL-5 levels in controls. CONCLUSIONS: Patients with NP have a defective Treg cell response after allergen stimulation which is related to excessive Th1 and Th2 responses to specific allergens. Atopy may increase the impairment of Treg and exacerbate NP through the defective suppression of Treg on Th1 and Th2.

Andrographolide suppresses IL-6/Stat3 signaling in peripheral blood mononuclear cells from patients with chronic rhinosinusitis with nasal polyps.

The mechanisms underlying the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely unknown. CRSwNP has garnered considerable public health concern owing to its high incidence and unsatisfactory treatment outcomes. Herbal remedies are promising candidates for the treatment of CRSwNP. We examined the utility of andrographolide, a diterpenoid lactone extracted from the Chinese herb Andrographis paniculata, an anti-inflammatory agent for CRSwNP treatment by evaluating interleukin (IL)-6 and IL-17 production and monitoring T helper 17 (Th17) differentiation of peripheral blood mononuclear cells (PBMCs) isolated from 20 Chinese CRSwNP patients and 11 control subjects. All CRSwNP patients exhibited clinical features of CRSwNP. Andrographolide significantly inhibited IL-6 and IL-17 production, suppressed p-Stat3 expression, and inhibited Th17 differentiation of PBMCs in vitro. These findings suggested that andrographolide has useful anti-inflammatory properties and could be used for the treatment of CRSwNP.

Allergen induced Th17 response in the peripheral blood mononuclear cells (PBMCs) of patients with nasal polyposis.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses. Th17 cells have been considered to play roles in allergic airway diseases and various chronic inflammatory disorders. AIM OF THE STUDY: This study aimed to investigate the population and function of peripheral Th17 cells in response to house dust mite extracts (HDM) allergen in NP patients, and evaluate the possible correlation between Th17 cells and atopy, to explore the role of atopy in the pathogenesis of NP. METHODS: Peripheral blood mononuclear cells (PBMCs) obtained from atopic NP patients, non-atopic NP patients, and controls were stimulated by phytohemagglutinin (PHA) or HDM plus PHA. The resulting frequency of Th17 cells was detected by flow cytometry and the expression of RORc was measured by real-time PCR. Then the concentrations of IL-17A, INF-γ, IL-4 and IL-5 in the supernatants were assayed by specific ELISAs. RESULTS: The population and function of Th17 cells in allergen stimulated PBMCs were significantly higher in atopic NP patients. In addition, in atopic group, HDM+PHA stimulation induced significant increase of Th17 population and IL-17A production versus those in PHA stimulated ones. However, the frequency of Th17 cells was not correlated with Th1, Th2 cytokine productions. CONCLUSION: Th17 immunity is involved in the systemic immune responses to allergen in atopic NP and atopy may aggravate NP by stimulating the increase of Th17 population and IL-17A production. The mechanism of Th17 cells response to allergen may be regulated differently from the regulation of Th1 and Th2 immunity in NP.

[Imbalance of Th17/Treg cell ratio in peripheral blood of patients with nasal polyposis and its clinical significance].

AIM: To observe the distribution of Th17 cells and Foxp3(+);CD4(+);CD25(+); regulatory T cells in peripheral blood of patients with nasal polyposis(NP) and their correlation with clinical patients' condition, and to explore the role of Th17/Treg cell ratio imbalance in pathogenesis of nasal polyposis and significance. METHODS: The frequencies of Th17 cells and Treg cells were determined in 46 patients with NP and 10 controls by flow cytometry. The 46 patients were divided into two groups according to endoscopy score and CT score: the 1 group (endoscopy score: 2-8 scores; CT score: 3-10 scores, n=23) and the 2 group (endoscopy score: 8-12 scores; CT score: 10-19 scores, n=23). RESULTS: Th17 cells were significantly higher in the blood of patients with NP compared with the control group (P<0.01), and the percentage was higher in the 2 group than the 1 group (P<0.05). The frequency of Treg cells was significantly decreased in patients with NP compared to the control group (P<0.01), whereas the difference between two groups was not significant. The ratio of Th17/Treg cells was highest in the 2 group (P<0.01), lower in the 1 group (P<0.01) and lowest in control subjects, and the differences were also significant between two groups (P<0.05). Furthermore, it was confirmed that the ratio of Th17/Treg positively correlated with endoscopy score and CT score (P<0.01). CONCLUSION: The imbalance of Th17/Treg cell ratio characterized by increased Th17 cells and decreased Treg cells exists in peripheral blood of NP patients and may play an important role in the onset and development of NP. The degree of Th17/Treg cell imbalance may associate with clinical presentation.

Significance of interleukin-17A in patients with nasal polyposis.

BACKGROUND: Interleukin-17A (IL-17A) is a key inflammatory cytokine in many disorders, while the significance of IL-17A in nasal polyposis (NP) is still obscure. This study aimed to investigate the expression of IL-17A in nasal polyps from both atopic and nonatopic patients and its associations with clinical and histological features. METHODS: In all, 30 patients with NP were included, and were grouped into atopic and nonatopic patients according to skin prick test (SPT). Disease severity was evaluated by symptom score, endoscopy score and CT score. Histological characteristics were assessed by eosinophilic infiltration, basement membrane (BM) thickness, epithelial damage, squamous metaplasia, and goblet cell hyperplasia. IL-17A expression in polyps was detected by ELISA and immunohistochemistry. RESULTS: Endoscopy score and CT score were significantly higher in atopic NP patients than in nonatopic NP patients (p < 0.05). IL-17A levels were significantly upregulated in both atopic (p < 0.01) and nonatopic (p < 0.05) patients versus controls. Furthermore, IL-17A levels were significantly higher in the atopic group versus nonatopic group. Significantly positive correlations were found between IL-17A levels and CT scores, eosinophilic infiltration and BM thicknesses. CONCLUSIONS: These results indicated that expression of IL-17A was significantly upregulated in NP patients and was more severe in atopic NP patients, suggesting that IL-17A may play an important role in the pathology of NP and atopy may contribute to NP by stimulating the production of IL-17A.

[Imbalance of Thl7/Treg cell ratio in peripheral blood of patients with nasal polyposis and its clinical significance].

AIM: To observe the distribution of Thl7 cells and Foxp3 CD4 * CD25 regulatory T cells in peripheral blood of patients with nasal polyposis(NP) and their correlation with clinical patients' condition, and to explore the role of Thl7/Treg cell ratio imbalance in pathogenesis of nasal polyposis and significance. METHODS: The frequencies of Thl7 cells and Treg cells were determined in 46 patients with NP and 10 controls by flow cytometry. The 46 patients were divided into two groups according to endoscopy score and CT score: the 1 group (endoscopy score: 2-8 scores; CT score: 3 -10 scores, n = 23) and the 2 group (endoscopy score: 8 -12 scores; CT score: 10 -19 scores, n = 23). RESULTS: Thl7 cells were significantly higher in the blood of patients with NP compared with the control group (P<0.01), and the percentage was higher in the 2 group than the 1 group (P<0.05). The frequency of Treg cells was significantly decreased in patients with NP compared to the control group (P < 0. 01), whereas the difference between two groups was not significant. The ratio of Thl7/Treg cells was highest in the 2 group (P < 0.01), lower in the 1 group (P<0.01) and lowest in control subjects, and the differences were also significant between two groups (P<0.05). Furthermore, it was confirmed that the ratio of Thl7/Treg positively correlated with endoscopy score and CT score (P <. 0.01). CONCLUSION: The imbalance of Thl7/Treg cell ratio characterized by increased Thl7 cells and decreased Treg cells exists in peripheral blood of NP patients and may play an important role in the onset and development of NP. The degree of Thl7/Treg cell imbalance may associate with clinical presentation.