Characteristics of upper respiratory tract rhinovirus in children with allergic rhinitis and its role in disease severity.

Allergic rhinitis (AR) is a global health challenge that particularly affects the quality of life of children. Human rhinovirus (HRV) infection usually causes common cold in the upper respiratory tract (URT) and can also affect airway allergy development, such as asthma exacerbation, but its relationship with AR is poorly understood. The study aimed to gain insight into the characteristics of HRV that is prevalent in AR children and its role in AR severity. A total of 362 children with symptomatic AR were enrolled from southwestern China during 2022-2023, and nasal lavage samples were collected for HRV molecular characterization and cytokine measurement. HRV was detected in 40% of the AR children, with peak detection in autumn. The positive rate was not correlated with whether the subjects were under allergen-specific immunotherapy (AIT). Among the detected HRVs, 42% were species A, 36% were species B, and 22% were species C, involving 21 A genotypes, 6 B genotypes, and 7 C genotypes. HRV positivity was significantly associated with symptom severity (visual analog scale [VAS] score) and elevated levels of local nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 in AR children who did not receive antiallergic treatment. All three species of HRV strains (A1B, A21, B27, B70, and C17) had been isolated and were able to infect respiratory epithelial tissue in vitro. Complete genome sequencing showed that the antigenic epitopes of the isolated HRVs had certain variations. Our work reveals the etiological characteristics of URT-HRV in AR children and suggests a role of HRV infection in the pathogenesis of childhood AR. IMPORTANCE: Our study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively associated with the symptom severity in AR children. Elevated nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 levels suggest a potential pathogenic mechanism by which HRV infection induces nasal type 2 immune/inflammation responses and local IgE production in AR patients. In addition, etiological analysis found that the main prevalent HRV species in AR children are A and B (~80%), which is different from acute respiratory infection and asthma exacerbation, where species A and C are dominant. The data reveal the distinct species prevalence characteristics of HRV infection in AR. Finally, we isolated all three species of HRV strains from nasal cavity of AR children with varying degrees of antigenic epitope mutations and in vitro infectivity, highlighting the importance of strengthening monitoring and intervention for respiratory HRV infection in AR children.

Nasal IgE production in allergic rhinitis: Impact of rhinovirus infection.

BACKGROUND: Rhinovirus (RV) infections exacerbate asthma in part by enhancing an allergic state, and these exacerbations can be mitigated via administration of anti-IgE. OBJECTIVE: We investigated the presence of local IgE production in the nose of allergic and non-allergic subjects and assessed whether this was enhanced by RV. METHODS: Local production of specific IgE was determined by comparing ratios of specific to total IgE concentrations between nasal and serum samples. Our initial studies were performed in subjects presenting to the emergency department for allergic and non-allergic respiratory complaints. Subsequently, we investigated influences of experimental RV infection on nasal sIgE production in an allergic cohort. RESULTS: We found evidence of local sIgE production to Dermatophagoides pteronyssinus in 30.3% and to Blomia tropicalis in 14.6% of allergic subjects. None of the non-allergic subjects demonstrated local IgE. Subjects with active RV infection were more than twice as likely to have local sIgE (45% vs 14%), and subjects with local sIgE being produced were ~3 times more likely to be having an asthma exacerbation. Experimental RV infection was able to induce local sIgE production. CONCLUSION: These studies confirm local IgE production in a large subset of allergic subjects and demonstrate that allergic asthmatics with local IgE are more likely to develop an asthma exacerbation when infected with RV. Our RV challenge studies demonstrate that at least some allergic asthmatics can be induced to secrete locally generated IgE in their nasal airway after RV infection.

Type III interferons are critical host factors that determine susceptibility to Influenza A viral infection in allergic nasal mucosa.

BACKGROUND: Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon (IFN)-related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown. OBJECTIVES: To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus (IAV) in allergic nasal mucosa could be controlled with IFN treatment. METHODS: Influenza A virus mRNA, viral titres and IFN expression were compared in IAV-infected normal human nasal epithelial (NHNE, N = 10) and allergic rhinitis nasal epithelial (ARNE, N = 10) cells. We used in vivo model of allergic rhinitis (BALB/c mice, N = 10) and human nasal mucosa from healthy volunteers (N = 72) and allergic rhinitis patients (N = 29) to assess the induction of IFNs after IAV infection. RESULTS: Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN-ß and IFN-λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN-λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN-λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN-λ treatment attenuated viral mRNA levels and viral titres in IAV-infected ARNE cells. In vivoAR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN-λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV-infected AR mouse. CONCLUSION: Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.

Correlation of symptomatic enterovirus infection and later risk of allergic diseases via a population-based cohort study.

Infants who are exposed to the rhinovirus or respiratory syncytial virus are at a higher risk of subsequently developing wheezing or asthma. This study aims to determine whether preschoolers with a history of symptomatic enterovirus infection are at an increased risk of developing allergic diseases or not.We used data from the Taiwan National Health Insurance Research Database from 1999 to 2006 for this nationwide population-based cohort study. The subsequent risks for allergic diseases, which included asthma (International Classification of Diseases [ICD]-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between herpangina (ICD-9: 074.0) and hand, foot, and mouth disease (HFMD; ICD-9: 074.3) throughout the follow-up period using the Cox proportional hazards model.In this database, 12,016 neonates were born between January 1999 and December 1999. Among them, we further evaluated 8337 subjects; 3267 children infected with either herpangina or HFMD served as the study cohort, and the other 5070 children made up the comparison cohort. Children in the herpangina group had a higher risk of developing AR and AD, with adjusted hazard ratios of 1.15 (1.02-1.30, 95% CI) and 1.38 (1.17-1.63. 95% CI), respectively, while children suffered from HFMD had decreased risks of asthma, with an adjusted hazard ratio of 0.76 (0.63-0.93, 95% CI).Children who previously suffered from herpangina experienced an increased risk of subsequently developing AD and AR. Meanwhile, children who had suffered from HFMD experienced a decrease in the subsequent occurrence of asthma compared to the general population.

Impaired virus replication and decreased innate immune responses to viral infections in nasal epithelial cells from patients with allergic rhinitis.

The aim of this study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. NECs were obtained from eight patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR-3 and TLR-7/8 agonists. Interferon (IFN)-λ1, IFN-α, IFN-ß and regulated on activation, normal T expressed and secreted (RANTES) release into the cell culture supernatants was assessed at 8, 24 and 48 h upon infection or 8 and 24 h after stimulation with poly(I:C) and R848. mRNA levels of IFNs, RANTES, interferon regulatory transcription factor (IRF)3, IRF7 and viral gene copy number were determined using real-time polymerase chain reaction (RT-PCR). PIV3 but not RV1B replication 48 h after infection was significantly lower (P < 0·01) in NECs from AR patients compared to HC. PIV3 infection induced significantly less IFN-λ1 (both protein and mRNA) in NECs from AR compared to HC. IFN-ß mRNA expression and RANTES protein release and mRNA expression tended to be smaller in AR compared HC cells in response to both viruses. Stimulation with TLR-3 agonist [poly (I:C)] induced similar IFN-λ1 and RANTES generation in AR and HC subjects. Viral infections in NECs induced IRF7 expression, which correlated with IFN and RANTES expression. These data suggest that virus proliferation rates and the immune response profile are different in nasal epithelial cells from patients with allergic rhinitis compared to healthy individuals.

Rhinitis in the first 18 months of life: exploring the role of respiratory viruses.

BACKGROUND: Rhinitis is common in early childhood, but allergic rhinitis is considered a later manifestation of the atopic march. This study aimed to evaluate rhinitis (allergic and non-allergic) in the first 18 months of life, its link with other atopic manifestations and the role of respiratory viruses. METHODS: Subjects (n = 1237) of the Singapore GUSTO birth cohort were followed up quarterly until 18 months of age with questionnaires to screen for rhinitis symptoms lasting at least 2 wk and with monthly calls to positive subjects to detect prolonged/recurrent rhinitis symptoms (total duration ≥ 4 wk). Anterior nasal swabbing for molecular-based virus detection was conducted during these visits and near (within a month) rhinitis episodes. Skin prick testing to common environmental and food allergens was conducted at the 18 month visit. RESULTS: Prolonged/recurrent rhinitis was significantly associated with history of parental atopy (mother: aOR = 2.17; father: aOR = 1.82) and atopic comorbidities of eczema (aOR = 2.53) and wheeze (aOR = 4.63) (p < 0.05), though not with allergen sensitization. Although the frequency of nasal respiratory virus detection during scheduled quarterly visits did not differ between prolonged/recurrent rhinitis and matched controls (p > 0.05), virus detection was higher in swabs obtained within a month following rhinitis episodes in prolonged/recurrent rhinitis subjects compared with scheduled visits (adjusted p = 0.04). CONCLUSIONS: Based on the duration of rhinitis symptoms, this study defined a subset of early childhood rhinitis which was associated with atopic predisposition and comorbidities. Persistent respiratory viral shedding may contribute to the symptomatology. Whether this entity is a precursor of subsequent childhood allergic rhinitis will require longer follow-up.

The relationship between allergic rhinitis and viral infections.

PURPOSE OF REVIEW: Viral airway inflammation is one of the most common respiratory conditions. The clinical symptoms of viral rhinitis, especially watery rhinorrhea and nasal congestion, may be similar to the symptoms of allergic rhinitis. Both conditions affect considerable numbers of patients and can lead to many upper airway consequences, especially secondary bacterial infection. Viral infection can also lead to lower respiratory traction conditions such as bronchitis, bronchiolitis, pneumonia and, especially, asthma. This article will review the existing scientific literature examining the linkage and relationship between viral infection and allergic airway disease. RECENT FINDINGS: The relationship between viral and allergic airway inflammation can be discussed in terms of the influence of pathogenesis from one condition to the other. Recently, many studies show how early infection can decrease the chance of allergic development. However, there is some evidence demonstrating that viral infection can deteriorate the clinical symptoms of airway allergy. SUMMARY: Viral infection can affect the immune system and allergy as both 'enhancing effect' and 'protective effect'. The influential factors depend on the virulence of the viral strain, the innate immune system and the environmental conditions.