This EAACI position paper aims at providing a state‐of‐the‐art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic ...noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug‐induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called “entopy” or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.
. Bachert C, Zhang N (Ghent University Hospital, Ghent, Belgium). Chronic rhinosinusitis and asthma: novel understanding of the role of IgE ‘above atopy’ (Review). J Intern Med 2012; 272: 133–143.
...Chronic rhinosinusitis (CRS) affects more than 10% of the European population and is often associated with asthma. Phenotypes of CRS can be differentiated based on mucosal remodelling and inflammatory patterns. Understanding the role of central mediators, such as interleukin‐5, in these different phenotypes may lead to the development of specific therapeutic approaches. The impact of staphylococcal superantigens has been shown to further modify the immune response, contributing to persistent severe disease via the activation of T and B cells and the formation of local IgE. It is clear that these mechanisms are involved in the systemic spread of upper airway disease with resulting asthma comorbidity, when IgE antibodies to staphylococcal enterotoxins are present at measurable levels in serum. Recent findings point to superantigens as possible causal agents in the intrinsic form of severe asthma, and an anti‐IgE strategy has shown promising therapeutic potential in nonatopic patients with nasal polyps and asthma. These findings should lead to a clinically relevant endotyping of patients with upper and lower airway disease and to a new understanding of the role of IgE ‘above atopy’.
The mucosal lining of the upper airways represents the outer surface of the body to the ambient air and its contents and is prepared for it as the first line of defense. Apart from the well‐described ...physical barrier and the mucociliary clearance, a variety of systems, including the airway microbiome, antimicrobial proteins, damage‐associated molecular patterns, innate lymphoid cells, epithelial‐derived cytokines and chemokines, and finally the adaptive immune system, as well as eosinophils as newly appreciated defense cells form different levels of protection against and response to any possible intruder. Of interest especially for allergic airway disease, mucosal germs might not just elicit a classical Th1/Th17‐biased inflammatory response, but may directly induce a type‐2 mucosal inflammation. Innovative therapeutic interventions may be possible at different levels also; however, whether modulations of the innate or adaptive immune responses will finally be more successful, and how the correction of the adaptive immune response might impact on the innate side, will be determined in the near future.
Background
The prevalence of allergic rhinitis (AR) has increased worldwide in recent decades. This study was conducted to investigate the prevalence of self‐reported AR and profiles of AR‐related ...comorbidities in the adult population of China over time.
Methods
This study surveyed residents of 18 major cities in mainland China. Telephone interviews were conducted with study participants after sampling target telephone numbers by random digit dialing. The questions asked during telephone interviews were based on those included in validated questionnaires and focused on topics regarding AR, nonallergic rhinitis (NAR), acute/chronic rhinosinusitis (ARS/CRS), asthma, and atopic dermatitis (AD).
Results
During 2011, a total of 47 216 telephone interviews were conducted, and the overall response rate was 77.5%. When compared with the AR prevalence in 11 cities surveyed in 2005, there was a significant increase in self‐reported adult AR in eight of those cities (P < 0.01). In 2011, the standardized prevalence of self‐reported adult AR in the 18 cities was 17.6%. The concentration of SO2 was positively correlated with the prevalence of AR (r = 0.504, P = 0.033). A multiple regression model showed that the absolute change in household yearly income was significantly associated with the change in the prevalence of AR (R2 = 0.68), after adjusting for PM10, SO2, NO2, temperature, and humidity. The overall prevalences of NAR, ARS, CRS, asthma, and AD in the general population were 16.4%, 5.4%, 2.1%, 5.8%, and 14%, respectively.
Conclusion
During a 6‐year period, there was a significant increase in the prevalence of self‐reported AR in the general Chinese adult population. The incidence of AR being accompanied by rhinosinusitis, asthma, or AD was significantly higher among individuals having self‐reported AR compared with the general population.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammation-mediated disease of the nasal mucosa and paranasal sinuses with an under-recognized clinical, humanistic, and ...economic burden. Patients with CRSwNP experience a high symptom burden, including nasal congestion, loss of smell, and rhinorrhea, which has a negative impact on physical and mental health-related quality of life, including sleep quality. Existing medical and surgical interventions, including local and systemic corticosteroids and endoscopic sinus surgery, may be associated with recurrence of nasal polyps and associated symptoms and with an increased risk of short- and long-term adverse effects, especially with repeated or long-term use. Because type 2 inflammation is implicated in the pathogenesis of several coexisting diseases, patients with CRSwNP often have comorbid asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. These patients, as well as those with high corticosteroid use and/or sinonasal surgical history, have more severe disease and associated symptom burden and represent a difficult-to-treat population under the existing management paradigm. This article reviews the clinical, humanistic, and economic burden of CRSwNP; it highlights the unmet need for effective and safe CRSwNP therapies that effectively control symptoms and minimize recurrence by targeting the underlying type 2 inflammatory disease pathophysiology.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex upper airway disease affecting up to 11% of the population of Western Europe. In these western countries, 85% of the CRSwNP disease ...reveals a type 2 inflammatory pattern. In the last 15 years, several randomized double-blind studies on monoclonal antibodies in CRSwNP were performed. These studies demonstrated for the first time that biologics targeting type 2 immune reactions might be successful in nasal polyps. The target proteins, interleukin (IL)-4, IL-5, IL-13, and IgE were previously identified as key mediators in studies using nasal polyp tissues to measure and to interact in ex-vivo settings. No biomarkers have been identified to predict response to a specific biologic or to monitor treatment success. These studies were characterized by small numbers of patients and heterogeneous populations. They did, however, pave the way for currently performed and analyzed phase 3 studies, which will possibly lead to the registration of the first biologic drug with the indication CRSwNP. The studies already provide indications on the effects to be expected from those biologics; the results of phase-3 studies in larger populations will be decisive for the indications, patient selection, and finally the stopping rules for those drugs in subjects with severe nasal polyps, in whom the current standard of care including topical and oral glucocorticosteroids, antibiotics and surgical procedures failed to control the disease. We may expect that those biologics will open new perspectives for those patients with severe polyposis with, but also independent of asthma, allowing to avoid the possible adverse events resulting from systemic glucocorticosteroids and surgery.
Airway diseases such as chronic rhinosinusitis, asthma, and chronic obstructive pulmonary disorder are characterized by inflammation and remodeling. Among inflammatory and extracellular matrix ...regulatory cytokines, transforming growth factor‐beta (TGF‐β) stands central, as it possesses both important immunomodulatory and fibrogenic activities, and should be considered a key for understanding inflammation and remodeling processes. This review will briefly summarize the recent findings on the role of TGF‐β1, from the view points of inflammation and remodeling, and discuss the role of TGF‐β in the upper and lower airway diseases. This may reveal new perspectives in the understanding of airway inflammation and remodeling processes and may open innovative treatment strategies for the regulation of TGF‐β1.
Background: Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of sinus diseases, which may cover different disease entities, or may represent a disease continuum. Studying ...inflammatory cells and mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases.
Methods: Sinonasal mucosal tissue from 10 nasal polyp (NP) patients, 13 cystic fibrosis patients (CF‐NP), eight CRS subjects without polyps, and nine control patients were stained for CD3, CD25, CD68, CD20, myeloperoxidase (MPO), CD138 and tissue homogenates were assayed for eotaxin, interleukin (IL)‐1β, IL‐2sRα, IL‐5, interferon (IFN)‐γ, IL‐8, transforming growth factor (TGF)‐β1, tumor necrosis factor‐α, and MPO by enzyme‐linked immunosorbent assay or UNICAP system.
Results: Nasal polyp and CF‐NP showed increased numbers and activation of T cells, while only NP displayed an increase in plasma cells. Nasal polyp had significantly higher levels of eosinophilic markers eosinophils, eotaxin, and eosinophil cationic protein (ECP) compared with CRS, controls and CF‐NP. Chronic rhinosinusitis was characterized by a Th1 polarization with high levels of IFN‐γ and TGF‐β, while NP showed a Th2 polarization with high IL‐5 and immunoglobulin (Ig) E concentrations. Nasal polyp and CF‐NP were discriminated by edema from CRS and controls, with CF‐NP displaying a very prominent neutrophilic inflammation.
Conclusion: Based on cellular and mediator profiles, we suggest that CRS, NP, and CF‐NP are distinct disease entities within the group of chronic sinus diseases.
State‐of‐the‐art documents like ARIA and EPOS provide clinicians with evidence‐based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently ...available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so‐called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline‐directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment‐related, diagnosis‐related and/or patient‐related factors. Treatment‐related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom‐oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient‐related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.
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