Local allergic rhinitis - a narrative review.

This narrative review aims to provide an up-to-date definition of local allergic rhinitis (LAR), its classification, mechanisms, comorbidities, recommendations for diagnosis and treatment, and define needs in this area. Both 'PubMed' and 'Science Direct' literature was reviewed systematically, and a manual search for studies not previously encountered in the databases was also carried out. Published studies were identified in PubMed covering the period from 1947 to 2022. The following keyword search strategy was used: (local allergic rhinitis* OR entopy* OR local Immunoglobulin E * OR nasal specific Immunoglobulin E). LAR involves Type 2 nasal inflammation with local IgE and cannot be diagnosed by systemic methods, such as skin prick or blood IgE tests. A nasal allergen challenge is necessary for diagnosis. LAR can respond to usual AR treatments, including allergen specific immunotherapy (AIT). LAR is a novel entity that requires additional investigation in terms of prevalence, proper diagnosis, treatment, and prognosis. The target outcomes and possible benefits of this review are to achieve a consensus for the study and diagnosis of LAR and increase interest in this area.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

The intranasal trigeminal system: roles in rhinitis (allergic and non-allergic).

The aim of this paper is to review intranasal trigeminal system and associated reflexes. The literature survey was performed on PubMed, ProQuest Central database of Kirikkale University and Google Scholar. The intranasal trigeminal system and associated reflexes play an important role in humans in both health and disease, including in rhinitis of non-allergic and mixed type. The intranasal trigeminal nerve provides sensory perception to the lining of the nose, supplying information on how patent the nasal airway is and responding to various chemical signals. The reflexes known to exist within the intranasal trigeminal system are nasobronchial reflex, trigemino-cardiac reflex, nasogastric reflex, and nasal cycle. The intranasal trigeminal system and its reflexes play a vital role in normal human physiology. Alterations in how this system operates may underlie multiple forms of rhinitis and more research is needed to fully understand the mechanisms involved.

Novel insight into Robert's cytoprotection: complex therapeutic effect of cytoprotective pentadecapeptide pentadecapeptide BPC 157 in rats with perforated stomach throughout modulation of nitric oxide-system. Comparison with L-arginine, ranitidine and pantoprazole therapy and L-NG-nitro-L-arginine methyl ester worsening.

Surgically perforated stomach (since direct injury in rats until persisting defect and huge adhesions (day 1, day 7)) fairly represent an unresolved cytoprotection issue, and thereby, we focused resolving of the immediate triad, particular vascular failure (vessels 'disappear'/empty), prolonged bleeding, debilitated defect large widening. Agents (mg/kg) or saline (controls) were given at 1 min post-injury as an abdominal bath (10 ml/rat throughout 2 min). Within 1 - 15 min post-injury period, with cytoprotective BPC 157 (0.01 µg), the rapidly restored vessels 'run' (vessels filled/reappeared) toward the perforated defect, and there is less bleeding, and defect contraction; advanced perforated lesion healing (day 1) to complete healing (day 7), and less adhesions. With pantoprazole (10 mg), early (vessels (worsening), bleeding (prolongation), defect (attenuated widening)) effect means eventual lesions and adhesions severity as in controls. Ranitidine (10 mg) early effect (vessels (improvement), bleeding (less bleeding), defect (eliminated widening, defect not changed)) means final lesions attenuation, but not complete healing, less adhesions. L-NAME (5 mg) early (vessels worsening, less bleeding, attenuated defect widening) and final (lesions aggravation, more adhesions) effect, versus L-arginine (100 mg) early (vessels improvement, more bleeding, attenuated defect widening) and final (lesions attenuation, less adhesions) effect, combined few simultaneously occurring nitric oxide (NO)-system distinct processes. Finally, in the stomach tissue surrounding defect, increased malondialdehyde (MDA)- and decreased NO-values, BPC 157 reversed to the normal healthy values, and mRNA expression studies (Cox2, VEGFa, Nos1, Nos 2, Nos3, Nkap (NF-kappa-B-activating protein gene)), done at that very early post-perforation-time, indicate a way how BPC 157 may act beneficially in the perforated stomach lesion throughout NO- and prostaglandinds-system.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

Multi-morbidities of allergic rhinitis in adults: European Academy of Allergy and Clinical Immunology Task Force Report.

This report has been prepared by the European Academy of Allergy and Clinical Immunology Task Force on Allergic Rhinitis (AR) comorbidities. The aim of this multidisciplinary European consensus document is to highlight the role of multimorbidities in the definition, classification, mechanisms, recommendations for diagnosis and treatment of AR, and to define the needs in this neglected area by a literature review. AR is a systemic allergic disease and is generally associated with numerous multi-morbid disorders, including asthma, eczema, food allergies, eosinophilic oesophagitis (EoE), conjunctivitis, chronic middle ear effusions, rhinosinusitis, adenoid hypertrophy, olfaction disorders, obstructive sleep apnea, disordered sleep and consequent behavioural and educational effects. This report provides up-to-date usable information to: (1) improve the knowledge and skills of allergists, so as to ultimately improve the overall quality of patient care; (2) to increase interest in this area; and (3) to present a unique contribution to the field of upper inflammatory disease.

Non-allergic rhinitis: Position paper of the European Academy of Allergy and Clinical Immunology.

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.

Severe Chronic Upper Airway Disease (SCUAD) in children. Definition issues and requirements.

OBJECTIVES: Upper airway diseases are extremely common, and a significant proportion of patients are not adequately controlled by contemporary treatment algorithms. The term SCUAD (Severe Chronic Upper Airway Disease) has been previously introduced to describe such cases. However, this term has not been adequately focused on children. METHODS: This study aims to address the necessity of the term, as well as further details specifically for children. For this purpose, a review was performed of the current literature, with specific focus on issues regarding SCUAD in children. RESULTS: Paediatric SCUAD represents a heterogeneous group of patients and has significant clinical and socioeconomic implications. Relevant literature is generally lacking and questions regarding definition and pathogenesis remain unanswered. CONCLUSIONS: Accurate definition and acknowledgement of paediatric SCUAD cases may lead to better design of future clinical and molecular research protocols. This may provide improved understanding of the underlying disease processes, more accurate data regarding socioeconomic burden, and, above all, more successful treatment and prevention strategies.

Algorithm for navigated ESS.

ENT navigation has given new opportunities in performing Endoscopic Sinus Surgery (ESS) and improving surgical outcome of the patients` treatment. ESS assisted by a navigation system could be called Navigated Endoscopic Sinus Surgery (NESS). As it is generally accepted that the NESS should be performed only in cases of complex anatomy and pathology, it has not yet been established as a state-of-the-art procedure and thus not used on a daily basis. This paper presents an algorithm for use of a navigation system for basic ESS in the treatment of chronic rhinosinusitis (CRS). The algorithm includes five units that should be highlighted using a navigation system. They are as follows: 1) nasal vestibule unit, 2) OMC unit, 3) anterior ethmoid unit, 4) posterior ethmoid unit, and 5) sphenoid unit. Each unit has a shape of a triangular pyramid and consists of at least four reference points or landmarks. As many landmarks as possible should be marked when determining one of the five units. Navigated orientation in each unit should always precede any surgical intervention. The algorithm should improve the learning curve of trainees and enable surgeons to use the navigation system routinely and systematically.

Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?

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.

Executive summary of European Task Force document on diagnostic tools in rhinology.

This Executive Summary of the EAACI Task Force document on Diagnostic Tools in Rhinology provides the readers with an over- view of the currently available tools for diagnosis of nasal and sino-nasal disease, published in full version in the first issue of Clini- cal and Translational Allergy. A panel of European experts in the field of Rhinology have contributed to this consensus document on Diagnostic Tools in Rhinology. Important issues related to history taking, clinical examination and additional investigative tools for evaluation of the severity of nasal and sinonasal disease are briefly highlighted in this executive summary.

Lack of efficacy of long-term, low-dose azithromycin in chronic rhinosinusitis: a randomized controlled trial.

BACKGROUND: In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long-term, low-dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo-controlled trial evaluating the efficacy of azithromycin (AZM) in CRS. METHODS: We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post-therapy. The assessments included Sino-Nasal Outcome Test-22 (SNOT-22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form-36 (SF-36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin' Sticks smell tests and endoscopically guided middle meatus cultures. RESULTS: Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT-22, Patient Response Rating Scale, VAS scores and SF-36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either. CONCLUSION: At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under-dosage of AZM and under-powering of the study. Therefore, more research is urgently required.

Capsaicin significantly reduces sinonasal polyps.

Some reports indicate that topical nasal treatment with capsaicin, which is usually effective in reducing symptoms of vasomotor rhinitis, may also reduce symptoms in patients with nasal polyps. The aim of this study was to investigate the effect of topical capsaicin treatment in severe sinonasal polyposis. Nine non-allergic, non-asthmatic patients with diffuse eosinophilic nasal polyposis were subjected to topical capsaicin treatment: for 3 consecutive days 0.5 ml 30 micromol/l capsaicin solution and on days 4 and 5 100 micromol/l capsaicin solution was sprayed into each nostril. Coronary computed tomography (CT) images were made shortly before treatment. Baseline nasal lavages and a questionnaire containing subjective symptoms and nasal endosocpy were taken just prior to the first application. Nasal lavages were performed prior to and after the last treatment and over 4 weeks, endoscopy and subjective scores at each weekly visit, and correspondent CT scans 4 weeks after the treatment. CT images were analysed by computer, calculating the nose sinuses air volume (NSAV) from the surface of aerated parts of nasal and sinus cavities for each slice per patient prior to and after treatment. Statistical analysis was performed comparing NSAV, subjective scores, endoscopy scores and eosinophil cationic protein (ECP) levels in nasal lavages prior to and after treatment. Topical treatment with capsaicin significantly increased NSAV and very significantly improved subjective and endoscopy scores, but did not significantly alter ECP levels in nasal lavages.

Effect of cromolyn pre-treatment on capsaicin-induced rhinitis in rats.

The effect of cromolyn sodium local pre-treatment on capsaicin-induced rhinitis in rats was studied by analyzing tissue changes due to edema, inflammatory cell infiltration and IgA upregulation. Nasal mucosa samples were stained with hematoxylin-eosin and examined immunohistochemically with monoclonal IgA antibodies. Changes were analyzed at 6, 12 and 72 h after capsaicin treatment and were scored semiquantitatively. Results showed that local cromolyn pre-treatment modified all parameters observed in the nasal mucosa following capsaicin-induced rhinitis in the rats.

Distilled water nasal provocation in hyperreactive patients.

Nonisotonic aerosol may act as a provocation agent in the upper and lower airways of hyperreactive individuals. The purpose of the study was to compare the results of nasal challenge with distilled water in patients with allergic rhinitis to those with noninfective nonallergic rhinitis (NINAR), with respect to the potential clinical use of the obtained data. A group of 68 ambulatory patients with allergic rhinitis or NINAR (39 perennial allergic, 6 seasonal, 23 NINAR) were challenged with 10 mL of distilled water aerosol after the baseline active anterior rhinomanometry. Patients with nasal polyposis at endoscopy, significant unilateral septal deviation, positive bacteriologic swab, recent nasal surgery, and uncertain anamnestic data about the medication taken 6 weeks before the provocation were excluded from the study. After 10 minutes of nasal provocation, rhinomanometry was repeated to assess the response. In 15 patients of the perennial allergic group, the same measurements were performed after a 2-week oral antihistamine and topical steroid therapy. Nasal resistance was significantly increased on the more patent side of the nose after nasal provocation with distilled water aerosol in allergic patients in comparison to the nasal resistance before provocation. In the patients with NINAR, the provocation resulted in a significant rise on the more patent side, but the total nasal airway resistance (NAR) levels were also significantly increased. The systemic antihistamine and topical steroid 2-week therapy in patients with perennial allergic rhinitis significantly reduced the response to nasal distilled water provocation. Nasal provocation with distilled water aerosol is a cheap, simple, and acceptable method that provides useful clinical data on the level of nonspecific nasal hyperreactivity and the therapy success.

Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.

Protection of BPC 157 on capsaicin-induced rhinitis was studied in Wistar rats for its effect on mastocyte infiltration, degranulation and inflammatory cell infiltration. Animals were pretreated with 10 microg/kg, 10 ng/kg or 2 ml saline i.p. and capsaicin (0.05 ml/nostril of 1750 nmol/l sol.) was applied intranasally. They were then euthanized at 1, 3 and 12 h after capsaicin provocation. Nasal mucosa was analyzed and scored for mastocyte infiltration, degranulation and inflammatory cell infiltration. BPC 157 pretreatment significantly prevented mastocyte infiltration at 1 h. Polymorphonuclear leukocyte infiltration was significantly reduced in rats pretreated with 10 microg/kg BPC 157. A dose-dependent effect of BPC 157 pretreatment was demonstrated only for polymorphonuclear leukocyte infiltration at 12 h.

Adaptation to oral breathing after anterior nasal packing.

We report the changes in blood gas tensions in a group of 17 patients during a five-day period of anterior nasal packing after endonasal surgery. Significant hypocapnia was observed in the early postoperative period, which was followed by significant hypoxemia within the first 48 h after surgery, and also shortly after removal of the nasal pack. Analyses of the changes in blood gas tensions suggested disturbances in the ventilation-perfusion ratio. Most subjects required a period of 48 h to adapt to oral breathing.

Compensatory mechanisms induced by high oropharyngeal airway resistance in rats.

Acid base balance changes were observed during 72 h following bilateral nasal obstruction in rats. Mouth breathing caused acute respiratory acidosis and marked aerophagia, leading to spontaneous death of the experimental animal 80 to 90 h postoperatively. Stenotic oropharyngeal airway, due to palatal-epiglottic approximation, is supposed to be responsible for respiratory insufficiency in the nose obstructed rats. The compensatory changes in respiratory mechanics caused by high oropharyngeal airway resistance, together with some possible reflex changes, may have caused either air swallowing or aspiration. As changes in acid base balance parameters did not show breakdown of the compensatory mechanisms during the first 72 h postoperatively, it is supposed that the increased air volume in stomach and guts, causing elevation of the diaphragm and paralytic ileus, contributed to the experimental animals' death.