Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations.

In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease.

This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work.

The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available.

Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed.

The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

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Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

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.

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European Position Paper on Rhinosinusitis and Nasal Polyps 2020

Background: Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat the approximately 500 million affected patients globally. Objective: To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. Methods: The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. Results: This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. Conclusion: These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions.

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Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 Revision

Metastasis involves the spread of cancer cells from the primary tumor to surrounding tissues and to distant organs and is the primary cause of cancer morbidity and mortality. In order to complete the metastatic cascade, cancer cells must detach from the primary tumor, intravasate into the circulatory and lymphatic systems, evade immune attack, extravasate at distant capillary beds, and invade and proliferate in distant organs. Currently, several hypotheses have been advanced to explain the origin of cancer metastasis. These involve an epithelial mesenchymal transition, an accumulation of mutations in stem cells, a macrophage facilitation process, and a macrophage origin involving either transformation or fusion hybridization with neoplastic cells. Many of the properties of metastatic cancer cells are also seen in normal macrophages. A macrophage origin of metastasis can also explain the long-standing "seed and soil" hypothesis and the absence of metastasis in plant cancers. The view of metastasis as a macrophage metabolic disease can provide novel insight for therapeutic management.

On the Origin of Cancer Metastasis

Background The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. Conclusion As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/alr.21695

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis.

Nasal obstruction can be monitored objectively by measurement of nasal airflow, as evaluated by nasal peak flow, or as airways resistance/conductance as evaluated by rhinomanometry. Peak flow can be measured during inspiration or expiration. Of these measurements, nasal inspiratory peak flow is the best validated technique for home monitoring in clinical trials. The equipment is portable, relatively inexpensive, and simple to use. One disadvantage, however, is that nasal inspiratory peak flow is influenced by lower airway as well as upper airway function. Rhinomanometry is a more sensitive technique that is specific for nasal measurements. The equipment, however, requires an operator, is more expensive, and is not portable. Thus, it is applicable only for clinic visit measures in clinical trials. Measurements require patient cooperation and coordination, and not all can achieve repeatable results. Thus, this objective measure is best suited to laboratory challenge studies involving smaller numbers of selected volunteers. A nonphysiological measure of nasal patency is acoustic rhinometry. This sonic echo technique measures internal nasal luminal volume and the minimum cross-sectional area. The derivation of these measures from the reflected sound waves requires complex mathematical transformation and makes several theoretical assumptions. Despite this, however, such measures correlate well with the nasal physiological measures, and the nasal volume measures have been shown to relate well to results obtained by imaging techniques such as computed tomography scanning or magnetic resonance imaging. Like rhinomanometry, acoustic rhinometry is not suitable for home monitoring and can be applied only to clinic visit measures or for laboratory nasal challenge monitoring. It has advantages in being easy to use, in requiring little patient cooperation, and in providing repeatable results. In addition to nasal obstruction, allergic rhinitis is recognized to be associated with impaired mucociliary clearance and altered nasal responsiveness. Measures exist for the monitoring of these aspects of nasal dysfunction. Although measures of mucociliary clearance are simple to perform, they have a poor record of reproducibility. Their incorporation into clinical trials is thus questionable, although positive outcomes from therapeutic intervention have been reported. Measures of nasal responsiveness are at present largely confined to research studies investigating disease mechanisms in allergic and nonallergic rhinitis. The techniques are insufficiently standardized to be applied to multicenter clinical trials but could be used in limited-center studies to gain insight into the regulatory effects of different therapeutic modalities.

https://www.jacionline.org/article/S0091-6749(04)03271-3/pdf

Objective monitoring of nasal patency and nasal physiology in rhinitis

Objectives/Hypothesis: The aim of this study was to evaluate the effects of a nonabsorbable packing (NAP) in the middle meatus (MM) for 5 days after sinus surgery.



Study Design: A randomized, partly blinded, controlled clinical trial.



Methods: Sixty-one patients (M/F = 30/31, mean age 42, range 18–72) with chronic or acute recurrent rhinosinusitis were included. Fifty-nine underwent surgery. Thirty-one had NAP in the MM for 5 days, and 28 served as controls with daily saline irrigations postoperatively. Primary outcome variables were nasal congestion, nasal pain, and headache the first 2 weeks rated on visual analogue scales (VAS; 0–100) and the amount of postoperative bleeding recorded on an ordinal scale (1–4). Secondary outcome variable was the extent of adhesions in MM 10 to 14 weeks after surgery judged by blinded evaluation of endoscopic video recordings.



Results: Fifty-eight patients completed a diary. No significant differences in primary outcome variables between the groups were found. Nasal congestion decreased most the first 5 to 7 days postoperatively. Removal of the NAP caused little pain (mean 23 on VAS). Temporary bleeding occurred in three patients. Bilateral adhesions were observed in 10 control patients but in none with NAP. Unilateral adhesions were found in nine control patients and in seven with NAP (exact P < .001).



Conclusions: NAP in the MM for 5 days significantly reduced the extent of adhesions in MM compared with saline irrigation alone. NAP did not cause additional discomfort.

Effects of nonabsorbable packing in middle meatus after sinus surgery.

Objectives/Hypothesis: It is still a matter of controversy to what extent the sense of nasal obstruction is associated with objective measures for nasal space and airflow. Knowledge about this is important in the evaluation of nasal complaints and the planning of its treatment. In this study, we evaluated the relationship between subjective nasal obstruction and the corresponding anatomic and physiological nasal parameters using acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF).



Study Design: Two thousand five hundred twenty-three consecutive patients were included in this cross-sectional study. Eligible subjects were adults referred to the Ear, Nose, and Throat Department, Sorlandet Hospital, Kristiansand, Norway, for evaluation of chronic nasal or sleep related complaints.



Methods: Subjects underwent AR and nasal flow measurements. Subjective grading of nasal obstruction was obtained by a nasal obstruction visual analogue scale. Associations between nasal obstruction visual analogue scale scores, AR, and PNIF were assessed using multiple linear regression, adjusting for age, gender, body mass index, and asthma, allergy, and smoking history.



Results: The sense of nasal obstruction was associated with nasal cavity volumes in both anterior and middle segments of the nasal cavities, with minimal cross-sectional areas in middle segments and for the nasal cavity as a whole, and with PNIF. Associations with minimal cross-sectional areas in anterior segments did not reach significance.



Conclusions: The present study demonstrates highly significant associations between the subjective sensation of nasal obstruction and corresponding measures for nasal cavity volume, area, and airflow. We conclude that AR and PNIF are valuable objective instruments for evaluation of subjective nasal obstruction.

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Does nasal obstruction mean that the nose is obstructed

A stationary tissue culture system for reaggregation cultures of rat brain cells is described. Aggregates were formed by placing cells at high concentrations in liquid overlay cultures on a nonadherent nutrient agar surface. No physical stress in the form of rotation or shaking was applied to the aggregating cell population. Transmission electron microscopy and immunohistochemistry showed that the cells developed from homogeneously dispersed, immature cells in Day 4 aggregates, to mature astrocytes, oligodendrocytes, and neurons in Day 20 aggregates. Twenty days and older aggregates had a tightly packed neuropil which was most prominent in a cell-sparse outer layer of the aggregates. When the aggregates were allowed to adhere to a substrate, both glial fibrillary acidic protein (GFAP) positive and negative cells were observed migrating out from the aggregates. Cells giving a positive reaction for neuron specific enolase (NSE) were also present. This reaggregation procedure, with transfer of selected brain cell aggregates into agar-coated multiwells is an alternative three-dimensional culture system which can be potentially useful in the study of morphogenesis and cell interactions in the nervous system.

Reaggregation of fetal rat brain cells in a stationary culture system. I: Methodology and cell identification.

Objectives/Hypothesis: The aim of this randomized, partly blinded, controlled clinical trial was to evaluate the effects of debridement 6 and 12 days after endoscopic sinus surgery.

Methods: Sixty patients (male/female = 26/34; mean age, 43.5 years; age range, 23–73 years) with chronic or acute recurrent rhinosinusitis were included. The patients were randomized to postoperative debridement or not. Primary outcome variables were adhesions between the middle turbinate and the lateral nasal wall 10 to 14 weeks after surgery judged by blinded evaluation of endoscopic video recordings. Secondary outcome variables were crusts in the nasal cavity 12 days after surgery and pain caused by debridement.

Results: We found a significant reduction in adhesions in the group that underwent debridement (P < .001). At 12 weeks, bilateral adhesions were observed in nine control patients but in only one debridement patient. Unilateral adhesions were found in 11 control patients and in nine debridement patients. Twelve days after surgery, we found significantly less severe crusts in the debridement group (P < .01). Patients with severe crusts in the middle meatus 12 days after surgery had more adhesions 12 weeks postoperatively. The debridement group used more analgesics the days after the first debridement (3.7 days [standard deviation 2.3] vs. 2.3 days [standard deviation 2.6] in the control group, P < .041).

Conclusions: Crusts in the middle meatus after sinus surgery is associated with postoperative adhesions. Debridement of the nasal cavity reduces crusts and postoperative adhesions significantly compared with saline irrigation only. However, the procedure induces more postoperative nasal pain.

Sverre K. Steinsvåg

Papers

Objective monitoring of nasal patency and nasal physiology in rhinitis

Effects of nonabsorbable packing in middle meatus after sinus surgery.

Does nasal obstruction mean that the nose is obstructed

Reaggregation of fetal rat brain cells in a stationary culture system. I: Methodology and cell identification.

The Effects of Debridement After Endoscopic Sinus Surgery