Royal National Throat Nose and Ear Hospital

Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, 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. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

A new auditory phenomenon has been identified in the acoustic impulse response of the human ear. Using a signal averaging technique, a study has been made of the response of the closed external acoustic meatus to acoustic impulses near to the threshold of audibility. Particular attention has been paid to the waveform of the response at post excitation times in excess of 5 ms. No previous worker appears to have extended observations into this region. The response observed after about 5 ms is not a simple extension of the initial response attributable to the middle ear. The oscillatory response decay time constant was found to change from approximately 1 ms to over 12 ms at about this time. The slowly decaying response component was present in all normal ears tested, but was not present in ears with cochlear deafness. This component of the response appears to have its origin in some nonlinear mechanism probably located in the cochlea, responding mechanically to auditory stimulation, and dependent upon the normal functioning of the cochlea transduction process. A cochlear reflection hypothesis received some support from these results.

OBJECTIVES: We set out to determine the psychometric validation of a disease-specific health related quality of life instrument for use in chronic rhinosinusitis, the 22 item Sinonasal Outcome Test (SNOT-22), a modification of a pre-existing instrument, the SNOT-20. DESIGN, SETTING AND PARTICIPANTS: The National Comparative Audit of Surgery for Nasal Polyposis and Chronic Rhinosinusitis was a prospective cohort study collecting data on 3128 adult patients undergoing sinonasal surgery in 87 NHS hospitals in England and Wales. Data were collected preoperatively and at 3 months after surgery, and analysed to determine validity of the SNOT-22. Test-retest reliability was assessed in a separate cohort of patients in a single centre. MAIN OUTCOME MEASURES: The SNOT-22, a derivative of the SNOT-20 was the main outcome measure. Patients were also asked to report whether they felt better, the same or worse following surgery. To evaluate the SNOT-22, the internal consistency, responsiveness, known group differences and validity were analysed. RESULTS: Preoperative SNOT-22 scores were completed by 2803 patients. 3-month postoperative SNOT-22 scores were available for 2284 patients of all patients who completed a preoperative form (81.5% response rate). The Cronbach's alpha scores for the SNOT-22 were 0.91 indicating high internal consistency. The test-retest reliability coefficient was 0.93, indicating high reliability of repeated measures. The SNOT-22 was able to discriminate between patients known to suffer with chronic rhinosinusitis and a group of healthy controls (P < 0.0001, t = 85.3). It was also able to identify statistically significant differences in sub-groups of patients with chronic rhinosinusitis. There was a statistically significant (P < 0.0001, t = 39.94) decrease in patient reported SNOT-22 scores at 3 months. At 3 months the overall effect size in all patients was 0.81, which is considered large. We found the minimally important difference that is the smallest change in SNOT-22 score that can be detected by a patient, to be 8.9 points. CONCLUSIONS: We have found the SNOT-22 to be valid and easy to use. It can be used to facilitate routine clinical practice to highlight the impact of chronic rhinosinusitis on the patient's quality of life, and may also be used to measure the outcome of surgical intervention. The minimally important difference allows us to interpret scores in a clinical context, and may help to improve patient selection for surgery.

EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. no immunosuppressants IV D no nasal saline irrigation Ib, no data in single use D yes for symptomatic relief topical antibiotics no data D no anti-IL-5 no data D unclear phytotherapy no data D no decongestant topical / oral no data in single use D no mucolytics no data D no oral antihistamine in allergic patients no data D no antimycotics -topical Ia (-) ** A(-) no antimycotics -systemic Ib (-)# A(-) $ no anti leukotrienes Ib (-) A(-) no anti-IgE Ib (-) A(-) no * Some of these studies also included patients with CRS with nasal polyps. % short term antibiotics shows one positive and one negative study. Therefore recommendation C. oral antibiotic short term <4 weeks Ib(-) # A(-)* no intravenous antibiotics III(-) ## C(-) ** no # Ib (-): Ib study with a negative outcome.

Severe acute respiratory syndrome-corona virus-2, which causes coronavirus disease 2019 (COVID-19), is highly contagious. Airway management of patients with COVID-19 is high risk to staff and patients. We aimed to develop principles for airway management of patients with COVID-19 to encourage safe, accurate and swift performance. This consensus statement has been brought together at short notice to advise on airway management for patients with COVID-19, drawing on published literature and immediately available information from clinicians and experts. Recommendations on the prevention of contamination of healthcare workers, the choice of staff involved in airway management, the training required and the selection of equipment are discussed. The fundamental principles of airway management in these settings are described for: emergency tracheal intubation; predicted or unexpected difficult tracheal intubation; cardiac arrest; anaesthetic care; and tracheal extubation. We provide figures to support clinicians in safe airway management of patients with COVID-19. The advice in this document is designed to be adapted in line with local workplace policies.

Contributing Authors Isam Alobid, MD, PhD 1 , Nithin D. Adappa, MD 2 , Henry P. Barham, MD 3 , Thiago Bezerra, MD 4 , Nadieska Caballero, MD 5 , Eugene G. Chang, MD 6 , Gaurav Chawdhary, MD 7 , Philip Chen, MD 8 , John P. Dahl, MD, PhD 9 , Anthony Del Signore, MD 10 , Carrie Flanagan, MD 11 , Daniel N. Frank, PhD 12 , Kai Fruth, MD, PhD 13 , Anne Getz, MD 14 , Samuel Greig, MD 15 , Elisa A. Illing, MD 16 , David W. Jang, MD 17 , Yong Gi Jung, MD 18 , Sammy Khalili, MD, MSc 19 , Cristobal Langdon, MD 20 , Kent Lam, MD 21 , Stella Lee, MD 22 , Seth Lieberman, MD 23 , Patricia Loftus, MD 24 , Luis Macias‐Valle, MD 25 , R. Peter Manes, MD 26 , Jill Mazza, MD 27 , Leandra Mfuna, MD 28 , David Morrissey, MD 29 , Sue Jean Mun, MD 30 , Jonathan B. Overdevest, MD, PhD 31 , Jayant M. Pinto, MD 32 , Jain Ravi, MD 33 , Douglas Reh, MD 34 , Peta L. Sacks, MD 35 , Michael H. Saste, MD 36 , John Schneider, MD, MA 37 , Ahmad R. Sedaghat, MD, PhD 38 , Zachary M. Soler, MD 39 , Neville Teo, MD 40 , Kota Wada, MD 41 , Kevin Welch, MD 42 , Troy D. Woodard, MD 43 , Alan Workman 44 , Yi Chen Zhao, MD 45 , David Zopf, MD 46 Contributing Author Affiliations 1 Universidad de Barcelona; 2 University of Pennsylvania; 3 Louisiana State University Health Sciences Center; 4 Universidade de São Paulo; 5 ENT Specialists of Illinois; 6 University of Arizona; 7 University of Oxford; 8 University of Texas; 9 University of Indiana; 10 Mount Sinai Beth Israel; 11 Emory University; 12 University of Colorado; 13 Wiesbaden, Germany; 14 University of Colorado; 15 University of Alberta; 16 University of Alabama at Birmingham; 17 Duke University; 18 Sungkyunkwan University; 19 University of Pennsylvania; 20 Universidad de Barcelona; 21 Northwestern University; 22 University of Pittsburgh; 23 New York University; 24 Emory University; 25 University of British Columbia; 26 Yale University School of Medicine; 27 Private Practice; 28 Department of Otolaryngology, Hôtel‐Dieu Hospital, Centre de Recherche du Centre Hospitalier de l'Université de Montréal; 29 University of Adelaide; 30 Pusan National University; 31 University of California, San Francisco; 32 University of Chicago; 33 University of Auckland; 34 Johns Hopkins University; 35 University of New South Wales, Australia; 36 Stanford University; 37 Washington University; 38 Harvard Medical School; 39 Medical University of South Carolina; 40 Singapore General Hospital; 41 Taho University; 42 Northwestern University; 43 Cleveland Clinic Foundation; 44 University of Pennsylvania; 45 University of Adelaide; 46 University of Michigan

I. EXECUTIVE SUMMARY: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. METHODS: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. RESULTS: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. CONCLUSION: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

OBJECTIVES: To evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage-PA) targeting antibiotic-resistant Pseudomonas aeruginosa in chronic otitis. DESIGN: Randomised, double-blind, placebo-controlled Phase I/II clinical trial approved by UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Central Office for Research Ethics Committees (COREC) ethical review process. SETTING: A single specialist university hospital. PARTICIPANTS: 24 patients with chronic otitis with a duration of several years (2-58). Each patient had, at the time of entry to the trial, an ear infection because of an antibiotic-resistant P. aeruginosa strain sensitive to one or more of the six phages present in Biophage-PA. Participants were randomised in two groups of 12 treated with either a single dose of Biophage-PA or placebo and followed up at 7, 21 and 42 days after treatment by the same otologist. Ears were thoroughly cleaned on each occasion and clinical and microbiological indicators measured. MAIN OUTCOME MEASURES: Physician assessed erythema/inflammation, ulceration/granulation/polyps, discharge quantity, discharge type and odour using a Visual Analogue Scale (VAS). Patients reported discomfort, itchiness, wetness and smell also using a VAS. Bacterial levels of P. aeruginosa and phage counts from swabs were measured initially and at follow-up. At each visit patients were asked about side effects using a structured form. Digital otoscopic images were obtained on days 0 and 42 for illustrative purposes only. RESULTS: Relative to day 0, pooled patient- and physician-reported clinical indicators improved for the phage treated group relative to the placebo group. Variation from baseline levels was statistically significant for combined data from all clinic days only for the phage treated group. Variation from baseline levels was statistically significant for the majority of the patient assessed clinical indicators only for the phage treated group. P. aeruginosa counts were significantly lower only in the phage treated group. No treatment related adverse event was reported. CONCLUSION: The first controlled clinical trial of a therapeutic bacteriophage preparation showed efficacy and safety in chronic otitis because of chemo-resistant P. aeruginosa.

Emergency and difficult tracheal intubations are hazardous undertakings where successive laryngoscopy-hypoxaemia-re-oxygenation cycles can escalate to airway loss and the 'can't intubate, can't ventilate' scenario. Between 2013 and 2014, we extended the apnoea times of 25 patients with difficult airways who were undergoing general anaesthesia for hypopharyngeal or laryngotracheal surgery. This was achieved through continuous delivery of transnasal high-flow humidified oxygen, initially to provide pre-oxygenation, and continuing as post-oxygenation during intravenous induction of anaesthesia and neuromuscular blockade until a definitive airway was secured. Apnoea time commenced at administration of neuromuscular blockade and ended with commencement of jet ventilation, positive-pressure ventilation or recommencement of spontaneous ventilation. During this time, upper airway patency was maintained with jaw-thrust. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) was used in 15 males and 10 females. Mean (SD [range]) age at treatment was 49 (15 [25-81]) years. The median (IQR [range]) Mallampati grade was 3 (2-3 [2-4]) and direct laryngoscopy grade was 3 (3-3 [2-4]). There were 12 obese patients and nine patients were stridulous. The median (IQR [range]) apnoea time was 14 (9-19 [5-65]) min. No patient experienced arterial desaturation < 90%. Mean (SD [range]) post-apnoea end-tidal (and in four patients, arterial) carbon dioxide level was 7.8 (2.4 [4.9-15.3]) kPa. The rate of increase in end-tidal carbon dioxide was 0.15 kPa.min(-1) . We conclude that THRIVE combines the benefits of 'classical' apnoeic oxygenation with continuous positive airway pressure and gaseous exchange through flow-dependent deadspace flushing. It has the potential to transform the practice of anaesthesia by changing the nature of securing a definitive airway in emergency and difficult intubations from a pressured stop-start process to a smooth and unhurried undertaking.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

BACKGROUND: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments for smell loss are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst the full set of recommendations are outlined in the main document, points include the following: - Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy with small diameter endoscopes. - Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. - Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. - Comprehensive chemosensory assessment should include gustatory screening. - Smell training can be helpful in patients with olfactory loss of several aetiologies. CONCLUSIONS: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Tumours affecting the nose, paranasal sinuses and adjacent skull base are fortunately rare. However, they pose significant problems of management due their late presentation and juxtaposition to important anatomical structures such eye and brain. The increasing application of endonasal endoscopic techniques to their excision offers potentially similar scales of resection but with reduced morbidity. The present document is intended to be a state-of-the art review for any specialist with an interest in this area 1. to update their knowledge of neoplasia affecting the nose, paranasal sinuses and adjacent skull base; 2. to provide an evidence-based review of the diagnostic methods; 3. to provide an evidence-based review of endoscopic techniques in the context of other available treatments; 4. to propose algorithms for the management of the disease; 5. to propose guidance for outcome measurements for research and encourage prospective collection of data. The importance of a multidisciplinary approach, adherence to oncologic principles with intent to cure and need for long-term follow-up is emphasised.

OBJECTIVES: The Lund-Mackay score is widely used in assessment of chronic rhinosinusitis. We aimed to describe its relationship to other measures of pre- and post-treatment health status. STUDY DESIGN: Multicenter prospective study of 1840 patients undergoing surgery for chronic rhinosinusitis in the UK. RESULTS: There was no absolute threshold for surgery, but patients with higher Lund-Mackay scores underwent more extensive surgery. There was no correlation between Lund-Mackay and SNOT-22 scores. The Lund-Mackay increased with increasing grade of polyposis. The Lund-Mackay score was associated with symptom reduction (coefficient = 0.24, P = 0.02) complication rates (odds ratio, 1.08, 95%CI 1.06 to 1.1), and revision rates (odds ratio, 1.03, 95% CI 1.001 to 1.06). CONCLUSIONS: The Lund-Mackay score measures a different aspect of disease to "subjective" symptom scores. However, it correlates well with other markers of disease severity, the nature of surgery offered, and its outcome. SIGNIFICANCE: This demonstrates the strengths and limitations of a commonly used staging system.

Tracheal extubation is a high-risk phase of anaesthesia. The majority of problems that occur during extubation and emergence are of a minor nature, but a small and significant number may result in injury or death. The need for a strategy incorporating extubation is mentioned in several international airway management guidelines, but the subject is not discussed in detail, and the emphasis has been on extubation of the patient with a difficult airway. The Difficult Airway Society has developed guidelines for the safe management of tracheal extubation in adult peri-operative practice. The guidelines discuss the problems arising during extubation and recovery and promote a strategic, stepwise approach to extubation. They emphasise the importance of planning and preparation, and include practical techniques for use in clinical practice and recommendations for post-extubation care.

Awake tracheal intubation has a high success rate and a favourable safety profile but is underused in cases of anticipated difficult airway management. These guidelines are a comprehensive document to support decision making, preparation and practical performance of awake tracheal intubation. We performed a systematic review of the literature seeking all of the available evidence for each element of awake tracheal intubation in order to make recommendations. In the absence of high-quality evidence, expert consensus and a Delphi study were used to formulate recommendations. We highlight key areas of awake tracheal intubation in which specific recommendations were made, which included: indications; procedural setup; checklists; oxygenation; airway topicalisation; sedation; verification of tracheal tube position; complications; management of unsuccessful awake tracheal intubation; post-tracheal intubation management; consent; and training. We recognise that there are a range of techniques and regimens that may be effective and one such example technique is included. Breaking down the key practical elements of awake tracheal intubation into sedation, topicalisation, oxygenation and performance might help practitioners to plan, perform and address complications. These guidelines aim to support clinical practice and help lower the threshold for performing awake tracheal intubation when indicated.

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.

It appears that uvulopalatopharyngoplasty (UVPP) is a reliable procedure for reducing snoring, but much less reliable when used as a treatment for OSAS. This is thought to be because of poor patient selection in that the site of the problem is not always the site of the operation. We present the technique of sleep nasendoscopy which allows direct visualization of the site or sites of obstruction in a sleeping patient. Our study has shown that there are patients with obstructive sleep apnoea syndrome (OSAS) in whom the only site of pharyngeal obstruction is at the velopharynx. These patients should do well with the relatively simple procedure of UVPP. This is not true for many other OSAS patients in whom we found that obstruction was multisegmental. This helps to explain the frequently poor results of UVPP in OSAS patients. We feel that this form of preoperative assessment will avoid unnecessary surgery.

BACKGROUND: The perceptions of patients and physicians regarding the symptoms and impact of allergic rhinitis (AR) were assessed in a prospective, cross-sectional, international survey. This paper presents the combined survey results from five European countries (Germany, France, Italy, Spain and the UK). METHODS: Data were recorded by 1,482 patients and matched with records from 415 primary care physicians and specialists. Diagnostic tests to confirm AR had been performed on 1,279 (86.3%) patients. Both physicians and patients recorded the presence, severity and impact of symptoms at the time of consultation in addition to those symptoms frequently, but not currently, present. Health-related quality of life (HRQoL) was assessed using the Mini Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: A large proportion of patients had moderate-severe disease (67.2%; n = 996), persistent disease (42.5%; n = 630) and comorbidities such as asthma (31.5%; n = 467). Overall, patients rated their disease as more severe than did physicians (P < 0.001). At the time of the consultation, one-third of all patients reported that their current nasal and ocular symptoms were moderate or severe in nature. According to the physicians' assessment, good control of nasal and ocular symptoms was achieved in 45.4% (n = 673) and 51.3% (n = 760) of patients, respectively, and poor symptom control in 18.0% (n = 267) and 12.1% (n = 179). Overall, 43.3% (n = 641) of those surveyed were using two or more medicines for their AR. Health-related quality of life was correlated with disease severity and with the number of days without symptoms in the previous 4 weeks. Allergic rhinitis had a significantly greater impact in patients with more persistent disease than in those with intermittent disease (2.3 +/- 1.3 vs 1.9 +/- 1.2; P < 0.001). Nonetheless, 81.8% (n = 601) of patients with intermittent disease reported some impairment of their daily life as a result of their AR. CONCLUSIONS: Allergic rhinitis remains a significant health problem because of the high burden of symptoms and its impact on general well being and HRQoL among patients consulting for this condition. Overall, there was a poor correlation between patients and physicians in the reporting of disease severity.

What happens to inorganic nanoparticles (NPs), such as plasmonic gold or silver, superparamagnetic iron oxide, or fluorescent quantum dot NPs after they have been administrated to a living being? This review discusses the integrity, biodistribution, and fate of NPs after in vivo administration. The hybrid nature of the NPs is described, conceptually divided into the inorganic core, the engineered surface coating comprising of the ligand shell and optionally also bio-conjugates, and the corona of adsorbed biological molecules. Empirical evidence shows that all of these three compounds may degrade individually in vivo and can drastically modify the life cycle and biodistribution of the whole heterostructure. Thus, the NPs may be decomposed into different parts, whose biodistribution and fate would need to be analyzed individually. Multiple labeling and quantification strategies for such a purpose will be discussed. All reviewed data indicate that NPs in vivo should no longer be considered as homogeneous entities, but should be seen as inorganic/organic/biological nano-hybrids with complex and intricately linked distribution and degradation pathways.