The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Personal protection and delivery of rhinologic and endoscopic skull base procedures during the COVID-19 outbreak.

On March 11th 2020, the World Health Organization (WHO) declared COVID-19 pandemic, with subsequent profound impact on the entire health care system. During the COVID-19 outbreak, activities in the rhinology outpatient clinic and operation rooms are limited to emergency care only. Health care practitioners are faced with the need to perform rhinological and skull base emergency procedures in patients with a positive or unknown COVID-19 status. This article aims to provide recommendations and relevant information for rhinologists, based on the limited amount of (anecdotal) data, to guarantee high-quality patient care and adequate levels of infection prevention in the rhinology clinic.

The Global Allergy and Asthma European Network (GALEN rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common yet under-recognised chronic inflammatory disease of the nose and paranasal sinuses that is classified according to the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. METHODS: This paper reports the methodology and descriptive results of the Global Allergy and Asthma European Network (GALEN) rhinosinusitis cohort. We established a large CRS cohort within the GALEN consortium (European FP6 research initiative) to identify inflammatory endotypes, the natural disease course, and its impact on health-related quality of life (HRQoL). Detailed information on the impact of CRS on HRQoL, comorbidity incidence, objective disease measures, and medical and surgical treatments were collected. RESULTS: This multicentre cross-sectional case-control study recruited 935 adults (869 eligible for analysis: 237 CRSsNP; 445 CRSwNP; 187 controls [reference group]). Comorbidities such as asthma, allergy, eczema, food allergy, urticaria, and chronic obstructive pulmonary disease were significantly more frequent in CRS patients. Nasal corticosteroids, antibiotics, and oral corticosteroids were the most common treatments. Significantly more CRSwNP patients reported previous sinonasal surgery. CONCLUSIONS: This study provides detailed information that facilitates studying CRS and its main phenotypes. However, patient distribution of this study does not necessarily reflect disease distribution in the general population.

The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life.

BACKGROUND: Chronic rhinosinusitis (CRS) significantly affects health-related quality of life (HRQoL). Few multinational observational studies have evaluated the impact of CRS with nasal polyps (CRSwNP) on patients’ HRQoL. This study aimed to assess HRQoL outcomes (including analyses by disease severity and impact of comorbidities and refractory disease) in CRSwNP patients from a large European database. METHODOLOGY: Data were analysed from the Global Allergy and Asthma European Network (GALEN) Rhinosinusitis Cohort, including sociodemographic data, patient-reported disease severity (visual analogue scale), and scores on the 36-Item ShortForm Health Survey (SF-36) questionnaire. Differences in mean SF-36 scores were evaluated between patients with CRSwNP and population norms and between subgroups of interest (disease severity, comorbidity, and refractory disease, defined by a history of sinonasal surgery). RESULTS: Patients with CRSwNP (N = 445) had significantly lower mean SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores vs population norms, demonstrating that CRSwNP negatively affects HRQoL. The presence of comorbidities affected HRQoL, as shown by significant differences in PCS scores in patients with asthma or non-steroidal antiinflammatory drug-exacerbated respiratory disease, compared with patients without asthma. Patients with moderate-to-severe disease had significantly lower PCS scores than patients with mild disease. Severe disease had a significant impact on MCS score. History of surgery had a clinically meaningful negative effect on HRQoL compared with no history of surgery. CONCLUSIONS: CRSwNP patients have significantly lower HRQoL compared with population norms. The impact is greater in patients with greater disease severity, comorbidities, or refractory disease.

Prospective study on the outcome of the sphenoid drill out procedure.

BACKGROUND: Chronic sphenoid sinusitis refractory to both medical therapy and sphenoidotomy requires a more extended intervention based on the principles of salvage surgery. Our aim is to describe the sphenoid drill out technique as a sphenoid salvage intervention and to outline its implications on clinical outcome and quality of life. METHODOLOGY: 12 patients with chronic sphenoiditis undergoing a sphenoid drill out procedure were examined by nasal endoscopy preoperatively and postoperatively for one year. Preoperative and postoperative quality of life questionnaires (RSOM-31 and SF-36) were obtained. RESULTS: All but one patient had a completely patent neostium without scar formation. No major complications occurred after this procedure. All patients reported at least an improvement of their symptoms, 50% of patients were even symptom free at one year after surgery. The median postoperative RSOM-31 score was significantly lower than the preoperative score. Both the physical component summary (PCS) and the mental component summary (MCS) of the SF-36 score improved significantly. None of the patients needed a revision procedure. CONCLUSION: Sphenoid drill out is a safe and effective technique with a high success rate. In patients with chronic sphenoid sinusitis refractory to medical therapy and surgery it could be a valid alternative to revision sphenoidotomy.

mySinusitisCoach: patient empowerment in chronic rhinosinusitis using mobile technology.

Mobile health technology is emerging to take a prominent position in the management of chronic diseases. These technologies aim at enhancing patient empowerment via education and self-management. To date, of all the different apps available for patients with sinus disease, none were developed by medical experts dealing with chronic rhinosinusitis (CRS). The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) has undertaken a multi-stakeholder approach for designing, developing and implementing a tool to support CRS patients in monitoring their symptoms and to provide patients with a digital support platform containing reliable medical information about their disease and treatment options. mySinusitisCoach has been developed by medical experts dealing with CRS in close collaboration with patients, primary care physicians and community pharmacists, meeting the needs of both patients and health care providers. From a research perspective, the generation of real life data will help to validate clinical studies, patient stratification and improve understanding of the socio-economic impact of CRS, thereby paving the way for better treatment strategies.

The effect of systemic treatments on periostin expression reflects their interference with the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Periostin is a recently discovered biomarker for eosinophilic inflammation. Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed chronic inflammatory airway disease. Medical treatments aim to relieve symptoms and maintain clinical control by interfering with the inflammatory cascade. The effect on nasal and serum periostin levels is however yet unknown. We aimed to evaluate the effect of omalizumab, mepolizumab, methylprednisolone and doxycycline on nasal and systemic periostin expression. METHODS: This study is based on 3 previously published trials. Nasal and systemic periostin were assessed in CRSwNP patients, randomly assigned to receive doxycycline (n=14), methylprednisolone (n=14), mepolizumab (n=20) or omalizumab (n=15). There was a control group for each treatment scheme. Doxycycline (200 mg on the first day, followed by 100 mg once daily) and methylprednisolone (32-8 mg once daily) were administered during 20 days; mepolizumab was injected at baseline and at 4 weeks. Omalizumab was injected every 2 or 4 weeks, following the official drug leaflet. RESULTS: Methylprednisolone and omalizumab significantly reduced serum periostin levels at 4 and 8 weeks, respectively, after the start of the treatment. The effect of methylprednisolone was transient. Nasal periostin levels decreased significantly after 8 weeks of treatment with mepolizumab. The periostin expression is in accordance with the previously reported effect on the eosinophilic inflammation and clinical outcome. CONCLUSION: All treatment options distinctly influence periostin expression, reflecting the interference with the local or systemic eosinophilic inflammatory cascade.

Prospective open-label evaluation of long-term low-dose doxycycline for difficult-to-treat chronic rhinosinusitis with nasal polyps.

BACKGROUND: This study aimed to assess clinical outcomes of long-term low-dose oral doxycycline therapy in difficult-to-treat chronic rhinosinusitis with polyps (CRSwNP). METHODS: This was a prospective, open-label study of 60 patients with difficult-to-treat CRSwNP who had undergone endoscopic sinus surgery. Patients were divided into two groups: 28 received nasal steroids, saline irrigation, and doxycycline (200 mg on the first day, followed by 100 mg once daily) for 12 weeks, while 30 received only nasal steroids and saline irrigation. The main outcome measure was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Other outcome measures were the SNOT-20, NOSE, and Lund-Kennedy scores. The following parameters were also analyzed: asthma, rhinitis, non-steroidal-exacerbated respiratory disease (NERD), and baseline serum IgG, IgA, IgE, IgM, ANCA, and eosinophil count. RESULTS: There was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Patients who received doxycycline also had significantly better outcomes regarding SNOT-20, NOSE, and Lund-Kennedy scores. There was a negative association among a clinically significant improvement of SNOT-20 and presence of asthma, NERD, and elevated serum IgE levels before treatment. CONCLUSION: These findings suggest that doxycycline may have a beneficial role for CRSwNP patients, especially for patients without asthma, NERD or high levels of serum IgE before treatment.

The response to nasal allergen provocation with grass pollen is reduced in patients with chronic rhinosinusitis with nasal polyposis and grass sensitization.

BACKGROUND: The majority of grass pollen-sensitized rhinitis patients develops allergic symptoms when exposed to the causal allergen and shows a positive nasal allergen provocation test (NAPT). Chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, also characterized by eosinophilic inflammation and local IgE production, can suffer from comorbid inhalant allergy, but may show a different response to allergens. OBJECTIVE: We aimed to explore the allergic response to grass pollen allergens by NAPT in grass pollen-sensitized CRSwNP patients. METHODS: Twelve grass pollen-sensitized CRSwNP patients underwent NAPT with grass pollen and were compared with 12 grass pollen allergic rhinitis patients, 12 control patients and 12 CRSwNP patients without grass pollen sensitization. A positive NAPT was based on change in nasal airflow and symptoms. Further, VAS scores of different symptoms were noted before and after NAPT. Biomarkers such as total IgE, grass pollen-specific IgE and tryptase were measured in serum and nasal secretions. RESULTS: NAPT was positive in 6 of 12 of the grass pollen-sensitized CRSwNP patients, and another four patients developed allergic symptoms not fulfilling the criteria of positivity. In contrast, all patients with allergic rhinitis developed a positive provocation test, whereas in the control group one of the patients and in the non-sensitized CRSwNP group two of the patients developed a positive provocation test. CONCLUSION AND CLINICAL RELEVANCE: These results show that allergen exposure induces an attenuated clinical response in patients with CRSwNP and sensitization to grass pollen as compared with grass pollen allergic rhinitis patients.

Traumatic CSF leaks of the anterior skull base.

Traumatic CSF leaks of the anterior skull base. Skull base fractures are a frequent complication of high-impact trauma; due to the inherent anatomic relationships of the skull base, they may be associated with significant intracranial complications, including CSF leakage, and their detection is therefore important. The ethmoid roof and the cribriform plate region are the sites most vulnerable to fractures and dural tears. Rhinorrhoea is a non-specific finding; the presence of CSF in a sample must be confirmed with beta 2 transferin or beta trace protein. Accurate identification of the leakage site is necessary for a successful surgical treatment. Various modalities are available for this purpose, such as CT scan and MRI. Persistent CSF rhinorrhoea necessitates surgical intervention, due to the risk of meningitis. Continued improvements in endoscopic reconstruction techniques have led to fewer open surgeries for repair. Smaller defects can be closed with fat gasket technique or free grafts, while larger defects necessitate a multilayer closure with local vascularized flaps. These techniques have shown consistently high success rates.

Endoscopic skull base reconstruction after endoscopic endonasal approach.

Recent advances in technology and techniques in neurosurgery and otolaryngology have revolutionised skull base surgery with the introduction of endoscopic endonasal approaches. One of the greatest limitations of endoscopic endonasal skull base surgery is the repair of osteodural defects. Numerous reconstructive techniques have been developed that maximise endoscopic endonasal approach efficacy and minimise complications. The choice of technique for closure depends on different factors and is based on an individual approach in each patient. In particular, size, the localisation of the defect and the presence of a high-flow CSF leak are major determinants of the reconstructive options. Free tissue transfer remains the mainstay for the reconstruction of smaller defects. However, local vascularised flaps and the nasoseptal flap in particular now play a pivotal role in the reconstruction of larger defects. These flaps have significantly reduced the morbidity and risk of post-operative CSF leaks after endoscopic endonasal approaches.

Type III frontal sinusotomy: surgical technique, indications, outcomes, a multi-university retrospective study of 120 cases.

Draf in 1991. The procedure--which is also known as the modified endoscopic Lothrop procedure--aims to create the largest possible anteroposterior and lateral to lateral opening between both frontal sinuses and the nasal cavities. This requires the resection of the medial floor of both frontal sinuses, the intersinus septum and the superior nasal septum. The authors present a retrospective study including a cohort of 120 patients who underwent surgery in six Belgian university ENT departments. Mean follow-up was 24.6 months (range: 5-36 months). This paper describes the surgical procedure and reviews the indications, comorbidities, outcomes and complications of the type III frontal sinusotomy. Some correlations are also established with the data published in the worldwide literature. The authors conclude that the Draf III is a demanding procedure requiring considerable expertise in endoscopic sinus surgery. The procedure is effective with a success rate of 87.5%. Indeed, 12.5% of patients only experienced closure of the neoostium while 20% of all the patients had unchanged or worse symptomatology. The percentage of post-operative complications is 7.5%. All complications were managed successfully.

Rhinosinusitis and asthma: a link for asthma severity.

The term rhinosinusitis describes an inflammation of the mucosal lining of the nose and sinuses; however, recent evidence points to the need to differentiate patients with chronic rhinosinusitis without nasal polyps from those with nasal polyps. Asthma comorbidity is especially common in nasal polyp disease and may be associated with aspirin-exacerbated respiratory disease. Of interest, asthma comorbidity is uncommon in some parts of the world but common in others. A further analysis of the inflammatory patterns also revealed that nasal polyps do not represent one single entity; interleukin (IL)-5-positive nasal polyps can be differentiated from IL-5-negative forms by different inflammatory patterns (predominance of eosinophils vs neutrophils). Staphylococcus aureus superantigens frequently colonize IL-5-positive nasal polyps and may amplify the eosinophilic inflammation, induce a polyclonal local IgE formation, and increase the risk of asthma comorbidity. Recent findings in severe asthma patients confirm the role of superantigens in lower airway disease.

Why do we prefer the external approach?

Open structure rhinoplasty (OSR) is an old technique that has gained in popularity amongst plastic surgeons and otolaryngologists over the past twenty years. Opponents of the external approach cite potential problems such as unnecessary scaring, reduction of tip support, extended operative time and excessive post-operative tip swelling. However, even relatively inexperienced rhinoplastic surgeons embrace this approach, especially in cases with more complex tip deformities and skeletal abnormalities. Concerns about scarring and post-operative tissue reaction due to the more "aggressive" external approach make it necessary to consider the indications for the open approach carefully. Various incisions have been described for open rhinoplasty to reduce scarring, such as the Z, V, reverse V, and W incisions. There should be a strong emphasis on post-operative care in open approach rhinoplasty since open structure rhinoplasty is generally considered to be a more traumatic technique than the endonasal approach. Careful incision and dissection of the skin flap in the right surgical plane and proper suturing are essential to avoid short- and long-term complications. In conclusion, the external approach is preferable in selected cases where extended exposure (asymmetry cases, for example), per-operative assessment (revision cases), grafting and suturing are required. It allows the surgeon to work bimanually during reconstruction and the better per-operative evaluation reduces the revision rate.

Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GALEN study.

Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA(2)LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.

The relation between paracetamol use and asthma: a GA2LEN European case-control study.

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (20-45 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations.

A case-control study of the relation between plasma selenium and asthma in European populations: a GAL2EN project.

BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

[Role of Staphylococcus aureus in upper respiratory infections]. / Rol van Staphylococcus aureus in bovenste luchtwegziekten.

Chronic rhinosinusitis with nasal polyps often represents a chronic severe inflammatory disease of the upper airways. Nasal polyps (chronic rhinosinusitis with nasal polyps) are characterized by a T-helper-2 dominated cytokine pattern including high interleukin-5 while chronic rhinosinusitis without polyps exhibits T-helper-1 biased cytokine releas with high IFN-gamma concentrations. S. aureus derived enterotoxins function as superantigens and in nasal polyps a significant higher colonisation and immune response to enterotoxins has been found. Furthermore, S. aureus derived enterotoxins influence local immunoglobulin synthesis and induce polyclonal immunoglobulin E production, which may contribute to severe inflammation via activation of mast cells. From this new understanding of chronic rhinosinusitis with nasal polyps, new therapeutic approaches emerge such as anti-interleukin-5, anti-immunoglobulin E, and antibiotic treatment. These may enlarge the nonsurgical armentarium. Furthermore more evidence is now available that this model of disease modification by superantigens is also applicable to lower airway diseases like late-onset asthma.

Chronic rhinonsinusitis and nasal polyposis: the etiopathogenesis revealed?

Nasal polyps represent a severe eosinophilic inflammation of the upper airways which is characterized by poor impact of therapeutic intervention and frequent recurrences. Based on distinct cytokine, mediator and cell profiles, chronic sinonasal disease in Caucasians can be differentiated into several subgroups such as chronic rhinosinusitis without nasal polyps, chronic rhinosinusitis with nasal polyps, and nasal polyps in cystic fibrosis patients,. In Caucasians, nasal polyps showed a Th2 polarisation with high IL-5 concentrations, while chronic rhinosinusitis without polyps was characterized by a Thl polarisation with high levels of IFN-gamma. In the Caucasian nasal polyps we found that significantly more nasal polyp patients are colonized with S. aureus and that colonization increased in patients with concomitant asthma and aspirin sensitivity. Although there was no major difference in the presence of enterotoxin genes in S. aureus strains derived from nasal polyp or control patients, we found an increased immune response to S. aureus enterotoxins in nasal polyps, which resulted in a more pronounced eosinophilic inflammation and higher total IgE production in those polyps affected. We suggest that S. aureus superantigens amplify the inflammation in about 50% of nasal polyps, resulting in a strong Th2 polarisation, eosinophil activation, and an overproduction of IgG4 and IgE. These findings imply new therapeutic approaches apart from the currently used topical and systemic steroid therapy for nasal polyposis. In three double blind placebo controlled studies it was shown that firstly, oral corticosteroids only led to a short term reduction of polyp size. Secondly that a low dose of doxycycline treatment for 20 days had a sustained clinically relevant effect on polyp size for more than 3 months and thirdly we also showed a significant effect on polyp size by selective antagonizing IL-5 with a monoclonal antibody.

Local immunoglobulin production in nasal polyposis is modulated by superantigens.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (NP) represents a persistent inflammation often characterized by local hyper-immunoglobulinaemia and the presence of specific IgE to Staphylococcus aureus enterotoxins (SAEs). We aimed to study the systemic and local production of Igs in relation to plasma cells, B cells and specific IgE to SAEs. METHODS: Concentrations of IgE, IgG, IgM, IgA, IgG subclasses and specific IgE to SAE were determined on tissue homogenates and serum from 15 CRS patients with NP, 15 CRS without NP and 10 control patients. Tissue cryo-sections were stained for CD19, CD20 and CD138 to demonstrate B and plasma cells. RESULTS: IgA, IgG and IgE concentrations were significantly higher in tissue homogenates, but not in serum, of NP compared with CRS and control subjects. NP with specific IgE to SAEs had significantly higher concentrations of IgG and IgE, and also showed a significantly higher fraction of IgG4 (P=0.003) and a lower fraction of IgG2 (P=0.04) than those without specific IgE production. Furthermore, naïve CD19(+) B cell and plasma cell counts (CD138(+)) were significantly higher in NP tissue compared with controls or CRS. CONCLUSIONS: The difference in IgE, IgG and IgA expression between NP tissue and serum, supported by increased numbers of plasma cells, suggests a local production of these Igs in NP in response to a chronic microbial trigger. The local immune response to SAE is associated with a further increased production of IgE and IgG, and a shift in IgG subclasses.