Dual and triple modulator therapy for chronic rhinosinusitis in cystic fibrosis patients.

BACKGROUND: The introduction of CFTR modulators has changed the landscape in the treatment of cystic fibrosis (CF) and early case series have shown improvements in sinonasal outcomes in this patient population. METHODOLOGY: A real-word data study was performed to evaluate the impact of dual therapy with tezacaftor/ivacaftor (TEZ/IVA) and triple therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) on CF-related chronic rhinosinusitis (CRS), by comparing subjective and objective outcome measures at baseline, 12 months after treatment with TEZ/IVA and six months after treatment with ELX/TEZ/IVA. RESULTS: In total, 43 CF patients, with a mean age of 32 years, were included. After triple therapy, significant improvements in overall visual analogue scale, SNOT-22, Lund Kennedy, nasal polyps, and Lund-Mackay scores were observed, whereas no beneficial effect could be seen in patients treated with dual therapy. Bacterial upper airway colonization did not differ pre- and postmodulator therapy in the present study. The number of responders to dual and triple therapy is 23.8% and 63.2% of the patients, respectively. CONCLUSIONS: Triple therapy with ELX/TEZ/IVA is superior to dual therapy with TEZ/IVA in the treatment of CF-CRS, as significantly reduced sinonasal complaints, nasal endoscopy and CT scores were observed after triple therapy, whereas this was not the case for dual therapy.

Nasal hyperreactivity in allergic rhinitis and chronic rhinosinusitis with polyps: a role for neuronal pathways.

BACKGROUND: Nasal hyperreactivity (NHR) is prevalent in all chronic upper airway inflammatory phenotypes, including allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Although NHR in patients with non-allergic rhinitis is mediated by neuronal pathways, AR and CRSwNP are mainly characterized by type 2 inflammation. METHODS: Eighteen healthy controls and 45 patients with symptomatic AR/CRSwNP underwent a cold, dry air (CDA) provocation test for objective diagnosis of NHR. Before and after, questionnaires were filled out and nasal secretions and biopsies were collected. Markers for neurogenic inflammation (substance P, calcitonin gene-related peptide, neurokinin A), epithelial activation (IL-33), and histamine were measured in secretions by ELISA; and expression of neuronal markers PGP9.5, TRPV1, and TRPM8 was studied in biopsies by RT-q-PCR. Effects of histamine on TRPV1/A1 were studied with Ca2+-imaging using murine trigeminal neurons. RESULTS: CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/patients CDA-provocation reduced peak nasal inspiratory flow (PNIF) of patients with subjective NHR but not of non-NHR controls/patients. Subjective (subjectively reported effect of CDA) and objective (decrease in PNIF) effects of CDA were significantly correlated. Levels of neuropeptides and histamine in nasal secretions and mRNA expression of PGP9.5, TRPV1, and TRPM8 correlated with CDA-induced PNIF-reduction. CDA-provocation induced an increase in IL-33-levels. Both TRPV1 and TRPA1 expressed on afferent neurons were sensitized by exposure to histamine. CONCLUSION: NHR is not an on/off phenomenon but spans a continuous spectrum of reactivity. A neurogenic inflammatory background and increased histamine-levels are risk factors for NHR in AR/CRSwNP.

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.

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.

Diversity and host specificity of monogenean gill parasites (Platyhelminthes) of cichlid fishes in the Bangweulu-Mweru ecoregion.

This study represents the first exploration of the parasite fauna of cichlid fishes in the Mweru-Luapula subregion (Central Africa). Twelve species of cichlids and 14 species of Monogenea from three genera (Cichlidogyrus, Gyrodactylus and Scutogyrus) were collected. We present a first record of the gill parasite fauna of eight host species, Oreochromis mweruensis, Orthochromis sp. 'Mambilima', Sargochromis mellandi, Serranochromis angusticeps, S. stappersi, S. thumbergi and Tylochromis mylodon. The host range of ten parasite species was expanded. The study further includes the description of Cichlidogyrus consobrini sp. n. from S. mellandi and Orthochromis sp. 'Mambilima'. A new morphotype of C. halli is characterized, and three species - C. papernastrema, C. quaestio and C. zambezensis - are redescribed. Furthermore, the biodiversity and host specificity of these parasites is compared with that of cichlid parasites from Lake Kariba and Cameroon. Two species, including C. consobrini sp. n. and a new morphotype of C. halli, are putative endemics. The parasite fauna in Bangweulu-Mweru is highly similar in species composition to Lake Kariba, but in Bangweulu-Mweru the same parasite species are more host-specific, probably because of hydrogeographical differences between the two regions.

Real-life study showing uncontrolled rhinosinusitis after sinus surgery in a tertiary referral centre.

RATIONALE: The European Position Paper on Sinusitis (EPOS) guidelines provide composite criteria to evaluate chronic rhinosinusitis (CRS) control, taking into consideration the severity of patients' symptoms, aspect of nasal mucosa and medical intake as parameters of CRS control. OBJECTIVES: To study the degree of CRS control using novel EPOS control criteria at 3-5 years after a functional endoscopic sinus surgery (FESS) and correlate these data to symptoms scores. METHODS: Adult CRS patients (n = 560) who had undergone bilateral FESS for chronic inflammatory sinonasal disease 3-5 years prior to the study were included. Patients received a postal questionnaire asking for control items according to EPOS control criteria, visual analogue scale (VAS) scores for total and individual sinonasal symptoms, sinonasal outcome test (SNOT)-22 and Short Form (SF)-36 questionnaires. MEASUREMENTS AND MAIN RESULTS: About 19.5% of CRS patients were well controlled, with 36.8% of patients being partly controlled and 43.7% uncontrolled. The levels of control corresponded to mean total VAS, SNOT-22 and SF-36 scores. Subgroup analysis revealed that female gender, aspirin intolerance and revision FESS were associated with higher prevalence of uncontrolled CRS, whereas allergy, asthma and smoking status did not alter the percentage of patients in each category of control. In 81 patients attending the outpatient clinic, nasal endoscopy changed classification in only four patients (4.9%). CONCLUSIONS: Based on the novel EPOS control criteria, at least 40% of CRS patients are uncontrolled at 3-5 years after FESS. Therefore, better treatment strategies leading to higher disease control are warranted in CRS care.

Draf III frontal sinusotomy: influence of patient characteristics on outcome.

Draf III frontal sinusotomy: influence of patient characteristics on outcome. OBJECTIVE: To identify positive and negative predictive outcome factors for the Draf III procedure based on the experience of a single center. METHODS: Seventy-two patients who underwent a Draf III procedure between 2005 and 2011 at the ENT department of University Hospitals Leuven were included. Patient demographics, history of frontal sinus surgery, clinical features, and computed tomographic evaluations were reviewed and analyzed for associations with symptom control and endoscopic outcome. RESULTS: The mean age was 48 years (16-82 years), and the male-to-female-ratio was 2:1. Major indications were chronic rhinosinusitis (with or without nasal polyps) and mucoceles. Supplementary frontal (recess) cells were found in the majority of patients. Osteoneogenesis was present in one out of four patients. At the end of follow-up (mean 35 months), the neo-ostium patency rate was 89%. Stenosis or closure of the neo-ostium was seen in 11% of patients, and 15% of patients required revision surgery. Subjective improvement was reported by 88%. CONCLUSION: The results of Draf III frontal sinusotomy were positive in the long term. Previous frontal sinus surgery, the presence of allergy or aspirin-exacerbated respiratory disease (AERD), asthma, smoking, and variants in frontal recess anatomy did not affect outcome. Osteoneogenesis and chronic mucosal inflammation could be controlled by creating a large drainage pathway.

Swallowing dysfunction in myotonic dystrophy: a retrospective study of symptomatology and radiographic findings.

BACKGROUND: Swallowing dysfunction is a common symptom of myotonic dystrophy, but it is poorly documented in large patient series. This retrospective study was designed to investigate the presence of swallowing symptoms in a large study population and to describe a specific pattern of clinical and radiographic abnormalities. METHODS: A retrospective analysis was made of 169 files of patients with confirmed MD. Neuromuscular assessment was made by means of a standardised neurological examination; clinical swallowing symptoms were listed, and video-fluoroscopic images were analysed. RESULTS: More than half the patients reported swallowing complaints. The major symptoms were frequent choking, difficult pharyngeal transport and piecemeal deglutition. The pharyngeal phase of swallowing was most frequently compromised. This was shown radiographicaly in reduced pharyngeal peristalsis, hypopharyngeal stasis and fragmented swallowing. Aspiration was seen in half of the patients, mostly during swallowing. A typical 'hung position' of the hyoid was also seen. Different onset types of MD seem to be accompanied by comparable subjective complaints and radiographic symptoms. CONCLUSIONS: Pharyngeal transport was most affected in this patient population. Muscular weakness seems to be the major contributor to swallowing impairment in MD. Swallowing abnormalities may be present even if patients report only a few symptoms and even if the severity of the disease is not pronounced.

Vascular endothelial growth factor receptor 1 expression in nasal polyp tissue.

BACKGROUND: Edema represents a key feature of nasal polyp (NP) disease. Members of the vascular endothelial growth factor (VEGF) family may be involved, but the precise role of VEGF-A, VEGF-B, placental growth factor (PlGF), and their receptors VEGFR1 and VEGFR2 in NP edema formation remains elusive. OBJECTIVE: Exploring the expression of VEGF family members and their receptors and their correlation with clinical, radiological, and edema markers in NP. METHODS: The expression of VEGF-A, VEGF-B, PlGF, VEGFR1, and VEGFR2 was measured in NP (n = 23) and control tissue (n = 22) at mRNA and protein level. Edema was evaluated by measuring albumin levels and wet/dry ratios. Computed tomography (CT) scans were scored using the Lund-Mackay scoring system. IL-5 mRNA expression was determined by real-time RT-PCR. Cell suspensions from NP (n = 10) and control tissue (n = 12) were stimulated in vitro with IL-1ß or TNFα. RESULTS: mRNA expression of VEGFR1 and VEGF-B was significantly higher in NP compared with control tissue. Expression levels of VEGF-B and VEGFR1 significantly correlated with NP albumin content (VEGF-B: P = 0.0208; VEGFR1: P = 0.0293), CT scan scores (VEGF-B: P = 0.0075; VEGFR1: P = 0.0068), and IL-5 mRNA (VEGF-B: P = 0.0027; VEGFR1: P = 0.0001). In vitro stimulation of control and NP tissue cell suspensions with IL-1ß or TNFα significantly reduced the expression of VEGFR2 in control tissue, without altering VEGFR1 and VEGF-B expression. hVEGF-B induced nitric oxide production in NP macrophages (P < 0.05). CONCLUSION: Expression levels of VEGFR1 and VEGF-B correlate with edema and clinical markers of NP disease and therefore represent potential therapeutic targets.

Nationwide survey on immunotherapy practice by ENT specialists.

BACKGROUND: According to the Federal Institution of Health Insurance, ENT doctors perform more skin prick tests for the diagnosis of allergic rhinitis (AR) than other medical specialties in Belgium. However, immunotherapy (IT) is not practiced by all. This study aims to obtain insight into IT practice by ENT doctors, the type of IT performed and the reasons not to perform IT. METHODOLOGY: A questionnaire was sent to all registered ENT doctors of Belgium (n=648), involving questions on type and duration of ENT practice, geography and gender. In addition, the questionnaire informed about diagnosis of AR, indication for IT, type of IT performed, and reasons not to perform IT and referral pattern. RESULTS: The response rate among ENT doctors was 54%, with 7% of responders being excluded as they do not diagnose AR. 81% of Belgian ENT doctors make the indication for IT in AR patients, with 19% neglecting the indication for IT in AR patients. The two main reasons for not indicating IT are lack of expertise and the perception of high costs associated with IT. 70% of ENT specialists are practicing IT themselves, with sublingual IT being mostly performed. Interestingly, IT is mostly frequently performed by those ENT doctors with long-standing ENT practice, in private practice and in Wallonia. CONCLUSION: Despite the high prevalence of AR in ENT practice, IT is most frequently performed by ENT doctors with longstanding practice, working in private practice and/or in the French speaking part of Belgium. Among the different types of IT, sublingual IT is the most frequently performed means of IT by ENT doctors.

Nasal manifestations of systemic diseases.

OBJECTIVES: Signs and symptoms of the sinonasal tract may be originated in any organ system. Distinguishing these from original sinonasal disease poses a great diagnostic challenge. The ENT specialist usually faces an unresponsive or relapsing case, with an atypical presentation. We address this issue by trying to provide a wider perspective when dealing with sinonasal manifestations. METHODOLOGY: We reviewed the literature exploring heterogeneous groups of diseases and systemic conditions that might interfere with normal sinonasal physiology. The most current and valid information have been included in an effort to delineate such manifestations and clarify the distinguishing signs and tests. RESULTS: A great variety of systemic conditions with sinonasal manifestations, including connective tissue, autoimmune, infectious, vascular, hematological, gastrointestinal, and endocrine diseases, were included. We address their distinguishing characteristics and diagnostic work-up. CONCLUSIONS: Signs and symptoms of the sinonasal tract can originate from either local or systemic disorders. The keys to dealing with such disorders are understanding the patterns in which systemic diseases can manifest, and using special diagnostic tools specific to each condition to confirm or rule out particular diagnoses.

Myospherulosis as a complication of functional endoscopic sinus surgery: a double case report.

INTRODUCTION: Paraffinomas (also known as 'sclerosing lipogranulomas' or 'myospherulosis') are a widely acknowledged complication of cosmetic paraffin injections but they are rare following functional endoscopic sinus surgery. CASE PRESENTATIONS: Our first case features a 45-year-old woman presenting with a peri-ocular swelling two weeks after functional endoscopic sinus surgery. The procedure was complicated by a fractured lamina papyracea. A nasal packing with antibiotic ointment was left in situ. Initially, the inflammation was controlled successfully with corticosteroids but the swelling persists to this day. Our second case is a 45-year-old man who suffered from a recurrent swelling of the right eyelid after endoscopic sinus surgery. Multiple treatments with oral antibiotics and corticosteroids brought about no improvement. Debulking surgery was performed and a PDS film was placed between the peri-orbita and the bony orbital floor but the swelling recurred. The patient finally consulted a plastic surgeon as a last resort, but the reconstructive procedure only exacerbated the clinical picture. In both cases a biopsy was performed which established the foreign body reaction typical of a paraffinoma. At present, both patients still suffer from this condition. CONCLUSION: The complete resection of a paraffinoma is seldom possible because of diffuse infiltration and recurrence is very likely. We therefore conclude that paraffin-based ointments should not be used with nasal packing after sinus surgery, especially when there has been a lesion involving the orbital wall.

Negative impact of occupational exposure on surgical outcome in patients with rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) is a frequent condition that is treated by functional endoscopic sinus surgery (FESS) when medical treatment fails. Endogenous as well as exogenous factors may be responsible for persisting symptoms after FESS. The role of occupational exposures on success of FESS has never been investigated. METHODS: In this case-control study, we tested the hypothesis that the outcome of FESS procedures is related to exposures at work. Questionnaires were sent to 890 patients who had undergone one or more FESS procedures and to 182 controls. Three independent experts assessed blindly the reported work exposures to inhaled agents. The relationship between exposure and the number of FESS procedures was analyzed. RESULTS: Relevant occupational exposure was reported by 25% of all responding patients undergoing FESS (n = 467) and 12% of controls (n = 69). The prevalence of occupational exposures increased linearly with the number of FESS procedures from 21% in those who had one FESS to 44% in those who had four or more FESS (χ(2)  = 12.74, P < 0.001). Logistic regression analysis with adjustments for potential confounders, including smoking, atopy, and asthma, confirmed that the odds ratio (OR) for reporting occupational exposures was significantly higher in those needing more than one FESS (OR = 1.64) or more than two FESS (OR = 1.97). These results were mainly driven by exposure to low molecular weight agents. CONCLUSION: Exposure at work appears to be a risk factor for the occurrence of CRS and for its recurrence or persistence, as evidenced by the need for revision surgery.

Long-term effects of cutting versus non-cutting instruments in FESS.

BACKGROUND: Currently most ENT surgeons advocate using cutting instruments in Functional Endoscopic Sinus Surgery (FESS), based on the assumption of superior wound healing due to mucosal preservation. However, there is no scientific evidence of superiority of the cutting instruments. METHODS: A prospective, randomized double blinded study was performed in 100 patients undergoing FESS, operated one side with non-cutting and the contra lateral side with cutting instruments. After a mean follow-up of 12 years after FESS, unilateral and global sino-nasal symptoms were scored by the patients using VAS, endoscopic abnormalities scored at both sides at the Outpatient clinic and radiologic abnormalities were described. RESULTS: No significant differences between the sides operated by cutting and non-cutting instruments were found for sino-nasal symptomatic or for radiologic abnormalities between both sides. For the endoscopic parameters there was no difference for secretion or mucosa. Only for the presence of endoscopic synechiae there was a statistically significant difference between both groups. At the non-cutting side more synechiae were noticed, but no interference with sinus access, neither ventilation nor drainage was observed. CONCLUSION: FESS performed with cutting instruments results in less synechiae formation compared to non-cutting instruments. However, the presence of synechiae is not associated with more symptoms or CT scan abnormalities.

Specific medical and surgical treatment for chronic inflammatory diseases in children.

Treatment for chronic inflammatory conditions in children should take into account the specific pathophysiological and clinical processes underlying these disorders. These guidelines provide a framework for both the medical and surgical treatment of chronic inflammatory diseases such as otitis media, allergic rhinitis and chronic rhinosinusitis, chronic inflammation of tonsils and adenoids, and laryngitis. In addition, the role of vaccinations and immunomodulatory therapies is discussed. Whenever possible, the evidence levels for specific treatments comply with the Oxford Levels of Evidence.

Adenocarcinomas of the sinonasal tract: current opinion.

Malignant tumours of the sinonasal tract represent a rare condition, accounting for only 0.5-1% of all malignancies in the Western population. Patients with malignant tumours of the nasal cavity and sinuses form a heterogeneous group when it comes to histology and treatment protocols. This review of adenocarcinoma of the sinonasal tract aims to provide a comprehensive overview of aetiological factors, histological subtypes, diagnostic workup, currently available treatment options, survival analysis and prognostic factors for treatment outcome. The current treatment of choice is surgical resection, using whichever approach allows access for the removal of the entire tumour with a curative intent.

Sensitization to common aeroallergens in patients at an outpatient ENT clinic.

OBJECTIVES: The epidemiology of specific sensitization to inhalant allergens remains unknown in patients at tertiary rhinology clinics. We used skin prick testing (SPT) to assess sensitization to major aeroallergens in order to evaluate the prevalence of specific rhinologic diseases, the frequency of polysensitization and the relationship between nasal symptoms, nasal endoscopy parameters, diagnosis and sensitization. METHODS: A retrospective review of medical records was conducted at the ENT Department of the Catholic University Hospital in Leuven, Belgium. The study analyzed the medical data of patients with rhinologic symptoms suspected of having allergies. RESULTS: The study included 1326 patients with a mean age of 35 +/- 18 years (range: 3-88 years); 52.8% were males. Rhinitis without nasal abnormalities (42.1%), chronic rhinosinusitis without nasal polyps (16.5%) and nasal abnormalities (16.1%) were the most prevalent findings. About 31.6% of patients were sensitive to at least one allergen, and the most common aeroallergens were dermatophagoides pteronyssinus (62.1%) and grass pollen (53.2%). Polysensitization was found in 54.2%. The most prevalent clinical symptoms in allergic rhinitis patients were nasal obstruction, clear/watery nasal discharge, sneezing, postnasal drip and headache. Clear nasal discharge, sneezing, and itchy nose and eyes (p < 0.05 for all) were significantly higher in sensitized patients. In contrast, postnasal drip, headache and purulent nasal discharge were also observed in non-sensitized patients (p < 0.05 for all). CONCLUSIONS: At a rhinology clinic at a university ENT clinic, 31.6% of the patients had positive SPT results, mainly to house dust mites and grass pollen. Among sensitized patients, 54.2% were polysensitized.

Malignant ectomesenchymoma of the paranasal sinuses with proptosis.

PROBLEM: A 36-year-old woman presented with a feeling of pressure in the right orbit and proptosis of the right eye after a "common cold". METHODOLOGY: Computed tomography (CT) of the maxillofacial region revealed, and endoscopy confirmed, a mass in the right ethmoid sinus, eroding the lamina papyracea and extending into the orbit. Pathology of multiple biopsies revealed a nasal neoplasm composed of neuroectodermal and mesenchymal neoplastic elements, suggestive of a malignant ectomesenchymoma (MEM). Magnetic resonance imaging was used for MEM staging. Computed tomography of the chest and abdomen show no evidence of distant metastases. RESULTS: Due to the intracranial and intraorbital extension of the tumour, radical surgery was not an option. Appropriate chemotherapy (6 cycles of vincristine/ifosfamide/adriamycin and 2 cycles of vincristine/ifosfamide/cisplatin) and intensity-modulated radiation therapy were administered. CONCLUSION: Twenty-eight months after treatment, there was no evidence of residual or metastatic disease.

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.