[Chronic rhinosinusitis in people with cystic fibrosis-an up-to-date review from the perspective of otorhinolaryngology]. / Chronische Rhinosinusitis bei Menschen mit zystischer Fibrose ­ eine aktuelle Übersicht aus der Perspektive der Hals­, Nasen­, Ohrenheilkunde.

BACKGROUND: Cystic fibrosis (CF) is a complex systemic disease involving numerous organ systems. With improved treatment options and increasing life expectancy of persons with CF (PwCF), extrapulmonary manifestations are coming increasingly into the focus. From birth, almost all PwCF have radiologically detectable pathologies in the upper airways attributable to CF-associated chronic rhinosinusitis (CF-CRS). OBJECTIVE: The aim of this work is to provide an up-to-date overview of CF-CRS from the otorhinolaryngology perspective and to provide the reader with background knowledge and current developments. PATHOPHYSIOLOGY: The cystic fibrosis transmembrane conductance regulator (CFTR) gene defect leads to increased viscosity of sinonasal secretions and reduced mucociliary clearance, causing chronic infection and inflammation in the upper airway segment and, consequently, to CF-CRS. CLINICAL PICTURE AND DIAGNOSTICS: The clinical picture of CF-CRS comprises a wide spectrum from asymptomatic to symptomatic courses. CF-CRS is diagnosed clinically and radiologically. THERAPY: Sinonasal saline irrigation is recommended as a conservative treatment measure. Topical corticosteroids are also commonly used. Surgical therapy is reserved for highly symptomatic treatment-refractory patients without a sufficient response to conservative treatment including CFTR modulator (CFTRm) therapies. Depending on the CFTR mutation, CFTRm therapies are the treatment of choice. They not only improve the pulmonary and gastrointestinal manifestations in PwCF, but also have positive effects on CF-CRS. CONCLUSION: The ENT specialist is part of the interdisciplinary team caring for PwCF. Depending on symptom burden and treatment responsiveness, CF-CRS should be treated conservatively and/or surgically. Modern CFTRm have a positive effect on the clinical course of CF-CRS.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (eGPA) are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of GPA and eGPA were collected and reported in this review. RESULTS: 467 references were discovered during literature review process. In total, 42 references for GPA and 35 references for eGPA were included in this review. CONCLUSION: GPA and eGPA are vasculitis syndromes which commonly present in the context of multisystem disease. For GPA, pulmonary and renal disease are common; for eGPA a history of asthma is nearly ubiquitous. Sinonasal disease is a very common feature for both disease processes and may precede the development of systemic symptoms in many patients. Clinical work up and diagnosis is complex and generally requires multidisciplinary care. Treatment primarily consists of immunosuppressive agents, and a number of steroids, steroid sparing agents, and biologics have been shown to be effective. The role of sinus surgery includes tissue biopsy for diagnosis, functional surgery for symptom management in select cases, and reconstruction of cosmetic and functional defects.

Trigeminal cold receptors and airflow perception are altered in chronic rhinosinusitis.

BACKGROUND: In chronic rhinosinusitis (CRS), nasal obstruction can often be explained by anatomical deformities, polyps, or congested nasal mucosa. However, in cases with little deformity or inflammation, perceived nasal obstruction may result from reduced airflow perception caused by an alteration of the intranasal trigeminal system. The aim of this study was to assess this association. METHODOLOGY: We performed a prospective case-control study of 15 CRS patients, 18 patients with a deviated nasal septum (DNS) and 16 healthy controls. We assessed olfactory function using the Sniffin' Sticks test and Visual Analog Scales (VAS). We used the Trigeminal Lateralization Task (TLT) with eucalyptol and cinnamaldehyde to examine intranasal trigeminal function. Further, we assessed nasal patency with Peak Nasal Inspiratory Flow and VAS. Finally, we measured protein levels of trigeminal receptors (TRPM8, TRPA1 and TRPV1) and inflammatory markers (IL-13, INF-y and eosinophils) in CRS and DNS patients' mucosal biopsies using Western Blots. RESULTS: CRS patients had significantly lower olfactory function than DNS and healthy controls. They also had significantly lower TLT scores for eucalyptol than both other groups. CRS patients had significantly lower nasal patency than controls; for DNS patients this was limited to subjective measures of nasal patency. In line with this, CRS patients exhibited significantly higher levels of sTRPM8-18 than DNS patients. CONCLUSIONS: Intranasal trigeminal function is decreased in CRS patients, possibly due to the overexpression of short isoforms of TRPM8 receptors.

Role of serum eosinophil cationic protein in distinct endotypes of chronic rhinosinusitis.

BACKGROUND: Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. METHODS: We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. RESULTS: In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 λg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 λg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. CONCLUSIONS: Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels >17.0 λg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.

Usefulness of post-operative endoscopic score for optimal treatment selection in recurrent eosinophilic chronic rhinosinusitis.

OBJECTIVE: This study retrospectively analysed post-operative endoscopic scores to determine the optimal post-operative treatment in patients with eosinophilic chronic rhinosinusitis undergoing functional endoscopic sinus surgery. METHODS: In total, 339 adults who underwent initial bilateral functional endoscopic sinus surgery for eosinophilic chronic rhinosinusitis were enrolled. Patients were divided into group A, which required no additional post-operative treatment; group B, which required local/systemic steroids post-operatively; and group C, which further required dupilumab and/or revision surgery. RESULTS: Sixty-five per cent of patients could be treated with initial functional endoscopic sinus surgery (group A). Post-operative steroids were required in 35 per cent of patients with a post-operative endoscopic score of 30 per cent (group B). Further advanced treatments with dupilumab and/or revision functional endoscopic sinus surgery were required in 10 per cent of patients with a post-operative endoscopic score of 65 per cent (group C). CONCLUSION: The post functional endoscopic sinus surgery endoscopic score can be used as an index to determine treatment at the time of eosinophilic chronic rhinosinusitis recurrence.

The association between chronic sinonasal inflammation and nasopharyngeal carcinoma - A systematic review and meta-analysis.

PURPOSE: There has been mounting evidence that inflammation is a key risk factor towards the development of certain cancers. Past studies have shown associations between nasopharyngeal carcinoma (NPC) and sinonasal tract inflammation. We aim to conduct a review and meta-analysis on the association between NPC and chronic sinus inflammation. MATERIALS AND METHODS: We conducted a meta-analysis, searching 4 international databases from 1 January 1973 to 28 March 2022 for studies reporting on sinonasal inflammation and NPC in adult patients (>18 years old). We included cohort, case-control or cross-sectional studies. These studies must examine the association between a prior history of sinonasal inflammation and the risk of developing NPC. The outcome is the incidence of NPC in patients who had prior sinonasal inflammation. RESULTS: 8 studies (8245 NPC; 1,036,087 non-NPC) were included. The overall odds ratio (OR) of patients having NPC after reporting sinonasal inflammation was 1.81 (95 % CI 1.73-1.89). Of note, chronic rhinosinusitis (CRS) (OR of 1.78 (95 %-CI: 1.68-1.90)) was more closely associated with an increased risk of NPC, as compared to allergic rhinitis (AR) (OR of 1.60 (95 %-CI: 1.52-1.68)). CONCLUSION: Chronic sinonasal inflammation is significantly associated with NPC in this systemic review and meta-analysis. The true cause-effect relationship and the potential effects of targeted screening need to be explored thoroughly with large scale prospective studies.

Chronic nasal dysfunction: A clinical case illustrating the concept in practice.

INTRODUCTION: We illustrate the diagnostic method for chronic nasal dysfunction by an observation in which the clinical history was compared to preoperative responses on the DyNaChron self-administered questionnaire, with ENT interpretation of the sinonasal CT scan preceding and guiding nasal endoscopy. CASE REPORT: The initial suspicion of rhinitis medicamentosa was transformed by the radiological and endoscopic findings of chronic respiratory rhinitis signs. Prick tests showing sensitivity to dust mites then suggested an allergic origin of the mucosal inflammation, which affected neither the olfactory nose nor the paranasal sinuses. A septal deviation hampering visualization of the right ethmoidal reliefs completed the clinical picture. Inferior turbinate hypertrophy secondary to allergic inflammation could have been aggravated by prolonged daily use of nasal vasoconstrictors. Failure of medical treatment combining nasal lavage, topical corticosteroids and an attempt at weaning led to effective medical and surgical management combining septoplasty, bilateral inferior turbinoplasty, continuation of topical corticosteroids and initiation of allergen immunotherapy. In addition to complete relief of nasal obstruction and abandonment of nasal vasoconstrictors, improved sense of smell completed the restoration of nasal comfort. DISCUSSION: It is helpful to conceive the nose as being anatomically and pathophysiologically a triple organ and to evaluate therapy in terms of improvement in each symptom.

A short history of nasal polyposis.

Nasal polyposis was initially considered a tumor, but came to be seen as a chronic inflammatory mucosal disease during the second half of the 20th century. Although pathogenesis remains unclear, this has not prevented progress in diagnosis and treatment, both surgical and medical, based on the hypotheses of chronic rhinosinusitis with type-2 inflammation and autoimmune inflammation maintained by the vestigial olfactory mucosa of the ethmoid.

General classification of rhinopaties: the need for standardization according to etiology and nasal cytology.

BACKGROUND: Rhinitis is as an inflammation of the nasal mucosa, characterized by high prevalence, widespread morbidity, and a significant financial burden on health care systems. Nevertheless, it is often considered as no more than a mere annoyance. This point of view has progressively led to underestimate and trivialize the disease. Therefore, there are numerous, mostly overlapping classifications of rhinopaties, but clear and standardized guidelines for diagnosis and treatment are still lacking. In the context of Precision Medicine, the development of a classification system focused on the endotypes of rhinitis to be widely adopted appears of utmost importance, also by virtue of study of the nasal immunophlogosis that, thanks to nasal cytology (NC), has recently allowed to better define the different forms of rhinitis, giving a new nosological dignity to several rhinopaties. AIM: We aimed to summarize the current knowledge regarding rhinitis and to propose a systematic classification of rhinitis, based on both etiology and cytological findings.

Complications of endoscopic sinus surgery for chronic rhinosinusitis in a tertiary care teaching hospital in Saudi Arabia.

OBJECTIVES: To aimed to determine the incidence of complications of endoscopic sinus surgery (ESS) and to investigate the factors associated with the occurrence of complications. METHODS: In this retrospective study, we reviewed the medical records of all patients who had undergone ESS at King Saud University Medical City (KSUMC) between January 2015 and March 2022. Patients who underwent ESS for complicated acute sinusitis, sinonasal malignancy, and cerebrospinal fluid leak repair, and those who underwent extended ESS for indications other than chronic rhinosinusitis were excluded. This study was approved by the KSUMC Institutional Review Board. RESULTS: We included 1395 patients, 3 of whom had major complications and 28 had minor complications, resulting in an overall major complication rate of 0.2% and a minor complication rate of 2%. The most common major complication was orbital hematoma, and the most common minor complication was synechia. Moreover, the duration of surgery and laterality increased the risk of complications, whereas the use of image guidance had no effect. CONCLUSION: The ESS is a safe procedure. The operative start time and laterality were associated with an increased risk of complications and warrant further investigation.

[Possibilities of differential diagnosis of chronic diseases of the nasal cavity after surgical treatment and topical antibiotic therapy]. / Vozmozhnosti differentsial'noi diagnostiki khronicheskikh zabolevanii polosti nosa posle khirurgicheskogo lecheniya i topicheskoi antibakterial'noi terapii.

OBJECTIVE: The study was performed to assess the endoscopic state of the nasal mucosa after the use of local anti-inflammatory and antibacterial therapy, in particular, Polydexa nasal spray with phenylephrine containing Dexamethasone sodium metasulfobenzoate + Neomycin + Polymyxin B + Phenylephrine, and for the treatment of granulomatosis with polyangiitis. MATERIAL AND METHODS: The study included 940 patients who underwent examination and treatment for chronic rhinosinusitis in the clinic of otorhinolaryngology of I.P. Pavlov SPbSMU surgical treatment of the paranasal sinuses underwent 907 patients. In the postoperative period, the first group (211 patients) underwent toileting of the nasal cavity. The second group (307 patients) received irrigation therapy. The third group (389 patients) received a topical treatment combined of Polydexa with phenylephrine. The dynamics of the condition was assessed on the 1st, 3rd and 7th days of treatment, the evaluation of the effectiveness of the treatment was carried out on the 3rd and 7th days. Differential diagnosis with granulomatosis with polyangiitis was carried out in 33 patients. All patients with granulomatosis with polyangiitis showed signs of chronic rhinosinusitis. Patients were prescribed local anti-inflammatory and antibacterial therapy with Polydexa with phenylephrine for 7 days with endoscopic control of the nasal cavity. CONCLUSION: The use of the combined topical drug Polydexa with phenylephrine in patients with chronic rhinosinusitis and in patients with granulomatosis with polyangiitis has a positive effect, which reduces the clinical manifestations of chronic rhinosinusitis.

Correlation between CT imaging and symptom scores in cystic fibrosis associated chronic sinusitis.

PURPOSE: There are limited guidelines for diagnosing and managing chronic rhinosinusitis (CRS) in the cystic fibrosis (CF) population. While CF patients are known to have significant opacification on paranasal computed tomography (CT), limited evidence suggests that CT findings are not indicative of patients' symptom burden and therefore not a reliable indicator for surgical intervention. This provides a diagnostic challenge for otolaryngologists taking care of this patient population. The purpose of this study is to better define the relationship between objective imaging findings and patients' symptom severity in the CF-CRS population with the goal of providing more selective and effective patient care. MATERIALS AND METHODS: In this retrospective cohort study, 67 patients with CF CRS had their CT scans scored according to a modified Lund Mackay CT score (LMCTS), which was compared to their Sinonasal Outcome Test scores (SNOT-22). Total SNOT-22 and individual domains were evaluated. Pearson's correlation was performed. RESULTS: The overall mean SNOT-22 score was 32.3. The mean LMCTS was 17.6. These metrics correlate with relatively low subjective symptom scores in comparison to the high objective presence of sinus disease. While patients had high LMCTS, there was no correlation found between LMCTS and total SNOT-22 or individual SNOT-22 domains. CONCLUSIONS: CT findings in CF CRS patients do not accurately reflect patients' symptom burden and should not be used as a primary driver in the clinical management of these patients.

Safety of a New Sinus Irrigation Device in Rhinosinusitis: A Pilot Study.

BACKGROUND: Puncture and lavage of the paranasal sinuses, previously the primary treatment for unresponsive acute bacterial rhinosinusitis before surgery, has been abandoned due to procedural discomfort and advancements in antibiotic efficacy and endoscopic surgery. The rise in antibiotic-resistant bacteria has renewed the interest in minimally invasive sinus lavage to both avoid aggressive surgical interventions and identify appropriate antibiotic therapy. In this article, we describe the safety and feasibility of a new device in human patients and evaluate its efficacy as a treatment before the traditional sinus surgery in acute rhinosinusitis. METHODS: The device with its seeker-shaped guiding tube and rotating wire can enter the sinus cavity through the natural ostium, pulverize the inspissated mucus, and enable lavage and culture sampling without the need for sinus puncturing. It was tested in 6 patients with chronic sinusitis under general anesthesia during endoscopic sinus surgery and in additional 10 patients with maxillary acute bacterial rhinosinusitis in outpatient settings under local anesthesia. RESULTS: The device enabled rapid, efficient, and atraumatic insertion of the wire into the occluded sinuses. The rotating wire permitted pulverization of the thick mucus, which enabled irrigation without mucosal damage or adverse events. Overall, 9 of 10 patients with acute bacterial rhinosinusitis demonstrated remarkable improvements and were discharged the following day with no acute symptoms. The visual analog scale score for pain dropped from 8.9 to 0.4. The remaining one patient underwent endoscopic sinus surgery subsequently. None of the patients treated during endoscopic sinus surgery developed any adverse events.

Occupational rhinitis caused by hypersensitivity to black pepper.

Black pepper (Piper nigrum) rarely leads to allergic inflammation of the nasal mucosa. This is a presentation of a 52-year-old female worker exposed to black pepper dust for 10 years suffering from allergic rhinitis and chronic rhinosinusitis. She complained of nasal obstruction, rhinorrhoea, and a weakened sense of smell. Clinical examination showed the bilateral presence of polypoid lesions arising from the middle turbinate. After surgery, histopathological examination confirmed the diagnosis of inflammatory nasal polyps. Duration of exposure to black pepper and serum concentration of specific immunoglobulin E antibodies indicating work-related exposure would support a causal link between exposure to these factors and the development of chronic inflammation in the nasal mucosa. Inflammatory nasal polyps may be noted in the nasal cavity in workers exposed to black pepper dust. The absence of exposure to black pepper resulted in no detectable circulating antibodies one year after the change of workplace.

Epidemiology and aetiology of chronic rhinosinusitis in Asia-A narrative review.

BACKGROUND: Despite having a similar prevalence to Western populations, literature on chronic rhinosinusitis (CRS) in the Asian population is sparse. There is limited data on the epidemiology and aetiology of CRS in Asia. OBJECTIVES: To review the current literature on the epidemiology and aetiology of CRS in Asia. METHODS: This is a narrative review of published data on the epidemiology and aetiology of CRS. Studies on CRS in Asian countries, published in English and indexed on PubMed or Google Scholar were reviewed. Where available, data extracted included epidemiology, endotype and cytokine profiles and genetic profiles. RESULTS AND CONCLUSION: The prevalence of CRS in Asia ranges widely from 2.1% to 28.4%. Type 2 inflammation has been reported in 5%-55% of Asian patients, with lower levels of Type 2 cytokines reported in head to head comparisons of Western versus Asian patients. Notably, there exists marked heterogeneity in criterion of the tissue eosinophilic infiltration for diagnosis of type 2 CRS. Our review suggests that differences in prevalence of CRS and proportion of eosinophilic CRS between Asia and Europe and the Americas requires further study. Large-scale Asian studies utilising standardised definitions are needed to bridge this gap. Head to head genetic and microbiomal analysis may also be useful in understanding differences in CRS between the Asian and Western populations.

Investigating the Relationship between Parental Education, Asthma and Rhinitis in Children Using Path Analysis.

Parental socioeconomic position (SEP) is a known determinant of a child's health. We aimed to investigate whether a low parental education, as proxy of SEP, has a direct effect on physician-diagnosed asthma, current asthma and current allergic rhinitis in children, or whether associations are mediated by exposure to other personal or environmental risk factors. This study was a secondary data analysis of two cross-sectional studies conducted in Italy in 2006. Data from 2687 adolescents (10-14 years) were analyzed by a path analysis model using generalized structural equation modelling. Significant direct effects were found between parental education and family characteristics (number of children (coefficient = 0.6229, p < 0.001) and crowding index (1.1263, p < 0.001)) as well as with exposure to passive smoke: during pregnancy (maternal: 0.4697, p < 0.001; paternal: 0.4854, p < 0.001), during the first two years of children's life (0.5897, p < 0.001) and currently (0.6998, p < 0.001). An indirect effect of parental education was found on physician-diagnosed asthma in children mediated by maternal smoking during pregnancy (0.2350, p < 0.05) and on current allergic rhinitis mediated by early environmental tobacco smoke (0.2002; p < 0.05). These results suggest the importance of promotion of ad-hoc health policies for promoting smoking cessation, especially during pregnancy.

The role of hypoxia in the pathophysiology of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nasal cavity characterized by excessive nasal mucus secretion and nasal congestion. The development of CRS is related to pathological mechanisms induced by hypoxia. Under hypoxic conditions, the stable expression of both Hypoxia inducible factor-1 (HIF-1) α and HIF-2α are involved in the immune response and inflammatory pathways of CRS. The imbalance in the composition of nasal microbiota may affect the hypoxic state of CRS and perpetuate existing inflammation. Hypoxia affects the differentiation of nasal epithelial cells such as ciliated cells and goblet cells, induces fibroblast proliferation, and leads to epithelial-mesenchymal transition (EMT) and tissue remodeling. Hypoxia also affects the proliferation and differentiation of macrophages, eosinophils, basophils, and mast cells in sinonasal mucosa, and thus influences the inflammatory state of CRS by regulating T cells and B cells. Given the multifactorial nature in which HIF is linked to CRS, this study aims to elucidate the effect of hypoxia on the pathogenic mechanisms of CRS.

Chronic Rhinosinusitis and COVID-19.

The COVID-19 pandemic has raised awareness about olfactory dysfunction, although a loss of smell was present in the general population before COVID-19. Chronic rhinosinusitis (CRS) is a common upper airway chronic inflammatory disease that is also one of the most common causes of olfactory dysfunction. It can be classified into different phenotypes (ie, with and without nasal polyps) and endotypes (ie, type 2 and non-type 2 inflammation). However, scientific information regarding CRS within the context of COVID-19 is still scarce. This review focuses on (1) the potential effects of severe acute respiratory syndrome coronavirus 2 infection on CRS symptoms, including a loss of smell, and comorbidities; (2) the pathophysiologic mechanisms involved in the olfactory dysfunction; (3) CRS diagnosis in the context of COVID-19, including telemedicine; (4) the protective hypothesis of CRS in COVID-19; and (5) the efficacy and safety of therapeutic options for CRS within the context of COVID-19.

Occupational and environmental exposures, the association with chronic sinusitis.

OBJECTIVES: To find the association between environmental and occupational exposures and chronic rhinosinusitis (CRS) development. METHODS: The Preferred Reporting Items Of Systematic Reviews Guidelines were used when a systematic literature review was conducted to find all published cases of CRS by searching PubMed database and Google Scholar. Published articles between 1989 and 2021 that reported chronic and occupational rhinosinusitis were included. However, articles that reported allergic rhinitis or upper airway diseases and non-English articles were excluded from this study. RESULTS: A total of 97 articles were extracted initially, and 15 articles were reviewed after excluding 82 articles that did not match our inclusion criteria. Most studies linked CRS development to smoke exposure (n=9734), followed by living in rural areas as farms (n=5504). Exposure to pesticides (n=4248) contributed to a higher prevalence of CRS. Blue-collar occupations, such as fire fighters, farmers, and fishermen were significantly related to CRS development in a total of 5260 patients. Chronic rhinosinusitis mainly affected more men (n=8912) than women (n=8076). CONCLUSION: We found that smoking was the most aggravating environmental factor. Chronic rhinosinusitis symptoms' severity increased with direct contact with allergens. Thus, the greatest proportion of patients with CRS was those with blue-collar occupations, such as firefighters, farmers, and fishermen.