Overall symptom severity as a patient-reported outcome measure for chronic rhinosinusitis: what it reflects and how to measure it.

BACKGROUND: The objective of this study was to identify how - and to what extent - overall symptom severity (OSS) score reflects individual chronic rhinosinusitis (CRS) symptoms and whether it can be measured using alternatives to the standard visual analog scale (VAS). METHODS: CRS patients from four sites across three continents rated their OSS scores, severities of nasal obstruction, nasal drainage, decreased sense of smell, facial pain/pressure and sleep disturbance using a standard VAS, VAS with labeled tick marks at every 1 centimeter, and by writing down their OSS on a scale of 0 - 100 (which was divided by 10), all of which lead to severity scores ranging from 0 - 10 in 0.1 intervals. Quality of life was measured using the SNOT-22 and EQ-5D VAS. RESULTS: In 311 CRS patients, OSS score was significantly correlated with SNOT-22 and EQ-5D VAS. OSS score was most greatly associated with the mean of all individual symptom severity scores. From individual CRS symptoms, OSS was most greatly associated with nasal obstruction followed by nasal drainage and facial pain/pressure severities. These results held true for participants with and without nasal polyps. Measurement of OSS and individual symptom severity scores using a standard VAS, tick-marked VAS, and write-in option had near-perfect consistency. CONCLUSIONS: We demonstrate for the first time that OSS largely reflects the mean of individual CRS symptom severities, although OSS is=== most weighted by nasal obstruction severity. OSS and individual symptom severity scores can be measured using a standard VAS, tick-marked VAS or write-in prompt with near-perfect consistency.

Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Consensus criteria for chronic rhinosinusitis disease control: an international Delphi Study.

BACKGROUND: Chronic rhinosinusitis (CRS) disease control is a global metric of disease status for CRS. While there is broad acceptance that it is an important treatment goal, there has been inconsistency in the criteria used to define CRS control. The objective of this study was to identify and develop consensus around essential criteria for assessment of CRS disease control. METHODS: Modified Delphi methodology consisting of three rounds to review a list of 24 possible CRS control criteria developed by a 12-person steering committee. The core authorship of the multidisciplinary EPOS 2020 guidelines was invited to participate. RESULTS: Thirty-two individuals accepted the invitation to participate and there was no dropout of participants throughout the entire study (3 rounds). Consensus essential criteria for assessment of CRS control were: overall symptom severity, need for CRS-related systemic corticosteroids in the prior 6 months, severity of nasal obstruction, and patient-reported CRS control. Near-consensus items were: nasal endoscopy findings, severity of smell loss, overall quality of life, impairment of normal activities and severity of nasal discharge. Participants’ comments provided insights into caveats of, and disagreements related to, near-consensus items. CONCLUSIONS: Overall symptom severity, use of CRS-related systemic corticosteroids, severity of nasal obstruction, and patient-reported CRS control are widely agreed upon essential criteria for assessment of CRS disease control. Consideration of near-consensus items to assess CRS control should be implemented with their intrinsic caveats in mind. These identified consensus CRS control criteria, together with evidence-based support, will provide a foundation upon which CRS control criteria with wide-spread acceptance can be developed.

Discordance of chronic rhinosinusitis disease control between EPOS guidelines and patient perspectives identifies utility of patient-rated control assessment.

BACKGROUND: The objective of this study was to determine concordance of patient-reported chronic rhinosinusitis (CRS) disease control with CRS disease control assessed according to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria. METHODS: In 421 participants, CRS disease control was determined using EPOS criteria which include the burden of 5 symptoms measured on a binary scale, use of rescue medications in the prior 6 months and presence of diseased mucosa on nasal endoscopy. Symptom severity was also assessed using a visual analogue scale (VAS). Participants rated their CRS disease control as "controlled","partly controlled" or "uncontrolled". RESULTS: Patient-reported and EPOS-based CRS disease control ratings agreed for 49.6% of participants. Amongst cases of disagreement, EPOS guidelines assessed worse CRS disease control relative to 92.9% of patients. Facial pain/pressure and impaired sense of smell distinctly associated with patient agreement with EPOS guidelines on having "uncontrolled" CRS. Higher VAS symptom scores were associated with worse patient-reported CRS disease control (i.e., agreeing with EPOS guidelines). Removal of the nasal endoscopy criterion improved agreement between patients' and EPOS control assessments, and replacement of this criterion with patient-reported control further aligned EPOS guidelines with patient perspectives. CONCLUSIONS: EPOS guidelines regularly assess worse CRS control than assessed by patients. The lack of more gradated symptom severity criteria and inclusion of nasal endoscopy may contribute to discordance of EPOS guidelines with patient-reported CRS control. Replacement of nasal endoscopy findings with a measure of patient-reported CRS disease control better aligns EPOS CRS disease control guidelines with patients' perspectives.

Disease control in chronic rhinosinusitis: a qualitative study of patient perspectives.

BACKGROUND: The definition of disease control in chronic rhinosinusitis (CRS) is an active area of study. However, investigations have not engaged CRS patients in how they think about disease control. This study seeks to understand the patient perspective on CRS disease control. METHODS: Qualitative phenomenological study using constant comparative methodology was applied. The research team conducted 10, one-on-one interviews with CRS patients ranging from 22 to 55 minutes in length. The content of the interview protocol was determined through iterative discussion amongst all authors. Two authors served as coders to identify recurrent themes. Themes were analyzed for meaning and conclusions were summarized. RESULTS: Three recurring themes determined from patients were that (1) use of the terminology control adequately represents this phenomenon, (2) components of control could be classified into four main themes relating to CRS symptomatology, exacerbation of comorbid disease, quality of life and acute exacerbations of CRS, and (3) when patients deem their CRS is uncontrolled they are more willing to escalate their treatment to include escalating their daily maintenance regimen, seeking otolaryngology referral, taking rescue medication or undergoing endoscopic sinus surgery. CONCLUSIONS: CRS patients consider their daily symptoms, the severity and frequency of CRS exacerbations, impact on quality of life as well as exacerbation of comorbid disease when thinking about their disease control. Disease control is a goal of treatment for patients and uncontrolled disease motivates patients to seek further treatment. Physicians should explore all components of CRS control when considering disease status and need for further treatment.

Endoscopic grading systems for nasal polyps: are we comparing apples to oranges?

Endoscopic grading of nasal polyps (NP) is typically a coprimary endpoint in clinical trials evaluating treatments for chronic rhinosinusitis with nasal polyps (CRSwNP). However, a consensus on the most effective way to grade nasal polyps has not been reached. Different scales have been used, hampering the interpretation of data across trials. This review compares the characteristics of NP grading systems used in registration trials for approved NP treatments. These fundamental differences in grading systems make quantitative comparison of outcomes between trials inaccurate and potentially misleading. In lieu of a universal grading system, reporting the baseline distribution of polyp grades (unilateral and/or summed/total grades), as well as changes from baseline over time by baseline grade may help improve interpretability of outcomes and reduce inaccuracy when attempting cross-trial comparisons and making therapeutic decisions.

Individual symptom visual analogue scale severity scores for determining EPOS guideline-based chronic rhinosinusitis disease control.

BACKGROUND: The goal of this study was to determine how to translate visual analogue scale (VAS) symptom scores to the binary, descriptive symptom scales used in the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria for chronic rhinosinusitis (CRS) disease control. METHODS: 309 CRS patients were recruited. All patients rated their burden of 5 symptoms (nasal blockage, rhinorrhea/postnasal drip, facial pain/pressure, smell loss, sleep disturbance or fatigue) using the binary EPOS descriptive symptom scales and a VAS (on a scale of 0 to 10). In addition, participants completed a 22-item Sinonasal Outcome Test (SNOT-22) and rated their overall CRS disease control as "controlled", "partly controlled" or "uncontrolled" Results: Symptom burdens measured by VAS, binary descriptive EPOS scale and SNOT-22 were associated with worsening CRS disease control reported by participants. Each symptom had a distinct VAS score cut-off that strongly predicted the uncontrolled option on the corresponding binary descriptive EPOS symptom scale. However, the predictive ability of VAS for rhinorrhea/ postnasal drip was disparately worse than the other 4 symptoms. When considering all symptom data simultaneously, a VAS score higher than 3.5 strongly predicted the uncontrolled option on the corresponding binary descriptive EPOS symptom scale for all 5 symptoms. CONCLUSIONS: A VAS symptom score of higher than 3.5 translates to the uncontrolled option in the binary, descriptive symptom scale of the EPOS control criteria. The rhinorrhea/postnasal drip descriptive symptom scale translates disparately worse to VAS scores and may be considered for revision in future criteria.

[Olfactory and gustatory disorders]. / Riech- und Schmeckstörungen.

This manuscript aims to provide an overview of the etiology and diagnosis of olfactory and gustatory disorders. Not only are they common with about 5% of the population affected, but olfactory and gustatory disorders have recently gained attention in light of the rising SARS-CoV­2 pandemic: sudden loss of smell and/or taste is regarded as one of the cardinal symptoms. Furthermore, in the early diagnostics of neurodegenerative diseases, olfactory disorders are of great importance. Patients with olfactory dysfunction often show signs of depression. The impact of olfactory/gustatory disorders is thus considerable, but therapeutic options are unfortunately still limited. Following a description of the etiology, the diagnostic and therapeutic options are discussed on the basis of current literature. Potential future treatments are also addressed, e.g. autologous mucosal grafts or olfactory implants.

Patient-reported chronic rhinosinusitis disease control is a valid measure of disease burden.

BACKGROUND: Disease control is an important treatment goal for chronic uncurable conditions such as chronic rhinosinusitis (CRS). The objective of this study was to determine whether patient-reported CRS disease control is a valid reflection of disease burden. METHODS: Prospective longitudinal study of 300 CRS patients (35% CRS with nasal polyps, 65% CRS without nasal polyps). At enrollment and at a subsequent follow-up timepoint, all participants were asked to rate their CRS disease control as 'not at all', 'a little', 'somewhat', 'very', 'completely' as well as to complete a 22-item Sinonasal Outcome Test (SNOT-22) and the 5-dimension EuroQol general health questionnaire from which the visual analogue scale (EQ-5D VAS) was used. RESULTS: At enrollment and follow-up timepoints, patient-reported CRS disease control was significantly correlated with SNOT-22 and EQ-5D VAS scores. The change in patient-reported CRS disease control was significantly correlated with change in SNOT-22 and change in EQ-5D VAS scores. There was significant cross-sectional and longitudinal correlation between patient-reported control and all SNOT-22 subdomain scores. A SNOT-22 score of ≤25 points or lower, or an EQ-5D VAS score of ≥77 was predictive of having well - (i.e. 'very' or 'completely') controlled CRS. CONCLUSIONS: Patient-reported CRS disease control is a valid measure of CRS disease burden and general QOL. A patient-reported assessment of CRS disease control could be considered as a component of a more comprehensive measure of CRS disease control.

Rhinology in review: from COVID-19 to biologicals.

We look back at the end of what soon will be seen as an historic year, from COVID-19 to real-world introduction of biologicals influencing the life of our patients. This review describes the important findings in Rhinology over the past year. A large body of evidence now demonstrates loss of sense of smell to be one of the most common symptoms of COVID-19 infection; a meta-analysis of 3563 patients found the mean prevalence of self-reported loss to be 47%. A number of studies have now shown long-term reduced loss of smell and parosmia. Given the high numbers of people affected by COVID-19, even with the best reported recovery rates, a significant number worldwide will be left with severe olfactory dysfunction. The most prevalent causes for olfactory dysfunction, besides COVID-19 and upper respiratory tract infections in general, are trauma and CRSwNP. For these CRSwNP patients a bright future seems to be starting with the development of treatment with biologics. This year the Nobel prize in Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch which has greatly enhanced our understanding of nasal hyperreactivity and understanding of intranasal trigeminal function. Finally, a new definition of chronic rhinitis has been proposed in the last year and we have seen many papers emphasizing the importance of endotyping patients in chronic rhinitis and rhinosinusitis in order to optimise treatment effect.

Multi-institutional minimal clinically important difference of the 22-item Sinonasal Outcome Test in medically managed chronic rhinosinusitis.

BACKGROUND: With a rapid proliferation of clinical trials to study novel medical treatments for CRS, the objective of this study was to study the minimal clinically important difference (MCID) of the 22-item Sinonasal Outcome Test (SNOT-22) in medically-managed CRS patients. METHODS: A total of 183 medically-treated CRS patients were recruited. All patients completed a SNOT-22 at enrollment and subsequent follow up visit. Distribution and anchor-based methods were used for MCID calculation. These data were combined with data from a previously published study on SNOT-22 MCID in 247 medically managed CRS patients to determine a final recommended MCID value using the combined cohort of 430 patients. RESULTS: In our cohort, distribution- and anchor-based methods -"using both sinus-specific and general health anchors-"provided greatest support for a 12-point SNOT-22 MCID, which had approximately 55% sensitivity but 81% specificity for detecting patients explicitly reporting improvement in their sinus symptoms and general health. In the combined cohort of 430 patients, we also found greatest support for a 12-point SNOT-22 MCID, which had approximately 57% sensitivity and 81% specificity for detecting patients explicitly reporting improvement in their sinus symptoms and general health. We also find evidence that the MCID value may be higher in CRS patients without nasal polyps compared to those with nasal polyps. CONCLUSIONS: Our results - which include data from patients from two different institutions and regions - confirm a SNOT-22 MCID of 12 in medically managed CRS patients. The SNOT-22 MCID was specific but not sensitive for identifying CRS patients experiencing improvement in symptoms or general health.

Individual importance of olfaction decreases with duration of smell loss.

BACKGROUND: The personal importance of a lost neurologic - motor or sensory - function in several conditions has been shown to decrease as the afflicted patient becomes accustomed to not having that function. It is unknown how the importance of olfaction changes with duration of olfactory dysfunction (OD). The aim of this study was to evaluate the association between duration of smell loss and individual significance of olfaction, and whether this relationship would be modulated by other factors, such as etiology of smell loss. METHODS: This is a retrospective study including a total 163 subjects with different degrees of olfactory function. Individual significance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). Demographics, olfactory function, duration and etiology of OD were evaluated. Group comparisons, bivariate correlations, analyses of variance and multivariate linear regression were applied to detect differences and associations with the outcome measure of IOQ. RESULTS: A significant negative correlation was found between duration of OD and the IOQ. Other important findings include a significantly higher IOQ in patients with posttraumatic- compared to idiopathic OD and in patients with higher aggravation scores compared to the lower aggravation group. Multivariate regression analysis further confirmed that duration of smell loss was independently associated with IOQ. CONCLUSIONS: The duration of smell loss is negatively correlated with the individual importance of olfaction, suggesting that patients develop coping mechanisms for adjusting to OD.

Validity of systemic antibiotics and systemic corticosteroid usage for chronic rhinosinusitis as metrics of disease burden.

BACKGROUND: The frequencies of systemic antibiotics and oral corticosteroids taken for chronic rhinosinusitis (CRS) indicate poor CRS disease control. We sought to determine the validity and responsiveness of these metrics as reflections of CRS disease burden. METHODOLOGY: One hundred and eighty-seven patients undergoing medical management for CRS were recruited. Participants were assessed at two time points: enrollment and a follow-up appointment three to nine months later. At each time point, CRS related antibiotic and oral corticosteroid usage in the previous three months was measured, while general and disease-specific quality of life (QOL) was measured using the visual analog scale of the 5-dimension EuroQol questionnaire (EQ-5D VAS) and the 22-item Sinonasal Outcome Test (SNOT-22), respectively. RESULTS: The frequency of CRS-related antibiotics and oral corticosteroids use was cross-sectionally correlated with EQ-5D VAS and SNOT-22 at the corresponding time points. For participants reporting usage of these medications at enrollment, there was a decrease of 1 course per 3 months for both CRS-related antibiotics and oral corticosteroids. Change in CRS-related antibiotics from enrollment to follow-up was correlated with change in both EQ-5D and SNOT-22 over the same timeframe. The change in CRSrelated oral corticosteroids was correlated with change in both EQ-5D VAS and SNOT-22). These correlations were stronger in the subset of patients who had a change in these metrics over the study period. CONCLUSIONS: The frequencies of CRS-related antibiotic use and oral corticosteroid use are valid and responsive measures of CRS disease burden.

Quality of life impairment due to chronic rhinosinusitis in asthmatics is mediated by asthma control.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma, when comorbid, may influence each other’s disease course and decrease quality of life (QOL). Our objective was to determine if poorer asthma control due to CRS symptoms could be a mechanism for decreased QOL in asthmatic CRS patients. METHODS: A total of 120 asthmatic CRS patients were recruited. CRS symptom burden was measured using the 22-item Sinonasal Outcome Test (SNOT-22) and patient-reported CRS symptom control, general health-related QOL was measured using the visual analog scale of the 5-dimensional EuroQol quality of life survey (EQ-5D VAS), and asthma control was measured using the Asthma Control Test (ACT). Association was sought between these outcome measures. A mediation model was created and validated to show that asthma control mediated the association between CRS symptom burden and decreased general health-related QOL. RESULTS: ACT score was associated with SNOT-22, EQ-5D VAS was associated with SNOT-22 score, and EQ-5D VAS was associated with ACT score. A statistically significant mediation effect for ACT score in the association between SNOT-22 and EQ-5D VAS), which represented 22.1% of the total effect of SNOT-22 on EQ-5D VAS, was identified. Similar findings were made for patientreported CRS symptom control instead of SNOT-22 score. CONCLUSIONS: In asthmatic CRS patients, a sizeable portion of CRS impact on QOL is indirectly mediated through the effect of CRS on poorer asthma control which may then drive decreased QOL.