Clinical Assessment of Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is a common disease that affects >10% of the adult population in Europe and the United States. It has been delineated phenotypically into CRS without nasal polyps and CRS with nasal polyps. Both have a high disease burden and an overlapping spectrum of symptoms such as nasal obstruction, olfactory dysfunction, facial pain, pressure, and nasal discharge. Primary assessment includes evaluation of patient symptoms and impact on quality of life, nasal endoscopic examination, and imaging. Significant progress has been made in the understanding of CRS pathophysiology. There is a move toward describing CRS in terms of the predominant endotype or inflammatory pattern pathomechanism rather than the traditional classification of patients with and without nasal polyps. An increased elucidation of the disease endotypes, as characterized by their inflammatory pathways and mediators, is leading to a tailored more personalized treatment approach to the different disease subtypes. Chronic rhinosinusitis (CRS) is a common disease that affects >10% of the adult population in Europe and the United States. It has been delineated phenotypically into CRS without nasal polyps and CRS with nasal polyps. Both have a high disease burden and an overlapping spectrum of symptoms such as nasal obstruction, olfactory dysfunction, facial pain, pressure, and nasal discharge. Primary assessment includes evaluation of patient symptoms and impact on quality of life, nasal endoscopic examination, and imaging. Significant progress has been made in the understanding of CRS pathophysiology. There is a move toward describing CRS in terms of the predominant endotype or inflammatory pattern pathomechanism rather than the traditional classification of patients with and without nasal polyps. An increased elucidation of the disease endotypes, as characterized by their inflammatory pathways and mediators, is leading to a tailored more personalized treatment approach to the different disease subtypes. INFORMATION FOR CATEGORY 1 CME CREDITCredit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions.Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI: In Practice Web site: www.jaci-inpractice.org/. The accompanying tests may only be submitted online at www.jaci-inpractice.org/. Fax or other copies will not be accepted.Date of Original Release: June 1, 2022. Credit may be obtained for these courses until May 31, 2023.Copyright Statement: Copyright © 2022-2024. All rights reserved.Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease.Target Audience: Physicians and researchers within the field of allergic disease.Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.List of Design Committee Members: Claire Hopkins, DM (Oxon), Stella E. Lee, MD, Ludger Klimek, PhD, and Zachary M. Soler, MD, MSc (authors); Michael Schatz, MD, MS (editor)Learning objectives: 1.To appreciate how available objective and subjective disease severity measures capture the diverse impacts of chronic rhinosinusitis (CRS).2.To list the co-primary endpoints utilized in phase 3 clinical trials for biologic mediations in the treatment of chronic rhinosinusitis with nasal polyps.3.To be able to differentiate inflammatory endotypes in patients with CRS based on clinical and inflammatory characteristics.4.To utilize current algorithms and employ shared decision-making approaches to fully understand and appropriately treat each individual CRS patient with available laboratory testing, recognition of comorbid conditions, and multi-disciplinary management.Recognition of Commercial Support: This CME has not received external commercial support.Disclosure of Relevant Financial Relationships with Commercial Interests: All authors and reviewers reported no relevant financial relationships. Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI: In Practice Web site: www.jaci-inpractice.org/. The accompanying tests may only be submitted online at www.jaci-inpractice.org/. Fax or other copies will not be accepted. Date of Original Release: June 1, 2022. Credit may be obtained for these courses until May 31, 2023. Copyright Statement: Copyright © 2022-2024. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma & Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Claire Hopkins, DM (Oxon), Stella E. Lee, MD, Ludger Klimek, PhD, and Zachary M. Soler, MD, MSc (authors); Michael Schatz, MD, MS (editor) Learning objectives: 1.To appreciate how available objective and subjective disease severity measures capture the diverse impacts of chronic rhinosinusitis (CRS).2.To list the co-primary endpoints utilized in phase 3 clinical trials for biologic mediations in the treatment of chronic rhinosinusitis with nasal polyps.3.To be able to differentiate inflammatory endotypes in patients with CRS based on clinical and inflammatory characteristics.4.To utilize current algorithms and employ shared decision-making approaches to fully understand and appropriately treat each individual CRS patient with available laboratory testing, recognition of comorbid conditions, and multi-disciplinary management. Recognition of Commercial Support: This CME has not received external commercial support. Disclosure of Relevant Financial Relationships with Commercial Interests: All authors and reviewers reported no relevant financial relationships. Chronic rhinosinusitis (CRS) diagnosis is made through clinical symptoms corroborated with imaging and endoscopic findings supportive of a local inflammatory process.1Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar Hallmark symptoms are nasal congestion and nasal discharge, accompanied by facial pain and pressure and/or reduced sense of smell. The symptoms must persist for more than 12 weeks and be supported by endoscopic findings of mucosal inflammation, discharge, and polypoid changes to the mucosa, and/or computed tomography (CT) imaging demonstrating mucosal thickening.1Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar,2Bachert C. Marple B. Schlosser R.J. Hopkins C. Schleimer R.P. Lambrecht B.N. et al.Adult chronic rhinosinusitis.Nat Rev Dis Primers. 2020; 6: 86Crossref PubMed Scopus (35) Google Scholar Demonstrating objective evidence of CRS is important, as studies suggest that a symptom-based definition alone has good sensitivity (89%) but poor specificity (2%-12%).3Hwang P.H. Irwin S.B. Griest S.E. Caro J.E. Nesbit G.M. Radiologic correlates of symptom-based diagnostic criteria for chronic rhinosinusitis.Otolaryngol Head Neck Surg. 2003; 128: 489-496Crossref PubMed Scopus (114) Google Scholar,4Bhattacharyya N. Lee L.N. Evaluating the diagnosis of chronic rhinosinusitis based on clinical guidelines and endoscopy.Otolaryngol Head Neck Surg. 2010; 143: 147-151Crossref PubMed Scopus (97) Google Scholar Adding endoscopy enhances specificity to 84%, using CgT scan as the diagnostic gold standard (with the Lund-Mackay score [LMS] ≥4 considered positive).4Bhattacharyya N. Lee L.N. Evaluating the diagnosis of chronic rhinosinusitis based on clinical guidelines and endoscopy.Otolaryngol Head Neck Surg. 2010; 143: 147-151Crossref PubMed Scopus (97) Google Scholar Clinical history is focused on the duration, frequency, and severity of sinonasal symptoms and their impact on quality of life (QOL) and ability to perform normal daily activities. Quantification of symptoms using a patient-rated outcome measure may facilitate assessment (see below). Evaluation of a patient’s history should consider comorbid conditions such as allergic rhinitis and lower respiratory disease such as asthma and bronchiectasis, and the control of disease, as this is important in guiding therapy.4Bhattacharyya N. Lee L.N. Evaluating the diagnosis of chronic rhinosinusitis based on clinical guidelines and endoscopy.Otolaryngol Head Neck Surg. 2010; 143: 147-151Crossref PubMed Scopus (97) Google Scholar Nonsteroidal anti-inflammatory drug (NSAID)-induced congestion or wheeze should also be determined.5Kowalski M.L. Agache I. Bavbek S. Bakirtas A. Blanca M. Bochenek G. et al.Diagnosis and management of NSAID-exacerbated respiratory disease (N-ERD)—a EAACI position paper.Allergy. 2019; 74: 28-39Crossref PubMed Scopus (156) Google Scholar Patients may also report symptom exacerbation by ingestion of alcohol.6Cardet J.C. White A.A. Barrett N.A. Feldweg A.M. Wickner P.G. Savage J. et al.Alcohol-induced respiratory symptoms are common in patients with aspirin exacerbated respiratory disease.J Allergy Clin Immunol Pract. 2014; 2: 208-213Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Prior treatments trialed and the response to these can be informative for diagnosis and making management decisions. Identifying patients with poor disease control can inform progression to surgery or, after surgery, the need for revision or other systemic treatment options such as corticosteroids and biologicals.1Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar,7Smith K.A. Orlandi R.R. Oakley G. Meeks H. Curtin K. Alt J.A. Long-term revision rates for endoscopic sinus surgery.Int Forum Allergy Rhinol. 2019; 9: 402-408Crossref PubMed Scopus (33) Google Scholar Many patients may have already undergone surgery—short duration of benefit is predictive of future risk of recurrence.8Hopkins C. Lund V. Does time from previous surgery predict subsequent treatment failure in chronic rhinosinusitis with nasal polyps?.Rhinology. 2021; 59: 277-283PubMed Google Scholar Once a diagnosis of CRS has been made, assessment should consider whether this is primary CRS (that is chronic inflammation originating in and limited to the paranasal sinuses) or secondary CRS, occurring as part of multisystem disease (eg, as a manifestation of autoimmune diseases or immunodeficiency) or arising from a source outside the sinuses (eg, odontogenic CRS). Even primary CRS is an umbrella term for a number of different subgroups, varying by location (isolated or diffuse), endotype, and role of allergy or infection. Clinical examination is focused on assessing the nasal airway patency and presence or absence of polyps. Anterior rhinosocopy can establish severe nasal polyps and any concomitant anatomical cause of nasal obstruction. Expansion of the nasal bridge or orbital signs may be present in severe CRS with nasal polyps (CRSwNP) in which bony remodeling has occurred.9Hopkins C. Chronic rhinosinusitis with nasal polyps.N Engl J Med. 2019; 381: 55-63Crossref PubMed Scopus (47) Google Scholar Nasal endoscopy is invaluable in the assessment of CRS and can inform diagnosis as well as response to therapy. It is a simple and well-tolerated part of the examination; local decongestion and anesthesia can be helpful but is often not required depending on the patient.10Singh V. Brockbank M.J. Todd G.B. Flexible transnasal endoscopy: is local anaesthetic necessary?.J Laryngol Otol. 1997; 111: 616-618Crossref PubMed Google Scholar Endoscopic evaluation of the nasal cavity provides important information on the status of the nasal mucosa (ie, edema or crusting), nasal discharge, anatomical abnormalities (eg, septal deviation, turbinate hypertrophy), evidence of visible obstruction of the nasal airway or ostiomeatal complex, evidence of previous surgery or adhesions in addition to allowing differentiation of the major phenotypical subgroups, based on the presence or absence of nasal polyps, which is often used to help inform treatment decisions in lieu of more detailed endotyping. Imaging is an important tool in CRS, used to confirm the diagnosis when endoscopy is equivocal, assess the severity or extent of disease, and guide treatment decisions. CT is the gold standard investigation for CRSwNP, usually without contrast.11Thwin M. Weitzel E.K. McMains K.C. Athanasiadis T. Psaltis A. Field J. et al.Validating the use of report-derived Lund-MacKay scores.Am J Rhinol Allergy. 2009; 23: 33-35Crossref Scopus (14) Google Scholar Plain X-rays are no longer recommended as they lack the sensitivity or specificity required to assess CRS. However, to minimize exposure to ionizing radiation, it is usually reserved for patients in whom medical treatment has failed and when surgical intervention or biological therapies are being considered. An exception to this is in the setting of symptoms suggestive of CRS but negative endoscopy, in which case upfront CT imaging has been shown to be both cost effective and to reduce unnecessary empiric medical treatment.12Leung R. Kern R. Jordan N. Almassian S. Conley D. Tan B.K. et al.Upfront computed tomography scanning is more cost-beneficial than empiric medical therapy in the initial management of chronic rhinosinusitis.Int Forum Allergy Rhinol. 2011; 1: 471-480Crossref PubMed Scopus (0) Google Scholar In the setting of unilateral nasal polyps, imaging should be considered at an early stage to exclude the rare occurrence of sinonasal malignancy or more common benign tumors such as inverted papilloma.13Paz Silva M. Pinto J.M. Corey J.P. Mhoon E.E. Baroody F.M. Naclerio R.M. Diagnostic algorithm for unilateral sinus disease: a 15-year retrospective review.Int Forum Allergy Rhinol. 2015; 5: 590-596Crossref PubMed Scopus (0) Google Scholar Low irradiation protocols should be used where possible. CT findings of importance include the extent and severity of nasal polyps and mucosal changes (Figure 1). The LMS14Lund V.J. Mackay IS. Staging in rhinosinusitus.Rhinology. 1993; 31: 183-184PubMed Google Scholar is a widely used, validated method based on the degree of opacification for the compartments of the sinuses and the ostiomeatal complex. This scoring system has been validated in several studies.11Thwin M. Weitzel E.K. McMains K.C. Athanasiadis T. Psaltis A. Field J. et al.Validating the use of report-derived Lund-MacKay scores.Am J Rhinol Allergy. 2009; 23: 33-35Crossref Scopus (14) Google Scholar,15Hopkins C. Browne J.P. Slack R. Lund V. Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict?.Otolaryngol Head Neck Surg. 2007; 137: 555-561Crossref PubMed Scopus (294) Google Scholar A limitation of CT imaging is that abnormalities are found in up to 39% of asymptomatic patients, and the mean LMS in a normal population is 4.16Lloyd G.A. CT of the paranasal sinuses: study of a control series in relation to endoscopic sinus surgery.J Laryngol Otol. 1990; 104: 477-481Crossref PubMed Google Scholar CT changes alone therefore have limited specificity and should be used in association with presenting symptoms. The disease subtype can be suggested by CT findings particularly in allergic fungal disease with bony remodeling and hyperdensities,17Bent 3rd, J.P. Kuhn F.A. Diagnosis of allergic fungal sinusitis.Otolaryngol Head Neck Surg. 1994; 111: 580-588Crossref PubMed Scopus (557) Google Scholar or central compartment atopic disease18DelGaudio J.M. Loftus P.A. Hamizan A.W. Harvey R.J. Wise S.K. Central compartment atopic disease.Am J Rhinol Allergy. 2017; 31: 228-234Crossref PubMed Scopus (49) Google Scholar (a phenotype of CRS related to inhalant allergies leading to centrally located polypoid changes), for example. The degree of osteoneogenesis in CRS indicates longstanding disease and poorer prognosis of treatment.19Bhandarkar N.D. Sautter N.B. Kennedy D.W. Smith T.L. Osteitis in chronic rhinosinusitis: a review of the literature.Int Forum Allergy Rhinol. 2013; 3: 355-363Crossref PubMed Scopus (35) Google Scholar,20Sacks P.L. Snidvongs K. Rom D. Earls P. Sacks R. Harvey R.J. The impact of neo-osteogenesis on disease control in chronic rhinosinusitis after primary surgery.Int Forum Allergy Rhinol. 2013; 3: 823-827Crossref PubMed Scopus (0) Google Scholar Opacification of the olfactory cleft is common in patients with hyposmia and correlates with psychophysical testing of olfaction.21Loftus C. Schlosser R.J. Smith T.L. Alt J.A. Ramakrishnan V.R. Mattos J.L. et al.Olfactory cleft and sinus opacification differentially impact olfaction in chronic rhinosinusitis.Laryngoscope. 2020; 130: 2311-2318Crossref PubMed Scopus (13) Google Scholar The anatomy revealed on CT sinus imaging reveals essential details for planning safe surgery including the presence of sphenoethmoidal cells, location of the optic nerve, anterior ethmoidal arteries, and the position and integrity of the lamina papyracea and cribriform plate. Magnetic resonance imaging can reveal the presence of sinonasal inflammation. It is most useful in the setting of allergic fungal disease or advanced disease with dehiscence of the skull base or orbits but does not provide the spatial and bony definition required for surgical planning.1Fokkens W.J. Lund V.J. Hopkins C. Hellings P.W. Kern R. Reitsma S. et al.European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Google Scholar Olfactory dysfunction has been shown to be a used marker of type 2 disease severity in CRS.22Mullol J. Marino-Sanchez F. Valls M. Alobid I. Marin C. The sense of smell in chronic rhinosinusitis.J Allergy Clin Immunol. 2020; 145: 773-776Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar A number of studies have compared self-reported olfactory assessments with psychophysical testing, usually noting weak-to-moderate correlations23Mattos J.L. Schlosser R.J. Storck K.A. Soler Z.M. Understanding the relationship between olfactory-specific quality of life, objective olfactory loss, and patient factors in chronic rhinosinusitis.Int Forum Allergy Rhinol. 2017; 7: 734-740Crossref PubMed Scopus (35) Google Scholar,24Desiato V.M. Levy D.A. Byun Y.J. Nguyen S.A. Soler Z.M. Schlosser R.J. The prevalence of olfactory dysfunction in the general population: a systematic review and meta-analysis.Am J Rhinol Allergy. 2020; (1945892420946254)Google Scholar; however, self-reported loss of sense of smell has a stronger correlation with the results of psychophysical testing in the setting of CRS.25Haxel B.R. Bertz-Duffy S. Fruth K. Letzel S. Mann W.J. Muttray A. Comparison of subjective olfaction ratings in patients with and without olfactory disorders.J Laryngol Otol. 2012; 126: 692-697Crossref Scopus (29) Google Scholar,26Hox V. Bobic S. Callebaux I. Jorissen M. Hellings P.W. Nasal obstruction and smell impairment in nasal polyp disease: correlation between objective and subjective parameters.Rhinology. 2010; 48: 426-432Crossref PubMed Scopus (52) Google Scholar Therefore, assessment of both patient-reported and subjective quantitative tests of olfaction provides the clearest assessment of olfactory impact. Olfactory testing should be able to discriminate between normal function and varying degrees of olfactory dysfunction. Many olfactory tests exist,27Hummel T. Whitcroft K.L. Andrews P. Altundag A. Cinghi C. Costanzo R.M. et al.Position paper on olfactory dysfunction.Rhinol Suppl. 2017; 54: 1-30Crossref PubMed Scopus (342) Google Scholar but the 40-Item University of Pennsylvania Smell Identification Test (UPSIT) and Sniffin’ Sticks tests are the most commonly used English-language–based tests both clinically and for research purposes.28Doty R.L. Frye R.E. Agrawal U. Internal consistency reliability of the fractionated and whole University of Pennsylvania Smell Identification Test.Percept Psychophys. 1989; 45: 381-384Crossref PubMed Scopus (185) Google Scholar,29Hummel T. Kobal G. Gudziol H. Mackay-Sim A. Normative data for the “Sniffin’ Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3000 subjects.Eur Arch Otorhinolaryngol. 2007; 264: 237-243Crossref PubMed Scopus (0) Google Scholar The UPSIT is a suprathreshold test that measures a subject’s ability to correctly identify odors in a forced-choice fashion. It can be self-administered and has extensive sex and age normative data. The Sniffin’ Sticks battery of tests includes Threshold, Discrimination, and Identification (TDI) testing, which is combined for a composite TDI score. The Sniffin’ Sticks test can be reused and also has extensive normative data, but requires trained personnel to administer. Evidence to support an association between CRS and allergy remains equivocal; a systematic review30Wilson K.F. McMains K.C. Orlandi R.R. The association between allergy and chronic rhinosinusitis with and without nasal polyps: an evidence-based review with recommendations.Int Forum Allergy Rhinol. 2014; 4: 93-103Crossref PubMed Scopus (68) Google Scholar included 24 studies, with an almost equal number either supporting or refuting an association. Furthermore, sensitization may not always correlate to clinical reactivity. The role of routine allergy testing in the assessment of CRS is therefore uncertain. Given the overlap in presenting features, it seems likely that identifying and treating coexisting allergy would be at least of symptomatic benefit. In addition, there are subgroups where there is a strong association with allergy, including allergic fungal rhinosinusitis and central compartment atopic disease. A single metric that accurately assesses disease severity in CRS should be easily quantifiable, reflect the impacts considered most important, and would directionally and proportionally change with disease exacerbations or treatments such that it could guide decision-making. Unfortunately, no single ideal metric exists to assess disease severity in CRS. The complexity of assessing severity in CRS is a result of several inherent disease characteristics. One major challenge is the heterogeneity of CRS. As discussed above, the diagnostic criteria for CRS are relatively broad, and in many ways CRS can be considered an umbrella diagnosis that includes conditions with very different phenotypes and/or endotypes. Metrics to assess disease severity in 1 subset of CRS may not apply in another. For example, the United States Food and Drug Administration (FDA) has required polyp grading to be included as a coprimary endpoint in pharmaceutical trials that include patients with CRSwNP.31Bachert C. Han J.K. Desrosiers M. Hellings P.W. Amin N. Lee S.E. et al.Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials.Lancet. 2019; 394: 1638-1650Abstract Full Text Full Text PDF PubMed Scopus (387) Google Scholar, 32Gevaert P. Omachi T.A. Corren J. Mullol J. Han J. Lee S.E. et al.Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials.J Allergy Clin Immunol. 2020; 146: 595-605Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar, 33Han J.K. Bachert C. Fokkens W. Desrosiers M. Wagenmann M. Lee S.E. et al.Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Respir Med. 2021; 9: 1141-1153Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 34Bachert C. Han J.K. Desrosiers M.Y. Gevaert P. Heffler E. Hopkins C. et al.Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: a randomized, placebo-controlled trial.J Allergy Clin Immunol. 2022; (e12.): 1309-1317Abstract Full Text Full Text PDF Scopus (13) Google Scholar However, this metric, like many other measures of disease severity, has not been formally validated and would be irrelevant in subtypes of CRS without nasal polyps (CRSsNP). The second challenge relates to the wide-ranging impacts of CRS. Although CRS may be defined based on classic symptoms, it is well established that disease impacts extend far beyond just these 4 symptoms and include sleep disturbance, fatigue, depression, cognitive function, and economic productivity loss.35Orlandi R.R. Kingdom T.T. Smith T.L. Bleier B. DeConde A. Luong A.U. et al.International consensus statement on allergy and rhinology: rhinosinusitis 2021.Int Forum Allergy Rhinol. 2021; 11: 213-739Crossref PubMed Scopus (101) Google Scholar In addition, the frequency and severity of impact can differ across CRS subtypes. The third challenge relates to the lack of strong correlation between patient-reported symptoms and objective measures of disease. This is particularly true for broad measures, such as patient-reported QOL scores and CT scoring systems.36Zheng Y. Zhao Y. Lv D. Liu Y. Qiao X. An P. et al.Correlation between computed tomography staging and quality of life instruments in patients with chronic rhinosinusitis.Am J Rhinol Allergy. 2010; 24: e41-e45Crossref PubMed Scopus (47) Google Scholar This can create situations where a patient might be considered severely impacted on a patient-reported scale but minimally impacted on an objective measure, or vice versa. The final challenge relates to variability in patient preference. Although certain symptoms or disease impacts tend to be rated more important than others across populations, this can vary for individuals. This is particularly significant in the light of research suggesting that patient satisfaction is tied to resolution of symptoms considered most important to individual patients.37Mattos J.L. Rudmik L. Schlosser R.J. Smith T.L. Mace J.C. Alt J. et al.Symptom importance, patient expectations, and satisfaction in chronic rhinosinusitis.Int Forum Allergy & Rhinol. 2019; 9: 593-600Crossref PubMed Scopus (0) Google Scholar The above discussion should make it clear that a suite of metrics is necessary to appropriately assess disease severity across a population of patients with CRS. For any individual patient or clinical/research scenario, 1 or more metrics may best capture the disease characteristics of interest to inform the question at hand. Certainly, combining complementary measures will be necessary in many instances to give the most complete understanding of disease severity for a particular patient. As our understanding of disease endotypes improves and classification becomes more precise, it is likely that core outcome sets will be developed that best reflect the underlying pathophysiology, unique impacts, and patient preferences of specific CRS subtypes.38Hopkins C. Hettige R. Soni-Jaiswal A. Lakhani R. Carrie S. Cervin A. et al.CHronic Rhinosinusitis Outcome MEasures (CHROME), developing a core outcome set for trials of interventions in chronic rhinosinusitis.Rhinology. 2018; 56: 22-32Crossref PubMed Google Scholar The sections that follow will describe major categories of disease severity assessments and highlight examples of metrics that are commonly employed. Patient-reported outcomes measures (PROMs) are widely used both in clinical decision-making and in outcomes research.39Weldring T. Smith S.M. Patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs).Health Serv Insights. 2013; 6: 61-68Crossref PubMed Google Scholar The appeal of PROMs is that they can be used longitudinally and reflect an individual patients’ perception of disease impact. This makes particular sense when one considers that CRS is rarely a life-threatening condition. Available PROMs can be broken down into QOL measures, symptom severity scales, and disease control instruments. A myriad of QOL instruments have been developed and/or adapted for use in CRS, and several reviews exist that describe their evidence base.40Quintanilla-Dieck L. Litvack J.R. Mace J.C. Smith T.L. Comparison of disease-specific quality-of-life instruments in the assessment of chronic rhinosinusitis.Int Forum Allergy Rhinol. 2012; 2: 437-443Crossref PubMed Scopus (56) Google Scholar,41Rudmik L. Hopkins C. Peters A. Smith T.L. Schlosser R.J. Soler Z.M. Patient-reported outcome measures for adult chronic rhinosinusitis: a systematic review and quality assessment.J Allergy Clin Immunol. 2015; 136 (1532-40.e2)Abstract Full Text Full Text PDF Scopus (93) Google Scholar Instruments that assess QOL in CRS can be categorized as sinus-specific instruments, general instruments, and instruments that capture extra-sinus manifestations related to CRS. The most commonly us