Observational Study

. 2024 Sep;134(9):3965-3973.

doi: 10.1002/lary.31438. Epub 2024 Apr 18.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis

Daniel M Beswick¹, Christine M Liu¹, Jonathan B Overdevest², Anna Zemke³, Aastha Khatiwada⁴, David A Gudis², Jessa E Miller¹, Adam Kimple⁵, Jeremy P Tervo², Emily DiMango⁶, Jennifer L Goralski⁷, Claire Keating⁶, Brent Senior⁵, Amanda L Stapleton⁸, Patricia H Eshaghian⁹, Jess C Mace¹⁰, Karolin Markarian¹¹, Jeremiah A Alt¹², Todd E Bodner¹³, Naweed I Chowdhury¹⁴, Anne E Getz¹⁵, Peter H Hwang¹⁶, Ashoke Khanwalker¹⁵, Jivianne T Lee¹, Douglas A Li⁹, Meghan Norris⁵, Jayakar V Nayak¹⁶, Cameran Owens¹⁵, Zara M Patel¹⁶, Katie Poch¹⁷, Rodney J Schlosser¹⁸, Kristine A Smith¹², Timothy L Smith¹⁰, Zachary M Soler¹², Jeffrey D Suh¹, Grant A Turner¹⁰, Marilene B Wang¹, Milene T Saavedra¹⁷, Jennifer L Taylor Cousar^{17

19}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, University of California, Los Angeles, California, U.S.A.
² Department of Otolaryngology-Head and Neck Surgery, Columbia University, New York, New York, U.S.A.
³ Division of Pulmonary Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
⁴ Department of Biostatistics, National Jewish Health, Denver, Colorado, U.S.A.
⁵ Department of Otolaryngology-Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
⁶ Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University, New York, New York, U.S.A.
⁷ Department of Pulmonary Medicine, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
⁸ Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
⁹ Department of Pulmonary Medicine, University of California, Los Angeles, California, U.S.A.
¹⁰ Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, Oregon, U.S.A.
¹¹ CTSI, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.A.
¹² Department of Otolaryngology-Head and Neck Surgery, University of Utah, Salt Lake City, Utah, U.S.A.
¹³ Department of Psychology, Portland State University, Portland, Oregon, U.S.A.
¹⁴ Department of Otolaryngology-Head and Neck Surgery, Vanderbilt Health, Nashville, Tennessee, U.S.A.
¹⁵ Department of Otolaryngology-Head and Neck Surgery, University of Colorado, Aurora, Colorado, U.S.A.
¹⁶ Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, U.S.A.
¹⁷ Department of Medicine, National Jewish Health, Denver, Colorado, U.S.A.
¹⁸ Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Greenville, South Carolina, U.S.A.
¹⁹ Department of Pediatrics, National Jewish Health, Denver, Colorado, U.S.A.

PMID: 38634358
PMCID: PMC11305934
DOI: 10.1002/lary.31438

Observational Study

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis

Daniel M Beswick et al. Laryngoscope. 2024 Sep.

. 2024 Sep;134(9):3965-3973.

doi: 10.1002/lary.31438. Epub 2024 Apr 18.

Authors

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, University of California, Los Angeles, California, U.S.A.
² Department of Otolaryngology-Head and Neck Surgery, Columbia University, New York, New York, U.S.A.
³ Division of Pulmonary Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
⁴ Department of Biostatistics, National Jewish Health, Denver, Colorado, U.S.A.
⁵ Department of Otolaryngology-Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
⁶ Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University, New York, New York, U.S.A.
⁷ Department of Pulmonary Medicine, University of North Carolina, Chapel Hill, North Carolina, U.S.A.
⁸ Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.
⁹ Department of Pulmonary Medicine, University of California, Los Angeles, California, U.S.A.
¹⁰ Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, Oregon, U.S.A.
¹¹ CTSI, David Geffen School of Medicine, University of California, Los Angeles, California, U.S.A.
¹² Department of Otolaryngology-Head and Neck Surgery, University of Utah, Salt Lake City, Utah, U.S.A.
¹³ Department of Psychology, Portland State University, Portland, Oregon, U.S.A.
¹⁴ Department of Otolaryngology-Head and Neck Surgery, Vanderbilt Health, Nashville, Tennessee, U.S.A.
¹⁵ Department of Otolaryngology-Head and Neck Surgery, University of Colorado, Aurora, Colorado, U.S.A.
¹⁶ Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, California, U.S.A.
¹⁷ Department of Medicine, National Jewish Health, Denver, Colorado, U.S.A.
¹⁸ Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Greenville, South Carolina, U.S.A.
¹⁹ Department of Pediatrics, National Jewish Health, Denver, Colorado, U.S.A.

PMID: 38634358
PMCID: PMC11305934
DOI: 10.1002/lary.31438

Abstract

Objectives: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF).

Methods: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22.

Results: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5.

Conclusion: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF.

Level of evidence: 3 Laryngoscope, 134:3965-3973, 2024.

Keywords: CFTR modulator therapy; chronic rhinosinusitis; cystic fibrosis; elexacaftor/tezacaftor/ivacaftor; minimal clinically important difference.

PubMed Disclaimer

Conflict of interest statement

DMB: In the last 36 months, DMB has received grant support from CF Foundation, International Society of Inflammation and Allergy of the Nose and the Sue Ann and John L. Weinberg Foundation, honoraria, and consulting fees from Amgen, on medicolegal cases and from Garner Health (equity).

CML: NIDCD grant related to work.

JBO: Grant support from NIDCD K23DC019678 for investigation not affiliated with this project.

AZ: none

AK: none

DAG: none

JEM: none

AK: Grant support from the CFF and consultant for AcclarENT not related to this work.

JPT: none

ED: Grant support from the CFF and Vertex Pharmaceuticals, unrelated to this work.

JLG: Grant support from the CF Foundation and NHLBI unrelated to this work. Honoraria from the CF Foundation and Vertex Pharmaceuticals unrelated to this work.

CK: Grant support from the CFF not related to this work.

BS: Consultant for Lyra Therapeutics, Medical Center Pharmacy, Stryker, and Neurent

ALS: none

PHE: none

JCM: Has received grant support from CF Foundation related to this work in the past 36 months (BESWIC20A0).

KM: None

JAA: Consultant for OptiNose and Medtronic. Speaker panel GSK. GlycoMira board and equity holder. Grant support from CF Foundation related to this work BESWIC20A0.

TEB: Has received grant support from CF Foundation related to this work in the past 36 months (BESWIC20A0)

NIC: Unrelated to this work, NIC has received grant support from the Burroughs Wellcome Fund, American Rhinologic Society, and the National Cancer Institute

AEG: None

PHH: Consultant for Stryker, Medtronic, Slate Therapeutics; Equity ownership in Sound Health Systems.

AK: None

JTL: None

DAL: In the last 36 months, DAL has received grant support from the CF Foundation unrelated to this work.

MN: None

JVN: None

CO: None

ZMP: Consultant/Advisory Board for Optinose, Medtronic, Dianosic, Wyndly, Third Wave Therapeutics, Regeneron/Sanofi, Mediflix, ConsumerMedical. Equity in Olfera Therapeutics.

KP: None

RJS: Consultant for OptiNose, Medtronic, Stryker, Cyrano. Medical Directory for Healthy Humming.

KAS: None

TLS: None

ZMS: Consultant for OptiNose, Regeneron, SanofiGenzyme, and Lyra. Medical Directory for Healthy Humming.

GAT: In the last 36 months, GAT has received grants from the CF Foundation unrelated to this work.

MBW: None related to this work.

MTS: MTS receives funding from CFF unrelated to this work.

JLTC: In the last 36 months, JLT-C has received grants from the CF Foundation related to this work as well as for work unrelated to the manuscript. Unrelated to this work, she has received grants to her institution from Vertex Pharmaceuticals Incorporated, Eloxx, and 4DMT; has received fees from Vertex Pharmaceuticals Incorporated related to consultation on clinical research design, participation on advisory boards, and speaking engagements; and has served on advisory boards and/or provided clinical trial design consultation for Insmed, 4DMT, and AbbVie. She served on a DMC for AbbVie. She serves as the adult patient care representative to the CFF Board of Trustees, and on the CF Foundation’s Clinical Research Executive Committee, Clinical Research Advisory Board, Racial Justice Working Group and as immediate past chair of the CF TDN’s Sexual Health, Reproduction and Gender Research Working Group, on the scientific advisory board for Emily’s Entourage, and on the ATS Respiratory Health Awards Working Group. She currently serves as the Chair-elect of the ATS International Conference Committee (and associated committees) and previously served on the ATS Scientific Grant Review and Clinical Problems Assembly Programming Committees. She is a member of the International Advisory Board for Lancet Respiratory Medicine and the Editorial Board for the Journal of Cystic Fibrosis.

Remaining authors did not respond with any financial disclosures.

References

1. Cystic Fibrosis Foundation Patient registry: 2022 Annual Data Report. Accessed November 30, 2023. https://www.cff.org/medical-professionals/patient-registry.
1. Hamilos DL. Chronic Rhinosinusitis in Patients with Cystic Fibrosis. J Allergy Clin Immunol Pract. 2016;4(4):605–612. doi: 10.1016/j.jaip.2016.04.013 - DOI - PubMed
1. Kimple AJ, Senior BA, Naureckas ET, et al. Cystic Fibrosis Foundation otolaryngology care multidisciplinary consensus recommendations. Int Forum Allergy Rhinol. 2022;12(9):1089–1103. doi: 10.1002/alr.22974 - DOI - PMC - PubMed
1. Chang EH. New insights into the pathogenesis of cystic fibrosis sinusitis. Int Forum Allergy Rhinol. 2014;4(2):132–137. doi: 10.1002/alr.21252 - DOI - PMC - PubMed
1. Illing EA, Woodworth BA. Management of the Upper Airway in Cystic Fibrosis. Curr Opin Pulm Med. 2014;20(6):623–631. doi: 10.1097/MCP.0000000000000107 - DOI - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis

Affiliations

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials