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Published in final edited form as: J Cyst Fibros. 2023 Nov 18;23(6):1195–1198. doi: 10.1016/j.jcf.2023.11.006

Olfactory Loss in People with Cystic Fibrosis: Community Perceptions and Impact

Jessa E Miller 1,*, Christine M Liu 2,*, Edith T Zemanick 3, Jason M Woods 4, Christopher H Goss 5, Jennifer L Taylor-Cousar 6,7, Daniel M Beswick 1
PMCID: PMC11210575  NIHMSID: NIHMS2004381  PMID: 37981480

Abstract

Background

Olfactory dysfunction (OD) is prevalent in people with cystic fibrosis (PwCF) and can negatively impact quality-of-life (QOL). This study evaluated perceptions of OD, investigated how OD impacts QOL, and assessed willingness to participate in OD research among the CF community.

Methods

A 21-question survey was distributed through the CF Foundation’s Community Voice program in 2023. The survey included questions on olfaction and interest in research. The Brief Questionnaire of Olfactory Disorders (BQOD), a validated person-reported outcome measure to assess QOL, was included.

Results

Seventy-six responses were received. Overall, 91% (69/76) reported olfactory problems. Mean BQOD score was 5.0 (standard deviation=4.8), indicating olfactory QOL impairment was present. Ninety-five percent (72/76) reported research on OD is worthwhile and were willing to participate in research.

Conclusion

Among PwCF, OD and olfactory-specific QOL impairments are prevalent. There is strong interest and willingness to participate in OD research among the CF community.

Keywords: olfactory dysfunction, cystic fibrosis, olfaction, quality of life, smell

Introduction

Olfaction is a critical sense that augments interpersonal communication, impacts nutritional status, and enables avoidance of certain dangers.1 Olfactory dysfunction (OD) is common in people with cystic fibrosis (PwCF) and has significant adverse effects. Existing studies demonstrate that OD is present in the majority of adults with CF, with rates of olfactory impairment exceeding 90% in certain reports.2–4 OD is associated with increased rates of depression and loneliness, negatively impacts quality-of-life (QOL), and is associated with a greater risk of mortality in the general population.1,5,6

The development of highly effective modulator therapies (HEMT) has dramatically improved outcomes and increased life expectancy for PwCF who are eligible for and tolerant of these medications.7 HEMT improves sinonasal symptoms as well as the radiologic and endoscopic components of chronic rhinosinusitis (CRS); however, OD, which stems from CRS, has been refractory to improvement with HEMT.8–12 Data from two prospective studies demonstrated that adults with CF who were treated with HEMT did not demonstrate improvements in OD.13,14 A third study among adolescents (mean age=17.3 years) did not show olfactory improvement after HEMT.15 It is possible that chronic upper airway inflammation leads to irreversible deficits in olfaction, stemming from inflammation near the nasal portion of the olfactory apparatus. Thus, despite the expansion and uptake of HEMT, OD continues to negatively impact many PwCF.

While OD is both prevalent and longstanding, limited research has been performed on the perceptions of this disease manifestation among PwCF. Therefore, the objectives of this study were to investigate perceptions of OD among members of the CF community, evaluate olfactory-specific QOL using a person-reported outcome measure (PROM), and assess the interest of PwCF in participating in OD research.

Methods

Following Institutional Review Board approval (UCLA#23-000107), a 21-question survey was constructed to ascertain demographic information, details on self-reported olfactory capability, and preferences on participating in OD research among PwCF (Supplemental Table). The survey included the Brief Questionnaire of Olfactory Disorders (BQOD), a validated PROM used to assess olfactory-specific QOL (range: 0–21 calculated as the sum of seven individual item scores; higher scores signifying worse QOL impairment).16,17 Descriptive statistics were performed for each BQOD question and for the total score. In March/April 2023, the survey was emailed twice to adults with CF and parents or caregivers of children with CF via the CF Foundation’s Community Voice program. Community Voice provides an empowering, virtual opportunity for people with cystic fibrosis and their family members to share their experiences, perspectives, priorities, and knowledge to impact CF research, care, and programs.18 1,194 members within Community Voice were invited to participate in the survey, and we used data from the 2021 CF Foundation Patient Registry to evaluate how respondents represented the broader CF community. Due to its sample size, the Community Voice is largely representative of the CF population in the U.S.19 Compared to the most recent 2021 CFF Patient Registry Report, fewer individuals in Community Voice were male, and there is a 2% and 4% discrepancy for those who identify as a person of color and Hispanic/Latinx, respectively. Responses were aggregated and analyzed by the Community Voice team and authors.

Results

Respondent Demographics

Of the 1,194 Community Voice members that were invited to participate in the survey, seventy-six survey responses were received, for a response rate of 6.6%. Among the survey participants, a 97% majority (74/76) were adults, and two responses were from parents of children <11 years old. Women constituted 78% (59/76), and 96% (73/76) identified as white. In terms of age distribution, half (38/76) were in the age group of 35–54 years, while 20% (15/76) fell in the 25–34 years bracket, and 18% (14/76) were between 55–64 years. Relative to data from the 2021 CF Foundation Registry Report, survey respondents were older, more likely to identify as a woman, and more likely to identify as white.

Olfaction and Quality-of-Life

When queried about olfaction, 91% (69/76) reported difficulty with their ability to smell odors and 76% (58/76) identified that their sense of smell has changed over time. More granularly, when questioned about their individual sense of smell, 51% (39/76) and 22% (17/76) said it was “poor” and “fair,” respectively (Figure 1). Overall, 24% (18/76) reported that olfactory function was “very important,” 37% (28/76) stated that it was “important,” and 21% (16/76) identified that it was “moderately important” (Figure 1). The mean BQOD score was 5.0 (SD=4.8, range=21) with 47% (35/75) of total scores ≥5. Over one-third of respondents reported that OD makes them feel angry, alters eating preference, and worsens isolation as part of the BQOD item responses (Figure 2).

Figure 1.

Figure 1.

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Olfactory function and importance ratings by 76 survey respondents.

Figure 2.

Figure 2.

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Responses to the Brief Questionnaire of Olfactory Disorders (N = 75). Total score ranges from 0 (no impact on quality of life (QOL)) to 21 (severe impact on QOL). Each item is rated on a scale of 0–3: 0=disagree, 1=disagree partly, 2=agree partly, 3=agree. The cohort mean (standard deviation (SD))= 5.0 (4.8). The mean (SD) for individual questions: Q1: 0.31 (0.61); Q2: 0.43 (0.79); Q3: 0.53 (0.89); Q4: 0.88 (1.03); Q5: 0.93 (1.08); Q6: 0.95 (1.05); Q7: 1.08 (1.05).

Interest in Future Research on Olfactory Dysfunction

Ninety-five percent (72/76) reported that OD in PwCF should be investigated further. Additionally, 91% (69/76) said they would be interested in a research study that investigated sense of smell and sinus disease. Of the 9% of respondents (7/76) who initially were not interested in a research study, 43% (3/7) became interested in research when presented with a follow-up question highlighting possible unrecognized OD in PwCF. Ninety-four percent (68/72) expressed willingness to participate in a short magnetic resonance imaging (MRI) scan and, of those, 99% (66/67) were open to participate in follow-up imaging.

Qualitative Survey Comments

In the survey, participants had the option to provide additional comments on olfaction and/or sinus disease. Representative comments are shown below.

  • “I have chronic sinus disease and 6–7 sinus surgeries, and loss of smell is never addressed sadly.”

  • “I lost my smell when I had a severe sinus infection. I got some smells back, but they are not correct. Like bacon smells bitter or flowers smell sour? It is weird and impacts my taste.”

Discussion

Optimizing extra-pulmonary disease and QOL have emerged as key components of CF care given recent treatment advances.7 Prior research has shown that OD occurs in the majority of adults with CF. This survey evaluated perceptions of OD and willingness to participate in olfactory research among the CF community. Findings from this study demonstrate that OD is a critical issue for PwCF and that survey respondents feel that olfactory research is important.

Results from this study indicate that most respondents (91%) identify olfactory problems, with 82% reporting that having a good sense of smell is “very important,” “important,” or “moderately important.” Despite the significance of olfaction for many PwCF, CF-related OD is not fully understood and may be underreported. For example, a prior study showed that although PwCF have OD on quantitative olfactory testing, these individuals do not commonly report significant olfactory-related QOL deficits.14 In contrast to most other organ systems, OD does not improve after HEMT initiation in adults or older adolescents with CF; therefore, many PwCF will have sustained OD despite HEMT.13–15 One unresolved question that is currently under investigation is if initiating HEMT in childhood may mitigate or prevent OD.

The BQOD is a validated measure of olfactory-specific QOL. No prior studies that we are aware of have specifically reported the BQOD in PwCF or established cut-offs of severity in this population. However, this tool has been employed in other populations, enabling comparisons to the current study population and providing context for the values reported in this study.17,20 In a report by Yuan et al., individuals with CRS and OD confirmed by Sniffin’ Sticks testing had a median total BQOD score of 5.5. Those with CRS and anosmia had a median score of 9.5, and individuals with CRS with normal olfactory test scores had a median score of 0. The BQOD’s threshold for predicting OD in CRS in Yuan et al. was 3.5. Our study found a mean BQOD score of 5.0, indicating impairment of olfactory-related QOL in PwCF comparable to CRS individuals with objectively measured OD.

Survey respondents reported high enthusiasm for participating in research on olfaction. Overall, 95% of participants from this study believe that research on CF-related OD is worthwhile and would be willing to undergo testing to contribute to studying this topic. These findings are important for CF clinicians and researchers and support that researching and improving olfaction is a priority for many PwCF.

Findings from this study should be interpreted in the context of potential limitations. A limitation of this survey is that the response rate is low. Importantly, these data do not suggest that the findings apply to all people with CF. However, results suggest that a subset of people with CF have olfactory problems that are relevant. While we incorporated methods for parents of children with CF to respond on their child’s behalf, survey respondents were primarily from an older population. To balance survey burden with knowledge gained, we did not collect self-reported information regarding CRS diagnoses or current medications of respondents, although this data would have been advantageous to have. It is possible that individuals who completed the survey were more burdened by OD than those who did not complete the study, which may limit the generalizability of the findings. However, based on previously reported high rates of OD in CF and the BQOD scores and reported rates of OD from this study, the burden of OD sustained by those who responded was high; therefore, OD remains an important and unaddressed problem for a subset of PwCF.2–4

Conclusions

OD is a critical topic for certain PwCF, and over 90% of respondents reported that they experience OD. Many PwCF have impairments in olfactory-specific QOL. PwCF are enthusiastic about future studies on olfaction and 95% of respondents would participate in research in this arena.

Supplementary Material

Supplement

Acknowledgements

The authors would like to thank the Cystic Fibrosis Foundation for facilitating research through Community Voice to support this work (Christie Moy, Enid Aliaj, Jamie Cary, Christina Romàn, Jessica Hudson, and others). Additionally, we would like to thank all the adults with cystic fibrosis and family members across the United States who participated for sharing their insights.

Conflicts of Interest

JEM: none.

CML: NIDCD grant related to this work.

ETZ: In the last 36 months, she has received grants to her institution from the Cystic Fibrosis Foundation, National Institutes of Health, and Vertex Pharmaceuticals Incorporated; has received fees from the Cystic Fibrosis Foundation and Vertex Pharmaceuticals Incorporated related to consultation, participation on advisory boards, and grant review committees. She served as chair of the CFF Therapeutics Development Network steering committee, reviewed grants for CF Canada, and received travel support from the European CF Society Clinical Trials Network for speaking at their annual meeting.

JMW: In the last 36 months, he has received grants to her institution from the Cystic Fibrosis Foundation, the National Institutes of Health, Vertex Pharmaceuticals Incorporated; has received fees from Polarean LLC related to consultation on clinical and translational research.

CHG: In the last 36 months, he has received grants from the National Institutes of Health, the Cystic Fibrosis Foundation, the Federal Drug Administration; has received fees from Enterprise Therapeutics for providing clinical trial design advice. He received honoraria from Gilead Sciences to serve as grant review committee chair and from Vertex Pharmaceuticals for speaking at the UK LEAD conference. He served as a DSMB Chair for a trial supported by Novartis and the European Commission. He serves as the Deputy Editor of the Annals of the American Thoracic Society. He has stock in Air Therapeutics.

JLTC: In the last 36 months, she has received grants to her institution from the Cystic Fibrosis Foundation, the National Institutes of Health, 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, as immediate past chair of the CF TDN’s Sexual Health, Reproduction and Gender Research Working Group, and as Co-Chair of the Heath Equity Team Science Awards study section. She also serves on the scientific advisory board for Emily’s Entourage, and on the ATS Respiratory Health Awards Working Group and as Chair-Elect of the International Conference Committee. She is an Associate Editor for the Journal of Cystic Fibrosis and a member of the International Advisory Board for the Lancet Respiratory Medicine Journal. She serves on the Clinical Trials Review (CTLR) Study section for the National Institutes of Health/National Heart. Blood, Lung Institute.

DMB: In the last 36 months, DMB has received grant support from CF Foundation related to this work as well as unrelated to this work. Unrelated to this work, DMB has received grant support from the International Society of Inflammation and Allergy of the Nose and the Sue Ann and John L. Weinberg Foundation, honoraria, and consulting fees on medicolegal cases and at Garner Health (equity).

Funding:

This work was supported by the Cystic Fibrosis Foundation (grant numbers BESWIC22A0-LAD and BESWIC22Y5). Research reported in this publication was supported by the National Institute on Deafness And Other Communication Disorders of the National Institutes of Health under Award Number R25DC020151 to Christine Liu. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

  • 1.Patel ZM, Holbrook EH, Turner JH, et al. International consensus statement on allergy and rhinology: Olfaction. Int Forum Allergy Rhinol. 2022;12(4):327–680. doi: 10.1002/alr.22929 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Laing DG, Armstrong JE, Aitken M, et al. Chemosensory function and food preferences of children with cystic fibrosis. Pediatr Pulmonol. 2010;45(8):807–815. doi: 10.1002/ppul.21261 [DOI] [PubMed] [Google Scholar]
  • 3.Di Lullo AM, Iacotucci P, Comegna M, et al. Cystic Fibrosis: The Sense of Smell. Am J Rhinol Allergy. 2020;34(1):35–42. doi: 10.1177/1945892419870450 [DOI] [PubMed] [Google Scholar]
  • 4.Beswick D, Humphries S, Balkissoon CD, et al. Olfactory Dysfunction in People with Cystic Fibrosis with at least One Copy of F508del. Int Forum Allergy Rhinol. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Sivam A, Wroblewski KE, Alkorta-Aranburu G, et al. Olfactory Dysfunction in Older Adults is Associated with Feelings of Depression and Loneliness. CHEMSE. 2016;41(4):293–299. doi: 10.1093/chemse/bjv088 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Liu DT, Prem B, Sharma G, Kaiser J, Besser G, Mueller CA. Depression Symptoms and Olfactory‐related Quality of Life. The Laryngoscope. 2022;132(9):1829–1834. doi: 10.1002/lary.30122 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.McBennett KA, Davis PB, Konstan MW. Increasing life expectancy in cystic fibrosis: Advances and challenges. Pediatric Pulmonology. 2022;57(S1). doi: 10.1002/ppul.25733 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Heijerman HGM, McKone EF, Downey DG, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. The Lancet. 2019;394(10212):1940–1948. doi: 10.1016/S0140-6736(19)32597-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381(19):1809–1819. doi: 10.1056/NEJMoa1908639 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Stapleton AL, Kimple AJ, Goralski JL, et al. Elexacaftor-Tezacaftor- Ivacaftor improves sinonasal outcomes in cystic fibrosis. J Cyst Fibros. Published online March 14, 2022:S1569-1993(22)00051-0. doi: 10.1016/j.jcf.2022.03.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.DiMango E, Overdevest J, Keating C, Francis SF, Dansky D, Gudis D. Effect of highly effective modulator treatment on sinonasal symptoms in cystic fibrosis. J Cyst Fibros. 2021;20(3):460–463. doi: 10.1016/j.jcf.2020.07.002 [DOI] [PubMed] [Google Scholar]
  • 12.Beswick DM, Humphries SM, Miller JE, et al. Objective and patient‐based measures of chronic rhinosinusitis in people with cystic fibrosis treated with highly effective modulator therapy. Int Forum Allergy Rhinol. 2022;12(11):1435–1438. doi: 10.1002/alr.23016 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Bacon DR, Stapleton A, Goralski JL, et al. Olfaction before and after initiation of elexacaftor-tezacaftor-ivacaftor in a cystic fibrosis cohort. Int Forum Allergy Rhinol. Published online October 28, 2021. doi: 10.1002/alr.22891 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Beswick DM, Humphries SM, Balkissoon CD, et al. Olfactory dysfunction in cystic fibrosis: Impact of CFTR modulator therapy. Journal of Cystic Fibrosis. Published online September 2021:S1569199321014193. doi: 10.1016/j.jcf.2021.09.014 [DOI] [PubMed] [Google Scholar]
  • 15.Castellanos CX, Osterbauer B, Hasday S, Keens TG, Koempel J, Ference EH. Improvement in sinonasal quality-of-life indicators for pediatric patients with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor. Int Forum Allergy Rhinol. 2023;13(1):72–75. doi: 10.1002/alr.23036 [DOI] [PubMed] [Google Scholar]
  • 16.Mattos JL, Bodner TE, Mace JC, et al. Psychometric properties of the brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2021;11(10):1436–1442. doi: 10.1002/alr.22800 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Mattos JL, Edwards C, Schlosser RJ, et al. A brief version of the questionnaire of olfactory disorders in patients with chronic rhinosinusitis. Int Forum Allergy Rhinol. 2019;9(10):1144–1150. doi: 10.1002/alr.22392 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Community Voice. https://www.cff.org/get-involved/community-voice
  • 19.Cystic Fibrosis Foundation. Patient Registry Report 2021. https://www.cff.org/sites/default/files/2021-11/Patient-Registry-Annual-Data-Report.pdf
  • 20.Yuan F, Wu D, Wei Y. Predictive significance of the questionnaire of olfactory disorders-negative statements for olfactory loss in patients with chronic rhinosinusitis. Eur Arch Otorhinolaryngol. 2022;279(11):5253–5262. doi: 10.1007/s00405-022-07438-z [DOI] [PMC free article] [PubMed] [Google Scholar]

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Supplementary Materials

Supplement
NIHMS2004381-supplement-Supplement.docx (21.2KB, docx)

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