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. 2022 Dec 12;8(4):00227-2022.
doi: 10.1183/23120541.00227-2022. eCollection 2022 Oct.

Diagnostic agreement among experts assessing adults presenting with possible cystic fibrosis: need for improvement and implications for patient care

Alessandro N Franciosi  1   2 , April Tanzler  1 , Jodi Goodwin  1   2 , Pearce G Wilcox  1   2 , George M Solomon  3 , Albert Faro  4 , Noel G McElvaney  5   6 , Damian G Downey  7 , Bradley S Quon  1   2
Affiliations

Diagnostic agreement among experts assessing adults presenting with possible cystic fibrosis: need for improvement and implications for patient care

Alessandro N Franciosi et al. ERJ Open Res. .

Abstract

Background: Increasing awareness of milder presentations of cystic fibrosis (CF) and greater interest in non-CF bronchiectasis are likely to lead to more CF screening by respiratory clinicians. As a result, adults who may not strictly fulfil CF diagnostic criteria yet display evidence of abnormal CF transmembrane conductance regulator (CFTR) function are being identified. The degree of agreement on diagnosis and care needs in these cases between CF clinicians remains unknown, and has implications for patient care, including access to CFTR modulator therapies.

Methods: We surveyed adult CF physicians in Canada, the USA, the UK and Ireland, and presented them with anonymised vignettes of adult patients referred for assessment of possible CF. Diagnostic inter-rater agreement over diagnosis, ease of classifying cases and appropriate follow-up was assessed using Krippendorff's reliability coefficient (α).

Results: Agreement over diagnosis (α=0.282), ease of classification (α= -0.01) and recommended follow-up (α=0.054) was weak. Clinician experience (>10 and 5-10 years versus <5 years) and location (UK and Ireland versus Canada) were associated with higher odds of recommending further testing compared with selecting a formal diagnosis (respectively, OR 2.87; p=0.022, OR 3.74; p=0.013 and OR 3.16; p=0.007). A modified standard of care was recommended in 28.7% of cases labelled as CF. 70% of respondents agreed with the statement that "Accurate distinction between CF and CFTR-related disorder has become significantly more pertinent with the advent of highly effective CFTR modulators".

Conclusions: Our results demonstrate low diagnostic concordance among CF specialists assessing cases of possible adult CF and highlight an area in need of improvement.

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Conflict of interest statement

Conflict of interest: A.N. Franciosi has received a Michael Smith Health Research BC Research Trainee Award (RT-2020-0493), outside the submitted work. P.G. Wilcox has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Vertex, outside the submitted work; and is member of the CF Foundation DSMB, outside the submitted work. G.M. Solomon has received grants or contracts from the NIH, CF Foundation and Vertex Pharmaceuticals, outside the submitted work; consulting fees from Electromed, Inc. and Spark Healthcare, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Electromed, Inc. and Insmed, outside the submitted work; has participated on a DSMB or advisory board from Electromed, Inc. and Insmed, Inc., outside the submitted work. N.G. McElvaney has received grants or contracts from Grifols (research grant for α1-antitrypsin deficiency), outside the submitted work; consulting fees from Vertex, Intellia and Inhibrx, outside the submitted work; has a patent issued for development of oxidation resistant α1-antitrypsin in CHO cells, outside the submitted work; is President of the Alpha 1 Foundation Ireland, outside the submitted work; has Nuimmune stock options, outside the submitted work; and has received plasma purified for α1-antitrypsin for research from Grifols, outside the submitted work. D.G. Downey has received consulting fees from Vertex Pharmaceuticals and Proteostasis Therapeutics, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Vertex Pharmaceuticals, Proteostasis Therapeutics and Chiesi, outside the submitted work; support for attending meetings and/or travel from Vertex Pharmaceuticals and Proteostasis Therapeutics, outside the submitted work; and has a leadership or fiduciary role in other board, society, committee or advocacy groups for the European CF Society Clinical Trials Network, outside the submitted work. B.S. Quon has received grants or contracts from CF Canada, CF Foundation, Gilead Sciences and BC Lung Association, outside the submitted work; personal speaker fees from Vertex Pharmaceuticals, outside the submitted work; and participated on advisory boards for Proteostasis Therapeutics and AbbVie, outside the submitted work. The remaining authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Case-specific breakdown of a) diagnoses and b) follow-up, selected by responders. Total diagnoses=number of raters (55)×number of cases (7)=385. CF: cystic fibrosis; CFTR: CF transmembrane conductance regulator.
FIGURE 2
FIGURE 2
Alluvial plot of the follow-up selection based on responder-selected diagnosis. 28.7% of adult cystic fibrosis (CF) diagnoses were assigned to modified CF standard of care follow-up. 22.5% of CF transmembrane conductance regulator-related disorder (CFTR-RD) diagnosis were assigned to full CF standard of care follow-up, while 80.9% of those recommended to need further testing were assigned to either no CF follow-up (21.3%) or modified CF follow-up (59.6%).
FIGURE 3
FIGURE 3
Subjective responder agreement with statements regarding implications of increased recognition and need for cystic fibrosis transmembrane conductance regulator-related disorder (CFTR-RD) assessments. CF: cystic fibrosis.
See this image and copyright information in PMC

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