Respiratory medicine · 2026
Baseline Sinonasal Phenotypes in Cystic Fibrosis Before Elexacaftor/Tezacaftor/ Ivacaftor Therapy: A Cross-Sectional Analysis.
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Gallardo Rebecca, Gehrke Rodrigo Delpino, Sartorelli Lorenzo Silvestrin, Teixeira de Almeida Andrea, Silva Bruna Santos, Machado Ligia, Ribeiro José Dirceu, Sakano Eulalia
Аннотация
BACKGROUND: Sinonasal disease is highly prevalent in cystic fibrosis (CF), yet pre-treatment disease burden remains incompletely characterized across CFTR genotype classes. As CFTR modulator therapy reshapes disease trajectories, establishing a genotype-stratified baseline of upper-airway disease before elexacaftor/ tezacaftor/ivacaftor (ETI) initiation is essential for contextualizing subsequent sinonasal responses.
METHODS: In this cross-sectional study, 45 individuals with CF underwent pre-ETI evaluation, including the SNOT-22 questionnaire, visual analog scale (VAS) for nasal obstruction, Lund-Kennedy (LK) endoscopic scoring, Lund-Mackay (LM) CT staging, and CCCRC olfactory identification testing. Disease burden was compared between heterozygous and F508del homozygous genotypes. Heterozygous patients were further stratified by the genetic class of the cystic fibrosis-causing mutation, ranging from class I to class VI, according to the type of mutation, and sinonasal outcomes were additionally compared by exocrine pancreatic status. Associations among symptoms, structural, and functional measures were assessed using Spearman correlations.
RESULTS: Mean VAS nasal obstruction was 4.15 ± 2.30 and mean SNOT-22 score 14.4 ± 11.2, indicating mild to moderate symptom burden. LK endoscopy showed mild to moderate disease (4.09 ± 1.54) and LM CT substantial opacification (14.17 ± 4.62). Olfactory scores varied widely (8.63 ± 3.08, D+E composite). No significant differences were found between genotype groups across any domain. VAS correlated strongly with SNOT-22 (ρ = 0.54, p < 0.001) and inversely with olfaction (ρ = -0.42, p = 0.02), but not with endoscopic or radiologic severity. Among heterozygotes, no domain differed between minimal-function and residual-function classes (VAS p = 0.129; SNOT-22 p = 0.177; LK p = 0.878; LM p = 0.225; olfaction p = 0.357), and none survived false-discovery-rate correction. Sinonasal scores likewise did not differ by exocrine pancreatic status, an analysis limited to 13 patients and therefore substantially underpowered.
CONCLUSIONS: Individuals with CF exhibit measurable sinonasal disease across symptomatic, structural, and functional domains before ETI therapy. The absence of significant differences by genotype, by CFTR functional class, and by pancreatic status indicates that baseline upper-airway disease is largely independent of CFTR functional severity as conventionally classified. These findings establish a multidomain pre-treatment reference for future longitudinal assessment of sinonasal and olfactory responses to CFTR modulator therapy.
METHODS: In this cross-sectional study, 45 individuals with CF underwent pre-ETI evaluation, including the SNOT-22 questionnaire, visual analog scale (VAS) for nasal obstruction, Lund-Kennedy (LK) endoscopic scoring, Lund-Mackay (LM) CT staging, and CCCRC olfactory identification testing. Disease burden was compared between heterozygous and F508del homozygous genotypes. Heterozygous patients were further stratified by the genetic class of the cystic fibrosis-causing mutation, ranging from class I to class VI, according to the type of mutation, and sinonasal outcomes were additionally compared by exocrine pancreatic status. Associations among symptoms, structural, and functional measures were assessed using Spearman correlations.
RESULTS: Mean VAS nasal obstruction was 4.15 ± 2.30 and mean SNOT-22 score 14.4 ± 11.2, indicating mild to moderate symptom burden. LK endoscopy showed mild to moderate disease (4.09 ± 1.54) and LM CT substantial opacification (14.17 ± 4.62). Olfactory scores varied widely (8.63 ± 3.08, D+E composite). No significant differences were found between genotype groups across any domain. VAS correlated strongly with SNOT-22 (ρ = 0.54, p < 0.001) and inversely with olfaction (ρ = -0.42, p = 0.02), but not with endoscopic or radiologic severity. Among heterozygotes, no domain differed between minimal-function and residual-function classes (VAS p = 0.129; SNOT-22 p = 0.177; LK p = 0.878; LM p = 0.225; olfaction p = 0.357), and none survived false-discovery-rate correction. Sinonasal scores likewise did not differ by exocrine pancreatic status, an analysis limited to 13 patients and therefore substantially underpowered.
CONCLUSIONS: Individuals with CF exhibit measurable sinonasal disease across symptomatic, structural, and functional domains before ETI therapy. The absence of significant differences by genotype, by CFTR functional class, and by pancreatic status indicates that baseline upper-airway disease is largely independent of CFTR functional severity as conventionally classified. These findings establish a multidomain pre-treatment reference for future longitudinal assessment of sinonasal and olfactory responses to CFTR modulator therapy.