Cryobiopsy for identification of usual interstitial pneumonia and other interstitial lung disease features : further lessons from COLDICE, a prospective multi-center study

Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease (ILD) diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE Study, however diagnostic confidence was frequently lower for TBLC than SLB. This secondary analysis aimed to characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. Methods: COLDICE was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. Participants underwent both procedures, with blinded pathologist analysis of specimens, applying international guideline criteria. TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. Results: 65 patients (66·1±9·3yrs; FVC 84·7±14·2%; DLCO 63·4±13·8%) participated in the COLDICE Study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ 0.61, 95% CI 0.38-0.77). The UIP guideline criteria of “predominantly subpleural or paraseptal fibrosis” was infrequently reported in TBLC (8/33, 24.2%), while “patchy fibrosis”, “fibroblast foci” and “absence of alternative diagnostic features” were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (OR 23.4, 95%CI 6.36-86.1, p<0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR 1.8, 95% CI 1.08-3.01, p=0.03). Predictors of discordance included older age, family history and radiologic asymmetry. Conclusion: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided other guideline criteria features were present. Diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken.