Respiratory Trials·org

Interstitial lung disease · Obtaining a tissue diagnosis

COLD randomised trial

Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy

COLD trial design and results
Design Randomised controlled trial
Treatment Transbronchial cryobiopsy first, with surgical lung biopsy only if inconclusive
Control Immediate surgical lung biopsy
Population 52 analysed patients with interstitial lung disease requiring tissue diagnosis
Follow-up Diagnostic pathway and in-hospital stay
Primary endpoint Diagnostic yield and patient burden
Result Unexpected chest tube drainage occurred in 3 of 28 (11%, 95% CI 4 to 27) in the step-up group, while the chest tube could not be removed within 24 hours in 11 of 24 (46%) after immediate surgical biopsy — absolute risk reduction 35% (11 to 56, p=0.0058). Multidisciplinary diagnostic yield after cryobiopsy alone was 82% (64 to 92), rising to 89% (73 to 96) when surgical biopsy followed an inconclusive cryobiopsy.
Secondary endpoints In-hospital stay, complications, need for surgical biopsy

In ILD diagnosis, if lung tissue assessment is required, a diagnostic strategy starting with transbronchial cryobiopsy, followed by SLB when transbronchial cryobiopsy is inconclusive, appears to result in a significant reduction of patient burden and in-hospital stay with a similar diagnostic yield.

The trial authors, in the published abstract

How it has aged

Turns the accuracy finding of COLDICE into a strategy: because cryobiopsy is usually sufficient, most patients avoid a thoracoscopy altogether. Only 52 analysed patients, so this establishes feasibility rather than settling the question.

Publications

Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy for diagnosing interstitial lung disease (the COLD study): a randomised controlled trial

Kalverda KA, Ninaber MK, Wijmans L, et al. Transbronchial cryobiopsy followed by as-needed surgical lung biopsy versus immediate surgical lung biopsy for diagnosing interstitial lung disease (the COLD study): a randomised controlled trial. Lancet Respir Med 2024 Jul;12(7):513-522.

  • Similar diagnostic yield to immediate surgical lung biopsy
  • Significant reduction in patient burden and in-hospital stay
  • Small trial, 52 patients analysed