Background: Specimens from transbronchial lung biopsies lack sufficient quality due to crush artifact and are generally too small for diagnosis of diffuse lung diseases. Flexible cryoprobes have been shown to be useful in therapeutic bronchoscopy. We introduce a novel technique for obtaining lung biopsies bronchoscopically, using a flexible cryoprobe. Objectives: The purpose of this study was to show the feasibility of using a cryoprobe to obtain lung biopsies during flexible bronchoscopy. Methods: Forty-one patients with radiographic signs of diffuse lung disease were selected for transbronchial biopsy. During flexible bronchoscopy, conventional transbronchial biopsies using forceps were done first. Then a flexible cryoprobe was introduced into the selected bronchus under fluoroscopic guidance. Once brought into position, the probe was cooled and then retracted with the frozen lung tissue being attached on the probe’s tip. The tissue was processed for histology. After establishing a diagnosis, the specimen area was measured using a digital morphometry system. Results: We evaluated the biopsy samples of 41 patients. The mean specimen area was 5.82 mm² (0.58–20.88 mm²) taken by forceps compared to 15.11 mm² obtained using the cryoprobe (2.15–54.15 mm², p < 0.01). Two patients had a pneumothorax which resolved with tube thoracostomy. Biopsy-associated bleeding did not require any intervention. Transbronchial cryobiopsy contributed in a substantial number of cases to a definitive diagnosis. Conclusions: Transbronchial cryobiopsy is a novel technique which allows to obtain large biopsy samples of lung parenchyma that exceed the size and quality of forceps biopsy samples. Prospective trials are needed to compare this technique with surgical lung biopsy for diagnosis of diffuse lung diseases.

Transbronchial cryobiopsies (TBCB) have recently been introduced as a promising and safer alternative to surgical lung biopsy in the diagnostic approach to diffuse parenchymal lung diseases (DPLD). Despite a substantial and expanding body of literature, the technique has not yet been standardized and its place in the diagnostic algorithm of DPLD remains to be defined. In part, this reflects concerns over the diagnostic yield and safety of the procedure, together with the rapid spread of the technique without competency and safety standards; furthermore, there is a substantial procedural variability among centers and interventional pulmonologists. We report this expert statement proposed during the third international conference on “Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease” (Ravenna, October 27–28, 2016), which formulates evidence- and expert-based suggestions on the indications, contraindications, patient selection, and procedural aspects of the procedure. The following 5 domains were reviewed: (1) what is the role of TBCB in the diagnostic evaluation of DPLD: patient selection; (2) pathological considerations; (3) contraindications and safety considerations; (4) how should TBCB be performed and in what procedural environment; and (5) who should perform TBCB. Finally, the existence of white paper recommendations may also reassure local hospital credentialing committees tasked with endorsing an adoption of the technique.

TBLB by cryoprobe is safe and potentially useful in the diagnosis of ILD. Larger multisite randomized trials are required to confirm the potential benefits of this procedure. Clinical trial registration at ClinicalTrials.gov: NCT01064609.

Background The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis. Methods The INBUILD trial was a randomised, double-blind, placebo-controlled, parallel group trial done at 153 sites in 15 countries. Participants had an investigator-diagnosed fibrosing ILD other than IPF, with chest imaging features of fibrosis of more than 10% extent on high resolution CT (HRCT), forced vital capacity (FVC) of 45% or more predicted, and diffusing capacity of the lung for carbon monoxide (DLco) of at least 30% and less than 80% predicted. Participants fulfilled protocol-defined criteria for ILD progression in the 24 months before screening, despite management considered appropriate in clinical practice for the individual ILD. Participants were randomly assigned 1:1 by means of a pseudorandom number generator to receive nintedanib 150 mg twice daily or placebo for at least 52 weeks. Participants, investigators, and other personnel involved in the trial and analysis were masked to treatment assignment until after database lock. In this subgroup analysis, we assessed the rate of decline in FVC (mL/year) over 52 weeks in patients who received at least one dose of nintedanib or placebo in five prespecified subgroups based on the ILD diagnoses documented by the investigators: hypersensitivity pneumonitis, autoimmune ILDs, idiopathic non-specific interstitial pneumonia, unclassifiable idiopathic interstitial pneumonia, and other ILDs. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02999178.