If Biopsy Needed for ILD Diagnosis, Start With Less-Invasive Option, Trial Suggests

When a biopsy is needed to diagnose interstitial lung disease (ILD), starting with a less-invasive approach can reduce patient burden while still achieving a diagnostic yield similar to surgical lung biopsy (SLB), a randomized trial suggested.

The step-up approach — where patients underwent a transbronchial lung cryobiopsy and SLB was reserved only for cases where more information was needed for diagnosis — significantly reduced the need for chest tube drainage when compared with immediate SLB, which requires hospital admission for post-surgical drainage.

For the study’s primary endpoint, unexpected chest tube drainage in the step-up arm occurred in 11% of patients, while 46% of patients in the immediate SLB arm required prolonged chest tube drainage (P=0.0058), reported researchers led by Kirsten Kalverda, MD, of Amsterdam University Medical Centers.

Furthermore, patients assigned to the step-up strategy had shorter in-hospital stays compared with immediate SLB (median 1 vs 5 days, respectively), fewer serious adverse events (4% vs 50%), and less pain, according to findings in Lancet Respiratory Medicine.

“A multidisciplinary team discussion, resulting in a consensus diagnosis, is considered the reference standard for diagnosing ILD,” explained Kalverda and colleagues. “In most cases, a high-confidence diagnosis can be established from clinical and radiological data, yet it is estimated that in 10-40% of newly diagnosed ILD, a lung biopsy is deemed necessary to establish a diagnosis or improve diagnostic confidence.”

Lung tissue sampling via SLB has been considered the gold standard and is the most commonly used method, though it is associated with high morbidity and even mortality. Transbronchial cryobiopsy, meanwhile, has more recently become an alternative, though it has a lower diagnostic yield.

In the study, diagnostic yield reached 82% with transbronchial cryobiopsy alone, 88% with immediate SLB, and 89% with the step-up strategy.

“Recently published guidelines from the European Respiratory Society suggest using transbronchial lung cryobiopsy in patients with undiagnosed ILD in whom a histological diagnosis is indicated and who are eligible for SLB,” wrote Margaret Salisbury, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and Kevin Flaherty, MD, of the University of Michigan in Ann Arbor, in an invited commentary.

“This recommendation was based on a balance between a lower rate of mortality and other serious complications against a lower performance on diagnostic outcomes,” they continued. “The guideline committee also suggested using a step-up SLB after a non-diagnostic transbronchial lung cryobiopsy.”

But, said Salisbury and Flaherty, no randomized trial supported these conditional recommendations.

As to the study results, they pointed out that some participants in the step-up arm should have gone on to SLB but did not, which could have affected the primary outcome. “It is also probable that many classifying diagnoses were made with low confidence,” they added.

Of the 28 patients initially assigned to the less-invasive approach, only three of the five without a classifying diagnosis went on to SLB following the cryobiopsy.

Treatment selection in ILD — a heterogeneous group of more than 10 disorders — relies on identifying a specific diagnosis for proper management, the editorialists noted. But in the step-up group, just 46% of pathologists were able to make a diagnosis with high confidence as compared with 74% for the immediate SLB group.

“Although this first-in-class randomized comparison of two valid diagnostic strategies for ILD provides important data in this field, we continue to walk a fine line balancing procedural complications against diagnostic accuracy,” the editorialists concluded.

The COLD study randomized 55 patients from six hospitals in the Netherlands to either the step-up approach (n=28) or immediate SLB (n=27). Patients were eligible for the study if their clinical and radiological data were insufficient to establish a classifying ILD diagnosis, and if multidisciplinary team discussion indicated obtaining lung tissue for diagnosis.

For the primary outcome, unexpected chest tube drainage in the step-up group was defined as any chest tube after transbronchial cryobiopsy while prolonged chest tube drainage after SLB was defined as drainage lasting more than 24 hours. Patients, pathologists, and clinicians were not masked to treatment assignment.

The average patient age was 66 years, 81% were men, and about three-fourths were former smokers. Following the biopsies, final diagnoses included hypersensitivity pneumonitis in 55%, idiopathic non-specific interstitial pneumonia in 13%, idiopathic pulmonary fibrosis in 8%, sarcoidosis in 4%, unclassifiable in 12%, and other in 12%.

Overall, adverse events occurred in 61% of patients in the step-up group and 75% of those in the immediate SLB group. Air leak, pneumonia, and uncontrolled pain were the most common serious adverse events.

Kalverda and colleagues noted that the small sample size and non-masked design may limit the study findings. Other potential limitations included that the large proportion of hypersensitivity pneumonitis cases, some differences in baseline measurements, and that all patients underwent intubated surgical procedures.

Elizabeth Short is a staff writer for MedPage Today. She often covers pulmonology and allergy & immunology. Follow

Disclosures

This study was supported by funding from the Netherlands Organisation for Health Research and Development and Amsterdam University Medical Centers.

No disclosures were reported by the study authors.

Salisbury reported relationships with the NIH, Boehringer Ingelheim, Orinove, and Roche. Flaherty reported relationships with the Pulmonary Fibrosis Foundation, Boehringer Ingelheim, Roche/Genentech, Bellerophon, Respivant, Shionogi, DevPro, AstraZeneca, Pure Health, Horizon, FibroGen, Sun Pharmaceuticals, Pliant, United Therapeutics, Arrowhead, Lupin, Polarean, PureTech, Trevi, CSL Behring, Daewoong, DisperSol, Immunet, NeRRe Therapeutics, Insilco, Vicore, GSK, Merck, and Chugai.

Primary Source

The Lancet Respiratory Medicine

Source Reference: Kalverda KA, 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; DOI:10.1016/S2213-2600(24)00074-2.

Secondary Source

The Lancet Respiratory Medicine

Source Reference: Salisbury ML, Flaherty KR “Optimising the approach to ILD diagnosis: the balance of procedural complications against diagnostic accuracy” Lancet Respir Med 2024; DOI:10.1016/S2213-2600(24)00113-9.

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