Diffuse Parenchymal Lung Disease (DPLD), also known as Interstitial Lung Disease (ILD), refers to a group of disorders that primarily affect the three main components of the lung: the endothelium, interstitium, and epithelium. DPLD includes over 140 different conditions, all of which typically lead to increased cellularity and fibrosis in the lungs. The prognosis and treatment options vary depending on the underlying cause, if known. Patients can experience outcomes ranging from complete remission (with or without treatment) to a progressive and severe course. Current guidelines recommend that a team of experts, including pulmonologists, radiologists, and pathologists, work together to reach a consensus diagnosis.

The first step in diagnosing DPLD is a comprehensive patient history, which should include details on domestic and occupational environmental exposures, potential connective tissue diseases (CTD), drug toxicity, and family history of pulmonary fibrosis. If a possible cause is found, the patient should be assessed to rule out other known causes, such as CTD, hypersensitivity pneumonitis (HP), pneumoconiosis, or iatrogenic factors like drugs or radiation. If no specific cause is identified, further testing is needed, including serology and blood work for CTD and HP, as well as a high-resolution CT (HRCT) scan of the chest to assess the pattern of lung involvement. HRCT may reveal specific patterns indicative of a particular diagnosis, such as usual interstitial pneumonia (UIP).

If DPLD is suspected, a multidisciplinary team discussion is crucial to decide if an invasive procedure is required. While a surgical lung biopsy is considered the gold standard for diagnosis, it may not be necessary in cases with certain HRCT patterns, such as UIP or some familial forms of pulmonary fibrosis. Additionally, surgical biopsy is not recommended for patients at high risk of complications like respiratory failure, DPLD exacerbation, or prolonged air leaks, particularly those with severe hypoxemia, pulmonary hypertension, or a significantly reduced diffusion capacity of carbon monoxide.

Diffuse parenchymal lung diseases (DPLD) represent a heterogeneous group of disorders with considerable variability in their pathogenesis, clinical manifestations, therapeutic approaches, and prognosis. In approximately 30 percent of interstitial lung disease (ILD) cases, a definitive diagnosis remains elusive despite clinical (including serological) evaluation and high-resolution computed tomography (HRCT) findings, leading to diagnostic uncertainty and the need for tissue biopsy for histopathological confirmation. Given that most ILDs exhibit a patchy distribution, obtaining large tissue samples or sampling multiple areas is often necessary to capture the full spectrum of histopathological features required for a definitive diagnosis. Traditionally, there have been two primary methods for obtaining biopsies in ILD: surgical lung biopsy (SLB) and bronchoscopic transbronchial forceps biopsy. Recently, transbronchial cryobiopsy has emerged as a promising alternative due to the limitations of the traditional techniques. 

While transbronchial forceps biopsy is considered relatively safe with high specificity, it suffers from limited sensitivity (10 to 30 percent) for diagnosing usual interstitial pneumonia (UIP), even when supplemented with clinical and HRCT data. Conversely, SLB offers high sensitivity and specificity (approximately 95 percent) for ILD diagnosis but is associated with significant risks, including infections, prolonged air leaks, and persistent pain. A large retrospective study of SLB performed for ILD in the United States reported an in-hospital mortality rate of 1.7 percent following elective procedures and 16 percent following nonelective procedures. Mortality risk was found to increase with advancing age, comorbidities, male sex, and provisional diagnoses such as idiopathic pulmonary fibrosis (IPF) or connective tissue disorders, all of which are commonly seen in ILD patients.

Transbronchial lung cryo-biopsy (TBLC) has recently gained recognition as a less invasive alternative to surgical lung biopsy (SLB) for diagnosing Diffuse Parenchymal Lung Diseases (DPLDs). The European Respiratory Society (ERS) has published guidelines with evidence-based recommendations on the clinical application of TBLC in patients with undiagnosed ILDs. Compared to conventional transbronchial lung biopsy using flexible forceps, TBLC provides larger, higher-quality tissue samples while avoiding the crush artifacts commonly associated with forceps biopsy. Recently, single-use cryoprobes with diameters of 1.1 mm, 1.7 mm, and 2.4 mm have been developed to replace the older reusable 1.9 mm and 2.4 mm probes. However, the diagnostic yield, complication rates, and tissue sample artifacts associated with these cryoprobes in ILD diagnosis have not yet been thoroughly examined. Cryoprobes with diameters of 1.9 mm and 2.4 mm are frequently used in transbronchial lung cryobiopsy (TBLC). According to the most recent CHEST Guidelines and Expert Panel Report, the 1.9-mm cryoprobe is recommended over the larger 2.4-mm cryoprobe for patients suspected of having interstitial lung disease (ILD) undergoing TBLC, as there is no significant difference in diagnostic yield. Previous research suggests that smaller cryoprobes may reduce the risk of pneumothorax during TBLC, although supporting evidence is limited. This randomized controlled study seeks to evaluate the safety and diagnostic effectiveness of lung biopsy samples obtained using the new 1.7 mm cryoprobe in comparison to the 1.1 mm cryoprobe for diagnosing diffuse parenchymal lung diseases.