Next-generation sequencing using tissue specimen collected with a 1.1 mm-diameter cryoprobe in patients with lung cancer.

BACKGROUND AND OBJECTIVE: Next-generation sequencing (NGS) analysis is considered standard for lung cancer diagnosis in clinical practice. Little is known about the feasibility of NGS using tumour tissue sampled with a 1.1 mm-diameter cryoprobe. We aimed to investigate the suitability of specimens obtained by transbronchial cryobiopsy (TBC) using a 1.1 mm-diameter cryoprobe for NGS analysis. METHODS: Patients with lung cancer who underwent TBC using a 1.1 mm-diameter cryoprobe for NGS testing between October 2020 and April 2023 were enrolled. A 4.0- or 3.0 mm-diameter bronchoscope with radial probe endobronchial ultrasound and virtual bronchoscopic navigation was used to detect peripheral lung lesions. All procedures were performed under fluoroscopic guidance. Data were analysed retrospectively. RESULTS: A total of 56 patients underwent TBC using a 1.1 mm cryoprobe for NGS testing, during the study period. Most patients (98%) were in the advanced stage of lung cancer (recurrent or inoperable disease of stages III or IV). The diagnostic yield of NGS for DNA and RNA sequencing was 95% each (53 of 56). Moderate bleeding was noted in three patients (5%) and none of the study patients developed life-threatening complications, such as pneumothorax or lung infection. CONCLUSION: TBC using a 1.1 mm-diameter cryoprobe is a useful and safe tool for NGS analysis, for both DNA and RNA sequencing.

Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study.

BACKGROUND: Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs. METHODS: Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC. RESULTS: A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283). CONCLUSIONS: The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.

Obesity may be a risk factor for transbronchial lung cryobiopsy-related adverse events in Japanese patients with interstitial lung disease.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is known to be associated with a high incidence of adverse events. However, few studies have investigated the correlation between obesity and the risk of TBLC-related adverse events, especially in Asians, who are known to have characteristic differences in height and weight as compared to individuals of other ethnicities. METHODS: We retrospectively assessed 102 Japanese patients who underwent TBLC for the diagnosis of interstitial lung disease to evaluate the correlation between patient characteristics and the occurrence of TBLC-related adverse events (hemorrhage, pneumothorax, and acute exacerbation of interstitial lung disease). RESULTS: TBLC-related adverse events occurred in 19 patients (18.6 %), with hemorrhage being the most common adverse event (in 14 patients, 13.7 %). There was no correlation between age, sex, or pulmonary function test results and the occurrence of adverse events. The body mass index (BMI) cut-off predicting the occurrence of all adverse events was 26.6 kg/m2 (sensitivity of 0.389 and specificity of 0.852), and that predicting the occurrence of adverse events of hemorrhage was 26.8 kg/m2 (sensitivity of 0.462 and specificity of 0.907). Among patients with a BMI >26.8 kg/m2, adverse events of hemorrhage occurred in 37.5 % of cases, which was higher than among those with a BMI <26.8 kg/m2. CONCLUSIONS: Obesity is a risk factor for the incidence of TBLC-related adverse events, particularly adverse events of hemorrhage, in Japanese patients. The BMI cut-off values that predicted an increased frequency of TBLC-related adverse events and hemorrhage specifically were 26.6 and 26.8 kg/m2, respectively.

Cryo-transbronchial lung biopsy in the diagnosis of IgG4-related lung disease.

IgG4-related lung disease is a diagnostic challenge as the presenting patterns can mimic other commonly seen pulmonary diseases like infections, interstitial pneumonia, malignancy, etc. The diagnosis of IgG4-related disease requires a correlation of clinical, radiological, biochemical, and histopathological features. Especially, an adequate tissue sample is necessary to diagnose this disease confidently. Conventionally surgical lung biopsy was needed for histopathology. But with the availability of the new less invasive technique-transbronchial cryo lung biopsy, adequate tissue can be obtained to clinch the diagnosis via bronchoscopy, thereby avoiding surgery. We report a case of IgG4-related interstitial lung disease diagnosed with the help of this technique in a tertiary care center in South India. Clinicoradiological features were inconclusive. Transbronchial cryo-lung biopsy helped to achieve the diagnosis.

Clinical Application of Confocal Laser Endomircoscopy Combined with Cryobiopsy in the Diagnosis of Interstitial Lung Disease.

INTRODUCTION: Confocal laser endomicroscopy (CLE) has the characteristics of high resolution, real-time imaging, and no radiation, which is helpful for the precise and effective implementation of transbronchial cryobiopsy (TBCB). The study aimed to compare the efficacy and safety of TBCB combined with CLE (CLE group) or fluoroscopy (fluoroscopy group) in the diagnosis of interstitial lung disease (ILD). METHODS: From a prospective randomized controlled trial, 80 patients with undiagnosed ILD or ILD requiring biopsy between January 2022 and November 2022 were randomly assigned to CLE group and fluoroscopy group. The rate to reach an etiological diagnosis of ILD, maximum cross-sectional area of specimens, operation time, and complications were compared between the two groups. RESULTS: The rate to reach an etiological diagnosis in the CLE group was significantly higher than that in the fluoroscopy group (95.0% vs. 80.0%, p < 0.05), but there was no difference in the maximum cross-sectional area of the specimens (42.1 ± 10.1 mm2 vs. 41.5 ± 10.3 mm2, p > 0.05). In terms of operation time, the CLE group was significantly shorter than the fluoroscopy group (37.6 ± 10.6 min vs. 54.8 ± 24.9 min, p < 0.05). The bleeding volume in the CLE group was significantly lower than that in the fluoroscopy group (4.9 ± 3.6 mL/case vs. 9.0 ± 9.2 mL/case, p < 0.05). Further analysis showed that the incidence of moderate bleeding was also lower in the CLE group (20.0% vs. 75.0%, p < 0.001). In addition, the incidence of pneumothorax in the CLE group was significantly lower than that in the fluoroscopy group (0 vs. 25.0%, p < 0.001). CONCLUSIONS: Compared with simple fluoroscopy, the combination of CLE significantly improves the rate of etiological diagnosis, shortens the operation time, and reduces complications such as bleeding and pneumothorax.

Unexpected diffuse lung lesions in a patient with pulmonary alveolar proteinosis: A case report.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) often presents nonspecifically and can be easily confused with: (1) Idiopathic interstitial lung fibrosis; (2) alveolar carcinoma; (3) pulmonary tuberculosis; and (4) other lung diseases such as viral pneumonia, mycoplasma pneumonia, and chlamydial pneumonia. CASE SUMMARY: Diagnosis: In this case, a patient was diagnosed with PAP through transbronchial cryobiopsy (TBCB) and quantitative metagenomic next-generation sequencing, which confirmed the impairment of surfactant turnover as the underlying cause of PAP. Interventions: High-volume total lung lavage was performed for this patient. Outcomes: The patient's clinical condition had improved significantly by the 6-month follow-up, with a 92% finger oxygen saturation. A repeat chest computed tomography scan revealed scattered patchy ground-glass shadows in both lungs, which was consistent with alveolar protein deposition but with a lower density than in the radiograph from October 23, 2022. CONCLUSION: TBCB has unique advantages in diagnosing atypical alveolar protein deposition, particularly for enabling the early detection of PAP. This information can help patients take preventive measures to prevent or halt PAP development by avoiding dusty environments and seeking treatment with total lung lavage and inhaled granulocyte macrophage colony-stimulating factor.

Combination of transbronchial cryobiopsy based clinic-radiologic-pathologic strategy and metagenomic next-generation sequencing for differential diagnosis of rapidly progressive diffuse parenchymal lung diseases.

Background: The complicated spectrum of rapidly progressive diffused parenchymal lung diseases (RP-DPLD) creates obstacles to the precise diagnosis and treatment. We evaluated the differential diagnostic value of transbronchial cryobiopsy (TBCB) based clinic-radiologic-pathologic (CRP) strategy combined with bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in RP-DPLD patients. Methods: RP-DPLD patients who underwent the diagnostic strategy of TBCB-based CRP combined with BALF mNGS at Shanghai East Hospital from May 2020 to Oct 2022 were retrospectively analyzed. Clinical characteristics were summarized, including demographic data, high-resolution computed tomography (HRCT) findings, histopathology of TBCB and microbiological results. Diagnostic value of the combined strategy, as well as the sensitivity, specificity, and positive detection rates of mNGS were evaluated. Results: A total of 115 RP-DPLD patients were enrolled, with a mean age of 64.4 years old and a male proportion of 54.8%. The pulmonary imaging findings in most patients were complex and diverse, with all patients showing bilateral lung diffuse lesions in HRCT, and progressively aggravated imaging changes within one month. After combining TBCB-based CRP strategy with mNGS, all participants received a corresponding diagnosis with 100% diagnostic yield. In these patients, 58.3% (67/115) were diagnosed with noninfectious RP-DPLD and 41.7% (48/115) with infection-related RP-DPLD. There were 86.1% of cases with known etiology according to the DPLD classification. BALF mNGS and traditional pathogen detection methods were performed in all patients, the positive detection rates were 50.4% (58/115) and 32.2% (37/115), respectively. Meanwhile, the mNGS showed significantly higher sensitivity and negative predictive value than the traditional pathogen detection methods for the diagnosis of infection-related RP-DPLD (100% vs 60.4% (p<0.001), 100% vs 75.6% (p<0.001), respectively). Among noninfectious RP-DPLD patients, the true negative rate of mNGS was 85.1% (57/67). All patients had their treatment regimen modified and the 30-day mortality was 7.0%. Conclusion: The novel strategy of TBCB-based CRP combined with mNGS provided dependable and sufficient evidence for the diagnosis, meanwhile further improved the accuracy of RP-DPLD treatment, as well as the prognosis of patients. Our results highlight the significant value of combined strategy in determining whether the RP-DPLD patients were infection associated or not.

Pulmonary tuberculosis associated acute fibrinous and organizing pneumonia: A case report and literature review.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare histological interstitial pneumonia pattern characterized by patches of "fibrin balls" distributed within the alveoli and organizing pneumonia. Currently, there is no consensus on the diagnosis and treatment of this disease. METHODS: We present the case of a 44-year-old male with AFOP secondary to Mycobacterium tuberculosis. We have further reviewed organizing pneumonia (OP) and AFOP caused by tuberculosis. CONCLUSION: Tuberculosis secondary to OP or AFOP is rare and challenging to diagnose. We need to constantly adjust the treatment plan based on the patient's symptoms, test results, and response to treatment in order to arrive at an accurate diagnosis and maximize treatment efficacy.

Pathologic Criteria for the Diagnosis of Usual Interstitial Pneumonia vs Fibrotic Hypersensitivity Pneumonitis in Transbronchial Cryobiopsies.

Transbronchial cryobiopsy (TBCB) is increasingly used for the diagnosis of fibrosing interstitial pneumonias, but there are few detailed descriptions of the pathologic findings in such cases. It has been proposed that a combination of patchy fibrosis and fibroblast foci with an absence of alternative features is diagnostic of usual interstitial pneumonia (UIP; ie, idiopathic pulmonary fibrosis [IPF]) in TBCB. In this study, we reviewed 121 TBCB in which a diagnosis of fibrotic hypersensitivity pneumonitis (FHP; n = 83) or IPF (n = 38) was made by multidisciplinary discussion and evaluated a range of pathologic features. Patchy fibrosis was found in 65 of 83 (78%) biopsies from FHP and 32of 38 (84%) biopsies from UIP/IPF cases. Fibroblast foci were present in 47 of 83 (57%) FHP and 27 of 38 (71%) UIP/IPF cases. Fibroblast foci/patchy fibrosis combined did not favor either diagnosis. Architectural distortion was seen in 54 of 83 (65%) FHP and 32 of 38 (84%) UIP/IPF cases (odds ratio [OR] for FHP, 0.35; P = .036) and honeycombing in 18 of 83 (22%) and 17 of 38 (45%), respectively (OR, 0.37; P = .014). Airspace giant cells/granulomas were present in 13 of 83 (20%) FHP and 1 of 38 (2.6%) UIP/IPF cases (OR for FHP, 6.87; P = .068), and interstitial giant cells/granulomas in 20 of 83 (24%) FHP and 0 of 38 (0%) UIP/IPF (OR, 6.7 x 106; P = .000). We conclude that patchy fibrosis plus fibroblast foci can be found in TBCB from both FHP and UIP/IPF. The complete absence of architectural distortion/honeycombing favors a diagnosis of FHP, as does the presence of airspace or interstitial giant cells/granulomas, but these measures are insensitive, and many cases of FHP cannot be separated from UIP/IPF on TBCB.

Diagnosis of pulmonary leiomyosarcoma extending into the main bronchus using repeated transbronchial cryobiopsy.

The diagnosis of pulmonary leiomyosarcoma using bronchoscopy is difficult, and surgical resection is often performed for definitive diagnosis and curative therapy. We report a case of pulmonary leiomyosarcoma, successfully diagnosed using repeated transbronchial cryobiopsy (TBCB). A 69-year-old-woman was found to have an oval mass in the left hilar region extending into the left main bronchus on computed tomography (CT). All transbronchial biopsy specimens were necrotic, but repeated TBCB removed the necrotic tissue from the tumour and finally led to the diagnosis of pulmonary leiomyosarcoma. Proton therapy was administered, which caused shrinkage of the tumour. Thus, TBCB is useful for definitive diagnosis of leiomyosarcoma without surgical biopsy. Repeated TBCB can reduce tumour volume, eliminate atelectasis, and reduce the extent of radiotherapy exposure.

Radial Endobronchial Ultrasound-guided Transbronchial Cryobiopsy versus Forceps Biopsy for the Diagnosis of Solitary Pulmonary Nodules: A Prospective Randomised Trial.

Background: Improvements in pulmonary diagnostic imaging and the development of lung cancer screening are increasing the prevalence of Solitary pulmonary nodules (SPNs). Fluoroscopically guided radial endobronchial ultrasound (EBUS) with transbronchial forceps biopsy (TB-FB) has been the conventional diagnostic method. Transbronchial cryobiopsy (TB-CB) is an alternative biopsy method. We sought to compare transbronchial cryobiopsy to transbronchial forceps biopsy for the diagnosis of SPNs. Methods: A prospective, single-centre, randomised controlled trial was conducted at the Royal Adelaide Hospital (RAH). Patients with SPNs were randomised to either 5 transbronchial forceps biopsies or one transbronchial cryobiopsy. Complete blinding of investigators and participants was not possible, as transbronchial cryobiopsy required general anaesthesia. The primary outcome was diagnostic yield with secondary outcomes of specimen size, diagnostic yield for subsets challenging to access with forceps and safety. Results: The overall diagnostic yield for the 28 enrolled subjects was 76.8%(22/28). The diagnostic yield was 91.7% (11/12 patients) for transbronchial cryobiopsy and 68.8% (11/16 patients) for forceps biopsy (p=0.14). Median biopsy sizes were consistently larger for the cryobiopsy arm at 7.0mm compared to 2.5mm(p<0.0001). An eccentric EBUS image signalling the probe was adjacent to the nodule occurred in 4/28 cases, and TB-CB confirmed a diagnosis in 3/3 randomised to this arm. There were no major complications with either technique. Conclusion: Transbronchial cryobiopsy under the guidance of fluoroscopy and radial EBUS facilitates larger biopsy specimens without a significant increase in major complications. Further research is required to confirm the effect on diagnostic yield; however, our study supports a role for TB-CB in the diagnosis of SPNs and small, nodule-adjacent biopsies. Clinical Trial Registration Number: Reference number of R20160213(HREC/16/RAH/37).

Extracorporeal Membrane Oxygenation Supported Transbronchial Cryobiopsy in the Diagnosis of Severe Organizing Pneumonia: A Case Report.

This case report describes a 58-year-old, never-smoking housewife with chief complaints of progressively worsening cough, dyspnea, and intermittent fever, who was initially misdiagnosed with community-acquired pneumonia (CAP). However, her pulse oximetry oxygen saturation continued to decline, and eventually, she underwent an endotracheal intubation. Fortunately, transbronchial cryobiopsy (TBCB) assisted by extracorporeal membrane oxygenation (ECMO) was performed in the most critical situation, and it revealed an organizing pneumonia (OP) pattern. OP describes a histological pattern of acute or subacute pulmonary damage, which may be idiopathic or associated with a known or unknown underlying disease. A definitive diagnosis of OP usually obtained from pathology, and surgical lung biopsy with large lung tissue is recommended. However, since the surgical lung biopsy was not convenient for this patient after mechanical ventilation, bedside TBCB supported by ECMO was selected. To our knowledge, we are the first to report the pathological diagnosis of ECMO assisted TBCB in acute respiratory failure. When oxygenation cannot be maintained after endotracheal intubation and surgical lung biopsy is not feasible, ECMO-supported TBCB may be a good choice to obtain lung tissue for histopathological diagnosis in patients with acute lung injury of unknown etiology.

Pulmonary amyloidosis diagnosed via transbronchial lung cryobiopsy without surgical lung biopsy: A case series.

Pulmonary amyloidosis is a rare disease characterized by abnormal extracellular deposition of amyloid fibril in the lung tissue, and the identification of amyloid deposits is essential for its diagnosis. Surgical lung biopsy (SLB) is a standard diagnostic method for pulmonary amyloidosis. However, it has a relatively high post-procedural mortality rate. Recently, transbronchial lung cryobiopsy (TBLC) has been gradually used for diagnosing interstitial lung disease. However, its diagnostic efficacy for pulmonary amyloidosis has not yet been validated. Here, we describe two cases of pulmonary amyloidosis with deposition of amyloid light chain detected via TBLC. Since SLB is a high-risk procedure for the patients due to age and complications, TBLC was performed. Both patients presented with Congo red-positive amyloid deposits. One patient with localized pulmonary amyloidosis had a good clinical course without therapeutic intervention and was followed up. The other with systemic amyloidosis received chemotherapy and presented with a stable clinical course. TBLC can collect a larger pulmonary specimen for pulmonary amyloidosis than forceps biopsy and has fewer complications and a lower mortality rate than SLB. Thus, it can be a diagnostic method for pulmonary amyloidosis.

Diagnostic yield of virtual bronchoscope navigation combined with radial endobronchial ultrasound guided transbronchial cryo-biopsy for peripheral pulmonary nodules: a prospective, randomized, controlled trial.

Background: Transbronchial lung biopsy (TBLB) was a useful method for the diagnosis of peripheral pulmonary nodules (PPNs), but the smaller tissue samples obtained often could not meet the subsequent molecular pathological diagnosis. The purposes of this study were to assess the diagnostic yield of virtual bronchoscope navigation (VBN) combined with radial endobronchial ultrasound (rEBUS) guided transbronchial cryo-biopsy (TBCB) and to compare it with TBLB. Methods: Patients with PPNs, who planned to undergo bronchoscopy and were admitted to Henan Provincial People's Hospital and Zhoukou Central Hospital from January 1, 2020 to December 31, 2020, were divided into the TBCB group (experimental group) and TBLB group (control group) using the block randomization method. TBCB and TBLB were performed with the guidance of VBN-rEBUS. The diagnostic yields, complications, specimen surface areas, and operation times were observed. The differences between the two groups were measured by the independent sample t-test or Chi-square test. Results: A total of 152 patients were enrolled, of whom 138 completed the study, and 102 received a definite diagnosis by bronchoscopy. The diagnostic yield showed no statistically significant difference between TBCB group and TBLB group (79.1% vs. 69.0%, P=0.124). For PPNs with the diameter <2 cm, TBCB group had a significantly higher diagnostic yield than TBLB group (76.5% vs. 50.0%, P=0.022); For PPNs with eccentric and adjacent radial ultrasonic images, TBCB group also had a significantly higher diagnostic yield than TBLB group (78.1% vs. 55.9%, P=0.023). The specimen surface area of TBCB group was larger than that of TBLB group (P=0.030). The incidence of moderate bleeding in TBCB group was higher than that in TBLB group (P=0.006), but no serious complications were observed in either group. Conclusions: Although the incidence rate of moderate bleeding was higher than that of TBLB, VBN-rEBUS guided TBCB is still a safe and effective diagnostic method for PPNs, and is superior to TBLB for PPNs with a diameter <2 cm or with an eccentric and adjacent radial ultrasonic image. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100054949.

Mass spectrometry detection of inhaled drug in distal fibrotic lung.

BACKGROUND: Currently the only available therapies for fibrotic Interstitial Lung Disease are administered systemically, often causing significant side effects. Inhaled therapy could avoid these but to date there is no evidence that drug can be effectively delivered to distal, fibrosed lung. We set out to combine mass spectrometry and histopathology with rapid sample acquisition using transbronchial cryobiopsy to determine whether an inhaled drug can be delivered to fibrotic, distal lung parenchyma in participants with Interstitial Lung Disease. METHODS: Patients with radiologically and multidisciplinary team confirmed fibrotic Interstitial Lung Disease were eligible for this study. Transbronchial cryobiopsies and endobronchial biopsies were taken from five participants, with Interstitial Lung Disease, within 70 min of administration of a single dose of nebulised ipratropium bromide. Thin tissue cryosections were analysed by Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging and correlated with histopathology. The remainder of the cryobiopsies were homogenised and analysed by Liquid Chromatography-tandem Mass Spectrometry. RESULTS: Drug was detected in proximal and distal lung samples from all participants. Fibrotic regions were identified in research samples of four of the five participants. Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry imaging showed co-location of ipratropium with fibrotic regions in samples from three participants. CONCLUSIONS: In this proof of concept study, using mass spectrometry, we demonstrate for the first-time that an inhaled drug can deposit in distal fibrotic lung parenchyma in patients with Interstitial Lung Disease. This suggests that drugs to treat pulmonary fibrosis could potentially be administered by the inhaled route. Trial registration A prospective clinical study approved by London Camden and Kings Cross Research Ethics Committee and registered on clinicaltrials.gov (NCT03136120).

Efficacy and Safety of Cryobiopsy vs. Forceps Biopsy for Interstitial Lung Diseases, Lung Tumors, and Peripheral Pulmonary Lesions: An Updated Systematic Review and Meta-Analysis.

Background: Cryobiopsy has emerged as a novel alternative to conventional forceps biopsy for the diagnosis of interstitial lung diseases (ILDs), lung tumors, and peripheral pulmonary lesions (PPLs). This study aims to compare cryobiopsy and forceps biopsy for the diagnosis of these lung pathologies with respect to efficacy and safety by performing a meta-analysis of updated evidence. Methods: A number of databases, such as PubMed, Embase, Web of Science, the Cochrane Library, OVID, CNKI, and Wanfang database, were searched for eligible studies. Randomized and non-randomized comparative studies investigating the efficacy and safety of cryobiopsy vs. forceps biopsy for lung pathologies were included. Pooled results were calculated as an odds ratio (OR) or standardized mean difference (SMD) with 95% CI. Results: A total of 39 studies, such as 9 RCTs with 3,586 biopsies (1,759 cryobiopsies and 1,827 flexible forceps biopsies) were analyzed. Cryobiopsy was associated with a significant increase in the diagnostic rates of ILDs (OR, 4.29; 95% CI, 1.85-9.93; p < 0.01), lung tumors (OR, 3.58; 95% CI, 2.60-4.93; p < 0.01), and PPLs (OR, 1.70; 95% CI, 1.23-2.34; p < 0.01). Cryobiopsy yielded significantly larger specimens compared with flexible forceps biopsy (SMD, 3.06; 95% CI, 2.37-3.74; p < 0.01). The cryobiopsy group had a significantly higher (moderate to severe) bleeding risk than the forceps group (OR, 2.17; 95% CI, 1.48-3.19; p < 0.01). No significant difference was observed in the incidence of pneumothorax between the groups (OR, 0.90; 95% CI, 0.44-1.85; p = 0.78). Conclusion: Our results demonstrate that cryobiopsy is a safe and efficacious alternative to conventional forceps biopsy.

Diagnostic Yield of Transbronchial Cryobiopsy Guided by Radial Endobronchial Ultrasound and Fluoroscopy in the Radiologically Suspected Lung Cancer: A Single Institution Prospective Study.

Transbronchial cryobiopsy (TBCB) is being studied in the diagnosis of peripheral lung lesions; however, there are only a few clinical studies around the world. The aim of our study was to evaluate the diagnostic values and safety of transbronchial cryobiopsy for radiologically suspected peripheral lung cancer. The prospective clinical study was executed from September 2019 to September 2021 at a tertiary clinical centre in Lithuania. A total of 48 patients out of 102 underwent combined procedures of transbronchial forceps biopsy (TBFB) and TBCB. Diagnostic values and safety outcomes of TBFB and TBCB were analysed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 72.9%, 100%, 100%, 7.7%, and 88.0% for TBFB, 85.1%, 100%, 100%, 12.5%, and 93% for TBCB, as well as 91.5%, 100%, 100%, 20.0% and 96.7% for the combined procedures, respectively, with a significantly higher accuracy for cryobiopsies compared to forceps biopsies (p < 0.05). The diagnostic values for transbronchial cryobiopsies were similar, irrespective of the radial mini probe endobronchial ultrasound (RP-EBUS) position, lesion size or bronchus sign, however, the sensitivity of the combined procedures in cases with RP-EBUS adjacent to the target was significantly higher compared to TBFB (86.2% vs. 64.3%, p = 0.016). Samples of cryobiopsies were significantly larger than forceps biopsies (34.62 mm2 vs. 4.4 mm2, p = 0.001). The cumulative diagnostic yield of transbronchial cryobiopsy was 80.0% after the second biopsy and reached a plateau of 84.1% after four biopsies. No severe bleeding, pneumothorax, respiratory failure or death was registered in our study. TBCB is a potentially safe procedure, which increases diagnostic values in diagnosing peripheral lung lesions compared to TBFB.

Delayed-onset Organizing Pneumonia Emerging after Recovery from Coronavirus Disease 2019: A Report of Three Cases Diagnosed Using Transbronchial Cryobiopsy and a Review of the Literature.

We present three cases with an atypical clinical course of organizing pneumonia (OP) secondary to coronavirus disease 2019 (COVID-19). Three patients were discharged with satisfactory improvement after standard steroid therapy for COVID-19. Shortly after the completion of treatment, the patients experienced a flare-up of symptoms. Imaging results showed new lesions in the lungs. Transbronchial lung cryobiopsy showed histological findings consistent with OP in all cases. Steroids were administered, and a good therapeutic response was observed. This report is the first to describe pathologically confirmed OP that developed after recovery from COVID-19. Careful follow-up is advisable for patients who have recovered from COVID-19.

Diagnosis of diffuse parenchymal lung diseases using transbronchial cryobiopsy guided by endobronchial ultrasound compared to clinicoradiological diagnosis.

BACKGROUND: This study aimed to evaluate the safety and effect of transbronchial cryobiopsy guided by radial probe endobronchial ultrasound (RP-EBUS) compared with clinicoradiological diagnoses in diffuse parenchymal lung diseases (DPLDs). METHODS: A total of 60 patients with DPLDs confirmed by chest computed tomography (CT) who underwent transbronchial lung cryobiopsy guided by RP-EBUS were enrolled. The ultrasound images were obtained and identified together with corresponding chest CT characteristics. The cryobiopsy samples were evaluated histopathologically and compared with CT imaging, and the complications were analyzed. RESULTS: The multidisciplinary diagnosis was clear in 51 (85%) participants but unclear in the remaining 9 (15%) participants. In transbronchial cryobiopsy guided by RP-EBUS, 36 (60%) participants had the biopsy in 1 lobe while 24 (40%) had a biopsy in 2 different lobes, with a mean biopsy specimen size of 43.17±15.25 mm2. The histopathologic diagnosis based on biopsy confirmed the preprocedural clinicoradiological diagnosis in 51 (85%) patients and clarified the diagnosis in the other 9 patients with unclear clinicoradiological diagnosis, including alveolated lung parenchyma with interstitial chronic inflammation in 4 (6.7%) cases and chronic bronchiolitis and interstitial lymphocytic infiltrates in the other 5 (8.3%). Intraprocedural complications occurred in 57 (95%) patients, including pneumothorax in 9 (15%), bleeding in 47 (78.3%), and hypoxemia in 1 (1.7%). The ultrasound images of DPLDs were normal, mesh (n=24), nodular (n=9), and alveolar type (n=27). CONCLUSIONS: Transbronchial cryobiopsy guided by RP-EBUS is safe and effective and can supply additional information to the clinicoradiological approach for correct diagnosis of DPLDs.