Uncoupling of macrophage inflammation from self-renewal modulates host recovery from respiratory viral infection.

Tissue macrophages self-renew during homeostasis and produce inflammatory mediators upon microbial infection. We examined the relationship between proliferative and inflammatory properties of tissue macrophages by defining the impact of the Wnt/ß-catenin pathway, a central regulator of self-renewal, in alveolar macrophages (AMs). Activation of ß-catenin by Wnt ligand inhibited AM proliferation and stemness, but promoted inflammatory activity. In a murine influenza viral pneumonia model, ß-catenin-mediated AM inflammatory activity promoted acute host morbidity; in contrast, AM proliferation enabled repopulation of reparative AMs and tissue recovery following viral clearance. Mechanistically, Wnt treatment promoted ß-catenin-HIF-1α interaction and glycolysis-dependent inflammation while suppressing mitochondrial metabolism and thereby, AM proliferation. Differential HIF-1α activities distinguished proliferative and inflammatory AMs in vivo. This ß-catenin-HIF-1α axis was conserved in human AMs and enhanced HIF-1α expression associated with macrophage inflammation in COVID-19 patients. Thus, inflammatory and reparative activities of lung macrophages are regulated by ß-catenin-HIF-1α signaling, with implications for the treatment of severe respiratory diseases.

Outpatient thoracoscopy: safety and practical considerations.

PURPOSE OF REVIEW: Medical thoracoscopy, also known as pleuroscopy, has been utilized by chest physicians for more than a century. Despite this, it has only recently re-emerged as an important tool for interventional pulmonologists to diagnose and treat pleural diseases. The purpose of this review is to critically assess the recent literature related to medical thoracoscopy, specifically as it pertains to its safety and feasibility as an outpatient procedure. RECENT FINDINGS: Recent data have reaffirmed the clinical utility of medical thoracoscopy and suggest that it can be safely performed in an outpatient setting. A single-center study of 51 patients published in the past year described both the feasibility and safety of outpatient medical thoracoscopy. This study highlights the notion that the majority of patients do not require hospital admission after a routine diagnostic thoracoscopy in the absence of talc poudrage. Another study this year described the successful use of chest physician-directed ultrasound-guided cutting needle biopsy when medical thoracoscopy was not technically possible. SUMMARY: The contribution of medical thoracoscopy in the diagnosis and management of pleural diseases is increasingly recognized. Evidence supports the routine practice of medical thoracoscopy on an outpatient basis in experienced centers.

Custom silicone Y-stents for the management of anastomotic stenosis in lung transplant recipients.

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

Feasibility and Efficacy of a Non-Opioid Based Pain Management After Medical Thoracoscopy.

BACKGROUND: Prescription opioids are a major cause of the opioid epidemic. Despite the minimally invasive nature of medical thoracoscopy (MT), data on the efficacy of non-opioid-based pain control after MT is lacking. The purpose of this study is to assess the feasibility and efficacy of a non-opioid-based pain management strategy in patients who underwent MT. METHODS: We performed a retrospective analysis of all patients who underwent MT in the Mayo Clinic (Minnesota and Arizona) outpatient setting. We assessed their pain level and the need for analgesia post-MT from August 1, 2019, to May 24, 2021. RESULTS: Forty patients were included. In the first 24 hours, 5/40 (12.5%) reported no pain. Twenty-eight patients out of 40 (70%) reported minor pain (pain scale 1-3), and 7/40 (17.5%) reported moderate pain (pain scale 4-6). No patients reported severe pain. Twenty-two out of 35 patients who experienced discomfort (63%) required acetaminophen, 6/35 patients (17%) required nonsteroidal anti-inflammatory drug, and 7/35 patients (20%) did not require analgesia. Of the 7 patients who had moderate pain, 5 (71%) reported that the moderate pain improved to mild at 72 hours post-MT. Zero patients required opioids, and none reported contacting any provider to manage the pain post-MT. Fourteen patients (78%) who had both parietal pleural biopsies and tunneled pleural catheter placed reported minor pain, 3 patients (17%) reported moderate pain, and 1 patient (6%) experienced no discomfort. CONCLUSION: MT is well-tolerated by patients with non-opioid-based pain management strategy as needed if there is no absolute contraindication.

Diagnostic Yield of 16S Ribosomal Ribonucleic Acid Gene-Based Targeted Metagenomic Sequencing for Evaluation of Pleural Space Infection: A Prospective Study.

Objective: To better understand the microbial profile of complicated parapneumonic effusions and empyema, and to evaluate whether antimicrobial selection would differ if guided by targeted metagenomic sequencing (tMGS) vs conventional cultures (CCs) alone. Patients and Methods: We analyzed the pleural fluid of a cohort of 47 patients undergoing thoracentesis from January 1, 2017 to August 31, 2019, to characterize their microbial profile. All samples underwent 16S ribosomal ribonucleic acid gene polymerase chain reaction, followed by tMGS. Results: Pleural space infection was deemed clinically present in 20 of the 47 (43%) participants. Of those, n=7 (35%) had positive pleural fluid cultures and n=14 (70%) had positive tMGS results. The organisms identified by tMGS were concordant with CCs; however, tMGS detected additional bacterial species over CCs alone. Streptococcus and Staphylococcus species were the most common organisms identified, with Streptococcus intermedius/constellatus identified in 5 patients. Polymicrobial infections were found in 6 of the 20 patients, with anaerobes being the most common organisms identified in these cases. Conclusion: Streptococci and staphylococci were the most common organisms identified in infected pleural fluid. Anaerobes were common in polymicrobial infections. When compared with CCs, tMGS had higher sensitivity than CCs. Targeted metagenomic sequencing identified additional organisms, not identified by CCs, with associated potential management implications.

Early thoracentesis correlated with survival benefit in patients with spontaneous bacterial empyema.

BACKGROUND: Spontaneous bacterial empyema (SBEM) is a rare complication of hepatic hydrothorax characterized by hydrothorax infection in the absence of pneumonia. AIMS AND METHODS: We conducted this study to compare clinical outcomes in SBEM patients who underwent early thoracentesis (ET) (≤ 24 h from presentation) versus those who underwent delayed thoracentesis (DT). All patients diagnosed with SBEM at Mayo Clinic Rochester, Minnesota from January 1st 1999 to December 31st 2020 were reviewed. Demographics, pleural fluid studies, laboratory results and clinical outcomes were analyzed. RESULTS: A total of 54 SBEM patients (27 ET and 27 DT) were identified with 38 (70.4%) of patients presenting with right-sided effusions. Both groups had similar baseline characteristics. The rate of ICU admission was significantly higher in the DT group (15 (55.6%) vs. 7 (25.9%) patients, P = 0.027). Patients with DT had similar rate of AKI (11 (40.7%) vs. 6 (22.2%) patients, P = 0.074). In-hospital mortality (11 (40.7%) vs. 2 (7.4%) patients, P = 0.004), 3-month mortality (16 (59.3%) vs. 2 (7.4%) patients, P < 0.001) and 1-year mortality rate (21 (77.8%) vs. 6 (22.2%) patients, P < 0.001) were higher in the DT group. CONCLUSION: Patients with SBEM who underwent thoracentesis after 24 h from presentation (DT) had higher rates of mortality and ICU admission compared to patients who received early thoracentesis. Thoracentesis should be performed early in patients with suspected SBEM since it may improve survival.

Bronchoscopic Lung Volume Reduction: A New Hope for Patients With Severe Emphysema and Air Trapping.

Chronic obstructive pulmonary disease (COPD) is common and has significant morbidity and mortality as the fourth leading cause of death in the United States. In many patients, particularly those with emphysema, COPD is characterized by markedly increased residual volume contributing to exertional dyspnea. Current therapies have limited efficacy. Surgical resection of diseased areas of the lung to reduce residual volume was effective in identified subgroups but also had significant mortality in and suboptimal cost effectiveness. Lung-volume reduction, using bronchoscopic techniques, has shown substantial benefits in a broader patient population with less morbidity and mortality. This review is meant to spread the awareness about bronchoscopic lung-volume reduction and to promote its consideration and early referral for patients with advanced COPD and emphysema frequently encountered by both primary care physicians and specialists. A search was conducted on PubMed (MEDLINE), EMbase, and Cochrane library for original studies, using the following keywords: "lung-volume reduction." "endobronchial valves," "intrabronchial valves," "bronchoscopic lung-volume reduction," and "endoscopic lung-volume reduction." We included reports from systematic reviews, narrative reviews, clinical trials, and observational studies. Two reviewers evaluated potential references. A total of 27 references were included in our review. Included studies report experience in the diagnosis and bronchoscopic treatment for emphysema; case reports and non-English or non-Spanish studies were excluded.

Utility of Transbronchial Biopsy in the Immunocompromised Host With New Pulmonary Radiographic Abnormalities.

OBJECTIVE: To assess how often transbronchial biopsy (TBBx) added unique positive findings apart from other synchronous bronchoscopic sampling techniques including the bronchoalveolar lavage-immunocompromised host (BAL-ICH) panel that justified changes in management in an array of immunocompromised patients with new pulmonary radiographic abnormalities. METHODS: We retrospectively reviewed all bronchoscopies performed at Mayo Clinic Rochester between January 2012 and December 2017; on the basis of the physician's selection of a BAL-ICH panel, we identified 192 immunocompromised patients who underwent bronchoscopy with both a BAL-ICH panel and TBBx. The results of the BAL-ICH panel and TBBx were compared and subsequent management decisions analyzed from clinical notes. We identified changes in immunosuppressive agents, antibiotics, chemotherapy, goals of care, and decisions on further evaluation and procedures. We assessed whether the TBBx findings added information not identified on the BAL-ICH panel and other bronchoscopic sampling methods performed during the same procedure that justified subsequent management changes. RESULTS: Of 192 bronchoscopic procedures performed on immunocompromised patients with acute and subacute pulmonary radiographic abnormalities, management changes justified by the unique positive results of the TBBx occurred 28% (51/192) of the time. Those immunocompromised by solid malignant neoplasms and receiving active immunosuppressive therapy had management changes justified 62.1% (18/29) of the time by the TBBx results. No additional fungal organisms were identified on TBBx that were accounted for on the BAL-ICH panel. CONCLUSION: Transbronchial biopsy may add information to other bronchoscopic findings in immunocompromised patients, especially those with solid malignant neoplasms receiving active immunosuppressive treatment. These potential benefits must be weighed against the risks inherent to the procedure.

Cavitary lung lesions caused by Pneumocystis jirovecii in setting of common variable immune deficiency.

Pneumocystis pneumonia affects immunocompromised hosts. The typical imaging finding is bilateral diffuse ground glass opacities. Here we presented a case of Pneumocystis causing biopsy-confirmed cavitary lung lesions in a patient with a predominant B cell defect with common variable immune deficiency.

Bronchoscopic Cryobiopsy and Forceps Biopsy for the Diagnostic Evaluation of Diffuse Parenchymal Lung Disease in Clinical Practice.

OBJECTIVE: To assess the contribution and safety of bronchoscopic cryobiopsy vs traditional forceps biopsy used in clinical practice for diagnosing diffuse parenchymal lung disease (DPLD). PATIENTS AND METHODS: We identified 271 patients who underwent bronchoscopic biopsy for DPLD at Mayo Clinic, MN (June 1, 2013, through September 30, 2017). Medical records were reviewed including prebiopsy clinical and radiographic impressions. Diagnostic yield was assessed in terms of a specific histologic pattern resulting in a diagnosis when combined with the clinical-radiologic context. Clinical utility was defined as a biopsy result deemed useful in patient management. RESULTS: The cohort included 120 cryobiopsy and 151 forceps biopsy cases with mean age 61±14 years and 143 (53%) men. Diagnostic yield (55% vs 41%; odds ratio [OR], 1.73; 95% CI, 1.07 to 2.83; P=.026) and clinical utility (60% vs 40%; OR, 2.21; 95% CI, 1.36 to 3.63; P=.001) were higher for the cryobiopsy group, and the association remained after control for prebiopsy clinical impressions (OR, 2.21; 95% CI, 1.22 to 4.08; P=.010 and OR, 3.23; 95% CI, 1.76 to 6.10; P<.001, respectively). However, pneumothorax (5.4% vs 0.7%; P=.022) and serious bleeding (7.1% vs 0%; P=.001) rates were higher for the cryobiopsy group. Thirty-day mortality was 1.6% in the cryobiopsy group vs 0% for the forceps biopsy group (P=.20). CONCLUSION: Bronchoscopic cryobiopsy revealed higher diagnostic yield and clinical utility than did forceps biopsy. However, procedure-related complications were higher in the cryobiopsy group. The choice of bronchoscopic biopsy procedure for patients with DPLD depends on the clinicalradiologic context.

The Safety of Ultrasound-Guided Thoracentesis in Patients on Novel Oral Anticoagulants and Clopidogrel: A Single-Center Experience.

OBJECTIVE: To assess the risk of hemorrhagic complications in patients taking novel oral anticoagulants (NOACs) and/or clopidogrel who underwent an ultrasound-guided thoracentesis. PATIENTS AND METHODS: A retrospective analysis was performed of ultrasound-guided thoracenteses completed at an academic institution between January 1, 2016, and November 14, 2017. All patients who underwent a thoracentesis while actively receiving treatment with an NOAC and/or clopidogrel were included in the study. Primary endpoints are any significant post-procedure bleeding complication; defined as a hemoglobin decrease of greater than 2 g/dL in 48 hours, hemothorax, chest wall hematoma, and bleeding requiring transfusion, surgery, or chest tube placement. RESULTS: A total of 115 thoracenteses were performed in 103 patients actively taking an NOAC (n=43) and/or clopidogrel (n=69). All patients used either the NOAC or clopidogrel within 24 hours before the procedure and continued using it daily thereafter. There were no bleeding complications. CONCLUSION: The overall risk of significant hemorrhage in patients taking an NOAC and/or clopidogrel while undergoing ultrasound-guided thoracentesis is very low. Albeit the total number of procedures reviewed may be insufficient to prove definitive safety, it is sufficient to provide a measure of relative risk when assessing benefits of thoracentesis in these patients.

Persistent air leak - review.

A persistent air leak (PAL) can be caused by either an alveolar-pleural fistula (APF) or bronchopleural fistula (BPF). Complications from PAL lead to an increase in morbidity and mortality, prolonged hospital stay, and higher resource utilization. Pulmonary physicians and thoracic surgeons are often tasked with the difficult and often times frustrating diagnosis and management of PALs. While most patients will improve with chest tube thoracostomy, many will fail requiring alternative bronchoscopic or surgical strategies. Herein, we review the bronchoscopic and surgical diagnostic and treatment options for PAL as it pertains to the field of interventional pulmonology and thoracic surgery.

Methylene Blue for Bronchopleural Fistula Localization.

A bronchopleural fistula (BPF) is a communication between the pleural space and the bronchial tree. BPFs are challenging to diagnose and are associated with a high morbidity and mortality. Sequential balloon occlusion is commonly used for localization of a BPF. We describe our experience with 4 cases of successful localization of the BPF by instillation of methylene blue into the pleural space through a pigtail catheter, with simultaneous bronchoscopic visualization of dye in the tracheobronchial tree. Two patients were treated with endobronchial valves and 3 had a surgical thoracic muscle flap placed.

Paclitaxel-coated balloon dilation for central airway obstruction.

INTRODUCTION: Central airway obstruction (CAO) often requires repeated interventional procedures which offer variable efficacy, a time-limited effect, and have inherent limitations. Paclitaxel has been used to prevent restenosis in blood vessels. The literature describing the use of paclitaxel to prevent recurrent airway stenosis is limited. We sought to describe our experience using a paclitaxel-coated balloon (PCB) for CAO. MATERIAL AND METHODS: We performed a retrospective review of all patients who underwent PCB airway dilation. We collected: basic demographics, details of the CAO, details of the bronchoscopes used, PCB size, PCB dilation pressure, duration of PCB inflation, concurrent non-PCB interventions, estimated pre- and post-PCB CAO luminal diameter, follow up bronchoscopy date and luminal diameter, and spirometry results. RESULTS: PCB dilation was performed in 10 cases on 5 patients. Eight PCB dilations were performed for CAO related to distal airway stent stenosis. Concurrent non-PCB interventions were performed with 6 PCB dilations. Nine cases documented improvements and 1 was unchanged immediately post-PCB dilation. Median luminal diameter pre-PCB dilation was 2 mm. Immediately post-PCB dilation, the median change in luminal diameter was 2 mm. Follow up bronchoscopy information was available for 9 cases. For these 9 cases, luminal diameter was unchanged in 5 and worse in 4 when compared to immediate post-PCB dilation. CONCLUSION: PCB dilation in benign CAO produced a modest effect in this cohort of challenging airways. Larger prospective studies are needed to assess how a PCB would perform when compared to a non-drug coated balloon.

Extracellular matrix fistula plug for repair of bronchopleural fistula.

INTRODUCTION: Bronchopleural fistula (BPF) is a feared complication of pulmonary resection. Fistula plugs (FP) have been described as an adequate treatment in anorectal disease. We describe our early experience placing an FP in the treatment of BPF. MATERIALS AND METHODS: We retrospectively reviewed 5 patients for whom a FP was placed for BPF at our institution. Demographic data, initial perioperative information, method and technique of FP placement, and success is reported. RESULTS: Five patients (4 male, 1 female) with a median age of 63 years (range, 57-76 years) underwent 6 FP placements for BPF. Two patients were post-pneumonectomy and 3 patients post-lobectomy. The median time to presentation following surgery was 118 days (range 22-218). Upon bronchoscopic or operative re-evaluation, 3 patients had successful cessation of their air leak at 0, 1 and 4 days. Two of three patients subsequently underwent a thoracic muscle flap placement to augment healing. One patient had a persistent air leak despite 2 separate FP placements. The air leak stopped with endobronchial valves (EBV) which were deployed proximal to the FP, 9 days after placement of the FP. Another patient had a successful muscle flap placed 80 days after FP placement. There were no complications associated with the FP. Three of five patients were deemed successfully treated with FP placement alone. CONCLUSION: In patients with a postoperative BPF and pleural window, placement of a FP had a modest success rate and can be considered as a treatment modality option for BPF.

Comparison of Programmed Death Ligand-1 Immunohistochemical Staining Between Endobronchial Ultrasound Transbronchial Needle Aspiration and Resected Lung Cancer Specimens.

BACKGROUND: In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor. METHODS: We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV. RESULTS: Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively. CONCLUSIONS: A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1.

Transbronchial Cryobiopsy in Diffuse Parenchymal Lung Disease: Retrospective Analysis of 74 Cases.

BACKGROUND: Diagnostic evaluation of patients with diffuse parenchymal lung disease (DPLD) is best achieved by a multidisciplinary team correlating clinical, radiological, and pathologic features. Surgical lung biopsy remains the gold standard for histopathologic diagnosis of idiopathic interstitial pneumonias. Emerging data suggest an increasing role for transbronchial cryobiopsy (TBC) in DPLD evaluation. We describe our experience with TBC in patients with DPLD. METHODS: We retrospectively reviewed medical records of patients with radiographic features of DPLD who underwent TBC at Mayo Clinic in Rochester, Minnesota from June 2013 to September 2015. RESULTS: Seventy-four patients (33 women [45%]) with a mean age of 63 years (SD, 13.8) were included. The mean maximal diameter of the samples was 9.2 mm (range, 2-20 mm [SD, 3.9]). The median number of samples per procedure was three (range, one to seven). Diagnostic yield was 51% (38 of 74 specimens). The most frequent histopathologic patterns were granulomatous inflammation (12 patients) and organizing pneumonia (OP) (11 patients), resulting in the final diagnoses of hypersensitivity pneumonitis (six patients), cryptogenic OP (six patients), connective tissue disease-associated OP (three patients), drug toxicity (three patients), infection-related OP (two patients), sarcoidosis (two patients), and aspiration (one patient). Other histopathologic patterns included respiratory bronchiolitis (three patients), acute fibrinous and organizing pneumonia (two patients), desquamative interstitial pneumonia (1 patient), diffuse alveolar damage (one patient), pulmonary alveolar proteinosis (one patient), amyloidosis (one patient), eosinophilic pneumonia (one patient), necrotizing vasculitis (one patient), bronchiolitis with food particles (one patient), and malignancy (three patients). Pneumothorax developed in one patient (1.4%), and bleeding occurred in 16 patients (22%). CONCLUSIONS: Our single-center cohort demonstrated a 51% diagnostic yield from TBC; the rates of pneumothorax and bleeding were 1.4% and 22%, respectively. The optimal use of TBC needs to be determined.

Pulmonary Abscess as a Complication of Transbronchial Lung Cryobiopsy.

We present the case of a 49-year-old man who developed pulmonary abscess as a complication of transbronchial lung cryobiopsy. He had been receiving prednisone therapy, but otherwise had no specific risk factors for lung abscess. Cryobiopsy is a novel technique for obtaining peripheral lung parenchymal tissue for the evaluation of diffuse parenchymal lung diseases. Cryobiopsy is being increasingly proposed as an alternative to surgical lung biopsy or conventional bronchoscopic transbronchial forceps biopsy, but the safety profile of the procedure has not been fully appreciated. Pulmonary abscess has been rarely reported as a complication of other bronchoscopic procedures such as endobronchial ultrasound-guided needle biopsy, however, to our knowledge this is the first reported case of pulmonary abscess complicating peripheral lung cryobiopsy.

Transbronchial Cryobiopsies in the Evaluation of Lung Allografts: Do the Benefits Outweigh the Risks?

CONTEXT: Transbronchial cryobiopsy technique yields larger biopsies with enhanced quality. The benefits and safety of cryobiopsies have not been thoroughly studied in lung allografts. OBJECTIVE: To compare size, quality, reproducibility of interpretation of rejection and complications of cryobiopsies with those of conventional biopsies from lung allografts. DESIGN: All cryobiopsies (March 2014-January 2015) of lung allografts performed at Mayo Clinic, Rochester, and medical records were reviewed. For comparison, conventional biopsies from the same patient or, if unavailable, from a random patient, were selected. Two pathologists blinded to outcome reviewed all biopsies. Specimen volume, number of alveoli, small airways, and pulmonary vessels were counted and statistically compared. RESULTS: Fifty-four biopsies (27 cryobiopsies) from 18 patients (11 men) were reviewed. A median of 3 (range, 2-5) and 10 (range, 6-12) specimens were obtained with cryobiopsies and conventional biopsies, respectively. Cryobiopsies were larger and contained more alveoli (P < .001, both) and small airways (P = .04). Conventional biopsies showed more fresh alveolar hemorrhage (procedural) and crush artifact/atelectasis (P < .001, both). Cryobiopsies contained more pulmonary veins and venules (P < .001). There was no significant difference between the types of biopsies with respect to the reviewers' agreement on grades of rejection. Complications were more frequent in the cryobiopsy group, though the difference was not statistically significant. CONCLUSIONS: Cryobiopsies of lung allografts are larger and have less artifact. However, complications occur and should be considered. Three cryobiopsy specimens appear sufficient for histopathologic evaluation of lung allografts.