The use of transbronchial cryobiopsy for diffuse parenchymal lung disease in critically ill patients with acute hypoxemic respiratory failure-A case series.

OBJECTIVES: Accurate diagnosis and management of undifferentiated diffuse parenchymal lung disease (DPLD) in critically ill patients is challenging. Transbronchial forceps biopsies have limited utility and surgical lung biopsies can be detrimental for critically ill patients. Transbronchial cryobiopsy (TBC) has shown increased diagnostic yield compared to conventional forceps biopsy in DPLD. However, TBC has not been studied in intensive care unit (ICU) patients. In this case series, we describe our experience with TBC for diagnosis of DPLD in ICU patients with acute hypoxemic respiratory failure. METHODS: This case series includes critically ill patients who underwent TBC at two different tertiary care hospitals. Procedures were performed by the same interventional pulmonologist using the two therapeutic bronchoscopes with a 2.8-mm working channel, and a 1.9- or 2.4-mm cryoprobe. RESULTS: We performed TBC in 17 patients of which 12 (70.1%) were performed at bedside in ICU without fluoroscopic guidance. Pathological diagnosis was made in 15 (88%) patients which resulted in changes in management in most of these patients. Six patients (35.3%) developed pneumothorax post-procedure with 5 (29.4%) requiring a chest tube. Moderate bleeding was noted in one (6%) patient and no severe or fatal bleeding occurred. Our 30-day ICU mortality was 47% (n = 8); however, no deaths were directly attributable to the procedure. CONCLUSIONS: TBC is a feasible technique with an acceptable complication rate and a fairly high histopathological yield in ICU patients with DPLD and acute hypoxemic respiratory failure. Appropriate diagnosis can be crucial in making management decisions for these patients.

MAPK mutations and cigarette smoke promote the pathogenesis of pulmonary Langerhans cell histiocytosis.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare smoking-related lung disease characterized by dendritic cell (DC) accumulation, bronchiolocentric nodule formation, and cystic lung remodeling. Approximately 50% of patients with PLCH harbor somatic BRAF-V600E mutations in cells of the myeloid/monocyte lineage. However, the rarity of the disease and lack of animal models have impeded the study of PLCH pathogenesis. Here, we establish a cigarette smoke-exposed (CS-exposed) BRAF-V600E-mutant mouse model that recapitulates many hallmark characteristics of PLCH. We show that CD11c-targeted expression of BRAF-V600E increases DC responsiveness to stimuli, including the chemokine CCL20, and that mutant cell accumulation in the lungs of CS-exposed mice is due to both increased cellular viability and enhanced recruitment. Moreover, we report that the chemokine CCL7 is secreted from DCs and human peripheral blood monocytes in a BRAF-V600E-dependent manner, suggesting a possible mechanism for recruitment of cells known to dominate PLCH lesions. Inflammatory lesions and airspace dilation in BRAF-V600E mice in response to CS are attenuated by transitioning animals to filtered air and treatment with a BRAF-V600E inhibitor, PLX4720. Collectively, this model provides mechanistic insights into the role of myelomonocytic cells and the BRAF-V600E mutation and CS exposure in PLCH pathogenesis and provides a platform to develop biomarkers and therapeutic targets.

Safety of performing transbronchial lung cryobiopsy on hospitalized patients with interstitial lung disease.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) has become a popular option for tissue diagnosis of interstitial lung disease (ILD), however reports vary regarding the safety of this procedure. Herein, we evaluate the safety of transbronchial cryobiopsy in hospitalized patients, comparing adverse events to outpatient procedures. METHODS AND MEASUREMENTS: This is a single center, retrospective chart review of all TBLC performed for suspected ILD between November 2013 and March 2017. Biopsies were performed by a board certified interventional pulmonologist or interventional pulmonology fellow using a two-scope technique. RESULTS: One hundred fifty-nine cryobiopsies were performed for the diagnosis of ILD. Rates of adverse events are as follows: pneumothorax 11%, persistent air leak 1.3%, moderate-severe bleeding 3.8%, ICU transfer within 48 h 3.1%, and all cause 30-day mortality 1.9%. No deaths were attributed to the procedure. Comparing adverse events between hospitalized patients and outpatients, rates of pneumothorax were 24% vs 9.9%, persistent air leak 5.9% vs 0.7%, ICU transfer 12% vs 2.1%, and 30-day mortality 5.9% vs 1.4%. However, no differences were statistically significant. CONCLUSION: Practitioners should recognize that while cryobiopsies are a high-yield, safe, and cost-effective alternative to surgical lung biopsy, not all procedures carry the same risk profiles. Hospitalized patients may have a greater propensity for pneumothorax, persistent air leak, transfer to the ICU, and 30-day mortality.