A comparison of standard and novel bronchoscopic endobronchial biopsy retrieval methods.

BACKGROUND: The targets of bronchoscopic biopsy now include not only adequate tissue for histologic diagnosis but also tissue for further analysis. We prospectively compared standard and novel bronchoscopic endobronchial biopsy (EBB) retrieval methods attempting to increase tissue yield. METHODS: EBB samples were retrieved using techniques A, B, and C using a standard forceps. Method A is routinely performed conventional method, where as in method B, biopsy forceps was left protruded from the bronchoscope and in method C, both valve and forceps were removed to prevent the loss of specimen. At least 6 EBB were retrieved per patient. Results were compared with gold standard composite of confirmatory pathological or clinic-radiologic follow up. RESULTS: A total of 42 of 43 patients completed the study. The final gold standard diagnosis was cancer [non-small cell lung cancer, metastatic, carcinoid, carcinoma in situ (24)], benign disease [sarcoid, amyloid, hamartoma, and chondroid tumor (4)], and benign/nonspecific inflammation (14). EBB retrieved using standard method A were smaller than novel methods B and C (P=0.03). However, the percentage of cases where blood was the predominant component (>50%) was less by standard methods A (4/42) than B (16/42) and C (20/42) (P=0.001). There was no difference in mean viable tumor area (n=23, sensitivity for EBB for cancer 96%) between groups A compared with B and C (P 0.27) and adequacy in benign cases by subepithelial depth (>0.3 mm) (P=0.38). CONCLUSION: Standard retrieval of endobronchial biopsies through the bronchoscope and cap does not reduce the size of viable tissue and reduces contaminating blood and necrotic material.

The phosphodiesterase type IV inhibitor cilomilast decreases pro-inflammatory cytokine production from primary bronchial epithelial cells in lung transplantation patients.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains the major cause of long-term morbidity and mortality after lung transplantation, and new therapeutic measures are needed. We speculated that cilomilast might reduce mediators of airway inflammation and angiogenesis from the airway epithelium, supporting a potential value in the treatment of BOS. We used an ex vivo primary bronchial epithelial cell culture (PBEC) model to investigate this hypothesis. Increasing evidence suggests the epithelium is central in stimulating both inflammatory and proliferative responses in the airway. METHODS: Bronchial brushings were taken from 7 stable lung allograft recipients and were used to establish sub-confluent PBECs. The effect of incubation for 48 hours with 0.1 to 10 micromol/liter cilomilast on basal production of interleukin (IL)-8, IL-6, granulocyte macrophage colony-stimulating factor (GMCSF), and vascular endothelial growth factor (VEGF) were assayed by multiplex analyser. RESULTS: There was a dose dependent fall in basal IL-8 and GMCSF levels with cilomilast. Median change for IL-8 was -25% (range, -66% to 5%; p = 0.035) at 1 micromol/liter , and -40% (range, -72% to -20; p = 0.022) at 10 micromol/liter. Median GMSCF change was -34% (range, -70% to 16%; p = 0.05) at 1 micromol/liter, and 37% (range, -80% to -8%; p = 0.04) at 10 micromol/liter. There were no effects on VEGF. CONCLUSION: The phosphodiesterase type IV inhibitor cilomilast reduced IL-8 and GMCSF release from PBECs. These cytokines are associated with the persistence of airway neutrophilic inflammation and airway remodelling seen in obliterative bronchiolitis. These ex vivo results suggest a potential for cilomilast in the treatment of BOS, which would need to be evaluated in appropriate clinical studies.