Hedgehog signaling in the airway epithelium of patients with chronic obstructive pulmonary disease.

Genome-wide association studies have linked gene variants of the receptor patched homolog 1 (PTCH1) with chronic obstructive pulmonary disease (COPD). However, its biological role in the disease is unclear. Our objective was to determine the expression pattern and biological role of PTCH1 in the lungs of patients with COPD. Airway epithelial-specific PTCH1 protein expression and epithelial morphology were assessed in lung tissues of control and COPD patients. PTCH1 mRNA expression was measured in bronchial epithelial cells obtained from individuals with and without COPD. The effects of PTCH1 siRNA knockdown on epithelial repair and mucous expression were evaluated using human epithelial cell lines. Ptch1+/- mice were used to assess the effect of decreased PTCH1 on mucous expression and airway epithelial phenotypes. Airway epithelial-specific PTCH1 protein expression was significantly increased in subjects with COPD compared to controls, and its expression was associated with total airway epithelial cell count and thickness. PTCH1 knockdown attenuated wound closure and mucous expression in airway epithelial cell lines. Ptch1+/- mice had reduced mucous expression compared to wildtype mice following mucous induction. PTCH1 protein is up-regulated in COPD airway epithelium and may upregulate mucous expression. PTCH1 provides a novel target to reduce chronic bronchitis in COPD patients.

Using pet-ct to reduce futile thoracotomy rates in non-small-cell lung cancer: a population-based review.

BACKGROUND: Combined positron-emission tomography and computed tomography (pet-ct) reduces futile thoracotomy (ft) rates in patients with non-small-cell lung cancer (nsclc). We sought to identify preoperative risk factors for ft in patients staged with pet-ct. METHODS: We retrospectively reviewed all patients referred to the BC Cancer Agency during 2009-2010 who underwent pet-ct and thoracotomy for nsclc. Patients with clinical N2 disease were excluded. An ft was defined as any of a benign lesion; an exploratory thoracotomy; pathologic N2 or N3, stage iiib or iv, or inoperable T3 or T4 disease; and recurrence or death within 1 year of surgery. RESULTS: Of the 108 patients who met the inclusion criteria, ft occurred in 27. The main reason for ft was recurrence within 1 year (14 patients) and pathologic N2 disease (10 patients). On multivariate analysis, an Eastern Cooperative Oncology Group performance status greater than 1, a pet-ct positive N1 status, a primary tumour larger than 3 cm, and a period of more than 16 weeks from pet-ct to surgery were associated with ft. N2 disease that had been negative on pet-ct occurred in 21% of patients with a pet-ct positive N1 status and in 20% of patients with tumours larger than 3 cm and non-biopsy mediastinal staging only. The combination of pet-ct positive N1 status and a primary larger than 3 cm had 85% specificity, and the presence of either risk factor had 100% sensitivity, for ft attributable to N2 disease. CONCLUSIONS: To reduce ft attributable to N2 disease, tissue biopsy for mediastinal staging should be considered for patients with pet-ct positive N1 status and with tumours larger than 3 cm even with a pet-ct negative mediastinum.