The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis, a disease characterized by chronic infection and inflammation. We recently reported that air pollutants such as cigarette smoke and cadmium negatively regulate the expression of CFTR by affecting several steps in the biogenesis of CFTR protein. MicroRNAs (miRNAs) have recently received a great deal of attention as both biomarkers and therapeutics due to their ability to regulate multiple genes. Here, we show that cigarette smoke and cadmium up-regulate the expression of two miRNAs (miR-101 and miR-144) that are predicted to target CFTR in human bronchial epithelial cells. When premature miR-101 and miR-144 were transfected in human airway epithelial cells, they directly targeted the CFTR 3′UTR and suppressed the expression of the CFTR protein. Since miR-101 was highly up-regulated by cigarette smoke in vitro, we investigated whether such increase also occurred in vivo. Mice exposed to cigarette smoke for 4 weeks demonstrated an up-regulation of miR-101 and suppression of CFTR protein in their lungs. Finally, we show that miR-101 is highly expressed in lung samples from patients with severe chronic obstructive pulmonary disease (COPD) when compared to control patients. Taken together, these results suggest that chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients.

The manifestation of PH, even with mild severity, is associated with significantly increased risk for death among patients with idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course.

The manifestation of PH is associated with significantly increased risk for death in CF patients with advanced lung disease.

Objectives Cystic fibrosis (CF) is characterized by infection and inflammation of the sinorespiratory tract. Functional endoscopic sinus surgery (FESS) is an option for patients with severe sinusitis. We sought to evaluate pulmonary function testing after FESS in pediatric and adult patients with CF. Study Design Retrospective chart review using data from all patients with CF who underwent FESS from January 2009 to July 2014. Setting Patients were from a single institution. Subjects and Methods Data were extracted for 181 patients and 320 surgeries. Lung function data, including the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, were retrieved within 1 year before and after surgery. Mixed-effects regression was used to compare FEV1 trajectories before and after surgery. The effect of surgery was stratified by presurgery FEV1 to compare patients with mild/no lung disease (FEV1 >80%) and moderate/severe lung disease (FEV1 <80%). Results Of the 181 patients reviewed, 131 with primary FESS had FEV1 data. Presurgery average age was 16 years (95% confidence interval [CI], 14.27-17.73), and FEV1 mean was 85% (95% CI, 81.02-88.98). There were 88 patients with FEV1 >80% and 43 patients with FEV1 <80%. For the entire cohort, lung function did not change related to FESS. Among patients with FEV1 <80%, FEV1 declined presurgery by 3.5% per year (95% CI, -6.1% to -0.8%; P = .010), which halted after surgery with these patients, then showing no subsequent change in FEV1 (95% CI, 0.9%-3.7%; P = .240). No benefit was identified for patients with FEV1 >80%. Conclusion Pulmonary function testing improved in patients with moderate/severe lung disease 1 year following FESS. This suggests FESS may benefit pulmonary outcomes.