Pharmacological management of Idiopathic Pulmonary Fibrosis: current and emerging options.

INTRODUCTION: Idiopathic Pulmonary Fibrosis is a chronic, progressive lung disease characterized by worsening lung scarring and the radiological/histological pattern of usual interstitial pneumonia. Substantial progress has been made in the clinical management of IPF in the last decade. The two novel antifibrotics, Nintedanib and Pirfenidone have changed the landscape of IPF, by hindering disease progression; however, the drugs have significant discontinuation rates, due to adverse events and do not offer a definitive cure, as such IPF remains a deleterious disease with poor survival. AREAS COVERED: In this review, the authors focus on the current and emerging pharmacological options in the treatment of IPF. They include a summary of the current approach including treatment of comorbidities and then discuss promising drugs in the drug pipeline. EXPERT OPINION: IPF remains a disease with detrimental outcomes. The plethora of emerging pharmacological treatments brings hope for the future. The current pharmacological 'one fits all' approach has been proven effective in slowing disease progression. The future lies in an oncological approach with combination of therapies. We expect to see a change in clinical trial endpoints and a more inclusive approach for the diagnosis of IPF. ABBREVIATION LIST: AE: Acute ExacerbationA-SMA: a smooth muscle actinATX: AutotaxinCOPD: Combined Obstructive Pulmonary DiseaseCPFE: Combined Pulmonary Fibrosis and EmphysemaGER: Gastro-esophageal refluxFVC: forced vital capacityECMO: extracorporeal membrane oxygenationILD: Interstitial Lung DiseaseIPF: Idiopathic Pulmonary FibrosisNAC: N-acetylcysteineLPA: Lysophosphatidic acidPH: Pulmonary RehabilitationPR: Pulmonary rehabilitationRCTs: randomized placebo-controlled trialsUIP: usual interstitial pneumonia.

Assessment of High Flow Nasal Cannula Oxygenation in Endobronchial Ultrasound Bronchoscopy: A Randomized Controlled Trial.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been widely implemented in evaluating mediastinal disease. EBUS-TBNA is performed with low flow oxygen systems or general anesthesia. Little data exist on use of high flow nasal cannula (HFNC) in EBUS-TBNA. METHODS: This was a single center parallel group randomized controlled trial comparing oxygenation through HFNC (Optiflow) against nasal prongs during EBUS. The primary end-point was the drop in oxygen saturations from procedure commencement, recorded by pulse oximetry, to the lowest level during EBUS-TBNA. Secondary end-points included changes in venous blood carbon dioxide, lowest oxygen saturation, changes in end-tidal CO2 during the procedure, intubation within 8 hours of the procedure and patient experience reported on a visual analog scale. RESULTS: We randomized 20 patients to each study arm. The primary outcome of oxygen desaturation during the procedure was statistically significant with a difference of 7.7 percentage points (95% confidence interval, 4.91-10.49, P<0.001). The secondary outcome measure of lowest oxygen saturation was also statistically significant with a difference of -9.2 (95% confidence interval, -11.96 to -6.44, P<0.001). There was no difference in safety outcomes, visual analog scale score or in their willingness to return for repeat procedure. CONCLUSION: This single institution study in a university, tertiary referral center confirms that EBUS-TBNA performed with HFNC is associated with a statistically significant lower drop in oxygen saturation. Additional studies are needed to assess if this translates into improved clinical outcomes postprocedure.

Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE): Protocol and preliminary data.

Chronic obstructive pulmonary disease (COPD) is a multisystem disease. Established comorbidities include cardiovascular disease, osteoporosis, loss of muscle mass and function, depression, and impaired quality of life. The natural history is not well understood. The Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE) is a longitudinal study of comorbidities in COPD. The primary aims are to delineate the progression and interrelationships of cardiovascular disease and associated comorbidities. Each year ARCADE aims to recruit 250 patients diagnosed with COPD and 50 comparators (free from respiratory disease). Assessments include spirometry, body composition, blood pressure, aortic stiffness (pulse wave velocity (PWV)), noninvasive measures of cardiac output, systemic inflammatory mediators, blood and urine biochemistry, and physical and health outcomes. These will be repeated at 2 and 5 years. In the first year of recruitment, 350 patients and 100 comparators were recruited. The reproducibility of aortic PWV, cardiac output, stroke volume, and cardiac index was evaluated and accepted in 30 patients free from overt cardiovascular disease. The preliminary data from ARCADE have demonstrated acceptable reproducibility of hemodynamic outcome measures. Further longitudinal data collection will increase knowledge of the progression and interactions between cardiovascular risk factors and other comorbidities in COPD.