ROCK STUDY in CF: sustained anti-inflammatory effects of lumacaftor-ivacaftor in sputum and peripheral blood samples of adult patients with cystic fibrosis-an observational study.

BACKGROUND: Previous studies showed that the combination of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) corrector and potentiator, lumacaftor-ivacaftor (LUMA-IVA) provides meaningful clinical benefits in patients with cystic fibrosis who are homozygous for the Phe508del CFTR mutation. However, little is known about the effect of LUMA-IVA on Proinflammatory Cytokines (PICs). OBJECTIVES: To investigate the impact of LUMA-IVA CFTR modulation on circulatory and airway cytokines before and after 12 months of LUMA-IVA treatment in a real-world setting. METHODS: We assessed both plasma and sputum PICs, as well as standard clinical outcomes including Forced Expiratory Volume in one second (FEV1) %predicted, Body Mass Index (BMI), sweat chloride and pulmonary exacerbations at baseline and prospectively for one year post commencement of LUMA-IVA in 44 patients with cystic fibrosis aged 16 years and older homozygous for the Phe508del CFTR mutation. RESULTS: Significant reduction in plasma cytokines including interleukin (IL)-8 (p<0.05), tumour necrosis factor (TNF)-α (p<0.001), IL-1ß (p<0.001) levels were observed while plasma IL-6 showed no significant change (p=0.599) post-LUMA-IVA therapy. Significant reduction in sputum IL-6 (p<0.05), IL-8 (p<0.01), IL-1ß (p<0.001) and TNF-α (p<0.001) levels were observed after LUMA-IVA therapy. No significant change was noted in anti-inflammatory cytokine IL-10 levels in both plasma and sputum (p=0.305) and (p=0.585) respectively. Clinically significant improvements in FEV1 %predicted (mean+3.38%, p=0.002), BMI (mean+0.8 kg/m2, p<0.001), sweat chloride (mean -19 mmol/L, p<0.001), as well as reduction in intravenous antibiotics usage (mean -0.73, p<0.001) and hospitalisation (mean -0.38, p=0.002) were observed after initiation of LUMA-IVA therapy. CONCLUSION: This real-world study demonstrates that LUMA-IVA has significant and sustained beneficial effects on both circulatory and airway inflammation. Our findings suggest that LUMA-IVA may improve inflammatory responses, which could potentially contribute to improved standard clinical outcomes.

Inhaler screw-up: A real world cystic fibrosis (CF) case.

A 40-year-old male with Cystic Fibrosis developed a sudden onset choking, cough, dyspnea and hemoptysis after using his inhaler. He presented to A&E. CT scan located a foreign body in his right bronchus intermedius (RBI). Rigid bronchoscopy was performed and removed a plastic rawl plug with screw from his RBI. He made a rapid recovery. On questioning he mentioned he had stored his inhaler uncapped in the same pocket he had this screw which he found at work. Small objects can lodge in inhalers due to their design/mouthpiece uncapping. This can result in endobronchial foreign body aspiration. This case highlights the importance of replacing inhaler cap when not in use.

Bronchoscopy in the investigation of outpatients with hemoptysis at a lung cancer clinic.

BACKGROUND: In the investigation of lung cancer, current practice in many healthcare systems would support bronchoscopy regardless of CT findings in patients with hemoptysis. We sought to identify the cause, the diagnostic yield of CT and bronchoscopy and the requirement for bronchoscopy in at risk patients with hemoptysis with a normal CT scan through our rapid access lung cancer clinic (RALC). METHODS: Initially, a chart review was performed on all patients with hemoptysis (2011-2012) and thereafter a prospective analysis was performed (2013-2016). RESULTS: Our analysis represents the largest study to date in outpatients with hemoptysis. In our retrospective study, 155 patients reported hemoptysis. Causes were lower respiratory tract infections (RTIs) (47%) and lung cancer (16%). Our prospective study included 182 patients. The causes of hemoptysis were RTIs (50%) and lung cancer (18%). There were no false negative CT-scans for lung cancer. 47/57 present with lung cancer underwent bronchoscopy and 43/47 were positive for lung cancer (92%). Patients with hemoptysis and lung cancer have a higher stage of malignancy with a predominance of squamous cell lung carcinoma. Smoking status, the duration of hemoptysis or description of hemoptysis were not predictive of lung cancer however lung cancer was not identified in patients age <50. CONCLUSIONS: One sixth of patients presenting with hemoptysis to our lung cancer clinic had lung cancer. No patient identified with cancer related haemoptysis had a CT negative for lung cancer and a combination of bronchoscopy plus endobronchial ultrasound trans-bronchial needle aspiration (EBUS-TBNA) in those patients with a CT suspicious of lung cancer is 92% sensitive for lung cancer causing hemoptysis.