The detection, assessment and clinical evolution of interstitial lung abnormalities identified through lung cancer screening

Introduction Interstitial lung abnormalities (ILAs) are common incidental findings in lung cancer screening; however, their clinical evolution and longer-term outcomes are less clear. The aim of this cohort study was to report 5-year outcomes of individuals with ILAs identified through a lung cancer screening programme. In addition, we compared patient-reported outcome measures (PROMs) in patients with screen-detected ILAs to newly diagnosed interstitial lung disease (ILD) to assess symptoms and health-related quality of life (HRQoL). Methods Individuals with screen-detected ILAs were identified, and 5-year outcomes, including ILD diagnoses, progression-free survival and mortality, were recorded. Risk factors associated with ILD diagnosis were assessed using logistic regression and survival using Cox proportional hazard analysis. PROMs were compared between a subset of patients with ILAs and a group of ILD patients. Results 1384 individuals underwent baseline low-dose computed tomography screening, with 54 (3.9%) identified as having ILAs. 22 (40.7%) were subsequently diagnosed with ILD. 14 (25.9%) individuals died, and 28 (53.8%) suffered disease progression within 5 years. Fibrotic ILA was an independent risk factor for ILD diagnosis, mortality and reduced progression-free survival. Patients with ILAs had lower symptom burden and better HRQoL in comparison to the ILD group. Breathlessness visual analogue scale (VAS) score was associated with mortality on multivariate analysis. Conclusions Fibrotic ILA was a significant risk factor for adverse outcomes including subsequent ILD diagnosis. While screen-detected ILA patients were less symptomatic, breathlessness VAS score was associated with adverse outcomes. These results could inform risk stratification in ILA

The role of measuring exhaled breath biomarkers in sarcoidosis: A systematic review

Introduction: Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is a growing need to identify non-invasive biomarkers to differentiate between clinical phenotypes, identify those at risk of disease progression and monitor response to treatment. Objectives: We undertook a systematic review and meta-analysis, to evaluate the utility of breath-based biomarkers in discriminating sarcoidosis from healthy controls, alongside correlation with existing non-breath based biomarkers used in clinical practice, radiological stage, markers of disease activity and response to treatment. Methods: Electronic searches were undertaken during November 2017 using PubMed, Ebsco, Embase and Web of Science to capture relevant studies evaluating breath-based biomarkers in adult patients with sarcoidosis. Results: 353 papers were screened; 21 met the inclusion criteria and assessed 25 different biomarkers alongside VOCs in exhaled breath gas or condensate. Considerable heterogeneity existed amongst the studies in terms of participant characteristics, sampling and analytical methods. Elevated biomarkers in sarcoidosis included 8-isoprostane, carbon monoxide, neopterin, TGF-β1, TNFα, CysLT and several metallic elements including chromium, silicon and nickel. Three studies exploring VOCs were able to distinguish sarcoidosis from controls. Meta-analysis of four studies assessing alveolar nitric oxide showed no significant difference between sarcoidosis and healthy controls (2.22ppb; 95% CI -0.83, 5.27) however, a high degree of heterogeneity was observed with an I2 of 93.4% (p<0.001). Inconsistent or statistically insignificant results were observed for correlations between several biomarkers and radiological stage, markers of disease activity or treatment. Conclusions: The evidence for using breath biomarkers to diagnose and monitor sarcoidosis remains inconclusive with many studies limited by small sample sizes and lack of standardisation. VOCs have shown promising potential but further research is required to evaluate their prognostic role

Current treatments in the management of idiopathic pulmonary fibrosis:Pirfenidone and nintedanib

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease associated with significant morbidity and mortality. Historically, IPF has been managed using combination immunosuppressive therapy; however, this has been shown to be associated with increased mortality. Over the past 5 years, 2 disease-modifying agents have been licensed for use in IPF. Pirfenidone is a novel therapy with antifibrotic and anti-inflammatory properties. Evidence from a number of randomised control trials has shown that pirfenidone slows the progression of decline in forced vital capacity in IPF. Nintedanib is a tyrosine kinase inhibitor with antifibrotic properties which has also been shown to significantly reduce disease progression. As head-to-head comparison data are lacking, treatment selection is based on patient and clinician preference and tolerability of side effects. In the future, combination therapy with pirfenidone and nintedanib or with additional therapies may further improve lung function preservation

Nintedanib in the management of idiopathic pulmonary fibrosis:clinical trial evidence and real-world experience

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease associated with significant morbidity and mortality. Previously, IPF has been managed using immunosuppressive therapy; however, it has been shown that this is associated with increased mortality. In the last 5 years, two disease-modifying agents have been licensed for use in IPF, namely pirfenidone and nintedanib. Nintedanib is a tyrosine kinase inhibitor with antifibrotic properties that has also been shown to significantly reduce the progression of the disease. The scientific evidence shows that nintedanib is effective and well tolerated for the treatment of IPF in mild, moderate and severe stages of the disease. Real-world experiences also support the findings of previously conducted clinical trials and show that nintedanib is effective for the management of IPF and is associated with reducing disease progression. Gastrointestinal events, mainly diarrhoea, are the main adverse events caused by the treatment. Recent real-word studies also suggest that nintedanib stabilizes lung function till lung transplantation, with no increased surgical complications or postoperative mortality after lung transplantation. In this review, we will discuss the clinical trial evidence and real-world experience for nintedanib in the management of IPF