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Use of non-invasive haemodynamic measurements to detect treatment response in precapillary pulmonary hypertension

Background

Haemodynamic measurements may be superior to the 6-min walk distance (6MWD) as outcome measures in pulmonary hypertension (PH) as they are directly linked to the mechanisms of disease and are not subject to a ceiling effect. The aim of this study was to determine if treatment response in precapillary PH could be detected by pulmonary blood flow (PBF) and stroke volume (SV) measured non-invasively by the inert gas rebreathing (IGR) method at rest and during submaximal constant-load cycle exercise.

Methods

Twenty-four patients with precapillary PH receiving de novo or modified disease-targeted therapy were studied. Isotime metabolic variables, PBF and SV were measured at rest and during constant-load cycle exercise at 40% maximal work rate alongside conventional outcome variables, at baseline and after 3 months of new therapy.

Results

At follow-up there was a significant increase in PBF (supine rest: mean 0.7±SD 0.9 l/min, erect rest: 0.7±0.8 l/min, exercise: 0.8±1.0 l/min, p<0.005) and SV (supine rest: 7±10 ml, erect rest: 10±11 ml, exercise: median 6 (IQR 3–11) ml, p<0.005). There was a trend for 6MWD to increase by 17±42 or 29 (13–47) m (p=0.061), whereas WHO functional class, N-terminal pro-brain natriuretic peptide or Cambridge Pulmonary Hypertension Outcome Review score were unchanged. In patients with higher baseline 6MWD, IGR measurements were more sensitive than 6MWD in detecting treatment response.

Conclusions

Non-invasive IGR haemodynamic measurements could be used to detect treatment response in patients with precapillary PH and may be more responsive to change than 6MWD in fitter patients.

Non-invasive phenotyping using exhaled volatile organic compounds in asthma

Background

Breath volatile organic compounds (VOCs) may be useful for asthma diagnosis and phenotyping, identifying patients who could benefit from personalised therapeutic strategies. The authors aimed to identify specific patterns of breath VOCs in patients with asthma and in clinically relevant disease phenotypes.

Methods

Breath samples were analysed by gas chromatography–mass spectrometry. The Asthma Control Questionnaire was completed, together with lung function and induced sputum cell counts. Breath data were reduced to principal components, and these principal components were used in multiple logistic regression to identify discriminatory models for diagnosis, sputum inflammatory cell profile and asthma control.

Results

The authors recruited 35 patients with asthma and 23 matched controls. A model derived from 15 VOCs classified patients with asthma with an accuracy of 86%, and positive and negative predictive values of 0.85 and 0.89, respectively. Models also classified patients with asthma based on the following phenotypes: sputum (obtained in 18 patients with asthma) eosinophilia ≥2% area under the receiver operating characteristics (AUROC) curve 0.98, neutrophilia ≥40% AUROC 0.90 and uncontrolled asthma (Asthma Control Questionnaire ≥1) AUROC 0.96.

Conclusions

Detection of characteristic breath VOC profiles could classify patients with asthma versus controls, and clinically relevant disease phenotypes based on sputum inflammatory profile and asthma control. Prospective validation of these models may lead to clinical application of non-invasive breath profiling in asthma.

Radiological evaluation of interstitial lung disease

Purpose of review: Chest radiograph, computed tomography and high-resolution computed tomography (HRCT) are an integral part in the diagnosis and evaluation of diffuse interstitial lung disease (DILD) and are reviewed briefly. This review then delves into the burgeoning interest associated with enhanced imaging and computational capabilities of multidetector HRCT in the automated evaluation of computer-aided recognition of different patterns associated with DILD, automated regional and global distribution and quantitation of DILD, and automated longitudinal comparison of HRCT scans to estimate progression of DILD. Recent findings: Problems associated with automatic segmentation of lung in DILD because of high-attenuation lesions in subpleural locations have been overcome to a large extent. Use of two-dimensional HRCT has made it possible to automate identification and quantification of patterns associated with DILD with an overall accuracy of 89%. Significant progress has been made with automated image registration and noise reduction, which are essential for sequential comparison of HRCT in DILD. Early experience with automated determination of progression or regression of DILD on two-dimensional HRCT, using the dissimilarity-based feature strategy, compared favorably with radiologist assessment and approached a concordance rate of 80%. Summary: The combination of multidetector HRCT, the support vector machine classifier and various computational algorithms have made it possible to fully automate isolation of lungs in DILD, recognize radiographic patterns associated with DILD and sequentially estimate progression of DILD. It is hoped there will be further improvement when these are extended to three-dimensional HRCT.

Stem cell therapy in pulmonary fibrosis

Purpose of review: In the last years, we have witnessed an explosion in preclinical data relating to the isolation, differentiation and application of mesenchymal stem cells (MSCs) as a treatment option in animal models of lung fibrosis and inflammation. The scope of this review is to summarize current knowledge regarding the roles of MSCs in lung tissue repair and regeneration and to highlight future therapeutic perspectives and clinical applications in safety and efficacy trials. Recent findings: Although there have been interesting studies of cell therapy for diseases of many systems, there has been a paucity of preclinical and clinical studies regarding pulmonary fibrosis. Today, we have made progress with respect to the understanding of the mechanisms of action and application of MSCs in animal models of lung fibrosis as regulators of tissue remodeling and immune response. There are only a few ongoing clinical trials involving MSCs in chronic lung diseases and extrapolation of these data to underline future therapeutic applications in patients with idiopathic pulmonary fibrosis. Summary: Adult MSCs may prove to be a valuable therapeutic option in lung tissue rescue and repair based on their ready availability, immunomodulatory effects and capacity for cell differentiation.

Newer modes of treating interstitial lung disease

Purpose of review: This review critically discusses recent advances in the treatment of idiopathic pulmonary fibrosis (IPF). Moreover, it also focuses on the practical approach of a patient diagnosed with IPF and uncovers challenges for the future. Recent findings: Treatment can be divided into three major parts. Firstly, many new agents have been tested, but only the combination of N-acetylcysteine with corticosteroids, azathioprine and pirfenidone was able to show some significant effects. In the mean time, many second-generation agents are under development. Lung transplantation has made some major progress by introducing an appropriate allocation system. Finally, as part of best supportive care, several studies show that pulmonary rehabilitation might induce some important effects on quality of life. Summary: So, it is clear that major progress has been made in the treatment of IPF, but we are convinced that an orchestrated effort will lead to a better understanding and treatment of this devastating condition.

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