Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the lung parenchyma, causing significant morbidity and mortality [1, 2]. The therapeutic options in IPF are limited to only two recently approved drugs, pirfenidone and nintedanib, which have been shown to slow progression but are not able to stop or reverse the disease [3, 4]. Better pathophysiological knowledge is needed to develop new therapeutic strategies in IPF. The current understanding of the disease is that fibroblastic foci, characterised by accumulation of myofibroblasts and overlying "activated" epithelium, represent "hot zones" of the disease and drivers of abnormal extracellular matrix (ECM) accumulation [5]. Transforming growth factor (TGF)-β1 is a key cytokine involved in the process of fibrogenesis. TGF-β1 causes myofibroblast proliferation and differentiation and increases the synthesis of collagen, fibronectin and many other ECM components [5]. The TGF-β1 signalling pathways are complex and occur essentially through serine/threonine kinase receptors, TGF-β receptors type I and II (TGF-βRI and TGF-βRII). TGF-βRII is constitutively active and activates TGF-βRI via phosphorylation upon ligand binding [6]. The cytoplasmic proteins Smad2 and Smad3 predominantly mediate signals from activated TGF-β1 receptors. Activation of Smad2 and Smad3 via phosphorylation makes them bind to Smad4, promoting translocation to the nucleus where numerous TGF-β1-responsive genes are activated. TGF-β1 pathways are undoubtedly very promising but also challenging targets to treat fibrosis and in particular IPF.

There is accumulating evidence in support of the significant improvement in survival rates and clinical outcomes when pulmonary arterial hypertension (PAH) is diagnosed at early stages. Nevertheless, it remains a major clinical challenge and the outcomes are dependent on invasive right heart catheterisation.

Resulting from pathophysiological processes and detectable in exhaled breath, volatile organic compounds (VOCs) have been proposed as noninvasive biomarkers for PAH. Studies have confirmed significant alterations of the exhaled VOCs among PAH patients when compared to controls and/or patients with other respiratory diseases. This suggests exhaled breath analysis as a potential noninvasive medical application in the field of PAH.

In this article, we review and discuss the progress made so far in the field of exhaled volatolomics (the omics of VOCs) as a potential noninvasive diagnostics of PAH. In addition, we propose a model including possible biochemical pathways on the level of the remodelled artery, in which specific VOCs could be detectable in exhaled breath during the early phases of PAH. We debate the different analytical approaches used and recommend a diagram including a "bottom–top" strategy, from basic to translational studies, required for promoting the field.

Hypertonic saline inhalation lowers airway mucous viscosity. Increased cough transportability may improve quality of life (QoL) in primary ciliary dyskinesia (PCD).

In this randomised controlled trial (RCT), PCD patients received twice-daily inhalations of hypertonic (7%) saline or isotonic (0.9%) saline for 12 weeks, with 4 weeks washout during crossover. Primary outcome was change in QoL measured by the St George's Respiratory Questionnaire (SGRQ) total score. Secondary outcomes were SGRQ subscores, Quality of Life Questionnaire-Bronchiectasis (QoL-B) scores, lower respiratory tract infection symptoms, exacerbations, spirometry, systemic and sputum inflammatory markers, adherence, and adverse events.

There was no significant change in median (interquartile range) SGRQ total score between hypertonic saline (–2.6 (–9.0–1.5)) and isotonic saline (–0.3 (–8.1–6.1)) in 22 patients (age range 22–73 years) (p=0.38). QoL-B Health Perception scale improved with hypertonic saline (p=0.03). Adverse events occurred more frequently with hypertonic saline, but were mild.

12 weeks of inhaled hypertonic saline did not improve SGRQ total score in adult PCD patients in this RCT, but the sample size was small. On the secondary and more disease-specific end-point of the QoL-B, a significant improvement was observed in the Health Perception scale. This study found little evidence to support the hypothesis that hypertonic saline improves QoL in PCD patients. We advise the use of disease-specific outcome measures in future trials.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension, classified as group 4 in the present clinical classification [1, 2]. CTEPH is generally considered a late complication of one or multiple episodes of acute pulmonary embolism that have not resolved despite at least 3 months of therapeutic anticoagulation. Haemodynamically, CTEPH is characterised by a mean pulmonary arterial pressure of at least 25 mmHg at rest, measured during right heart catheterisation.