The use of thoracic ultrasound outside the radiology department and in everyday clinical practice is becoming increasingly common, having been incorporated into standards of care for many specialties. For the majority of practitioners, their experience of, and exposure to, thoracic ultrasound will be in its use as an adjunct to pleural and thoracic interventions, owing to the widely recognised benefits for patient safety and risk reduction. However, as clinicians become increasingly familiar with the capabilities of thoracic ultrasound, new directions for its use are being sought which might enhance practice and patient care. This article reviews the ways in which the advent of thoracic ultrasound is changing the approach to the investigation and treatment of respiratory disease from an interventional perspective. This will include the impact of thoracic ultrasound on areas including patient safety, diagnostic and therapeutic procedures, and outcome prediction; and will also consider potential future research and clinical directions.

Idiopathic pulmonary fibrosis (IPF) is the most severe form of chronic lung fibrosis. Circulating monocytes have been implicated in immune pathology in IPF but their phenotype is unknown. In this work, we determined the immune phenotype of monocytes in IPF using multi-colour flow cytometry, RNA sequencing and corresponding serum factors, and mapped the main findings to amount of lung fibrosis and single cell transcriptomic landscape of myeloid cells in IPF lungs. We show that monocytes from IPF patients displayed increased expression of CD64 (FcγR1) which correlated with amount of lung fibrosis, and an amplified type I IFN response ex vivo. These were accompanied by markedly raised CSF-1 levels, IL-6, and CCL-2 in serum of IPF patients. Interrogation of single cell transcriptomic data from human IPF lungs revealed increased proportion of CD64hi monocytes and “transitional macrophages” with higher expression of CCL-2 and type I IFN genes. Our study shows that monocytes in IPF patients are phenotypically distinct from age-matched controls, with a primed type I IFN pathway that may contribute to driving chronic inflammation and fibrosis. These findings strengthen the potential role of monocytes in the pathogenesis of IPF.

IntroductionThere is currently no readily accessible measure to specifically quantify the amount of fibrosis in idiopathic pulmonary fibrosis (IPF). Such a measure could isolate contribution of fibrosis from other comorbidities to lung function abnormality and deterioration of disease, and potentially help determine if there has been response to antifibrotic treatment.MethodsIn a pilot study of 39 IPF patients, we used a CT-based visual scoring method to examine the correlation between the sum of all fibrotic features (all traction bronchiectasis, ground glass with traction bronchiectasis, honeycombing and reticulation; referred to as Total Fibrosis Score, TFS) or the individual fibrotic features, with lung function, Composite Physiologic Index (CPI) and time to death in the 5 years following CT measurement.ResultsTFS measurements were highly reproducible (r=0.982; p<0.001) and correlated significantly with TLCO, FVC and CPI. Traction bronchiectasis score was superior to others in its correlation to lung function and CPI, and as good as TFS. TFS and traction bronchiectasis score were also the best correlates (individually) to time to death (r=0.60 for both, and p=0.002 and p=0.004, respectively).ConclusionWe suggest that TFS and our 6-slices method of quantifying traction bronchiectasis on CT scans could be readily accessible and simple methods of quantifying lung fibrosis in IPF. These scores could assist in determining if clinical deterioration is due to worsening fibrosis, for correlation of research findings to amount of lung fibrosis, and to stratify patients for established drug treatment and clinical trials. Our findings also provide a basis for larger studies to validate these findings and determine if the scores could measure change in fibrosis.

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IntroductionThe central mechanism in IPF is a dysfunctional alveolar epithelial-fibroblast interaction resulting in an aberrant repair process. This defect is influenced by other immune processes; one of these is the macrophage pathway. Macrophages are heterogeneous immune cells that can control all phases of the repair process. ‘M2’ or ‘reparative’ macrophages have anti inflammatory and reparative phenotype, with high scavenger activities. We investigate how monocytes (precursors of monocyte-derived lung macrophages) might contribute to fibrogenesis in IPF.Methods35 IPF patients (25 sampled while stable and 10 with AE-IPF) diagnosed according to the 2011 ATS/ERS/JRS/ALAT guidelines, with ‘definite’ or ‘probable’ IPF and age and gender-matched healthy controls were recruited over a one-year period. Those with emphysema greater than 25%, current smokers and malignancy were excluded. Lung function and CT fibrosis score1 were performed. Phenotype and function of purified monocytes and monocyte-derived macrophages (MDMs) were determined using qPCR and multi-flow cytometry for selected M1 and M2 genes and proteins (M1 – CD64 M2 – CD163 and CD200R by FACS; and 26 M1 and M2 macrophage markers against three house keeping genes). The ability of MDMs to phagocytose (using pHrodo method) and ROS content (using H2DCFDA assays) ex vivo were also examined.Results and discussionCirculating monocyte levels were significantly higher in IPF compared to healthy controls (p < 0.001) and correlated negatively with lung function (FVC r = −0.6, p = 0.003) and CT fibrosis score (r = 0.45, p = 0.007). IPF monocytes displayed higher M2:M1 ratio profile compared to healthy controls – with higher IL10, CD163, IL1R2, FGL2 and lower TNFa and CXCL10 gene expression. When these monocytes were differentiated to macrophages (MDMs) ex vivo, IPF macrophages showed a significantly higher level of M2 markers and CD14 expression, reduced phagocytosis and produce lower levels of ROS –supporting M2 and pro-repair phenotype.ConclusionsOur data show that circulating monocytes in IPF are elevated compared to age-matched controls, correlate positively with disease severity, and are different from those found in age-matched healthy controls. They have pro-repair, M2-like features and differentiate to pro-repair monocyte-derived macrophages and may contribute to the aberrant repair process in IPF.ReferenceBest AC, et al. Idiopathic pulmonary fibrosis: physiologic tests, quantitative CT indexes, and CT visual scores as predictors of mortality. Radiology 2008; 246:935–40.