The exercise definition of pulmonary hypertension was eliminated from the pulmonary hypertension guidelines in part due to uncertainty of the upper limits of normal (ULNs) for exercise haemodynamics in subjects >50 years old.The present study, therefore, evaluated the pulmonary haemodynamic responses to maximum upright incremental cycling exercise in consecutive subjects who underwent an invasive cardiopulmonary exercise testing for unexplained exertional intolerance, deemed normal based on preserved exercise capacity and normal resting supine haemodynamics. Subjects aged >50 years old (n=41) were compared with subjects ≤50 years old (n=25). ULNs were calculated as mean+2sd.Peak exercise mean pulmonary arterial pressure was not different for subjects >50 and ≤50 years old (23±5versus22±4 mmHg, p=0.22), with ULN of 33 and 30 mmHg, respectively. Peak cardiac output was lower in older subjects (median (interquartile range): 12.1 (9.4–14.2)versus16.2 (13.8–19.2) L·min⁻¹, p<0.001). Peak pulmonary vascular resistance was higher in older subjects compared with younger subjects (mean±sd: 1.20±0.45versus0.82±0.26 Wood units, p50 and ≤50 years old have different pulmonary vascular responses to exercise. Older subjects have higher pulmonary vascular resistance at peak exercise, resulting in different exercise haemodynamics ULNs compared with the younger population.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three‐dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small‐vessel volume: 2.7 [interquartile range (IQR): 2.5–3.0] vs. 3.2 [3.0–3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30–0.41] vs. 0.23 [0.21–0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%–5.21%] vs. 4.63% [4.39%–4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

Staphylococcal superantigens cause toxic shock syndrome, which is characterized by massive T cell activation and a predominant Th1 profile of cytokine production. However, superantigen-producing Staphylococcus aureus strains are often part of the human nasal microbiome, and this carrier state has often been associated with some type 2 immune responses such as chronic sinusitis with polyps and atopic dermatitis. We have previously reported that the S. aureus cell wall downregulates the human T cell response to superantigens through a TLR2-dependent, IL-10–mediated mechanism. In this study, we show that S. aureus also regulates the profile of superantigen-induced T cell recruitment. The staphylococcal superantigen SEE induced the production of Th1 cell–recruiting chemokines, including IP-10, through an IFN-γ–dependent mechanism. Such an induction was suppressed by the concomitant presence of S. aureus. The downregulation of IP-10 by S. aureus was mediated by components of its cell wall, but was not due to peptidoglycan-induced IL-10 production. Instead, S. aureus triggered activation of MAPKs p38 and ERK, as well as inhibition of STAT1 signaling in monocytes, altogether contributing to the downregulation of IP-10 and other Th1 cell–recruiting chemokines (e.g., CXCL9 and CXCL11). These effects translated into inhibition of superantigen-induced Th1 cell recruitment. Taken together, our data may explain why colonization of superantigen-producing S. aureus can induce, under some circumstances, mucosal type 2 immune responses.