Correlation between lung function tests and peak oxygen consumption in post-TB lung disease.

BACKGROUND: After TB treatment, many patients have post-TB lung disease (PTLD), associated with increased mortality and morbidity. Nevertheless, relationships between lung function testing and exercise capacity in people with PTLD are poorly understood.METHODS: This single-centre study investigated the association between lung function testing and peak oxygen consumption (VO2peak) and percentage-predicted VO2peak (VO2peak (%pred)) in adults with PTLD investigated for surgery.RESULTS: Eighty-two patients (52 males, 30 females) with a mean age of 43.2 years (SD 11.3) were included. Spirometric values of forced vital capacity (FVC) percentage predicted (%pred) and forced expiratory volume in 1 sec (FEV1) %pred suggested significant correlations with VO2peak (%pred) (P < 0.001 and P < 0.001), whereas FEV1/FVC did not. Diffusing capacity for carbon monoxide (DLCO) %pred also correlated significantly with VO2peak (%pred) (P = 0.002). However, the magnitude of all significant correlation coefficients were weak. No significant correlations for any plethysmographic values with VO2peak (%pred) could be robustly concluded. Correlations with VO2peak (ml/kg/min) for most physiological variables were less robust than for VO2peak (%pred).CONCLUSIONS: Although statistically significant, the correlations between any measure of lung function and VO2peak or VO2peak (%pred) were weak, with only FVC correlation coefficient surpassing 0.50.

A fast full-wave solver for calculating ultrasound propagation in the body.

Therapeutic ultrasound is a promising non-invasive method for inducing various beneficial biological effects in the human body. In cancer treatment applications, high-power ultrasound is focused at a target tissue volume to ablate the malignant tumour. The success of the procedure depends on the ability to accurately focus ultrasound and destroy the target tissue volume through coagulative necrosis whilst preserving the surrounding healthy tissue. Patient-specific treatment planning strategies are therefore being developed to increase the efficacy of such therapies, while reducing any damage to healthy tissue. These strategies require to use high-performance computing methods to solve ultrasound wave propagation in the body quickly and accurately. For realistic clinical scenarios, all numerical methods which employ volumetric meshes require several hours or days to solve the full-wave propagation on a computer cluster. The boundary element method (BEM) is an efficient approach for modelling the wave field because only the boundaries of the hard and soft tissue regions require discretisation. This paper presents a multiple-domain BEM formulation with a novel preconditioner for solving the Helmholtz transmission problem (HTP). This new formulation is efficient at high-frequencies and where high-contrast materials are present. Numerical experiments are performed to solve the HTP in multiple domains comprising: (i) human ribs, an idealised abdominal fat layer and liver tissue, (ii) a human kidney with a perinephric fat layer, exposed to the acoustic field generated by a high-intensity focused ultrasound (HIFU) array transducer. The time required to solve the equations associated with these problems on a single workstation is of the order of minutes. These results demonstrate the great potential of this new BEM formulation for accurately and quickly solving ultrasound wave propagation problems in large anatomical domains which is essential for developing treatment planning strategies.

Regulation of YKL-40 expression by corticosteroids: effect on pro-inflammatory macrophages in vitro and its modulation in COPD in vivo.

BACKGROUND: Macrophages constitute a heterogeneous cell population with pro- (MΦ1) and anti-inflammatory (MΦ2) cells. The soluble chitinase-like-protein YKL-40 is expressed in macrophages and various other cell types, and has been linked to a variety of inflammatory diseases, including COPD. Dexamethasone strongly reduces YKL-40 expression in peripheral blood mononuclear cells (PBMC) in vitro. We hypothesized that: a) YKL-40 is differentially expressed by MΦ1 and MΦ2, b) is decreased by corticosteroids and c) that long-term treatment with inhaled corticosteroids (ICS) affects YKL-40 levels in serum and sputum of COPD patients. METHODS: Monocytes of healthy subjects were cultured in vitro for 7 days with either GM-CSF or M-CSF (for MΦ1 and MΦ2, respectively) and stimulated for 24 h with LPS, TNFα, or oncostatin M (OSM). MΦ1 and MΦ2 differentiation was assessed by measuring secretion of IL-12p40 and IL-10, respectively. YKL-40 expression in macrophages was measured by quantitative RT-PCR (qPCR) and ELISA; serum and sputum YKL-40 levels were analyzed by ELISA. RESULTS: Pro-inflammatory MΦ1 cells secreted significantly more YKL-40 than MΦ2, which was independent of stimulation with LPS, TNFα or OSM (p < 0.001) and confirmed by qPCR. Dexamethasone dose-dependently and significantly inhibited YKL-40 protein and mRNA levels in MΦ1. Serum YKL-40 levels of COPD patients were significantly higher than sputum YKL-40 levels but were not significantly changed by ICS treatment. CONCLUSIONS: YKL-40 secretion from MΦ1 cells is higher than from MΦ2 cells and is unaffected by further stimulation with pro-inflammatory agents. Furthermore, YKL-40 release from cultured monocyte-derived macrophages is inhibited by dexamethasone especially in MΦ1, but ICS treatment did not change YKL-40 serum and sputum levels in COPD. These results indicate that YKL-40 expression could be used as a marker for MΦ1 macrophages in vitro, but not for monitoring the effect of ICS in COPD. TRIAL REGISTRATION: ClinicalTrials.gov, registration number: NCT00158847.

The global peripheral chemoreflex drive in patients with systemic sclerosis: a rebreathing and exercise study.

BACKGROUND: Exercise intolerance (EI) in systemic sclerosis (SSc) is difficult to manage by the clinician. The peripheral chemoreflex drive compensates for metabolic acidosis during exercise and may be related to EI. AIM: To assess the global peripheral chemoreflex drive (GPCD) in patients with SSc at rest and during exercise. METHODS: Consecutively tested SSc patients (n = 49) were evaluated by pulmonary function tests, carbon dioxide (CO2) rebreathing studies and non-invasive cardiopulmonary exercise testing (CPET). Results of their CO2 rebreathing tests were compared with those of controls (n = 32). Respiratory compensation for metabolic acidosis during CPET was defined by the occurrence of a sharp increase in minute ventilation (VdotE) and the ventilatory equivalent for CO2 (V'E and V'CO2) at the end of the isocapnic buffer phase. Euoxic (eVHR) and hyperoxic (hVHR) ventilatory responses to hypercapnia were measured and its difference (eVHR - hVHR) was considered to reflect the GPCD. RESULTS: In 45 patients with SSc, CPET results showed respiratory compensation at the occurrence of metabolic acidosis. eVHR - hVHR in patients with diffuse cutaneous SSc (dcSSc) differed significantly from that in patients with limited cutaneous SSc (lcSSc) and from that in controls (0.47 ± 0.38 (dcSSc) vs. 0.90 ± 0.77 (lcSSc) and 0.90 ± 0.49 (controls) l/min/mmHg; P = 0.04 and P = 0.03, respectively). CONCLUSIONS: Respiratory compensation for metabolic acidosis occurred in all patients. However, the GPCD was diminished in dcSSc patients, suggesting an altered control of breathing. Its assessment may help the clinician to better understand reported EI and exertional dyspnea in dcSSc patients.