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Revathy Munuswamy,1,* Jana De Brandt,2,* Chris Burtin,2 Wim Derave,3 Joseph Aumann,4 Martijn A Spruit,5,6,* Luc Michiels1,* 1Faculty of Medicine and Life Sciences, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 2Faculty of Rehabilitation Sciences, Rehabilitation Research Center REVAL, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 3Department of Movement and Sports Sciences, Ghent University, Ghent, Belgium; 4Department of Pneumology, Jessa Hospital, Hasselt, Belgium; 5Department of Research and Development, CIRO, Horn, the Netherlands; 6Department of Respiratory Medicine, Maastricht University Medical Centre, Faculty of Health, Medicine and Life Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands*These authors contributed equally to this workCorrespondence: Luc Michiels Email luc.michiels@uhasselt.beAbstract: Chronic low-grade systemic inflammation is frequently observed in patients with chronic obstructive pulmonary disease (COPD), e.g., elevated pentameric CRP (pCRP). However, pCRP can dissociate to form monomeric CRP (mCRP) which exhibits a clear pro-inflammatory behaviour in contrast to the more anti-inflammatory properties of pCRP. Therefore, mCRP may be an informative biomarker to demonstrate chronic low-grade systemic inflammation. This was confirmed by analysing serum samples from 38 patients with COPD and 18 non-COPD control persons (NCCP). mCRP was significantly elevated in patients with COPD vs. NCCP, indicating that mCRP might be considered as a new sensitive marker of chronic low-grade systemic inflammation.Keywords: COPD, low-grade systemic inflammation, pCRP, mCRP

Carlos A Camillo,1,2 Daniel Langer,1,2 Christian R Osadnik,1,3–5 Lisa Pancini,2 Heleen Demeyer,1,2 Chris Burtin,1,6 Rik Gosselink,1,2 Marc Decramer,2 Wim Janssens,2 Thierry Troosters1,2 1KU Leuven, Department of Rehabilitation Sciences, Leuven, Belgium; 2University Hospital Leuven, Respiratory Division and Rehabilitation, Leuven, Belgium; 3Monash University, Department of Physiotherapy, Melbourne, VIC, Australia; 4Institute for Breathing and Sleep, Melbourne, VIC, Australia; 5Monash Health, Monash Lung and Sleep, Melbourne, VIC, Australia; 6Hasselt University, Rehabilitation Research Centre, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium Abstract: The impact of rehabilitation-induced changes in 6-minute walk distance (6MWD) on the survival of patients with chronic obstructive pulmonary disease (COPD) has not been fully elucidated. This study sought to determine the association of baseline 6MWD and its changes after pulmonary rehabilitation (PR) with 5-year survival in patients with COPD. Patients who were referred to a 12-week outpatient PR program were followed up for 5 years postcompletion, and survival status was verified. Survival was analyzed according to four groups based upon initial 6MWD (6MWDi) and its changes (Δ6MWD) after PR (Group 1: 6MWDi ≥350 m and Δ6MWD ≥30 m; Group 2: 6MWDi ≥350 m and Δ6MWD 30 m after PR are associated with worse 5-year survival in patients with COPD. Keywords: pulmonary disease, chronic obstructive, exercise training, mortality, 6-minute walk test, minimally important difference

The acoustic birefringence method has been used since a long time for metallic materials to detect residual stresses. This method is rarely used for polymers and composites due to the strong attenuation of the acoustic signal. Moreover, for thermoplastic polymer, with a slight anisotropy (known as texture for metals), coupling with applied stresses, extends the complexity of the residual stresses determination. The slight anisotropy of thermoplastic polymer should be studied with shear waves prior to the residual stress determination. If the material is perfectly isotropic, we are able to detect and quantify the residual stresses. If the material is slightly anisotropic, it is also possible to evaluate residual stresses by taking into account the directions of the principal axes of material anisotropy., INTRODUCTION Residual stresses have been discussed for a long time since they are critical for the mechanical behavior of polymers and composites and can cause warpage, delamination, and so on [...]

Oxidative/carbonyl stress is elevated in lower-limb muscles of patients with chronic obstructive pulmonary disease (COPD). Carnosine is a skeletal muscle antioxidant particularly present in fast-twitch fibers. The aims of the present study were to compare muscle carnosine, oxidative/carbonyl stress, antioxidants, and fiber characteristics between patients with COPD and healthy controls (HCs) and between patients after stratification for airflow limitation (mild/moderate vs. severe/very severe), as well as to investigate correlates of carnosine in patients with COPD. A vastus lateralis muscle biopsy was obtained from 40 patients with stable COPD and 20 age- and sex-matched HCs. Carnosine, oxidative/carbonyl stress, antioxidants, fiber characteristics, quadriceps strength and endurance (QE), VO2peak (incremental cycle test), and physical activity (PA) were determined. Patients with COPD had a similar carnosine concentration [4.16mmol/kg wet weight (WW; SD = 1.93)] to HCs [4.64mmol/kg WW (SD = 1.71)] and significantly higher percentage of fast-twitch fibers and lower QE, V_O2peak, and PA versus HCs. Patients with severe/very severe COPD had a 31% lower carnosine concentration [3.24mmol/kg WW (SD = 1.79); n = 15] versus patients with mild/moderate COPD [4.71mmol/kg WW (SD = 1.83); n = 25; P = 0.02] and significantly lower VO2peak and PA versus patients with mild/moderate COPD. Carnosine correlated significantly with QE (rs = 0.427), VO2peak (rs = 0.334), PA (rs = 0.379), and lung function parameters in patients with COPD. In conclusion, despite having the highest proportion of fast-twitch fibers, patients with severe/very severe COPD displayed a 31% lower muscle carnosine concentration compared with patients with mild/moderate COPD. As no other markers of oxidative/carbonyl stress or antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities. [ABSTRACT FROM AUTHOR]

To determine the association between quadriceps muscle strength (QMS) and endurance (QME) and exercise capacity in patients with COPD after stratification for sex and resting lung function (LF). Data were collected from 3,246 patients with COPD (60% men, 64 ± 9 yr), including measures of exercise capacity [peak aerobic capacity (peakV̇o2), 6-min walk distance (6MWD)] and isokinetic QMS and QME. Patients were stratified for sex, forced expiratory volume in 1 s (>50/≤50% predicted), single breath carbon monoxide diffusing capacity (>50/≤50% predicted), and residual volume (>140/≤140% predicted). After stratification for resting LF, QMS and QME were significantly associated with peakV̇o2 (r range: 0.47-0.61 and 0.49-0.65 for men and 0.53-0.66 and 0.48-0.67 for women, respectively) and 6MWD (r range: 0.29-0.42 and 0.44-0.55 for men and 0.25-0.54 and 0.34-0.55 for women, respectively) (P < 0.001). Regression models demonstrated that QMS and QME were significant determinants of peakV̇o2 (explained variance R2 range: 35.6%-48.8% for men and 36.8%-49.0% for women) and 6MWD (R2 range: 24.3%-43.3% for men and 28.4%-40.3% for women), independent of age and fat-free mass. Quadriceps muscle function was significantly associated with peakV̇o2 and 6MWD in male and female patients with COPD after stratification for resting LF, in which QME appear to be a more important determinant than QMS. This underlines the importance of systematically evaluating both quadriceps muscle strength and endurance in in all patients with COPD. [ABSTRACT FROM AUTHOR]

The aim of this article is to examine in vitro the immune response to penicillin of non allergic controls. In addition to lymphocyte transformation test (LTT), three other tests were used: passive hemagglutination which detects anti-pencilloyl IgG or 1gM; passive anaphylaxis on monkey lung tissue for detection of serum anti-penicillin IgE; and leucocyte migration test. With daily evaluation it was seen that all the patients tolerated well the course of penicillin. The positive LTT prior to treatment was also found to be negative, as was LTT, with the treatment.

To examine the possibility that mast cells have a central role in the pathogenesis of hypersensitivity pneumonitis, 20 patients with this disease were studied with the aim of seeking evidence for mast cell degranulation. The number of mast cells recovered by bronchoalveolar lavage from patients with hypersensitivity pneumonitis was more than 1,000 times greater than those recovered from normal individuals. Furthermore, discontinuation of antigen exposure resulted in an increase in the number of mast cells observed, consistent with the possibility that antigen exposure had induced mast cell degranulation. Cessation of antigen exposure also resulted in a rapid decrease in the number of neutrophils and eosinophils recovered by lavage, followed by an increase in the number of T8+ T lymphocytes present. In each case the time course of the changes was consistent with the possibility that mast cell degranulation had been important in regulating the number of the immune and inflammatory cells present in the lung. Histamine was present in lavage fluid supernatant from patients with hypersensitivity pneumonitis. The amount of histamine present was, however, closely correlated with the number of mast cells present and not with the interval since last antigen exposure. Delay in separating cells from lavage fluid supernatant resulted in an increase in histamine content. These results suggest that the free histamine in lavage fluid resulted from the degranulation of mast cells induced by the lavage procedure as histamine released in vivo has a short half life. We suggest that hypersensitivity pneumonitis results from a "late phase reaction" initiated by antigen induced mast cell degranulation. [ABSTRACT FROM AUTHOR]

The release of mediators from human basophils is strongly enhanced by IL-3. However, the signalling pathways of IL-3 arc poorly defined in these cells. Since external Ca2+ and Na+ play important regulating roles in histamine release, the possibility that these cations could be involved in the potentiation by IL-3 of the anti-IgE-induced hisiamine release from human basophils was considered, and it was observed that: (i) IL-3 dramatically decreased the external Ca2+ requirement for IgE-mediated histamine release. However, histamine release from IL-3-treated basophils became only partially independent of external Ca2+, since addition of EGTA in the external medium abolished the effect of IL-3; (ii) decreasing Na+ influx by lowering external Na+ concentration in isosmotic medium inhibited the potentiating effect of IL-3 on IgE-mediated release; (iii) amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchanges, and its derivative, benzamil, more specific for Na+/ Ca2+ exchanges, inhibited the release potentiated by IL-3. In contrast, the amiloride derivative 5-(N, N-dimethyl)-amiloride, more specific for Na+/H+ exchanges, slightly increased the IL-3-enhanced release. Thus, the decreased requirement for external Ca2+ and the dependence on external Na+. taken with the effect of the Na+/Ca2+ exchange inhibitors, suggest that Na+/Ca2+ exchanges are involved in the IL-3-induced enhancement of IgE-mediated human basophil histamine release. [ABSTRACT FROM AUTHOR]