clinicaltrials.gov Identifier: NCT00729794.

clinicaltrials.gov Identifier: NCT00411879.

It is known that non-cachectic patients with chronic obstructive pulmonary disease (COPD) respond well to pulmonary rehabilitation, but whether cachectic COPD patients are capable of adaptive responses is both important and unknown.10 cachectic and 19 non-cachectic COPD patients undertook high-intensity cycling training, at the same relative intensity, for 45 min?day -1 , 3 days?week -1 for 10 weeks. Before and after rehabilitation vastus lateralis muscle biopsies were analysed morphologically and for the expression of muscle remodelling factors (insulin-like growth factor (IGF)-I, myogenic differentiation factor D (MyoD), tumour necrosis factor (TNF)-a, nuclear factor (NF)-kB and myostatin) and key components of ubiquitin-mediated proteolytic systems (muscle ring finger protein (MURF)-1 and Atrogin-1).Rehabilitation improved peak work-rate and the 6-min walk distance similarly in non-cachectic (18¡3% and 42¡13 m, respectively) and cachectic (16¡2% and 53¡16 m, respectively) patients, but quality of life only improved in non-cachectic COPD. Mean muscle fibre cross-sectional area increased in both groups, but significantly less in cachectic (7¡2%) than in non-cachectic (11¡2%) patients. Both groups equally decreased the proportion of type IIb fibres and increased muscle capillary/fibre ratio. IGF-I mRNA expression increased in both groups, but IGF-I protein levels increased more in non-cachectic COPD. MyoD was upregulated, whereas myostatin was downregulated at the mRNA and protein level only in non-cachectic patients. Whilst rehabilitation had no effect on TNF-a expression, it decreased the activation of the transcription factor NF-kB in both groups by the same amount. Atrogin-1 and MURF-1 expression were increased in cachectic COPD, but it was decreased in non-cachectic patients.Cachectic COPD patients partially retain the capacity for peripheral muscle remodelling in response to rehabilitation and are able to increase exercise capacity as much as those without cachexia, even if they exhibit both quantitative and qualitative differences in the type of muscle fibre remodelling in response to exercise training.

No abstract

We have previously shown (Am. J. Respir. Crit. Care Med. 1995;152:1248-1255) that in patients needing mechanical ventilation, the load imposed on the inspiratory muscles is excessive relative to their neuromuscular capacity. We have therefore hypothesized that weaning failure may occur because at the time of the trial of spontaneous breathing there is insufficient reduction of the inspiratory load. We therefore prospectively studied patients who initially had failed to wean from mechanical ventilation (F) but had successful weaning (S) on a later occasion. Compared with S, during F patients had greater intrinsic positive end-expiratory pressure (6. 10 +/- 2.45 versus 3.83 +/- 2.69 cm H2O), dynamic hyperinflation (327 +/- 180 versus 213 +/- 175 ml), total resistance (Rmax, 14.14 +/- 4.95 versus 11.19 +/- 4.01 cm H2O/L/s), ratio of mean to maximum inspiratory pressure (0.46 +/- 0.1 versus 0.31 +/- 0.08), tension time index (TTI, 0.162 +/- 0.032 versus 0.102 +/- 0.023) and power (315 +/- 153 versus 215 +/- 75 cm H2O x L/min), less maximum inspiratory pressure (42.3 +/- 12.7 versus 53.8 +/- 15.1 cm H2O), and a breathing pattern that was more rapid and shallow (ratio of frequency to tidal volume, f/VT 98 +/- 38 versus 62 +/- 21 breaths/min/L). To clarify on pathophysiologic grounds what determines inability to wean from mechanical ventilation, we performed multiple logistic regression analysis with the weaning outcome as the dependent variable. The TTI and the f/VT ratio were the only significant variables in the model. We conclude that the TTI and the f/VT are the major pathophysiologic determinants underlying the transition from weaning failure to weaning success.

First, patients' serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis.

Coagulation system and platelets are strongly activated in sepsis. In this stage, only factor XII is decreased. In contrast, in severe sepsis and mainly in septic shock, most of the coagulation factors are depleted, PTL is decreased, and global coagulation tests are prolonged, indicating exhaustion of hemostasis. Finally, Gram-positive, Gram-negative, and other microorganisms produce identical impairment of coagulation.

Electronic cigarettes (e-cig) are advertised as a less harmful nicotine delivery system or as a new smoking cessation tool. We aimed to assess the in vivo effects of e-cigarette vapor in the lung and to compare them to those of cigarette smoke (CS). We exposed C57BL/6 mice for either 3 days or 4 weeks to ambient air, CS or e-cig vapor containing: i) propylene glycol/vegetable glycerol (1:1; PG:VG-Sol), ii) PG:VG with nicotine (G:VG-N), or iii) PG:VG with nicotine and flavor (PG:VG- N+F) and determined oxidative stress, inflammation and pulmonary mechanics. E-cig vapors, especially PG:VG- N+F, increased bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers at least comparably and in many cases more than CS. BALF protein content at both time points studied was only elevated in the PG:VG- N+F group. After 3 days, PG:VG-Sol altered tissue elasticity, static compliance and airway resistance, while after 4 weeks, CS was the only treatment adversely affecting these parameters. Airway hyperresponsiveness in response to methacholine was increased similarly in the CS and PGVG-N+F groups. Our findings suggest that exposure to e-cig vapor can trigger inflammatory responses and adversely affect respiratory system mechanics. In many cases, the added flavor in e-cigs exacerbated the detrimental effects of e-cig vapor. We conclude that both e-cig vaping and conventional cigarette smoking negatively impact lung biology.