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Physiological changes during low and high "intensity " noninvasive ventilation.

In a physiological randomized cross-over study, performed in stable hypercapnic COPD patients,

we have assessed the short term effects of two settings of non-invasive ventilation, one aimed at maximally reducing Pa,CO2 level (Hi-NPPV:27.6±2.1 cmH2O of IPAP, 4±0 cmH2O of EPAP and respiratory rate of 22·min(-1)) and one according to the usual parameters used in earlier studies (Li-NPPV:17.7±1.6 cmH2O of IPAP, 4±0 cmH2O of EPAP and respiratory rate of 12·min(-1)).

Both modes of ventilation significantly improved gas exchange compared to spontaneous breathing (SB), but to a greater extent using Hi-NPPV (PCO2:59.3±7.5, 55.2±6.9 and 49.4±7.8 mmHg, for SB, Li-NPPV and Hi-NPPV respectively). Similarly Hi-NPPV induced a greater reduction in the Pressure Time Product of the diaphragm per minute from 323±149 cmH2O*sec·min(-1) during SB to 132±139 cmH2O*sec·min(-1) during Li-NPPV and 40±69 cmH2O*sec·min(-1) during Hi-NPPV, while in 9/15 patients completely abolished spontaneous breathing activity. Hi-NPPV also induced a marked reduction in cardiac output measured noninvasively with a Finometer, compared to Li-NPPV.

We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas exchange and in reducing inspiratory effort, it induces a marked reduction in cardiac output, which needs to be considered when Hi-NPPV is applied to patients with pre-existing cardiac disease.

Clinical presentation and outcome of venous thromboembolism in chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is a moderate risk factor for venous thromboembolism (VTE), but neither the clinical presentation nor the outcome of VTE in COPD patients is well known.

The clinical presentation of VTE, namely pulmonary embolism (PE) or deep venous thrombosis (DVT) and the outcome at 3 months (death, recurrent VTE or bleeding) were compared between 2984 COPD patients and 25936 non-COPD patients included in the RIETE registry. This ongoing international multicentre registry includes patients with proven symptomatic PE or DVT.PE was the more frequent VTE presentation in COPD patients (1761, 59%).

PE presentation was significantly more associated with COPD patients than with non-COPD patients (OR: 1.64 [1.49 - 1.80]). During the 3-month follow-up, mortality (10.8% vs 7.6%), minor bleeding (4.5% vs 2.3%) or first VTE recurrences as PE (1.5% vs 1.1%) were significantly higher in COPD patients than in non-COPD patients. PE was the first cause of death.

COPD patients presented more frequently with PE than with DVT. It may explain the worse prognosis of COPD patients, with a higher risk of death, bleeding or VTE recurrences as PE compared with non-COPD patients. Further therapeutic options are needed.

Evolution of Dyspnea during Exercise in COPD: Impact of Critical Volume Constraints.

Patients with COPD primarily describe their exertional dyspnea using descriptors alluding to increased effort or work of breathing and unsatisfied inspiration or inspiratory difficulty.

Objective: The purpose of this study was to examine the impact of changes in dynamic respiratory mechanics during incremental (INCR) and high-intensity constant work-rate (CWR) cycle exercise on the evolution of dyspnea intensity and its major qualitative dimensions in patients with moderate-to-severe COPD.

Methods: Sixteen COPD subjects performed symptom-limited INCR and CWR cycle exercise tests. Measurements included: dyspnea intensity and qualitative descriptors, breathing pattern, operating lung volumes and esophageal pressure (Pes).

Measurements and Main Results: During both exercise tests, there was an inflection in the relation between tidal volume (VT) and ventilation. This inflection occurred significantly earlier in time during CWR versus INCR exercise but at a similar ventilation, VT and tidal Pes swing. Beyond this inflection, there was no further change in VT despite a continued increase in ventilation and tidal Pes. During both tests, "work/effort" was the dominant dyspnea descriptor selected up to the inflection point, whereas after this point dyspnea intensity and the selection frequency of "unsatisfied inspiration" rose sharply.

CONCLUSIONS: Regardless of the exercise test protocol, the inflection (or plateau) in the VT response marked the point where dyspnea intensity rose abruptly and there was a transition in the dominant qualitative descriptor choice from "work/effort" to "unsatisfied inspiration". Intensity and quality of dyspnea evolve separately and are strongly influenced by mechanical constraints on VT expansion during exercise in COPD.

CA-125 Level Is Associated with Right Ventricular Echocardiographic Parameters in Patients with COPD.

OBJECTIVE: : A few studies have shown that elevated CA-125 levels are associated with chronic obstructive pulmonary disease (COPD). However, there are no data concerning the associaton between serum CA-125 levels and right ventricular (RV) function in COPD patients. This study aimed to evaluate the relationship between CA-125 level and RV echocardiographic parameters in COPD patients.

METHODS: : Fifty-two patients with COPD (39 male/13 female, mean age 68.9 ± 5.7 years) were studied. The control group consisted of 30 age-sex matched healthy volunteers (23 male/7 female, mean age 64.2 ± 6.3 years). Patients were divided into two subgroups: patients without pulmonary hypertension (group I, n = 25) and with pulmonary hypertension (group II, n = 27). Conventional echocardiographic parameters, tissue Doppler imaging (TDI) and CA-125 level measurements were performed in all subjects.

RESULTS: : Patients in group II had significantly higher CA-125 levels than those in group I and controls (P < 0.01). CA-125 levels in group I were also higher than control group (P < 0.05). CA-125 levels were correlated with left ventricle E/A ratio, systolic pulmonary artery pressure (sPAP), RV myocardial performance index, and RV fractional area change (r = 0.37, 0.56, 0.34, and - 0.42, respectively, all with P < 0.05). There was an independent correlation between CA-125 levels and sPAP values (β = 0.76, P < 0.001)

CONCLUSIONS: : Our results show an independent correlation between CA-125 levels and systolic pulmonary artery pressure in COPD patients. The clinical utility of these results at this point in time is unknown and deserves future research.

Extrinsic Threshold PEEP Reduces Post-exercise Dyspnea in COPD Patients: A Placebo-controlled, Double-blind Cross-over Study.

Purpose: Most patients with chronic obstructive pulmonary disease (COPD) complain of dyspnea during and following exercise, and the development of intrinsic positive end-expiratory pressure (PEEP) is thought to contribute to lung hyperinflation and dyspnea. Many people with COPD use pursed lip breathing (PLB) in an attempt to produce extrinsic PEEP to reduce lung hyperinflation and dyspnea during and following exertion. We hypothesized that the use of a threshold, extrinsic PEEP device would reduce post-exercise dyspnea in people with COPD.

Methods: A double blind, crossover study was conducted on post-exercise dyspnea in 8 patients with COPD whose exercise tolerance was limited by dyspnea. Subjects performed two identical 6-minute treadmill bouts that led to a Borg dyspnea rating of at least 5/10. Dyspnea, heart rate, and oxygen-hemoglobin saturation (SpO(2)) were recorded at rest, every 2 minutes during exercise and at 2, 5, and 10 minutes post-exercise. Immediately following the exercise bouts, the subjects used either a threshold PEEP device for 6 breaths at 10 cm H(2)O or a Sham device.

Results: Heart rate and SpO(2) were not different between treatments any time point before, during, or after exercise. Dyspnea ratings were not different between devices at rest or during exercise, but were lower in the post-exercise period following use of PEEP (p < 0.05). When asked which device, if any, the subjects would prefer to use to relieve post-exercise dyspnea, 7 of 8 chose the PEEP device and one had no preference.

Conclusions: We found that the use of a PEEP device can help reduce postexercise dyspnea in patients with COPD.

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