No abstract

No abstract

No abstract

No abstract

Inhaled corticosteroids (ICS) are important in reducing exacerbation frequency associated with chronic obstructive pulmonary disease (COPD). However, little is known about the risk of associated infections.In a post hoc analysis of the TOwards a Revolution in COPD Health (TORCH) study, we analysed and identified potential risk factors for adverse event reports of pneumonia in this randomised, double-blind trial comparing twice-daily inhaled salmeterol (SAL) 50 mg, fluticasone propionate (FP) 500 mg, and the combination (SFC) with placebo in 6,184 patients with moderateto-severe COPD over 3 yrs.Despite a higher withdrawal rate in the placebo arm, after adjusting for time on treatment, a greater rate of pneumonia was reported in the FP and SFC treatment arms (84 and 88 per 1,000 treatment-yrs, respectively) compared with SAL and placebo (52 and 52 per 1,000 treatmentyrs, respectively). Risk factors for pneumonia were age o55 yrs, forced expiratory volume in 1 s ,50% predicted, COPD exacerbations in the year prior to the study, worse Medical Research Council dyspnoea scores and body mass index ,25 kg?m -2. No increase in pneumonia deaths with SFC was observed; this could not be concluded for FP.Despite the benefits of ICS-containing regimens in COPD management, healthcare providers should remain vigilant regarding the possible development of pneumonia as a complication in COPD patients receiving such therapies.

Expiratory flow limitation (EFL) during tidal breathing is a major determinant of dynamic hyperinflation and exercise limitation in chronic obstructive pulmonary disease (COPD). Current methods of detecting this are either invasive or unsuited to following changes breath-by-breath. It was hypothesised that tidal flow limitation would substantially reduce the total respiratory system reactance (Xrs) during expiration, and that this reduction could be used to reliably detect if EFL was present.To test this, 5-Hz forced oscillations were applied at the mouth in seven healthy subjects and 15 COPD patients (mean¡SD forced expiratory volume in one second was 36.8¡11.5 % predicted) during quiet breathing. COPD breaths were analysed (n=206) and classified as flow-limited if flow decreased as alveolar pressure increased, indeterminate if flow decreased at constant alveolar pressure, or nonflow-limited.Of these, 85 breaths were flow-limited, 80 were not and 41 were indeterminate. Among other indices, mean inspiratory minus mean expiratory Xrs (DXrs) and minimum expiratory Xrs (Xexp,min) identified flow-limited breaths with 100% specificity and sensitivity using a threshold between 2. Unlike healthy subjects who do not develop expiratory flow limitation (EFL) even during exhaustive exercise [1], many chronic obstructive pulmonary disease (COPD) patients are flow-limited (FL) at rest [2]. These patients can only increase their expiratory flow rate during exercise by allowing their end-expiratory lung volume (VL) to rise, an energetically inefficient strategy that is accompanied by severe dyspnoea that reduces exercise duration [3,4]. The severity of dyspnoea in COPD is better predicted by the presence of EFL during tidal breathing than by the forced expiratory volume in one second (FEV1) [5,6]. Thus, a simple method of detecting EFL during tidal breathing would be a potentially useful clinical tool. Several noninvasive methods have been proposed to detect tidal EFL in COPD patients, but each has its limitations and, to the best of the authors9 knowledge, to date none has been tested against any form of "gold standard" in spontaneously breathing patients.In 1993, PESLIN et al. [7] reported that some COPD patients during mechanical ventilation developed large negative swings in the respiratory system input reactance (Xrs, i.e. the imaginary part of total input impedance) measured by a forced oscillation technique (FOT). Similar behaviour was observed in a simplified mechanical model of the respiratory system when a flow-limiting segment was included [8] and in mechanically ventilated rabbits [9] after intravenous methacholine infusion. This phenomenon occurs because the linear velocity of gas passing through flow-limiting segments (choke points) equals the local speed of wave propagation [10]. Normally the reactance reflects the elastic and inertial properties of the respiratory system but when flow limitation is present, the oscillatory signal cannot pass through the choke points and reach the alveoli, producing a ...

Background: Dynamic hyperinflation of the lungs impairs exercise performance in chronic obstructive pulmonary disease (COPD). However, it is unclear which patients are affected by dynamic hyperinflation and how the respiratory muscles respond to the change in lung volume. Methods: Using optoelectronic plethysmography, total and regional chest wall volumes were measured non-invasively in 20 stable patients with COPD (mean (SD) forced expiratory volume in 1 second 43.6 (11.6)% predicted) and dynamic hyperinflation was tracked breath by breath to test if this was the mechanism of exercise limitation. Resting ventilation, breathing pattern, symptoms, rib cage and abdominal volumes were recorded at rest and during symptom limited cycle ergometry. Pleural, abdominal, and transdiaphragmatic pressures were measured in eight patients. Results: End expiratory chest wall volume increased by a mean (SE) of 592 (80) ml in 12 patients (hyperinflators) but decreased by 462 (103) ml in eight (euvolumics). During exercise, tidal volume increased in euvolumic patients by reducing end expiratory abdominal volume while in hyperinflators tidal volume increased by increasing end inspiratory abdominal and rib cage volumes. The maximal abdominal pressure was 22.1 (9.0) cm H 2 O in euvolumic patients and 7.6 (2.6) cm H 2 O in hyperinflators. Euvolumic patients were as breathless as hyperinflators but exercised for less time and reached lower maximum workloads (p,0.05) despite having better spirometric parameters and a greater expiratory flow reserve. Conclusions: Dynamic hyperinflation is not the only mechanism limiting exercise performance in patients with stable COPD. Accurate measurement of chest wall volume can identify the different patterns of respiratory muscle activation during exercise.

We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced expiratory volume in 1 s (FEV1) ,60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month.Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV1 % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7-0.8 (p,0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1-1.2 (p,0.001)). The effect of season was independent of these risk factors.COPD exacerbations and hospitalisations were more frequent in winter.