Dynamic hyperinflation (DH) is a major pathophysiologic consequence of airflow limitation during exercise in patients with chronic obstructive pulmonary disease (COPD) and an important contributing factor to breathlessness. In this study we aimed to examine the effect of inhaled beta agonist therapy on DH during exercise in these patients and the relationship between changes in DH and breathlessness. In 13 COPD patients (mean age 65.1 +/- 2.0, FEV1 1.20 +/- 0.17, FEV1/FVC 40 +/- 3) we measured pulmonary function tests, exercise breathlessness by Borg score, and exercise flow volume and pressure volume loops on two separate days. Prior to testing, patients randomly received inhaled placebo or albuterol on the first test day and the alternative medication on the second test day. From measurements of exercise inspiratory capacity (IC), we calculated the end-expiratory and end-inspiratory lung volumes (EELV, EILV). We used esophageal pressure recordings to measure peak inspiratory esophageal pressure (Pesins) during exercise and this was related to the maximal capacity for pressure generation taking into account lung volume and airflow changes (Pcapi). Bronchodilator caused significant increase in both FEV1 and FVC (+0.23 and +0.51, p<0.01). Comparisons of breathlessness, exercise volumes, and pressures were made at the highest equivalent work load. There was a significant reduction in the peak exercise EELV/TLC (80 +/- 0.02% to 76 +/- 0.02%, p<0.05) while the peak EILV/TLC decreased by 2% (97 +/- 1% to 95 +/- 1%, p<0.05). The peak Pesins/Pcapi decreased (0.79 +/- 0.10 to 0.57 +/- 0.05, p<0.05), and the Pcapi - Pesins increased (7.4 +/- 3 to 13.0 +/- 3 cm H2O, p<0.05). There was significant improvement in neuroventilatory coupling for volume change (Pesins/Pcapi/VT/TLC 5.45 +/- 0.5 to 3.25 +/- 1.0, p<0.05). There was a significant reduction in breathlessness as measured by Borg score (4.5 +/- 0.7 to 3.1 +/- 0.5, p<0.05) and there was a significant correlation between delta Borg and delta EILV/TLC (r=0.771, p<0.01) with a trend for Pesins/Pcapi/VT/TLC (r=0.544, p=0.067). There was also a significant correlation between delta EELV/TLC and delta Pesins/Pcapi/VT/TLC (r=0.772, p<0.01). The relationships between delta Borg, delta resting volumes, and flow rates were not significant. We conclude that in patients with COPD, inhaled bronchodilator reduces exercise DH and improves inspiratory pressure reserve and neuroventilatory coupling. Changes in DH and neuroventilatory coupling were the main determinants of reduced breathlessness.
The response of skeletal muscle to training is influenced by both the intensity and nature of the training stimulus. In this study we investigated the characteristics of the ventilatory load applied to the ventilatory muscles during several different modes of ventilatory muscle training. Patients with chronic obstructive pulmonary disease (COPD) performed the following breathing maneuvers: (1) Unloaded hyperpnea (UH), (2) resistive breathing through a fixed orifice (0.5 cm diameter) at frequencies of 15 and 30 breaths/min (RT15, RT30), (3) loaded breathing through a threshold valve set at 30% of the PImax at frequencies of 15 and 30 breaths/min (TT15, TT30), and (4) repetitive maximal inspiratory maneuvers against a closed shutter (PImax). During these maneuvers were recorded airflow and pressures at the month and esophagus, and from these measurements we derived VE and the work of breathing (WOB), tension time index (TTI), and pressure time product (PTP). The VE during UH was significantly higher than all other modes (p < 0.01), whereas the Pesmax was significantly lower during UH than during the resistive and loaded maneuvers (p < 0.01). The WOB did not differ during UH, TT30, and RT30, but was significantly higher in all three modes than at TT15 and RT15 (p < 0.05). During RT30 the TTI was higher than during TT30, TT15, and RT15 (p < 0.05), whereas the TTI during UH was significantly lower than during other maneuvers (p < 0.01). As expected, the highest Pesmax and PTP were found during the PImax maneuver. These data show that important qualitative differences in ventilatory muscle loading can be achieved by means of different devices and breathing strategies.(ABSTRACT TRUNCATED AT 250 WORDS)
Intranasal corticosteroids are widely prescribed for the treatment of perennial allergic rhinitis (PAR). The aim of this analysis was to determine whether the beneficial effects of once-daily (q.d.) fluticasone furoate nasal spray (FFNS) effectively improved individual nasal symptoms of PAR. An integrated analysis was performed on data from three randomized, double-blind, placebo-controlled, parallel-group trials designed to evaluate the efficacy and safety of FFNS at 110 micrograms, q.d. in subjects with PAR. The analysis included 460 subjects who received FFNS and 459 who received placebo for 4 weeks. All subjects evaluated the severity of individual nasal symptoms of nasal congestion, nasal itching, rhinorrhea, and sneezing on a four-point categorical scale. The main efficacy measures included change from baseline in daily reflective total nasal symptom score (rTNSS), reflective daily scores for each individual symptom, and predose instantaneous TNSS (iTNSS). Over 4 weeks of treatment, FFNS significantly improved rTNSS, iTNSS, and the reflective scores for each individual symptom compared with placebo. The least squares (LS) mean treatment difference over weeks 1-4 between FFNS and placebo for rTNSS was -0.93, ranging from -0.20 to -0.28 for the individual nasal symptoms (p < 0.001 for all versus placebo). For the iTNSS, the LS mean treatment difference between FFNS and placebo over weeks 1-4 was -0.95 (95% CI,-1.24, -0.66; p < 0.001). FFNS at 110 micrograms q.d. effectively relieved all nasal symptoms of PAR including nasal congestion over a 24-hour period.
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