Understanding sex differences in the qualitative dimensions of exertional dyspnea may provide insight into why women are more affected by this symptom than men. This study explored the evolution of the qualitative dimensions of dyspnea in 70 healthy, young, physically active adults (35 M and 35 F). Participants rated the intensity of their breathing discomfort (Borg 0-10 scale) and selected phrases that best described their breathing from a standardized list (work/effort, unsatisfied inspiration, and unsatisfied expiration) throughout each stage of a symptom-limited incremental-cycle exercise test. Following exercise, participants selected phrases that described their breathing at maximal exercise from a list of 15 standardized phrases. Intensity of breathing discomfort was significantly higher in women for a given ventilation, but differences disappeared when ventilation was expressed as a percentage of maximum voluntary ventilation. The dominant qualitative descriptor in both sexes throughout exercise was increased work/effort of breathing. At peak exercise, women were significantly more likely to select the following phrases: "my breathing feels shallow," "I cannot get enough air in," "I cannot take a deep breath in," and "my breath does not go in all the way." Women adopted a more rapid and shallow breathing pattern and had significantly higher end-inspiratory lung volumes relative to total lung capacity throughout exercise relative to men. These findings suggest that men and women do not differ in their perceived quality of dyspnea during submaximal exercise, but subjective differences appear at maximal exercise and may be related, at least in part, to underlying sex differences in breathing patterns and operating lung volumes during exercise.

We conclude that EFL in women can largely be explained by anatomical factors that influence the capacity to generate flow and volume during exercise rather than fitness per se.

Dyspnoea is a major source of distress and is the hallmark symptom of patients with interstitial lung disease (ILD). Supplemental oxygen may alleviate dyspnoea by attenuating arterial oxygen desaturation, increasing oxygen delivery and reducing the drive to breathe; however, previous studies show conflicting results on the effectiveness of supplemental oxygen on dyspnoea and exercise performance in ILD [1][2][3][4][5][6]. Methodological factors in these studies likely led to underestimation of the potential magnitude of improvement, including an insufficient fraction of inspired oxygen (FIO 2 ) and/or the use of self-paced walking tests and incremental cycle tests rather than constant-load exercise protocols [3][4][5][6][7][8]. Dyspnoea was also either not evaluated or only evaluated at peak exercise [1,[3][4][5][6], which is insensitive to change compared to more clinically relevant submaximal exercise [8]. Finally, some studies were retrospective and did not include a blinded room-air exercise trial, making it difficult to rule out the potential placebo effect [4,5]. The purpose of this study was to determine the effects of hyperoxia on exercise endurance as well as the intensity and qualitative dimensions of exertional dyspnoea in patients with fibrotic ILD.This prospective, single-blind, randomised, placebo-controlled, crossover study (ClinicalTrials.gov: NCT01781793) received ethical approval and included 20 fibrotic ILD patients with isolated lung involvement (age 66±9 yrs; body mass index 29±5 kg·m −2 ; forced vital capacity 72±16% predicted; total lung capacity (TLC) 64±11% predicted; diffusing capacity of the lung for carbon monoxide 46±13% predicted; peak oxygen uptake 68±22% predicted). Visit 1 included medical history, pulmonary function testing and a symptom-limited incremental cycle test for familiarisation purposes. Visit 2 included the same incremental test to determine peak work-rate. Visits 3 and 4 each included symptom-limited constant-load cycle tests at 75% of peak work-rate while breathing room air (FIO 2 21%) or hyperoxia (FIO 2 60%), in randomised order. Subjects were blinded to the gas mixtures, which were delivered into a non-diffusing Douglas bag connected to a two-way non-rebreathing valve. Breath-by-breath metabolic and ventilatory responses were measured using a commercially available metabolic cart.

Inspiratory muscle training (IMT) has consistently been shown to reduce exertional dyspnea in health and disease; however, the physiological mechanisms remain poorly understood. A growing body of literature suggests that dyspnea intensity can be explained largely by an awareness of increased neural respiratory drive, as measured indirectly using diaphragmatic electromyography (EMGdi). Accordingly, we sought to determine whether improvements in dyspnea following IMT can be explained by decreases in inspiratory muscle electromyography (EMG) activity. Twenty-five young, healthy, recreationally active men completed a detailed familiarization visit followed by two maximal incremental cycle exercise tests separated by 5 wk of randomly assigned pressure threshold IMT or sham control (SC) training. The IMT group ( = 12) performed 30 inspiratory efforts twice daily against a 30-repetition maximum intensity. The SC group ( = 13) performed a daily bout of 60 inspiratory efforts against 10% maximal inspiratory pressure (MIP), with no weekly adjustments. Dyspnea intensity was measured throughout exercise using the modified 0-10 Borg scale. Sternocleidomastoid and scalene EMG was measured using surface electrodes, whereas EMGdi was measured using a multipair esophageal electrode catheter. IMT significantly improved MIP (pre: -138 ± 45 vs. post: -160 ± 43 cmHO, < 0.01), whereas the SC intervention did not. Dyspnea was significantly reduced at the highest equivalent work rate (pre: 7.6 ± 2.5 vs. post: 6.8 ± 2.9 Borg units, < 0.05), but not in the SC group, with no between-group interaction effects. There were no significant differences in respiratory muscle EMG during exercise in either group. Improvements in dyspnea intensity ratings following IMT in healthy humans cannot be explained by changes in the electrical activity of the inspiratory muscles. Exertional dyspnea intensity is thought to reflect an increased awareness of neural respiratory drive, which is measured indirectly using diaphragmatic electromyography (EMGdi). We examined the effects of inspiratory muscle training (IMT) on dyspnea, EMGdi, and EMG of accessory inspiratory muscles. IMT significantly reduced submaximal dyspnea intensity ratings but did not change EMG of any inspiratory muscles. Improvements in exertional dyspnea following IMT may be the result of nonphysiological factors or physiological adaptations unrelated to neural respiratory drive.

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AimAdverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced adverse drug events and increase drug effectiveness. Our aim was to quantify the clinical effectiveness of genotype-guided prescribing.MethodsThree electronic databases were searched from January 1980 through December 2013. Studies were eligible if they were RCTs comparing genotype-guided prescribing with non-genetic informed prescribing, reported drug specific adverse drug events and clinical effectiveness outcomes. Two reviewers independently screened titles and abstracts, extracted data and assessed study quality. Meta-analyses of specific outcomes were conducted where data allowed.ResultsFifteen studies, involving 5688 patients and 19 drugs, met the inclusion and exclusion criteria. Eight studies had statistically significant results for their primary outcome in favour of genotype-guided prescribing. Nine studies evaluated genotype-guided warfarin dosing. Analysis of percentage of time in therapeutic international normalized ratio range (1952 individuals) showed a statistically significant benefit in favour of genotype-guided warfarin dosing (mean difference = 6.67; 95% CI 1.34, 12.0, I2 = 80%). There was a statistically significant reduction in numbers of warfarin-related minor bleeding, major bleeding and thromboembolisms associated with genotype guided warfarin dosing, relative risk 0.57 (95% CI 0.33, 0.99; I2 = 60%). It was not possible to meta-analyze genotype-guided dosing for other drugs. Of the six non-warfarin genotype-guided trials, two demonstrated a statistically significant benefit for their primary outcome, odds ratio 0.03 (95% CI 0.00, 0.62, P < 0.001) for abacavir.ConclusionsThere is evidence of improved clinical effectiveness associated with genotype-guided warfarin dosing.

Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung disease (ILD) is incomplete. The aims of this study were two-fold: 1) to determine whether dyspnoea intensity is better predicted by neural respiratory drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1 comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted of constant-load cycling while breathing room air or 60% oxygen to address Aim 2. Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was calculated as the ratio between EMGdi (%max) and tidal volume (%vital capacity).On adjusted analysis, NMU and its constituents were all significantly associated with dyspnoea ratings during incremental cycling, with EMGdi having the strongest correlation. The between-treatment change in dyspnoea ratings during constant load cycling was only correlated with change in exercise endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was better predicted by improvements in NMU.

The purpose of this study was to evaluate cardiorespiratory fitness and reasons for exercise curtailment in a contemporary adult cystic fibrosis (CF) cohort with mild lung disease. Adults with mild CF (n = 19, forced expiratory volume in 1 s = 95 ± 17% predicted) were age-, sex-, ethnicity-, and body mass index-matched to healthy controls (n = 19) and underwent a detailed cardiopulmonary cycle exercise test. While CF subjects had a reduced peak oxygen uptake compared with controls, the values were normal when expressed as %predicted in 14/19 (74%) of subjects. Both groups demonstrated a normal cardiovascular limitation to exercise and stopped exercise primarily because of leg fatigue. Despite not being exercise-limited by respiratory factors, there was some evidence of ventilatory abnormalities as patients with mild CF had increased end-inspiratory lung volumes and reached an inflection/plateau in tidal volume relative to minute ventilation at lower exercise intensities compared with controls. Subjects with CF were not more likely to demonstrate expiratory flow limitation compared with controls and did not have evidence of dynamic hyperinflation during exercise. Despite increased end-inspiratory lung volumes and an earlier tidal volume inflection/plateau, CF subjects did not experience higher levels of dyspnea. In an exploratory analysis, a significant inverse correlation was observed between sweat chloride and peak work rate. Adult CF subjects with relatively well preserved spirometry have normal exercise performance relative to reference values and are primarily limited by nonrespiratory factors. However, ventilatory abnormalities were detected even in this mild CF cohort and should be evaluated in future therapeutic trials focused on disease-modifying therapies in mild CF.