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Introduction: Contrary to common belief, a growing body of evidence suggests that unsatisfied inspiration (UI), an inherently uncomfortable quality of dyspnea, is experienced by ostensibly healthy adults during high-intensity exercise. Based on our understanding of the mechanisms of UI among people with chronic respiratory conditions, this analysis tested the hypothesis that the experience of UI at peak exercise in young, healthy adults reflects the combination of high ventilatory demand and critical inspiratory constraints., Methods: In a retrospective analysis design, data included 321 healthy individuals (129 females) aged 25 ± 5 yr. Data were collected during one visit to the laboratory, which included anthropometrics, spirometry, and an incremental cardiopulmonary cycling test to exhaustion. Metabolic and cardiorespiratory variables were measured at peak exercise, and qualitative descriptors of dyspnea at peak exercise were assessed using a list of 15 descriptor phrases., Results: Thirty-four percent of participants ( n = 109) reported sensations of UI at peak exercise. Compared with the non-UI group, the UI group achieved a significantly higher peak work rate (243 ± 77 vs 235 ± 69 W, P = 0.016, d = 0.10), rate of O 2 consumption (3.32 ± 1.02 vs 3.27 ± 0.96 L·min -1 , P = 0.018, d = 0.05), minute ventilation (120 ± 38 vs 116 ± 35 L·min -1 , P = 0.047, d = 0.11), and breathing frequency (50 ± 9 vs 47 ± 9 breaths per minute, P = 0.014, d = 0.33), while having a lower exercise-induced change (peak-baseline) in inspiratory capacity (0.07 ± 0.41 vs 0.20 ± 0.49 L, P = 0.023, d = 0.29). The inspiratory reserve volume to minute ventilation ratio at peak exercise was also lower in the UI versus non-UI group. Dyspnea intensity and unpleasantness ratings were significantly higher in the UI versus non-UI group at peak exercise (both P < 0.001)., Conclusions: Healthy individuals reporting UI at peak exercise have relatively greater inspiratory constraints compared with those who do not select UI., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Several bedside assessments are used to evaluate respiratory muscle function and to predict weaning from mechanical ventilation in patients on the intensive care unit. It remains unclear which assessments perform best in predicting weaning success. The primary aim of this systematic review and meta-analysis was to summarize and compare the accuracy of the following assessments to predict weaning success: maximal inspiratory (PImax) and expiratory pressures, diaphragm thickening fraction and excursion (DTF and DE), end-expiratory (Tdi ee ) and end-inspiratory (Tdi ei ) diaphragm thickness, airway occlusion pressure (P0.1), electrical activity of respiratory muscles, and volitional and non-volitional assessments of transdiaphragmatic and airway opening pressures., Methods: Medline (via Pubmed), EMBASE, Web of Science, Cochrane Library and CINAHL were comprehensively searched from inception to 04/05/2023. Studies including adult mechanically ventilated patients reporting data on predictive accuracy were included. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate the SROC curves of each assessment method. Meta-regression was used to compare SROC curves. Sensitivity analyses were conducted by excluding studies with high risk of bias, as assessed with QUADAS-2. Direct comparisons were performed using studies comparing each pair of assessments within the same sample of patients., Results: Ninety-four studies were identified of which 88 studies (n = 6296) reporting on either PImax, DTF, DE, Tdi ee , Tdi ei and P0.1 were included in the meta-analyses. The sensitivity to predict weaning success was 63% (95% CI 47-77%) for PImax, 75% (95% CI 67-82%) for DE, 77% (95% CI 61-87%) for DTF, 74% (95% CI 40-93%) for P0.1, 69% (95% CI 13-97%) for Tdi ei , 37% (95% CI 13-70%) for Tdi ee , at fixed 80% specificity. Accuracy of DE and DTF to predict weaning success was significantly higher when compared to PImax (p = 0.04 and p < 0.01, respectively). Sensitivity and direct comparisons analyses showed that the accuracy of DTF to predict weaning success was significantly higher when compared to DE (p < 0.01)., Conclusions: DTF and DE are superior to PImax and DTF seems to have the highest accuracy among all included respiratory muscle assessments for predicting weaning success. Further studies aiming at identifying the optimal threshold of DTF to predict weaning success are warranted., Trial Registration: PROSPERO CRD42020209295, October 15, 2020., (© 2024. The Author(s).)

Background: Unilateral diaphragm dysfunction (UDD) is an underdiagnosed cause of dyspnoea. Inspiratory muscle training (IMT) is the only conservative treatment for UDD, but the mechanisms of improvement are unknown. We characterised the effects of IMT on dyspnoea, exercise tolerance and respiratory muscle function in people with UDD., Methods: 15 people with UDD (73% male, 61±8 years) were randomised to 6 months of IMT (50% maximal inspiratory mouth pressure ( P I,max ), n=10) or sham training (10% P I,max , n=5) (30 breaths twice per day). UDD was confirmed by phrenic nerve stimulation and persisted throughout the training period. Symptoms were assessed by the transitional dyspnoea index (TDI) and exercise tolerance by constant-load cycle tests performed pre- and post-training. Oesophageal ( P es ) and gastric ( P ga ) pressures were measured with a dual-balloon catheter. Electromyography (EMG) and oxygenation (near-infrared spectroscopy) of respiratory muscles were assessed continuously during exercise., Results: The IMT group (from 45±6 to 62±23% P I,max ) and sham group (no progression) completed 92 and 86% of prescribed sessions, respectively. P I,max , TDI scores and cycle endurance time improved significantly more after IMT versus sham (mean between-group differences: 28 (95% CI 13-28) cmH 2 O, 3.0 (95% CI 0.9-5.1) points and 6.0 (95% CI 0.4-11.5) min, respectively). During exercise at iso-time, P es , P ga and EMG of the scalene muscles were reduced and the oxygen saturation indices of the scalene and abdominal muscles were higher post- versus pre-training only in the IMT group (all p<0.05)., Conclusion: The effects of IMT on dyspnoea and exercise tolerance in UDD were not mediated by an improvement in isolated diaphragm function, but may reflect improvements in strength, coordination and/or oxygenation of the extra-diaphragmatic respiratory muscles., Competing Interests: Conflict of interest: Training devices were provided on loan for the study duration by HaB International Ltd. R. Gosselink reports personal fees from Elsevier. D. Langer reports a grant from Research Foundation Flanders and a leadership role with the European Respiratory Society. M.R. Schaeffer, Z. Louvaris, A. Rodrigues, D. Poddighe, G. Gayan-Ramirez, T. Gojevic, L. Geerts, E. Heyndrickx, M. Van Hollebeke, L. Janssens and D. Testelmans do not have any disclosures., (Copyright ©The authors 2023.)

Objectives: Dyspnoea is a common persistent symptom post-coronavirus disease 2019 (COVID-19) illness. However, the mechanisms underlying dyspnoea in the post-COVID-19 syndrome remain unclear. The aim of our study was to examine dyspnoea quality and intensity, burden of mental health symptoms, and differences in exercise responses in people with and without persistent dyspnoea following COVID-19., Methods: 49 participants with mild-to-critical COVID-19 were included in this cross-sectional study 4 months after acute illness. Between-group comparisons were made in those with and without persistent dyspnoea (defined as modified Medical Research Council dyspnoea score ≥1). Participants completed standardised dyspnoea and mental health symptom questionnaires, pulmonary function tests, and incremental cardiopulmonary exercise testing., Results: Exertional dyspnoea intensity and unpleasantness were increased in the dyspnoea group. The dyspnoea group described dyspnoea qualities of suffocating and tightness at peak exercise (p<0.05). Ventilatory equivalent for carbon dioxide ( V ' E / V ' CO 2 ) nadir was higher (32±5 versus 28±3, p<0.001) and anaerobic threshold was lower (41±12 versus 49±11% predicted maximum oxygen uptake, p=0.04) in the dyspnoea group, indicating ventilatory inefficiency and deconditioning in this group. The dyspnoea group experienced greater symptoms of anxiety, depression and post-traumatic stress (all p<0.05). A subset of participants demonstrated gas-exchange and breathing pattern abnormalities suggestive of dysfunctional breathing., Conclusions: People with persistent dyspnoea following COVID-19 experience a specific dyspnoea quality phenotype. Dyspnoea post-COVID-19 is related to abnormal pulmonary gas exchange and deconditioning and is linked to increased symptoms of anxiety, depression and post-traumatic stress., Competing Interests: Conflict of interest: K.L. Lavoie reports consulting fees from AbbVie, Takeda, Astellas, Boehringer Ingelheim, AstraZeneca, Janssen, Novartis, GSK, Bausch and Sojecci Inc., outside the submitted work; payment or honoraria from AbbVie, Boehringer Ingelheim, Takeda, Pfizer, Merck, GSK, Astra-Zeneca, Novartis, Janssen, Bayer, Mundi Pharma, Bayer, Air Liquide, Astellas and Xfacto, outside the submitted work; and participation on a Data Safety Monitoring Board or Advisory Board for Astra-Zeneca, GSK and Bausch, outside the submitted work. Conflict of interest: J. Cowan reports support for the present manuscript from The Ottawa Hospital Foundation; grants or contracts from Octapharma and Takeda, outside the submitted work; payment or honoraria from GSK, Sanofi, EMD Serono, Alexion and Takeda, outside the submitted work; and support for attending meetings and/or travel from Octapharma, outside the submitted work. Conflict of interest: J.A. Chirinos reports grants or contracts from University of Pennsylvania research grants from National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft and Abbott, outside the submitted work; consulting fees from Bayer, Sanifit, Fukuda-Denshi, Bristol-Myers Squibb, JNJ, Edwards Life Sciences, Merck, NGM Biopharmaceuticals and the Galway-Mayo Institute of Technology, outside the submitted work; patents planned, issued or pending: inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of Heart Failure and Preserved Ejection Fraction and for the use of biomarkers in heart failure with preserved ejection fraction, outside the submitted work; participant on advisory board for BMS, outside the submitted work; Vice President of North American Artery Society, outside the submitted work; received research device loans from Atcor Medical, Fukuda-Denshi, Uscom, NDD Medical Technologies, Microsoft and MicroVision Medical, outside the submitted work; received payments for editorial roles from the American Heart Association, the American College of Cardiology and Wiley, outside the submitted work. Conflict of interest: J.A. Guenette is an associate editor of this journal. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: During the coronavirus disease 2019 pandemic, public health officials widely adopted the use of face masks (FM) to minimize infections. Despite consistent evidence that FMs increase dyspnea, no studies have examined the multidimensional components of dyspnea or their underlying physiological mechanisms., Methods: In a randomized crossover design, 16 healthy individuals ( n = 9 women, 25 ± 3 yr) completed incremental cycling tests over three visits, where visits 2 and 3 were randomized to either surgical FM or no mask control. Dyspnea intensity and unpleasantness were assessed throughout exercise (0-10 Borg scale), and the Multidimensional Dyspnea Profile was administered immediately after exercise. Crural diaphragmatic EMG and esophageal pressure were measured using a catheter to estimate neural respiratory drive and respiratory muscle effort, respectively., Results: Dyspnea unpleasantness was significantly greater with the FM at the highest equivalent submaximal work rate achieved by a given participant in both conditions (iso-work; 5.9 ± 1.7 vs 3.9 ± 2.9 Borg 0-10 units, P = 0.007) and at peak exercise (7.8 ± 2.1 vs 5.9 ± 3.4 Borg 0-10 units, P = 0.01) with no differences in dyspnea intensity ratings throughout exercise compared with control. There were significant increases in the sensory quality of "smothering/air hunger" ( P = 0.01) and the emotional response of "anxiousness" ( P = 0.04) in the FM condition. There were significant increases in diaphragmatic EMG and esophageal pressure at select submaximal work rates, but no differences in heart rate, pulse oximetry-derived arterial oxygen saturation, or breathing frequency throughout exercise with FMs compared with control. FMs significantly reduced peak work rate and exercise duration (both P = 0.02)., Conclusions: FMs negatively impact the affective domain of dyspnea and increase neural respiratory drive and respiratory muscle effort during exercise, although the impact on other cardiorespiratory responses are minimal., (Copyright © 2022 by the American College of Sports Medicine.)

After a bout of isolated inspiratory work, such as inspiratory pressure threshold loading (IPTL), the human diaphragm can exhibit a reversible loss in contractile function, as evidenced by a decrease in transdiaphragmatic twitch pressure (P DI,TW ). Whether or not diaphragm fatigability after IPTL is affected by neural mechanisms, measured through voluntary activation of the diaphragm (D-VA) in addition to contractile mechanisms, is unknown. It is also unknown if changes in D-VA are similar between sexes given observed differences in diaphragm fatigability between males and females. We sought to determine whether D-VA decreases after IPTL and whether this was different between sexes. Healthy females (n = 11) and males (n = 10) completed an IPTL task with an inspired duty cycle of 0.7 and targeting an intensity of 60% maximal transdiaphragmatic pressure until task failure. P DI,TW and D-VA were measured using cervical magnetic stimulation of the phrenic nerves in combination with maximal inspiratory pressure maneuvers. At task failure, P DI,TW decreased to a lesser degree in females vs. males (87 ± 15 vs. 73 ± 12% baseline, respectively, p = 0.016). D-VA decreased after IPTL but was not different between females and males (91 ± 8 vs. 88 ± 10% baseline, respectively, p = 0.432). When all participants were pooled together, the decrease in P DI,TW correlated with both the total cumulative diaphragm pressure generation (R 2  = 0.43; p = 0.021) and the time to task failure (TTF, R 2 = 0.40; p = 0.30) whereas the decrease in D-VA correlated only with TTF (R 2  = 0.24; p = 0.041). Our results suggest that neural mechanisms can contribute to diaphragm fatigability, and this contribution is similar between females and males following IPTL., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Fatigue is a common, debilitating, and poorly understood symptom post-COVID-19. We sought to better characterize differences in those with and without post-COVID-19 fatigue using cardiopulmonary exercise testing. Despite elevated dyspnoea intensity ratings, V̇O 2 peak (ml/kg/min) was the only significant difference in the physiological responses to exercise (19.9 ± 7.1 fatigue vs. 24.4 ± 6.7 ml/kg/min non-fatigue, p = 0.04). Consistent with previous findings, we also observed a higher psychological burden in those with fatigue in the context of similar resting cardiopulmonary function. Our findings suggest that lower cardiorespiratory fitness and/or psychological factors may contribute to post-COVID-19 fatigue symptomology. Further research is needed for rehabilitation and symptom management following SARS-CoV-2 infection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Importance: It has been suggested that Mohs surgery for skin cancer among individuals with limited life expectancy may be associated with needless risk and discomfort, along with increased health care costs., Objective: To investigate patient- and tumor-specific indications considered by clinicians for treatment of nonmelanoma skin cancer in older individuals., Design, Setting, and Participants: This multicenter, prospective cohort study was conducted using data from US private practice and academic centers. Included patients were those older than age 85 years presenting for skin cancer surgery and referred for Mohs surgery, with reference groups of those younger than age 85 years receiving Mohs surgery and those older than age 85 years not receiving Mohs surgery. Data were analyzed from November 2018 through January 2019., Exposures: Mohs surgery for nonmelanoma skin cancer., Main Outcomes and Measures: Reason for treatment selection., Results: Among 1181 patients older than age 85 years referred for Mohs surgery (724 [61.9%] men among 1169 patients with sex data; 681 individuals aged >85 to 88 years [57.9%] among 1176 patients with age data) treated at 22 sites, 1078 patients (91.3%) were treated by Mohs surgery, and 103 patients (8.7%) received alternate treatment. Patients receiving Mohs surgery were more likely to have tumors on the face (738 patients [68.5%] vs 26 patients [25.2%]; P < .001) and nearly 4-fold more likely to have high functional status (614 patients [57.0%] vs 16 patients [15.5%]; P < .001). Of 15 distinct reasons provided by surgeons for opting to proceed with Mohs surgery, the most common were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%])., Conclusions and Relevance: This study found that older patients who received Mohs surgery often had high functional status, high-risk tumors, and tumors located on the face. These findings suggest that timely surgical treatment may be appropriate in older patients given that their tumors may be aggressive, painful, disfiguring, and anxiety provoking.

Introduction: The female diaphragm develops less fatigue after high-intensity exercise compared with males. Diaphragm fatigability is typically defined as a decrease in transdiaphragmatic twitch pressure (Pdi,TW) and represents the contractile function of the muscle. However, it is unclear whether this sex difference persists when examining changes in voluntary activation, which represents a neural mechanism contributing to fatigability., Purpose: This study aimed to determine if high-intensity cycling results in a decrease in diaphragm voluntary activation (D-VA) and to explore if the decrease in D-VA is different between sexes., Methods: Twenty-five participants (15 females) completed a single bout of high-intensity constant load cycling. D-VA and Pdi,TW were measured before and after exercise using cervical magnetic stimulation of the phrenic nerves to assess diaphragm fatigability., Results: Participants were of similar aerobic fitness when expressed relative to predicted values (females: 114% ± 25% predicted, males: 111% ± 11% predicted; P = 0.769). Pdi,TW decreased relative to baseline to 85.2% ± 16.7% and 70.3% ± 12.4% baseline (P = 0.012) in females and males, respectively, immediately after exercise. D-VA also decreased in both females and males immediately after exercise. The decrease in D-VA was less in females compared with males (95.4% ± 4.9% baseline vs 87.4% ± 10.8% baseline, respectively; P = 0.018)., Conclusions: D-VA decreases after whole-body exercise in both females and males, although the magnitude of the decrease is not as large in females compared with males. The findings of this study suggest that the female diaphragm is more resistant to both contractile and neural mechanisms of fatigability after whole-body exercise., (Copyright © 2022 by the American College of Sports Medicine.)

Obesity is a health epidemic associated with greater morbidity and mortality in the general population. Mass loading of the thorax from obesity leads to a restrictive pulmonary defect that reduces lung capacity in obese individuals without pulmonary disease, and may exacerbate the restrictive pulmonary physiology that is characteristic of interstitial lung disease (ILD). The purpose of this study was to test the association of body mass index (BMI) with pulmonary function, functional capacity, and patient-reported outcomes (dyspnea and quality of life) in patients with ILD. We analyzed 3169 patients with fibrotic ILD from the Canadian Registry for Pulmonary Fibrosis. Patients were subcategorized as underweight (BMI<18.5 kg/m 2 ), normal weight (18.5≤BMI<25), overweight (25≤BMI<30), obese I (30≤BMI<35), obese II (35≤BMI<40), and obese III (BMI>40). Analysis was performed using a linear regression with adjustment for common prognostic variables. Overweight and obese BMI categories were associated with worse pulmonary function, functional capacity, dyspnea, and quality of life compared to normal weight. This is likely a result of mass loading on the thorax, and we speculate that intentional weight-loss may improve lung function and functional capacity in obese patients with fibrotic ILD. The underweight BMI category was also associated with worse functional capacity compared to normal weight, which may reflect greater disease severity or the presence of other comorbidities. Future work should explore the clinical utility of BMI to improve patient outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD., Research Question: Does exposure before exercise to TRAP (DE titrated to 300 μg/m 3 particulate matter < 2.5 μm in diameter [DE 300 ]) show greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild to moderate COPD compared with former smokers with normal spirometry and healthy control participants?, Study Design and Methods: In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy control participants, nine former smokers without COPD, and nine former smokers with COPD were separately exposed to filtered air (FA) and DE 300 for 2 h separated by a minimum of 4 weeks. Participants performed symptom-limited constant load cycling tests within 2.5 h of exposure with detailed cardiorespiratory and exertional symptom measurements., Results: A significant negative effect of TRAP on exercise endurance time was found in healthy control participants (DE 300 vs FA, 10.2 ± 8.2 min vs 12.9 ± 9.5 min, respectively; P = .03), but not in former smokers without COPD (10.1 ± 6.9 min vs 12.2 ± 8.0 min, respectively; P = .57) or former smokers with COPD (9.8 ± 6.4 min vs 8.4 ± 6.6 min, respectively; P = .31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy control participants., Interpretation: Contrary to our hypothesis, it was the healthy control participants, rather than the former smokers with and without COPD, who were negatively impacted by TRAP during exercise., Trial Registry: ClinicalTrials.gov; No.: NCT02236039; URL: www., Clinicaltrials: gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

This case report characterizes the physiological responses to incremental cycling and determines the effects of 12 wk of inspiratory muscle training (IMT) on respiratory muscle strength, exercise capacity, and dyspnea in a physically active 59-yr-old female, 4 years after a left-sided extrapleural pneumonectomy (EPP). On separate days, a symptom-limited incremental exercise test and a constant work rate (CWR) test at 75% of peak work rate (WR) were completed, followed by 12 wk of IMT and another CWR test. IMT consisted of two sessions of 30 repetitions twice daily for 5 days per week. Physiological and perceptual variables were measured throughout each exercise test. The participant had a total lung capacity that was 43% predicted post-EPP. A rapid and shallow breathing pattern was adopted throughout exercise, and the ratio of minute ventilation to carbon dioxide output was elevated for a given work rate. Oxygen uptake was 71% predicted and WR was 88% predicted. Following IMT, maximal inspiratory pressure improved by 36% (-27.1 cmH 2 O) and endurance time by 31 s, with no observable changes in any submaximal or peak cardiorespiratory variables during exercise. The intensity and unpleasantness of dyspnea increased by 2 and 3 Borg 0-10 units, respectively, at the highest equivalent submaximal exercise time achieved on both tests. Despite having undergone a significant reduction in lung volume post-EPP, the participant achieved a relatively normal peak incremental WR, which may reflect a high level of physical conditioning. This case report also demonstrates that IMT can effectively increase respiratory muscle strength several years following EPP. NEW & NOTEWORTHY Constraints on tidal volume expansion and the adoption of a rapid and shallow breathing pattern result in a ventilatory limitation and increased ventilatory inefficiency during exercise in a patient several years after extrapleural pneumonectomy (EPP). Inspiratory muscle training can effectively increase respiratory muscle strength after EPP.

Ventilatory efficiency can be evaluated using the relationship between minute ventilation ( V ' E ) and the rate of CO 2 production ( V ' CO 2 ). In accordance with the modified alveolar ventilation equation, this relationship is determined by changes in dead space volume ( V D ) and/or the arterial CO 2 tension ( P aCO 2 ) equilibrium point. In this review, we summarise the physiological factors that may account for normative ageing and pregnancy induced increases in V ' E / V ' CO 2 during exercise. Evidence suggests that age-related increases in V D and pregnancy-related decreases in the P aCO 2 equilibrium point are mechanistically linked to the increased V ' E / V ' CO 2 during exercise. Importantly, the resultant increase in V ' E / V ' CO 2 (ratio or slope), with normal ageing or pregnancy, remains below the critical threshold for prognostic indication in cardiopulmonary disease, is not associated with increased risk of adverse health outcomes, and does not affect the respiratory system's ability to fulfil its primary role of eliminating CO 2 and maintaining arterial oxygen saturation during exercise., Competing Interests: Conflict of interest: M.R. Schaeffer has nothing to disclose. Conflict of interest: J.A. Guenette has nothing to disclose. Conflict of interest: D. Jensen has nothing to disclose., (Copyright ©ERS 2021.)

Introduction: The Turbine™ is a nasal dilator marketed to athletes to increase airflow, which may serve to reduce dyspnea and improve exercise performance, presumably via reductions in the work of breathing (WOB). However, the unpublished data supporting these claims were collected in individuals at rest that were exclusively nasal breathing. These data are not indicative of how the device influences breathing during exercise at higher ventilations when a larger proportion of breathing is through the mouth. Accordingly, the purpose of this study was to empirically test the efficacy of the Turbine™ during exercise. We hypothesized that the Turbine™ would modestly reduce the WOB at rest and very low exercise intensities but would have no effect on the WOB at moderate to high exercise intensities., Methods: We conducted a randomized crossover study in young, healthy individuals (7M:1F; age = 27 ± 5 yr) with normal lung function. Each participant performed two incremental cycle exercise tests to exhaustion with the Turbine™ device or under a sham control condition. For the sham control condition, participants were told they were breathing a low-density gas to reduce the WOB, but they were actually breathing room air. The WOB was determined through the integration of ensemble averaged esophageal pressure-volume loops. Standard cardiorespiratory measures were recorded using a commercially available metabolic cart. Dyspnea was assessed throughout exercise using the 0-10 Borg scale., Results: Peak V˙O2 and work rate were not different between conditions (P = 0.70 and P = 0.35, respectively). In addition, there was no interaction or main effect of condition on dyspnea, ventilation, or WOB throughout the exercise (all P > 0.05)., Conclusion: These findings suggest that the Turbine™ does not reduce the WOB and has no effect on dyspnea or exercise capacity.

Purpose: (1) To determine whether healthy humans can distinguish between the intensity and unpleasantness of exertional dyspnoea; (2) to evaluate the reliability of qualitative dyspnoea descriptors during exercise; and (3) to assess the reliability of the Multidimensional Dyspnoea Profile (MDP) METHODS: Forty-four healthy participants (24M:20F, 25 ± 5 years) completed maximal incremental cycling tests on three visits. During visit 1, participants rated the intensity and unpleasantness of dyspnoea simultaneously throughout exercise using the modified 0-10 category-ratio Borg scale. On visits 2 and 3, participants rated either the intensity or unpleasantness of dyspnoea alone at the same measurement times as visit 1. On all visits, participants selected qualitative descriptors throughout all exercise intensities from a list of 4, selected relevant qualitative descriptors from a list of 15 at peak exercise, and completed the MDP., Results: Participants rated their dyspnoea intensity significantly higher for a given minute ventilation ([Formula: see text]) compared to dyspnoea unpleasantness (dyspnoea-[Formula: see text] slope: 0.08 ± 0.02 vs. 0.07 ± 0.03 Borg 0-10/L min -1 , p < 0.001) during visit 1. The onset of intensity ratings occurred at a significantly lower work rate compared to unpleasantness ratings measured on the same exercise test (52 ± 41 vs. 91 ± 53 watts, p < 0.001). Dyspnoea intensity and unpleasantness remained significantly different for a given ventilation even when measured independently on separate exercise tests (p < 0.05). There was good-to-excellent reliability (ICC > 0.60) for the use of qualitative dyspnoea descriptors and the MDP to measure dyspnoea at peak exercise., Conclusion: Exercise-induced dyspnoea in healthy adults can differ in the sensory and affective dimensions, and can be measured reliably using qualitative descriptors and the MDP.

Key Points: Diaphragm fatigue may increase the intensity (sensory dimension) and unpleasantness (affective dimension) of dyspnoea, which may partially explain why diaphragm fatigue negatively affects exercise performance. We hypothesized that diaphragm fatigue would negatively affect exercise performance via increases in both the intensity and unpleasantness of dyspnoea, and that the increase in dyspnoea would be mechanistically linked to an increase in diaphragmatic EMG (EMG di ), a surrogate measure of neural respiratory drive. Fatiguing the diaphragm prior to exercise reduced cycling performance and increased both the intensity and unpleasantness of dyspnoea. The change in submaximal dyspnoea unpleasantness was significantly correlated with the change in cycling performance. Pre-fatigue of the diaphragm did not increase EMG di during exercise and is therefore unrelated to the increase in either the sensory or affective dimension of exertional dyspnoea., Abstract: The purpose of this study was to examine the effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography (EMG di ) during cycling. Sixteen healthy males (age = 27 ± 5 yr, V ̇ O 2 max  = 45.8 ± 9.8 ml kg -1  min -1 ) completed two high-intensity, time-to-exhaustion cycling tests in randomized order: (i) inspiratory pressure threshold loading (PTL) prior to exercise to induce diaphragm fatigue (pre-DF) and (ii) no PTL (control). Diaphragm fatigue after PTL was confirmed via cervical magnetic stimulation of the phrenic nerves. Dyspnoea intensity and unpleasantness were measured throughout exercise with the 0-10 category-ratio Borg scale and following exercise using the Multidimensional Dyspnoea Profile (MDP). EMG di was continuously recorded via a multipair oesophageal electrode catheter. Time-to-exhaustion decreased with pre-DF vs. control (9.0 ± 5.5 vs. 10.7 ± 7.5 min, P = 0.023). Pre-DF increased dyspnoea intensity ratings by 0.6 ± 1.0 Borg 0-10 units at the highest equivalent submaximal exercise time (HESET) a participant could achieve in both conditions (P = 0.020). Dyspnoea unpleasantness ratings increased with pre-DF by 0.5 ± 1.0, 0.7 ± 1.2 and 0.9 ± 1.4 (all P < 0.05) Borg 0-10 units during the 2nd, 3rd and 4th minutes of exercise, respectively. There was a significant correlation between the change in breathing unpleasantness ratings at HESET and the change in time-to-exhaustion (r = 0.66, P = 0.006). The immediate perception domain, a combination of peak unpleasantness and specific dyspnoea descriptor intensity ratings, was the only component of the MDP that was significantly increased with pre-DF (4.3 ± 1.9 vs. 3.6 ± 1.8, P = 0.04). There were no significant differences in EMG di . In conclusion, diaphragm fatigue has negative effects on multiple domains of dyspnoea, which may partially explain why exercise performance decreases with it., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

Interstitial lung disease (ILD) is a heterogeneous group of conditions characterized by fibrosis and/or inflammation of the lung parenchyma. The pathogenesis of ILD consistently results in exertional dyspnea and exercise intolerance. Cardiopulmonary exercise testing (CPET) provides important information concerning the pathophysiology of ILD that can help inform patient management. Despite the purported benefits of CPET, its clinical utility in ILD is not well defined; however, there is a growing body of evidence that provides insight into the potential value of CPET in ILD. Characteristic responses to CPET in patients with ILD include exercise-induced arterial hypoxemia, an exaggerated ventilatory response, a rapid and shallow breathing pattern, critically low inspiratory reserve volume, and elevated sensations of dyspnea and leg discomfort. CPET is used in ILD to determine cause(s) of symptoms such as exertional dyspnea, evaluate functional capacity, inform exercise prescription, and determine the effects of pharmacological and non-pharmacological interventions on exercise capacity and exertional symptoms. However, preliminary evidence suggests that CPET in ILD may also provide valuable prognostic information and can be used to ascertain the degree of exercise-induced pulmonary hypertension. Despite these recent advances, additional research is required to confirm the utility of CPET in patients with ILD. This brief review outlines the clinical utility of CPET in patients with ILD. Typical patterns of response are described and practical issues concerning CPET interpretation in ILD are addressed. Additionally, important unanswered questions relating to the clinical utility of CPET in the assessment, prognostication, and management of patients with ILD are identified., (Copyright © 2020 Molgat-Seon, Schaeffer, Ryerson and Guenette.)

Purpose of Review: This article presents a summary of the evidence relating to supplemental oxygen use for the management of dyspnea in patients with interstitial lung disease (ILD)., Recent Findings: In contrast to the majority of the available literature, recent findings suggest that supplemental oxygen can significantly reduce exertional dyspnea in ILD. ILD patients' need for supplemental oxygen often surpasses the levels that the most commonly used oxygen delivery systems provide. More effective delivery of supplemental oxygen has the potential for greater relief of dyspnea. There is also evidence suggesting that indications for supplemental oxygen may differ in ILD compared with other chronic lung diseases., Summary: Large clinical trials are needed to determine if the reductions in dyspnea with supplemental oxygen observed in the laboratory setting can translate into meaningful benefits in everyday life for patients with ILD. More effective and practical oxygen delivery systems are needed. Future guidelines should consider including recommendations addressing the potential role of supplemental oxygen for mildly hypoxemic patients with ILD as well as recommendations specific to supplemental oxygen use for exercise training in ILD.

Unsatisfied inspiration is commonly reported during exercise by patients with interstitial lung disease (ILD). However, the physiological basis of perceived dyspnea quality in this population has not been evaluated. We examined the relationship between dyspnea quality and indices of ventilatory-mechanical limitations during exercise in patients with fibrotic ILD. Sixteen fibrotic ILD patients (12 male) with a median age of 64 years (range 49-81), FVC 71%-predicted (51-100), and DL CO 47%-predicted (27-77) performed incremental and constant work-rate cycle exercise tests to exhaustion. Ventilatory responses were recorded at rest, throughout exercise, and at peak exercise. Dyspnea quality was serially assessed using a 4-item list from which participants selected the phrase that best described their breathing compared to rest. Increased work/effort was the dominant descriptor of dyspnea throughout exercise, but with increased selection of unsatisfied inspiration following the inflection point of tidal volume relative to ventilation. Delaying or preventing ILD patients from reaching a critically reduced IRV may have implications for symptom management., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Interstitial lung disease (ILD) is a heterogeneous group of disorders that primarily affect the lung parenchyma. Patients with ILD have reduced lung volumes, impaired pulmonary gas exchange, and decreased cardiovascular function. These pathologic features of ILD become exacerbated during physical exertion, leading to exercise intolerance and abnormally high levels of exertional dyspnea. In this review, the authors summarize the primary pathophysiologic features of patients with ILD and their effect on the integrative response to exercise., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Recent increase in skin biopsies has been attributed to an epidemic of skin cancer. This may be avoidable, with potential savings., Objective: To determine whether the increase in skin biopsies is attributable to increasing frequency of biopsies associated with histology lacking pathological cutaneous disease. Pathological cutaneous disease was defined as (1) a malignancy, precancerous lesion, or lesion of uncertain behavior; or (2) disease symptomatic or associated with adverse quality of life impact., Patients and Methods: Retrospective cohort study, 2006 to 2013 of dermatology practice serving Florida and Ohio. Data were a consecutive sample of skin biopsies for diagnosis of dermatologic disease., Results: A total of 267,706 biopsies by an average of 52 providers per month from January 06 to December 13 were analyzed. Number of biopsies per visit increased 2% per year (RR: 1.02, CI: 1.00-1.04). Likelihood of biopsy associated with histology indicative of nonpathological cutaneous disease did not increase over time (OR: 0.99, CI: 0.95-1.03, p = .6302)., Conclusion: Rates of biopsies associated with nonpathological cutaneous disease is not increasing. Overall biopsy rates per visit have gradually increased; this seems attributable to greater rates of detection of pathological dermatologic disease.

Key Points: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea., Abstract: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (W b ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH 2 O L -1  s -1 to increase W b ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in W b (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, W b (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on W b (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Purpose: To characterize the effects of age, sex, and their interaction on inspiratory muscle activation patterns during exercise., Methods: Twenty younger (20-30 yr, n = 10 women) and 20 older (60-80 yr, n = 10 women) subjects performed an incremental cycle exercise test. Electromyography (EMG) of the scalene (EMGsca) and EMG of the sternocleidomastoid (EMGscm) muscles were measured using skin surface electrodes, whereas diaphragm EMG (EMGdi) and esophageal and transdiaphragmatic pressures were measured using an esophageal catheter. Electromyography data were transformed into root mean square with a 100-ms time constant. Esophageal and diaphragmatic pressure-time products were used as indices of total inspiratory muscle pressure production and diaphragmatic pressure production, respectively., Results: At absolute minute ventilations (V˙E), women and older subjects had greater EMGdi than men and younger subjects, respectively (all P < 0.05), but no differences were noted when V˙E was expressed in relative terms (all P > 0.05). Women had greater EMGsca activity than men at absolute and relative levels of V˙E (all P < 0.05). Older subjects had greater EMGsca than younger subjects when V˙E was expressed in relative (all P < 0.05) but not absolute terms (all P > 0.05). At absolute and relative levels of V˙E, women and older subjects had greater EMGscm than men and younger subjects, respectively (all P < 0.05). Women and older subjects had a greater esophageal and diaphragmatic pressure-time products at a V˙E of 70 L·min than men and younger subjects, respectively (both P < 0.05), but no differences were noted when V˙E was expressed in relative terms (all P > 0.05). No significant interactions between age and sex were noted (all P > 0.05)., Conclusions: Age and sex significantly affect inspiratory muscle activation patterns during exercise; however, the extent of the effects depends on whether comparisons are made at absolute or relative V˙E.

Purpose of Review: Breathlessness is a common and distressing symptom in patients with chronic obstructive pulmonary disease (COPD) and fibrotic interstitial lung disease (ILD), particularly during exercise. Effective medical management of exertional breathlessness in people living with COPD and fibrotic ILD is challenging for healthcare providers and requires an understanding of its mechanisms. Thus, in this brief review we summarize recent advances in our understanding of the pathophysiological mechanisms of exertional breathlessness in COPD and fibrotic ILD., Recent Findings: The collective results of recent physiological and clinical trials suggest that higher intensity ratings of exertional breathlessness in both COPD and fibrotic ILD compared to healthy control individuals is mechanistically linked to the awareness of greater neural respiratory drive (quantified using inspiratory muscle electromyography) needed to compensate for pathophysiological abnormalities in respiratory mechanics and pulmonary gas exchange efficiency., Summary: Any therapeutic intervention capable of decreasing intrinsic mechanical loading of the respiratory system and/or increasing pulmonary gas exchange efficiency has the potential to decrease the prevalence and severity of activity-related breathlessness and improve related clinical and patient-reported outcomes (e.g., exercise tolerance and health-related quality of life) by decreasing neural respiratory drive in people with COPD and fibrotic ILD.

We examined the effects of age, sex, and their interaction on mechanical ventilatory constraint and dyspnea during exercise in 22 older (age = 68 ± 1 yr; n = 12 women) and 22 younger (age = 25 ± 1 y, n = 11 women) subjects. During submaximal exercise, older subjects had higher end-inspiratory (EILV) and end-expiratory (EELV) lung volumes than younger subjects (both P < 0.05). During maximal exercise, older subjects had similar EILV ( P > 0.05) but higher EELV than younger subjects ( P < 0.05). No sex differences in EILV or EELV were observed. We noted that women had a higher work of breathing (W b ) for a given minute ventilation (V̇e) ≥65 l/min than men ( P < 0.05) and older subjects had a higher W b for a given V̇e ≥60 l/min ( P < 0.05). No sex or age differences in W b were present at any submaximal relative V̇e. At absolute exercise intensities, older women experienced expiratory flow limitation (EFL) more frequently than older men ( P < 0.05), and older subjects were more likely to experience EFL than younger subjects ( P < 0.05). At relative exercise intensities, women and older individuals experienced EFL more frequently than men and younger individuals, respectively (both P < 0.05). There were significant effects of age, sex, and their interaction on dyspnea intensity during exercise at absolute, but not relative, intensities (all P < 0.05). Across subjects, dyspnea at 80 W was significantly correlated with indexes of mechanical ventilatory constraint (all P < 0.05). Collectively, our findings suggest age and sex have significant impacts on W b , operating lung volumes, EFL, and dyspnea during exercise. Moreover, it appears that mechanical ventilatory constraint may partially explain sex differences in exertional dyspnea in older individuals. NEW & NOTEWORTHY We found that age and sex have a significant effect on mechanical ventilatory constraint and the perception of dyspnea during exercise. We also observed that the perception of exertional dyspnea is associated with indexes of mechanical ventilatory constraint. Collectively, our results suggest that the combined influences of age and biological sex on mechanical ventilatory constraint during exercise contributes, in part, to the increased perception of dyspnea during exercise in older women.

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., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

Although women experience greater ventilatory constraints and have a higher work of breathing during exercise, they are less susceptible to diaphragm fatigue compared to men. The mechanisms for diaphragmatic fatigue resistance in women is unknown but may be related to sex differences in respiratory muscle recruitment. Accordingly, the purpose of this study was to determine if electromyography (EMG) of the diaphragm (EMGdi) and extra-diaphragmatic inspiratory muscles differ between sexes during exercise. Forty subjects (21M:19F) completed a constant load cycling test at 85% of maximum work rate until exhaustion, while instrumented with an oesophageal electrode catheter to measure EMGdi and surface electrodes to measure EMG of the sternocleidomastoid (EMGscm) and scalene (EMGsca) muscles. No sex difference in EMGdi was observed at any measurement time. However, EMGscm and EMGsca were higher throughout all submaximal exercise times in women (p<0.01). These results suggest greater reliance on the extra-diaphragmatic inspiratory muscles in women relative to men, which may serve as a strategy to minimize diaphragmatic fatigue., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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 ( n = 12) performed 30 inspiratory efforts twice daily against a 30-repetition maximum intensity. The SC group ( n = 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 cmH 2 O, P < 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, P < 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. NEW & NOTEWORTHY 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., (Copyright © 2017 the American Physiological Society.)

Background: Intracutaneous lidocaine is used for anesthesia in dermatologic surgery for skin cancer excision and repair with exceedingly low incidence of reported adverse events., Objective: To measure (1) the quantity of lidocaine typically used for facial skin cancer excision and reconstruction; and (2) the frequency and character of associated adverse events., Methods: Survey study of dermatologic surgeons with longitudinal reporting. Reported practice during 10 business days: (1) mean volume of 1% lidocaine per skin cancer excision; (2) maximum per excision; (3) mean per reconstruction; and (4) maximum per reconstruction., Results: A total of 437 of 1,175 subjects contacted (37.2%) responded. Mean per excision was 3.44 mL (SD: 2.97), and reconstruction 11.70 mL (10.14). Maximum per excision was 6.54 mL (4.23), and reconstruction was 15.85 mL (10.39). No cases of lidocaine toxicity were reported, diagnosed, or treated. Incidence of adverse events possibly anesthesia related was >0.15%, with most (0.13%) being mild cases of dizziness, drowsiness, or lightheadedness from epinephrine tachycardia., Conclusion: Toxicity associated with local anesthesia other than lidocaine was not studied. Volumes of lidocaine in skin cancer excision and repair are modest and within safe limits. Lidocaine toxicity is exceedingly rare to entirely absent. For comparable indications, lidocaine is safer than conscious sedation or general anesthesia.

Background: Randomized controlled trials are the gold standard for comparing safety and effectiveness of surgical interventions. Reporting guidelines are available for conveying the results of such trials., Objective: To assess adherence to standard reporting guidelines among randomized controlled trials in dermatologic surgery., Materials and Methods: Systematic review. Data source was randomized controlled trials in the journal Dermatologic Surgery, per PubMed search, 1995 to 2014. Studies were appraised for the number of the 37 CONSORT 2010 Checklist criteria reported in each. Analysis included comparison of reporting across 4 consecutive periods., Results: Three hundred sixty-three studies were eligible. The mean number of items reported per study increased monotonically from 14.5 in 1995 to 1999 to 16.2 in 2002 to 2004, 17.7 in 2005 to 2009, and 18.0 in 2010 to 2014 (p < .0001). A limitation was that study procedures may have been performed without being reported., Conclusion: Completeness of reporting in randomized controlled trials in dermatologic surgery has improved significantly during the preceding 2 decades. Some elements are still reported at lower rates.

No studies of cystic fibrosis (CF) have systematically characterized the evolution of the qualitative dimensions of exertional dyspnea. Adults with CF (n = 25) and control individuals matched for sex, age, and body mass index (n = 25) underwent cardiopulmonary cycle exercise testing with a detailed evaluation of ventilatory and dyspnea responses. The qualitative dimensions of dyspnea were examined during each exercise stage by having subjects select phrases that best described their breathing (i.e., "work/effort," "unsatisfied inspiration," and "unsatisfied expiration"). Subjects also selected phrases that described the quality of their breathing at peak exercise using an established 15-item questionnaire, which was then clustered into different categories. Subjects with CF had greater ventilatory requirements, higher end-inspiratory and end-expiratory lung volumes (% total lung capacity), and an earlier inflection/plateau in tidal volume during exercise compared with control subjects. Increased work/effort was the dominant qualitative descriptor in both groups throughout exercise. Unsatisfied inspiration was selected by 48% of subjects with CF and 40% of controls at some point during exercise. The onset of unsatisfied inspiration in these subjects occurred at a significantly lower relative exercise intensity in subjects with CF vs. controls (72 ± 21 vs. 94 ± 11% Wmax, P < 0.01). Chest tightness was the only qualitative descriptor cluster that was selected more frequently by subjects with CF vs. controls (36 vs. 0%, respectively, P < 0.05) at peak exercise. Therapeutic interventions that reduce ventilatory requirements and improve lung volumes may delay the onset of distressing sensations such as unsatisfied inspiration and chest tightness in adults with CF., (Copyright © 2016 the American Physiological Society.)

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., (Copyright © 2015 the American Physiological Society.)

Background: There is a lack of studies objectively comparing the efficacy of topical antiperspirants in reducing sweat., Objective: To objectively and quantitatively compare the efficacy of two aluminum salt solutions for the reduction of induced sweating., Methods: A subject, rater, and statistician-blinded, randomized, controlled trial. Nineteen subjects were exposed to a standardized heat challenge for 3 h. Topical agent A (20% aluminum chloride hexahydrate) was randomized to either axilla, and topical agent B (1% aluminum acetate) assigned to the contralateral side. A sauna suit induced sweating during three 30-min heat intervals: (1) with no study agents (pre); (2) with both study agents, one on each side; and (3) after the agents were washed off (post). Sweat levels were measured by securing Whatman(®) filter paper to each axilla and measuring the paper weight after each heat interval. The difference in paper weight following each heat interval between Study Agent A and Study Agent B was measured by a gravimetric scale., Results: Topical agent A had a significantly greater effect at reducing axillary sweating than B (P = 0.0002)., Conclusion: In a sweating simulation, 20% aluminum chloride hexahydrate quantitatively and objectively appeared to reduce sweat more effectively than 1% aluminum acetate., (© 2015 Wiley Periodicals, Inc.)

In a randomized cross-over study of 15 healthy men aged 20-30 years, we compared physiological and perceptual responses during treadmill and cycle exercise test protocols matched for increments in work rate - the source of increased locomotor muscle metabolic and contractile demands. The rates of O2 consumption and CO2 production were higher at the peak of treadmill versus cycle testing (p ≤ 0.05). Nevertheless, work rate, minute ventilation, tidal volume (VT), breathing frequency (fR), inspiratory capacity (IC), inspiratory reserve volume (IRV), tidal esophageal (Pes,tidal) and transdiaphragmatic pressure swings (Pdi,tidal), peak expiratory gastric pressures (Pga,peak), the root mean square of the diaphragm electromyogram (EMGdi,rms) expressed as a percentage of maximum EMGdi,rms (EMGdi,rms%max), and dyspnea ratings were similar at the peak of treadmill versus cycle testing (p > 0.05). Ratings of leg discomfort were higher at the peak of cycle versus treadmill exercise (p ≤ 0.05), even though peak O2 consumption was lower during cycling. Oxygen consumption, CO2 production, minute ventilation, fR, Pes,tidal, Pdi,tidal and Pga,peak were higher (p ≤ 0.05), while VT, IC, IRV, EMGdi,rms%max, and ratings of dyspnea and leg discomfort were similar (p > 0.05) at all or most submaximal work rates during treadmill versus cycle exercise. Our findings highlight important differences (and similarities) in physiological and perceptual responses at maximal and submaximal work rates during incremental treadmill and cycle exercise testing protocols. The lack of effect of exercise test modality on peak work rate advocates for the use of this readily available parameter to optimize training intensity determination, regardless of exercise training mode.

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., (Copyright © 2015 the American Physiological Society.)

Importance: Transcutaneous injection through smaller hollow-bore needles may decrease patient discomfort, but current evidence is equivocal., Objective: To compare injection discomfort in patients treated with botulinum toxin type A with 30- and 32-gauge needles., Design, Setting, and Participants: Split-face, patient- and injector-blinded randomized clinical trial at the dermatology service of an urban university medical center. The 20 participants were women aged 25 to 70 years in good health and with moderate dynamic forehead and glabellar wrinkles. Data were collected from November 20, 2013, through January 16, 2014. Follow-up was complete on January 16, 2014. Data from the per-protocol population were analyzed from July 1 to July 31, 2014., Interventions: One side of each patient'sforehead received botulinum toxin type A in saline injected with a 32-gauge needle; the other side received the same treatment injected with a 30-gauge needle. In addition, each patient received randomized injections of saline only to both upper inner arms with the same types of needles., Main Outcomes and Measures: Primary outcomes included the patient-reported pain rating on a visual analog scale (VAS) on either side of the face and arms and the proportion of patients whose VAS ratings corresponded with more than moderate (ie, clinically significant) pain. The secondary outcome consisted of patient-reported information about the character of the pain at both sites using the expanded and revised version of the Short-Form McGill Pain Questionnaire., Results: All 20 patients completed the study. Overall, facial and arm injections were nominally but not significantly more painful with 30-gauge needles (mean [SD] VAS ratings for the face, 4.16 [2.55] vs 3.41 [2.31], P = .34; for the arm, 1.66 [2.07] vs 1.21 [1.65], P = .45). For facial injections, the likelihood of clinically significant pain (VAS rating, ≥5.4) was significantly greater with 30-gauge needles, which were associated with such pain in 8 patients (40%) compared with the 32-gauge needles, which were associated with such pain in 3 patients (15%) (odds ratio, 3.80 [95% CI, 1.05-13.78]; P = .04). No difference was found in the character of pain associated with needle bore (P > .05 for all comparisons)., Conclusions and Relevance: For facial injections of neurotoxin in saline, 30-gauge needles were associated with greater incidence of clinically significant pain than 32-gauge needles. For patients prone to experience clinically significant pain with facial injections, use of 32-gauge needles may minimize this discomfort., Trial Registration: clinicaltrials.gov Identifier: NCT01981174.

Ivacaftor is a novel oral pharmacologic agent that specifically targets the genetic defect of cystic fibrosis (CF) by augmenting chloride conductance through the CF transmembrane regulator (CFTR) protein. For individuals with CF and at least one copy of the G551D gating mutation, improvements in sweat chloride, nutritional parameters, lung function, respiratory symptoms, and exercise tolerance (i.e., 6-min walk distance) are attained within 2 weeks of initiating ivacaftor. However, there are no reports detailing the physiological and sensory implications of these improvements and their underlying mechanisms. We performed detailed cardiopulmonary exercise testing pre- and post-initiation of ivacaftor in a 27-year old male with CF (CFTR genotype F508del/G551D) and chronic airflow obstruction (FEV1/FVC=0.44). An improvement of FEV1 (by 16%) following ivacaftor was accompanied by clinically significant improvements in exercise capacity (by 14%) and exertional dyspnea (by up to 5 Borg scale units). These improvements were attributable, at least in part, to favorable alterations in the ventilatory response to exercise, including improvements in breathing patterns (e.g., increased tidal volume and reduced breathing frequency) and dynamic operating lung volumes (e.g., increased inspiratory reserve volume and inspiratory capacity) and decreases in dynamic mechanical ventilatory constraints., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We tested the hypothesis that neuromechanical uncoupling of the respiratory system forms the mechanistic basis of dyspnea during exercise in the setting of "abnormal" restrictive constraints on ventilation (VE). To this end, we examined the effect of chest wall strapping (CWS) sufficient to mimic a "mild" restrictive lung deficit on the interrelationships between VE, breathing pattern, dynamic operating lung volumes, esophageal electrode-balloon catheter-derived measures of the diaphragm electromyogram (EMGdi) and the transdiaphragmatic pressure time product (PTPdi), and sensory intensity and unpleasantness ratings of dyspnea during exercise. Twenty healthy men aged 25.7 ± 1.1 years (means ± SE) completed symptom-limited incremental cycle exercise tests under two randomized conditions: unrestricted control and CWS to reduce vital capacity (VC) by 21.6 ± 0.5%. Compared with control, exercise with CWS was associated with 1) an exaggerated EMGdi and PTPdi response; 2) no change in the relationship between EMGdi and each of tidal volume (expressed as a percentage of VC), inspiratory reserve volume, and PTPdi, thus indicating relative preservation of neuromechanical coupling; 3) increased sensory intensity and unpleasantness ratings of dyspnea; and 4) no change in the relationship between increasing EMGdi and each of the intensity and unpleasantness of dyspnea. In conclusion, the increased intensity and unpleasantness of dyspnea during exercise with CWS could not be readily explained by increased neuromechanical uncoupling but likely reflected the awareness of increased neural respiratory drive (EMGdi) needed to achieve any given VE during exercise in the setting of "abnormal" restrictive constraints on tidal volume expansion.

New Findings: What is the central question of this study? Does the combination of a higher neural respiratory drive and greater dynamic mechanical ventilatory constraints during exercise in healthy women versus men form the mechanistic basis of sex differences in activity-related dyspnoea? What is the main finding and its importance? Sex differences in activity-related dyspnoea in health primarily reflected the awareness of a higher neural respiratory drive needed to achieve any given ventilation during exercise in the setting of relatively greater dynamic mechanical ventilatory constraints in women. These findings may have implications for our understanding of the mechanisms of sex differences in exertional dyspnoea in variants of health (e.g. the elderly) and in patients with cardiorespiratory disease. The purpose of this study was to elucidate the physiological mechanisms of sex differences in exertional dyspnoea. We compared detailed measures of neural respiratory motor drive [diaphragmatic EMG (EMGdi) expressed as a percentage of maximal EMGdi (EMGdi%max)], breathing pattern, operating lung volumes, dynamic respiratory mechanics [tidal oesophageal (P(oes,tida)l%peak) and transdiaphragmatic pressure swings (P(di,tidal)%peak) expressed as a percentage of their respective peak values] and sensory intensity and unpleasantness ratings of dyspnoea during symptom-limited incremental cycle exercise in healthy young women (n = 25) and men (n = 25). The tidal volume to forced vital capacity ratio (V(T)%FVC), breathing frequency, EMGdi%max, P(oes,tidal)%peak, P(di,tidal)%peak and sensory intensity and unpleasantness ratings of dyspnoea were higher, while dynamic inspiratory capacity and inspiratory reserve volume were lower at a standardized absolute ventilation of 55 l min(-1) during submaximal exercise in women versus men (all P < 0.05). In contrast, sex had no demonstrable effect on the inter-relationships between exercise-induced increases in V(T)%FVC, EMGdi%max and sensory intensity and unpleasantness ratings of dyspnoea. The results of this study suggest that sex differences in the intensity and unpleasantness of exertional dyspnoea in health are likely to reflect the awareness of a relatively higher neural respiratory motor drive (or EMGdi%max) needed to achieve any given ventilation during exercise in the setting of relatively greater dynamic mechanical constraints on V(T) expansion in women.