The effect of proportional assist ventilation on the electrical activity of the human diaphragm during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease. ABSTRACT: We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMGdi ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure-time product of the diaphragm (PTPdi ) was lower across PAV unloading conditions (P < 0.05). The EMGdi was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMGdi with PAV unloading were 14, 22 and 39%, respectively. The change in EMGdi for a given lowering of PTPdi with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease.

Impaired Ventilatory Efficiency, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study.

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [[Formula: see text]e/[Formula: see text]co2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD). Objectives: To determine 1) the association between high [Formula: see text]e/[Formula: see text]co2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort. Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing, and chest computed tomography. Impaired exercise ventilatory efficiency was defined by a nadir [Formula: see text]e/[Formula: see text]co2 above the upper limit of normal (ULN), using population-based normative values. Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD, and 200 with GOLD 2-4 COPD. Participants with [Formula: see text]e/[Formula: see text]co2 above the ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale ⩾ 2; odds ratio [5-95% confidence intervals], 1.77 [1.31 to 2.39]) and abnormally low peak [Formula: see text]o2 ([Formula: see text]o2peak below the lower limit of normal; odds ratio, 4.58 [3.06 to 6.86]). The Kco had a stronger correlation with nadir [Formula: see text]e/[Formula: see text]co2 (r = -0.38; P < 0.001) than other relevant lung function and computed tomography metrics. The prevalence of [Formula: see text]e/[Formula: see text]co2 above the ULN was 24% in COPD (similar in GOLD 1 and 2 through 4), which was greater than in never-smokers (13%) and ever-smokers (12%). Conclusions: [Formula: see text]e/[Formula: see text]co2 above the ULN was associated with greater dyspnea and low [Formula: see text]o2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.

Inflammation associated with lung function abnormalities in COVID-19 survivors.

BACKGROUND: Activation of inflammatory pathways promotes organ dysfunction in COVID-19. Currently, there are reports describing lung function abnormalities in COVID-19 survivors; however, the biological mechanisms remain unknown. The aim of this study was to analyze the association between serum biomarkers collected during and following hospitalization and pulmonary function in COVID-19 survivors. METHODS: Patients recovering from severe COVID-19 were prospectively evaluated. Serum biomarkers were analyzed from admission to hospital, peak during hospitalization, and at the time of discharge. Pulmonary function was measured approximately 6 weeks after discharge. RESULTS: 100 patients (63% male) were included (age 48 years, SD ± 14) with 85% having at least one comorbidity. Patients with a restrictive spirometry pattern (n = 46) had greater inflammatory biomarkers compared to those with normal spirometry (n = 54) including peak Neutrophil-to-Lymphocyte ratio (NLR) value [9.3 (10.1) vs. 6.5 (6.6), median (IQR), p = 0.027] and NLR at hospital discharge [4.6 (2.9) vs. 3.2 (2.9) p = 0.005] and baseline C-reactive protein value [164.0 (147.0) vs. 106.5 (139.0) mg/dL, p = 0.083). Patients with an abnormal diffusing capacity (n = 35) had increased peak NLR [8.9 (5.9) vs. 5.6 (5.7) mg/L, p = 0.029]; baseline NLR [10.0 (19.0) vs. 4.0 (3.0) pg/ml, p = 0.002] and peak Troponin-T [10.0 (20.0) vs. 5.0 (5.0) pg/ml, p = 0.011] compared to patients with normal diffusing capacity (n = 42). Multivariable linear regression analysis identified predictors of restrictive spirometry and low diffusing capacity, but only accounted for a low degree of variance in pulmonary function outcome. CONCLUSION: Overexpression of inflammatory biomarkers is associated with subsequent lung function abnormalities in patients recovered from severe COVID-19.

Incorporating remote patient monitoring in virtual pulmonary rehabilitation programs.

Most pulmonary rehabilitation (PR) programs have had to adapt due to the COVID-19 pandemic and associated restrictions. Current alternative home-based programs have limitations and require modification. In this paper, we outline a novel method to monitor home-based PR programs, which has the potential to improve PR safety and efficacy. This new method is based on a remote patient monitoring (RPM) system with connected smart devices that enables the Respiratory Therapist (RT) to have real-time access to patient data including heart rate and peripheral oxygen saturation during exercise. The RPM system also monitors daily physical activity, sedentary time, sleep quality, rescue inhaler use, and maintenance inhaler adherence, among other variables, which has the added advantage of predicting patterns consistent with symptoms that may require medical intervention. To increase privacy, data are anonymized at all levels and only the RT has access to patient information. RPM systems have the potential to give practitioners a holistic view of the participants' health status to better evaluate them during the entire PR program and to improve self-management. As this is not a formal research study, we cannot make definitive conclusions about the efficacy of the system, and further research is needed to examine safety and to compare our approach to other ways of conducting PR.

The effect of diaphragm fatigue on the multidimensional components of dyspnoea and diaphragm electromyography during exercise in healthy males.

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 (EMGdi ), 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 EMGdi 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 (EMGdi ) during cycling. Sixteen healthy males (age = 27 ± 5 yr, V̇O2max  = 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). EMGdi 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 EMGdi . In conclusion, diaphragm fatigue has negative effects on multiple domains of dyspnoea, which may partially explain why exercise performance decreases with it.

Short-term effects of Lumacaftor/Ivacaftor (Orkambi™) on exertional symptoms, exercise performance, and ventilatory responses in adults with cystic fibrosis.

RATIONALE: Lumacaftor/ivacaftor (LUM/IVA) modestly improves lung function following 1 month of treatment but it is unknown if this translates into improvements in exercise endurance and exertional symptoms. METHODS: Adult CF participants completed a symptom-limited constant load cycling test with simultaneous assessments of dyspnea and leg discomfort ratings pre- and 1 month post-initiation of LUM/IVA. RESULTS: Endurance time, exertional dyspnea and leg discomfort ratings at submaximal exercise did not change significantly. There was a significant inverse correlation between changes in leg discomfort and endurance time (r = - 0.88; p = 0.009) following 1-month of LUM/IVA. CONCLUSIONS: Overall, 1-month of LUM/IVA did not increase endurance time or modify exertional dyspnea or leg discomfort ratings. However, individuals who experienced a reduction in leg discomfort following LUM/IVA had an improvement in endurance time. Future studies with a larger sample size are needed to verify these findings and to assess the long-term effects of LUM/IVA on exercise outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02821130. Registered July 1, 2016.

Near-infrared spectroscopy measures of sternocleidomastoid blood flow during exercise and hyperpnoea.

NEW FINDINGS: What is the central question of this study? How does sternocleidomastoid blood flow change in response to increasing ventilation and whole-body exercise intensity? What is the main finding and its importance? Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole-body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid. ABSTRACT: Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood-flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near-infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole-body exercise.

A multidimensional assessment of dyspnoea in healthy adults during exercise.

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.

Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

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 (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; 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 Wb (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, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (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.

Ventilatory and sensory responses to incremental exercise in adults with a Fontan circulation.

Many adults with single-ventricle congenital heart disease who have undergone a Fontan procedure have abnormal pulmonary function resembling restrictive lung disease. Whether this contributes to ventilatory limitations and increased dyspnea has not been comprehensively studied. We recruited 17 Fontan participants and 17 healthy age- and sex-matched sedentary controls. All participants underwent complete pulmonary function testing followed by a symptom-limited incremental cardiopulmonary cycle exercise test with detailed assessments of dyspnea and operating lung volumes. Fontan participants and controls were well matched for age, sex, body mass index, height, and self-reported physical activity levels (all P > 0.05), although Fontan participants had markedly reduced cardiorespiratory fitness and peak work rates ( P < 0.001). Fontan participants had lower values for most pulmonary function measurements relative to controls with 65% of Fontan participants showing evidence of a restrictive ventilatory defect. Relative to controls, Fontan participants had significantly higher breathing frequency, end-inspiratory lung volume (% total lung capacity), ventilatory inefficiency (high ventilatory equivalent for CO2), and dyspnea intensity ratings at standardized absolute submaximal work rates. There were no between-group differences in qualitative descriptors of dyspnea. The restrictive ventilatory defect in Fontan participants likely contributes to their increased breathing frequency and end-inspiratory lung volume during exercise. This abnormal ventilatory response coupled with greater ventilatory inefficiency may explain the increased dyspnea intensity ratings in those with a Fontan circulation. Interventions that enhance the ventilatory response to exercise in Fontan patients may help optimize exercise rehabilitation interventions, resulting in improved exercise tolerance and exertional symptoms. NEW & NOTEWORTHY This is the first study to comprehensively characterize both ventilatory and sensory responses to exercise in adults that have undergone the Fontan procedure. The majority of Fontan participants had a restrictive ventilatory defect. Compared with well-matched controls, Fontan participants had increased breathing frequency, end-inspiratory lung volume, and ventilatory inefficiency. These abnormal ventilatory responses likely form the mechanistic basis for the increased dyspnea intensity ratings observed in our Fontan participants during exercise.

ERS statement on respiratory muscle testing at rest and during exercise.

Assessing respiratory mechanics and muscle function is critical for both clinical practice and research purposes. Several methodological developments over the past two decades have enhanced our understanding of respiratory muscle function and responses to interventions across the spectrum of health and disease. They are especially useful in diagnosing, phenotyping and assessing treatment efficacy in patients with respiratory symptoms and neuromuscular diseases. Considerable research has been undertaken over the past 17 years, since the publication of the previous American Thoracic Society (ATS)/European Respiratory Society (ERS) statement on respiratory muscle testing in 2002. Key advances have been made in the field of mechanics of breathing, respiratory muscle neurophysiology (electromyography, electroencephalography and transcranial magnetic stimulation) and on respiratory muscle imaging (ultrasound, optoelectronic plethysmography and structured light plethysmography). Accordingly, this ERS task force reviewed the field of respiratory muscle testing in health and disease, with particular reference to data obtained since the previous ATS/ERS statement. It summarises the most recent scientific and methodological developments regarding respiratory mechanics and respiratory muscle assessment by addressing the validity, precision, reproducibility, prognostic value and responsiveness to interventions of various methods. A particular emphasis is placed on assessment during exercise, which is a useful condition to stress the respiratory system.

Analysis of maximal expiratory flow-volume curves in adult survivors of preterm birth.

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE (n = 19), BPD (n = 25), and CON (n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD (P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20-30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

Modelling the effects of age and sex on the resistive and viscoelastic components of the work of breathing during exercise.

NEW FINDINGS: What is the central question of this study? What is the effect of age and sex on the resistive and viscoelastic components of work of breathing (Wb ) during exercise? What is the main finding and its importance? The resistive and viscoelastic components of Wb were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of Wb was higher in females than in males, regardless of age. These findings contribute to improving our understanding of the effects of ageing and sex on the mechanical ventilatory response to exercise. ABSTRACT: Healthy ageing and biological sex each affect the work of breathing (Wb ) for a given minute ventilation ( V̇E ). Age-related structural changes to the respiratory system lead to an increase in both the resistive and viscoelastic components of Wb ; however, it is unclear whether healthy ageing differentially alters the mechanics of breathing in males and females. We analysed data from 22 older (60-80 years, n = 12 females) and 22 younger (20-30 years, n = 11 females) males and females that underwent an incremental cycle exercise test to exhaustion. V̇E and Wb were assessed at rest and throughout exercise. Wb - V̇E data for each participant were fitted to a non-linear equation (i.e. Wb  = a V̇E3 + b V̇E2 ) that partitions Wb into resistive (i.e. a V̇E3 ) and viscoelastic (i.e. b V̇E2 ) components. We then modelled the effects of healthy ageing and biological sex on each component of Wb . Overall, the model fit was excellent (r2 : 0.99 ± 0.01). There was a significant main effect of age and sex on the resistive component of Wb (both P < 0.05), and a significant main effect of age (P < 0.001), but not sex (P = 0.309), on the viscoelastic component of Wb . No significant interactions between age and sex on a V̇E3 or b V̇E2 were noted (both P > 0.05). Our findings indicate that during exercise: (i) the higher total Wb in females relative to males is due to a higher resistive, but not viscoelastic, component of Wb , and (ii) regardless of sex, the higher Wb in older adults relative to younger adults is due to higher resistive and viscoelastic components of Wb .

Impact of Psychological Deficits and Pain on Physical Activity of Patients with Interstitial Lung Disease.

PURPOSE: The impact of psychological deficits and pain on physical activity has not been adequately studied in patients with fibrotic interstitial lung disease (ILD). We aimed to determine the association of depression, anxiety, sleep quality, and pain with physical activity in fibrotic ILD. METHODS: Waist ActiGraph activity monitors were worn for seven consecutive days to track step counts and moderate-to-vigorous physical activity (MVPA) minutes at baseline and 6-month follow-up. Psychological deficits and pain were assessed using the Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Quality Index, and the Brief Pain Inventory. Multivariable linear regression was used to determine if each deficit independently predicted physical activity when adjusted for potential confounders. RESULTS: A total of 111 patients were recruited, with 91 of these patients completing the 6-month follow-up. Median step count and MVPA minutes were 3853 steps/day (interquartile range 2236-6805) and 87 (17-225) min/week at baseline, respectively, with no significant changes at follow-up. Borderline or abnormal depression and anxiety scores were present in 19% and 22% of patients, respectively. Poor sleep quality and moderate-to-severe pain were present in 61% and 9% of patients. Higher depression scores were associated with fewer baseline and follow-up step counts and lower MVPA minutes at follow-up on unadjusted analysis; higher pain severity scores were associated with fewer baseline step count. Pain severity remained an independent predictor of reduced step count after adjusting for patient's age, smoking status, ILD severity, and weather variables. CONCLUSIONS: Pain severity may be a potentially modifiable determinant of physical activity in patients with fibrotic ILD.

Sex differences in diaphragmatic fatigue: the cardiovascular response to inspiratory resistance.

KEY POINTS: Diaphragmatic fatigue (DF) elicits a sympathetically mediated metaboreflex resulting in increased heart rate, blood pressure and limb vascular resistance. Women may be more resistant to DF compared to men, and therefore it was hypothesised that women would experience an attenuated inspiratory muscle metaboreflex during inspiratory pressure-threshold loading (PTL) performed to task failure. At the time of PTL task failure, the severity of DF was not different between sexes; however, inspiratory muscle endurance time was significantly longer in women than in men. For a given cumulative diaphragmatic force output, the severity of DF was less in women than in men. Women exhibited a blunted cardiovascular response to inspiratory resistance (i.e. metaboreflex) that may have implications for exercise tolerance. ABSTRACT: Diaphragmatic fatigue (DF) elicits reflexive increases in sympathetic vasomotor outflow (i.e. metaboreflex). There is some evidence suggesting women may be more resistant to DF compared to men, and therefore may experience an attenuated inspiratory muscle metaboreflex. To this end, we sought to examine the cardiovascular response to inspiratory resistance in healthy young men (n = 9, age = 24 ± 3 years) and women (n = 9, age = 24 ± 3 years). Subjects performed isocapnic inspiratory pressure-threshold loading (PTL, 60% maximal inspiratory mouth pressure) to task failure. Diaphragmatic fatigue was assessed by measuring transdiaphragmatic twitch pressure (Pdi,tw ) using cervical magnetic stimulation. Heart rate (HR) and mean arterial pressure (MAP) were measured beat-by-beat throughout PTL via photoplethysmography, and low-frequency systolic pressure (LFSBP ; a surrogate for sympathetic vasomotor tone) calculated from arterial waveforms using power spectrum analysis. At PTL task failure, the degree of DF was similar between sexes (∼23% reduction in Pdi,tw ; P = 0.33). However, time to task failure was significantly longer in women than in men (27 ± 11 vs. 16 ± 11 min, respectively; P = 0.02). Women exhibited less of an increase in HR (13 ± 8 vs. 19 ± 12 bpm; P = 0.02) and MAP (10 ± 8 vs. 14 ± 9 mmHg; P = 0.01), and significantly lower LFSBP (23 ± 11 vs. 34 ± 8 mmHg2 ; P = 0.04) during PTL compared to men. An attenuation of the inspiratory muscle metaboreflex may influence limb and respiratory muscle haemodynamics with implications for exercise performance.

Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease.

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.

Exertional hypoxemia is more severe in fibrotic interstitial lung disease than in COPD.

BACKGROUND AND OBJECTIVE: Despite its clinical and prognostic significance, few studies have evaluated the severity of exertional oxygen desaturation in fibrotic interstitial lung disease (ILD). Our objectives were to identify clinical and physiological variables that predict the extent of exertional oxygen desaturation in fibrotic ILD and to quantify the severity of desaturation compared to chronic obstructive pulmonary disease (COPD). METHODS: This retrospective study compared the results of 6-min walk test (6MWT) performed while breathing room air in fibrotic ILD patients and COPD patients eligible for pulmonary rehabilitation. Outcomes included the oxygen saturation (SpO2 ) nadir and the change in SpO2 from rest during a 6MWT. Predictor variables were identified on unadjusted analysis, followed by multivariate analysis to identify independent predictors of desaturation. RESULTS: The study included 134 patients with fibrotic ILD and 274 patients with COPD. The ILD and COPD cohorts had similar age, sex, frequency of major comorbidities, walk distance, baseline SpO2 and baseline Borg dyspnoea scores. DLCO was the strongest predictor of desaturation in both cohorts. Compared to patients with COPD, ILD patients had significantly lower SpO2 nadir values (88.1 ± 6.4 vs 91.0 ± 4.6) and greater decrease in SpO2 from baseline (7.4 ± 5.2 vs 4.5 ± 3.7) after adjusting for demographic features and pulmonary physiology (P < 0.0005), with greater between-group differences at lower DLCO values. CONCLUSION: Patients with fibrotic ILD have greater oxygen desaturation during 6MWT compared to patients with COPD when adjusting for demographic features and pulmonary physiology. These findings suggest the need for disease-specific studies to evaluate the potential utility of ambulatory oxygen in fibrotic ILD.

A Comparison of Pain, Fatigue, Dyspnea and their Impact on Quality of Life in Pulmonary Rehabilitation Participants with Chronic Obstructive Pulmonary Disease.

In addition to dyspnea and fatigue, pain is a prevalent symptom in chronic obstructive pulmonary disease (COPD). Understanding the relative prevalence, magnitude, and interference with aspects of daily living of these symptoms can improve COPD management. Therefore, the purposes of this study were to: (1) compare the prevalence and magnitude of dyspnea, fatigue, and pain and how each limits aspects of daily living; (2) determine the association between pain and the other two symptoms; and (3) assess the impact of these symptoms on quality of life in COPD. Participants were recruited from pulmonary rehabilitation programs. Pain, dyspnea, and fatigue were measured using the Brief Pain Inventory (BPI), Brief Fatigue Inventory (BFI), and Dyspnea Inventory (DI), respectively. Quality of life was measured using the Clinical COPD Questionnaire (CCQ). The prevalence of dyspnea, fatigue, and pain were 93%, 77%, and 74%, respectively. Individuals with COPD reported similar severity scores of the three symptoms. Dyspnea interfered with general activity more than pain (F1.7,79.9 = 3.1, p < 0.05), whilst pain interfered with mood (F1.8, 82.7 = 3.6, p < 0.05) and sleep (F1,46 = 7.4, p < 0.01) more than dyspnea and fatigue. These three symptoms were moderately-to-highly correlated with each other (ρ = 0.49-0.78, p < 0.01) and all individually impacted quality of life. In summary, pain is a common symptom in addition to dyspnea and fatigue in COPD; all three interfere similarly among aspects of daily living with some exceptions. Accordingly, management of COPD should include a multifaceted approach that addresses pain as well as dyspnea and fatigue.

Comorbidities That Cause Pain and the Contributors to Pain in Individuals With Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To determine comorbidities that cause pain and the potential contributors to pain in individuals with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective cross-sectional survey study. SETTING: Pulmonary rehabilitation programs of 6 centers. PARTICIPANTS: A convenience sample of individuals with COPD (N=137) who attended pulmonary rehabilitation programs. In total, 100 (73%) returned the survey packages. Of those responders, 96 participants (70%) were included in the analyses. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pain was measured using the Brief Pain Inventory. The questionnaire used to obtain information about health conditions that might contribute to pain and a medication record asked, in lay terms, about comorbidities that cause pain. The health conditions that cause pain were then validated by health professionals. Demographics, fatigue, dyspnea, quality of life, and self-efficacy were also measured using questionnaires. RESULTS: Pain was reported in 71% (68/96) of participants. Low back pain was the most common location (41%). Arthritis (75%), back problems (47%), and muscle cramps (46%) were the most common comorbidities that caused pain. Lower self-efficacy, and renting rather than home ownership increased the likelihood of pain (P<.05). Pain severity and Brief Fatigue Inventory scores contributed to pain interference scores (P<.05). CONCLUSIONS: Pain was highly prevalent in pulmonary rehabilitation program participants with COPD. The most common causes of pain were musculoskeletal conditions. Pain severity and higher levels of fatigue contributed to how pain interfered with daily aspects of living. The assessment and management of pain need to be addressed within the overall care of individuals with COPD.