Borg Dyspnea Scale Research Articles

Validity and reliability of the Multidimensional Dyspnoea Profile in older adults.

Breathlessness is a common and distressing symptom in older adults and an independent predictor of adverse outcomes and yet its multidimensional assessment has not been validated in older adults. We apply and validate the Multidimensional Dyspnoea Profile (MDP) in a sample of adults 75 years and older in Belgium.Breathlessness was rated with the MDP, the modified Borg Dyspnoea Scale (mBDS), the Short Physical Performance Battery (SPPB, a numerical rating scale for intensity and unpleasantness both before and after exertion), as well as with the Medical Research Council (MRC) Dyspnoea Scale. The Hospital Anxiety and Depression Scale (HADS) assessed the affective status. Factor structure was analysed with exploratory principal components analysis, internal consistency with Cronbach's alpha and concurrent validity with Spearman's correlation coefficients with other breathlessness scales, HADS and SPPB scores.In 96 participants (mean age 85 years; 34% men) who rated breathlessness at both assessment points, exploratory principal components analysis identified two components: Immediate Perception (IP) and Emotional Reaction (ER), explaining most of the MDP item variance (65.37% before and 71.32% after exertion). Internal consistency was moderate to high for MDP-IP (Cronbach's alpha = 0.86 before and 0.89 after exertion) and MDP-ER (Cronbach's alpha = 0.89 before and 0.91 after exertion). The correlation patterns of MDP-IP and MDP-ER with other tests confirmed concurrent validity.The domain structure, reliability and concurrent validity of MDP for breathlessness before and after exertion were confirmed in a sample of adults 75 years and older, supporting its use and further research for the multidimensional profiling of breathlessness in older adults.

Physical Therapist Management of COVID-19 in the Intensive Care Unit: The West China Hospital Experience.

ObjectiveCoronavirus disease 2019 (COVID-19) has dominated the attention of health care systems globally since January 2020. Various health disciplines including physical therapists are still exploring the best way to manage this new disease. The role and involvement of physical therapists in the management of COVID-19 are not yet well defined and are limited in many hospitals. This article reports a physical therapy service specially commissioned by the Health Commission of Sichuan Province to manage COVID-19 during patients’ stay in the intensive care unit (ICU) at the Public Health Clinical Center of Chengdu in China.MethodsPatients diagnosed with COVID-19 were classified into 4 categories under a directive from the National Health Commission of the People’s Republic of China. Patients in the “severe” and “critical” categories were admitted to the ICU irrespective whether mechanical ventilation was required. Between January 31, 2020, and March 8, 2020, a cohort of 16 patients was admitted to the ICU at the Public Health Clinical Center of Chengdu. The median (minimum to maximum) hospital and ICU stays for these patients were 27 (11–46) and 15 (6–38) days, respectively. Medical management included antiviral, immunoregulation and supportive treatment of associated comorbidities. Physical therapist interventions included body positioning, airway clearance techniques, oscillatory positive end-expiratory pressure, inspiratory muscle training, and mobility exercises. All patients had at least 1 comorbidity. Three of the 16 patients required mechanical ventilation and were excluded for outcome measures that required understanding of verbal instructions. In the remaining 13 patients, respiratory outcomes—including the Borg Dyspnea Scale, peak expiratory flow rate, Pao2/Fio2 ratio, maximal inspiratory pressure, strength outcomes, Medical Research Council Sum Score, and functional outcomes (including the Physical Function in Intensive Care Test score, De Morton Mobility Index, and Modified Barthel Index)—were measured on the first day the patient received the physical therapist intervention and at discharge.ResultsAt discharge from the ICU, while most outcome measures were near normal for the majority of the patients, 61% and 31% of these patients had peak expiratory flow rate and maximal inspiratory pressure below 80% of the predicted value and 46% had De Morton Mobility Index values below the normative value.ConclusionThe respiratory and physical functions of some patients remained poor at ICU discharge, suggesting that long-term rehabilitation may be required for these patients.ImpactOur experience in the management of patients with COVID-19 has revealed that physical therapist intervention is safe and appears to be associated with an improvement in respiratory and physical function in patients with COVID-19 in the ICU.

Safety and Efficacy of Early Ambulation on an Alternative Oxygen Delivery Device for Patients Receiving Bedside Heated Humidified High-Flow Nasal Cannula Therapy

Purpose: Patients in the intensive care unit (ICU) receiving heated humidified high-flow nasal cannula (HHFNC) therapy for acute respiratory failure have limited ambulation distance due to restrictions in supplying HHFNC away from bedside. This study investigated the safety and efficacy of transitioning patients requiring HHFNC to a portable high-flow oxygen (HFO2) device for ambulation. Methods: Twenty-three patients with acute respiratory failure participated in this prospective longitudinal observational study. Three diagnostic groups were formed (cardiac n = 8; pulmonary n = 11; and other n = 4). Initial aerobic tolerance was established through bedside marching on HHFNC, then participants transitioned to HFO2 for ambulation. During each phase, vital signs were monitored. Results: No differences were found among diagnostic groups or sexes during ambulation for blood pressure, heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2), or the Borg dyspnea scale (BDS) (all P > .05). Outcomes during marching and ambulation differed from outcomes at rest and during recovery for HR, RR, SpO2, and BDS (all P < .001). Transitory adverse events during ambulation included anxiety (n = 2), hypotension (n = 1), and arrhythmia (n = 2). Conclusions: Results indicate it is safe and efficacious for patients in the ICU with acute respiratory failure requiring HHFNC to ambulate on HFO2 under the supervision of a physical therapist.

Effects of perioperative respiratory rehabilitation in lung cancer resection: a pilot study

The aim of this study is to evaluate the impact of short term Preoperative Respiratory Rehabilitation (PRR) on thechanges of respiratory functions and clinical conditions in patients with malignant lung cancer lesion and reducedrespiratory functions, with high risk to develop postoperative pulmonary complications (PPCs). A total of 15 patientswere treated with PRR protocol. The rehabilitation programme was concluded by all patients. They showed a statistically significant improvement of lung functionality Forced Vital Capacity (FVC) (p=0,004), Forced Expiration Valuein the first second (FEV1) (p<0,001) and walking distance (p<0,001). In addition, there was a significant enhancement of Partial Oxygen Saturation (SpO2) (p=0,002), Hart Rate (HR) (p=0,002) and Borg Dyspnoea Scale values(p=0,003) indicate a better cardiorespiratory functionality.In conclusion a short feasible PRR is suitable in patients’ candidate to thoracic surgery.

Effects of perioperative respiratory rehabilitation in lung cancer resection: a pilot study

The aim of this study is to evaluate the impact of short term Preoperative Respiratory Rehabili-tation (PRR) on the changes of respiratory functions and clinical conditions in patients with ma-lignant lung cancer lesion and reduced respiratory functions, with high risk to develop postop-erative pulmonary complications (PPCs). A total of 15 patients were treated with PRR protocol. The rehabilitation programme was concluded by all patients. They showed a statistically signifi-cant improvement of lung functionality Forced Vital Capacity (FVC) (p=0,004), Forced Expira-tion Value in the first second (FEV1) (p<0,001) and walking distance (p<0,001). In addition, there was a significant enhancement of Partial Oxygen Saturation (SpO2) (p=0,002), Hart Rate (HR) (p=0,002) and Borg Dyspnoea Scale values (p=0,003) indicate a better cardiorespiratory functionality. In conclusion a short feasible PRR is suitable in patients’ candidate to thoracic surgery.

Dyspnea perception and neurological symptoms in non-severe COVID-19 patients.

IntroductionThe relationship between dyspnea and COVID-19 is unknown. In COVID-19 patients, the higher prevalence of neurological symptoms and the lack of dyspnea may suggest common underlying pathogenetic mechanisms. The aim of this preliminary study is to address whether there is a lack of dyspnea in COVID-19 patients and if there is a relationship between neurological symptoms and the perception of dyspnea.MethodsA structured interview regarding the occurrence of subjective neurological symptoms was performed and coupled with a questionnaire about the intensity and qualities of dyspnea. Respiratory rate (RR) and an arterial blood gas on room air were concurrently evaluated.ResultsTwenty-two patients (age 68.4 ± 13.9 years, 13 males and 9 females) were included and divided into two groups according to the Borg dyspnea scale: dyspneic patients BU ≥ 1(DYSP) and non-dyspneic patients BU < 1 (NDYSP). The prevalence of dyspnea overall was 31.8%. The prevalence of neurological symptoms, dyspnea descriptors, RR, pH, PaCO2, PaO2, or lactate was similar between groups.ConclusionThis study confirms that the prevalence of dyspnea is low in non-severe COVID-19 patients, but contrary to our hypothesis of a relationship between shortness of breath and neurological symptoms, we have not been able to find any evidence of an impairment in dyspnea perception, either in the DYSP or NDYSP group.

Which are the factors influencing NIV adaptation and tolerance in ALS patients?

Amyotrophic lateral sclerosis (ALS) is a multisystemic disease compromising both the neuromuscular system and the cognitive status. Non-invasive ventilation (NIV) has been shown to improve survival and quality of life in ALS patients with respiratory failure, but scanty literature investigated which are the predictors of NIV tolerance. The aim of this study was to evaluate the impact of functional, cognitive, neurobehavioral, and respiratory status on NIV compliance and tolerance in patients with ALS. We retrospectively evaluated clinical data of ALS patients who consecutively underwent a NIV trial during hospitalization. Cognitive and neurobehavioral assessments have been performed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Hospital Anxiety and Depression Scale (HADS), the Frontal Assessment Battery (FAB), the Raven's 47 Colored Progressive Matrices (PM47), and the Neurobehavioral Rating Scale Revised (NRSR). Seventy-two patients (mean age ± SD; 63.9 ± 10.6 years) were included. Patients adapted were 63/72 (87.5%). The average time of adaptation was 7.82 ± 5.27 days. The time required to reach a satisfying NIV adaptation was significantly related to the presence of sialorrhea (p = 0.02), respiratory status (Borg Dyspnoea Scale, p = 0.006, and ALS-FRS-R respiratory subscore, p = 0.03) and behavioral and cognitive impairment (NRSR-F1, p = 0.04, NRSR- F5, p = 0.04). Presence of sialorrhea and neurobehavioral impairment, and absence of respiratory symptoms are negative predictors of NIV adaptation. This study highlights the need of a multidisciplinary patient-tailored approach including cognitive-behavioral assessment and a psychological support program to optimize patient's training and compliance to NIV.

High flow oxygen for dyspnea in hospitalized patients with cancer: A 4x4 crossover randomized clinical trial.

12077 Background: Dyspnea is common in hospitalized cancer patients and highly distressing. High flow oxygen (HFOx) is administered for oxygenation in this setting; however, its effect on dyspnea has not been well examined, particularly among non-hypoxemic patients. In this phase II trial, we assessed the effect of HFOx, high flow air (HFAir), low flow oxygen (LFOx) and low flow air (LFAir) on dyspnea. We hypothesized that HFO and HFA can alleviate dyspnea. Methods: This double-blind, 4x4 crossover clinical trial enrolled hospitalized patients with cancer who were dyspneic (NRS ≥3 at rest) and non-hypoxemic (SpO2&gt;90% on room air). Patients were randomized to 10 minutes of HFOx, HFAir, LFOx and LFAir in different orders. The flow rate was titrated between 20-60 L/min in the high flow groups and 2 L/min in the low flow groups. The primary outcome was dyspnea 0-10 numeric rating scale (NRS) “now”, where 0=none and 10=worst. Secondary outcomes included modified Borg scale dyspnea intensity and unpleasantness, adverse effects, and overall preference. We compared among the interventions with a linear mixed model adjusting for time, treatment effect, period effect and carryover effect. Results: 17 patients completed 55 interventions in a random order. Mean age 51, 58% female, mean baseline dyspnea NRS 6.3 (SD 1.7). The absolute change of dyspnea NRS between 0 and 10 minutes was -1.8 (SD 1.7) for HFOx, -1.8 (2.0) for HFAir, -0.5 (0.8) for LFOx and -0.6 (1.2) for LFAir. In mixed model analysis, HFOx group provided greater dyspnea relief than LFOx (mean difference [95% CI] -0.80 [-1.45, -0.15], P=0.02) and LFAir (-1.24 [-1.90, -0.57], P&lt;0.001). HFAir also provided a significantly greater dyspnea relief than LFOx (-0.95 [-1.61, -0.30], P=0.005) and LFAir (-1.39 [-2.05, -0.73], P&lt;0.001). No difference was found between HFOx and HFAir nor between LFOx and LFAir. There was no significant carryover effect. Dyspnea Borg scale intensity and unpleasantness showed similar changes. Oxygen saturation increased in the HFOx group (97.2% to 99.7%) and LFOx group (95.5% to 98.2%) but not HFAir nor LFAir groups. HFOx was well tolerated. At the end of the study, 7 (54%), 4 (31%), 1 (8%) and 1 (8%) patients blindly preferred HFOx, HFAir, LFOx and LFAir, respectively. Conclusions: For the first time, we found that HFOx and HFAir provided a rapid and clinically significant reduction of dyspnea at rest in hospitalized cancer patients even when they were non-hypoxemic, supporting a role for high flow devices to provide palliation beyond oxygenation. Larger studies are needed to confirm these findings. Clinical trial information: NCT02932332 .

P159 Current patient reported outcomes (PROs) poorly reflect changes in lung function in patients with systemic sclerosis

Abstract Background In a recent clinical trail the reduction of FVC was not accompanied by a benefit with respect to health-related quality of life and patient-reported outcomes (PROs). The aim of this study is to assess how the change in Pulmonary Function Test (PFTs) parameters correlates with the patient reported outcomes (PROs) in an observational cohort of patients with systemic sclerosis (SSc). Methods We conducted a retrospective study of 330 clinic episodes from 121 unselected patients diagnosed with systemic sclerosis according to EULAR/ACR 2013 criteria, in annual follow-up (for a total of 165 patients/year) with PFTs, Health Assessment Questionnaire Disability Index (HAQ-DI), Scleroderma Health Assessment Questionnaire (sHAQ), Modified Borg Dyspnea Scale (Borg) and Cochin Hand Function Score (CHFS). We assessed the correlation between the HAQ and the Visual Analogical Scale 1-7 at baseline (VAS1 pain, VAS2 disease severity, VAS3 arthritis activity, VAS4 intestinal problems, VAS5 dyspnea, VAS6 Raynaud’s phenomenon, VAS7 digital ulcers). We evaluated the correlation of PFTs with PROs at every time period and the correlation between the change of PFTs parameters (δFVC, δDLCO) with the change of the PROs over a year of follow-up. Following analysis of distribution, Spearman or Pearson Test were used to determine correlation coefficients, as appropriate (Prism 7). Results The median disease duration was 5 years (IQR 3-10). The median of 12 months δFVC% and δDLCO% were 0 (IQR -5.81 to 3.28) and -2.439 (IQR -8.76 to 5.98), respectively. The analysis evidenced a strong positive correlation between VAS1-7 and HAQ. We observed also significant correlation between FVC%, DLCO% and HAQ-DI (r= -0.355 and -0.266, respectively; p &amp;lt; 0.0001 for both), Borg (r= -0.403 and -0.379, respectively; p &amp;lt; 0.0001) and CHFS (r = -0.355 and -0.256, respectively; p &amp;lt; 0.0001). Nevertheless, in longitudinal setting there was no significant correlation between δPROs and changes lung function, as continuous variables, neither there was any significant PROs difference in patients that did or did not lose more than 10% of FVC and DLCO over a year of follow-up. Conclusion This analysis of a monocentric non-selected population evidenced that the current commonly used PROs in SSc while showing a good correlation with lung function are poorly sensitive to change or to reflect changes in lung function over 12 months. In this sense, prudent interpretation of the lack of correlation between FVC and patient-reported outcomes in studies of phase 3 is warranted. Disclosures F. Danzo: None. K. Gjeloshi: None. G. Abignano: None. A. Dean: None. F. Masini: None. G. Cuomo: None. F. del Galdo: None.

Predictors of Successful Oxygen Weaning in Older Patients Undergoing Pulmonary Rehabilitation

ObjectivesTo identify clinical and/or functional variables predictive of successful oxygen-weaning among older patients affected by respiratory insufficiency undergoing pulmonary rehabilitation. DesignRetrospective study. Setting and ParticipantsData are from 154 patients aged 65 years and older (mean age = 78.1 years; female 50.6%) admitted to a pulmonary rehabilitation unit to follow an in-patient program. Patients must require oxygen therapy at admission. MethodsAll patients performed the 6-Minute Walking Test at admission and before discharge as well as a spirometry at a steady state. Multivariate logistic regressions were performed to identify positive and negative predictors of successful oxygen weaning. ResultsSuccessful oxygen weaning was obtained in 47 participants (30.5%). The restrictive pattern was associated with a 4-fold likelihood of successful oxygen weaning at the end of the rehabilitation program compared with the obstructive one. A positive association was also found for arterial oxygenation index (PaO2/FiO2 ratio) at baseline. A decreased likelihood of successful oxygen weaning was reported for the subjective dyspnea perception score at exertion evaluated with a modified Borg scale. Conclusions and ImplicationsThe restrictive pattern, PaO2/FiO2 ratio, and modified Borg dyspnea scale score under exertion were significantly associated with successful oxygen-weaning. The identified predictors may support clinicians at precociously identifying patients who may not require oxygen therapy after discharge. Therefore, these findings would make it possible for clinicians to better tailor the rehabilitation program.

Effectiveness of Pulmonary Rehabilitation in Patients with COPD

Background: Pulmonary rehabilitation (PR) is beneficial for patients with COPD, with improvement in exercise capacity and health-related quality of life. Despite these overall benefits, the responses to PR vary significantly among different individuals. It is not clear if PR is beneficial for patients with COPD and normal exercise capacity. Although it is believed that longer pulmonary rehabilitation programs can provide better results, most of the evidence comes from short-term programs.&#x0D; Objective: The objective of this analysis was to determine the effectiveness of respiratory services provided in the hospital or community by respiratory therapists (RTs) in reducing health care utilization and improving patient outcomes. The aim was to evaluate the outcomes of a comprehensive pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease.&#x0D; Methodology: All 65 Pakistani patients who met the inclusion criteria with ages between 40 to 65 years, including both male and female, with mild to severe COPD were enrolled in the study on the basis of convenient sampling. Informed consent was taken from each patient starting about the study and their rights to withdraw from study. A demographics detail (name, age, sex) was noted along with the necessary medical history. A questionnaire was made to see the effects of pulmonary rehabilitation in patients with COPD. All necessary tests were performed to evaluate the patient betterment completely.&#x0D; Results: The mean FEV1 in the subjects was 1.29 ± 0.47 L/min, 64.8 ± 23.0% of predicted. Clinically there is a little effect on CXR pattern, FEV1 and FEV1/FVC after pulmonary rehabilitation. But overall quality of life improved after pulmonary rehabilitation. Mainly improvement occurs in peak expiratory flow rate, BORG dyspnea scale, 6 mint walk test distance (meters) and Oxygen saturation after rehabilitation.&#x0D; Conclusion: These results showed that patients with COPD had benefited from a comprehensive PR program in an out-patient setting regardless of disease severity. Exercise training can result in significant improvement in health-related quality of life, exercise capacity, respiratory muscle strength, and exertional dyspnea in subjects with COPD and normal exercise capacity.

Impact Of Peak Oxygen Pulse On Patients With Chronic Obstructive Pulmonary Disease.

IntroductionPatients with chronic obstructive pulmonary disease (COPD) are at an increased risk of cardiovascular comorbidities such as pulmonary hypertension or heart failure. Impaired cardiovascular function often has a significant impact on patients with COPD. Oxygen pulse (O2P) is a surrogate for stroke volume. However, studies regarding O2P, health-related quality of life (HRQL), and exercise capacity in patients with COPD are lacking. We aimed to confirm the association between O2P, HRQL, exercise capacity, severe exacerbation of COPD, and other parameters in exercise testing.Materials and methodsThis study included 79 patients with COPD who underwent lung function testing, a cardiopulmonary exercise test (CPET), Borg Dyspnea Scale evaluation, completion of the St. George’s Respiratory Questionnaire, and echocardiography. Cardiovascular comorbidities, COPD-related hospitalizations, and emergency room visits were recorded. We compared these parameters between two groups of patients: those with normal peak O2P and those with impaired peak O2P. The relationships of peak O2P with CPET and lung function were analyzed using simple linear regression.ResultsPatients with normal peak O2P had higher exercise capacity (peak oxygen uptake and work rate), better HRQL, lower dyspnea score, lower COPD-related hospitalizations, and higher circulatory and ventilator parameters than patients with impaired peak O2P. According to a simple linear regression analysis, the anaerobic threshold (AT) and forced expiratory volume in one second (FEV1) showed a significant association with peak O2P, and the Pearson correlation coefficients (Pearson’s r) were 0.756 and 0.461, respectively.ConclusionPeak O2P has a significant impact on exercise capacity, HRQL, dyspnea, COPD-related hospitalization, and circulatory and ventilatory functions in patients with COPD. The AT and FEV1 have strong and moderate associations with peak O2P, respectively. Therefore, peak O2P is an important indicator of disease severity for patients with COPD.

Cognitive function during exacerbations of chronic obstructive pulmonary disease.

The reported prevalence of cognitive impairment in patients with stable chronic obstructive pulmonary disease (COPD) ranges 36-77%. Few studies report the prevalence of cognitive impairment in acutely unwell COPD patients. To determine the prevalence and time course of cognitive impairment in patients with COPD during and after an admission to hospital with an exacerbation of the disease. Patients admitted to hospital with an exacerbation of COPD between October 2013 and November 2014 were administered the Montreal Cognitive Assessment tool, COPD assessment test and modified Borg dyspnoea scale at three points in time: within 24 h of admission, between 48 and 72 h after admission and 6 weeks post discharge. Twenty-five patients agreed to participate. Four withdrew from the study after the initial evaluation. The mean (range) COPD assessment test score 24 h after admission was 26 (18-37). Cognitive impairment was found in 19/25 (76%) patients at the initial evaluation, 16/21 (76%) patients at the second evaluation. Overall, 22/25 (88%) showed cognitive impairment within 72 h of an exacerbation of COPD. Fourteen out of 21 (66%) patients showed cognitive impairment at the final evaluation. The mean Montreal Cognitive Assessment scores improved from admission (22.6) to the second evaluation (23.3) to the final evaluation 3 (24.4), but this change was not statistically significant. Cognitive impairment is highly prevalent during hospital admissions with an exacerbation of COPD. This impairment does improve with time, but only a minority recover within a normal range. This will affect patients' abilities to understand and remember information given to them in hospital and adhere to medication regimens.

Effectiveness of pulmonary rehabilitation in severe asthma: a retrospective data analysis

Background: Pulmonary Rehabilitation (PR) is a multimodal treatment that is still poorly investigated in severe asthma where respiratory symptoms remain “uncontrolled” despite intensive pharmacological therapy. Bronchiectasis and obstructive sleep apnea (OSAS) are common comorbidities which may worsen asthma control.Aim: Aim of the present study is to investigate the effectiveness of PR on functional exercise, dyspnea, and muscle fatigue in patients with severe asthma.Methods: A total of 317 patients affected from severe asthma according to GINA guidelines who underwent a multidisciplinary 3 weeks rehabilitation program with an adherence of >80% to PR and able to complete a Six Minute Walking Test (6MWT) were retrospectively included in the analysis. Pulmonary rehabilitation included endurance training, educational meetings, chest physiotherapy, breathing exercises, and psychological support. Six-minute walking distance and Borg scale for dyspnea and muscle fatigue were recorded before and after the rehabilitation.Results: A total of 371 patients were analyzed, 39 had bronchiectasis (10.5%), 163 (43.9%) OSAS and 17 had both (4.6%). PR significantly improved 6MWT distance, Borg dyspnea and muscle fatigue (p value < 0.0001 for all outcomes) and mean SpO2 recorded during 6MWT (p value < 0.0001). Median (IQR) delta 6 minute walking distance was 33 (14–60) m. 6MWT distance (p < 0.0001) and the oxygen saturation (p < 0.01) significantly improved in severe asthma with bronchiectasis and/or OSAS.Conclusions: Our study provides evidence for the first time on a large sample of patients with severe asthma that a multidisciplinary PR program is effective in terms of exercise capacity and symptoms. In addition, exercise capacity improved in the presence of bronchiectasis and/or OSAS.

Resting Hemodynamics and Response to Exercise Using the 6-Minute Walk Test in Late Pregnancy: An International Prospective Multicentre Study.

Cardiac disease is the leading cause of maternal death. Assessment of cardiovascular fitness is important in pregnant women because it is linked to increased risk of cardiac disease but is rarely undertaken or studied. The 6-Minute Walk Test (6MWT) is a safe exercise test but is not used in pregnancy. We determined the 95% reference interval for resting heart rate (HR) and distance walked for the 6MWT, as well as hemodynamic recovery variables, and quantified expectations and actual experiences of exertion and breathlessness with exercise in late pregnancy. After institutional research board approval (Australian and New Zealand Clinical Trials Registry Number: 12615000964516), 300 healthy term nulliparous pregnant women performed the 6MWT at 3 tertiary referral obstetric hospitals using a standardized protocol. Each woman underwent two 6MWT with maximum 15-minute recovery period after each test. Hemodynamic variables were measured at rest and after exercise. Participants were asked 4 questions, 2 regarding expectation and 2 regarding actual experience, using the Rating of Perceived Exertion scale and Modified Borg Dyspnea scale. Participant characteristics and resting variables were mean (standard deviation [SD]); age, 31 years (4.2 years); body mass index, 27 kg/m (2.9 kg/m); gestational age, 37 weeks (1.3 weeks); HR, 85 bpm (10.8 bpm) with 95% reference interval 64-106 bpm; systolic blood pressure, 112 mm Hg (10.2 mm Hg); diastolic blood pressure, 72 mm Hg (8.6 mm Hg); oxygen saturation, 98% (0.9%); and respiratory rate, 18 breaths/min (5.7 breaths/min). The mean (SD) average distance walked was 488 m (94.9 m) with a speed of 3.0 mph (0.64 mph) with a 95% reference interval of 302-674 m. The mean (SD) HR increase with exercise was 12 bpm (11.0 bpm) with a median [quartile] recovery time of 5.0 minutes [1-8 minutes]. A lower resting HR was associated with increased distance walked (r = -0.207; 95% confidence interval, -0.313 to -0.096; P < .001). A greater HR change with exercise was associated with increased recovery time from exercise (r = 0.736; 95% confidence interval, 0.697-0.784; P < .001). Sixty-three percent and 83% of participants, respectively, expected to be more exerted and breathless than they actually were with exercise. The 6MWT is feasible and applicable in term pregnant women. The reference intervals for resting HR and distance walked in the 6MWT have been generated. HR increases by approximately 12 bpm with submaximal exercise, and half of the women recovered within 5 minutes of submaximal exercise. Women expected to be more exerted and breathless than they actually were with exercise.

Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial

ContextThe optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined. ObjectivesWe examined the effect of two doses of prophylactic FSS on exertional dyspnea. MethodsIn this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%–45% (high dose) or 15%–25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0–10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function. ResultsThirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change −1.42; 95% CI −2.37, −0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change −0.47; 95% CI −1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected. ConclusionProphylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials.

Pain during exacerbation of chronic obstructive pulmonary disease: A prospective cohort study.

Background and objectivePain, a symptom often present in patients with Chronic Obstructive Pulmonary Disease (COPD), alters quality of life. COPD exacerbation augments several mechanisms that may cause pain (dyspnea, hyperinflation and inflammation) and therefore we hypothesized that pain might be increased during exacerbation.MethodsA prospective cohort study was conducted in patients admitted for acute exacerbations of COPD (AECOPD) in two emergency departments in France and Canada. Patients with cancer-related pain or recent trauma were not included. The Short Form McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory (BPI) scale were used to evaluate pain intensity and location. Patients also completed the Borg Dyspnea Scale and Hospital Anxiety and Depression Scale. The questionnaires were completed again during an outpatient assessment in the stable phase. The primary outcome was difference in pain intensity (SF-MPQ) between the exacerbation and stable phases.ResultsFifty patients were included. During exacerbation, 46 patients (92%) reported pain compared to 29 (58%) in the stable phase (p<0.001). Pain intensity was higher during exacerbation (SF-MPQ 29.7 [13.6–38.2] vs. 1.4 [0.0–11.2]; p<0.001). Pain was predominantly located in the chest during exacerbation and in the limbs during the stable phase. Pain intensity during exacerbation correlated with anxiety score.ConclusionThe frequency and intensity of pain were higher during AECOPD, with a specific distribution. Pain should therefore be routinely assessed and treated in patients with AECOPD.

Evaluation of Clinical Outcomes and Simultaneous Digital Tracking of Daily Physical Activity, Heart Rate, and Inhalation Behavior in Patients With Pulmonary Arterial Hypertension Treated With Inhaled Iloprost: Protocol for the Observational VENTASTEP Study.

BackgroundPulmonary arterial hypertension (PAH)—a progressive, ultimately fatal disease—patients often experience dyspnea, which can limit their daily physical activities. Iloprost is an inhaled therapy for PAH that has shown efficacy in clinical trials. However, clinical trials in PAH have provided only limited data on daily physical activity. Digital monitoring of daily physical activity in PAH is therefore attracting growing interest. To fully understand a patient’s response to treatment, monitoring of treatment adherence is also required. The Breelib nebulizer for administration of iloprost saves inhalation data, thus allowing digital monitoring of adherence.ObjectiveThis study aims to perform parallel digital tracking of daily physical activity parameters, heart rate, and iloprost inhalation data in patients with PAH, before and after starting inhaled iloprost treatment. The primary objective is to investigate correlations between changes in digital measures of daily physical activity and traditional clinical measures. Secondary objectives are to assess iloprost inhalation behavior, the association between daily physical activity measures and time since last inhalation, changes in sleep quality and heart rate, the association of heart rate with daily physical activity measures and iloprost inhalation, and adverse events.MethodsVENTASTEP is a digital, prospective, observational, multicenter, single-arm cohort study of adults with PAH in Germany, starting inhaled iloprost treatment via the Breelib nebulizer, in addition to existing PAH therapy. The study comprises a baseline period without iloprost treatment (≤2 weeks) and an observation period with iloprost treatment (3 months±2 weeks). The Apple Watch Series 2 and iPhone 6s are used with a dedicated study app to continuously measure digital daily physical activity parameters and heart rate during the baseline and observation periods; the watch is also used with a 6-min walk distance (6MWD) app to measure digital 6MWD at baseline and the end-of-observation visit. Inhalation frequency, completeness, and duration are monitored digitally via the nebulizer and the BreeConnect app. Sleep quality is assessed using the Pittsburgh Sleep Quality Index at baseline and the end-of-observation visit. Changes in traditional outcome measures (6MWD, Borg dyspnea scale, EuroQol 5-dimensions questionnaire, functional class, and brain natriuretic peptide [BNP] or N-terminal proBNP) between baseline and the end-of-observation visit will be correlated with changes in digital daily physical activity parameters and digital 6MWD as the primary analysis.ResultsThe first participant was enrolled in February 2018 (estimated study completion by July 2019; planned sample size: 80 patients).ConclusionsThe VENTASTEP study will inform future research on the utility of digital parameters as outcome assessment tools for disease monitoring in PAH. The study will also provide insight into clinical outcomes, daily physical activity, and quality of life in patients adding inhaled iloprost, to existing PAH therapy.Trial RegistrationClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407 (Archived by WebCite at http://www.webcitation.org/6ywPGcn4I)International Registered Report Identifier (IRRID)DERR1-10.2196/12144

Adipose-Derived Mesenchymal Stem Cells Can Ameliorate Airway Remodelling and Improve Oxidative Stress: An Open Label and Randomized Clinical Trial Study on Sulfur Mustard Exposed Patients

Background: Lung is a primary target for sulfur mustard (SM) toxicity. Here, we investigated the potential efficacy and safety of adipose derived mesenchymal stem cell (AdMSC) on respiratory quality, lung regeneration, oxidative stress, and airway remodelling in patients with mustard lung. Methods: In this clinical trial study, 10 patients received 100x106 cells every 20 days for 4 injections over 8 weeks. The pulmonary function tests (PFT), chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), Borg Scale Dyspnea Assessment (BSDA), and 6 Minute Walk Test (6MWT) were evaluated. Total antioxidant capacity (TAC), malondialdehyde (MDA) and glutathione (GSH) were measured in the sputum of all samples. Changes in expression of metallothionein 3 (MT3), glutathione reductase (GR), glutathione peroxidase (GPX), and lacto peroxidase (LPO), as well as matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), transforming growth factor-b1 (TGF-b), vascular endothelial growth factor (VEGF), metallopeptidase inhibitor 1 (TIMP1), and metallopeptidase inhibitor 2 (TIMP2) were assessed using real-time PCR. Clara cell protein 16 (CC16) and Mucin-1 protein (KL-6) were measured in the sputum all samples as biomarkers of lung injury using enzyme immunoassay method. This study is registered with ClinicalTrials.gov (NCT02749448). Findings: Spirometry test results were slightly improved after each injection. A gradual improvement was observed in the mean of 6MWT scores. CASA-Q and VAS scores were increased, while means of CAT and Borg-Score were decreased. A significant improvement was found for the mean of KL-6 (p=0.022) and CC16 (p=0.005) levels. Sputum levels of TAC and GSH had a tendency to be higher after each injection, while MDA content was decreased. An improvement was observed for antioxidants genes, especially for GSR, MT3 and LPO, compared to the baseline. A gradual upregulation was found for VEGF and TGF-β expression after MSCs therapy. MSCs caused a balance between MMP9/TIMP1 and MMP2/TIMP2 ratio. The MMP2/TIMP2 ratio was decreased from 4.9 on baseline to 0.71 on day 180 (p<0.001), while the MMP9/TIMP1 ratio was declined from 16.35 on baseline to 0.64 on day 180 (p<0.001). Interpretation: The findings suggest that MSCs therapy can be safely used for improvement of lung injury and regeneration in these patients without any adverse effects. Trial Registration Number: This study is registered with ClinicalTrials.gov (NCT02749448). Funding: Iran National Science Foundation and Veterans Foundation. Declaration of Interest: The authors confirm that there are no conflicts of interest. Ethical Approval: The ethics review board of the Baqiyatallah University of Medical Sciences (Cod: IR.BMSU.REC.1393.32) approved this survey and all patients signed an informed consent letter before the study.

Riociguat improves health‐related quality of life for patients with pulmonary arterial hypertension: results from the phase 4 MOTION study

Pulmonary arterial hypertension (PAH) is characterized by progressive dyspnea and exercise limitation and is associated with reduced health-related quality of life. Few clinical studies have evaluated the primary effects of treatment of PAH from the patient perspective. Here, we present the impact of riociguat on patient-reported outcomes (PROs) in treatment-naïve patients with PAH. MOTION (NCT02191137) was an open-label, phase 4 trial of riociguat monotherapy in treatment-naïve patients with PAH. The primary endpoint was the change in total score from baseline to Week 24 in the Living with Pulmonary Hypertension (LPH) questionnaire. The Short Form-12 Health Survey and Work Limitations Questionnaire 8 were also utilized to assess PROs. Other secondary endpoints included change from baseline in World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), Modified Borg Dyspnea Scale, and safety. At week 24 (n = 66), the mean (standard deviation [SD]) total LPH score was 37.17 (24.61), for a mean (SD) change from baseline of -10.99 (22.51). At last visit, with week 24 imputed, the mean (SD) total score was 40.63 (28.38), for a mean (SD) change from baseline of -5.40 (27.8) (n = 75; P = 0.0484). Improvement in LPH questionnaire total score was observed by week 4 and was maintained through week 24. Improvements were observed in WHO FC, Modified Borg Dyspnea Scale, and accelerometer-measured 6MWD at week 24. Treatment with riociguat had a positive impact on PROs in treatment-naïve patients with PAH and was well tolerated, with a similar safety profile to that observed in placebo-controlled phase 3 trials.