Treatable traits for long COVID.

Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health condition that typically includes multiple symptoms that cross organ systems and fluctuate over time; a one-size-fits-all approach is, therefore, not likely to be appropriate nor relevant for long COVID treatment. 'Treatable Traits' is a personalized medicine approach, purpose-built to address the complexity and heterogeneity of complex chronic conditions. This comprehensive review aimed to understand how a treatable traits approach could be applied to long COVID, by first identifying the most prevalent long COVID treatable traits and then the available evidence for strategies to target these traits. An umbrella review of 22 systematic reviews identified 34 symptoms and complications common with long COVID, grouped into eight long COVID treatable trait clusters: neurological, chest, psychological, pain, fatigue, sleep impairment, functional impairment and other. A systematic review of randomized control trials identified 18 studies that explored different intervention approaches for long COVID prevention (k = 4) or management (k = 14). While a single study reported metformin as effective for long COVID prevention, the findings need to be replicated and consensus is required around how to define long COVID as a clinical trial endpoint. For long COVID management, current evidence supports exercise training or respiratory muscle training for long COVID treatable traits in the chest and functional limitation clusters. While there are studies exploring interventions targeting other long COVID treatable traits, further high-quality RCTs are needed, particularly targeting treatable traits in the clusters of fatigue, psychological, pain and sleep impairment.

A collaborative approach to adopting/adapting guidelines. The Australian 24-hour movement guidelines for children (5-12 years) and young people (13-17 years): An integration of physical activity, sedentary behaviour, and sleep.

BACKGROUND: In 2018, the Australian Government updated the Australian Physical Activity and Sedentary Behaviour Guidelines for Children and Young People. A requirement of this update was the incorporation of a 24-hour approach to movement, recognising the importance of adequate sleep. The purpose of this paper was to describe how the updated Australian 24-Hour Movement Guidelines for Children and Young People (5 to 17 years): an integration of physical activity, sedentary behaviour and sleep were developed and the outcomes from this process. METHODS: The GRADE-ADOLOPMENT approach was used to develop the guidelines. A Leadership Group was formed, who identified existing credible guidelines. The Canadian 24-Hour Movement Guidelines for Children and Youth best met the criteria established by the Leadership Group. These guidelines were evaluated based on the evidence in the GRADE tables, summaries of findings tables and recommendations from the Canadian Guidelines. We conducted updates to each of the Canadian systematic reviews. A Guideline Development Group reviewed, separately and in combination, the evidence for each behaviour. A choice was then made to adopt or adapt the Canadian recommendations for each behaviour or create de novo recommendations. We then conducted an online survey (n=237) along with three focus groups (n=11 in total) and 13 key informant interviews. Stakeholders used these to provide feedback on the draft guidelines. RESULTS: Based on the evidence from the Canadian systematic reviews and the updated systematic reviews in Australia, the Guideline Development Group agreed to adopt the Canadian recommendations and, apart from some minor changes to the wording of good practice statements, maintain the wording of the guidelines, preamble, and title of the Canadian Guidelines. The Australian Guidelines provide evidence-informed recommendations for a healthy day (24-hours), integrating physical activity, sedentary behaviour (including limits to screen time), and sleep for children (5-12 years) and young people (13-17 years). CONCLUSIONS: To our knowledge, this is only the second time the GRADE-ADOLOPMENT approach has been used to develop movement behaviour guidelines. The judgments of the Australian Guideline Development Group did not differ sufficiently to change the directions and strength of the recommendations and as such, the Canadian Guidelines were adopted with only very minor alterations. This allowed the Australian Guidelines to be developed in a shorter time frame and at a lower cost. We recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines that was developed using the GRADE approach is available with all supporting materials. Other countries may consider this approach when developing and/or revising national movement guidelines.

The Association between Fat-Free Mass and Exercise Test Outcomes in People with Chronic Obstructive Pulmonary Disease: A Systematic Review.

People with chronic obstructive pulmonary disease (COPD) tend to have abnormally low levels of fat-free mass (FFM), which includes skeletal muscle mass as a central component. The purpose of this systematic review was to synthesise available evidence on the association between FFM and exercise test outcomes in COPD. MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus were searched. Studies that evaluated exercise-related outcomes in relation to measures of FFM in COPD were included. Eighty-three studies, containing 18,770 (39% female) COPD participants, were included. Considerable heterogeneity was identified in the ways that FFM and exercise test outcomes were assessed; however, higher levels of FFM were generally associated with greater peak exercise capacity. This association was stronger for some exercise test outcomes (e.g. peak rate of oxygen consumption during incremental cycle exercise testing) than others (e.g. six-minute walking distance). This review identified heterogeneity in the methods used for measuring FFM and exercise capacity. There was, in general, a positive association between FFM and exercise capacity in COPD. There was also an identified lack of studies investigating associations between FFM and temporal physiological and perceptual responses to exercise. This review highlights the significance of FFM as a determinant of exercise capacity in COPD.

Multidimensional breathlessness assessment during cardiopulmonary exercise testing in healthy adults.

PURPOSE: This study explored if healthy adults could discriminate between different breathlessness dimensions when rated immediately one after another (successively) during symptom-limited incremental cardiopulmonary cycle exercise testing (CPET) using multiple single-item rating scales. METHODS: Fifteen apparently healthy adults (60% male) aged 22 ± 2 years performed six incremental cycle CPETs separated by ≥ 48 h. During each CPET (at rest, every 2-min and at end exercise), participants rated different breathlessness sensations using the 0-10 modified Borg scale using one of six assessment protocols, randomized for order: (1) 'BREATHLESSALL' = breathlessness sensory intensity (SI), breathlessness unpleasantness (UN), work/effort of breathing (SQW/E), and unsatisfied inspiration (SQUI) assessed; (2) SI and UN assessed; and (3-6) SI, UN, SQW/E, and SQUI each assessed alone. Physiological responses to CPET were also evaluated. RESULTS: Physiological and breathlessness responses to CPET were comparable across the six protocols, with the exception of SI rated lower at the highest submaximal power output (220 ± 56 watts) during the BREATHLESSALL protocol (0-10 Borg units 4.2 ± 1.7) compared to SI + UN (5.2 ± 2.1, p = 0.03) and SI alone (5.1 ± 1.9, p = 0.04) protocols. Ratings of SI and SQW/E were not significantly different when assessed in the same protocol, and were significantly higher than UN and SQUI, which were comparable. CONCLUSION: In healthy younger adults, use of two separate single-item rating scales to assess breathlessness during CPET is feasible and enables the distinct sensory intensity and affective dimensions of exertional breathlessness to be assessed.

Compliance With Mobile Ecological Momentary Assessment of Self-Reported Health-Related Behaviors and Psychological Constructs in Adults: Systematic Review and Meta-analysis.

BACKGROUND: Mobile ecological momentary assessment (mEMA) permits real-time capture of self-reported participant behaviors and perceptual experiences. Reporting of mEMA protocols and compliance has been identified as problematic within systematic reviews of children, youth, and specific clinical populations of adults. OBJECTIVE: This study aimed to describe the use of mEMA for self-reported behaviors and psychological constructs, mEMA protocol and compliance reporting, and associations between key components of mEMA protocols and compliance in studies of nonclinical and clinical samples of adults. METHODS: In total, 9 electronic databases were searched (2006-2016) for observational studies reporting compliance to mEMA for health-related data from adults (>18 years) in nonclinical and clinical settings. Screening and data extraction were undertaken by independent reviewers, with discrepancies resolved by consensus. Narrative synthesis described participants, mEMA target, protocol, and compliance. Random effects meta-analysis explored factors associated with cohort compliance (monitoring duration, daily prompt frequency or schedule, device type, training, incentives, and burden score). Random effects analysis of variance (P≤.05) assessed differences between nonclinical and clinical data sets. RESULTS: Of the 168 eligible studies, 97/105 (57.7%) reported compliance in unique data sets (nonclinical=64/105 [61%], clinical=41/105 [39%]). The most common self-reported mEMA target was affect (primary target: 31/105, 29.5% data sets; secondary target: 50/105, 47.6% data sets). The median duration of the mEMA protocol was 7 days (nonclinical=7, clinical=12). Most protocols used a single time-based (random or interval) prompt type (69/105, 65.7%); median prompt frequency was 5 per day. The median number of items per prompt was similar for nonclinical (8) and clinical data sets (10). More than half of the data sets reported mEMA training (84/105, 80%) and provision of participant incentives (66/105, 62.9%). Less than half of the data sets reported number of prompts delivered (22/105, 21%), answered (43/105, 41%), criterion for valid mEMA data (37/105, 35.2%), or response latency (38/105, 36.2%). Meta-analysis (nonclinical=41, clinical=27) estimated an overall compliance of 81.9% (95% CI 79.1-84.4), with no significant difference between nonclinical and clinical data sets or estimates before or after data exclusions. Compliance was associated with prompts per day and items per prompt for nonclinical data sets. Although widespread heterogeneity existed across analysis (I2>90%), no compelling relationship was identified between key features of mEMA protocols representing burden and mEMA compliance. CONCLUSIONS: In this 10-year sample of studies using the mEMA of self-reported health-related behaviors and psychological constructs in adult nonclinical and clinical populations, mEMA was applied across contexts and health conditions and to collect a range of health-related data. There was inconsistent reporting of compliance and key features within protocols, which limited the ability to confidently identify components of mEMA schedules likely to have a specific impact on compliance.

Title: Blood flow restricted exercise training: Perspectives of people with chronic obstructive pulmonary disease and health professionals.

OBJECTIVE: This descriptive qualitative study explored perspectives of people with chronic obstructive pulmonary disease (COPD) and health professionals concerning blood flow restricted exercise (BFRE) training. METHODS: People living with COPD and health professionals (exercise physiologists, physiotherapists, and hospital-based respiratory nurses and doctors) participated in interviews or focus groups, which included information about BFRE training and a facilitated discussion of positive aspects, barriers and concerns about BFRE training as a possible exercise-based intervention. Sessions were audio-recorded, and transcript data analysed using inductive content analysis. RESULTS: Thirty-one people participated (people with COPD n = 6; health professionals n = 25). All participant groups expressed positive perceptions of BFRE as a potential alternative low-intensity exercise mode where health benefits might be achieved. Areas of overlap in perceived barriers and concerns included the need to address the risk of potential adverse events, suitability of training sites and identifying processes to appropriately screen potential candidates. DISCUSSION: While potential benefits were identified, concerns about determining who is safe and suitable to participate, delivery processes, health professional training and effects on a variety of health-related outcomes need to be addressed before implementation of BFRE training for people with COPD.

Behaviour change techniques to optimise participation in physical activity or exercise in adolescents and young adults with chronic cardiorespiratory conditions: a systematic review.

Participation in regular physical activity decreases the risk of developing cardiometabolic disease. However, the proportion of people who participate in the recommended amount of physical activity is low, with common barriers including competing interests and inclement weather. In people with chronic cardiorespiratory conditions, participation in physical activity is reduced further by disease-specific barriers, time burden of treatment and unpleasant symptoms during physical activity. Addressing these barriers during adolescence and early adulthood may promote greater physical activity participation into older age. The aim of this review was to classify interventions aimed at optimising participation in physical activity as 'promising' or 'not promising' in people aged 15-45 years with chronic cardiorespiratory conditions and categorise the behaviour change techniques (BCT) within these interventions. Nine databases and registries were searched (October 2017) for studies that reported objective measures of physical activity before and after an intervention period. Interventions were classified as 'promising' if a between-group difference in physical activity was demonstrated. Michie et al.'s (2013) v1 Taxonomy was used to unpack the BCT within interventions. Across the six included studies (n = 396 participants), 19 (20%) of 93 BCT were described. The interventions of three studies were classified as 'promising'. The most commonly used BCT comprised goal setting, action planning and social support. Five BCT were solely used in 'promising' interventions. Our review demonstrated that only 20% of BCT have been utilised, and those BCT that were used only in 'promising' physical activity interventions in adolescents and adults with chronic cardiorespiratory conditions were isolated.

Life on holidays: study protocol for a 3-year longitudinal study tracking changes in children's fitness and fatness during the in-school versus summer holiday period.

BACKGROUND: Emerging evidence suggests that children become fatter and less fit over the summer holidays but get leaner and fitter during the in-school period. This could be due to differences in diet and time use between these distinct periods. Few studies have tracked diet and time use across the summer holidays. This study will measure rates of change in fatness and fitness of children, initially in Grade 4 (age 9 years) across three successive years and relate these changes to changes in diet and time use between in-school and summer holiday periods. METHODS: Grade 4 Children attending Australian Government, Catholic and Independent schools in the Adelaide metropolitan area will be invited to participate, with the aim of recruiting 300 students in total. Diet will be reported by parents using the Automated Self-Administered 24-h Dietary Assessment Tool. Time use will be measured using 24-h wrist-worn accelerometry (GENEActiv) and self-reported by children using the Multimedia Activity Recall for Children and Adults (e.g. chores, reading, sport). Measurement of diet and time use will occur at the beginning (Term 1) and end (Term 4) of each school year and during the summer holiday period. Fitness (20-m shuttle run and standing broad jump) and fatness (body mass index z-score, waist circumference, %body fat) will be measured at the beginning and end of each school year. Differences in rates of change in fitness and fatness during in-school and summer holiday periods will be calculated using model parameter estimate contrasts from linear mixed effects model. Model parameter estimate contrasts will be used to calculate differences in rates of change in outcomes by socioeconomic position (SEP), sex and weight status. Differences in rates of change of outcomes will be regressed against differences between in-school and summer holiday period diet and time use, using compositional data analysis. Analyses will adjust for age, sex, SEP, parenting style, weight status, and pubertal status, where appropriate. DISCUSSION: Findings from this project may inform new, potent avenues for intervention efforts aimed at addressing childhood fitness and fatness. Interventions focused on the home environment, or alternatively extension of the school environment may be warranted. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry, identifier ACTRN12618002008202 . Retrospectively registered on 14 December 2018.

Physical activity, sedentary behaviour and sleep in COPD guidelines: A systematic review.

OBJECTIVES: Physical activity, sedentary and sleep behaviours have strong associations with health. This systematic review aimed to identify how clinical practice guidelines (CPGs) for the management of chronic obstructive pulmonary disease (COPD) report specific recommendations and strategies for these movement behaviours. METHODS: A systematic search of databases (Medline, Scopus, CiNAHL, EMbase, Clinical Guideline), reference lists and websites identified current versions of CPGs published since 2005. Specific recommendations and strategies concerning physical activity, sedentary behaviour and sleep were extracted verbatim. The proportions of CPGs providing specific recommendations and strategies were reported. RESULTS: From 2370 citations identified, 35 CPGs were eligible for inclusion. Of these, 21 (60%) provided specific recommendations for physical activity, while none provided specific recommendations for sedentary behaviour or sleep. The most commonly suggested strategies to improve movement behaviours were encouragement from a healthcare provider (physical activity n = 20; sedentary behaviour n = 2) and referral for a diagnostic sleep study (sleep n = 4). CONCLUSION: Since optimal physical activity, sedentary behaviour and sleep durations and patterns are likely to be associated with mitigating the effects of COPD, as well as with general health and well-being, there is a need for further COPD-specific research, consensus and incorporation of recommendations and strategies into CPGs.

Development and validation of reference equations for dual-energy X-ray absorptiometry-derived measures of fat-free mass in adults aged 45-85 years: results from the Canadian Longitudinal Study on Aging.

Reference equations for fat-free mass (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy X-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45-85 years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted aka index (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1881 healthy participants (57% male) aged 55 [IQR: 50-61] years. Reference equations performed comparably in the validation cohort and discriminated reference values between ostensibly healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45-85 years, although additional validation may be required for those >75 years.

Explain Breathlessness: Could 'Usual' Explanations Contribute to Maladaptive Beliefs of People Living with Breathlessness?

BACKGROUND: Explanations provided by healthcare professionals contribute to patient beliefs. Little is known about how healthcare professionals explain chronic breathlessness to people living with this adverse sensation. METHODS: A purpose-designed survey disseminated via newsletters of Australian professional associations (physiotherapy, respiratory medicine, palliative care). Respondents provided free-text responses for their usual explanation and concepts important to include, avoid, or perceived as difficult to understand by recipients. Content analysis coded free text into mutually exclusive categories with the proportion of respondents in each category reported. RESULTS: Respondents (n = 61) were predominantly clinicians (93%) who frequently (80% daily/weekly) conversed with patients about breathlessness. Frequent phrases included within usual explanations reflected breathlessness resulting from medical conditions (70% of respondents) and physiological mechanisms (44%) with foci ranging from multifactorial to single-mechanism origins. Management principles were important to include and phrases encouraging maladaptive beliefs were important to avoid. The most frequent difficult concept identified concerned inconsistent relationships between oxygenation and breathlessness. Where explanations included the term 'oxygen', a form of cognitive shortcut (heuristic) may contribute to erroneous beliefs. CONCLUSIONS: This study presents examples of health professional explanations for chronic breathlessness as a starting point for considering whether and how explanations could contribute to adaptive or maladaptive breathlessness beliefs of recipients.

Abnormal Exertional Breathlessness on Cardiopulmonary Cycle Exercise Testing in Relation to Self-Reported and Physiologic Responses in Chronic Airflow Limitation.

BACKGROUND: Exertional breathlessness is a cardinal symptom of cardiorespiratory disease. RESEARCH QUESTION: How does breathlessness abnormality, graded using normative reference equations during cardiopulmonary exercise testing (CPET), relate to self-reported and physiologic responses in people with chronic airflow limitation (CAL)? STUDY DESIGN AND METHODS: An analysis was done of people aged ≥ 40 years with CAL undergoing CPET in the Canadian Cohort Obstructive Lung Disease study. Breathlessness intensity ratings (Borg CR10 scale [0-10 category-ratio scale for breathlessness intensity rating]) were evaluated in relation to power output, rate of oxygen uptake, and minute ventilation at peak exercise, using normative reference equations as follows: (1) probability of breathlessness normality (probability of having an equal or greater Borg CR10 rating among healthy people; lower probability reflecting more severe breathlessness) and (2) presence of abnormal breathlessness (rating above the upper limit of normal). Associations with relevant participant-reported and physiologic outcomes were evaluated. RESULTS: We included 330 participants (44% women): mean ± SD age, 64 ± 10 years (range, 40-89 years); FEV1/FVC, 57.3% ± 8.2%; FEV1, 75.6% ± 17.9% predicted. Abnormally low exercise capacity (peak rate of oxygen uptake < lower limit of normal) was present in 26%. Relative to peak power output, rate of oxygen uptake, and minute ventilation, abnormally high breathlessness was present in 26%, 25%, and 18% of participants. For all equations, abnormally high exertional breathlessness was associated with worse lung function, exercise capacity, self-reported symptom burden, physical activity, and health-related quality of life; and greater physiologic abnormalities during CPET. INTERPRETATION: Abnormal breathlessness graded using CPET normative reference equations was associated with worse clinical, physiological, and functional outcomes in people with CAL, supporting construct validity of abnormal exertional breathlessness.

Prevalence of Long COVID and the Impact on Diabetes Management and Physical Activity Participation in Adults With Type 2 Diabetes: An Australia-wide Cross-sectional Online Survey.

OBJECTIVES: The aim of this research was to understand the prevalence and impact of long COVID on adults with type 2 diabetes (T2D). Specifically, we sought to identify the proportion of adults with T2D who have had COVID-19 and experienced long COVID symptoms. We also explored how these ongoing symptoms impact diabetes management and physical activity participation. METHODS: Our study was carried out using an online survey of adults in Australia with T2D who had confirmed COVID-19 ≥12 weeks before participation. Respondents were asked to report the presence (and severity) of long COVID-19 symptoms, and, for those with long COVID, the impact of their symptoms on diabetes management (blood glucose, body weight) and physical activity participation (activities of daily living, work/study, exercise). RESULTS: Survey responses were provided by 1,046 adults with T2D (median age 61.0 [interquartile range 49.8 to 70.0] years; 56.0% men, 42.1% women, and 1% nonbinary/transgender; median T2D duration 10.0 [5.0 to 18.0] years and median time since COVID-19 infection 33.0 [20.3 to 36.1] weeks). Almost one third (30%) of respondents reported long COVID symptoms (present ≥12 weeks after most recent infection); 40% of respondents with long COVID symptoms reported a worsening of their diabetes management since their COVID-19 infection, with 29% reporting trouble controlling their blood glucose and 43% reporting a higher body weight. Two thirds of respondents with ongoing symptoms reported that these symptoms moderately to severely impacted their ability to perform activities of daily living, work, and/or exercise. The majority of those with long COVID reported reducing the frequency, duration, and/or intensity of exercise since their COVID-19 infection, with 36.1% not yet returning to their preinfection exercise levels; 66% cited ongoing symptoms as the primary reason for these limitations. CONCLUSIONS: Physical activity is a crucial component of diabetes management. However, the high prevalence of long COVID is hindering participation in this population, as well as deleteriously impacting diabetes management. Developing strategies to support adults with T2D and long COVID to recommence safe levels of physical activity is of critical importance.

Normative Reference Equations for Breathlessness Intensity during Incremental Cardiopulmonary Cycle Exercise Testing.

Rationale: Cardiopulmonary exercise testing (CPET) is the gold standard to evaluate exertional breathlessness, a common and disabling symptom. However, the interpretation of breathlessness responses to CPET is limited by a scarcity of normative data. Objectives: We aimed to develop normative reference equations for breathlessness intensity (Borg 0-10 category ratio) response in men and women aged ⩾40 years during CPET, in relation to power output (watts), oxygen uptake, and minute ventilation. Methods: Analysis of ostensibly healthy people aged ⩾40 years undergoing symptom-limited incremental cycle CPET (10 W/min) in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study. Participants had smoking histories <5 pack-years and normal lung function and exercise capacity. The probability of each Borg 0-10 category ratio breathlessness intensity rating by power output, oxygen uptake, and minute ventilation (as an absolute or a relative value [percentage of predicted maximum]) was predicted using ordinal multinomial logistic regression. Model performance was evaluated by fit, calibration, and discrimination (C statistic) and externally validated in an independent sample (n = 86) of healthy Canadian adults. Results: We included 156 participants (43% women) from CanCOLD; the mean age was 65 (range, 42-91) years, and the mean body mass index was 26.3 (standard deviation, 3.8) kg/m2. Reference equations were developed for women and men separately, accounting for age and/or body mass. Model performance was high across all equations, including in the validation sample (C statistic for men = 0.81-0.92, C statistic for women = 0.81-0.96). Conclusions: Normative reference equations are provided to compare exertional breathlessness intensity ratings among individuals or groups and to identify and quantify abnormal breathlessness responses (scores greater than the upper limit of normal) during CPET.

Physical capacity and inactivity in obstructive airway diseases: a "can do, do do" analysis.

Introduction: Physical capacity is an important determinant of physical activity in people with obstructive airway disease (OAD). This study aimed to extend the "can do, do do" concept in people with OAD, to identify if people categorised into quadrants based on physical capacity and activity differ by clinical and movement behaviour characteristics. Methods: A total of 281 participants (bronchiectasis n=60, severe asthma n=93, COPD n=70 and control n=58) completed assessments to characterise physical capacity as "can do" versus "can't do" (6-min walk distance < or ≥70% pred) and physical activity as "do do" versus "don't do" (accelerometer-derived moderate to vigorous intensity physical activity (MVPA) < or ≥150 min·week-1). Results: The control group had a greater proportion of people in the "can do, do do" quadrant compared with the OAD groups (76% versus 10-33%). People with OAD in the "can't do, don't do" quadrant had worse clinical characteristics (airflow limitation, comorbidities, quality of life and functional dyspnoea) and spent less time doing light-intensity physical activity (LPA) and more time being sedentary compared with the "can do, do do" quadrant. Discussion: This study highlights that many people with OAD may be inactive because they do not have the physical capacity to participate in MVPA, which is further impacted by greater disease severity. It is important to consider the potential benefits of addressing LPA and sedentary behaviour due to suboptimal levels of these movement behaviours across different quadrants. Future research is needed to investigate if tailoring intervention approaches based on quadrant allocation is effective in people with OAD.

Understanding Breathlessness Burden and Psychophysiological Correlates in Asthma.

BACKGROUND: Breathlessness is a disabling symptom, with complexity that is often under-recognized and undertreated in asthma. OBJECTIVE: To highlight the burden of breathlessness in people with severe compared with mild-to-moderate asthma and identify psychophysiological correlates of breathlessness. METHODS: This was a cross-sectional study of people with mild-to-severe asthma, who attended 2 in-person visits to complete a multidimensional assessment. The proportion of people with mild-to-moderate versus severe asthma who reported physically limiting breathlessness (modified Medical Research Council [mMRC] dyspnea score ≥2) was compared. Psychophysiological factors associated with breathlessness in people with asthma were identified via a directed acyclic graph and explored with multivariate logistic regression to predict breathlessness. RESULTS: A total of 144 participants were included, of whom, 74 (51%) had mild-to-moderate asthma and 70 (49%) severe asthma. Participants were predominantly female (n = 103, 72%) with a median (quartile 1, quartile 3) age of 63.4 (50.5, 69.5) years and body mass index (BMI) of 31.3 (26.2, 36.0) kg/m2. The proportion of people reporting mMRC ≥2 was significantly higher in those with severe- (n = 37, 53%) than those with mild-to-moderate (n = 21, 31%) asthma (P = .013). Dyspnoea-12 Total (8.00 [4.75, 17.00] vs 5.00 [2.00, 11.00], P = .037) score was also significantly higher in the severe asthma group. Significant predictors of physically limiting breathlessness were BMI, asthma control, exercise capacity, and hyperventilation symptoms. Airflow limitation and type 2 inflammation were poor breathlessness predictors. CONCLUSIONS: Over half of people with severe asthma experience physically limiting breathlessness despite treatment. Targeting psychophysiological factors, or traits, associated with breathlessness may help relieve this distressing symptom, which is of high priority to people with asthma.

Pulmonary Rehabilitation with and without a Cognitive Behavioral Intervention for Breathlessness in People Living with Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial.

(1) Background: Most controlled trials of cognitive behavior therapy (CBT) in people living with chronic obstructive pulmonary disease (COPD) have targeted anxiety and depression. (2) Methods: This pragmatic randomized controlled trial explored whether a comprehensive pulmonary rehabilitation program (CPRP) with CBT for breathlessness or social group control (CPRP + SC) significantly improved health outcomes. (3) Results: People with moderate-to-severe COPD were block randomized (CPRP + CBT n = 52 or CPRP + SC n = 49). Primary outcomes (Hospital Anxiety and Depression scale (HADs), six-minute walk distance (6MWD)) and secondary outcomes (breathlessness, quality of life and habitual physical activity) were assessed before and 1, 6 and 12 months post intervention. Between-group differences were calculated with mixed models for each time point to baseline (intention to treat (ITT)). Participants (n = 101, mean ± SD age 70 ± 8.5 years, 54 (53%) males, FEV1% pred 47.7 ± 16.3) were similar between groups. Post intervention, primary outcomes did not differ significantly between groups at 1 (6MWD mean difference -7.5 [95% CI -34.3 to 19.4], HADs-A -0.3 [-1.4 to 0.9], HADs-D 0.2 [-0.8 to 1.3]), 6 (6MWD -11.5 [-38.1 to 15.1], HADs-A 1.1 [0.0 to 2.2], HADs-D 0.2 [-0.9 to 1.3]), or 12 months (6MWD -3.8 [-27.2 to 19.6], HADS-A -0.4 [-1.5 to 0.6], HADs-D -0.7 [-1.7 to 0.4]). (4) Conclusions: In this cohort, combining CBT with a CPRP did not provide additional health benefits beyond those achieved by a standard CPRP.

Impact of trigeminal nerve and/or olfactory nerve stimulation on activity of human brain regions involved in the perception of breathlessness.

Breathlessness is a centrally processed symptom, as evidenced by activation of distinct brain regions such as the insular cortex and amygdala, during the anticipation and/or perception of breathlessness. Inhaled L-menthol or blowing cool air to the face/nose, both selective trigeminal nerve (TGN) stimulants, relieve breathlessness without concurrent improvements in physiological outcomes (e.g., breathing pattern), suggesting a possible but hitherto unexplored central mechanism of action. Four databases were searched to identify published reports supporting a link between TGN stimulation and activation of brain regions involved in the anticipation and/or perception of breathlessness. The collective results of the 29 studies demonstrated that TGN stimulation activated 12 brain regions widely implicated in the anticipation and/or perception of breathlessness, including the insular cortex and amygdala. Inhaled L-menthol or cool air to the face activated 75% and 33% of these 12 brain regions, respectively. Our findings support the hypothesis that TGN stimulation contributes to breathlessness relief by altering the activity of brain regions involved in its central neural processing.

Impact of trigeminal and/or olfactory nerve stimulation on measures of inspiratory neural drive: Implications for breathlessness.

The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on the trigeminal nerve (TGN) with TGN agonists such as menthol or cool air to the face/nose has been hypothesized to reduce breathlessness by decreasing IND. The aim of this systematic scoping review was to identify and summarize the results of studies in animals and humans reporting on the impact of TGN stimulation or blockade on measures of IND. Thirty-one studies were identified, including 19 in laboratory animals and 12 in human participants. Studies in laboratory animals consistently reported that as TGN activity increased, measures of IND decreased (e.g., phrenic nerve activity). In humans, stimulation of the TGN with a stream of cool air to the face/nose decreased the sensitivity of the ventilatory chemoreflex response to hypercapnia. Otherwise, TGN stimulation with menthol or cool air to the face/note had no effect on measures of IND in humans. This review provides new insight into a potential neural mechanism of breathlessness relief with selected TGN agonists.

Key Considerations When Addressing Physical Inactivity and Sedentary Behaviour in People with Asthma.

People with asthma tend to be less physically active and more sedentary than people without asthma. This narrative review aimed to present key considerations when addressing physical inactivity and sedentary behaviour in people with asthma by identifying barriers and facilitators, determinants and correlates, and intervention approaches. Using a search strategy, electronic databases were searched for relevant studies. Data extracted from studies were qualitatively synthesised. A total of 26 studies were included in the review. Six studies reported asthma symptoms as a barrier to physical activity, while four studies reported having a supportive network as a physical activity facilitator. Across studies, physical activity correlates/determinants were pulmonary function, exercise capacity, body mass index, dyspnoea, psychological health, and asthma control. Interventions that effectively improved physical activity in the short term were a step-based prescription programme, a weight loss programme incorporating aerobic and resistance training, and a weight loss lifestyle intervention, while a high-intensity interval training pulmonary rehabilitation program was effective in the long term. The collective findings suggest that a personalised physical activity programme incorporating different strategies is needed. There was minimal evidence to provide recommendations to optimise sedentary behaviour in asthma, and more research is needed on the topic.