Functional Recovery of Adults Following Acute COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to investigate the objective, functional recovery of patients more than 3 months after acute COVID-19 infection. METHODS: Comprehensive database searches of EMBASE, PubMed/MEDLINE, Cochrane COVID-19 Study Register, CINAHL, and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were carried out until October 19, 2022. Data were extracted and agreed in duplicate. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method. RESULTS: One-hundred six papers covering 20,063 patients who were either hospitalized or not hospitalized with acute COVID-19 who were followed-up between 3 to 24 months were included. Percentage predicted 6-minute walk distance at 3 months to <5 months was 84.3% (95% CI = 79.2-89.3; n = 21; I2 = 98.3%) and 92.5% (95% CI = 89.8-95.3; n = 9; I2 = 94.5%) at ≥11 months. Cardiopulmonary exercise testing revealed percentage predicted peak oxygen consumption rate ($peak\dot{\mathrm{V}}{\mathrm{o}}_2$) at 3 months to <5 months was 77.3% (95% CI = 71.0-83.7; n = 6; I2 = 92.3%) and 95.4% (95% CI = 87.1-103.6; n = 2; I2 = 77.3%) at ≥11 months. Mean handgrip strength was greatest at ≥11 months at 31.16 kg (95% CI = 19.89-42.43; n = 2; I2 = 98.3%) of all time points. All analyses showed marked heterogeneity. CONCLUSION: Patients have reduced physical function more than 3 months after COVID-19 infection. Better physical function in multiple physical domains is found after a longer recovery time. IMPACT: Physical function as measured by the 6-minute walk test, hand grip strength, and cardiopulmonary exercise testing is reduced at 3 months after COVID-19 infection and can remain over 11 months of follow-up. This protracted recovery following acute COVID-19 infection supports the need to assess physical function at any clinical follow-up, and further research into rehabilitation programs and intervention for patients who have not recovered.

Accelerated elastin degradation by age-disease interaction: a common feature in age-related diseases.

Aging is a major driving force for many diseases but the relationship between chronological age, the aging process and age-related diseases is not fully understood. Fragmentation and loss of ultra-long-lived elastin are key features in aging and several age-related diseases leading to increased mortality. By comparing the relationship between age and elastin turnover with healthy volunteers, we show that accelerated elastin turnover by age-disease interaction is a common feature of age-related diseases.

Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

Balancing the value and risk of exercise-based therapy post-COVID-19: a narrative review.

Coronavirus disease 2019 (COVID-19) can lead to ongoing symptoms such as breathlessness, fatigue and muscle pain, which can have a substantial impact on an individual. Exercise-based rehabilitation programmes have proven beneficial in many long-term conditions that share similar symptoms. These programmes have favourably influenced breathlessness, fatigue and pain, while also increasing functional capacity. Exercise-based rehabilitation may benefit those with ongoing symptoms following COVID-19. However, some precautions may be necessary prior to embarking on an exercise programme. Areas of concern include ongoing complex lung pathologies, such as fibrosis, cardiovascular abnormalities and fatigue, and concerns regarding post-exertional symptom exacerbation. This article addresses these concerns and proposes that an individually prescribed, symptom-titrated exercise-based intervention may be of value to individuals following infection with severe acute respiratory syndrome coronavirus 2.

Nepalese indoor cookstove smoke extracts alter human airway epithelial gene expression, DNA methylation and hydroxymethylation.

Household air pollution caused by inefficient cooking practices causes 4 million deaths a year worldwide. In Nepal, 86% of the rural population use solid fuels for cooking. Over 25% of premature deaths associated with air pollution are respiratory in nature. Here we aimed to identify molecular signatures of different cookstove and fuel type exposures in human airway epithelial cells, to understand the mechanisms mediating cook stove smoke induced lung disease. Primary human airway epithelial cells in submerged culture were exposed to traditional cook stove (TCS), improved cook stove (ICS) and liquefied petroleum gas (LPG) stove smoke extracts. Changes to gene expression, DNA methylation and hydroxymethylation were measured by bulk RNA sequencing and HumanMethylationEPIC BeadChip following oxidative bisulphite conversion, respectively. TCS smoke extract alone reproducibly caused changes in the expression of 52 genes enriched for oxidative stress pathways. TCS, ICS and LPG smoke extract exposures were associated with distinct changes to DNA methylation and hydroxymethylation. A subset of TCS induced genes were associated with differentially methylated and/or hydroxymethylated CpGs sites, and enriched for the ferroptosis pathway and the upstream regulator NFE2L2. DNA methylation and hydroxymethylation changes not associated with a concurrent change in gene expression, were linked to biological processes and molecular pathways important to airway health, including neutrophil function, transforming growth factor beta signalling, GTPase activity, and cell junction organisation. Our data identified differential impacts of TCS, ICS and LPG cook stove smoke on the human airway epithelium transcriptome, DNA methylome and hydroxymethylome and provide further insight into the association between indoor air pollution exposure and chronic lung disease mechanisms.

Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis.

OBJECTIVE: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19. DESIGN: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations. SETTING: 64 UK acute hospital Trusts. PARTICIPANTS: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19. MAIN OUTCOME MEASURES: Self-reported swallow, communication, voice and cognitive compromise. RESULTS: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001). CONCLUSION: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.

Circulating testosterone levels and health outcomes in chronic obstructive pulmonary disease: results from ECLIPSE and ERICA.

The relationship of circulating testosterone levels with health outcomes in people with chronic obstructive pulmonary disease (COPD) is unknown. AIM: To determine whether serum testosterone levels predict hospitalised acute exacerbations of COPD (H-AECOPD), cardiovascular disease outcome, and mortality in people with COPD. METHODS: Separate analyses were carried out on two observational, multicentre COPD cohorts, Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) and Evaluation of the Role of Inflammation in Chronic Airways Disease (ERICA), both of which had serum testosterone measured using a validated liquid chromatography assay at the same laboratory. Data from 1296 male participants in ECLIPSE and 386 male, 239 female participants in ERICA were analysed. All analyses were sex-specific. Multivariate logistic regression was used to determine associations with H-AECOPD during follow-up (3 years ECLIPSE, 4.5 years ERICA), a composite endpoint of cardiovascular hospitalisation and cardiovascular death, and all-cause mortality. RESULTS: Mean (SD) testosterone levels were consistent across cohorts; 459 (197) and 455 (200) ng/dL for males in ECLIPSE and ERICA, respectively, and in ERICA females: 28 (56) ng/dL. Testosterone was not associated with H-AECOPD (ECLIPSE: OR: 0.76, p=0.329, ERICA males: OR (95% CI): 1.06 (0.73 to 1.56), p=0.779, ERICA females: OR: 0.77 (0.52 to 1.12), p=0.178) or cardiovascular hospitalisation and death. Testosterone was associated with all-cause mortality in Global Initiative for Obstructive Lung Disease (GOLD) stage 2 male patients only, in ECLIPSE (OR: 0.25, p=0.007) and ERICA (OR: (95% CI): 0.56 (0.32 to 0.95), p=0.030). CONCLUSIONS: Testosterone levels do not relate to H-AECOPD or cardiovascular outcome in COPD, but are associated with all-cause mortality in GOLD stage 2 COPD male patients, although the clinical significance of this finding is uncertain.

Association between antidepressants with pneumonia and exacerbation in patients with COPD: a self-controlled case series (SCCS).

OBJECTIVE: To assess whether antidepressant prescriptions are associated with an increased risk of pneumonia and chronic obstructive pulmonary disease (COPD) exacerbation. METHODS: A self-controlled case series was performed to investigate the rates of pneumonia and COPD exacerbation during periods of being exposed to antidepressants compared with non-exposed periods. Patients with COPD with pneumonia or COPD exacerbation and at least one prescription of antidepressant were ascertained from The Health Improvement Network in the UK. Incidence rate ratios (IRR) and 95% CI were calculated for both outcomes. RESULTS: Of 31 253 patients with COPD with at least one antidepressant prescription, 1969 patients had pneumonia and 18 483 had a COPD exacerbation. The 90-day risk period following antidepressant prescription was associated with a 79% increased risk of pneumonia (age-adjusted IRR 1.79, 95% CI 1.54 to 2.07). These associations then disappeared once antidepressants were discontinued. There was a 16% (age-adjusted IRR 1.16, 95% CI 1.13 to 1.20) increased risk of COPD exacerbation within the 90 days following antidepressant prescription. This risk persisted and slightly increased in the remainder period ((age-adjusted IRR 1.38, 95% CI 1.34 to 1.41), but diminished after patients discounted the treatment. CONCLUSION: Antidepressants were associated with an increased risk of both pneumonia and exacerbation in patients with COPD, with the risks diminished on stopping the treatment. These findings suggest a close monitoring of antidepressant prescription side effects and consideration of non-pharmacological interventions.

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study.

BACKGROUND: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. METHODS: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2-7 months after hospital discharge and a later time point 10-14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4-6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5-8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (-19%; 95% CI -20 to -16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18-39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27-41% of this effect. INTERPRETATION: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. FUNDING: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

Domesticating cleaner cookstoves for improved respiratory health: Using approaches from the sanitation sector to explore the adoption and sustained use of improved cooking technologies in Nepal.

Drawing on village-based data from Nepal, this paper explores the transferability of the Integrated Behavioural Model for Water, Sanitation and Hygiene (IBM-WASH) to the clean cooking sector and its potential to elucidate how barriers to improved cookstove adoption and sustained use intersect at different scales. The paper also explores the potential of IBM-WASH, behaviour settings theory and domestication analysis to collectively inform effective behaviour change techniques and interventions that promote both adoption and sustained use of health-promoting technologies. Information on cookstove use in the community since 2012 enables valuable insights to be gained on how kitchen settings and associated cooking behaviour were re-configured as homes and stoves were re-built following the April 2015 earthquake. The methodological approach comprised of semi-structured interviews, focus group discussions, direct observation and household surveys. The findings indicated that the IBM-WASH framework translated well to the improved cookstove sector, capturing key influences on clean cooking transitions across the model's three dimensions (context, psychosocial and technology) at all five levels. Understandings gained from utilising IBM-WASH were enhanced - especially at the individual and habitual levels - by domestication analysis and settings theory which elucidated how different cooking technologies were incorporated (or not) within physical structures, everyday lives and routine behaviour. The paper concludes that this combination of approaches has potential applicability for initiatives seeking to promote improved environmental health at community-wide scales.

Joint patient and clinician priority setting to identify 10 key research questions regarding the long-term sequelae of COVID-19.

Given the large numbers of people infected and high rates of ongoing morbidity, research is clearly required to address the needs of adult survivors of COVID-19 living with ongoing symptoms (long COVID). To help direct resource and research efforts, we completed a research prioritisation process incorporating views from adults with ongoing symptoms of COVID-19, carers, clinicians and clinical researchers. The final top 10 research questions were agreed at an independently mediated workshop and included: identifying underlying mechanisms of long COVID, establishing diagnostic tools, understanding trajectory of recovery and evaluating the role of interventions both during the acute and persistent phases of the illness.

Impact of Coexisting Dementia on Inpatient Outcomes for Patients Admitted with a COPD Exacerbation.

Purpose: People with COPD are at a higher risk of cognitive dysfunction than the general population. However, the additional impact of dementia amongst such patients is not well understood, particularly in those admitted with a COPD exacerbation. We assessed the impact of coexisting dementia on inpatient mortality and length of stay (LOS) in patients admitted to hospital with a COPD exacerbation, using the United States based National Inpatient Sample database. Patients and Methods: Patients aged over 40 years and hospitalised with a primary diagnosis of COPD exacerbation from 2011 to 2015 were included. Cases were grouped into patients with and without dementia. Multivariable logistic regression analysis, stratified by age, was used to assess risk of inpatient deaths. Cox regression was carried out to compare death rates and competing risk analysis gave estimates of discharge rates with time to death a competing variable. Results: A total of 576,381 patients were included into the analysis, of which 35,372 (6.1%) had co-existent dementia. There were 6413 (1.1%) deaths recorded. The odds of inpatient death were significantly greater in younger patients with dementia (41-64 years) [OR (95% CI) dementia vs without: 1.75 (1.04-2.92), p=0.03]. Cases with dementia also had a higher inpatient mortality rate in the first 4 days [HR (95% CI) dementia vs without: 1.23 (1.08-1.41), p=0.002] and a longer LOS [sub-hazard ratio (95% CI) dementia vs without: 0.93 (0.92-0.94), p<0.001]. Conclusion: Dementia as a comorbidity is associated with worse outcomes based on inpatient deaths and LOS in patients admitted with COPD exacerbations.

Patient-related outcomes in patients referred to a respiratory clinic with persisting symptoms following non-hospitalised COVID-19.

Survivors of COVID-19 can present with varied and persisting symptoms, regardless of hospitalisation. We describe the ongoing symptoms, quality of life and return to work status in a cohort of non-hospitalised COVID-19 survivors with persisting respiratory symptoms presenting to clinic, who consented and completed patient-reported outcome measures. We identified fatigue, reduced quality of life and dysregulated breathing alongside the breathlessness. Those with co-existent fatigue had worse mood and quality of life and were less likely to have returned to normal working arrangements compared to those without fatigue. For non-hospitalised people with persisting symptoms following COVID-19 referred to a respiratory assessment clinic, there was a need for a wider holistic assessment, including return to work strategies.

Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake (V'O2 peak), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle-level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic exercise training (AET) at a matched relative intensity and subsequent exercise withdrawal period we aimed to elucidate the whole-body and muscle mitochondrial responsiveness of healthy young (HY), healthy older (HO) and COPD volunteers to whole-body exercise. METHODS: HY (n=10), HO (n=10) and COPD (n=20) volunteers were studied before and after 8 weeks of AET (65% V'O2 peak) and after 4 weeks of exercise withdrawal. V'O2 peak, muscle maximal mitochondrial ATP production rate (MAPR), mitochondrial content, mitochondrial DNA (mtDNA) copy number and abundance of 59 targeted fuel metabolism mRNAs were determined at all time-points. RESULTS: Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mtDNA copy number relative to a nuclear-encoded housekeeping gene (mean±sd) was greater in HY (804±67) than in HO (631±69; p=0.041). AET increased V'O2 peak in HO (17%; p=0.002) and HY (21%; p<0.001), but not COPD (p=0.603). Muscle MAPR for palmitate increased with training in HO (57%; p=0.041) and HY (56%; p=0.003), and decreased with exercise withdrawal in HO (-45%; p=0.036) and HY (-30%; p=0.016), but was unchanged in COPD (p=0.594). mtDNA copy number increased with AET in HY (66%; p=0.001), but not HO (p=0.081) or COPD (p=0.132). The observed changes in muscle mRNA abundance were similar in all groups after AET and exercise withdrawal. CONCLUSIONS: Intrinsic mitochondrial function was not impaired by ageing or COPD in the untrained state. Whole-body and muscle mitochondrial responses to AET were robust in HY, evident in HO, but deficient in COPD. All groups showed robust muscle mRNA responses. Higher relative exercise intensities during whole-body training may be needed to maximise whole-body and muscle mitochondrial adaptation in COPD.

The Effects of Household Air Pollution (HAP) on Lung Function in Children: A Systematic Review.

The World Health Organization (WHO) estimates that around 3 billion people today are exposed to smoke from the household combustion of solid fuels. While the household use of solid fuels has decreased over the last few decades, it remains a leading modifiable risk factor for the global burden of disease. This systematic review analyzed the impact of Household Air Pollution (HAP) on lung function in children (under 18 years of age), as this is the time period of accelerated growth rate until full skeletal maturity. Data from 11 published studies demonstrated that exposure to smoke from solid fuel was associated with a lower growth rate of several lung function indices (FVC, FEV1, FEF25-75) in children. However, there was no observed association between HAP and the FEV1/FVC ratio over time. Although the evidence suggests an inverse association between high exposure to HAP and lung function indices, there is a lack of longitudinal data describing this association. Therefore, precaution is needed to reduce the smoke exposure from solid fuel burning.

Early Changes and Indicators Characterizing Lung Aging in Neonatal Chronic Lung Disease.

Infants suffering from neonatal chronic lung disease, i.e., bronchopulmonary dysplasia, are facing long-term consequences determined by individual genetic background, presence of infections, and postnatal treatment strategies such as mechanical ventilation and oxygen toxicity. The adverse effects provoked by these measures include inflammatory processes, oxidative stress, altered growth factor signaling, and remodeling of the extracellular matrix. Both, acute and long-term consequences are determined by the capacity of the immature lung to respond to the challenges outlined above. The subsequent impairment of lung growth translates into an altered trajectory of lung function later in life. Here, knowledge about second and third hit events provoked through environmental insults are of specific importance when advocating lifestyle recommendations to this patient population. A profound exchange between the different health care professionals involved is urgently needed and needs to consider disease origin while future monitoring and treatment strategies are developed.