Children's Health in London and Luton (CHILL) cohort: a 12-month natural experimental study of the effects of the Ultra Low Emission Zone on children's travel to school.

BACKGROUND: The Ultra-Low Emission Zone (ULEZ), introduced in Central London in April 2019, aims to enhance air quality and improve public health. The Children's Health in London and Luton (CHILL) study evaluates the impact of the ULEZ on children's health. This analysis focuses on the one-year impacts on the shift towards active travel to school. METHODS: CHILL is a prospective parallel cohort study of ethnically diverse children, aged 6-9 years attending 84 primary schools within or with catchment areas encompassing London's ULEZ (intervention) and Luton (non-intervention area). Baseline (2018/19) and one-year follow-up (2019/20) data were collected at school visits from 1992 (58%) children who reported their mode of travel to school 'today' (day of assessment). Multilevel logistic regressions were performed to analyse associations between the introduction of the ULEZ and the likelihood of switching from inactive to active travel modes, and vice-versa. Interactions between intervention group status and pre-specified effect modifiers were also explored. RESULTS: Among children who took inactive modes at baseline, 42% of children in London and 20% of children in Luton switched to active modes. For children taking active modes at baseline, 5% of children in London and 21% of children in Luton switched to inactive modes. Relative to the children in Luton, children in London were more likely to have switched from inactive to active modes (OR 3.64, 95% CI 1.21-10.92). Children in the intervention group were also less likely to switch from active to inactive modes (OR 0.11, 0.05-0.24). Moderator analyses showed that children living further from school were more likely to switch from inactive to active modes (OR 6.06,1.87-19.68) compared to those living closer (OR 1.43, 0.27-7.54). CONCLUSIONS: Implementation of clean air zones can increase uptake of active travel to school and was particularly associated with more sustainable and active travel in children living further from school.

Assessing the Impact of Non-Exhaust Emissions on the Asthmatic Airway (IONA) Protocol for a Randomised Three-Exposure Crossover Study.

BACKGROUND: People living with asthma are disproportionately affected by air pollution, with increased symptoms, medication usage, hospital admissions, and the risk of death. To date, there has been a focus on exhaust emissions, but traffic-related air pollution (TRAP) can also arise from the mechanical abrasion of tyres, brakes, and road surfaces. We therefore created a study with the aim of investigating the acute impacts of non-exhaust emissions (NEEs) on the lung function and airway immune status of asthmatic adults. METHODS: A randomised three-condition crossover panel design will expose adults with asthma using a 2.5 h intermittent cycling protocol in a random order at three locations in London, selected to provide the greatest contrast in the NEE components within TRAP. Lung function will be monitored using oscillometry, fractional exhaled nitric oxide, and spirometry (the primary outcome is the forced expiratory volume in one second). Biomarkers of inflammation and airborne metal exposure will be measured in the upper airway using nasal lavage. Symptom responses will be monitored using questionnaires. Sources of exhaust and non-exhaust concentrations will be established using source apportionment via the positive matrix factorisation of high-time resolution chemical measures conducted at the exposure sites. DISCUSSION: Collectively, this study will provide us with valuable information on the health effects of NEE components within ambient PM2.5 and PM10, whilst establishing a biological mechanism to help contextualise current epidemiological observations.

Investigating the impact of London's ultra low emission zone on children's health: children's health in London and Luton (CHILL) protocol for a prospective parallel cohort study.

BACKGROUND: Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children's Health in London and Luton) to evaluate the impacts of the introduction of London's Ultra Low Emission Zone (ULEZ) on children's health. METHODS: CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6-9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO2], particulate matter with a diameter of less than 2.5micrograms [PM2.5], and less than 10 micrograms [PM10]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV1) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. DISCUSSION: CHILL's prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children's respiratory health. With increasing proportions of the world's population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. CLINICALTRIALS: GOV: NCT04695093 (05/01/2021).

Ethical and Information Governance Considerations for Promoting Digital Social Interventions in Primary Care.

Promoting online peer support beyond the informal sector to statutory health services requires ethical considerations and evidence-based knowledge about its impact on patients, health care professionals, and the wider health care system. Evidence on the effectiveness of digital interventions in primary care is sparse, and definitive guidance is lacking on the ethical concerns arising from the use of social media as a means for health-related interventions and research. Existing literature examining ethical issues with digital interventions in health care mainly focuses on apps, electronic health records, wearables, and telephone or video consultations, without necessarily covering digital social interventions, and does not always account for primary care settings specifically. Here we address the ethical and information governance aspects of undertaking research on the promotion of online peer support to patients by primary care clinicians, related to medical and public health ethics.

Non-randomised feasibility study testing a primary care intervention to promote engagement in an online health community for adults with troublesome asthma: protocol.

INTRODUCTION: In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a 'survey leading to a trial' design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention. METHODS AND ANALYSIS: Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention. ETHICS AND DISSEMINATION: Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05829265.

Device-Measured Change in Physical Activity in Primary School Children During the UK COVID-19 Pandemic Lockdown: A Longitudinal Study.

BACKGROUND: Lockdown measures, including school closures, due to the COVID-19 pandemic have caused widespread disruption to children's lives. The aim of this study was to explore the impact of a national lockdown on children's physical activity using seasonally matched accelerometry data. METHODS: Using a pre/post observational design, 179 children aged 8 to 11 years provided physical activity data measured using hip-worn triaxial accelerometers worn for 5 consecutive days prepandemic and during the January to March 2021 lockdown. Multilevel regression analyses adjusted for covariates were used to assess the impact of lockdown on time spent in sedentary and moderate to vigorous physical activity. RESULTS: A 10.8-minute reduction in daily time spent in moderate to vigorous physical activity (standard error: 2.3 min/d, P < .001) and a 33.2-minute increase in daily sedentary activity (standard error: 5.5 min/d, P < .001) were observed during lockdown. This reflected a reduction in daily moderate to vigorous physical activity for those unable to attend school (-13.1 [2.3] min/d, P < .001) during lockdown, with no significant change for those who continued to attend school (0.4 [4.0] min/d, P < .925). CONCLUSION: These findings suggest that the loss of in-person schooling was the single largest impact on physical activity in this cohort of primary school children in London, Luton, and Dunstable, United Kingdom.

Patient and public involvement in research: the need for budgeting PPI staff costs in funding applications.

BACKGROUND: Patient and Public Involvement (PPI) groups are becoming more established as collaborators with academic researchers and institutions to ensure that research is important and relevant to end users, and to identify areas that might have ethical considerations, as well as to advise on solutions. The National Institute for Health and Care Research UK Standards for Public Involvement in Research embody best practice for PPI, including support and learning opportunities that build confidence and skills for members of the public to play an invaluable and mutually productive role in research. However, the pivotal role of research and professional services (management and administrative) staff within academic institutions for sustaining and making this involvement successful is often overlooked. MAIN BODY: It takes significant effort to develop and sustain effective PPI in research. The six UK Standards for Public Involvement highlight the need for consistent, inclusive, well-governed and mutually respectful working relationships to sustain effective PPI contributions in health research. Productivity across a team of lay and academic members requires organisation and experience of implementing these standards by a dedicated PPI team, yet advice on PPI finances is usually focused on costs for patient panel members, and budgets in funding applications rarely consider the wider PPI team behind this involvement. As an exemplar, we reflect on how the Asthma UK Centre for Applied Research (AUKCAR) has developed a dedicated PPI Platform, with guidance for how PPI should be embedded throughout the research lifecycle, and detailed information to support the costing of PPI in funding applications. AUKCAR's work with established researchers, as well as Early Career Researchers and PhD students, is at the heart of a campaign to raise awareness of the importance of PPI in effective research planning. CONCLUSION: Focusing attention on the staff behind best practice involvement in health research may stimulate a much-needed discussion to ensure flourishing PPI capacity, with significant patient and public benefit. With adaptation, the PPI expertise within AUKCAR can be translated more widely.

Patient and Public Involvement (PPI) is important for high-quality research. It makes research more relevant to patients, and makes the results more useful for the health service. To make patient involvement effective, we need skilled staff with experience of involving lay members in research, as well as engaging researchers in PPI activities. There is little guidance about staff time needed to recruit and support lay members and researchers properly. This means that we still do not understand the true cost of including patients and the public in research, and we often under cost this in funding applications. As an example, we reflect on how the Asthma UK Centre for Applied Research (AUKCAR) has organised staff to support for its patient involvement. We give some thoughts on how to cost PPI staff time in funding applications. By focusing attention on the team behind the lay volunteers, we hope to encourage a much-needed discussion about the support involved, and deliver more patient benefits. The AUKCAR experience can be adapted to other research topics and contexts.

Impact of London's low emission zone on air quality and children's respiratory health: a sequential annual cross-sectional study.

BACKGROUND: Low emission zones (LEZ) are an increasingly common, but unevaluated, intervention aimed at improving urban air quality and public health. We investigated the impact of London's LEZ on air quality and children's respiratory health. METHODS: We did a sequential annual cross-sectional study of 2164 children aged 8-9 years attending primary schools between 2009-10 and 2013-14 in central London, UK, following the introduction of London's LEZ in February, 2008. We examined the association between modelled pollutant exposures of nitrogen oxides (including nitrogen dioxide [NO2]) and particulate matter with a diameter of less than 2·5 µm (PM2·5) and less than 10 µm (PM10) and lung function: postbronchodilator forced expiratory volume in 1 s (FEV1, primary outcome), forced vital capacity (FVC), and respiratory or allergic symptoms. We assigned annual exposures by each child's home and school address, as well as spatially resolved estimates for the 3 h (0600-0900 h), 24 h, and 7 days before each child's assessment, to isolate long-term from short-term effects. FINDINGS: The percentage of children living at addresses exceeding the EU limit value for annual NO2 (40 µg/m3) fell from 99% (444/450) in 2009 to 34% (150/441) in 2013. Over this period, we identified a reduction in NO2 at both roadside (median -1·35 µg/m3 per year; 95% CI -2·09 to -0·61; p=0·0004) and background locations (-0·97; -1·56 to -0·38; p=0·0013), but not for PM10. The effect on PM2·5 was equivocal. We found no association between postbronchodilator FEV1 and annual residential pollutant attributions. By contrast, FVC was inversely correlated with annual NO2 (-0·0023 L/µg per m3; -0·0044 to -0·0002; p=0·033) and PM10 (-0·0090 L/µg per m3; -0·0175 to -0·0005; p=0·038). INTERPRETATION: Within London's LEZ, a smaller lung volume in children was associated with higher annual air pollutant exposures. We found no evidence of a reduction in the proportion of children with small lungs over this period, despite small improvements in air quality in highly polluted urban areas during the implementation of London's LEZ. Interventions that deliver larger reductions in emissions might yield improvements in children's health. FUNDING: National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London, NHS Hackney, Lee Him donation, and Felicity Wilde Charitable Trust.

Air pollution, ethnicity and telomere length in east London schoolchildren: An observational study.

BACKGROUND: Short telomeres are associated with chronic disease and early mortality. Recent studies in adults suggest an association between telomere length and exposure to particulate matter, and that ethnicity may modify the relationship. However associations in children are unknown. OBJECTIVES: We examined associations between air pollution and telomere length in an ethnically diverse group of children exposed to high levels of traffic derived pollutants, particularly diesel exhaust, and to environmental tobacco smoke. METHODS: Oral DNA from 333 children (8-9years) participating in a study on air quality and respiratory health in 23 inner city London schools was analysed for relative telomere length using monochrome multiplex qPCR. Annual, weekly and daily exposures to nitrogen oxides and particulate matter were obtained from urban dispersion models (2008-10) and tobacco smoke by urinary cotinine. Ethnicity was assessed by self-report and continental ancestry by analysis of 28 random genomic markers. We used linear mixed effects models to examine associations with telomere length. RESULTS: Telomere length increased with increasing annual exposure to NOx (model coefficient 0.003, [0.001, 0.005], p<0.001), NO2 (0.009 [0.004, 0.015], p<0.001), PM2.5 (0.041, [0.020, 0.063], p<0.001) and PM10 (0.096, [0.044, 0.149], p<0.001). There was no association with environmental tobacco smoke. Telomere length was increased in children reporting black ethnicity (22% [95% CI 10%, 36%], p<0.001) CONCLUSIONS: Pollution exposure is associated with longer telomeres in children and genetic ancestry is an important determinant of telomere length. Further studies should investigate both short and long-term associations between pollutant exposure and telomeres in childhood and assess underlying mechanisms.

Effects of Air Pollution and the Introduction of the London Low Emission Zone on the Prevalence of Respiratory and Allergic Symptoms in Schoolchildren in East London: A Sequential Cross-Sectional Study.

The adverse effects of traffic-related air pollution on children's respiratory health have been widely reported, but few studies have evaluated the impact of traffic-control policies designed to reduce urban air pollution. We assessed associations between traffic-related air pollutants and respiratory/allergic symptoms amongst 8-9 year-old schoolchildren living within the London Low Emission Zone (LEZ). Information on respiratory/allergic symptoms was obtained using a parent-completed questionnaire and linked to modelled annual air pollutant concentrations based on the residential address of each child, using a multivariable mixed effects logistic regression analysis. Exposure to traffic-related air pollutants was associated with current rhinitis: NOx (OR 1.01, 95% CI 1.00-1.02), NO2 (1.03, 1.00-1.06), PM10 (1.16, 1.04-1.28) and PM2.5 (1.38, 1.08-1.78), all per µg/m3 of pollutant, but not with other respiratory/allergic symptoms. The LEZ did not reduce ambient air pollution levels, or affect the prevalence of respiratory/allergic symptoms over the period studied. These data confirm the previous association between traffic-related air pollutant exposures and symptoms of current rhinitis. Importantly, the London LEZ has not significantly improved air quality within the city, or the respiratory health of the resident population in its first three years of operation. This highlights the need for more robust measures to reduce traffic emissions.

Carbon in airway macrophages from children with asthma.

BACKGROUND: Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. METHODS: AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (µm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. RESULTS: AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). CONCLUSIONS: Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.

Dyspnea on exertion in obese men.

Recently, we reported that dyspnea on exertion is strongly associated with an increased oxygen cost of breathing in otherwise healthy obese women; the mechanism of dyspnea on exertion in obese men is unknown. Obese men underwent measurements of body composition, fat distribution, pulmonary function, steady state and maximal graded cycle ergometry, and oxygen cost of breathing. Nine men (34 ± 8 years, 35 ± 4 BMI) with ratings of perceived breathlessness of ≤2 during cycling, and ten men (36 ± 9 years, 38 ± 5 BMI) with ratings of perceived breathlessness ≥4 were studied (ratings of perceived breathlessness: 1.8 ± 0.4 vs. 4.7 ± 0.8, respectively; p<0.0001). Groups had only minor differences in fat distribution, pulmonary function, and steady state exercise. There was no association between ratings of perceived breathlessness and oxygen cost of breathing; but ratings of perceived breathlessness was strongly correlated with ratings of perceived exertion (RPE, rho=0.87, p<0.0001). The differences in exercise intensity, ventilatory demand, cardiovascular conditioning and/or the quality of respiratory sensation did not appear to play a role in the development of dyspnea on exertion. The mechanism of dyspnea on exertion in obese men seems unrelated to the oxygen cost of breathing.

Short-term modulation of the exercise ventilatory response in younger and older women.

The exercise ventilatory response (EVR; defined as the slope of the relationship between ventilation and CO(2) production) is reversibly augmented within a single exercise trial with increased respiratory dead space (DS) in both younger (Wood, H.E., Mitchell, G.S., Babb, T.G., 2008. Short-term modulation of the exercise ventilatory response in young men. J. Appl. Physiol. 104, 244-252) and older (Wood, H.E., Mitchell, G.S., Babb, T.G., 2010. Short-term modulation of the exercise ventilatory response in older men. Respir. Physiol. Neurobiol. 173, 37-46) men. The neural mechanism accounting for this augmentation is known as short-term modulation (STM) of the EVR. Since the effects of female sex hormones on STM are unknown, we examined the capacity for STM in healthy adult women of two age groups; nine younger (29±3 yrs, eumenorrheic) and seven older (69±3 yrs, postmenopausal) women were studied at rest and during cycle exercise (10 W, 30 W; not randomized) in control conditions and with added external DS (200 mL, 400 mL; randomized). Within groups, the main effects of DS and work rate on EVR were analyzed with a two-way repeated measures ANOVA; EVR comparisons between groups were made with unpaired t-tests. In both groups, EVR increased progressively with increasing DS volume (e.g. at 10 W 31±4 and 35±6 in control, 40±11 and 40±6 with 200 mL, 48±12 and 49±11 with 400 mL DS in younger and older women, respectively). In younger women, the effects of DS on EVR differed between work rates (significant interaction, p<0.05), although this was not the case for older women. In both groups, [Formula: see text] regulation was similar between DS and control; hence, increased EVR was not due to altered chemoreceptor feedback from rest to exercise. EVR with and without added DS did not differ between age groups. We conclude that the capacity for STM of the EVR with added DS is similar in healthy younger and older women.

Short-term modulation of the exercise ventilatory response in older men.

During exercise with added dead space (DS), the exercise ventilatory response (DeltaV(E)/ DeltaV(CO(2))) is augmented in younger men, via short-term modulation (STM) of the exercise ventilatory response. We hypothesized that STM would be diminished or absent in older men due to age-related changes in respiratory function and ventilatory control. Men were studied at rest and during cycle exercise with and without added DS. DeltaV(E)/ DeltaV(CO(2)) increased progressively with increasing DS volume (p<0.01), such that CO(2) was not retained with added DS versus without. Hence, the increase in DeltaV(E)/ DeltaV(CO(2)) was not due to increased chemoreceptor feedback from rest to exercise. Increasing exercise intensity diminished the DeltaV(E)/ DeltaV(CO(2)) (p<0.01), and the size of this effect varied by DS volume (p<0.05). We conclude that STM of the exercise ventilatory response is robust in older men; hence, despite age-related changes in lung function and ventilatory control, the exercise ventilatory response can still adapt to increased DS, in order to maintain isocapnia during exercise relative to rest.

Short- and long-term modulation of the exercise ventilatory response.

The importance of adaptive control strategies (modulation and plasticity) in the control of breathing during exercise has become recognized only in recent years. In this review, we discuss new evidence for modulation of the exercise ventilatory response in humans, specifically, short- and long-term modulation. Short-term modulation is proposed to be an important regulatory mechanism that helps maintain blood gas homeostasis during exercise.

Breathing mechanics during exercise with added dead space reflect mechanisms of ventilatory control.

Small increases in external dead space (V(D)) augment the exercise ventilatory response via a neural mechanism known as short-term modulation (STM). We hypothesized that breathing mechanics would differ during exercise, increased V(D) and STM. Men were studied at rest and during cycle exercise (10-50W) without (Control) and with added V(D) (200-600ml). With added V(D), V(T) increased via increased end-inspiratory lung volume (EILV), with no change in end-expiratory lung volume (EELV), indicating recruitment of inspiratory muscles only. With exercise, V(T) increased via both decreased EELV and increased EILV, indicating recruitment of both expiratory and inspiratory muscles. A significant interaction between the effects of exercise and V(D) on mean inspiratory flow indicated that the augmented exercise ventilatory response with added V(D) (i.e. STM) resulted from increased drive to the inspiratory muscles. These results reveal different patterns of respiratory muscle recruitment among experimental conditions. Hence, we conclude that fundamental differences exist in the neural control of ventilatory responses during exercise, increased V(D) and STM.

Ventilatory responses to exercise and hypercapnia following 18 days of head-down rest.

INTRODUCTION: The effects of head-down rest (HDR) and microgravity on cardiovascular control have been widely studied; however, their effects on ventilatory control are less clear. An increased ventilatory response to exercise and/or to hypercapnia (HCVR) could cause significantly increased ventilatory demand and/or dyspnea, and thus limit the ability of flight crew to perform high-intensity exercise during or after spaceflight. Based on limited previous studies, we hypothesized that the ventilatory response to exercise would be increased, while the HCVR would be decreased after HDR. METHODS: In 21 healthy subjects, ventilatory responses to submaximal exercise and to hypercapnia were tested before and immediately after 18 d of HDR. Subjects were randomly assigned to either daily supine cycle exercise (Exercise group; N = 14, 2 women) or no exercise (Rest group; N = 7, 1 woman) during HDR. RESULTS: The exercise ventilatory response (DeltaV(E)/DeltaV(CO2)) and the HCVR were unchanged following HDR in both groups. However, ventilation was significantly elevated after HDR at rest, during submaximal exercise, and while breathing 6% CO2. End-tidal P(CO2) was significantly reduced at rest, during submaximal exercise, and while breathing 3% CO2, indicating a decrease in the CO2 set point. DISCUSSION: Although HDR had no effect on the ventilatory responses to exercise and hypercapnia, the CO2 set point appeared to be reduced, suggesting an increase in drive to breathe that occurred regardless of whether or not subjects undertook exercise during HDR. These preliminary results indicate that further study of the effects of HDR on ventilatory control is warranted.

Short-term modulation of the exercise ventilatory response in young men.

Arterial isocapnia is a hallmark of moderate exercise in humans and is maintained even when resting arterial Pco(2) (Pa(CO(2))) is raised or lowered from its normal level, e.g., with chronic acid-base changes or acute increases in respiratory dead space. When resting ventilation and/or Pa(CO(2)) are altered, maintenance of isocapnia requires active adjustments of the exercise ventilatory response [slope of the ventilation (Ve)-CO(2) production (Vco(2)) relationship, DeltaVe/DeltaVco(2)]. On the basis of animal studies, it has been proposed that a central neural mechanism links the exercise ventilatory response to the resting ventilatory drive without need for changes in chemoreceptor feedback from rest to exercise, a mechanism referred to as short-term modulation (STM). We tested the hypothesis that STM is elicited by increased resting ventilatory drive associated with added external dead space (DS) in humans. Twelve young men were studied in control conditions and with added DS (200, 400, and 600 ml; randomized) at rest and during mild-to-moderate cycle exercise. DeltaVe/DeltaVco(2) increased progressively as DS volume increased (P < 0.0001). While resting end-tidal Pco(2) (Pet(CO(2))) increased with DS, the change in Pet(CO(2)) from rest to exercise was not increased, indicating that increased chemoreceptor feedback from rest to exercise cannot account for the greater exercise ventilatory response. We conclude that STM of the exercise ventilatory response is induced in young men when resting ventilatory drive is increased with external DS, confirming the existence of STM in humans.

Prior sustained hypoxia attenuates interaction between hypoxia and exercise as ventilatory stimuli in humans.

Both exercise and hypoxia increase pulmonary ventilation. However, the combined effects of the two stimuli are more than additive, such that exercise may be considered to potentiate the acute ventilatory response to hypoxia (AHVR), and vice versa. Exposure to sustained hypoxia of 8 h duration or more has been shown to increase the acute chemoreflex responses to hypoxia and hypercapnia. The purpose of this study was to determine whether sustained exposure to hypoxia also changed the stimulus interaction between the effects of exercise and hypoxia on ventilation. Ten subjects undertook two main protocols on two separate days. On one day, subjects were exposed to isocapnic hypoxia (IH) at an end-tidal partial pressure of O(2) of 55 mmHg and on the other day, subjects were exposed to air as a control (C). Before and after each exposure, the sensitivity of AHVR was assessed during both resting conditions and exercise at 35% of the subjects' maximal oxygen uptake capacity. Average values (means +/- s.d.) obtained for the sensitivity of AHVR from protocol IH were 0.85 +/- 0.35 (rest, prehypoxic exposure), 1.60 +/- 0.66 (exercise, prehypoxic exposure), 1.69 +/- 0.63 (rest, posthypoxic exposure) and 1.81 +/- 0.86 l min(-1) %(-1) (exercise, posthypoxic exposure). A non-dimensional variable, Phi, was used to quantify the interaction present between exercise and hypoxia. The variable Phi fell significantly following the sustained exposure to hypoxia (P < 0.02, ANOVA), indicating that the degree of stimulus interaction between acute hypoxia and exercise had declined. We suggest that the mechanisms by which sustained hypoxia modifies peripheral chemoreflex function may also modify the effects of exercise on the peripheral chemoreflex.