Effects of the angle of head-down tilt on dynamic cerebral autoregulation during combined exposure to cephalad fluid shift and mild hypercapnia.

Astronauts experience combined exposure to a cephalad fluid shift and mild hypercapnia during space missions, potentially contributing to health problems. Such combined exposure may weaken dynamic cerebral autoregulation. The magnitude of cephalad fluid shift varies between individuals, and dynamic cerebral autoregulation may be affected more by greater cephalad fluid shift during combined exposure. We evaluated the dose-dependent effects of head-down tilt (HDT) on dynamic cerebral autoregulation during acute combined exposure to HDT and 3% CO2 inhalation. Twenty healthy participants were randomly exposed to three angles of HDT (-5°HDT+CO2, -15°HDT+CO2 and -30°HDT+CO2). After 15 min of rest, participants inhaled room air for 10 min in a horizontal body position, then inhaled 3% CO2 for 10 min under HDT. The last 6 min of data were used for analysis in each stage. Arterial pressure waveforms were obtained using finger blood pressure, and blood velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was evaluated by transfer function analysis between waveforms. Statistical analysis was performed by two-way repeated-measures analysis of variance. The index of transfer function gain in the low-frequency range increased significantly with -15°HDT+CO2 and -30°HDT+CO2, but no changes were seen with -5°HDT+CO2. Phase in the low-frequency range decreased significantly with all three protocols. These results of significant changes in indexes of both gain and phase during combined exposure to steep HDT (-15° to -30°) and 3% CO2 inhalation suggest weakened dynamic cerebral autoregulation with the combination of moderate cephalad fluid shift and mild hypercapnia.

A fluorescent probe for monitoring carboxylesterases in pulmonary cells under permissive hypercapnia condition.

Herein, by combining the benzofuranone-derived fluorophore and the carbamate recognition group, a fluorescent probe named BFO-CarE was developed for monitoring the carboxylesterase (CarE) level in pulmonary cells under the permissive hypercapnia condition. It showed a notable fluorescence response towards CarE at 570 nm under the excitation of 510 nm. The in-solution tests revealed the advantages of BFO-CarE including high sensitivity, high specificity, relatively rapid response, and high steadiness. It was also low-toxic upon the pulmonary cell lines. During the intracellular imaging in pulmonary cells, BFO-CarE achieved the monitoring of the CarE level in both inhibition and activation status. In particular, BFO-CarE realized the visualization of the affection of the permissive hypercapnia condition on the CarE level, which indicated the hypoxia tolerance of CarE. This work was informative for investigating the impact of hypoxia in pulmonary cells, and the corresponding anaesthesia-related approaches.

Pathophysiology of Chronic Hypercapnic Respiratory Failure.

Chronic hypercapnic respiratory failure occurs in several conditions associated with hypoventilation. The mechanisms underlying the development of chronic hypercapnia include a combination of processes that increase metabolic CO2 production, reduce minute ventilation (V'e), or increase dead space fraction (Vd/Vt). Fundamental to the pathophysiology is a mismatch between increased load and a reduction in the capacity of the respiratory pump to compensate. Though neural respiratory drive may be decreased in a subset of central hypoventilation disorders, it is more commonly increased in attempting to maintain the load-capacity homeostatic balance.

Assessment of Chronic Hypercapnic Respiratory Failure.

Undiagnosed chronic hypercapnic respiratory failure may be encountered during the evaluation of sleep-related breathing disorders at the sleep clinic. This article reviews the mechanism of chronic hypercapnic respiratory failure and the systematic approach to the assessment of specific sleep disorders associated with nocturnal hypoventilation encountered in clinical practice.

Interfaces for Home Noninvasive Ventilation.

The choice of interface used to deliver noninvasive ventilation (NIV) is a critical element in successfully and safely establishing home NIV in people with sleep hypoventilation syndromes. Both patient-related and equipment-related factors need to be considered when selecting an interface. Recognizing specific issues that can occur with a particular style of mask is important when troubleshooting NIV problems and attempting to minimize side effects. Access to a range of mask styles and designs to use on a rotational basis is especially important for patients using NIV on a more continuous basis, those at risk of developing pressure areas, and children.

The Role of High Flow Nasal Therapy in Chronic Respiratory Failure.

High-flow nasal therapy (HFNT) has an increasing role in the management of acute hypoxic respiratory failure. Due to its tolerable interface and ease of use, its role in chronic hypercapnic respiratory failure (CHRF) is emerging. This article examines the literature to date surrounding the short and long-term mechanisms of HFNT in sleep and wakefulness of CHRF patients. It is likely HFNT will have an increasing role in those patients intolerant of non-invasive ventilation.

Alterations of cerebrovascular reactivity following pediatric mild traumatic brain injury are independent of neurodevelopmental changes.

Cerebrovascular dysfunction following mild traumatic brain injury (mTBI) is understudied relative to other microstructural injuries, especially during neurodevelopment. The blood-oxygen level dependent response was used to investigate cerebrovascular reactivity (CVR) in response to hypercapnia following pediatric mTBI (pmTBI; ages 8-18 years), as well as pseudocontinuous arterial spin labeling to measure cerebral blood flow (CBF). Data were collected ∼1-week (N = 107) and 4 months (N = 73) post-injury. Sex- and age-matched healthy controls (HC) underwent identical examinations at comparable time points (N = 110 and N = 91). Subtle clinical and cognitive deficits existed at ∼1 week that resolved for some, but not all domains at 4 months post-injury. At both visits, pmTBI showed an increased maximal fit between end-tidal CO2 regressor and the cerebrovascular response across multiple regions (primarily fronto-temporal), as well as increased latency to maximal fit in independent regions (primarily posterior). Hypoperfusion was also noted within the bilateral cerebellum. A biphasic relationship existed between CVR amplitude and age (i.e., positive until 14.5 years, negative thereafter) in both gray and white matter, but these neurodevelopment effects did not moderate injury effects. CVR metrics were not associated with post-concussive symptoms or cognitive deficits. In conclusion, cerebrovascular dysfunction may persist for up to four months following pmTBI.

The complexity of cerebral blood flow regulation: the interaction of posture and vasomotor reactivity.

Arterial carbon dioxide (PaCO2) and posture influence the middle (MCAv) and posterior (PCAv) cerebral artery blood velocitiesbut there is paucity of data about their interaction and need for an integrated model of their effects, including dynamic cerebral autoregulation (dCA). In 22 participants (11 male, age 30.2 ± 14.3 years), blood pressure (BP, Finometer), dominant MCAv and non-dominant PCAv (transcranial Doppler ultrasound), end-tidal CO2 (EtCO2, capnography) and heart rate (HR, ECG) were recorded continuously. Two recordings (R) were taken when the participant was supine (R1, R2), two taken when the participant was sitting (R3, R4), and two taken when the participant was standing (R5, R6). R1, R3 and R5 consisted of 3 minutes of 5% CO2 through a mask and R2, R4 and R6 consisted of 3 minutes of paced hyperventilation. The effects of PaCO2 were expressed with a logistic curve model (LCM) for each parameter. dCA was expressed by the autoregulation index (ARI), dervived by transfer function analysis. Standing shifted LCM to the left for MCAv (p<0.001), PCAv (p<0.001), BP (p=0.03) and ARI (p=0.001); downwards for MCAv and PCAv (both p<0.001), and upwards for HR (p<0.001). For BP, LCM was shifted downwards by sitting and standing (p=0.024). For ARI, the hypercapnic range of LCM was shifted upwards during standing (p<0.001). A more complete mapping of the combined effects of posture and arterial CO2 on the cerebral circulation and peripheral variables can be obtained with the LCM over a broad physiological range of EtCO2 values.

Carbon dioxide induced cerebral vasomotor reactivity in moderate-to-severe cerebral venous thrombosis patients and its impact on prognosis: A transcranial doppler-based prospective exploratory study.

Hyperventilation-induced intracranial pressure reduction might be impaired in cerebral venous thrombosis (CVT) patients. Using transcranial Doppler, we assessed carbon dioxide-vasomotor reactivity (CO2-VMR) within 24 hours of admission in CVT patients and studied its correlation with patient outcomes. Adult moderate-severe CVT patients (participants of another large observational study) were included. CO2-VMR was calculated as the percentage change in peak flow velocities during maximal hypercapnia and hypocapnia. Outcome was assessed with the modified Rankin scale (mRS) at one - month post-discharge, dichotomized into favourable (mRS≤2) and unfavourable (mRS>2). Twenty patients' data was analysed. Impaired CO2-VMR (<70 %) was observed in 13 patients in the affected hemisphere; among them, 10 had impairments in both hemispheres. CO2-VMR correlated negatively with mRS (Rho = -0.688, p = 0.001). Odds for unfavourable outcomes were reduced by 92 % in patients with intact VMR on the ipsilateral hemisphere (Odds ratio (OR) 0.08, Confidence interval (CI) 0.006---0.636, p = 0.027) and by 94 % with VMR intact on the contralateral hemisphere (OR 0.063, CI 0.003---0.569, p = 0.03). Thus, impaired CO2-VMR in moderate to severe CVT patients is associated with unfavourable outcomes, and has the potential to prognosticate CVT patients objectively.

The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection.

Many biological mechanisms of aging well converge with radiation's biological effects. We used scientific insights from the field of aging to establish a novel hypoxic-hypercapnic environment (HHE) concept for radioprotection. According to this concept, HHE which possesses an anti-aging and longevity-promoting potential, should also act as a radiomitigator and radioprotector. As such, it might contribute greatly to the safety and wellbeing of individuals exposed to high levels of radiation, whether in planned events (e.g. astronauts) or in unplanned events (e.g. first responders in nuclear accidents).

Translational insights into the hormetic potential of carbon dioxide: from physiological mechanisms to innovative adjunct therapeutic potential for cancer.

Background: Carbon dioxide (CO2), traditionally viewed as a mere byproduct of cellular respiration, plays a multifaceted role in human physiology beyond simple elimination through respiration. CO2 may regulate the tumor microenvironment by significantly affecting the release of oxygen (O2) to tissues through the Bohr effect and by modulating blood pH and vasodilation. Previous studies suggest hypercapnia (elevated CO2 levels) might trigger optimized cellular mechanisms with potential therapeutic benefits. The role of CO2 in cellular stress conditions within tumor environments and its impact on O2 utilization offers a new investigative area in oncology. Objectives: This study aims to explore CO2's role in the tumor environment, particularly how its physiological properties and adaptive responses can influence therapeutic strategies. Methods: By applying a structured translational approach using the Work Breakdown Structure method, the study divided the analysis into six interconnected work packages to comprehensively analyze the interactions between carbon dioxide and the tumor microenvironment. Methods included systematic literature reviews, data analyses, data integration for identifying critical success factors and exploring extracellular environment modulation. The research used SMART criteria for assessing innovation and the applicability of results. Results: The research revealed that the human body's adaptability to hypercapnic conditions could potentially inform innovative strategies for manipulating the tumor microenvironment. This could enhance O2 utilization efficiency and manage adaptive responses to cellular stress. The study proposed that carbon dioxide's hormetic potential could induce beneficial responses in the tumor microenvironment, prompting clinical protocols for experimental validation. The research underscored the importance of pH regulation, emphasizing CO2 and carbonic acid's role in modulating metabolic and signaling pathways related to cancer. Conclusion: The study underscores CO2 as vital to our physiology and suggests potential therapeutic uses within the tumor microenvironment. pH modulation and cellular oxygenation optimization via CO2 manipulation could offer innovative strategies to enhance existing cancer therapies. These findings encourage further exploration of CO2's therapeutic potential. Future research should focus on experimental validation and exploration of clinical applications, emphasizing the need for interdisciplinary and collaborative approaches to tackle current challenges in cancer treatment.

Developmental plasticity of the cardiovascular system in oviparous vertebrates: effects of chronic hypoxia and interactive stressors in the context of climate change.

Animals at early life stages are generally more sensitive to environmental stress than adults. This is especially true of oviparous vertebrates that develop in variable environments with little or no parental care. These organisms regularly experience environmental fluctuations as part of their natural development, but climate change is increasing the frequency and intensity of these events. The developmental plasticity of oviparous vertebrates will therefore play a critical role in determining their future fitness and survival. In this Review, we discuss and compare the phenotypic consequences of chronic developmental hypoxia on the cardiovascular system of oviparous vertebrates. In particular, we focus on species-specific responses, critical windows, thresholds for responses and the interactive effects of other stressors, such as temperature and hypercapnia. Although important progress has been made, our Review identifies knowledge gaps that need to be addressed if we are to fully understand the impact of climate change on the developmental plasticity of the oviparous vertebrate cardiovascular system.

Central and peripheral mechanisms underlying respiratory deficits in a mouse model of accelerated senescence.

Aging invariably decreases sensory and motor stimuli and affects several neuronal systems and their connectivity to key brain regions, including those involved in breathing. Nevertheless, further investigation is needed to fully comprehend the link between senescence and respiratory function. Here, we investigate whether a mouse model of accelerated senescence could develop central and peripheral respiratory abnormalities. Adult male Senescence Accelerated Mouse Prone 8 (SAMP8) and the control SAMR1 mice (10 months old) were used. Ventilatory parameters were assessed by whole-body plethysmography, and measurements of respiratory input impedance were performed. SAMP8 mice exhibited a reduction in the density of neurokinin-1 receptor immunoreactivity in the entire ventral respiratory column. Physiological experiments showed that SAMP8 mice exhibited a decreased tachypneic response to hypoxia (FiO2 = 0.08; 10 min) or hypercapnia (FiCO2 = 0.07; 10 min). Additionally, the ventilatory response to hypercapnia increased further due to higher tidal volume. Measurements of respiratory mechanics in SAMP8 mice showed decreased static compliance (Cstat), inspiratory capacity (IC), resistance (Rn), and elastance (H) at different ages (3, 6, and 10 months old). SAMP8 mice also have a decrease in contractile response to methacholine compared to SAMR1. In conclusion, our findings indicate that SAMP8 mice display a loss of the NK1-expressing neurons in the respiratory brainstem centers, along with impairments in both central and peripheral respiratory mechanisms. These observations suggest a potential impact on breathing in a senescence animal model.

Changes in cerebral vascular reactivity following mild repetitive head injury in awake rats: modeling the human experience.

The changes in brain function in response to mild head injury are usually subtle and go undetected. Physiological biomarkers would aid in the early diagnosis of mild head injury. In this study we used hypercapnia to follow changes in cerebral vascular reactivity after repetitive mild head injury. We hypothesized head injury would reduce vascular reactivity. Rats were maintained on a reverse light-dark cycle and head impacted daily at 24 h intervals over three days. All head impacts were delivered while rats were fully awake under red light illumination. There was no neuroradiological evidence of brain damage. After the 3rd impact rats were exposed to 5% CO2 and imaged for changes in BOLD signal. All imaging was done while rats were awake without the confound of anesthesia. The data were registered to a 3D MRI rat atlas with 171 segmented brain areas providing site specific information on vascular reactivity. The changes in vascular reactivity were not uniform across the brain. The prefrontal cortex, somatosensory cortex and basal ganglia showed the hypothesized decrease in vascular reactivity while the cerebellum, thalamus, brainstem, and olfactory system showed an increase in BOLD signal to hypercapnia.

Nasal high flow or noninvasive ventilation? navigating hypercapnic COPD exacerbation treatment: A randomized noninferiority clinical trial.

BACKGROUND: Noninvasive ventilation (NIV) has been the cornerstone for managing acute exacerbations of COPD (AECOPD) with hypercapnic respiratory failure. Nasal high flow (NHF) oxygen therapy has emerged as a potential alternative, offering a more tolerable modality with promising outcomes. The aim of the present study was to evaluate whether NHF respiratory support is noninferior to NIV with respect to treatment failure, in patients with mild-to-moderate hypercapnic AECOPD. METHODS: In this multi-center, randomized, noninferiority trial, 105 patients with AECOPD and respiratory failure type II were enrolled. Participants were randomly assigned to receive either NHF therapy or NIV. The primary endpoint was the frequency of treatment failure, defined as the need for intubation and invasive mechanical ventilation or a switch to the alternative treatment group. Secondary endpoints included changes in respiratory parameters, patient comfort indicators, and the occurrence of complications. RESULTS: The findings revealed no significant difference in the primary outcome between the groups, with a treatment failure rate of 19.6 % (10 out of 51) in the NHF group and 14.8 % (8 out of 54) in the NIV group. Interestingly, NHF users reported significantly lower levels of dyspnea and discomfort at multiple follow-up points. Despite the differences in patient comfort, respiratory parameters such as respiratory rate, arterial blood gases, and use of accessory muscles of respiration showed no significant disparities between the groups throughout the study period. CONCLUSIONS: NHF therapy was similar to NIV in preventing treatment failure among patients with hypercapnic AECOPD, offering a viable alternative with enhanced comfort. TRIAL REGISTRATION: The study was prospectively registered in ClinicalTrials.gov (Identifier: NCT03466385) on March 15, 2018.

Increased risk of respiratory events during endobronchial ultrasound examination in patients with reduced forced expiratory volume: a prospective observational study.

Background: The incidence of adverse events during endobronchial ultrasound is low. Nevertheless, it is unclear, whether patients with impaired pulmonary function have an increased risk of respiratory events during the intervention. Methods: A monocentric prospective observational study was performed at the Department of Respiratory Medicine, University Hospital Frankfurt/Main, Germany. Adult patients undergoing an endobronchial ultrasound examination with propofol-sedation were included. Pre-interventional screening included pulmonary function testing, laboratory tests and electrocardiogram. The occurrence of hypercapnia >55 mmHg or reduced oxygen saturation <85% was defined as a respiratory event was recorded and compared between patients with normal and impaired pulmonary function tests. Results: In total, 126 patients were included. Pulmonary function testing revealed a median FEV1 of 2.2 l (range 0.4-6.04l) and a predicted FEV1 of 79.5% (range 20-127.8%) respectively. The median FVC was 3.0 l (range 0.87-7.28l), the median predicted FVC was 82% (range 31.4-128.4%). In 72 examinations (60%) pCO2 levels >55 mmHg were measured. Transient oxygen desaturation <85% occurred in 31 cases (25.8%). The Mann Whitney U-test showed a significantly lower FEV1 (% predicted value) in patients with respiratory events (p = 0.007). ROC analysis identified a predicted FEV1 of 78.5% as the optimal cut-off with a sensitivity of 58% and a specificity of 71%. Using Z-score instead of predicted values, there was no significant association between a lower Z- score of FEV or FVC and hypercapnic or hypoxic events. However, both a lower absolute value of FEV1/FVC and a lower Z-score of the FEV1/FVC index were associated with the occurrence of respiratory events. In binary logistic regression analysis, we could not demonstrate any association with other relevant parameters (age, BMI, sedation dosage, sedation duration, or ASA-score). Conclusions: An impaired forced expiratory volume is associated with the frequency of respiratory events during endobronchial ultrasound examination under propofol-sedation.

Expert perspectives on ECCO2R for acute hypoxemic respiratory failure: consensus of a 2022 European roundtable meeting.

BACKGROUND: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. RESULTS: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4-6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14-15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5-3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14-15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. CONCLUSIONS: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14-15 cmH2O suggested as the primary inclusion criterion.

Characterising cerebrovascular reactivity and the pupillary light response-a comparative study.

Introduction: Smooth muscle is integral to multiple autonomic systems, including cerebrovascular dynamics through vascular smooth muscle cells and in ocular muscle dynamics, by regulating pupil size. In the brain, smooth muscle function plays a role in cerebrovascular reactivity (CVR) that describes changes in blood vessel calibre in response to vasoactive stimuli. Similarly, pupil size regulation can be measured using the pupillary light response (PLR), the pupil's reaction to changes in light levels. The primary aim of this study was to explore the interplay between cerebral blood flow and pupil dynamics, evaluated using CVR and PLR, respectively. Methods: A total of 20 healthy adults took part in a CVR gas stimulus protocol and a light and dark flash PLR protocol. CVR was calculated as the blood flow velocity change in the middle cerebral artery, measured using transcranial Doppler ultrasound in response to a 5% increase in CO2. Multiple PLR metrics were evaluated with a clinical pupillometer. Results: CVR and PLR metrics were all within the expected physiological ranges for healthy adults. Nine different PLR metrics, assessed through the light and dark flash protocols, were compared against CVR. A significant negative relationship was observed between the latency of the PLR in the dark flash protocol and CVR. No statistically significant relationships were found between CVR and other PLR metrics. Conclusion: This is the first study to investigate the relationship between cerebral blood flow and pupil dynamics. A significant relationship between dark flash latency and CVR was observed. Future work includes evaluating these relationships using more robust CVR and PLR measurement techniques in a larger, more diverse cohort. Notably, more research is warranted into the PLR using a dark flash protocol and its connection to cerebrovascular function.

A Rare Case of Bare Lymphocyte Syndrome Presenting As Chronic Type 2 Respiratory Failure.

Type 2 respiratory failure, or hypercapnic respiratory failure, is brought on by low oxygenation (hypoxemia) and inadequate breathing (hypercapnia). It is produced by factors that can create an imbalance between the requirement and capacity of the respiratory system. The factors can include an increased requirement for muscles of respiration, reduction in their strength or effectiveness, or impediment of the ventilatory drive. Rarely, it can be caused by the bare lymphocyte syndrome (BLS), which usually affects young children and has a poor prognosis with accompanying debilitating disabilities. This is a case report that shares the unique findings of a 13-year-old patient with type 1 BLS and atopy, who is suffering from type 2 respiratory failure. She is susceptible to respiratory tract infections and has been treated for bronchopneumonia and tuberculosis in the past. She has been on assisted ventilation for the past 3.5 months, along with supplementary nutrition. She has been evaluated meticulously and methodically, ruling out other causes of her respiratory failure. Recognizing the root cause aided in her therapy and preventing mortality. This has been determined using clinical findings, lab results, and radiological reports. The diagnosis of hypercapnic respiratory failure was confirmed via an arterial blood gas analysis, whereas that of BLS was confirmed through a whole genome sequence test. Management entailed addressing the underlying cause, optimizing ventilation, and using mechanical ventilation to maintain respiratory function. Early detection and timely intervention were critical in enhancing the outcome for the patient.

FFP2 induced breathing resistance does not affect metabolism and well-being during brisk walking and stair climbing - a randomized controlled trial.

OBJECTIVES: N95 or Type II filtering face pieces (FFP2) are often worn during work hours or on public transportation to prevent airborne infection. The aim of this randomized controlled crossover study is to assess the impact of FFP2 induced breathing resistance on pulmonary function, blood gas values and discomfort during walking and stair climbing. METHODS: N = 16 healthy adults (24.8 ± 2.2 years; 10 females, ) participated. Interventions included (1) six minutes of walking in a 16-meter-long hallway (612 m) and (2) eight minutes of stair climbing in a two-story staircase (420 stairs), both with and without a FFP2 (> 48 h wash-out). Spiroergometric data (Ventilation, breathing frequency, tidal volume, oxygen uptake and carbon dioxide exhalation (primary outcome), end tidal carbon dioxide- and oxygen pressure) and self-reported response (Perceived exertion, dyspnoea and pain) were assessed during activities. Blood gas analysis (capillary carbon dioxide- (pCO2) (primary outcome) and oxygen partial pressure (pO2), pH, lactate and base excess) was measured immediately after cessation of activities. Manipulation effects (FFP2 versus no mask) were tested using repeated measures analyses of variance. RESULTS: Analysis showed no effect of FFP2 on pCO2 or other blood-gas parameters but on carbon dioxide exhalation during walking: (mean 1067, SD 209 ml/min) (mean 1908, SD 426 ml/min) (F(15) = 19.5; p < 0.001; ηp2 = 0.566) compared to no mask wearing (mean 1237, SD 173 ml/min; mean 1908, SD 426 ml/min). Ventilation was decreased and dyspnoea was increased by FFP2 during activities. FFP2 led to lower oxygen uptake and lower end tidal oxygen but higher end tidal carbon dioxide during stair climbing. CONCLUSIONS: FFP2 decreased ventilation based on slower breathing patterns and led to limitations in pulmonary gas exchange and increased subjective dyspnoea. However, invasive diagnostics revealed no signs of clinically relevant metabolic effects immediately after everyday physical activities.