Non-immersive virtual reality based treatment for children with unilateral cerebral palsy: Preliminary results.

PURPOSE: Unilateral cerebral palsy (UCP) represents about 30-40% of overall cerebral palsy diagnoses. Upper limb impairment has a significant negative impact on activities of daily living (ADL), and recent studies have shown that the use of virtual reality (VR) can increase motivation and promote an improvement in ADL. This preliminary study was aimed at exploring the acceptability and usability of a VR rehabilitation treatment, using the VITAMIN Platform, for children with UCP. A secondary goal of the study was to compare the results of usual standardized clinical scales and questionnaires with kinematic results as well as with the quantitative measures acquired by the VITAMIN platform in each exercise of the rehabilitation sessions. METHODS: Six children with UCP (aged 7-15) were recruited for a preliminary investigation in using a non-immersive VR system. The treatment was composed of 10 weekly sessions of 45 minutes. Each child played five types of exergames, using the impaired upper limb to hit virtual objects projected on a wide screen. Standardized clinical scales, kinematic analysis, and questionnaires were used to extensively assess upper limb function before and at the end of treatment. Five typically-developing children provided a reference for the instrumented kinematic assessment. RESULTS: At the end of the treatment, Melbourne Assessment 2 (MA2) scores increased for all the participants (mean increase in range of movement (ROM) + 19.1%, accuracy + 4.6%, dexterity + 13.1%, fluency + 10.3%). Shoulder flexion-extension ROM also improved (mean increase + 10.5°), and according to the kinematic analysis, shoulder movements became more similar to reference profiles. These results were confirmed by a general improvement in performing ADL, assessed by the ABILHAND-Kids questionnaire. Finally, a general agreement among the different measures and indexes emerged from the acquired data. CONCLUSION: The results show that VR treatment with the VITAMIN platform could be engaging and functional for rehabilitation of children with UCP. The good agreement among the qualitative and quantitative measures and indexes confirms the potential of such novel treatment. However, due to the limited sample size and small number of sessions, further and larger investigations are required to evaluate the effectiveness and to generalize the results.

Physical Activity in Cerebral Palsy: A Current State Study.

This document analyzes a survey conducted in three geographical areas in Spain, focusing on centers for individuals with cerebral palsy (CP). The study aims to determine the adherence rate to recommended physical activity guidelines, assess if there is a decline in interest in physical activity over time, identify the stage at which this decline occurs, and explore potential mechanisms, tools, or strategies to sustain long-term engagement in regular physical activity for this population. The 36-item questionnaire comprises multiple-choice, open-ended, and Likert scale-type questions. Data were collected on physical activity frequency and duration, daily living activities, and demographics. Statistical analysis identified patterns and relationships between variables. Findings reveal that only a 17.6% meets the World Health Organization (WHO) recommendations regarding regular physical activity (RPA), decreasing in frequency or number of days a week, (3.7 d/w to 2.9 d/w; p < 0.01) and duration (50.5 min/d to 45.2 min/d; p < 0.001) with age, especially for those with higher Gross Motor Function Classification System (GMFCS) mobility levels. Obesity slightly correlates with session duration (ρ = -0.207; p < 0.05), not mobility limitations. Gender has no significant impact on mobility, communication, or physical activity, while age affects variables such as body mass index (BMI) and engagement (p < 0.01). A substantial proportion follows regular physical activities based on health professionals' advice, with interest decreasing with age. To improve adherence, focusing on sports-oriented goals, group sessions, and games is recommended. These findings emphasize the importance of personalized programs, particularly for older individuals and those with greater mobility limitations.

Virtual reality rehabilitation program on executive functions of children with specific learning disorders: a pilot study.

Background: The application of Virtual Reality (VR) in the field of rehabilitation has been widely studied, because it has already proven to be an effective intervention for a variety of physical and cognitive conditions. Nevertheless, its application in pediatric rehabilitation is more recent. This pilot study aims to examine whether a VR-rehabilitation program may have positive effects on the Executive Functions (EFs) of children with Specific Learning Disorders (SLD). Materials and methods: Twenty-four children with diagnosis of SLD participated to the study (range 7-11 years) and performed the VR-training across 6 weeks in the CARE Lab, that was designed with appropriate structural measures and ad hoc fittings, to hide the sophisticated technology necessary to allow the child to experience a rehabilitative setting with recreational and semi-immersive features. Children were evaluated across three main time-points: T0, assessment of cognitive level and EFs immediately before the start of the intervention; T1, assessment of EFs immediately after the end of VR intervention; T2, follow-up of EFs after 6 months from the end of the VR intervention. The rehabilitation programs were customized according to clinical needs and/or single patient's characteristics, proposing different games with variable complexity levels. Results: Results showed that scores for visual attention, inhibition, flexibility, and planning abilities were significantly higher than before the intervention, and the most part of these ameliorations were maintained after 6 months. Conclusion: These findings provide important inputs for the development of new innovative rehabilitation interventions for children with SLD that must be founded in ecological and evidence-based approaches.

Impact of reboxetine plus oxybutynin treatment for obstructive sleep apnea on cardiovascular autonomic modulation.

The combination of noradrenergic (reboxetine) plus antimuscarinic (oxybutynin) drugs (reb-oxy) reduced obstructive sleep apnea (OSA) severity but no data are available on its effects on cardiac autonomic modulation. We sought to evaluate the impact of 1-week reb-oxy treatment on cardiovascular autonomic control in OSA patients. OSA patients were randomized to a double-blind, crossover trial comparing 4 mg reboxetine plus 5 mg oxybutynin to a placebo for OSA treatment. Heart rate (HR) variability (HRV), ambulatory blood pressure (BP) monitoring (ABPM) over 24 h baseline and after treatment were performed. Baroreflex sensitivity was tested over beat-to-beat BP recordings. 16 subjects with (median [interquartile range]) age 57 [51-61] years and body mass index 30 [26-36]kg/m2 completed the study. The median nocturnal HR was 65 [60-69] bpm at baseline and increased to 69 [64-77] bpm on reb-oxy vs 66 [59-70] bpm on placebo (p = 0.02). The mean 24 h HR from ABPM was not different among treatment groups. Reb-oxy administration was not associated with any modification in HRV or BP. Reb-oxy increased the baroreflex sensitivity and did not induce orthostatic hypotension. In conclusion, administration of reb-oxy did not induce clinically relevant sympathetic overactivity over 1-week and, together with a reduction in OSA severity, it improved the baroreflex function.

Heart Rate Variability from Wearable Photoplethysmography Systems: Implications in Sleep Studies at High Altitude.

The interest in photoplethysmography (PPG) for sleep monitoring is increasing because PPG may allow assessing heart rate variability (HRV), which is particularly important in breathing disorders. Thus, we aimed to evaluate how PPG wearable systems measure HRV during sleep at high altitudes, where hypobaric hypoxia induces respiratory disturbances. We considered PPG and electrocardiographic recordings in 21 volunteers sleeping at 4554 m a.s.l. (as a model of sleep breathing disorder), and five alpine guides sleeping at sea level, 6000 m and 6800 m a.s.l. Power spectra, multiscale entropy, and self-similarity were calculated for PPG tachograms and electrocardiography R-R intervals (RRI). Results demonstrated that wearable PPG devices provide HRV measures even at extremely high altitudes. However, the comparison between PPG tachograms and RRI showed discrepancies in the faster spectral components and at the shorter scales of self-similarity and entropy. Furthermore, the changes in sleep HRV from sea level to extremely high altitudes quantified by RRI and PPG tachograms in the five alpine guides tended to be different at the faster frequencies and shorter scales. Discrepancies may be explained by modulations of pulse wave velocity and should be considered to interpret correctly autonomic alterations during sleep from HRV analysis.

Reboxetine Plus Oxybutynin for OSA Treatment: A 1-Week, Randomized, Placebo-Controlled, Double-Blind Crossover Trial.

BACKGROUND: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. RESEARCH QUESTION: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? STUDY DESIGN AND METHODS: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. RESULTS: Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P < .001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P < .001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P < .001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. INTERPRETATION: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04449133; URL: www.clinicaltrials.gov.

The Arrows and Colors Cognitive Test (ACCT): A new verbal-motor free cognitive measure for executive functions in ALS.

BACKGROUND AND OBJECTIVE: The presence of executive deficits in patients with Amyotrophic Lateral Sclerosis is well established, even if standardized measures are difficult to obtain due to progressive physical disability of the patients. We present clinical data concerning a newly developed measure of cognitive flexibility, administered by means of Eye-Tracking (ET) technology in order to bypass verbal-motor limitations. METHODS: 21 ALS patients and 21 age-and education-matched healthy subjects participated in an ET-based cognitive assessment, including a newly developed test of cognitive flexibility (Arrows and Colors Cognitive Test-ACCT) and other oculomotor-driven measures of cognitive functions. A standard screening of frontal and working memory abilities and global cognitive efficiency was administered to all subjects, in addition to a psychological self-rated assessment. For ALS patients, a clinical examination was also performed. RESULTS: ACCT successfully discriminated between patients and healthy controls, mainly concerning execution times obtained at different subtests. A qualitative analysis performed on error distributions in patients highlighted a lower prevalence of perseverative errors, with respect to other type of errors. Correlations between ACCT and other ET-based frontal-executive measures were significant and involved different frontal sub-domains. Limited correlations were observed between ACCT and standard 'paper and pencil' cognitive tests. CONCLUSIONS: The newly developed ET-based measure of cognitive flexibility could be a useful tool to detect slight frontal impairments in non-demented ALS patients by bypassing verbal-motor limitations through the oculomotor-driven administration. The findings reported in the present study represent the first contribution towards the development of a full verbal-motor free executive test for ALS patients.

Computer Assisted REhabilitation (CARE) Lab: A novel approach towards Pediatric Rehabilitation 2.0.

Pediatric Rehabilitation therapists have always worked using a variety of off-the-shelf or custom-made objects and devices, more recently including computer based systems. These Information and Communication Technology (ICT) solutions vary widely in complexity, from easy-to-use interactive videogame consoles originally intended for entertainment purposes to sophisticated systems specifically developed for rehabilitation.This paper describes the principles underlying an innovative "Pediatric Rehabilitation 2.0" approach, based on the combination of suitable ICT solutions and traditional rehabilitation, which has been progressively refined while building up and using a computer-assisted rehabilitation laboratory. These principles are thus summarized in the acronym EPIQ, to account for the terms Ecological, Personalized, Interactive and Quantitative. The paper also presents the laboratory, which has been designed to meet the children's rehabilitation needs and to empower therapists in their work. The laboratory is equipped with commercial hardware and specially developed software called VITAMIN: a virtual reality platform for motor and cognitive rehabilitation.

Brain-Computer Interface for Clinical Purposes: Cognitive Assessment and Rehabilitation.

Alongside the best-known applications of brain-computer interface (BCI) technology for restoring communication abilities and controlling external devices, we present the state of the art of BCI use for cognitive assessment and training purposes. We first describe some preliminary attempts to develop verbal-motor free BCI-based tests for evaluating specific or multiple cognitive domains in patients with Amyotrophic Lateral Sclerosis, disorders of consciousness, and other neurological diseases. Then we present the more heterogeneous and advanced field of BCI-based cognitive training, which has its roots in the context of neurofeedback therapy and addresses patients with neurological developmental disorders (autism spectrum disorder and attention-deficit/hyperactivity disorder), stroke patients, and elderly subjects. We discuss some advantages of BCI for both assessment and training purposes, the former concerning the possibility of longitudinally and reliably evaluating cognitive functions in patients with severe motor disabilities, the latter regarding the possibility of enhancing patients' motivation and engagement for improving neural plasticity. Finally, we discuss some present and future challenges in the BCI use for the described purposes.

An eye-tracker controlled cognitive battery: overcoming verbal-motor limitations in ALS.

We assessed language, attention, executive, and social cognition abilities in a sample of patients with Amyotrophic Lateral Sclerosis (ALS) by means of a recently developed cognitive battery based on oculomotor control with eye-tracking (ET) technology. Twenty-one ALS patients and 21 age- and education-matched healthy subjects underwent the ET-based cognitive assessment, together with the standard cognitive screening tools [Frontal Assessment Battery (FAB); Montreal Cognitive Assessment (MoCA); and Digit Sequencing Task]. Psychological measures of anxiety (State-Trait Anxiety Inventory-Y) and depression (Beck Depression Inventory) were also collected, and an ET usability questionnaire was administered. For patients, clinical and respiratory examinations were also performed, together with behavioural assessment (Frontal Behavioural Inventory). The developed battery discriminated among patients and controls with regard to measures of verbal fluency, frontal abilities, and social cognition. Measures of diagnostic utility confirmed a higher diagnostic accuracy of such ET-based tests with respect to FAB; similar diagnostic accuracy emerged when comparing them to the other standard cognitive tools (MoCA, WM). Usability ratings about the ET tests were comparable among the two groups. The ET-based neuropsychological battery demonstrated good levels of diagnostic accuracy and usability in a clinical population of non-demented ALS patients, compared to matched healthy controls. Future studies will be aimed at further investigate validity and usability components by recruiting larger sample of patients, both in moderate-to-severe stages of the disease and affected by more severe cognitive impairment.

An eye-tracking controlled neuropsychological battery for cognitive assessment in neurological diseases.

Traditional cognitive assessment in neurological conditions involving physical disability is often prevented by the presence of verbal-motor impairment; to date, an extensive motor-verbal-free neuropsychological battery is not available for such purposes. We adapted a set of neuropsychological tests, assessing language, attentional abilities, executive functions and social cognition, for eye-tracking (ET) control, and explored its feasibility in a sample of healthy participants. Thirty healthy subjects performed a neuropsychological assessment, using an ET-based neuropsychological battery, together with standard "paper and pencil" cognitive measures for frontal (Frontal Assessment Battery-FAB) and working memory abilities (Digit Sequencing Task) and for global cognitive efficiency (Montreal Cognitive Assessment-MoCA). Psychological measures of anxiety (State-Trait Anxiety Inventory-Y-STAI-Y) and depression (Beck Depression Inventory-BDI) were also collected, and a usability questionnaire was administered. Significant correlations were observed between the "paper and pencil" screening of working memory abilities and the ET-based neuropsychological measures. The ET-based battery also correlated with the MoCA, while poor correlations were observed with the FAB. Usability aspects were found to be influenced by both working memory abilities and psychological components. The ET-based neuropsychological battery developed could provide an extensive assessment of cognitive functions, allowing participants to perform tasks independently from the integrity of motor or verbal channels. Further studies will be aimed at investigating validity and usability components in neurological populations with motor-verbal impairments.

Cognitive assessment in Amyotrophic Lateral Sclerosis by means of P300-Brain Computer Interface: a preliminary study.

OBJECTIVE: To investigate the use of P300-based Brain Computer Interface (BCI) technology for the administration of motor-verbal free cognitive tests in Amyotrophic Lateral Sclerosis (ALS). METHODS: We recruited 15 ALS patients and 15 age- and education-matched healthy subjects. All participants underwent a BCI-based neuropsychological assessment, together with two standard cognitive screening tools (FAB, MoCA), two psychological questionnaires (BDI, STAI-Y) and a usability questionnaire. For patients, clinical and respiratory examinations were also performed, together with a behavioural assessment (FBI). RESULTS: Correlations were observed between standard cognitive and BCI-based neuropsychological assessment, mainly concerning execution times in the ALS group. Moreover, patients provided positive rates concerning the BCI perceived usability and subjective experience. Finally, execution times at the BCI-based neuropsychological assessment were useful to discriminate patients from controls, with patients achieving lower processing speed than controls regarding executive functions. CONCLUSIONS: The developed motor-verbal free neuropsychological battery represents an innovative approach, that could provide relevant information for clinical practice and ethical issues. Its use for cognitive evaluation throughout the course of ALS, currently not available by means of standard assessment, must be addressed in further longitudinal validation studies. Further work will be aimed at refining the developed system and enlarging the cognitive spectrum investigated.

Sex and acetazolamide effects on chemoreflex and periodic breathing during sleep at altitude.

OBJECTIVE: Nocturnal periodic breathing occurs more frequently in men than in women with various clinical and pathophysiologic conditions. The mechanisms accounting for this sex-related difference are not completely understood. Acetazolamide effectively counteracts nocturnal periodic breathing, but it has been investigated almost exclusively in men. Our aim was to explore possible determinants of nocturnal periodic breathing in a high-altitude setting both in men and in women. We hypothesized that increased hypoxic chemosensitivity in men could be associated with the development of nocturnal periodic breathing at altitude more frequently than in women, and that acetazolamide, by leftward shifting the CO2 ventilatory response, could improve nocturnal periodic breathing at altitude in a sex-independent manner. METHODS: Forty-four healthy lowlanders (21 women), randomized to acetazolamide or placebo, underwent cardiorespiratory sleep studies at sea level off treatment and under treatment on the first night after arrival at a 4,559-m altitude. Hypoxic and hypercapnic chemosensitivities were assessed at sea level. RESULTS: Men, more frequently than women, exhibited increased hypoxic chemosensitivity and displayed nocturnal periodic breathing at altitude. Acetazolamide leftward shifted the CO2 set point and, at altitude, improved oxygenation and reduced periodic breathing in both sexes, but to a larger extent in men. Hypoxic chemosensitivity directly correlated with the number of apneas/hypopneas at altitude in the placebo group but not in the acetazolamide group. CONCLUSIONS: The greater severity of periodic breathing during sleep displayed by men at altitude could be attributed to their increased hypoxic chemosensitivity. Acetazolamide counteracted the occurrence of periodic breathing at altitude in both sexes, modifying the apneic threshold and improving oxygenation. TRIAL REGISTRY: EU Clinical Trials Register, EudraCT; No.: 2010-019986-27; URL: https://www.clinicaltrialsregister.eu.

Wearable seismocardiography for the beat-to-beat assessment of cardiac intervals during sleep.

Seismocardiogram (SCG) can be detected during sleep by a textile-based wearable system. This pilot study preliminarily explores the feasibility of a beat-to-beat estimation of cardiac mechanical features (RR interval, RRI, Pre-Ejection Period, PEP, Isovolumic Contraction Time, ICT, Left Ventricular Ejection Time, LVET, Isovolumic Relaxation Time, IRT) from the joint ECG and SCG assessment during sleep. The analysis of two 30-min sleep data segments from one healthy subject, indicated that 1) respiration largely influence the dynamics of most of the parameters; 2) variability of cardiac intervals is only marginally influenced by the RRI variability; 3) appreciable spectral power at frequencies ≤ 0.1 is only observed in the RRI spectrum and not in the spectra of the other indexes; 4) IRT has a broadband variability, that is clearly different from the dynamics of the other indexes. These findings represent the very first description of the beat-to-beat variability of cardiac mechanical indexes. Further investigations on a larger population are in progress to confirm the present results.

A textile-based wearable system for the prolonged assessment of cardiac mechanics in daily life.

Seismocardiogram, SCG, can be detected over the 24 hours in ambulant subjects by a textile-based wearable system together with the electrocardiogram, ECG and respiration. In this pilot study we explored the possibility to derive 24 h profiles of cardiac time intervals, i.e. indexes of heart mechanical function, from the SCG recordings performed in daily life conditions by the above wearable system. Two healthy subjects were recruited for the study. They worn the system for 24 hours during a working day. From each recording, every 30 minutes the following parameters were derived from the ECG and SCG signals: RR interval, RRI, Pre-Ejection Period, PEP, Isovolumic Contraction Time, ICT, Left Ventricular Ejection Time, LVET, Isovolumic Relaxation Time, IRT. From the analysis it appears that 1) all parameters are characterized by a coefficient of variation in the same order of magnitude, and 2) 24 h LVET time profiles mirrors the long term RRI behavior. Common trends in PEP and ICT profiles were observed in one subject. This study indicates that indexes of cardiac mechanics can be derived from SCG recordings performed over the 24 hours. The obtained positive results encourage further studies to refine this methodology and confirm the present findings.

Rehabilitation of children with hemiparesis: a pilot study on the use of virtual reality.

BACKGROUND: A wide range of treatments have been used to improve upper arm motor performances in children with congenital hemiplegia. Recent findings are suggesting that virtual reality based intervention could be a promising tool also in pediatric rehabilitation. METHODS: Six patients with congenital hemiplegia (age: 4-16 years) were recruited among those treated in the Child Neuropsychiatry and Rehabilitation Unit of the IRCCS "Santa Maria Nascente" (Milan, Italy), for a preliminary investigation about using nonimmersive virtual reality for upper limb rehabilitation. Ten sessions using VRRS system (Khymeia, Padova, Italy) were weekly administered as a part of the rehabilitative treatment. Melbourne Assessment of Unilateral Limb Movement, Ashworth Scale, and Arm's PROM were selected as main outcome measures. At the end of treatment, participants filled in an ad hoc satisfaction questionnaire. RESULTS: All subjects completed the proposed treatment, and they also gave a positive judgment regarding this rehabilitative method. Melbourne score increased in all patients. CONCLUSION: Our findings seem to support the evidence that VR treatment could be a promising and engaging tool for pediatric rehabilitation. However, the limited size of the population and the small number of sessions require further investigations and RCTs to confirm our positive results.

Beat-to-beat estimation of LVET and QS2 indices of cardiac mechanics from wearable seismocardiography in ambulant subjects.

Seismocardiogram (SCG) is the measure of the minute vibrations produced by the beating heart. We previously demonstrated that SCG, ECG and respiration could be recorded over the 24 h during spontaneous behavior by a smart garment, the MagIC-SCG system. In the present case study we explored the feasibility of a beat-to-beat estimation of two indices of heart contractility, the Left Ventricular Ejection Time (LVET) and the electromechanical systole (QS2) from SCG and ECG recordings obtained by the MagIC-SCG device in one subject. We considered data collected during outdoor spontaneous behavior (while sitting in the metro and in the office) and in a laboratory setting (in supine and sitting posture, and during recovery after 100 W and 140 W cycling). LVET was estimated from SCG as the time interval between the opening and closure of the aortic valve, QS2 as the time interval between the Q wave of the ECG and the closure of the aortic valve. In every condition, LVET and QS2 could be estimated on a beat-to-beat basis from the SCG collected by the smart garment. LVET and QS2 are characterized by important beat-to-beat fluctuations, with standard deviations in the same order of magnitude of RR Interval. In all settings, spectral profiles are different for LVET, QS2 and RR Interval. This suggests that the biological mechanisms impinging on the heart exert a differentiated influence on the variability of each of these three indices.

Acute high-altitude exposure reduces lung diffusion: data from the HIGHCARE Alps project.

The causes and development of lung fluid, as well as the integrity of the alveolar-capillary membrane at high altitude, are undefined. This study was conceived to see whether fluid accumulates within the lung with acute high altitude exposure, and whether this is associated with alveolar capillary membrane damage. We studied lung carbon monoxide diffusion (DLCO), its components - membrane diffusion (DM) and capillary volume (VC) and alveolar volume (VA) measured in 43 healthy subjects in Milan (122 m) and after 1 and 3 days at Capanna Regina Margherita (4559 m). DLCO measurement was adjusted for hemoglobin and inspired oxygen. We also measured plasma surfactant derived protein B (SPB) and Receptor of Advanced Glycation End-products (RAGE) as markers of alveolar-capillary membrane damage, and ultrasound lung comets as a marker of extravascular lung water. 21 subjects received acetazolamide and 22 placebo. DLCO was lower at Capanna Regina Margherita (day 1: 24.3 ± 4.7 and day 3: 23.6 ± 5.4 mL/mmHg/min), than in Milan (25.8 ± 5.5; p<0.001 vs. day 1 and 3) due to DM reduction (Milan: 50.5 ± 14.6 mL/mmHg/min, Capanna Regina Margherita day 1: 45.1 ± 11.5 mL/mmHg/min, day 3: 43.2 ± 13.9 mL/mmHg/min; p<0.05 Milan vs. day 3) with a partially compensatory VC increase (Milan: 96 ± 37 mL, Capanna Regina Margherita day 1: 152 ± 66 mL, day 3: 153 ± 59 mL; p<0.001 Milan vs. day 1 and day 3). Acetazolamide did not prevent the fall in DLCO albeit, between day 1 and 3, such a trend was observed. Regardless of treatment lung comets increased from 0 to 7.2 ± 3.6 (p<0.0001). SPB and RAGE were unchanged. Lung fluid increased at high altitude without evidence from plasma measurements, supporting alveolar-capillary damage.

High-altitude hypoxia and periodic breathing during sleep: gender-related differences.

High-altitude exposure is characterized by the appearance of periodic breathing during sleep. Only limited evidence is available, however, on the presence of gender-related differences in this breathing pattern. In 37 healthy subjects, 23 male and 14 female, we performed nocturnal cardio-respiratory monitoring in the following conditions: (1) sea level; (2) first/second night at an altitude of 3400 m; (3) first/second night at an altitude of 5400 m and after a 10 day sojourn at 5400 m. At sea level, a normal breathing pattern was observed in all subjects throughout the night. At 3400 m the apnea-hypopnea index was 40.3 ± 33.0 in males (central apneas 77.6%, central hypopneas 22.4%) and 2.4 ± 2.8 in females (central apneas 58.2%, central hypopneas 41.8%; P < 0.01). During the first recording at 5400 m, the apnea-hypopnea index was 87.5 ± 35.7 in males (central apneas 60.0%, central hypopneas 40.0%) and 41.1 ± 44.0 in females (central apneas 73.2%, central hypopneas 26.8%; P < 0.01), again with a higher frequency of central events in males as seen at lower altitude. Similar results were observed after 10 days. With increasing altitude, there was also a progressive reduction in respiratory cycle length during central apneas in males (26.9 ± 3.4 s at 3400 m and 22.6 ± 3.7 s at 5400 m). Females, who displayed a significant number of central apneas only at the highest reached altitude, were characterized by longer cycle length than males at similar altitude (30.1 ± 5.8 s at 5400 m). In conclusion, at high altitude, nocturnal periodic breathing affects males more than females. Females started to present a significant number of central sleep apneas only at the highest reached altitude. After 10 days at 5400 m gender differences in the apnea-hypopnea index similar to those observed after acute exposure were still observed, accompanied by differences in respiratory cycle length.