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International audience; Bruxism is a heterogeneous condition related to various underlying mechanisms, including the presence of OSA. This case report illustrates that sleep mandibular movement monitoring and analysis could provide a useful opportunity for detection of both sleep bruxism and respiratory effort. The current case suggests that tracking of respiratory effort could enable evaluation of bruxism and its potential interactions. Successful treatment of sleep-related respiratory effort may lead to improved or resolution of bruxism in cases where such a causal relationship does exist.

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

Objective The earliest possible detection of individuals with COVID-19 has been essential to curb the spread of infection. Existing digital tools have been scaled up to address this issue. Every night telemonitoring data on continuous positive airway pressure (CPAP) device use, the first-line therapy for obstructive sleep apnoea (OSA), is collected worldwide. We asked whether the changes in CPAP adherence patterns of might constitute an alert for COVID-19. Methods We analysed preliminary results of telemonitoring data, recorded between February 1 and April 30, 2020, on OSA patients followed by our sleep clinics and diagnosed with COVID-19. Results CPAP telemonitoring data from the first 19 patients diagnosed with COVID-19 showed a clear decrease or halt in adherence in the 20 days immediately preceding COVID-19 diagnosis compared to an earlier period (p Conclusion Patterns of continuous positive airway pressure device use by obstructive sleep apnoea patients collected through telemonitoring can indicate the onset of COVID-19 symptoms. Existing telemonitoring platforms could be immediately used to screen for COVID-19, and for other respiratory infections, in this large at-risk population.

Background Given the high prevalence and risk for outcomes associated with pediatric obstructive sleep apnea (OSA), there is a need for simplified diagnostic approaches. A prospective study in 140 children undergoing in-laboratory polysomnography (PSG) evaluates the accuracy of a recently developed system (Sunrise) to estimate respiratory efforts by monitoring sleep mandibular movements (MM) for the diagnosis of OSA (Sunrise™). Methods Diagnostic and severity were defined by an obstructive apnea/hypopnea index (OAHI) ≥ 1 (mild), ≥ 5 (moderate), and ≥ 10 events/h (severe). Agreement between PSG and Sunrise™ was assessed by Bland-Altman method comparing respiratory disturbances hourly index (RDI) (obstructive apneas, hypopneas, and respiratory effort-related arousals) during PSG (PSG_RDI), and Sunrise RDI (Sr_RDI). Performance of Sr_RDI was determined via ROC curves evaluating the device sensitivity and specificity at PSG_OAHI ≥ 1, 5, and 15 events/h. Results A median difference of 1.57 events/h, 95% confidence interval: -2.49 to 8.11 was found between Sr_RDI and PSG_RDI. Areas under the ROC curves of Sr_RDI were 0.75 (interquartile range [IQR]: 0.72-0.78), 0.90 (IQR: 0.86-0.92) and 0.95 (IQR: 0.90-0.99) for detecting children with PSG_OAHI ≥ 1, PSG_OAHI ≥ 5, or PSG_ OAHI ≥ 10, respectively. Conclusion MM automated analysis shows significant promise to diagnose moderate-to-severe pediatric OSA.

Context: Automated sleep stages scoring from surrogate signals is challenging. Mandibular movements (MM) are reliable markers of the neural respiratory drive, with activity patterns reflecting sleep stages. We introduce a new automated sleep stage scoring method using MM signal. Method: Study was conducted on 96 adults (18 to 58 yrs, AHI MM signals were split into 30 seconds epochs, from which 217 features were extracted to classify 3 labels: wake, nonREM and REM sleep. The model was trained on PSG data from 68 subjects consisting of 169 hrs of nonREM, 26 hrs of REM and 21 hrs of wake. The model was validated on unseen data from 28 subjects composed of 147 hrs of nonREM, 38 hrs of REM sleep and 33 hrs of wake. Results: Subjects had a mean total sleep time of 7.14 hrs (CI: 5.53 to 8.49), a mean AHI of 3.57 events/h (CI: 1.00 to 6.92) and a mean arousal index of 9.22 events/h (CI: 4.36 to 16.69). The model showed good global performances, with a balanced accuracy of 0.79 (CI: 0.78 to 0.80) and an area under the receiver operating curve of 0.94, 0.91 and 0.93 for wake, nonREM and REM. Conclusion: This study demonstrated for the first time that MM signals are suitable for automated sleep stage scoring, providing a promising solution for home monitoring of sleep architecture.

CPAP is the first-line treatment for moderate to severe OSA syndrome. Up to 25% of patients with OSA syndrome discontinue CPAP treatment due to side effects. Unintentional leakage and its associated annoying consequences are the most frequently reported adverse effects of CPAP. Successive technological improvements have not succeeded in addressing this issue. A systematic review was conducted (1) to assess the impact of different technological advances on unintentional leaks and (2) to determine if any patient characteristics have already been identified as determinants of unintentional leakage. No CPAP modality was superior to another in reducing unintentional leaks and, surprisingly, oronasal masks were associated with higher unintentional leaks. Nasal obstruction, older age, higher BMI, central fat distribution, and male sex might be associated with an increased risk of unintentional leakage. Such leaks remain an important problem. Further studies are needed to improve the understanding of underlying clinical factors so that patients at risk of unintentional leaks may be identified and individualized solutions applied.

Context: Accurate discrimination between obstructive and central hypopneas requires quantitative assessments of respiratory effort by esophageal pressure (OeP) measurements, which preclude widespread implementation in sleep medicine practice. Mandibular Movement (MM) signals are closely associated with diaphragmatic effort during sleep.Objective: We aimed at reliably detecting obstructive off central hypopneas events using MM statistical characteristics.Methods: A bio-signal learning approach was implemented whereby raw MM fragments corresponding to normal breathing (NPB; n = 501), central (n = 263), and obstructive hypopneas (n = 1861) were collected from 28 consecutive patients (mean age = 54 years, mean AHI = 34.7 n/h) undergoing in-lab polysomnography (PSG) coupled with a MM magnetometer, and OeP recordings. Twenty three input features were extracted from raw data fragments to explore distinctive changes in MM signals. A Random Forest model was built upon those input features to classify the central and obstructive hypopnea events. External validation and interpretive analysis were performed to evaluate the model's performance and the contribution of each feature to the model's output.Results: Obstructive hypopneas were characterized by a longer duration (21.9 vs. 17.8 s, p < 10−6), more extreme low values (p < 10−6), a more negative trend reflecting mouth opening amplitude, wider variation, and the asymmetrical distribution of MM amplitude. External validation showed a reliable performance of the MM features-based classification rule (Kappa coefficient = 0.879 and a balanced accuracy of 0.872). The interpretive analysis revealed that event duration, lower percentiles, central tendency, and the trend of MM amplitude were the most important determinants of events.Conclusions: MM signals can be used as surrogate markers of OeP to differentiate obstructive from central hypopneas during sleep.

Objective: We explored the causal relationship between Head-Body positions (HBp) and Sleep obstructive apnea/hypopnea (OAH) to fill the evidence gap in this topic. Methods: Rotations (pitch/yaw) and directions (prone, supine, up/left, supine, right) of HBp were captured by two miniaturized sensors under 45° segments during type1 PSG in 20 consecutive OSA patients. Sequential categorical data of Arousals (A, n=559) and OAH events (n=630) (accordingly to AASM2012) associated with HBp status (n=1633) were built. A timestamps-based algorithm was applied to extract every possible combinations between changes in HBp and events. The association between HBp and events risk was evaluated with Lasso-logistic and RandomForest models Results: Head and body prone pitching (PP) and right yawing (RY) were found significantly associated to either A or OAH events. Head position played the most important role (OR=2.2 for PP and 3.9 for RY), compared to that of body postural changes (OR=1.2 for RY and OR=1.1 for PP). Chronological order analysis showed that HBp changes occurred after A (73.7%) or OAH (72.6%) episodes. A and OAH events were triggered by HBp in only 23% observations. Rarely, A and OAH events occurred during a long and stable HBp (2.5%). Conclusion: Prone pitching and right yawing were the most important positions contributing to the classification of A and OAH events. HBp seemed here more likely consequences than causes of A or OAH risk.

Background and objective Mandibular movements (MMs) and position during sleep reflect respiratory efforts related to increases in upper airway resistance and micro-arousals. The study objective was to assess whether MM identifies sleep-disordered breathing (SDB) in patients with moderate to high pre-test probability. Methods This was a prospective study of 87 consecutive patients referred for an in-laboratory sleep test. Magnetometer-derived MM signals were incorporated into standard polysomnography (PSG). Respiratory events detected with MM analysis were compared with PSG for respiratory disturbance index (RDI) with a blinded scoring. All records were scored manually according to American Academy of Sleep Medicine rules. Primary outcome was to rule-in obstructive sleep apnoea syndrome (OSAS) defined as RDI cut-off value ≥5 or 15/h total sleep time (TST). Results High concordance emerged between MM and PSG-derived RDI with high temporal coincidence between events (R2 = 0.906; P

BACKGROUNDPatients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin-5.METHODSWe performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy. In METREX, unselected patients in the modified intention-to-treat population with an eosinophilic phenotype were stratified according to blood eosinophil count (>= 150 per cubic millimeter at screening or >= 300 per cubic millimeter during the previous year). In METREO, all patients had a blood eosinophil count of at least 150 per cubic millimeter at screening or at least 300 per cubic millimeter during the previous year. The primary end point was the annual rate of moderate or severe exacerbations. Safety was also assessed.RESULTSIn METREX, the mean annual rate of moderate or severe exacerbations in the modified intention-to-treat population with an eosinophilic phenotype (462 patients) was 1.40 per year in the mepolizumab group versus 1.71 per year in the placebo group (rate ratio, 0.82; 95% confidence interval [CI], 0.68 to 0.98; adjusted P = 0.04); no significant between-group differences were found in the overall modified intention-to-treat population (836 patients) (rate ratio, 0.98; 95% CI, 0.85 to 1.12; adjusted P>0.99). In METREO, the mean annual rate of moderate or severe exacerbations was 1.19 per year in the 100-mg mepolizumab group, 1.27 per year in the 300-mg mepolizumab group, and 1.49 per year in the placebo group. The rate ratios for exacerbations in the 100-mg and 300-mg mepolizumab groups versus the placebo group were 0.80 (95% CI, 0.65 to 0.98; adjusted P = 0.07) and 0.86 (95% CI, 0.70 to 1.05; adjusted P = 0.14), respectively. A greater effect of mepolizumab, as compared with placebo, on the annual rate of moderate or severe exacerbations was found among patients with higher blood eosinophil counts at screening. The safety profile of mepolizumab was similar to that of placebo.CONCLUSIONSMepolizumab at a dose of 100 mg was associated with a lower annual rate of moderate or severe exacerbations than placebo among patients with COPD and an eosinophilic phenotype. This finding suggests that eosinophilic airway inflammation contributes to COPD exacerbations.

Background and objective During continuous positive airway pressure (CPAP) treatment, some patients with obstructive sleep apnoea syndrome (OSAS) require an oronasal mask (ONM) to prevent excessive mouth leakage. Factors contributing to sleep-related mouth opening under CPAP treatment remain known. We compared mouth opening during sleep in patients treated with CPAP by nasal mask (NM) versus ONM. Methods Cross-sectional prospective study: patients treated with CPAP for at least 4 months underwent a sleep recording using a type 4 monitoring device (Brizzy-Nomics) that records mouth opening via a magnetometric distance meter. Clinical assessment included anthropometry, smoking status and the Mallampati score. Nasal obstruction was assessed by the Nasal Obstruction Symptom Evaluation questionnaire. Results Thirty-eight patients were included, 34 analysed (22 men; age = 57.4 (53; 62) years; body mass index = 32.6 (29.1; 35.2) kg/m2; median (25th; 75th)). Twenty-seven patients were treated with NM and seven with ONM. Patients with ONM were more often active smokers and trended to have greater nasal obstruction and lower forced expiratory volume in 1 s. They also exhibited a greater mouth opening during sleep (median (25th;75th) = 13.0 (11.0; 15.0) vs 6.0 (5.0; 10.0) mm, P

Context: Mandibular movements (MM) during sleep disordered breathing (SDB) are considered as related to the intensity of respiratory effort (RE). However this relationship has never been objectively documented by assessing RE with crural diaphragmatic EMG activity (EMGd). Objective: To assess the link between the MM and EMGd signals during sleep. Methods: 25 consecutive patients with SDB were explored during a type 2 PSG including a magnetometer (Brizzy®Nomics, BE) and an Edi-catheter (Getinge, SWE) to record MM and EMGd, respectively. The PSG scoring was performed according to AASM-2012 rules. Peak to peak distance of MM (MMd, expressed in 1/10mm) and EMGd (in mV) were extracted by envelope processing. Preliminary analysis showed a strong cross-correlation between both signals. A dataset of 14000 randomized, equal segments were used for fitting mixed linear model. Results: Patients characteristics were: Age= 49.8±12.5 yrs; BMI =30.2±6.6 kg/m2; TST=370±61.6min and AHI=24.8 ± 27.5 events/hour. There was a significant strong relationship between MMd and EMGd (MMd ~ 0.01 EMGd; p Pairwise comparisons indicated significant differences in MMd between Normal breathing and RE events, including RERA, Obstructive, Mixed and Central Apneas. Conclusion: Peak to peak Mandibular Movements change in proportion to crural diaphragmatic EMG, and allow identifying RE during sleep.

Chest surface EMG at diaphragmatic insertions (IC-EMG) is an alternative way for capturing respiratory effort (RE) during SAHOS.IC-EMG wasn9t investigated with regards to oesophageal crural diaphragmatic EMG (DI-EMG). Our study aimed to assess the similarity between IC and DI-EMG and the ability of IC-EMG to classify RE episodes. Methods 14 adults SAHOS underwent a lab-based PSG study with IC-EMG and DI-EMG. 70 periods of normal breathing (NB),309 RE events (including 135 RERA,70 OH and104 OA) were randomly selected for analysis in R-studio. After noise reduction, AUC and peak-to-peak distance (d) were calculated for both signals. Similarity between 2 signals was evaluated by cross-correlation as a function of the lag of one relative to the other. Correlation and d-value were compared among 4 groups of RE levels. Ability of each signal to detect RE was evaluated by multiclass CART algorithm. Results Patients have a mean age of 42.8±10.7 yrs and BMI of 31.1±8.6 kg/m2.Their averaged TST and AHI were 347±51.9 min and 35.3±25.1 n/h respectively. IC and DI-EMG signals are cross-correlated in either NB or RE events (r=0.6 to 0.86) by a lag of 0.5-0.9 second. AUC was also correlated (r=0.96). IC showed a significant difference in d-value among 4 groups (NB:14.6 vs RERA:21.9, OH:19.8 and OA:44.2). Using cut-offs at 17.8 and 31.5, IC distance allows classifying RERA, OAH and NB with accuracy, inter-class agreement and specificity of 0.8, 0.63 and 0.91, respectively. Conclusions IC-EMG is a useful method to assess RE and the obstructive nature of AH .

Background The patterns of mandibular movements (MM) during sleep can be used to identify increased respiratory effort periodic large-amplitude MM (LPM), and cortical arousals associated with “sharp” large-amplitude MM (SPM). We hypothesized that Cheyne Stokes breathing (CSB) may be identified by periodic abnormal MM patterns. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. The present study aims to evaluate prospectively the concordance between CSB detected by periodic MM and polysomnography (PSG) as gold-standard. Methods In 573 consecutive patients attending an in-laboratory PSG for suspected sleep disordered breathing (SDB), MM signals were acquired using magnetometry and scored manually while blinded from the PSG signal. Data analysis aimed to verify the concordance between the CSB identified by PSG and the presence of LPM or SPM. The data were randomly divided into training and validation sets (985 5-min segments/set) and concordance was evaluated using 2 classification models. Results In PSG, 22 patients (mean age ± SD: 65.9 ± 15.0 with a sex ratio M/F of 17/5) had CSB (mean central apnea hourly indice ± SD: 17.5 ± 6.2) from a total of 573 patients with suspected SDB. When tested on independent subset, the classification of CSB based on LPM and SPM is highly accurate (Balanced-accuracy = 0.922, sensitivity = 0.922, specificity = 0.921 and error-rate = 0.078). Logistic models based odds-ratios for CSB in presence of SPM or LPM were 172.43 (95% CI: 88.23–365.04; p

It has been suggested that increased pulmonary vascular reserve, as defined by reduced pulmonary vascular resistance (PVR) and increased pulmonary transit of agitated contrast measured by echocardiography, might be associated with increased exercise capacity. Thus, at altitude, where PVR is increased because of hypoxic vasoconstriction, a reduced pulmonary vascular reserve could contribute to reduced exercise capacity. Furthermore, a lower PVR could be associated with higher capillary blood volume and an increased lung diffusing capacity. We reviewed echocardiographic estimates of PVR and measurements of lung diffusing capacity for nitric oxide (DL(NO)) and for carbon monoxide (DL(CO)) at rest, and incremental cardiopulmonary exercise tests in 64 healthy subjects at sea level and during 4 different medical expeditions at altitudes around 5000 m. Altitude exposure was associated with a decrease in maximum oxygen uptake (VO2max), from 42±10 to 32±8 mL/min/kg and increases in PVR, ventilatory equivalents for CO2 (V(E)/VCO2), DL(NO), and DL(CO). By univariate linear regression VO2max at sea level and at altitude was associated with V(E)/VCO2 (p0.001), mean pulmonary artery pressure (mPpa, p0.05), stroke volume index (SVI, p0.05), DL(NO) (p0.02), and DL(CO) (p=0.05). By multivariable analysis, VO2max at sea level and at altitude was associated with V(E)/VCO2, mPpa, SVI, and DL(NO). The multivariable analysis also showed that the altitude-related decrease in VO2max was associated with increased PVR and V(E)/VCO2. These results suggest that pulmonary vascular reserve, defined by a combination of decreased PVR and increased DL(NO), allows for superior aerobic exercise capacity at a lower ventilatory cost, at sea level and at high altitude.

Background: Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis, severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity. Methods: Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test. Results: The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE ( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold, of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arte rial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively ( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001). Conclusions: The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume.

Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (V̇o2 max). The diffusing capacities for nitric oxide (DLNO) and carbon monoxide (DLCO) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DLCO (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DLCO, DLNO, and Dm but a slight decrease in Vc. Exercise at altitude decreased DLNO and Dm. Sitaxsentan intake improved V̇o2 max together with an increase in resting and postexercise DLNO and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DLNO. Both DLCO and DLNO were correlated to V̇o2 max at sea level ( r = 0.41–0.42, P < 0.1) and more so at altitude ( r = 0.56–0.59, P < 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high-altitude newcomers, which may contribute to exercise capacity.

Lung carbon monoxide (CO) transfer and pulmonary capillary blood volume (Vc) at high altitudes have been reported as being higher in native highlanders compared to acclimatised lowlanders but large discrepancies appears between the studies. This finding raises the question of whether hypoxia induces pulmonary angiogenesis. Eighteen highlanders living in Bolivia and 16 European lowlander volunteers were studied. The latter were studied both at sea level and after acclimatisation to high altitude. Membrane conductance (Dm(CO)) and Vc, corrected for the haemoglobin concentration (Vc(cor)), were calculated using the NO/CO transfer technique. Pulmonary arterial pressure and left atrial pressures were estimated using echocardiography. Highlanders exhibited significantly higher NO and CO transfer than acclimatised lowlanders, with Vc(cor)/VA and Dm(CO)/VA being 49 and 17% greater (VA: alveolar volume) in highlanders, respectively. In acclimatised lowlanders, Dm(CO) and Dm(CO)/VA values were lower at high altitudes than at sea level. Echocardiographic estimates of cardiac output and pulmonary arterial pressure were significantly elevated at high altitudes as compared to sea level. The decrease in Dm(CO) in lowlanders might be due to altered gas transport in the airways due to the low density of air at high altitudes. The disproportionate increase in Vc in Andeans compared to the change in Dm(CO) suggests that the recruitment of capillaries is associated with a thickening of the blood capillary sheet. Since there was no correlation between the increase in Vc and the slight alterations in haemodynamics, this data suggests that chronic hypoxia might stimulate pulmonary angiogenesis in Andeans who live at high altitudes.

International audience; Membrane conductance (Dm) and capillary lung volume (Vc) derived from NO and CO lung transfer measurements in humans depend on the blood conductance (θ) values of both gases. Many θ values have been proposed in the literature. In the present study, measurements of CO and NO transfer while breathing 15% or 21% O2 allowed the estimation of θNO and the calculation of the optimal equation relating 1/θCO to pulmonary capillary oxygen pressure (PcapO2). In 10 healthy subjects, the mean calculated θNO value was similar to the θNO value previously reported in the literature (4.5mmHgmin(-1)) provided that one among three θCO equations from the literature was chosen. Setting 1/θCO=a·PcapO2+b, optimal values of a and b could be chosen using two methods: 1) by minimizing the difference between Dm/Vc ratios for any PcapO2, 2) by establishing a linear equation relating a and b. Using these methods, we are proposing the equation 1/θCO=0.0062·PcapO2+1.16, which is similar to two equations previously reported in the literature. With this set of θ values, DmCO reached the morphometric range.

Just a few clinicians routinely measure the subcomponents of the lung diffusing capacity for Carbone monoxide (DLCO ). This is because the measurement of membrane and blood conductances for CO (DmCO and DbCO = θCO × Vc , respectively) by the classic Roughton and Forster method is complicated and time consuming. In addition, it mistakenly assumes a close relationship between alveolar oxygen partial pressure (PAO2 ) and mean intracapillary oxygen partial pressure (PcapO2 ) which is the true determinant of specific conductance of haemoglobin for CO (θCO ). Besides that, the critical multistep oxygenation method along with different linear equations relating 1/θCO to PcapO2 gave highly scattered DmCO and Vc values. The Dm and Vc can also be derived from a simultaneous measurement of DLNO and DLCO with the blood resistance for NO assumed to be negligible. However, recent in vitro and in vivo experiments point towards a finite value of θNO (about 4·5 mlNO × mlblood-1 × min-1 × mmHg-1 ). Putting together the arguments and our clinical data allows us to report here the state of the art in partitioning the CO diffusing capacity into its constitutive components, with the goal to encourage further studies examining the sensitivity of DmCO and Vc to alterations observed in parenchymal diseases.

Obstructive sleep apnea-hypopnea (OAH) diagnosis in children is based on the quantification of flow and respiratory effort (RE). Pulse transit time (PTT) is one validated tool to recognize RE. Pattern analysis of mandibular movements (MM) might be an alternative method to detect RE. We compared several patterns of MM to concomittant changes in PTT during OAH in children with adenotonsillar hypertrophy.33 consecutive children with snoring and symptoms/signs of OAH.MMs were measured during polysomnography with a magnetometer device (Brizzy Nomics, Liege, Belgium) placed on the chin and forehead. Patterns of MM were evaluated representing peak to peak fluctuations0.3 mm in mandibular excursion (MML), mandibular opening (MMO), and sharp MM (MMS), which closed the mouth on cortical arousal (CAr).The median (95% CI) hourly rate of at least 1 MM (MML, or MMO, or MMS) was 18.1 (13.2-36.3) and strongly correlated with OAHI (p = 0.003) but not with central apnea-hypopnea index (CAHI; p = 0.292). The durations when the MM amplitude was0.4 mm and PTT15 ms were strongly correlated (p0.001). The mean (SD) of MM peak to peak amplitude was larger during OAH than CAH (0.9 ± 0.7 mm and 0.2 ± 0.3 mm; p0.001, respectively). MMS at the termination of OAH had larger amplitude compared to MMS with CAH (1.5 ± 0.9 mm and 0.5 ± 0.7 mm, respectively, p0.001).MM0.4 mm occurred frequently during periods of OAH and were frequently terminated by MMS corresponding to mouth closure on CAr. The MM findings strongly correlated with changes in PTT. MM analysis could be a simple and accurate promising tool for RE characterization and optimization of OAH diagnosis in children.

To the Editor: As our team analysed in detail the physiological meaning of the transfer factor of the lung for nitric oxide ( T LNO)/transfer factor of the lung for carbon monoxide ( T LCO) ratio [1], it seems interesting to extend the analysis to patients. This has been done elegantly by Hughes and van der Lee [2]. This ratio, which has the advantage of simplicity, nevertheless has some disadvantages. 1) In a given cohort of homogenous patients, values are widely scattered and a given value cannot, therefore, be used as a strong predictor of a disease. For example, pulmonary hypertension patients have, as a mean, higher T LNO/ T LCO than healthy controls; however, a normal value does not …

High-altitude exposure is a cause of pulmonary hypertension and decreased exercise capacity, but associated changes in cardiac function remain incompletely understood. The aim of this study was to investigate right ventricular (RV) and left ventricular function in acclimatized Caucasian lowlanders compared with native Bolivian highlanders at high altitudes. Standard echocardiography and tissue Doppler imaging studies were performed in 15 healthy lowlanders at sea level;24 hours after arrival in La Paz, Bolivia, at 3,750 m; and after 10 days of acclimatization and ascent to Huayna Potosi, at 4,850 m, and the results were compared with those obtained in 15 age- and body size-matched inhabitants of Oruro, Bolivia, at 4,000 m. Acute exposure to high altitude in lowlanders caused an increase in mean pulmonary arterial pressure, to 20 to 25 mm Hg, and altered RV and left ventricular diastolic function, with prolonged isovolumic relaxation time, an increased RV Tei index, and maintained RV systolic function as estimated by tricuspid annular plane excursion and the tricuspid annular S wave. This profile was essentially unchanged after acclimatization and ascent to 4,850 m, except for higher pulmonary arterial pressure. The native highlanders presented with relatively lower pulmonary arterial pressures but more pronounced alterations in diastolic function, decreased tricuspid annular plane excursion and tricuspid annular S waves, and increased RV Tei indexes. In conclusion, cardiac adaptation to high altitude was qualitatively similar in acclimatized Caucasian lowlanders and in Bolivian native highlanders. However, lifelong exposure to high altitude may be associated with different cardiac adaptation to milder hypoxic pulmonary hypertension.

Venous thromboembolic disease is a well-documented complication of Klinefelter’s syndrome, even if mechanisms underlying this prothrombotic state have not been conclusively established. On the contrary, arterial thrombosis is far less frequent, and a case of a patient with Klinefelter’s syndrome presenting with simultaneous venous thrombtoembolic disease and a complete thrombosis of the left subclavian artery is presented. Elevated levels of type 1 plasminogen activator inhibitor, in the absence of other usual thrombophilic abnormalities, raise the question of the role played by this inhibitor of the fibrinolysis in the arterial and venous thromboses presented by this patient.