Obesity in women with asthma: Baseline disadvantage plus greater small-airway responsiveness.

BACKGROUND: Obesity is known to diminish lung volumes and worsen asthma. However, mechanistic understanding is lacking, especially as concerns small-airway responsiveness. The objective of this study was therefore to compare small-airway responsiveness, as represented by the change in expiratory:inspiratory mean lung density ratios (MLDe/i , as determined by computed tomography [CT]) throughout methacholine testing in obese versus non-obese women with asthma. METHODS: Thoracic CT was performed during methacholine bronchoconstriction challenges to produce standardized response curves (SRC: response parameter versus ln[1 + % PD20], where PD20 is the cumulative methacholine dose) for 31 asthma patients (n = 18 non-obese and n = 13 obese patients). Mixed models evaluated obesity effects and interactions on SRCs while adjusting for age and bronchial morphology. Small airway responsiveness as represented by SRC slope was calculated for each third of the MLDe/i response and compared between groups. RESULTS: Obesity-associated effects observed during experimental bronchoconstriction included: (i) a significant baseline effect for forced expiratory volume in 1 second with lower values for the obese (73.11 ± 13.44) versus non-obese (82.19 ± 8.78; p = 0.002) groups prior to methacholine testing and (ii) significantly higher responsiveness in small airways as estimated via differences in MLDe/i slopes (group×ln(1 + % PD20 interaction; p = 0.023). The latter were pinpointed to higher slopes in the obese group at the beginning 2/3 of SRCs (p = 0.004 and p = 0.021). Significant obesity effects (p = 0.035 and p = 0.008) indicating lower forced vital capacity and greater % change in MLDe/I (respectively) throughout methacholine testing, were also observed. CONCLUSION: In addition to baseline differences, small-airway responsiveness (as represented by the change in MLDe/i ) during methacholine challenge is greater in obese women with asthma as compared to the non-obese.

Did COVID-19 impact Positive Airway Pressure adherence in 2020? A cross-sectional study of 8477 patients with sleep apnea.

BACKGROUND: Whether the COVID-19 pandemic impacts Positive Airway Pressure (PAP) adherence over the long-term is unknown and only preliminary short-term data have been reported. METHODS: With the aim of describing the impact of the first and second waves of COVID-19 on PAP adherence during 2020 in France, we designed a cross-sectional study of Sleep-Apnea (SA)-patients under PAP telemonitoring. To examine PAP adherence in adult SA patients, we assessed de-identified data from a non-profit healthcare provider database during the period January 1, 2019 to December 31, 2020. Included patients met the following criteria: (i) PAP-treated for at least 4 months before January 1, 2019 and with continuous PAP during both 2019 and 2020; (ii) ≥ 360 daily PAP telemonitored data per year. For PAP adherence, data were collected using the PAP-software. RESULTS: 8477/10482 patients were finally included in the analysis [72.4% male, median age 70 years (IQ25-75: 61-77], 25.6% < 62 years old, initial Apnea-Hypopnea Index (AHI) of 41 (31-59)/h. Median PAP adherence was 7.21 (6.12-8.10) h/day in 2020 versus 7.12 (6.05-8.02) h/day in 2019, p < 0.001. The median difference in PAP adherence between the first 2020 lockdown and the corresponding 2019 weeks was 9.75 (CI95% 8.75-10.75) min/day, p < 0.001. The median difference in PAP adherence between the second 2020 lockdown and the corresponding 2019 weeks was 5.00 (CI95% 4.00-6.00) min/day, p < 0.001. If we consider the minimal clinically important difference of 30 min for PAP adherence, 30.4% and 26% of the patients increased their PAP adherence by at least 30 min during the first and second lockdowns respectively; 17.6% and 19.3% of the patients lowered their PAP adherence by at least 30 min in the first and second lockdowns, respectively. CONCLUSION: During the first and second lockdowns, the COVID-19 pandemic had a clinically irrelevant effect on PAP adherence for the study population. Future studies are needed to describe COVID-19 pandemic impact on PAP adherence not only for long-term PAP-treated SA patients but also for incident cases. Trial registration The COVADENE study was registered on March 1st, 2021 on ClinicalTrials.gov (Identifier: NCT04775966).

Expert Consensus on the Tapering of Oral Corticosteroids for the Treatment of Asthma. A Delphi Study.

Rationale: There is a need to minimize oral corticosteroid (OCS) use in patients with asthma to prevent their costly and burdensome adverse effects. Current guidelines do not provide recommendations for OCS tapering in patients with asthma.Objectives: To develop expert consensus on OCS tapering among international experts.Methods: A modified Delphi method was used to develop expert consensus statements relating to OCS use, tapering, adverse effects, adrenal insufficiency, and patient-physician shared decision-making. Initial statements proposed by experts were categorized, filtered for repetition, and presented back to experts over three ranking rounds to obtain consensus (≥70% agreement).Measurements and Main Results: One hundred thirty-one international experts participated in the study, and 296 statements were ranked. Numerous recommendations and guidance regarding appropriate OCS use were established. Experts agreed that OCS tapering should be attempted in all patients with asthma receiving maintenance OCS therapy, with personalization of tapering rhythm and speed. The importance of recognizing individual adverse effects was also established; however, a unified approach to the assessment of adrenal insufficiency was not reached. Shared decision-making was considered an important goal during the tapering process.Conclusions: In this Delphi study, expert consensus statements were generated on OCS use, tapering, adverse-effect screening, and shared decision-making, which may be used to inform clinical practice. Areas of nonconsensus were identified, highlighting uncertainty among the experts around some aspects of OCS use in asthma, such as adrenal insufficiency, which underscores the need for further research in these domains.

Mask side-effects in long-term CPAP-patients impact adherence and sleepiness: the InterfaceVent real-life study.

BACKGROUND: For some patients, Continuous Positive Airway Pressure (CPAP) remains an uncomfortable therapy despite the constant development of technological innovations. To date, no real life study has investigated the relationship between mask related side-effects (MRSEs) and CPAP-non-adherence (defined as < 4 h/day) or residual-excessive-sleepiness (RES, Epworth-Sleepiness-Scale (ESS) score ≥ 11) in the long-term. METHODS: The InterfaceVent-CPAP study is a prospective real-life cross-sectional study conducted in an apneic adult cohort undergoing at least 3 months of CPAP with unrestricted mask-access (34 different masks). MRSEs were evaluated using visual-analogue-scales, CPAP-data using CPAP-software, sleepiness using ESS. RESULTS: 1484 patients were included in the analysis (72.2% male, median age 67 years (IQ25-75: 60-74), initial Apnea-Hypopnea-Index (AHI) of 39 (31-56)/h, residual AHIflow was 1.9 (0.9-4) events/h), CPAP-treatment lasted 4.4 (2.0-9.7) years, CPAP-usage was 6.8 (5.5-7.8) h/day, the prevalence of CPAP-non-adherence was 8.6%, and the prevalence of RES was 16.17%. Leak-related side-effects were the most prevalent side-effects (patient-reported leaks concerned 75.4% of responders and had no correlation with CPAP-reported-leaks). Multivariable logistic regression analyses evaluating explanatory-variable (demographic data, device/mask data and MRSEs) effects on variables-of-interest (CPAP-non-adherence and RES), indicated for patient-MRSEs significant associations between: (i) CPAP-non-adherence and dry-mouth (p = 0.004); (ii) RES and patient-reported leaks (p = 0.007), noisy mask (p < 0.001), dry nose (p < 0.001) and harness pain (p = 0.043). CONCLUSION: In long-term CPAP-treated patients, leak-related side-effects remain the most prevalent side-effects, but patient-reported leaks cannot be predicted by CPAP-reported-leaks. Patient-MRSEs can be independently associated with CPAP-non-adherence and RES, thus implying a complementary role for MRSE questionnaires alongside CPAP-device-reported-data for patient monitoring. Trial registration InterfaceVent is registered with ClinicalTrials.gov (NCT03013283).

Patterns of adaptive servo-ventilation settings in a real-life multicenter study: pay attention to volume! : Adaptive servo-ventilation settings in real-life conditions.

BACKGROUNDS: To explain the excess cardiovascular mortality observed in the SERVE-HF study, it was hypothesized that the high-pressure ASV default settings used lead to inappropriate ventilation, cascading negative consequences (i.e. not only pro-arrythmogenic effects through metabolic/electrolyte abnormalities, but also lower cardiac output). The aims of this study are: i) to describe ASV-settings for long-term ASV-populations in real-life conditions; ii) to describe the associated minute-ventilations (MV) and therapeutic pressures for servo-controlled-flow versus servo-controlled-volume devices (ASV-F Philips®-devices versus ASV-V ResMed®-devices). METHODS: The OTRLASV-study is a cross-sectional, 5-centre study including patients who underwent ASV-treatment for at least 1 year. The eight participating clinicians were free to adjust ASV settings, which were compared among i) initial diagnosed sleep-disordered-breathing (SBD) groups (Obstructive-Sleep-Apnea (OSA), Central-Sleep-Apnea (CSA), Treatment-Emergent-Central-Sleep-Apnea (TECSA)), and ii) unsupervised groups (k-means clusters). To generate these clusters, baseline and follow-up variables were used (age, sex, body mass index (BMI), initial diagnosed Obstructive-Apnea-Index, initial diagnosed Central-Apnea-Index, Continuous-Positive-Airway-Pressure used before ASV treatment, presence of cardiopathy, and presence of a reduced left-ventricular-ejection-fraction (LVEF)). ASV-data were collected using the manufacturer's software for 6 months. RESULTS: One hundred seventy-seven patients (87.57% male) were analysed with a median (IQ25-75) initial Apnea-Hypopnea-Index of 50 (38-62)/h, an ASV-treatment duration of 2.88 (1.76-4.96) years, 61.58% treated with an ASV-V. SDB groups did not differ in ASV settings, MV or therapeutic pressures. In contrast, the five generated k-means clusters did (generally described as follows: (C1) male-TECSA-cardiopathy, (C2) male-mostly-CSA-cardiopathy, (C3) male-mostly-TECSA-no cardiopathy, (C4) female-mostly-elevated BMI-TECSA-cardiopathy, (C5) male-mostly-OSA-low-LVEF). Of note, the male-mostly-OSA-low-LVEF-cluster-5 had significantly lower fixed end-expiratory-airway-pressure (EPAP) settings versus C1 (p = 0.029) and C4 (p = 0.007). Auto-EPAP usage was higher in the male-mostly-TECSA-no cardiopathy-cluster-3 versus C1 (p = 0.006) and C2 (p < 0.001). MV differences between ASV-F (p = 0.002) and ASV-V (p < 0.001) were not homogenously distributed across clusters, suggesting specific cluster and ASV-algorithm interactions. Individual ASV-data suggest that the hyperventilation risk is not related to the cluster nor the ASV-monitoring type. CONCLUSIONS: Real-life ASV settings are associated with combinations of baseline and follow-up variables wherein cardiological variables remain clinically meaningful. At the patient level, a hyperventilation risk exists regardless of cluster or ASV-monitoring type, spotlighting a future role of MV-telemonitoring in the interest of patient-safety. TRIAL REGISTRATION: The OTRLASV study was registered on ClinicalTrials.gov (Identifier: NCT02429986 ). 1 April 2015.

Poor Concordance between Sequential Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy in the Diagnosis of Diffuse Interstitial Lung Diseases.

Rationale: The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. Objectives: To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. Methods: A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (T.V.C.). Kappa-concordance coefficients and percentage agreement were computed for: TBLC versus SLB, MDA2 versus TBLC, MDA2 versus SLB, and blinded pathology versus routine pathology. Measurements and Main Results: Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range, 5-8 mm). SLB biopsy sizes averaged 46.1 ± 13.8 mm. Concordance coefficients and percentage agreement were: TBLC versus SLB: κ = 0.22 (95% confidence interval [CI], 0.01-0.44), percentage agreement = 38% (95% CI, 18-62%); MDA2 versus TBLC: κ = 0.31 (95% CI, 0.06-0.56), percentage agreement = 48% (95% CI, 26-70)%; MDA2 versus SLB: κ = 0.51 (95% CI, 0.27-0.75), percentage agreement = 62% (95% CI, 38-82%); two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11 of 21 (52%) of cases. Conclusions: Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA.

What is the remaining status of adaptive servo-ventilation? The results of a real-life multicenter study (OTRLASV-study) : Adaptive servo-ventilation in real-life conditions.

BACKGROUNDS: As a consequence of the increased mortality observed in the SERVE-HF study, many questions concerning the safety and rational use of ASV in other indications emerged. The aim of this study was to describe the clinical characteristics of ASV-treated patients in real-life conditions. METHODS: The OTRLASV-study is a prospective, 5-centre study including patients who underwent ASV-treatment for at least 1 year. Patients were consecutively included in the study during the annual visit imposed for ASV-reimbursement renewal. RESULTS: 177/214 patients were analysed (87.57% male) with a median (IQ25-75) age of 71 (65-77) years, an ASV-treatment duration of 2.88 (1.76-4.96) years, an ASV-usage of 6.52 (5.13-7.65) hours/day, and 54.8% were previously treated via continuous positive airway pressure (CPAP). The median Epworth Scale Score decreased from 10 (6-13.5) to 6 (3-9) (p < 0.001) with ASV-therapy, the apnea-hypopnea-index decreased from 50 (38-62)/h to a residual device index of 1.9 (0.7-3.8)/h (p < 0.001). The majority of patients were classified in a Central-Sleep-Apnea group (CSA; 59.3%), whereas the remaining are divided into an Obstructive-Sleep-Apnea group (OSA; 20.3%) and a Treatment-Emergent-Central-Sleep-Apnea group (TECSA; 20.3%). The Left Ventricular Ejection Fraction (LVEF) was > 45% in 92.7% of patients. Associated comorbidities/etiologies were cardiac in nature for 75.7% of patients (neurological for 12.4%, renal for 4.5%, opioid-treatment for 3.4%). 9.6% had idiopathic central-sleep-apnea. 6.2% of the patients were hospitalized the year preceding the study for cardiological reasons. In the 6 months preceding inclusion, night monitoring (i.e. polygraphy or oximetry during ASV usage) was performed in 34.4% of patients, 25.9% of whom required a subsequent setting change. According to multivariable, logistic regression, the variables that were independently associated with poor adherence (ASV-usage ≤4 h in duration) were TECSA group versus CSA group (p = 0.010), a higher Epworth score (p = 0.019) and lack of a night monitoring in the last 6 months (p < 0.05). CONCLUSIONS: In real-life conditions, ASV-treatment is often associated with high cardiac comorbidities and high compliance. Future research should assess how regular night monitoring may optimize devices settings and patient management. TRIAL REGISTRATION: The OTRLASV study is registered on ClinicalTrials.gov (Identifier: NCT02429986 ) on 1 April 2015.

Is the 2013 American Thoracic Society CPAP-tracking system algorithm useful for managing non-adherence in long-term CPAP-treated patients?

BACKGROUND: Whereas telemedicine usage is growing, the only clinical algorithm for Continuous Positive Airway Pressure (CPAP) adherence management is that stipulated by the 2013 American Thoracic Society (ATS). The capacity of the latter to predict non-adherence in long-term CPAP-treated patients has not been validated. METHODS: Patients from the prospective real-life InterfaceVent study (NCT03013283, study conducted in an adult cohort undergoing at least 3 months of CPAP) and eligible for ATS algorithm usage were analysed. The residual device Apnea-Hypopnea-Index (AHIflow) and High Large Leak (HLL) thresholds proposed in the ATS algorithm were evaluated for predicting adherence (i.e. AHIflow > 10/h, HLLs 95th > 24 L/min for ResMed® devices and ResMed® nasal mask, HLLs 95th > 36 l/min for ResMed® devices and ResMed® oronasal masks, HLLs > 1 h for Philips® devices and HHLs > 60 l/min for Fisher & Paykel® devices). Adherence was defined according to the 2013 ATS algorithm (i.e. CPAP use > 4 h/j for at least 70% of days). RESULTS: 650/1484 patients eligible for ATS algorithm usage were analysed (15.38% non-adherent, 74% male with a median (IQ25-75) age of 68 (61-77) years, a body mass index of 30.8 (27.7-34.5) kg/m2, an initial AHI of 39 (31-55) events/h, and CPAP-treatment-duration of 5.1 (2.2-7.8) years). Logistic regression analysis demonstrated no significant relationship between the ATS proposed AHIflow or HLL thresholds and non-adherence. Complementary ROC curve analysis failed to determine satisfactory AHIflow and HLL thresholds. CONCLUSION: When managing non-adherence in long-term CPAP-treated patients, our data do not validate absolute AHIflow or HLL thresholds in general. TRIAL REGISTRATION: The INTERFACE-VENT study is registered on ClinicalTrials.gov (Identifier: study ( NCT03013283 ).

Health-related quality of life and disease progression in pulmonary arterial hypertension patients: a 3-year study.

OBJECTIVES: The role of health-related quality of life (HRQoL) and psychological variables in pulmonary arterial hypertension (PAH) progression remains poorly quantified. We aimed to investigate the relationship between disease progression in PAH patients and HRQoL and psychological characteristics. METHODS: A 3-year longitudinal cohort was initiated. Patients with stable PAH (groups I-IV ineligible for angioplasty/endarterectomy) were included (n=55). Standard clinical variables, including invasive haemodynamic parameters, were prospectively recorded. A battery of questionnaires was used to characterise the psychological status of patients upon study initiation, and HRQoL was quantified using the SF-36 Questionnaire every 3 months for 24 months, and then again at 36 months. Guideline-defined disease progression and progression-free survival were recorded for 36 months. MEASUREMENTS AND MAIN RESULTS: Psychological distress was highly prevalent at baseline. The Physical Component Summary (PCS) and the Mental Component Summary (MCS) of the HRQoL were poor (PCS=37.13±8.18; MCS=42.42±10.88) but stable over 3 years of follow-up. Among PCS subscales, Physical Functioning (PF) (p=0.012) was identified as being independently associated with disease progression (Cox survival model), along with mean pulmonary arterial pressure (p=0.003) and cardiac output (p=0.005). Depression was the unique independent psychological characteristic associated with PF (p=0.0001). CONCLUSIONS: PAH patients have poor HRQoL. In addition to already known criteria related to disease severity, the HRQoL PF subscale is independently associated with disease progression in PAH. This may be explained by depression.

Anti-interleukin 5 therapies failure criteria in severe asthma: a Delphi-consensus study.

BACKGROUND: Current practices for assessing response to anti-interleukin 5/R treatment in severe asthma patients are heterogeneous. The objective of this study was to achieve an expert consensus defining failure criteria for anti-interleukin 5/R treatment in severe asthma patients. METHODS: Experts were invited to a 5-round Delphi exercise if they were pulmonologists managing ⩾30 patients at a nationally recognized severe asthma expert centre. Following two rounds of statement-generating brainstorming, the expert panel ranked each statement according to a 5-point Likert-type scale during three additional rounds. Positive consensus was considered achieved when ⩾80% of experts agreed with a statement with >50% strong agreement and <15% disagreement. RESULTS: Twenty experts participated in the study. All experts agreed that predefined treatment goals defining effectiveness should be personalized during shared decision making via a patient contract. Treatment failure was defined as (1) absence of a reduction in exacerbation rates by ⩾25% or (2) absence of a reduction in oral corticosteroid therapy by ⩾25% of the initial dosage or (3) occurrence of emergency room visits or hospitalizations after 6 months of treatment. Treatment failure should result in discontinuation. For partial responders, treatment discontinuation was not recommended unless an alternative from another therapeutic class exists and should be discussed in a multidisciplinary consultation. CONCLUSION: The present study provides objective criteria for anti IL5 or IL5R failure in severe asthma and suggests consensus based guidelines for prescription, evaluation and discontinuation decision-making.

Sacubitril-valsartan initiation in chronic heart failure patients impacts sleep apnea: the ENTRESTO-SAS study.

AIMS: Optimizing medical cardiac treatment for sleep apnoea (SA) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is an expert Grade C recommendation based on six studies encompassing a total of 67 patients only. Whether sacubitril-valsartan (SV), a cornerstone of HFrEF medical treatment, impacts SA is unknown and requires evaluation. METHODS AND RESULTS: The ENTRESTO-SAS trial is a six-centre, prospective, open-label real-life cohort study (NCT02916160). Ambulatory patients eligible for SV (i.e. HFrEF adults who remain symptomatic despite optimal treatment) were evaluated before and after 3 months of SV (including nocturnal ventilatory polygraphy); 118 patients were final analysed [median age was 66 (IQ25-75 : 56-73) years, 81.4% male, 36.5% New York Heart Association III-IV, N-terminal pro-B-type natriuretic peptide level of 1564 (701-3376) ng/L, left ventricular ejection fraction of 30 (25-34)%, 60.7% ischaemic HFrEF, 97.5% initially treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, 83.9% with beta-blockers, 64.4% with mineralocorticoid receptor antagonists, and 74.6% with diuretics]. Three groups were defined according to initial central/obstructive apnoea-hypopnoea indices (AHIs): G1 (n = 49, AHIcentral  ≥ 5/h and AHIobstructive  < 15/h); G2 (n = 27, AHIobstructive  ≥ 15/h); and G3 (n = 42, AHIcentral  < 5/h and AHIobstructive  < 15/h). At 3 months, the AHI (main predefined outcome) decreased significantly by -7.10/h (IQ25-75 : -16.10 to 0.40; P < 0.001) in G1 + G2 without positive airway pressure treatment (45 patients, median initial AHI of 24.20 (IQ25-75 : 16.40-43.50)/h). Of these, 24.4% presented an AHI decrease ≥50% and 37.78% had a final AHI < 15/h (tendency for improvement from an initial value of 20%: P = 0.0574). For G1 patients (n = 37), AHI significantly decreased from a median of 22.90 (16.00-43.50)/h to 19.20 (12.70-31.10)/h (P = 0.002). For G2 patients (n = 8), AHI decreased from a median of 30.10 (26.40-47.60)/h to 22.75 (14.60-36.90)/h (statistically non-significant, P = 0.059). CONCLUSIONS: In this real-life population, SV treatment for 3 months in SA patients is associated with a significant decrease in AHI. These results support the current guidelines that recommend first an optimization of the HFrEF treatment in patients with HFrEF and central SA. A potential positive airway pressure sparing effect merits further investigation.

Feasibility of Type 3 Polygraphy for Evaluating Leak Determinants in CPAP-Treated OSA Patients: A Step Toward Personalized Leak Management.

BACKGROUND: Unintentional leaks (ULs) are frequent adverse effects in CPAP-treated patients. We previously published a novel methodology for analyzing the determinants of UL using polysomnography. We now propose a simplified recording system using a type 3 polygraphic device (Somnolter; Nomics S.A.). RESEARCH QUESTION: (1) To describe individual UL determinants provided by the Somnolter software in automatic-CPAP-treated OSA patients; (2) To subsequently describe the clinical consensus of four physicians on how to manage each individual UL situation. STUDY DESIGN AND METHODS: Somnoler recordings performed under nasal automatic-CPAP were automatically analyzed with APIOS software. For each polygraphic recording, APIOS provided the OR and the CIs for potential determinants of UL: mouth opening, CPAP pressure, body position, and mandibular oscillation. Based on these results, each of four physicians was asked to choose one of four strategies: (1) increase or decrease therapeutic pressure; (2) change nasal mask for oro-nasal mask/chinstrap; (3) favor a nonsupine or supine position; (4) no action for individual leak management. Subsequently, a meeting was held to determine a consensus choice for each individual case. RESULTS: Seventy-eight consecutive patients underwent home-polygraphy with Somnolter. Fifty recordings were analyzed (16 females; 65 [57-75] years of age; BMI = 31.1 [27.4-35.3]). Individual diagnosis of UL was routinely feasible. The determinants of UL were heterogeneous in the population, and diagnosis of UL was not feasible in 10 patients. Based on the results from this analysis, we established consensus leak management strategies at the individual level. The average Cohen κ coefficient for the four raters was 0.58. Pressure modification was proposed in 36% of patients, no action in 24%, installation of a facial mask/chinstrap in 22%, and positional treatment in 18%. INTERPRETATION: The use of type 3 polygraphy for characterizing leak determinants in patients treated with nasal automatic-CPAP is feasible in routine practice. Leak determinants are patient specific. Interrater concordance for determining individual leak management strategies demonstrated a "fair" level of agreement. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03381508; URL: www.clinicaltrials.gov).

Impact of psychological factors on the health-related quality of life of patients treated for pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare and life-threatening disease well-marked by under diagnosis, delayed diagnosis and atypical treatments. Few data are available on the quality of life (QoL) and psychosocial characteristics of patients with PAH. Our aim is to describe the impact of psychological factors on the health-related quality of life (HRQoL) of treated PAH patients in a cross-sectional study. METHODS: Consecutive patients presenting at our Competency Centre for PAH were recruited. The aetiology, New York Heart Association (NYHA) stage, haemodynamics, 6-min walk distance (6MWD), delta SPO2 (Pulse oximeter oxygen saturation; baseline lowest value during 6-min walk test (6MWT), current treatments and psychological history were recorded. HRQoL, anxiety, depression and coping strategies were explored using self-administered questionnaires (SF-36, HADS, STAI-Y, CHIP and WCC). RESULTS: A total of 55 patients were included. The HRQoL of PAH patients was poor with altered results on several scales. Anxiety and depression were high and coping was focused on medical information strategies. Multivariate analysis indicated a positive relationship between 6MWD and the Physical Composite Score for QoL (p=0.004), as well as a negative relationship between delta SPO2 and the Mental Composite Score (p=0.02), irrespective of other known prognostic factors (such as haemodynamics at right heart catheterization). Depression and Trait-Anxiety were associated with a lower physical (p=0.001) and mental (p<0.001) QoL, respectively. CONCLUSIONS: Psychological factors impact the HRQoL of treated patients. A longitudinal and qualitative study should refine these results. TRIAL REGISTRATION: Clinical trial N°: NCT01380054.

Profiling the biological effects of wastewater samples via bioluminescent bacterial biosensors combined with estrogenic assays.

Various water samples were successfully evaluated using a panel of different recombinant bioluminescent bacteria and estrogenic activity analysis. The bioluminescent bacteria strains induced by oxidative (superoxide radical or hydroxyl radical), protein damage, cell membrane damage, or cellular toxicity were used. Estrogenic activities were examined by using the yeast strain BY4741, which carries the ß-galactosidase reporter gene under the control of the estrogen-responsive element (ERE). A total of 14 samples from three wastewater treatment plants, one textile factory, and seawater locations in Tunisia were analyzed. A wide range of bio-responses were described. Site/sample heterogeneity was prevalent, in combination with generally high relative bioluminescence scores for oxidative stress (OH•). Estrogenic activity was detected at all sites and was particularly elevated at certain sites. Our perspectives include the future exploration of the variation detected in relation to treatment plant operations and environmental impacts. In conclusion, this new multi-experimental method can be used for rapid bio-response profile monitoring and the evaluation of environmental samples spanning a wide range of domains. This study confirms that bio-reactive wastewater treatment plant (WWTP) effluents are discharged into seawater, where they may impact coastal populations.