Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function.

BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).

Phase 2, Double-Blind, Placebo-controlled Trial of a c-Jun N-Terminal Kinase Inhibitor in Idiopathic Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. Objectives: We sought to assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. Methods: In a Phase 2, randomized (1:1:1), double-blind, placebo-controlled study (ClinicalTrials.gov ID: NCT03142191), patients received CC-90001 (200 or 400 mg) or placebo once daily for 24 weeks. Background antifibrotic treatment (pirfenidone) was allowed. The primary endpoint was change in the percentage of predicted FVC (ppFVC) from baseline to Week 24; secondary endpoints included safety. Measurements and Main Results: In total, 112 patients received at least one dose of study drug. The study was terminated early because of a strategic decision made by the sponsor. Ninety-one patients (81%) completed the study. The least-squares mean changes from baseline in ppFVC at Week 24 were -3.1% (placebo), -2.1% (200 mg), and -1.0% (400 mg); the differences compared with placebo were 1.1% (200 mg; 95% confidence interval: -2.1, 4.3; P = 0.50) and 2.2% (400 mg; 95% confidence interval: -1.1, 5.4; P = 0.19). Adverse event frequency was similar in patients in the combined CC-90001 arms versus placebo. The most common adverse events were nausea, diarrhea, and vomiting, which were more frequent in patients in CC-90001 arms versus placebo. Fewer patients in the CC-90001 arms than in the placebo arm experienced cough and dyspnea. Conclusions: Treatment with CC-90001 over 24 weeks led to numerical improvements in ppFVC in patients with idiopathic pulmonary fibrosis compared with placebo. CC-90001 was generally well tolerated, which was consistent with previous studies. Clinical trial registered with www.clinicaltrials.gov (NCT03142191).

Specific Medication Literacy in Older Adults with Asthma.

Purpose: To explore specific medication literacy (SML) of older adults and associations of SML strength. Methods: This was an observational study. Participants were at least 60 years old, with an asthma diagnosis and in good health. Data were collected by a registered nurse researcher. The SML data collection instrument gathered information about each medication a participant used: name, purpose, how taken, special instructions, adverse effects, and drug-drug or drug-disease interactions. An SML scoring rubric was developed. Results: All could provide name, and most provided purpose, how taken. The lowest SML domains were side effects and interactions. Age at time of asthma diagnosis correlated with stronger SML scores and living in a disadvantaged neighborhood correlated with lower SML scores. Discussion: Gaps in medication literacy may create less ability to self-monitor. Patients want medication literacy but struggle with appropriate, individualized, information. Conclusion: The study provides insights on gaps and opportunities for SML.

Do Interviews Really Matter in Generating Programs and Applicants' Rank Lists for the Match?

OBJECTIVE: A paucity of data exists on the role of the interview day in programs and applicants' final rank list. The objective of our study was to investigate the impact interview day has on our programs and our interviewees' final rank list. METHODS: For the 2020 appointment year, our program used an Electronic Residency Application System Application Scoring Tool and Interview Scoring Tool to generate the preliminary rank list for our pulmonary and critical care fellowship applicants. The final rank list was decided after interviewers' discussion during the program's rank list meeting. We aimed to correlate the preliminary and final lists. We also surveyed applicants on the importance of interview day in generating their rank list. RESULTS: The final and the preliminary rank lists were strongly correlated (rs(47) = 0.87, P < 0.001). There was a stronger correlation between the final rank and the rank based on the application score (rs(47) = 0.84, P < 0.001) than the rank based on the interview score (rs(47) = 0.64, P < 0.001). For the postinterview survey, 48 applicants were surveyed-20 replied with a response rate of 42% and 18 respondents (90%) rated the interview experience as important or very important in their rank list decisions. CONCLUSIONS: The programs rank list correlated more with the candidates' written application than their interview day performance; however, interview experience greatly influenced the applicants' rank lists. In the coronavirus disease 2019 pandemic, in which all interviews are virtual, programs should make diligent efforts to construct virtual interview days, given their importance to applicants in generating their final rank list for the match.

Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.

BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score. RESULTS: In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group. CONCLUSIONS: Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).

Controlled Frequency Breathing Reduces Inspiratory Muscle Fatigue.

Burtch, AR, Ogle, BT, Sims, PA, Harms, CA, Symons, TB, Folz, RJ, and Zavorsky, GS. Controlled frequency breathing reduces inspiratory muscle fatigue. J Strength Cond Res 31(5): 1273-1281, 2017-Controlled frequency breathing (CFB) is a common swim training modality involving holding one's breath for approximately 7-10 strokes before taking another breath. We sought to examine the effects of CFB training on reducing respiratory muscle fatigue. Competitive college swimmers were randomly divided into either the CFB group that breathed every 7-10 strokes or a control group that breathed every 3-4 strokes. Twenty swimmers completed the study. The training intervention included 5-6 weeks (16 sessions) of 12 × 50-m repetitions with breathing 8-10 breaths per 50-m (control group) or 2-3 breaths per 50-m (CFB group). Inspiratory muscle fatigue was defined as the decrease in maximal inspiratory pressure (MIP) between rest and 46 seconds after a 200-yard freestyle swimming race (115 seconds [SD 7]). Aerobic capacity, pulmonary diffusing capacity, and running economy were also measured pre- and posttraining. Pooled results demonstrated a 12% decrease in MIP at 46 seconds post-race (-15 [SD 14] cm H2O, effect size = -0.48, p < 0.01). After 4 weeks of training, only the CFB group prevented a decline in MIP values before to 46 seconds after race (-2 [13] cm H2O, p > 0.05). However, swimming performance, aerobic capacity, pulmonary diffusing capacity, and running economy did not improve (p > 0.05) posttraining in either group. In conclusion, CFB training appears to prevent inspiratory muscle fatigue; yet, no difference was found in performance outcomes.

Regulation of Oxidative Stress in Pulmonary Artery Endothelium. Modulation of Extracellular Superoxide Dismutase and NOX4 Expression Using Histone Deacetylase Class I Inhibitors.

An imbalance between oxidants and antioxidants is considered a major factor in the development of pulmonary vascular diseases. Oxidative stress seen in pulmonary vascular cells is regulated by increased expression of prooxidant enzymes (e.g., nicotinamide adenine dinucleotide phosphate reduced oxidases) and/or decreased production of antioxidants and antioxidant enzymes (e.g., superoxide dismutases). We and others have shown that expression of antioxidant genes in pulmonary artery cells is regulated by epigenetic mechanisms. In this study, we investigate the regulation of oxidative stress in pulmonary artery cells using inhibitors of histone deacetylases (HDACs). Human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells were exposed to an array of HDAC inhibitors followed by analysis of anti- and prooxidant gene expression using quantitative RT-PCR and quantitative RT-PCR array. We found that exposure of HPAECs to scriptaid, N-[4-[(hydroxyamino)carbonyl]phenyl]-α-(1-methylethyl)-benzeneacetamide, and trichostatin A for 24 hours induced expression of extracellular superoxide dismutase (EC-SOD) up to 10-fold, whereas expression of the prooxidant gene NADPH oxidase 4 was decreased by more than 95%. We also found that this differential regulation of anti- and prooxidant gene expression resulted in significant attenuation in the cellular levels of reactive oxygen species. Induction of EC-SOD expression was attenuated by the Janus kinase 2 protein kinase inhibitor AG490 and by silencing Janus kinase 2 expression. Augmentation of EC-SOD expression using scriptaid was associated with increased histone H3 (Lys27) acetylation and H3 (Lys4) trimethylation at the gene promoter. We have determined that oxidative stress in pulmonary endothelial cells is regulated by epigenetic mechanisms and can be modulated using HDAC inhibitors.

The c10orf10 gene product is a new link between oxidative stress and autophagy.

The human c10orf10 gene product, also known as decidual protein induced by progesterone (DEPP), is known to be differentially regulated in mouse tissues in response to hypoxia and oxidative stress, however its biological function remains unknown. We found that mice lacking extracellular superoxide dismutase (EC-SOD) show attenuated expression of DEPP in response to acute hypoxia. DEPP mRNA levels, as well as the activity of a reporter gene expressed under the control of the DEPP 5'-flanking region, were significantly upregulated in Hep3B and Vero cells overexpressing EC-SOD. Subcellular fractionation and immunofluorescent microscopy indicated that overexpressed DEPP is co-localized with both protein aggregates and aggresomes. Further biochemical characterization indicates that DEPP protein is unstable and undergoes rapid degradation. Inhibition of proteasome activities significantly increases DEPP protein levels in soluble and insoluble cytosolic fractions. Attenuation of autophagosomal activity by 3-methyladenine increases DEPP protein levels while activation of autophagy by rapamycin reduced DEPP protein levels. In addition, ectopic overexpression of DEPP leads to autophagy activation, while silencing of DEPP attenuates autophagy. Collectively, these results indicate that DEPP is a major hypoxia-inducible gene involved in the activation of autophagy and whose expression is regulated by oxidative stress.

Correction: Detection of obstructive sleep apnea using Belun Sleep Platform wearable with neural network-based algorithm and its combined use with STOP-Bang questionnaire.

[This corrects the article DOI: 10.1371/journal.pone.0258040.].

Polypharmacy Interactions Impacting Methacholine Challenge Testing for Asthma Assessment in Older People.

Objective To investigate potential reasons for unusually high incidence of negative Methacholine Challenge Tests (MCT), following standardized MCT medication-hold protocol, in older people with physician-diagnosed asthma. Design An analysis of a longitudinal observational parent study of asthma. Setting Community-dwelling participants were evaluated in an outpatient clinic and at home. Participants Screening inclusion criteria for the parent study included 60 years of age or older, physician diagnosis of asthma, and a positive response to at least one of six asthma screening questions. Participants were enrolled in the study if they also demonstrate either: (1) a postbronchodilator administration response showing an increase of at least 12% and 200 mL in forced expiratory volume or an increase of at least 12% and 200 mL in forced vital capacity, or (2) an MCT result of PC20 ≤ 16 mg/mL (indicating bronchial hyper-responsiveness, MCT positive). Exclusion criteria included diagnosis of cognitive impairment or dementia, residing in a long-term care facility, more than 20 pack/ year smoking history or a history of smoking within the previous five years, inability to perform pulmonary function testing maneuvers, and a Prognostic Index score of greater than 10. Interventions Analysis of participant data for non-medication- and medication-exposure factors for association with negative MCT results. Results Anticholinergic burden and statin use were positively associated with negative MCT. Conclusion Medications not accounted for in medication-hold protocols, and concurrently in use, may impact clinical tests and outcomes.

Belun Ring (Belun Sleep System BLS-100): Deep learning-facilitated wearable enables obstructive sleep apnea detection, apnea severity categorization, and sleep stage classification in patients suspected of obstructive sleep apnea.

GOAL AND AIMS: Our objective was to evaluate the performance of Belun Ring with second-generation deep learning algorithms in obstructive sleep apnea (OSA) detection, OSA severity categorization, and sleep stage classification. FOCUS TECHNOLOGY: Belun Ring with second-generation deep learning algorithms REFERENCE TECHNOLOGY: In-lab polysomnography (PSG) SAMPLE: Eighty-four subjects (M: F = 1:1) referred for an overnight sleep study were eligible. Of these, 26% had PSG-AHI<5; 24% had PSG-AHI 5-15; 23% had PSG-AHI 15-30; 27% had PSG-AHI ≥ 30. DESIGN: Rigorous performance evaluation by comparing Belun Ring to concurrent in-lab PSG using the 4% rule. CORE ANALYTICS: Pearson's correlation coefficient, Student's paired t-test, diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Cohen's kappa coefficient (kappa), Bland-Altman plots with bias and limits of agreement, receiver operating characteristics curves with area under the curve, and confusion matrix. CORE OUTCOMES: The accuracy, sensitivity, specificity, and kappa in categorizing AHI ≥ 5 were 0.85, 0.92, 0.64, and 0.58, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 15 were 0.89, 0.91, 0.88, and 0.79, respectively. The accuracy, sensitivity, specificity, and Kappa in categorizing AHI ≥ 30 were 0.91, 0.83, 0.93, and 0.76, respectively. BSP2 also achieved an accuracy of 0.88 in detecting wake, 0.82 in detecting NREM, and 0.90 in detecting REM sleep. CORE CONCLUSION: Belun Ring with second-generation algorithms detected OSA with good accuracy and demonstrated a moderate-to-substantial agreement in categorizing OSA severity and classifying sleep stages.

An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome.

RATIONALE: Acute lung dysfunction of noninfectious etiology, known as idiopathic pneumonia syndrome (IPS), is a severe complication following hematopoietic stem cell transplantation (HSCT). Several mouse models have been recently developed to determine the underlying causes of IPS. A cohesive interpretation of experimental data and their relationship to the findings of clinical research studies in humans is needed to better understand the basis for current and future clinical trials for the prevention/treatment of IPS. OBJECTIVES: Our goal was to perform a comprehensive review of the preclinical (i.e., murine models) and clinical research on IPS. METHODS: An ATS committee performed PubMed and OVID searches for published, peer-reviewed articles using the keywords "idiopathic pneumonia syndrome" or "lung injury" or "pulmonary complications" AND "bone marrow transplant" or "hematopoietic stem cell transplant." No specific inclusion or exclusion criteria were determined a priori for this review. MEASUREMENTS AND MAIN RESULTS: Experimental models that reproduce the various patterns of lung injury observed after HSCT have identified that both soluble and cellular inflammatory mediators contribute to the inflammation engendered during the development of IPS. To date, 10 preclinical murine models of the IPS spectrum have been established using various donor and host strain combinations used to study graft-versus-host disease (GVHD). This, as well as the demonstrated T cell dependency of IPS development in these models, supports the concept that the lung is a target of immune-mediated attack after HSCT. The most developed therapeutic strategy for IPS involves blocking TNF signaling with etanercept, which is currently being evaluated in clinical trials. CONCLUSIONS: IPS remains a frequently fatal complication that limits the broader use of allogeneic HSCT as a successful treatment modality. Faced with the clinical syndrome of IPS, one can categorize the disease entity with the appropriate tools, although cases of unclassifiable IPS will remain. Significant research efforts have resulted in a paradigm shift away from identifying noninfectious lung injury after HSCT solely as an idiopathic clinical syndrome and toward understanding IPS as a process involving aspects of both the adaptive and the innate immune response. Importantly, new laboratory insights are currently being translated to the clinic and will likely prove important to the development of future strategies to prevent or treat this serious disorder.

Histone acetylation regulates the cell-specific and interferon-γ-inducible expression of extracellular superoxide dismutase in human pulmonary arteries.

Extracellular superoxide dismutase (EC-SOD) is the major antioxidant enzyme present in the vascular wall, and is responsible for both the protection of vessels from oxidative stress and for the modulation of vascular tone. Concentrations of EC-SOD in human pulmonary arteries are very high relative to other tissues, and the expression of EC-SOD appears highly restricted to smooth muscle. The molecular basis for this smooth muscle-specific expression of EC-SOD is not known. Here we assessed the role of epigenetic factors in regulating the cell-specific and IFN-γ-inducible expression of EC-SOD in human pulmonary artery cells. The analysis of CpG site methylation within the promoter and coding regions of the EC-SOD gene demonstrated higher levels of DNA methylation within the distal promoter region in endothelial cells compared with smooth muscle cells. Exposure of both cell types to DNA demethylation agents reactivated the transcription of EC-SOD in endothelial cells alone. However, exposure to the histone deacetylase inhibitor trichostatin A (TSA) significantly induced EC-SOD gene expression in both endothelial cells and smooth muscle cells. Concentrations of EC-SOD mRNA were also induced up to 45-fold by IFN-γ in smooth muscle cells, but not in endothelial cells. The IFN-γ-dependent expression of EC-SOD was regulated by the Janus tyrosine kinase/signal transducers and activators of transcription proteins signaling pathway. Simultaneous exposure to TSA and IFN-γ produced a synergistic effect on the induction of EC-SOD gene expression, but only in endothelial cells. These findings provide strong evidence that EC-SOD cell-specific and IFN-γ-inducible expression in pulmonary artery cells is regulated, to a major degree, by epigenetic mechanisms that include histone acetylation and DNA methylation.

Home environment allergen exposure scale in older adult cohort with asthma.

OBJECTIVES: Home environmental exposures are a primary source of asthma exacerbation. There is a gap in decision support models that efficiently aggregate the home exposure assessment scores for focused and tailored interventions. Three development methods of a home environment allergen exposure scale for persons with asthma (weighted by dimension reduction, unweighted, precision biomarker-based) were compared, and racial disparity tested. METHODS: Baseline measures from a longitudinal cohort of 187 older adults with asthma were analyzed using humidity and particulate matter sensors, allergy testing, and a home environment checklist. Weights for the dimension reduction scale were obtained from factor analysis, applied for loadings > 0.35. Scales were tested in linear regression models with asthma control and asthma quality of life outcomes. Racial disparities were tested using t tests. Scale performance was tested using unadjusted regression analyses with asthma control and asthma quality of life outcomes, separately. RESULTS: The 7-item empirically weighted scale demonstrated best performance with asthma control associations (F = 4.65, p = 0.03, R2 = .02) and quality of life (F = 6.45, p = 0.01, R2 = .03) as follows: evidence of roach/mice, dust, mold, tobacco smoke exposure, properly venting bathroom fan, self-report of roach/mice/rats, and access to a HEPA filter vacuum. Pets indoors loaded on a separate scale. Racial differences were observed (t = - 3.09, p = 0.004). CONCLUSION: The Home Environment Allergen Exposure Scale scores were associated with racial disparities. Replicating these methods in populations residing in high-risk/low-income housing may generate a clinically meaningful, tailored assessment of asthma triggers. Further consideration for variables that address allergic reactivity and biomarker results is indicated to enhance the potential for a precision prevention score.

RéSUMé: OBJECTIFS: Les expositions environnementales à domicile sont une source principale d'exacerbation de l'asthme. Il existe une lacune dans les modèles de soutien à la décision qui regroupent efficacement les scores d'évaluation de l'exposition à domicile pour des interventions ciblées et adaptées. Trois méthodes de développement d'une échelle d'exposition aux allergènes de l'environnement domestique pour les personnes atteints d'asthme (pondérée par réduction de dimension, non pondérée, basée sur un biomarqueur de précision) ont été comparées et la disparité raciale testée. MéTHODES: Les mesures de base d'une cohorte longitudinale de 187 personnes âgées asthmatiques ont été analysées à l'aide de capteurs d'humidité et de particules, de tests d'allergie et d'une liste de contrôle de l'environnement domestique. Les poids pour l'échelle de réduction des dimensions ont été obtenus à partir de l'analyse factorielle, appliquée aux charges > 0,35. Les échelles ont été testées dans des modèles de régression linéaire avec contrôle de l'asthme et résultats de la qualité de vie avec asthme. Les disparités raciales ont été testées à l'aide de tests t. La performance de l'échelle a été testée à l'aide d'analyses de régression non pondérées avec contrôle de l'asthme et résultats de la qualité de vie avec asthme, séparément. RéSULTATS: L'échelle pondérée empiriquement en 7 éléments a démontré les meilleures performances avec les associations de contrôle de l'asthme (F = 4,65, p = 0,03, R2 = 0,02) et la qualité de vie (F = 6,45, p = 0,01, R2 = 0,03) comme suit : preuve d'exposition aux cafards/souris, à la poussière, à la moisissure, à la fumée de tabac, ventilateur de salle de bain correctement aéré, auto-déclaration des cafards/souris/rats et accès à un aspirateur à filtre HEPA. Les animaux de compagnie à l'intérieur ont été mesurés sur une échelle séparée. Des différences raciales ont été observées (t = -3,09, p = 0,004). CONCLUSION: Les scores de l'échelle d'exposition aux allergènes de l'environnement domestique étaient associés à des disparités raciales. La reproduction de ces méthodes dans des populations résidant dans des logements à haut risque/à faible revenu peut générer une évaluation cliniquement significative et adaptée des déclencheurs de l'asthme. Un examen plus approfondi des variables qui traitent de la réactivité allergique et des résultats des biomarqueurs est indiqué pour améliorer le potentiel d'un score de prévention de précision.

Detection of obstructive sleep apnea using Belun Sleep Platform wearable with neural network-based algorithm and its combined use with STOP-Bang questionnaire.

Many wearables allow physiological data acquisition in sleep and enable clinicians to assess sleep outside of sleep labs. Belun Sleep Platform (BSP) is a novel neural network-based home sleep apnea testing system utilizing a wearable ring device to detect obstructive sleep apnea (OSA). The objective of the study is to assess the performance of BSP for the evaluation of OSA. Subjects who take heart rate-affecting medications and those with non-arrhythmic comorbidities were included in this cohort. Polysomnography (PSG) studies were performed simultaneously with the Belun Ring in individuals who were referred to the sleep lab for an overnight sleep study. The sleep studies were manually scored using the American Academy of Sleep Medicine Scoring Manual (version 2.4) with 4% desaturation hypopnea criteria. A total of 78 subjects were recruited. Of these, 45% had AHI < 5; 18% had AHI 5-15; 19% had AHI 15-30; 18% had AHI ≥ 30. The Belun apnea-hypopnea index (bAHI) correlated well with the PSG-AHI (r = 0.888, P < 0.001). The Belun total sleep time (bTST) and PSG-TST had a high correlation coefficient (r = 0.967, P < 0.001). The accuracy, sensitivity, specificity in categorizing AHI ≥ 15 were 0.808 [95% CI, 0.703-0.888], 0.931 [95% CI, 0.772-0.992], and 0.735 [95% CI, 0.589-0.850], respectively. The use of beta-blocker/calcium-receptor antagonist and the presence of comorbidities did not negatively affect the sensitivity and specificity of BSP in predicting OSA. A diagnostic algorithm combining STOP-Bang cutoff of 5 and bAHI cutoff of 15 events/h demonstrated an accuracy, sensitivity, specificity of 0.938 [95% CI, 0.828-0.987], 0.944 [95% CI, 0.727-0.999], and 0.933 [95% CI, 0.779-0.992], respectively, for the diagnosis of moderate to severe OSA. BSP is a promising testing tool for OSA assessment and can potentially be incorporated into clinical practices for the identification of OSA. Trial registration: ClinicalTrial.org NCT03997916 https://clinicaltrials.gov/ct2/show/NCT03997916?term=belun+ring&draw=2&rank=1.

Belun Ring Platform: a novel home sleep apnea testing system for assessment of obstructive sleep apnea.

STUDY OBJECTIVES: The objective of the study is to validate the performance of Belun Ring Platform, a novel home sleep apnea testing system using a patented pulse oximeter sensor and a proprietary cloud-based neural networks algorithm. METHODS: The Belun Ring captures oxygen saturation, photoplethysmography, and accelerometer signals. The Belun Ring total sleep time is derived from features extracted from accelerometer, oxygen saturation, and photoplethysmography signals. The Belun Ring respiratory event index is derived from Belun Ring total sleep time and features extracted from heart rate variability and oxygen saturation changes. A total of 50 adults without significant cardiopulmonary or neuromuscular comorbidities and heart rate affecting medications were evaluated. In-lab sleep studies were performed simultaneously with the Ring and the studies were manually scored using the American Academy of Sleep Medicine Scoring Manual 4% desaturation criteria. RESULTS: The Belun Ring respiratory event index correlated well with the polysomnography-apnea-hypopnea index (AHI; r = .894, P < .001). The sensitivity and specificity in categorizing AHI ≥ 15 events/h were 0.85 and 0.87, respectively, and the positive predictive value and negative predictive value were 0.88 and 0.83, respectively. The Belun Ring total sleep time also correlated well with the polysomnography-total sleep time (r = .945, P < .001). Although the Belun Ring Platform has a good overall performance, it tends to overestimate AHI in individuals with AHI under 15 events/h and underestimate AHI in those with AHI over 15 events/h. Conclusions: In this proof-of-concept study, the Belun Ring Platform demonstrated a reasonable accuracy in predicting AHI and total sleep time in patients without significant comorbidities and heart rate-affecting medications. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Validation of a Novel Device for Screening Patients With Symptoms of Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/NCT04121923; Identifier: NCT04121923.

Correction: The Effect of Protandim® Supplementation on Athletic Performance and Oxidative Blood Markers in Runners.

[This corrects the article DOI: 10.1371/journal.pone.0160559.].

Current Bronchodilator Responsiveness Criteria Underestimate Asthma in Older Adults.

BACKGROUND: Asthma is common in older adults and is confirmed by demonstration of variable expiratory air-flow limitations, typically evaluated by spirometric assessment of bronchodilator responsiveness. However, many patients with clinically suspected asthma and documented air-flow obstruction do not exhibit a post-bronchodilator response that meets or exceeds current established guidelines. We investigated if extending the time from bronchodilator administration to assessment of bronchodilator response increases the yield of spirometry for the diagnosis of asthma in older adults. METHODS: This was a cross-sectional study. The subjects were non-smokers, ≥ 60 y old, and with suspected asthma. Subjects were characterized as (1) those with a positive bronchodilator response on the 30-min post-bronchodilator spirometry, (2) those with a positive bronchodilator response on the 60-min post-bronchodilator spirometry, and (3) those without a positive bronchodilator response but with a positive methacholine challenge test. Factors associated with a late response to bronchodilator were evaluated by using bivariate analysis and by multivariate analysis by using a logistic regression model. RESULTS: This study enrolled 165 subjects. Of these, 81 (49.1%) had a positive bronchodilator response on 30-min post-bronchodilator spirometry; 25 (15.2%) had a positive bronchodilator response on the 1-h post-bronchodilator spirometry; and 59 (35.8%) had no positive bronchodilator response but had a positive methacholine challenge test. On multivariable regression analysis, those with a higher baseline percentage of predicted FEV1, higher scores on a standard asthma control test, and wheezing and/or cough after exercise were more likely to either have a late bronchodilator response or no bronchodilator response. CONCLUSIONS: Our study showed that a late positive response to bronchodilator use was more common than previously presumed in older subjects with suspected asthma. Pulmonary function testing laboratories should consider routinely reassessing spirometry at 1 h after bronchodilator use if the earlier assessment did not reveal a significant response.

Restoring Pulmonary and Sleep Services as the COVID-19 Pandemic Lessens. From an Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society-coordinated Task Force.

Background: In March 2020, many elective medical services were canceled in response to the coronavirus disease 2019 (COVID-19) pandemic. The daily case rate is now declining in many states and there is a need for guidance about the resumption of elective clinical services for patients with lung disease or sleep conditions.Methods: Volunteers were solicited from the Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society. Working groups developed plans by discussion and consensus for resuming elective services in pulmonary and sleep-medicine clinics, pulmonary function testing laboratories, bronchoscopy and procedure suites, polysomnography laboratories, and pulmonary rehabilitation facilities.Results: The community new case rate should be consistently low or have a downward trajectory for at least 14 days before resuming elective clinical services. In addition, institutions should have an operational strategy that consists of patient prioritization, screening, diagnostic testing, physical distancing, infection control, and follow-up surveillance. The goals are to protect patients and staff from exposure to the virus, account for limitations in staff, equipment, and space that are essential for the care of patients with COVID-19, and provide access to care for patients with acute and chronic conditions.Conclusions: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a dynamic process and, therefore, it is likely that the prevalence of COVID-19 in the community will wax and wane. This will impact an institution's mitigation needs. Operating procedures should be frequently reassessed and modified as needed. The suggestions provided are those of the authors and do not represent official positions of the Association of Pulmonary, Critical Care, and Sleep Division Directors or the American Thoracic Society.