Showing papers in "American Journal of Respiratory and Critical Care Medicine in 2017"
University of Marburg1, Temple University2, NewYork–Presbyterian Hospital3, University of Texas Health Science Center at San Antonio4, National Institutes of Health5, McGill University Health Centre6, Brigham and Women's Hospital7, Guangzhou Medical University8, Katholieke Universiteit Leuven9, University of Modena and Reggio Emilia10, Flinders University11, Royal Devon and Exeter Hospital12, University of the Republic13, Hokkaido University14, University of Paris15, University of Barcelona16, University of British Columbia17, University of Manchester18
TL;DR: The assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation, and the concept of deescalation of therapy is introduced in the treatment assessment scheme.
Abstract: This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.
2,547 citations
TL;DR: Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline, which is strong for mechanical ventilation using lower tidal volumes and lower inspiratory pressures.
Abstract: Background: This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS).Methods: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: For all patients with ARDS, the recommendation is strong for mechanical ventilation using lower tidal volumes (4–8 ml/kg predicted body weight) and lower inspiratory pressures (plateau pressure < 30 cm H2O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positiv...
1,022 citations
TL;DR: Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time‐varying confounders but was associated with delayed MERS coronavirus RNA clearance.
Abstract: Rationale: Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational stu...
906 citations
TL;DR: It is argued that application of a lung-protective ventilation, today best applied with sedation and endotracheal intubation, might be considered a prophylactic therapy, rather than just a supportive therapy, to minimize the progression of lung injury from a form of patient self-inflicted lung injury.
Abstract: Mechanical ventilation is used to sustain life in patients with acute respiratory failure. A major concern in mechanically ventilated patients is the risk of ventilator-induced lung injury, which is partially prevented by lung-protective ventilation. Spontaneously breathing, nonintubated patients with acute respiratory failure may have a high respiratory drive and breathe with large tidal volumes and potentially injurious transpulmonary pressure swings. In patients with existing lung injury, regional forces generated by the respiratory muscles may lead to injurious effects on a regional level. In addition, the increase in transmural pulmonary vascular pressure swings caused by inspiratory effort may worsen vascular leakage. Recent data suggest that these patients may develop lung injury that is similar to the ventilator-induced lung injury observed in mechanically ventilated patients. As such, we argue that application of a lung-protective ventilation, today best applied with sedation and endotracheal intubation, might be considered a prophylactic therapy, rather than just a supportive therapy, to minimize the progression of lung injury from a form of patient self-inflicted lung injury. This has important implications for the management of these patients.
774 citations
TL;DR: In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours.
Abstract: Rationale: Prior sepsis studies evaluating antibiotic timing have shown mixed results.Objectives: To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration.Methods: Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors.Measurements and Main Results: The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4–3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registrat...
544 citations
TL;DR: This nationwide investigation provided robust evidence of the associations between short‐term exposure to PM2.5 and increased mortality from various cardiopulmonary diseases in China.
Abstract: Rationale: Evidence concerning the acute health effects of air pollution caused by fine particulate matter (PM2.5) in developing countries is quite limited.Objectives: To evaluate short-term associations between PM2.5 and daily cause-specific mortality in China.Methods: A nationwide time-series analysis was performed in 272 representative Chinese cities from 2013 to 2015. Two-stage Bayesian hierarchical models were applied to estimate regional- and national-average associations between PM2.5 concentrations and daily cause-specific mortality. City-specific effects of PM2.5 were estimated using the overdispersed generalized additive models after adjusting for time trends, day of the week, and weather conditions. Exposure–response relationship curves and potential effect modifiers were also evaluated.Measurements and Main Results: The average of annual mean PM2.5 concentration in each city was 56 μg/m3 (minimum, 18 μg/m3; maximum, 127 μg/m3). Each 10-μg/m3 increase in 2-day moving average of PM2.5 concentrat...
470 citations
TL;DR: Commonly used early warning scores are more accurate than the qSOFA score for predicting death and ICU transfer in non‐ICU patients, and these results suggest that the qsoFA score should not replace general earlywarning scores when risk‐stratifying patients with suspected infection.
Abstract: Rationale: The 2016 definitions of sepsis included the quick Sepsis-related Organ Failure Assessment (qSOFA) score to identify high-risk patients outside the intensive care unit (ICU).Objectives: We sought to compare qSOFA with other commonly used early warning scores.Methods: All admitted patients who first met the criteria for suspicion of infection in the emergency department (ED) or hospital wards from November 2008 until January 2016 were included. The qSOFA, Systemic Inflammatory Response Syndrome (SIRS), Modified Early Warning Score (MEWS), and the National Early Warning Score (NEWS) were compared for predicting death and ICU transfer.Measurements and Main Results: Of the 30,677 included patients, 1,649 (5.4%) died and 7,385 (24%) experienced the composite outcome (death or ICU transfer). Sixty percent (n = 18,523) first met the suspicion criteria in the ED. Discrimination for in-hospital mortality was highest for NEWS (area under the curve [AUC], 0.77; 95% confidence interval [CI], 0.76–0.79), fol...
469 citations
TL;DR: In the ARDS environment, MSCs promote an antiinflammatory and highly phagocytic macrophage phenotype through EV‐mediated mitochondrial transfer.
Abstract: Rationale: Acute respiratory distress syndrome (ARDS) remains a major cause of respiratory failure in critically ill patients. Mesenchymal stromal cells (MSCs) are a promising candidate for a cell-based therapy. However, the mechanisms of MSCs’ effects in ARDS are not well understood. In this study, we focused on the paracrine effect of MSCs on macrophage polarization and the role of extracellular vesicle (EV)-mediated mitochondrial transfer.Objectives: To determine the effects of human MSCs on macrophage function in the ARDS environment and to elucidate the mechanisms of these effects.Methods: Human monocyte–derived macrophages (MDMs) were studied in noncontact coculture with human MSCs when stimulated with LPS or bronchoalveolar lavage fluid (BALF) from patients with ARDS. Murine alveolar macrophages (AMs) were cultured ex vivo with/without human MSC-derived EVs before adoptive transfer to LPS-injured mice.Measurements and Main Results: MSCs suppressed cytokine production, increased M2 macrophage marker...
458 citations
TL;DR: This document presents a reporting format in test‐specific units for spirometry, lung volumes, and diffusing capacity that can be assembled into a report appropriate for a laboratory's practice that can improve the interpretation, communication, and understanding of test results.
Abstract: Background: The American Thoracic Society committee on Proficiency Standards for Pulmonary Function Laboratories has recognized the need for a standardized reporting format for pulmonary function tests. Although prior documents have offered guidance on the reporting of test data, there is considerable variability in how these results are presented to end users, leading to potential confusion and miscommunication.Methods: A project task force, consisting of the committee as a whole, was approved to develop a new Technical Standard on reporting pulmonary function test results. Three working groups addressed the presentation format, the reference data supporting interpretation of results, and a system for grading quality of test efforts. Each group reviewed relevant literature and wrote drafts that were merged into the final document.Results: This document presents a reporting format in test-specific units for spirometry, lung volumes, and diffusing capacity that can be assembled into a report appropriate fo...
436 citations
University of Milan1, University of Toronto2, University of Paris3, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico4, University of Belgrade5, University of Angers6, University of Lausanne7, Canberra Hospital8, Australian National University9, Uppsala University10, Queen's University Belfast11, Mayo Clinic12, King Saud bin Abdulaziz University for Health Sciences13, Sapienza University of Rome14, Catholic University of the Sacred Heart15, Harvard University16, Leipzig University17
TL;DR: NIV was used in 15% of patients with ARDS, irrespective of severity category, and NIV seems to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mm Hg.
Abstract: Rationale: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse.Objectives: To determine whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful.Methods: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome.Measurements and Main Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV fa...
429 citations
TL;DR: Although hyperbaric oxygen significantly reduces the permanent neurological and affective effects of CO poisoning, a portion of survivors still have substantial morbidity, and there has been some early success in therapies targeting the downstream inflammatory and oxidative effects ofCO poisoning.
Abstract: Carbon monoxide (CO) poisoning affects 50,000 people a year in the United States. The clinical presentation runs a spectrum, ranging from headache and dizziness to coma and death, with a mortality rate ranging from 1 to 3%. A significant number of patients who survive CO poisoning suffer from long-term neurological and affective sequelae. The neurologic deficits do not necessarily correlate with blood CO levels but likely result from the pleiotropic effects of CO on cellular mitochondrial respiration, cellular energy utilization, inflammation, and free radical generation, especially in the brain and heart. Long-term neurocognitive deficits occur in 15–40% of patients, whereas approximately one-third of moderate to severely poisoned patients exhibit cardiac dysfunction, including arrhythmia, left ventricular systolic dysfunction, and myocardial infarction. Imaging studies reveal cerebral white matter hyperintensities, with delayed posthypoxic leukoencephalopathy or diffuse brain atrophy. Management of thes...
TL;DR: In patients with AHRF, HFNC exerts multiple physiologic effects including less inspiratory effort and improved lung volume and compliance, which might underlie the clinical efficacy of HFNC.
Abstract: Rationale: High-flow nasal cannula (HFNC) improves the clinical outcomes of nonintubated patients with acute hypoxemic respiratory failure (AHRF).Objectives: To assess the effects of HFNC on gas exchange, inspiratory effort, minute ventilation, end-expiratory lung volume, dynamic compliance, and ventilation homogeneity in patients with AHRF.Methods: This was a prospective randomized crossover study in nonintubated patients with AHRF with PaO2/setFiO2 less than or equal to 300 mm Hg admitted to the intensive care unit. We randomly applied HFNC set at 40 L/min compared with a standard nonocclusive facial mask at the same clinically set FiO2 (20 min/step).Measurements and Main Results: Toward the end of each phase, we measured arterial blood gases, inspiratory effort, and work of breathing by esophageal pressure swings (ΔPes) and pressure time product, and we estimated changes in lung volumes and ventilation homogeneity by electrical impedance tomography. We enrolled 15 patients aged 60 ± 14 years old with P...
TL;DR: Hypersensitivity Pneumonitis: Perspectives in Diagnosis and Management Martina Vasakova, Ferran Morell, Simon Walsh, Kevin Leslie, and Ganesh Raghu.
Abstract: Hypersensitivity Pneumonitis: Perspectives in Diagnosis and Management Martina Vasakova, Ferran Morell, Simon Walsh, Kevin Leslie, and Ganesh Raghu Department of Respiratory Medicine, First Faculty of Medicine of Charles University, Thomayer Hospital Prague, Prague, Czech Republic; Vall d’Hebron Institut de Recerca, Servei de Pneumologı́a, Hospital Universitari Vall d’Hebron, Departament de Medicina, Universitat Autonóma de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Respiratoria, Barcelona, Catalonia, Spain; King’s College National Health Service Hospital Foundation Trust, Denmark Hill, London, United Kingdom; Mayo Clinic, Scottsdale, Arizona; and Center for Interstitial Lung Diseases, University of Washington Medical Center, Seattle, Washington
TL;DR: It remains to be determined whether chelating intracellular calcium without regulating MCU levels in PASM cells under PAH conditions reverses the acquired cancer cell–like proliferative phenotype to a normal contractile state and may initiate new avenues of mechanistic research in the PAH field.
Abstract: stores, decreased sequestration by the sarcoplasmic reticulum, or by diminished removal from the cells. Thus, a question arises concerning whether an increase in intracellular calcium through any one of these pathways can stimulate PASM cells to switch from a contractile to cancer cell–like phenotype. In addition, it remains to be determined whether chelating intracellular calcium without regulating MCU levels in PASM cells under PAH conditions reverses the acquired cancer cell–like proliferative phenotype to a normal contractile state. Thus, the results of the study by Hong and colleagues (1) may initiate new avenues of mechanistic research in the PAH field. MCU is targeted by miR-25 (7), and this study showed that up-regulation of miR-25 and miR-138 decreased MCU expression and activity. Interestingly, increasing miR-138 and/or miR-25 restored MCU expression and ameliorated monocrotaline-induced pulmonary hypertension. Although these findings are intriguing, miRs have multiple targets (8) and their downor up-regulation can affect the expression of multiple proteins in cells. Because miR-138 and miR-25 regulated MCU in PASM cells, this raises a possibility that multiple pathways exist in regulating the expression of MCU. Therefore, an RNA-sequencing analysis with in silico analysis in future could be beneficial to provide insight concerning whether regulation of MCU is sufficient or whether it works in conjunction with other effector targets of miR-138 or miR-25 to modulate intracellular calcium in the PASM cells of patients with PAH and experimental models. PAH is a two-hit disease, and therefore it is likely that MCU requires other partners such as factors/pathways to dampen signaling that provokes PAH. In this study, the authors have reported mostly end-point measurements, and from these data it is not clear whether down-regulation of MCU is a trigger for PAH or a contributor to the development and maintenance/progression of PAH. In this regard, a time course study of MCU down-regulation and the development of PAH would have been helpful to interpret these results. Moreover, do MCU knockout mice spontaneously develop pulmonary hypertension or do they develop severe pulmonary hypertension when challenged with a second hit? Measurement of PAH and pulmonary artery structure in MCU knockout mice will answer these questions and will be important in establishing the significance of the role of mitochondrial calcium regulation through MCU in the pathogenesis of PAH, as elegantly demonstrated in the current study.n
TL;DR: Diaphragm dysfunction is twice as frequent as limb muscle weakness and has a direct negative impact on weaning outcome, and limb muscle Weakness was associated with longer duration of MV and hospital stay and the two types of muscle weakness have only limited overlap.
Abstract: Rationale: Intensive care unit (ICU)- and mechanical ventilation (MV)-acquired limb muscle and diaphragm dysfunction may both be associated with longer length of stay and worse outcome. Whether they are two aspects of the same entity or have a different prevalence and prognostic impact remains unclear.
Objectives: To quantify the prevalence and coexistence of these two forms of ICU-acquired weakness and their impact on outcome.
Methods: In patients undergoing a first spontaneous breathing trial after at least 24 hours of MV, diaphragm dysfunction was evaluated using twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (a pressure <11 cm H2O defined dysfunction) and ultrasonography (thickening fraction [TFdi] and excursion). Limb muscle weakness was defined as a Medical Research Council (MRC) score less than 48.
Measurements and Main Results: Seventy-six patients were assessed at their first spontaneous breathing trial: 63% had diaphragm dysfunction, 34% had limb muscle weakness, and 21% had both. There was a significant but weak correlation between MRC score and twitch pressure (ρ = 0.26; P = 0.03) and TFdi (ρ = 0.28; P = 0.01), respectively. Low twitch pressure (odds ratio, 0.60; 95% confidence interval, 0.45–0.79; P < 0.001) and TFdi (odds ratio, 0.84; 95% confidence interval, 0.76–0.92; P < 0.001) were independently associated with weaning failure, but the MRC score was not. Diaphragm dysfunction was associated with higher ICU and hospital mortality, and limb muscle weakness was associated with longer duration of MV and hospital stay.
Conclusions: Diaphragm dysfunction is twice as frequent as limb muscle weakness and has a direct negative impact on weaning outcome. The two types of muscle weakness have only limited overlap.
TL;DR: Investigation of mouse models of Chlamydia and Haemophilus respiratory infection‐mediated, ovalbumin‐induced severe, steroid‐resistant allergic airway disease found NLRP3 inflammasome responses drive experimental severe, steroids‐resistant asthma and are potential therapeutic targets in this disease.
Abstract: Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain–like receptor family, pyrin domain–containing 3 (NLRP3) inflammasome and concomitant IL-1β responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma.Objectives: To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1β in severe, steroid-resistant asthma.Methods: We developed mouse models of Chlamydia and Haemophilus respiratory infection–mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including ele...
TL;DR: It is found that ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D‐CFTR mutations, raising the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established.
Abstract: Rationale: Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established.
Objectives: To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections.
Methods: We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans.
Measurements and Main Results: Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging.
Conclusions: Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.
TL;DR: This Core Outcome Measurement Set is recommended for use in all clinical research evaluating ARF survivors after hospital discharge and should be evaluated for outcomes not reaching consensus.
Abstract: Rationale: Research evaluating acute respiratory failure (ARF) survivors’ outcomes after hospital discharge has substantial heterogeneity in terms of the measurement instruments used, creating barriers to synthesizing study data.Objectives: To identify a minimum set of core outcome measures that are essential to include in all clinical research studies evaluating ARF survivors after discharge.Methods: We conducted a three-round modified Delphi consensus process with 77 participants (47% female, 55% outside the United States), including clinical researchers from more than 16 countries across six continents, patients/caregivers, clinicians, and research funders. Participants reviewed standardized information on measure instruments for seven consensus-derived outcomes plus one recommended outcome.Measurements and Main Results: Response rates were 91 to 97% across the three rounds. Among 75 measurement instruments evaluated, the following met a priori consensus criteria: EQ-5D and 36-item Short Form Health Su...
TL;DR: Adolescent e‐cigarette users had increased rates of chronic bronchitic symptoms and further investigation is needed to determine the long‐term effects of e‐cigarettes on respiratory health.
Abstract: Rationale: Rates of adolescent electronic (e-) cigarette use are increasing, but there has been little study of the chronic effects of use. Components of e-cigarette aerosol have known pulmonary to...
TL;DR: The results indicate that e‐cigarette use alters the profile of innate defense proteins in airway secretions, inducing similar and unique changes relative to cigarette smoking, challenging the concept that e-cigarettes are a healthier alternative to cigarettes.
Abstract: Rationale: E-cigarettes have become increasingly popular and little is known about their potential adverse health effects.Objectives: To determine the effects of e-cigarette use on the airways.Methods: Induced sputum samples from cigarette smokers, e-cigarette users, and nonsmokers were analyzed by quantitative proteomics, and the total and individual concentrations of mucins MUC5AC and MUC5B were determined by light scattering/refractometry and labeled mass spectrometry, respectively. Neutrophil extracellular trap (NET) formation rates were also determined for the same groups.Measurements and Main Results: E-cigarette users exhibited significant increases in aldehyde-detoxification and oxidative stress–related proteins associated with cigarette smoke compared with nonsmokers. The levels of innate defense proteins associated with chronic obstructive pulmonary disease, such as elastase and matrix metalloproteinase-9, were significantly elevated in e-cigarette users as well. E-cigarette users’ sputum also u...
TL;DR: The results of the FULFIL trial support the benefits of single‐inhaler triple therapy compared with ICS/LABA therapy in patients with advanced COPD.
Abstract: Rationale: Randomized data comparing triple therapy with dual inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) are limited.Objectives: We compared the effects of once-daily triple therapy on lung function and health-related quality of life with twice-daily ICS/LABA therapy in patients with COPD.Methods: The FULFIL (Lung Function and Quality of Life Assessment in Chronic Obstructive Pulmonary Disease with Closed Triple Therapy) trial was a randomized, double-blind, double-dummy study comparing 24 weeks of once-daily triple therapy (fluticasone furoate/umeclidinium/vilanterol 100 μg/62.5 μg/25 μg; ELLIPTA inhaler) with twice-daily ICS/LABA therapy (budesonide/formoterol 400 μg/12 μg; Turbuhaler). A patient subgroup remained on blinded treatment for up to 52 weeks. Co–primary endpoints were change from baseline in trough FEV1 and in St. George’s Respiratory Questionnaire (SGRQ) total score at Week 24.Measurements and Main Results...
Temple University1, St. Joseph's Hospital and Medical Center2, University of Alabama at Birmingham3, University of Louisville4, University of Pittsburgh5, Imperial College London6, Duke University7, University of California, Davis8, University of São Paulo9, University of California, San Francisco10, Beth Israel Deaconess Medical Center11, Medical University of South Carolina12, Houston Methodist Hospital13, Orlando Regional Medical Center14, University of Southern California15, Cleveland Clinic16, Los Angeles Biomedical Research Institute17, Stanford University18, University Hospital of Wales19, Southern Illinois University School of Medicine20, Palo Alto Medical Foundation21, University Medical Center Groningen22
TL;DR: EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile.
Abstract: Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilatio...
Boston Children's Hospital1, University of Utah2, University of Pennsylvania3, University of Michigan4, University of Southern California5, Children's National Medical Center6, University of Pittsburgh7, University of California, Los Angeles8, Washington University in St. Louis9, National Institutes of Health10
TL;DR: In this article, a prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals, carried out from December 2012 to September 2014, was carried out to measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support.
Abstract: Rationale: Extracorporeal membrane oxygenation (ECMO) is used for respiratory and cardiac failure in children but is complicated by bleeding and thrombosis.Objectives: (1) To measure the incidence of bleeding (blood loss requiring transfusion or intracranial hemorrhage) and thrombosis during ECMO support; (2) to identify factors associated with these complications; and (3) to determine the impact of these complications on patient outcome.Methods: This was a prospective, observational cohort study in pediatric, cardiac, and neonatal intensive care units in eight hospitals, carried out from December 2012 to September 2014.Measurements and Main Results: ECMO was used on 514 consecutive patients under age 19 years. Demographics, anticoagulation practices, severity of illness, circuitry components, bleeding, thrombotic events, and outcome were recorded. Survival was 54.9%. Bleeding occurred in 70.2%, including intracranial hemorrhage in 16%, and was independently associated with higher daily risk of mortality....
TL;DR: It is found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group, which supports the idea that microbiota form the mediator between early‐life environmental risk factors for and susceptibility to RTIs over the firstyear of life.
Abstract: RATIONALE: Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time. OBJECTIVES: To investigate common environmental drivers, including birth mode, feeding type, antibiotic exposure, and crowding conditions, in relation to respiratory tract microbiota maturation and stability, and consecutive risk of RTIs over the first year of life. METHODS: In a prospectively followed cohort of 112 infants, we characterized the nasopharyngeal microbiota longitudinally from birth on (11 consecutive sample moments and the maximum three RTI samples per subject; in total, n = 1,121 samples) by 16S-rRNA gene amplicon sequencing. MEASUREMENTS AND MAIN RESULTS: Using a microbiota-based machine-learning algorithm, we found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group (0-2 RTIs/yr). The altered microbiota maturation process coincided with decreased microbial community stability, prolonged reduction of Corynebacterium and Dolosigranulum, enrichment of Moraxella very early in life, followed by later enrichment of Neisseria and Prevotella spp. Independent drivers of these aberrant developmental trajectories of respiratory microbiota members were mode of delivery, infant feeding, crowding, and recent antibiotic use. CONCLUSIONS: Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life.
TL;DR: Accumulating evidence indicates that spontaneous breathing in mechanical ventilation may cause—or worsen—acute lung injury, especially if acute respiratory distress syndrome is severe and spontaneous effort is vigorous.
Abstract: Spontaneous respiratory effort during mechanical ventilation has long been recognized to improve oxygenation, and because oxygenation is a key management target, such effort may seem beneficial Also, disuse and loss of peripheral muscle and diaphragm function is increasingly recognized, and thus spontaneous breathing may confer additional advantage Reflecting this, epidemiologic data suggest that the use of partial (vs full) support modes of ventilation is increasing Notwithstanding the central place of spontaneous breathing in mechanical ventilation, accumulating evidence indicates that it may cause-or worsen-acute lung injury, especially if acute respiratory distress syndrome is severe and spontaneous effort is vigorous This Perspective reviews the evidence for this phenomenon, explores mechanisms of injury, and provides suggestions for clinical management and future research
TL;DR: Elevated sputum elastase activity was associated with a higher frequency of exacerbations but was not independently associated with mortality, and candidate biomarkers were tested for their relationship with cross‐sectional markers of disease severity and future risk in adults with bronchiectasis.
Abstract: Rationale: Sputum neutrophil elastase and serum desmosine, which is a linked marker of endogenous elastin degradation, are possible biomarkers of disease severity and progression in bronchiectasis. This study aimed to determine the association of elastase activity and desmosine with exacerbations and lung function decline in bronchiectasis.Methods: This was a single-center prospective cohort study using the TAYBRIDGE (Tayside Bronchiectasis Registry Integrating Datasets, Genomics, and Enrolment into Clinical Trials) registry in Dundee, UK. A total of 433 patients with high-resolution computed tomography–confirmed bronchiectasis provided blood samples for desmosine measurement, and 381 provided sputum for baseline elastase activity measurements using an activity-based immunosassay and fluorometric substrate assay. Candidate biomarkers were tested for their relationship with cross-sectional markers of disease severity, and with future exacerbations, mortality and lung function decline over 3 years.Measureme...
TL;DR: This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence‐based recommendations to optimize liberation from mechanical ventilation in critically ill adults.
Abstract: Background: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence-based recommendations to optimize liberation from mechanical ventilation in critically ill adults.Methods: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation. The methodologists appraised the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach and summarized the results in evidence profiles. The guideline panel then formulated recommendations after considering the balance of desirable consequences (benefits) versus undesirable consequences (burdens, adverse effects, and costs), the certainty in the evidence, and the feasibility and acceptability of various interve...
TL;DR: Frailty is common in critically ill adults aged 18 years and older and is independently associated with increased mortality and greater disability.
Abstract: Rationale: The prevalence of frailty (diminished physiologic reserve) and its effect on outcomes for those aged 18 years and older with critical illness is unclear.Objectives: We hypothesized greater frailty would be associated with subsequent mortality, disability, and cognitive impairment, regardless of age.Methods: At enrollment, we measured frailty using the Clinical Frailty Scale (range, 1 [very fit] to 7 [severely frail]). At 3 and 12 months post-discharge, we assessed vital status, instrumental activities of daily living, basic activities of daily living, and cognition. We used multivariable regression to analyze associations between Clinical Frailty Scale scores and outcomes, adjusting for age, sex, education, comorbidities, baseline disability, baseline cognition, severity of illness, delirium, coma, sepsis, mechanical ventilation, and sedatives/opiates.Measurements and Main Results: We enrolled 1,040 patients who were a median (interquartile range) of 62 (53–72) years old and who had a median Cl...
TL;DR: Nintedanib with add‐on pirfenidone had a manageable safety and tolerability profile in patients with IPF, in line with the adverse event profiles of each drug.
Abstract: Rationale: Nintedanib and pirfenidone slow the progression of idiopathic pulmonary fibrosis (IPF), but the disease continues to progress. More data are needed on the safety and efficacy of combinat...
University of Wisconsin-Madison1, National Institutes of Health2, University of Texas Southwestern Medical Center3, Columbia University4, Cincinnati Children's Hospital Medical Center5, Henry Ford Health System6, University of Colorado Denver7, Children's National Medical Center8, Boston University9, Children's Memorial Hospital10
TL;DR: In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses, providing direct evidence that blocking IgE decreases susceptibility to RV infections and illness.
Abstract: Rationale: Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.Objectives: To test whether omalizumab treatmen...