Showing papers in "American Journal of Respiratory and Critical Care Medicine in 2016"
TL;DR: In this paper, the authors systematically searched 15 citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years.
Abstract: Rationale: Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale.Objectives: To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies.Methods: We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years.Measurements and Main Results: The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215–386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98–226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, th...
2,212 citations
University of California, San Francisco1, University of British Columbia2, Royal Prince Alfred Hospital3, University of Nottingham4, Columbia University5, University of Colorado Denver6, National Institutes of Health7, University of Crete8, Ludwig Maximilian University of Munich9, Claude Bernard University Lyon 110, Nagasaki University11, Yale University12, University of Ulsan13, McMaster University14, University of Michigan15, University of Washington16, National Institute for Health Research17, Cornell University18
TL;DR: To better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation.
Abstract: Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.
897 citations
TL;DR: Findings derived from this large-scale prospective study suggest that long-term ambient O3 contributes to risk of respiratory and circulatory mortality and substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O3 concentrations.
Abstract: Rationale: Tropospheric ozone (O3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O3 are scarce and inconclusive.Objectives: In this study, we examined associations between chronic ambient O3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults.Methods: Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O3 concentrations at the participant’s residence from a hierarchical Bayesian space–time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 μm [PM2.5]) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates.Measurements and Main Results: In single-pollutant mo...
547 citations
TL;DR: This analysis confirms the presence of two ARDS subphenotypes that can be accurately identified with a limited number of variables and that responded differently to randomly assigned fluid management.
Abstract: Rationale: We previously identified two acute respiratory distress syndrome (ARDS) subphenotypes in two separate randomized controlled trials with differential response to positive end-expiratory pressure.Objectives: To identify these subphenotypes in a third ARDS cohort, to test whether subphenotypes respond differently to fluid management strategy, and to develop a practical model for subphenotype identification.Methods: We used latent class analysis of baseline clinical and plasma biomarker data to identify subphenotypes in FACTT (Fluid and Catheter Treatment Trial; n = 1,000). Logistic regression was used to test for an interaction between subphenotype and treatment for mortality. We used stepwise modeling to generate a model for subphenotype identification in FACTT and validated its accuracy in the two cohorts in which we previously identified ARDS subphenotypes.Measurements and Main Results: We confirmed that a two-class (two-subphenotype) model best described the study population. Subphenotype 2 wa...
507 citations
TL;DR: Routine prescription of CPAP to patients with CAD with nonsleepy OSA did not significantly reduce long-term adverse cardiovascular outcomes in the intention-to-treat population, and there was a significant reduction after adjustment for baseline comorbidities and compliance with the treatment.
Abstract: RATIONALE: Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), many of whom do not report daytime sleepiness. First-line treatment for symptomatic OSA is continu ...
470 citations
University of Texas MD Anderson Cancer Center1, St. Elizabeth's Medical Center2, Veterans Health Administration3, Henry Ford Health System4, Pennsylvania State University5, Johns Hopkins University6, Yale University7, Memorial Hospital of South Bend8, Munroe Regional Medical Center9, University of Texas Health Science Center at Houston10
TL;DR: Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused, and the diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.
Abstract: Rationale: Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy.Objectives: To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations.Methods: We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions.Measurements and Main Results: Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN al...
355 citations
University of Wisconsin-Madison1, Pennsylvania State University2, Case Western Reserve University3, University of California, San Francisco4, Harvard University5, Washington University in St. Louis6, Wake Forest University7, University of Pittsburgh8, Cleveland Clinic9, University of Virginia10, Emory University11, Virginia Commonwealth University12
TL;DR: Blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency in the SARP‐3 multivariable model, and EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies.
Abstract: Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (≥3). Replication of a multivariable model was performed with data from the SARP-1 + 2 cohort.Measurements and Main Results: Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency...
318 citations
TL;DR: Male sex, increasing age, increasing comorbidity, open surgery, and a provisional diagnosis of idiopathic pulmonary fibrosis or connective tissue disease-related interstitial lung disease were risk factors for increased mortality in in-hospital mortality after elective surgical lung biopsy.
Abstract: Rationale: Surgical lung biopsy can help to determine a specific diagnosis in interstitial lung disease but has associated risks Most currently available mortality data are derived from case series and may not be generalizable to broader populationsObjectives: To assess in-hospital mortality after surgical lung biopsy for interstitial lung disease in a national secondary care dataset from the United StatesMethods: Data were obtained from the 2000–2011 Nationwide Inpatient Sample Cases were identified using International Classification of Diseases codes for interstitial lung disease and surgical lung biopsies Lung resections and cases of lung cancer were excluded Weighted data were used to estimate numbers of biopsies nationwide and in-hospital mortality, and multivariable logistic regression was used to adjust for sex, age, geographic region, comorbidity, type of operation, and provisional diagnosisMeasurements and Main Results: We estimated there to be around 12,000 surgical lung biopsies performe
317 citations
TL;DR: The data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.
Abstract: Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem.Objectives: To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection.Methods: We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity.M...
315 citations
TL;DR: Among individuals with COPD in the general population, increased blood eosinophil levels above 0.34 × 10(9) cells per liter were associated with a 1.76-fold increased risk of severe exacerbations.
Abstract: Rationale: Whether high blood eosinophils are associated with chronic obstructive pulmonary disease (COPD) exacerbations among individuals with COPD in the general population is largely unknown.Objectives: To test the hypothesis that high blood eosinophils predict COPD exacerbations.Methods: Among 81,668 individuals in the Copenhagen General Population Study, we examined 7,225 with COPD based on spirometry. We recorded blood eosinophils at baseline and future COPD exacerbations longitudinally, defined as moderate (short-course treatment with systemic corticosteroids) or severe (hospitalization). We also assessed exacerbation risk in a subgroup of 203 individuals with clinical COPD, defined as participants with a smoking history of at least 10 pack-years, FEV1 less than 70% of predicted value, and at least one moderate or severe exacerbation in the year before baseline.Measurements and Main Results: During a median of 3.3 years of follow-up (range, 0.03–8.1), 1,439 severe and 2,864 moderate COPD exacerbati...
306 citations
TL;DR: This is the first study to find a reduction in intensity of end-of-life care with similar or improved family distress and Communication facilitators may be associated with decreased family depressive symptoms at 6 months.
Abstract: Rationale: Communication with family of critically ill patients is often poor and associated with family distress.Objectives: To determine if an intensive care unit (ICU) communication facilitator reduces family distress and intensity of end-of-life care.Methods: We conducted a randomized trial at two hospitals. Eligible patients had a predicted mortality greater than or equal to 30% and a surrogate decision maker. Facilitators supported communication between clinicians and families, adapted communication to family needs, and mediated conflict.Measurements and Main Results: Outcomes included depression, anxiety, and post-traumatic stress disorder (PTSD) among family 3 and 6 months after ICU and resource use. We identified 488 eligible patients and randomized 168. Of 352 eligible family members, 268 participated (76%). Family follow-up at 3 and 6 months ranged from 42 to 47%. The intervention was associated with decreased depressive symptoms at 6 months (P = 0.017), but there were no significant difference...
TL;DR: Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality and factors associated with hospital mortality in multivariable analysis.
Abstract: Rationale: Optimization of β-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis.Objectives: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.Methods: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.Measurements and Main Results: We identified three randomized c...
TL;DR: Five distinct recovery phenotypes are identified on the basis of the clinical course over the first week after AKI manifestation that may identify patients amenable to therapeutic intervention and are associated with recovery status at hospital discharge.
Abstract: Rationale: Little is known about how acute kidney injury (AKI) resolves, and whether patterns of reversal of renal dysfunction differ among patients with respect to ultimate recovery.Objectives: We sought to examine different patterns for AKI reversal that are found in patients and assess how they relate to postdischarge outcomes.Methods: We studied 16,968 critically ill patients with Kidney Disease Improving Global Outcomes stage 2 or 3 AKI, using an electronic database. Reversal of AKI was defined as alive and no longer meeting criteria for even stage 1. Recovery was defined as reversal at hospital discharge.Measurements and Main Results: We observed five patterns. The most common (4,508; 26.6%) was early reversal that was sustained through discharge, but almost as many patients (4,496; 26.5%) had no reversal at all. The remaining patients had late reversal after Day 7 (9.7%); early reversal with one or more relapses, but with ultimate recovery (22.5%); and relapsing without recovery (14.7%). Outcomes f...
TL;DR: BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF.
Abstract: Rationale: Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable.Objectives: To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF.Methods: In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels.Measurements and Main Results: We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 ...
TL;DR: This was a multinational prospective multicenter observational study over 3 months of all patients receiving mechanical ventilation in 36 intensive care units, with daily collection of ventilation and weaning modalities, which led to a new operational classification working for all patients under ventilation.
Abstract: Rationale: The weaning process concerns all patients receiving mechanical ventilation. A previous classification into simple, prolonged, and difficult weaning ignored weaning failure and presupposed the use of spontaneous breathing trials.Objectives: To describe the weaning process, defined as starting with any attempt at separation from mechanical ventilation and its prognosis, according to a new operational classification working for all patients under ventilation.Methods: This was a multinational prospective multicenter observational study over 3 months of all patients receiving mechanical ventilation in 36 intensive care units, with daily collection of ventilation and weaning modalities. Pragmatic definitions of separation attempt and weaning success allowed us to allocate patients in four groups.Measurements and Main Results: A total of 2,729 patients were enrolled. Although half of them could not be classified using the previous definition, 99% entered the groups on the basis of our new definition a...
University of Alabama at Birmingham1, University of California, San Diego2, University of Texas Health Science Center at San Antonio3, Baylor College of Medicine4, University of California, Los Angeles5, Harvard University6, University of Iowa7, Johns Hopkins University8, University of British Columbia9, University of Minnesota10, Colorado School of Public Health11, University of Colorado Denver12, University of Michigan13, Temple University14, University of Edinburgh15
TL;DR: CT-assessed functional small airway disease and emphysema are associated with FEV1 decline, but the association with functional smallAirway disease has greatest importance in mild-to-moderate stage chronic obstructive pulmonary disease where the rate of FEV 1 decline is the greatest.
Abstract: Rationale: The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.Objectives: We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.Methods: We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRMemph) and functional small airways disease (PRMfSAD), a measure of nonemphysematous air trapping.Measurements and Main Results: Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0–4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31...
TL;DR: Older participants, those with chronic obstructive pulmonary disease, and those with more than 35 pack-years of smoking had a significantly increased risk of death due to lung cancer, with nonsignificantly fewer deaths in the screening group.
Abstract: Rationale: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening.Objectives: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening.Methods: A total of 4,104 participants aged 50–70 years at the time of inclusion and with a minimum 20 pack-years of smoking were randomized to have five annual low-dose CT scans (study group) or no screening (control group).Measurements and Main Results: Follow-up information regarding date and cause of death, lung cancer diagnosis, cancer stage, and histology was obtained from national registries. No differences between the two groups in lung cancer mortality (hazard ratio, 1.03; 95% confidence interval, 0.66–1.6; P = 0.888) or all-cause mortality (hazard ratio, 1.02; 95% confidence interval, 0.82–1.27; P = 0.867) were observed. More cancers were found in the screening group than in the no-screening group (100 vs. 53, re...
TL;DR: An intensive PT program did not improve long-term physical functional performance compared with a standard-of-care program and there were no differences in the total CS-PFP-10 scores at all three time points.
Abstract: Rationale: Early physical therapy (PT) interventions may benefit patients with acute respiratory failure by preventing or attenuating neuromuscular weakness. However, the optimal dosage of these interventions is currently unknown.Objectives: To determine whether an intensive PT program significantly improves long-term physical functional performance compared with a standard-of-care PT program.Methods: Patients who required mechanical ventilation for at least 4 days were eligible. Enrolled patients were randomized to receive PT for up to 4 weeks delivered in an intensive or standard-of-care manner. Physical functional performance was assessed at 1, 3, and 6 months in survivors who were not currently in an acute or long-term care facility. The primary outcome was the Continuous Scale Physical Functional Performance Test short form (CS-PFP-10) score at 1 month.Measurements and Main Results: A total of 120 patients were enrolled from five hospitals. Patients in the intensive PT group received 12.4 ± 6.5 sessi...
TL;DR: EBV in patients with homogeneous emphysema without collateral ventilation results in clinically meaningful benefits of improved lung function, exercise tolerance, and quality of life.
Abstract: Rationale: Endobronchial valves (EBVs) have been successfully used in patients with severe heterogeneous emphysema to improve lung physiology. Limited available data suggest that EBVs are also effective in homogeneous emphysema.Objectives: To evaluate the efficacy and safety of EBVs in patients with homogeneous emphysema with absence of collateral ventilation assessed with the Chartis system.Methods: Prospective, multicenter, 1:1 randomized controlled trial of EBV plus standard of care (SoC) or SoC alone. Primary outcome was the percentage change in FEV1 (liters) at 3 months relative to baseline in the EBV group versus the SoC group. Secondary outcomes included changes in FEV1, St. George’s Respiratory Questionnaire (SGRQ), 6-minute-walk distance (6MWD), and target lobe volume reduction.Measurements and Main Results: Ninety-three subjects (age, 63.7 ± 6.1 yr [mean ± SD]; FEV1, % predicted, 29.3 ± 6.5; residual volume, % predicted, 275.4 ± 59.4) were allocated to either the EBV group (n = 43) or the SoC gr...
TL;DR: Inspired by a 2015 American Thoracic Society International Conference Symposium entitled "Lumpers and Splitters: Phenotyping in Critical Illness", promising approaches to uncovering patient subtypes that may predict treatment responsiveness and not just differences in prognosis are highlighted.
Abstract: Both quality improvement and clinical research efforts over the past few decades have focused on consensus definition of sepsis and acute respiratory distress syndrome (ARDS). Although clinical definitions based on readily available clinical data have advanced recognition and timely use of broad supportive treatments, they likely hinder the identification of more targeted therapies that manipulate select biological mechanisms underlying critical illness. Sepsis and ARDS are by definition heterogeneous, and patients vary in both their underlying biology and their severity of illness. We have long been able to identify subtypes of sepsis and ARDS that confer different prognoses. The key is that we are now on the verge of identifying subtypes that may confer different response to therapy. In this perspective, inspired by a 2015 American Thoracic Society International Conference Symposium entitled “Lumpers and Splitters: Phenotyping in Critical Illness,” we highlight promising approaches to uncovering patient...
Mount Sinai Hospital, Toronto1, Université de Sherbrooke2, Sunnybrook Health Sciences Centre3, University of Ottawa4, Université de Montréal5, Toronto Rehabilitation Institute6, St. Michael's Hospital7, American Physical Therapy Association8, St. Paul's Hospital9, University Health Network10, McMaster University11, University of Toronto12
TL;DR: ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay to stratify patients for post-ICU disability and recovery to 1 year after critical illness.
Abstract: Rationale: Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design.Objectives: To stratify patients for post-ICU disability and recovery to 1 year after critical illness.Methods: We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling.Measurements and Main Results: The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk...
TL;DR: The present article reviews the diagnostic criteria, prevalence, causative factors, and consequences of burnout syndrome, and discusses potential interventions that may be used to prevent and treat BOS.
Abstract: Burnout syndrome (BOS) occurs in all types of health-care professionals and is especially common in individuals who care for critically ill patients. The development of BOS is related to an imbalance of personal characteristics of the employee and work-related issues or other organizational factors. BOS is associated with many deleterious consequences, including increased rates of job turnover, reduced patient satisfaction, and decreased quality of care. BOS also directly affects the mental health and physical well-being of the many critical care physicians, nurses, and other health-care professionals who practice worldwide. Until recently, BOS and other psychological disorders in critical care health-care professionals remained relatively unrecognized. To raise awareness of BOS, the Critical Care Societies Collaborative (CCSC) developed this call to action. The present article reviews the diagnostic criteria, prevalence, causative factors, and consequences of BOS. It also discusses potential interventions that may be used to prevent and treat BOS. Finally, we urge multiple stakeholders to help mitigate the development of BOS in critical care health-care professionals and diminish the harmful consequences of BOS, both for critical care health-care professionals and for patients.
TL;DR: It is demonstrated that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.
Abstract: Rationale: The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated.Objectives: To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study.Methods: ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality).Measurements and Main Results: During the follow-up period 660 (35%) participants did not have ILA on either CT scan, 37 (2%) had stable to improving ILA, and 118 (6%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment fo...
TL;DR: These guidelines provide recommendations for the diagnosis and treatment of patients with LAM, which included recommendations for sirolimus treatment and vascular endothelial growth factor D testing and recommendations against doxycycline and hormonal therapy.
Abstract: Background: Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that primarily affects women. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of LAM.Methods: Systematic reviews were performed to summarize evidence pertinent to our questions. The evidence was summarized and discussed by a multidisciplinary panel. Evidence-based recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After considering the panel’s confidence in the estimated effects, the balance of desirable (i.e., benefits) and undesirable (i.e., harms and burdens) consequences of treatment, patient values and preferences, cost, and feasibility, recommendations were formulated for or against specific interventions. These included recommendations for sirolimus treatment and vascular endothelial growth factor D testing and recommendations against doxycycline and hormonal therapy.Conclusions: ...
TL;DR: This study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV, and larger randomized controlled trials of this intervention appear justified.
Abstract: Rationale: There are no randomized controlled trials comparing different oxygenation targets for intensive care unit (ICU) patients.Objectives: To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation (IMV).Methods: At four multidisciplinary ICUs, 103 adult patients deemed likely to require IMV for greater than or equal to 24 hours were randomly allocated to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88–92% (n = 52) or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% (n = 51).Measurements and Main Results: The mean area under the curve and 95% confidence interval (CI) for SpO2 (93.4% [92.9–93.9%] vs. 97% [96.5–97.5%]), SaO2 (93.5% [93.1–94%] vs. 96.8% [96.3–97.3%]), PaO2 (70 [68–73] mm Hg vs. 92 [89–96] mm Hg), and FiO2 (0.26 [0.25–0.28] vs. 0.36 [0.34–0.39) in the conservative versus li...
TL;DR: Pooled data from the INPULSIS trials support a consistent effect of nintedanib across a range of IPF phenotypes by slowing disease progression across a number of prespecified subgroups.
Abstract: Rationale: In the two replicate, placebo-controlled, 52-week, phase III INPULSIS trials, nintedanib 150 mg twice daily significantly reduced the annual rate of decline in FVC, the primary endpoint, in subjects with idiopathic pulmonary fibrosis (IPF). It is unknown if this effect was uniform across all subjects treated with nintedanib.Objectives: To investigate the potential association of demographic and clinical variables with the effect of nintedanib in subjects with IPF.Methods: Subgroup analyses of pooled data from the INPULSIS trials were prespecified. Subgroups were analyzed by sex, age ( 70%), baseline St. George’s Respiratory Questionnaire (SGRQ) total score (≤40, >40), smoking status (never, ex/current), systemic corticosteroid use (yes/no), and bronchodilator use (yes/no).Measurements and Main Results: A total of 1,061 subjects were treated (nintedanib n = 638, placebo n = 423). There was no statistically significant di...
University of Alabama at Birmingham1, Veterans Health Administration2, United States Department of Veterans Affairs3, University of Minnesota4, University of Colorado Denver5, University of Texas Health Science Center at San Antonio6, Temple University7, University of Michigan8, Baylor College of Medicine9, Johns Hopkins University10, Harvard University11
TL;DR: Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease, and trials are needed to test existing and novel therapies in Subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease.
Abstract: Rationale: Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown.Objectives: To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up.Methods: We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follo...
TL;DR: This work discusses the contribution of macrophages to an intrinsic pathway, driven by genetic alterations that lead to neoplasia and inflammation, and an extrinsic pathway,driven by inflammatory conditions that increase cancer risk.
Abstract: Lung cancer is the leading cause of cancer mortality worldwide, and at only 18%, it has one of the lowest 5-year survival rates of all malignancies. With its highly complex mutational landscape, treatment strategies against lung cancer have proved largely ineffective. However with the recent success of immunotherapy trials in lung cancer, there is renewed enthusiasm in targeting the immune component of tumors. Macrophages make up the majority of the immune infiltrate in tumors and are a key cell type linking inflammation and cancer. Although the mechanisms through which inflammation promotes cancer are not fully understood, two connected hypotheses have emerged: an intrinsic pathway, driven by genetic alterations that lead to neoplasia and inflammation, and an extrinsic pathway, driven by inflammatory conditions that increase cancer risk. Here, we discuss the contribution of macrophages to these pathways and subsequently their roles in established tumors. We highlight studies investigating the association of macrophages with lung cancer prognosis and discuss emerging therapeutic strategies for targeting macrophages in the tumor microenvironment.
TL;DR: Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6‐minute‐walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease.
Abstract: Rationale: Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease.Objectives: In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease.Methods: During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events.Measurements and Main Results: The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients c...
TL;DR: In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactants alone significantly decreased the incidence of BPD or death without immediate adverse effect.
Abstract: Rationale: Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD.Objectives: To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD.Methods: A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required in...