Showing papers in "American Journal of Respiratory and Critical Care Medicine in 2015"

An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline

Abstract: Background: This document updates the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline on idiopathic pulmonary fibrosis treatment.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize all available evidence pertinent to our questions. The evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and then discussed by a multidisciplinary panel. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists.Results: After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications to health equity, recommendations were made for or against specific treatment interventions.Conclusion...

Global Epidemiology of Pediatric Severe Sepsis: The Sepsis Prevalence, Outcomes, and Therapies Study

Abstract: Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: A point prevalence study was conducted on 5 days throughout 2013–2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. Measurements and Main Results: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6–8.9%). The patients’ median age was 3.0 (interquartile range [IQR], 0.7–11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0–25), and vasoactive-free days were 23 (IQR, 12–28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5–10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,437 patients per group. Conclusions: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.

Middle East Respiratory Syndrome

Abstract: Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a novel single-stranded, positive-sense RNA betacoronavirus (MERS-CoV). Dromedary camels, hosts for MERS-CoV, are implicated in direct or indirect transmission to human beings, although the exact mode of transmission is unknown. The virus was fi rst isolated from a patient who died from a severe respiratory illness in June, 2012, in Jeddah, Saudi Arabia. As of May 31, 2015, 1180 laboratory-confi rmed cases (483 deaths; 40% mortality) have been reported to WHO. Both community-acquired and hospital-acquired cases have been reported with little human-to-human transmission reported in the community. Although most cases of MERS have occurred in Saudi Arabia and the United Arab Emirates, cases have been reported in Europe, the USA, and Asia in people who travelled from the Middle East or their contacts. Clinical features of MERS range from asymptomatic or mild disease to acute respiratory distress syndrome and multiorgan failure resulting in death, especially in individuals with underlying comorbidities. No specifi c drug treatment exists for MERS and infection prevention and control measures are crucial to prevent spread in health-care facilities. MERS-CoV continues to be an endemic, low-level public health threat. However, the virus could mutate to have increased interhuman transmissibility, increasing its pandemic potential.

An Official American Thoracic Society/European Respiratory Society Policy Statement: Enhancing Implementation, Use, and Delivery of Pulmonary Rehabilitation

Abstract: Rationale: Pulmonary rehabilitation (PR) has demonstrated physiological, symptom-reducing, psychosocial, and health economic benefits for patients with chronic respiratory diseases, yet it is underutilized worldwide. Insufficient funding, resources, and reimbursement; lack of healthcare professional, payer, and patient awareness and knowledge; and additional patient-related barriers all contribute to the gap between the knowledge of the science and benefits of PR and the actual delivery of PR services to suitable patients.Objectives: The objectives of this document are to enhance implementation, use, and delivery of pulmonary rehabilitation to suitable individuals worldwide.Methods: Members of the American Thoracic Society (ATS) Pulmonary Rehabilitation Assembly and the European Respiratory Society (ERS) Rehabilitation and Chronic Care Group established a Task Force and writing committee to develop a policy statement on PR. The document was modified based on feedback from expert peer reviewers. After cycl...

Association of hospital-level volume of extracorporeal membrane oxygenation cases and mortality: Analysis of the extracorporeal life support organization registry

Abstract: Rationale: Recent pediatric studies suggest a survival benefit exists for higher-volume extracorporeal membrane oxygenation (ECMO) centers.Objectives: To determine if higher annual ECMO patient volume is associated with lower case-mix–adjusted hospital mortality rate.Methods: We retrospectively analyzed an international registry of ECMO support from 1989 to 2013. Patients were separated into three age groups: neonatal (0–28 d), pediatric (29 d to <18 yr), and adult (≥18 yr). The measure of hospital ECMO volume was age group–specific and adjusted for patient-level case-mix and hospital-level variance using multivariable hierarchical logistic regression modeling. The primary outcome was death before hospital discharge. A subgroup analysis was conducted for 2008–2013.Measurements and Main Results: From 1989 to 2013, a total of 290 centers provided ECMO support to 56,222 patients (30,909 neonates, 14,725 children, and 10,588 adults). Annual ECMO mortality rates varied widely across ECMO centers: the interquar...

An Official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units.

Abstract: Background: There is controversy about how to manage requests by patients or surrogates for treatments that clinicians believe should not be administered.Purpose: This multisociety statement provides recommendations to prevent and manage intractable disagreements about the use of such treatments in intensive care units.Methods: The recommendations were developed using an iterative consensus process, including expert committee development and peer review by designated committees of each of the participating professional societies (American Thoracic Society, American Association for Critical Care Nurses, American College of Chest Physicians, European Society for Intensive Care Medicine, and Society of Critical Care).Main Results: The committee recommends: (1) Institutions should implement strategies to prevent intractable treatment conflicts, including proactive communication and early involvement of expert consultants. (2) The term “potentially inappropriate” should be used, rather than futile, to describe...

Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort

Abstract: Rationale: Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown.Objectives: To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon.Methods: In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound.Measurements and Main Results: Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time follow...

Sleep in the intensive care unit.

Abstract: Sleep is an important physiologic process, and lack of sleep is associated with a host of adverse outcomes. Basic and clinical research has documented the important role circadian rhythm plays in biologic function. Critical illness is a time of extreme vulnerability for patients, and the important role sleep may play in recovery for intensive care unit (ICU) patients is just beginning to be explored. This concise clinical review focuses on the current state of research examining sleep in critical illness. We discuss sleep and circadian rhythm abnormalities that occur in ICU patients and the challenges to measuring alterations in circadian rhythm in critical illness and review methods to measure sleep in the ICU, including polysomnography, actigraphy, and questionnaires. We discuss data on the impact of potentially modifiable disruptors to patient sleep, such as noise, light, and patient care activities, and report on potential methods to improve sleep in the setting of critical illness. Finally, we review the latest literature on sleep disturbances that persist or develop after critical illness.

Therapeutic Effects of Human Mesenchymal Stem Cell–derived Microvesicles in Severe Pneumonia in Mice

Abstract: Rationale: Microvesicles (MVs) are anuclear fragments of cells released from the endosomal compartment or shed from surface membranes. We and other investigators demonstrated that MVs released by mesenchymal stem cells (MSCs) were as effective as the cells themselves in inflammatory injuries, such as after endotoxin-induced acute lung injury. However, the therapeutic effects of MVs in an infectious model of acute lung injury remain unknown.Objectives: We investigated the effects of human MSC MVs on lung inflammation, protein permeability, bacterial clearance, and survival after severe bacterial pneumonia.Methods: We tested the effects of MVs derived from human MSCs on Escherichia coli pneumonia in mice. We also studied the interactions between MVs and human monocytes and human alveolar epithelial type 2 cells.Measurements and Main Results: Administration of MVs derived from human MSCs improved survival in part through keratinocyte growth factor secretion and decreased the influx of inflammatory cells, cyt...

Recent Trends in the Identification of Incidental Pulmonary Nodules

Abstract: Rationale: Pulmonary nodules are common incidental findings, but information about their incidence in the era of computed tomography (CT) is lacking.Objectives: To examine recent trends in pulmonary nodule identification.Methods: We used electronic health records and natural language processing to identify members of an integrated health system who had nodules measuring 4 to 30 mm. We calculated rates of chest CT imaging, nodule identification, and receipt of a new lung cancer diagnosis within 2 years of nodule identification, and standardized rates by age and sex to estimate the frequency of nodule identification in the U.S. population in 2010.Measurements and Main Results: Between 2006 and 2012, more than 200,000 adult members underwent 415,581 chest CT examinations. The annual frequency of chest CT imaging increased from 1.3 to 1.9% for all adult members, whereas the frequency of nodule identification increased from 24 to 31% for all scans performed. The annual rate of chest CT increased from 15.4 to 2...

Blood Eosinophils: A Biomarker of Response to Extrafine Beclomethasone/Formoterol in Chronic Obstructive Pulmonary Disease

Abstract: To the Editor: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition (1). The identification of COPD phenotypes may allow stratified treatment approaches that modulate discrete disease mechanisms. Peripheral blood eosinophilia is both a common and repeatable finding in COPD (2). In addition, the presence of a blood/sputum eosinophilia is associated with a significant proportion of COPD exacerbations (3, 4) and a favorable response to systemic steroids (5). However, the role of blood eosinophils in stratifying treatment response to inhaled corticosteroid/long-acting β-agonist combinations is poorly understood. The FORWARD (Foster 48-Week Trial to Reduce Exacerbations in COPD) study was a randomized, double-blind, parallel group trial that compared 48 weeks of treatment with extrafine beclomethasone dipropionate plus formoterol fumarate (BDP/FF), 100/6 μg pressurized metered-dose inhaler, two inhalations twice a day, versus FF 12 μg pressurized metered-dose inhaler, one inhalation twice a day, in patients with severe COPD with a history of exacerbations (clinical trial registered with www.clinicaltrials.gov [NCT 00929851]). The results of the study have been reported (6) and showed a significant reduction in exacerbation rate (28%) and improvement in lung function with BDP/FF compared with FF treatment. Here we evaluate the hypothesis that these treatment differences differ according to the baseline blood eosinophil count by performing a post hoc analysis on the FORWARD study data. Methods The median (quartile 1; quartile 3) baseline blood eosinophil count was 181.6 (110.4; 279.8), and the distribution of counts is shown in Figure E1 in the online supplement. The patients (n = 1,184) were stratified into quartile groups on the basis of the baseline eosinophil count. The clinical characteristics of the study population across the quartiles of baseline blood eosinophils are reported in Table E1. The following endpoints were analyzed: COPD exacerbation rate over the course of 48 weeks, using a negative binomial model for adjusted exacerbation rates, Kaplan-Meier analysis, and Cox proportional hazard model for time to first exacerbation event; change from baseline in predose morning FEV1 at 48 weeks, using a linear mixed model for repeated measurements; and change from baseline in St. George’s Respiratory Questionnaire total score at 48 weeks, using an analysis of covariance model. Further details of the models are provided in the online supplement. Additional analyses using percentage eosinophil count thresholds and considering absolute counts as a continuous variable were also performed. A predictive model (see online supplement for details) for future COPD exacerbation rate was estimated, accounting for a variety of baseline factors that may influence exacerbations (7). The effect of baseline blood eosinophil count on adverse events, and in particular pneumonia, was also evaluated.

Glycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis

Abstract: Rationale: Dysregulation of cellular metabolism has been shown to participate in several pathologic processes. However, the role of metabolic reprogramming is not well appreciated in the pathogenesis of organ fibrosis.Objectives: To determine if glycolytic reprogramming participates in the pathogenesis of lung fibrosis and assess the therapeutic potential of glycolytic inhibition in treating lung fibrosis.Methods: A cell metabolism assay was performed to determine glycolytic flux and mitochondrial respiration. Lactate levels were measured to assess glycolysis in fibroblasts and lungs. Glycolytic inhibition by genetic and pharmacologic approaches was used to demonstrate the critical role of glycolysis in lung fibrosis.Measurements and Main Results: Augmentation of glycolysis is an early and sustained event during myofibroblast differentiation, which is dependent on the increased expression of critical glycolytic enzymes, in particular, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Augment...

Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography

Abstract: Rationale: Screening for lung cancer with low-dose spiral computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20% compared with screening with chest X-ray (CXR) in the National Lung Screening Trial, but uncertainty remains concerning the efficacy of LDCT screening in a community setting.Objectives: To explore the effect of LDCT screening on lung cancer mortality compared with no screening. Secondary endpoints included incidence, stage, and resectability rates.Methods: Male smokers of 20+ pack-years, aged 60 to 74 years, underwent a baseline CXR and sputum cytology examination and received five screening rounds with LDCT or a yearly clinical review only in a randomized fashion.Measurements and Main Results: A total of 1,264 subjects were enrolled in the LDCT arm and 1,186 in the control arm. Their median age was 64.0 years (interquartile range, 5), and median smoking exposure was 45.0 pack-years. The median follow-up was 8.35 years. One hundred four patients (8.23%) were diagnosed ...

Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia.

Abstract: Rationale: Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of pulmonary vascular disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown.Objectives: To prospectively evaluate the relationship of early echocardiogram signs of pulmonary vascular disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA).Methods: Prospectively enrolled preterm infants with birthweights 500–1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH.Measurements and Main Results: A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% ...

Hospital Incidence and Outcomes of the Acute Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition

Abstract: Rationale: Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings.Objectives: To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph.Methods: We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography whe...

Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients.

Abstract: Rationale: Tools that screen inpatients for sepsis use the systemic inflammatory response syndrome (SIRS) criteria and organ dysfunctions, but most studies of these criteria were performed in intensive care unit or emergency room populations.Objectives: To determine the incidence and prognostic value of SIRS and organ dysfunctions in a multicenter dataset of hospitalized ward patients.Methods: Hospitalized ward patients at five hospitals from November 2008 to January 2013 were included. SIRS and organ system dysfunctions were defined using 2001 International Consensus criteria. Patient characteristics and in-hospital mortality were compared among patients meeting two or more SIRS criteria and by the presence or absence of organ system dysfunction.Measurements and Main Results: A total of 269,951 patients were included in the study, after excluding 48 patients with missing discharge status. Forty-seven percent (n = 125,841) of the included patients met two or more SIRS criteria at least once during their w...

Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease.

Abstract: Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expressi...

Understanding the Short- and Long-Term Respiratory Outcomes of Prematurity and Bronchopulmonary Dysplasia.

Abstract: Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease associated with premature birth that primarily affects infants born at less than 28 weeks’ gestational age. BPD is the most common serious complication experienced by premature infants, with more than 8,000 newly diagnosed infants annually in the United States alone. In light of the increasing numbers of preterm survivors with BPD, improving the current state of knowledge of long-term respiratory morbidity for infants with BPD is a priority. We undertook a comprehensive review of the published literature to analyze and consolidate current knowledge of the effects of BPD that are recognized at specific stages of life, including infancy, childhood, and adulthood. In this review, we discuss both the short-term and long-term respiratory outcomes of individuals diagnosed as infants with the disease and highlight the gaps in knowledge needed to improve early and lifelong management of these patients.

A Dose-Ranging Trial to Optimize the Dose of Rifampin in the Treatment of Tuberculosis

Abstract: Rationale: Rifampin at a dose of 10 mg/kg was introduced in 1971 based on pharmacokinetic, toxicity, and cost considerations. Available data in mice and humans showed that an increase in dose may shorten the duration of tuberculosis treatment.Objectives: To evaluate the safety and tolerability, the pharmacokinetics, and the extended early bactericidal activity of increasing doses of rifampin.Methods: Patients with drug-susceptible tuberculosis were enrolled into a control group of eight patients receiving the standard dose of 10 mg/kg rifampin, followed by consecutive experimental groups with 15 patients each receiving rifampin 20, 25, 30, and 35 mg/kg, respectively, for 14 days. In all patients isoniazid, pyrazinamide, and ethambutol were added in standard doses for the second 7 days of treatment. Safety, pharmacokinetics of rifampin, and fall in bacterial load were assessed.Measurements and Main Results: Grade 1 and 2 adverse events were equally distributed between the five dose groups; there were five ...

TOLLIP, MUC5B, and the Response to N-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis

Abstract: Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. The genes TOLLIP and MUC5B play important roles in lung host defense, which is an immune process influenced by oxidative signaling. Whether polymorphisms in TOLLIP and MUC5B modify the effect of immunosuppressive and antioxidant therapy in individuals with IPF is unknown.Objectives: To determine whether single-nucleotide polymorphisms (SNPs) within TOLLIP and MUC5B modify the effect of interventions in subjects participating in the Evaluating the Effectiveness of Prednisone, Azathioprine, and N-Acetylcysteine in Patients with Idiopathic Pulmonary Fibrosis (PANTHER-IPF) clinical trial.Methods: SNPs within TOLLIP (rs5743890/rs5743894/rs5743854/rs3750920) and MUC5B (rs35705950) were genotyped. Interaction modeling was conducted with multivariable Cox regression followed by genotype-stratified survival analysis using a composite endpoint of death, transplantation, hospitalization, or a decline of ≥10% in FVC.Meas...

Developing a clinically feasible personalized medicine approach to pediatric septic shock.

Abstract: Rationale: Using microarray data, we previously identified gene expression–based subclasses of septic shock with important phenotypic differences The subclass-defining genes correspond to adaptive immunity and glucocorticoid receptor signaling Identifying the subclasses in real time has theranostic implications, given the potential for immune-enhancing therapies and controversies surrounding adjunctive corticosteroids for septic shockObjectives: To develop and validate a real-time subclassification method for septic shockMethods: Gene expression data for the 100 subclass-defining genes were generated using a multiplex messenger RNA quantification platform (NanoString nCounter) and visualized using gene expression mosaics Study subjects (n = 168) were allocated to the subclasses using computer-assisted image analysis and microarray-based reference mosaics A gene expression score was calculated to reduce the gene expression patterns to a single metric The method was tested prospectively in a separate

Long-term exposure to traffic emissions and fine particulate matter and lung function decline in the Framingham heart study.

Abstract: Rationale: Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults.Objectives: To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low.Methods: FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, tim...

Prenatal Particulate Air Pollution and Asthma Onset in Urban Children. Identifying Sensitive Windows and Sex Differences

Abstract: Rationale: The influence of particulate air pollution on respiratory health starts in utero. Fetal lung growth and structural development occurs in stages; thus, effects on postnatal respiratory disorders may differ based on timing of exposure.Objectives: We implemented an innovative method to identify sensitive windows for effects of prenatal exposure to particulate matter with a diameter less than or equal to 2.5 μm (PM2.5) on children's asthma development in an urban pregnancy cohort.Methods: Analyses included 736 full-term (≥37 wk) children. Each mother’s daily PM2.5 exposure was estimated over gestation using a validated satellite-based spatiotemporal resolved model. Using distributed lag models, we examined associations between weekly averaged PM2.5 levels over pregnancy and physician-diagnosed asthma in children by age 6 years. Effect modification by sex was also examined.Measurements and Main Results: Most mothers were ethnic minorities (54% Hispanic, 30% black), had 12 or fewer years of education...

Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.

Abstract: Rationale: A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown.Objectives: To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.Methods: We quantified influenza A(H3N2) virus–specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases.Measurements and Main Results: A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in parti...

Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease

Abstract: Rationale: The mechanisms that underlie the pathogenesis of chronic rhinosinusitis without nasal polyps (CRSsNP), chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD) are not clear.Objectives: To first evaluate the inflammatory profiles of CRSsNP and CRSwNP tissues and then to investigate whether clinical differences observed between CRSwNP and AERD are in part secondary to differences in inflammatory mediator expression within nasal polyp (NP) tissues.Methods: Expression levels of numerous inflammatory mediators were determined by quantitative real-time polymerase chain reaction, ELISA, and multiplex immunoassay.Measurements and Main Results: CRSwNP NP had increased levels of type 2 mediators, including IL-5 (P < 0.001), IL-13 (P < 0.001), eotaxin-2 (P < 0.001), and monocyte chemoattractant protein (MCP)-4 (P < 0.01), compared with sinonasal tissue from subjects with CRSsNP and control subjects. Expression of IFN-γ messenger RNA or protein was low and not...

Evolving Concepts of Asthma

Abstract: Our understanding of asthma has evolved over time from a singular disease to a complex of various phenotypes, with varied natural histories, physiologies, and responses to treatment. Early therapie...

Pulmonary Hypertension in Heart Failure. Epidemiology, Right Ventricular Function, and Survival.

Abstract: Rationale: Patients with pulmonary hypertension due to left heart disease (PH-LHD) and a diastolic pulmonary vascular pressure gradient ≥7 mm Hg, representing PH out of proportion to pulmonary arterial wedge pressure, have pulmonary vascular disease and increased mortality. Little information exists on this condition, recently labeled as “combined pre- and post-capillary PH” (Cpc-PH).Objectives: To investigate epidemiology, risk factors, right ventricular function, and outcomes in patients with chronic heart failure and Cpc-PH.Methods: The study population was identified from a retrospective chart review of a clinical database of 3,107 stable patients who underwent first diagnostic right heart catheterization and from a prospective cohort of 800 consecutive patients at a national university-affiliated tertiary center.Measurements and Main Results: The retrospective cohort had 664 patients with systolic heart failure (SHF) and 399 patients with diastolic heart failure (DHF), 12% of whom were classified as ...

Early Chest Computed Tomography Scan to Assist Diagnosis and Guide Treatment Decision for Suspected Community-acquired Pneumonia

Abstract: Rationale: Clinical decision making relative to community-acquired pneumonia (CAP) diagnosis is difficult. Chest radiograph is key in establishing parenchymal lung involvement. However, radiologic performance may lead to misdiagnosis, rendering questionable the use of chest computed tomography (CT) scan in patients with clinically suspected CAP.Objectives: To assess whether early multidetector chest CT scan affects diagnosis and management of patients visiting the emergency department with suspected CAP.Methods: A total of 319 prospectively enrolled patients with clinically suspected CAP underwent multidetector chest CT scan within 4 hours. CAP diagnosis probability (definite, probable, possible, or excluded) and therapeutic plans (antibiotic initiation/discontinuation, hospitalization/discharge) were established by emergency physicians before and after CT scan results. The adjudication committee established the final CAP classification on Day 28.Measurements and Main Results: Chest radiograph revealed a ...

Timing of Low Tidal Volume Ventilation and Intensive Care Unit Mortality in Acute Respiratory Distress Syndrome. A Prospective Cohort Study

Abstract: Rationale: Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood.Objectives: To evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time.Methods: Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight [PBW]) and daily assessment of other mortality predictors.Measurements and Main Results: An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval [CI], 1.06–1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard rati...

An official American Thoracic Society/American College of Chest Physicians policy statement: implementation of low-dose computed tomography lung cancer screening programs in clinical practice.

Abstract: Rationale: Annual low-radiation-dose computed tomography (LDCT) screening for lung cancer has been shown to reduce lung cancer mortality among high-risk individuals and is now recommended by multiple organizations. However, LDCT screening is complex, and implementation requires careful planning to ensure benefits outweigh harms. Little guidance has been provided for sites wishing to develop and implement lung cancer screening programs.Objectives: To promote successful implementation of comprehensive LDCT screening programs that are safe, effective, and sustainable.Methods: The American Thoracic Society (ATS) and American College of Chest Physicians (CHEST) convened a committee with expertise in lung cancer screening, pulmonary nodule evaluation, and implementation science. The committee reviewed the evidence from systematic reviews, clinical practice guidelines, surveys, and the experience of early-adopting LDCT screening programs and summarized potential strategies to implement LDCT screening programs su...