IL-13 is a T-helper cell type 2 cytokine that plays an important role in the pathogenesis of asthma. IL-13 exposure for 14 days transforms cultured normal human bronchial epithelial cells to a goblet cell phenotype. We hypothesized that goblet cells would have a different pattern of cytokine secretion than ciliated airway cells.

Microscopic vascular invasion (MVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong predictor of poor outcomes but it has not been a descriptor of the TNM classification. The purposes of this study were to determine whether the presence of MVI is related to a predictor of poor outcomes and to explore the degree of MVI according to tumor size.

Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results.

Increased blood lactate concentration (hyperlactatemia) and lactic acidosis (hyperlactatemia and serum pH < 7.35) are common in patients with severe sepsis or septic shock and are associated with significant morbidity and mortality. In some patients, most of the lactate that is produced in shock states is due to inadequate oxygen delivery resulting in tissue hypoxia and causing anaerobic glycolysis. However, lactate formation during sepsis is not entirely related to tissue hypoxia or reversible by increasing oxygen delivery. In this review, we initially outline the metabolism of lactate and etiology of lactic acidosis; we then address the pathophysiology of lactic acidosis in sepsis. We discuss the clinical implications of serum lactate measurement in diagnosis, monitoring, and prognostication in acute and intensive care settings. Finally, we explore treatment of lactic acidosis and its impact on clinical outcome.

Although ethnicity may influence response to treatment of patients with asthma, this approach is controversial. The objective of this study was to determine if ethnicity influences the response to IM steroid use (eliminating adherence as an issue).

There exists a high prevalence of OSA in the general population, a great proportion of which remains undiagnosed. The snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and male gender (STOP-Bang) questionnaire was specifically developed to meet the need for a reliable, concise, and easy-to-use screening tool. It consists of eight dichotomous (yes/no) items related to the clinical features of sleep apnea. The total score ranges from 0 to 8. Patients can be classified for OSA risk based on their respective scores. The sensitivity of STOP-Bang score ≥ 3 to detect moderate to severe OSA (apnea-hypopnea index [AHI] > 15) and severe OSA (AHI > 30) is 93% and 100%, respectively. Corresponding negative predictive values are 90% and 100%. As the STOP-Bang score increases from 0 to 2 up to 7 to 8, the probability of moderate to severe OSA increases from 18% to 60%, and the probability of severe OSA rises from 4% to 38%. Patients with a STOP-Bang score of 0 to 2 can be classified as low risk for moderate to severe OSA whereas those with a score of 5 to 8 can be classified as high risk for moderate to severe OSA. In patients whose STOP-Bang scores are in the midrange (3 or 4), further criteria are required for classification. For example, a STOP-Bang score of ≥ 2 plus a BMI > 35 kg/m(2) would classify that patient as having a high risk for moderate to severe OSA. In this way, patients can be stratified for OSA risk according to their STOP-Bang scores.

Insomnia in children is complex and frequently multifactorial. This review discusses the major categories of insomnia as well as common causes. The consequences of insomnia, including issues with mood, behavior, and cognition, are discussed. Sleep disorders are much more prevalent in certain pediatric populations, such as children with autism spectrum disorders. The evaluation of insomnia in children includes a focused history and examination and occasionally actigraphy or polysomnography. Behavioral and pharmacological therapies are discussed, as are future directions for research and clinical practice.

The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality.

Evidence-based guidelines recommend the use of parenteral prostaglandin (PP) therapy in patients with advanced pulmonary arterial hypertension (PAH). Despite this, many patients with PAH die without PP therapy. We sought to examine the frequency of PP use at a large referral center and characterize patients with PAH who died without receiving PP.

Idiopathic pulmonary fibrosis (IPF) is a devastating and incurable progressive fibrotic lung condition associated with a significant disease burden. In recent years there has been an exponential increase in the number of preclinical and clinical studies performed in IPF. IPF is defined according to rigid diagnostic criteria; hence, a significant subset of patients with unclassifiable disease has been excluded from these studies. The traditional diagnostic classification of all progressive fibrotic lung diseases uses specific clinical, radiological, and histopathological features to define each condition. However, the considerable heterogeneity within each form of pulmonary fibrosis has raised the possibility of distinct pathophysiological mechanisms culminating in a common phenotype. Thus, the classification of fibrotic lung diseases according to the driving molecular mechanisms rather than specific user-defined histopathological and radiological features could improve several aspects of clinical care. Discoveries from basic science research have defined multiple complex molecular pathways involved in the pathogenesis of pulmonary fibrosis that may provide markers for the molecular endotyping of this disease. In addition, these molecular pathways have revealed potential therapeutic targets. Reclassifying progressive fibrotic lung diseases according to molecular endotypes may allow for more accurate assessment of prognosis and individualized treatment. Furthermore, recent developments that have been applied to a narrow group of patients with IPF may be applicable to those with other progressive fibrotic lung diseases. This review presents the latest developments from translational research in this area and explains how molecular endotyping could revolutionize the diagnosis, stratification, and treatment of pulmonary fibrosis.

After a hemorrhagic stroke, it is uncertain whether this event scores one point (either for stroke or bleeding) or two points (one point each for stroke and bleeding) on the bleeding risk score termed HAS-BLED (hypertension, abnormal renal/liver function [one or two points], stroke, bleeding history or predisposition, labile international normalized ratio [INR], elderly [> 65 years], drugs/alcohol concomitantly [one or two points]). We investigated the value of a recalibration of the HAS-BLED score to account for two points from a hemorrhagic stroke. Data were analyzed from the Danish nationwide cohort of patients with incident atrial fibrillation (AF) from January 1999 to December 2013. The primary outcome in this observational study was major bleeding. The original and the recalibrated HAS-BLED scores were assessed, and the event rates of major bleeding were calculated. The predictive accuracy of major bleeding was compared by using C-statistics, the net reclassification index (NRI), and integrated discrimination improvement (IDI). An event rate for major bleeding of 4.3 per 100 person-years was recorded in the 210,299 patients with AF. The C-statistics for the two scores were modest: 0.613 (95% CI, 0.607-0.619) for the original score and 0.616 (95% CI, 0.610-0.622) for the recalibrated score. The NRI was 10.0% (95% CI, 7.6-12.4). The relative IDI was 23.6% (95% CI, 15.7-31.5), reflecting that the recalibrated HAS-BLED score more accurately predicted bleeding events. Recalibration of the "S" component in the HAS-BLED score (counting two points for a hemorrhagic stroke) resulted in an increase in the C-statistics, NRI, and IDI. This approach could potentially aid physicians in more accurate assessments of bleeding risk in patients with AF.

Epidemiologic research has revealed a substantial portion of the general population with abnormal spirometry results that are characterized by decreased FEV1 and FVC but a preserved FEV1/FVC ratio. This restrictive spirometry pattern (RSP) is inconsistently defined in the literature and not well addressed by current guidelines; there is an accumulating body of evidence, however, that RSP is prevalent to a similar degree as airflow obstruction. Genetic and other risk factors for RSP, such as inhalational injuries and early life exposures, continue to be actively described. Although it seems that RSP is closely associated with the metabolic syndrome, diabetes, and systemic inflammation, it is not a simple marker of obesity. RSP is associated with adverse cardiovascular outcomes, as well as mortality, and it may be an underappreciated cause of functional impairments and respiratory symptoms. Improvement in outcomes in this population will require that clinicians have an appreciation for the significance of this spirometry pattern; additional research into the clinical and radiologic phenotype of these subjects is also needed. This article provides an overview of the recent developments in our understanding of this prevalent and highly morbid spirometry pattern.

Use of appropriate cough pathways or algorithms may reduce the morbidity of chronic cough, lead to earlier diagnosis of chronic underlying illness, and reduce unnecessary costs and medications. We undertook three systematic reviews to examine three related key questions (KQ): In children aged ?14 years with chronic cough (> 4 weeks' duration), KQ1, do cough management protocols (or algorithms) improve clinical outcomes? KQ2, should the cough management or testing algorithm differ depending on the duration and/or severity? KQ3, should the cough management or testing algorithm differ depending on the associated characteristics of the cough and clinical history?

The Choosing Wisely recommendations from the Society of Thoracic Surgeons include avoiding brain imaging in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). We aimed to describe use of brain imaging among National Lung Screening Trial participants with stage IA NSCLC and to identify factors associated with receipt of brain imaging.

Preliminary reports suggest that a small left atrium (LA) is associated with severe acute pulmonary embolism (PE). This study used data derived from volumetric analyses of computed tomographic pulmonary angiography (CTPA) to investigate whether a reduced LA volume can predict adverse outcome in a large series of patients with acute PE.

We sought to determine whether quantitative analysis of lung adenocarcinoma manifesting as a ground-glass opacity (GGO) nodule (GGN) on initial CT scans can predict further CT scanning change or rate of growth.

Obesity hypoventilation syndrome is becoming an increasingly encountered condition both in respiratory outpatient clinics and in hospitalized patients. The health consequences and social disadvantages of obesity hypoventilation syndrome are significant. Unfortunately, the diagnosis and institution of appropriate therapy is commonly delayed when the syndrome is not recognized or misdiagnosed. Positive airway pressure therapy remains the mainstay of treatment and is effective in controlling sleep-disordered breathing and improving awake blood gases in the majority of individuals. Evidence supporting one mode of therapy over another is limited. Both continuous and bilevel therapy modes can successfully improve daytime gas exchange, with adherence to therapy an important modifiable factor in the response to treatment. Despite adherence to therapy, these individuals continue to experience excess mortality primarily due to cardiovascular events compared with those with eucapnic sleep apnea using CPAP. This difference likely arises from ongoing systemic inflammation secondary to the morbidly obese state. The need for a comprehensive approach to managing nutrition, weight, and physical activity in addition to reversal of sleep-disordered breathing is now widely recognized. Future studies need to evaluate the impact of a more aggressive and comprehensive treatment plan beyond managing sleep-disordered breathing. The impact of early identification and treatment of sleep-disordered breathing on the development and reversal of cardiometabolic dysfunction also requires further attention.

Asthma-COPD overlap syndrome (ACOS) has been recently described by international guidelines. A stepwise approach to diagnosis using usual features of both diseases is recommended although its clinical application is difficult.

E-cigarettes (e-cigs) have attained widespread popularity, yet knowledge of their physiologic effects remains minimal. The aim of this study was to evaluate the effect of a single exposure to e-cig vapor on cough reflex sensitivity.

We sought to determine the impact of OSA syndrome (OSAS) on symptoms and quality of life (QoL) among patients with posttraumatic stress disorder (PTSD). In addition, we assessed adherence and response to positive airway pressure (PAP) therapy in this population.