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Respiratory Tract Diseases - Top 30 Publications

Osimertinib in EGFR T790M-Positive Lung Cancer.

Mast Cells and KIT as Potential Therapeutic Targets in Severe Asthma.

KIT Inhibition by Imatinib in Patients with Severe Refractory Asthma.

Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma.

Osimertinib in EGFR T790M-Positive Lung Cancer.

Osimertinib in EGFR T790M-Positive Lung Cancer.

Non-Mask-based Therapies for Central Sleep Apnea in Patients with Heart Failure.

Central sleep apnea is common in heart failure and contributes to morbidity and mortality. Symptoms are often similar to those associated with heart failure and a high index of suspicion is needed. Testing is typically done in the sleep laboratory, but home testing equipment can distinguish between central and obstructive events. Treatments are limited. Mask-based therapies have been the primary treatment. Oxygen has some data but lacks long-term studies. Neurostimulation of the phrenic nerve is a new technology that has demonstrated improvement. Coordination of care between sleep specialists and cardiologists is important as the field of central sleep apnea continues to develop.

Device Therapy for Sleep-Disordered Breathing in Patients with Cardiovascular Diseases and Heart Failure.

Pathophysiologic components of upper airway obstruction, reduced tidal volume, and disturbed respiratory drive characterize sleep-disordered breathing. Positive airway pressure (PAP) devices address these components by stabilizing the upper airways (continuous PAP), applying air volumes and mandatory breaths (bilevel PAP), or counterbalancing ventilation (adaptive servoventilation). Although PAP therapies have been shown to improve breathing disturbances, daytime symptoms, and left ventricular function in obstructive sleep apnea and cardiovascular diseases, the effects on mortality are controversial, especially in heart failure and central sleep apnea. Optimal treatment is selected based on polysomnographic findings and symptoms, and applied based on the underlying pathophysiologic components.

Sleep-Disordered Breathing and Arrhythmia in Heart Failure Patients.

Heart failure (HF) treatment remains complex and challenging, with current recommendations aiming at consideration and treatment of comorbidities in patients with HF. Sleep-disordered breathing (SDB) and arrhythmia come into play, as both are associated with quality of life deterioration, and morbidity and mortality increase in patients with HF. Interactions of these diseases are versatile and may appear intransparent in daily practice. Nevertheless, because of their importance for patients' condition and prognosis, SDB and arrhythmia individually, but also through interaction on one another, necessitate attention, following the fact that treatment is requested and desired considering latest research findings and outcomes.

Central Sleep Apnea in Patients with Congestive Heart Failure.

Central sleep apnea and Cheyne-Stokes respiration are commonly observed breathing patterns during sleep in patients with congestive heart failure. Common risk factors are male gender, older age, presence of atrial fibrillation, and daytime hypocapnia. Proposed mechanisms include augmented peripheral and central chemoreceptor sensitivity, which increase ventilator instability during both wakefulness and sleep; diminished cerebrovascular reactivity and increased circulation time, which impair the normal buffering of Paco2 and hydrogen ions and delay the detection of changes in Paco2 during sleep; and rostral fluid shifts that predispose to hypocapnia.

A Practical Approach to the Identification and Management of Sleep-Disordered Breathing in Heart Failure Patients.

Sleep-disordered breathing (SDB) is a major health problem affecting much of the general population. Although SDB is responsible for rapid progression of heart failure (HF) and the worsening morbidity and mortality, advanced HF state is associated with accelerated development of SDB. In the face of recent developments in SDB treatment and availability of effective therapeutic options known to improve quality of life, exercise tolerance, and heart function, most HF patients with SDB are left unrecognized and untreated. This article provides an overview of SDB in HF with focus on practical approaches intended to facilitate screening and treatment.

Rehabilitation of Cardiovascular Disorders and Sleep Apnea.

Obstructive sleep apnea (OSA) is present in more than 50% of patients referred to cardiac rehabilitation units. However, it has been under-recognized in patients after stroke and heart failure. Those with concurrent OSA have a worse clinical course. Early treatment of coexisting OSA with continuous positive airway pressure (CPAP) results in improved rehabilitation outcomes and quality of life. Possible mechanisms by which CPAP may improve recovery include decreased blood pressure fluctuations associated with apneas, and improved left ventricular function, cerebral blood flow, and oxygenation. Early screening and treatment of OSA should be integral components of patients entering cardiac rehabilitation units.

Sleep and the Cardiovascular System in Children.

Subspecialty pediatric practice provides comprehensive medical care for a range of ages, from premature infants to children, and often includes adults with complex medical and surgical issues that warrant multidisciplinary care. Normal physiologic variations involving different body systems occur during sleep and these vary with age, stage of sleep, and underlying health conditions. This article is a concise review of the cardiovascular (CV) physiology and pathophysiology in children, sleep-disordered breathing (SDB) contributing to CV morbidity, congenital and acquired CV pathology resulting in SDB, and the relationship between SDB and CV morbidity in different clinical syndromes and systemic diseases in the expanded pediatric population.

Reassessment of an Asthma Diagnosis-Reply.

Reassessment of an Asthma Diagnosis.

Reassessment of an Asthma Diagnosis.

Accuracy of diagnostic tests for Legionnaires' disease: a systematic review.

Rapid and effective diagnosis of Legionnaires' disease (LD) cases is extremely important so that timely and appropriate therapy can be provided, thereby lowering the morbidity and mortality rates and reducing the health and economic costs associated with this disease.

Importance of adhesins in the recurrence of pharyngeal infections caused by Streptococcus pyogenes.

Pharyngo-amygdalitis is the most common infection caused by Streptococcus pyogenes (S. pyogenes). Reinfection with strains of different M types commonly occurs. However, a second infection with a strain of the same M type can still occur and is referred to as recurrence. We aimed to assess whether recurrence of S. pyogenes could be associated to erythromycin resistance, biofilm formation or surface adhesins like fibronectin-binding proteins and pilus proteins, both located in the fibronectin-binding, collagen-binding, T-antigen (FCT) region.

Prevalence of Burkholderia species, including members of Burkholderia cepacia complex, among UK cystic and non-cystic fibrosis patients.

We aimed to establish the prevalence of different Burkholderia species among UK cystic fibrosis (CF) and non-CF patients over a 2 year period.

Bactericidal mechanisms and effector targets of TiO2 and  Ag-TiO2 against Staphylococcus aureus.

In our previous study, Ag+-loaded TiO2 and Ag+-loaded SiO2 coatings for tracheal intubation were prepared to prevent ventilator-associated pneumonia (VAP), but the antimicrobial targets and the underlying mechanisms of TiO2 and Ag-TiO2 (Ag+) are still unclear. We attempted to elucidate the antimicrobial activity and potential mechanisms against Staphylococcus aureus.

Pulmonary Tuberculosis Is Associated With Biomass Fuel Use Among Rural Women in Pakistan: An Age- and Residence-Matched Case-Control Study.

Facility-based, age- and residential area-matched case-control study was conducted in Sindh, Pakistan to determine association between biomass fuel use for cooking and pulmonary tuberculosis (TB). Cases were women with pulmonary TB, and controls were those suffering from other diseases. Current users of biomass fuel were at higher risk of pulmonary TB (adjusted matched odds ratio [mOR] = 3.0; 95% CI = 1.1-4.9) compared with nonusers. In comparison with former biomass users (women not using biomass for >10 years), recent biomass users (women who switched from biomass to nonbiomass ≤10 years ago), and current (lifetime) users were at a higher risk in a dose-response manner (adjusted mOR = 2.8, 95% CI = 0.9-8.2 and adjusted mOR = 3.9, 95% CI = 1.4-10.7, respectively). Population attributable fraction for TB related to biomass fuel use was 40.6% (95% CI = 35.5%-45.7%). This study strengthens the evidence that biomass fuel use for cooking is associated with pulmonary TB and risk increases with duration of exposure.

Community Mitigation Guidelines to Prevent Pandemic Influenza - United States, 2017.

When a novel influenza A virus with pandemic potential emerges, nonpharmaceutical interventions (NPIs) often are the most readily available interventions to help slow transmission of the virus in communities, which is especially important before a pandemic vaccine becomes widely available. NPIs, also known as community mitigation measures, are actions that persons and communities can take to help slow the spread of respiratory virus infections, including seasonal and pandemic influenza viruses.These guidelines replace the 2007 Interim Pre-pandemic Planning Guidance: Community Strategy for Pandemic Influenza Mitigation in the United States - Early, Targeted, Layered Use of Nonpharmaceutical Interventions ( Several elements remain unchanged from the 2007 guidance, which described recommended NPIs and the supporting rationale and key concepts for the use of these interventions during influenza pandemics. NPIs can be phased in, or layered, on the basis of pandemic severity and local transmission patterns over time. Categories of NPIs include personal protective measures for everyday use (e.g., voluntary home isolation of ill persons, respiratory etiquette, and hand hygiene); personal protective measures reserved for influenza pandemics (e.g., voluntary home quarantine of exposed household members and use of face masks in community settings when ill); community measures aimed at increasing social distancing (e.g., school closures and dismissals, social distancing in workplaces, and postponing or cancelling mass gatherings); and environmental measures (e.g., routine cleaning of frequently touched surfaces).Several new elements have been incorporated into the 2017 guidelines. First, to support updated recommendations on the use of NPIs, the latest scientific evidence available since the influenza A (H1N1)pdm09 pandemic has been added. Second, a summary of lessons learned from the 2009 H1N1 pandemic response is presented to underscore the importance of broad and flexible prepandemic planning. Third, a new section on community engagement has been included to highlight that the timely and effective use of NPIs depends on community acceptance and active participation. Fourth, to provide new or updated pandemic assessment and planning tools, the novel influenza virus pandemic intervals tool, the Influenza Risk Assessment Tool, the Pandemic Severity Assessment Framework, and a set of prepandemic planning scenarios are described. Finally, to facilitate implementation of the updated guidelines and to assist states and localities with prepandemic planning and decision-making, this report links to six supplemental prepandemic NPI planning guides for different community settings that are available online (

Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.

Tuberculosis (TB) is a serious public health problem in developing countries such as Pakistan. Rapid diagnosis of TB and detection of drug resistance are very important for timely and appropriate management of multidrug-resistant TB (MDR-TB).

Integrating Transcriptomics, Proteomics, and Metabolomics Profiling with System Pharmacology for the Delineation of Long-Term Therapeutic Mechanisms of Bufei Jianpi Formula in Treating COPD.

In previous work, we identified 145 active compounds from Bufei Jianpi formula (BJF) by system pharmacology and found that BJF showed short-term effect on chronic obstructive pulmonary disease (COPD) rats. Here, we applied the transcriptomic, proteomic, and metabolomics approaches to illustrate the long-term anti-COPD action and its system mechanism of BJF. BJF has obvious anti-COPD effect through decreasing inflammatory cytokines level, preventing protease-antiprotease imbalance and collagen deposition on week 32 by continuous oral administration to rats from weeks 9 to 20. Subsequently, applying the transcriptomic, proteomic, and metabolomics techniques, we detected a number of regulated genes, proteins, and metabolites, mainly related to antioxidant activity, focal adhesion, or lipid metabolism, in lung tissues of COPD and BJF-treated rats. Afterwards, we integrated system pharmacology target, transcript, protein, and metabolite data sets and found that many genes, proteins, and metabolites in rats BJF-treated group and the target proteins of BJF were mainly attributed to lipid metabolism, inflammatory response, oxidative stress, and focal adhesion. Taken together, BJF displays long-term anti-COPD effect probably by system regulation of the lipid metabolism, inflammatory response pathways oxidative stress, and focal adhesion.

Lethal Trauma Pulmonary Embolism Is a Black Swan Event in Patients at Risk for Deep Vein Thrombosis: An Evidence-Based Review.

We delineated the incidence of trauma patient pulmonary embolism (PE) and risk conditions by performing a systematic literature review of those at risk for deep vein thrombosis (DVT). The PE proportion was 1.4 per cent (95% confidence interval = 1.2-1.6) in at-risk patients. Of 10 conditions, PE was only associated with increased age (P < 0.01) or leg injury (P < 0.01; risk ratio = 1.6). As lower extremity DVT (LEDVT) proportions increased, mortality proportions (P = 0.02) and hospital stay (P = 0.0002) increased, but PE proportions did not (P = 0.13). LEDVT was lower with chemoprophylaxis (CP) (4.9%) than without CP (19.1%; P < 0.01). PE was lower with CP (1.0%) than without CP (2.2%; P = 0.0004). Mortality was lower with CP (6.6%) than without CP (11.6%; P = 0.002). PE was similar with (1.2%) and without (1.9%; P = 0.19) mechanical prophylaxis (MP). LEDVT was lower with MP (8.5%) than without MP (12.2%; P = 0.0005). PE proportions were similar with (1.3%) and without (1.5%; P = 0.24) LEDVT surveillance. Mortality was higher with LEDVT surveillance (7.9%) than without (4.8%; P < 0.01). A PE mortality of 19.7 per cent (95% confidence interval = 18-22) × a 1.4 per cent PE proportion yielded a 0.28 per cent lethal PE proportion. As PE proportions increased, mortality (P = 0.52) and hospital stay (P = 0.13) did not. Of 176 patients with PE, 76 per cent had no LEDVT. In trauma patients at risk for DVT, PE is infrequent, has a minimal impact on outcomes, and death is a black swan event. LEDVT surveillance did not improve outcomes. Because PE was not associated with LEDVT and most patients with PE had no LEDVT, preventing, diagnosing, and treating LEDVT may be ineffective PE prophylaxis.

Acute Respiratory Distress Syndrome Incidence, But Not Mortality, Has Decreased Nationwide: A National Trauma Data Bank Study.

Acute respiratory distress syndrome (ARDS) incidence is reported to have decreased in recent years. However, no large-scale study to date has exclusively examined ARDS in the critically injured. We sought to examine the national incidence of ARDS and its associated outcomes exclusively in adult trauma patients. The National Trauma Data Bank (NTDB) was queried to evaluate the incidence of ARDS and associated outcomes over a 6-year study period (2007-2012). Included patients were ≥18 years old, with at least one ventilator day, and complications recorded. ARDS-associated outcomes and complications were also analyzed. Mean age increased over the study period (48.1-51.4 years, P < 0.003). ARDS incidence decreased from 21.5 to 8.5 per cent (P < 0.001). Length of stay (LOS), intensive care unit LOS (ICU LOS), and ventilator days decreased over time. Mortality increased from 21.3 to 24.9 per cent (P < 0.002). Incidence of pneumonia and acute kidney injury increased marginally (39.5-40.9% and 11.4-12.3%, respectively). Sepsis trended down from 2007 to 2010, after which comparable NTDB data were not available. ARDS incidence in mechanically ventilated adult trauma patients has decreased significantly in recent years. We theorize this is likely attributable to improved critical care strategies. Unlike ARDS incidence, mortality in this patient population has not improved despite these advancements.

Randomized Trial Comparing a Web-Mediated Follow-up With Routine Surveillance in Lung Cancer Patients.

The use of web-based monitoring for lung cancer patients is growing in interest because of promising recent results suggesting improvement in cancer and resource utilization outcomes. It remains an open question whether the overall survival (OS) in these patients could be improved by using a web-mediated follow-up rather than classical scheduled follow-up and imaging.

The significance of Candida in the human respiratory tract: our evolving understanding.

Candida is an opportunistic pathogen and the most commonly isolated fungal genus in humans. Though Candida is often detected in respiratory specimens from humans with and without lung disease, its significance remains undetermined. While historically considered a commensal organism with low virulence potential, the status of Candida as an innocent bystander has recently been called into question by both clinical observations and animal experimentation. We here review what is currently known and yet to be determined about the clinical, microbiological and pathophysiological significance of the detection of Candida spp. in the human respiratory tract.

Genetic profiling of putative breast cancer stem cells from malignant pleural effusions.

A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were further sorted for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally, sphere forming efficiency of CSC and non-CSC subpopulations was determined. In order to genetically characterize the different tumor subpopulations, DNA was isolated from pleural effusions before and after cell sorting, and compared with corresponding DNA copy number profiles from primary tumors or bone metastasis using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells had a higher potential to form spheres when compared to CSC subpopulations. In most cases, cell sorting did not yield sufficient cells for copy number analysis. A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant copy number profiles similar to the respective primary tumor. However, most sorted subpopulations showed a balanced profile indicating an insufficient amount of tumor cells and low sensitivity of the sequencing method. Finally, we were able to establish a long term cell culture from one pleural effusion sample, which was characterized in detail. In conclusion, we confirm that pleural effusions are a suitable source for enrichment of putative CSC. However, sequencing based molecular characterization is impeded due to insufficient sensitivity along with a high number of normal contaminating cells, which are masking genetic alterations of rare cancer (stem) cells.

Comorbidities of rheumatoid arthritis: Results from the Korean National Health and Nutrition Examination Survey.

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.

Correlation of EGFR or KRAS mutation status with 18F-FDG uptake on PET-CT scan in lung adenocarcinoma.

18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on glucose metabolism. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV) of 18F-FDG PET scanning has not been fully elucidated.