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exacerbations - Top 30 Publications

Outcome Measures Used in Pulmonary Rehabilitation in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review.

Conflicting results about the effects of community-based pulmonary rehabilitation in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) exist, possibly because the variety of outcome measures used and the lack of appropriate measurement properties hinder the development of pulmonary rehabilitation guidelines.

Corticosteroid Faceoff: Which is best for treating asthma and COPD exacerbations?

Models of care for non-invasive ventilation in the Acute COPD Comparison of three Tertiary hospitals (ACT3) study.

Non-invasive ventilation (NIV) improves clinical outcomes in hypercapnic acute exacerbations of COPD (AECOPD), but the optimal model of care remains unknown.

Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study.

Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults.

Biomarkers for severe eosinophilic asthma.

The last decade has seen the approval of several new biologics for the treatment of severe asthma-targeting specific endotypes and phenotypes. This review will examine how evidence generated from the mepolizumab clinical development program showed that blood eosinophil counts, rather than sputum or tissue eosinophil counts, evolved as a pharmacodynamic and predictive biomarker for the efficacy of treatment with mepolizumab in patients with severe eosinophilic asthma. Based on the available evidence and combined with clinical judgement, a baseline blood eosinophil threshold of 150 cells/μL or greater or a historical blood eosinophil threshold of 300 cells/μL or greater will allow selection of patients with severe eosinophilic asthma who are most likely to achieve clinically significant reductions in the rate of exacerbations with mepolizumab treatment.

Uncontrolled and under-diagnosed asthma in a Damascus shelter during the Syrian crisis.

Studies have shown that poor shelter or dwelling conditions may lead to deteriorations in health. Those with asthma may be more susceptible to compromised living conditions and stress leading to a higher risk of asthma exacerbations. To describe the asthma control and quality of life of individuals with diagnosed asthma living in a shelter in Damascus, Syria and estimate the prevalence of respiratory symptoms in shelter dwellers without diagnosed asthma.

Association of adrenal hormone metabolites and mortality over a 6-year follow-up in COPD patients with acute exacerbation.

The release of hormones from the adrenal gland is vital in acute and chronic illnesses such as chronic obstructive pulmonary disease (COPD) involving recurrent exacerbations. Using a metabolomic approach, we aim to investigate associations of different adrenal hormone metabolites with short- and long-term mortality in COPD patients.

Asthma phenotypes: do cough and wheeze predict exacerbations in persistent asthma?

Little is known of the long-term symptom profile in uncontrolled asthma and whether symptoms can predict distinct phenotypes. The primary objective of these analyses was to assess diurnal profile of cough and wheeze in an uncontrolled asthma population. Secondary outcomes were to examine how these symptom profiles influence response to treatment.Twice-daily electronically recorded data from 1701 patients were examined in relation to the population demographics. Reliever treatment with salbutamol was then compared with extra-fine beclometasone/formoterol maintenance and reliever therapy (MART). Exacerbation frequency was then correlated with the symptom profile.Symptoms were commoner in older patients with an increased body mass index. In most patients, reported cough and wheeze were closely correlated (r=0.73). Two phenotypes of cough- and wheeze-predominant patients were identified; the former were overweight, older females and the latter older males. Diurnal symptoms of cough and wheeze were similarly attenuated by both therapies. MART reduced exacerbation frequency by a third compared with salbutamol, and this effect was greatest in patients with fewest reported symptoms.While cough and wheeze are highly correlated in uncontrolled asthma, some patients predominantly have cough whereas others wheeze. Symptoms and exacerbation frequency appear poorly associated, suggesting an alternative pathophysiology. MART may be the preferred option in those with fewest symptoms.

Diet and rosacea: the role of dietary change in the management of rosacea.

Dietary change may play a role in the therapy of rosacea. Certain foods and beverages may act as "triggers" for rosacea exacerbations. These may be divided into heat-related, alcohol-related, capsaicin-related, and cinnamaldehyde-related. One potential pathogenic mechanism may be via the activation of transient receptor potential cation channels, which result in neurogenic vasodilatation. Further research is needed on the role of the gut skin connection in rosacea. Epidemiologic studies suggest that patients with rosacea have a higher prevalence of gastrointestinal disease, and one study reported improvement in rosacea following successful treatment of small intestinal bacterial overgrowth. While further research is required in this area, patients may be advised on measures to support a healthy gut microbiome, including the consumption of a fiber-rich (prebiotic) diet.

Omalizumab in Children with Severe Allergic Asthma: The Italian Real-Life Experience.

Anti-IgE treatment represents a major breakthrough in the therapeutic management of severe allergic asthma. To date, omalizumab is the only biological drug currently licensed as add-on therapy in children aged > 6 years with moderate-to-severe and severe allergic asthma uncontrolled after treatment with high dose of inhaled corticosteroids plus long-acting inhaled beta2-agonist. The clinical efficacy and safety of omalizumab treatment in the pediatric population has been extensively documented in specific trials and consistently expanded from real-life studies. Our aim is to describe the impact of omalizumab on asthma management, by reporting the results of the first Italian multicenter observational study conducted in children and adolescents with severe allergic asthma.

Quantitation of salbutamol using micro-volume blood sampling - applications to exacerbations of pediatric asthma.

A novel gas chromatography-mass spectrometry (GC-MS) method has been developed to quantify salbutamol in micro-volumes (10 µL) of blood. A potential application is paediatric therapeutic dose monitoring (TDM) in acute severe asthma.

Efficacy and safety of benralizumab for eosinophilic asthma: A systematic review and meta-analysis of randomized controlled trials.

Benralizumab is a humanized monoclonal antibody that targets the α chain of the IL-5 receptor (IL-5Rα) and is currently being assessed in clinical trials for asthma control.

Acute stress disorder and defense mechanisms: a study of physical trauma patients admitted to an emergency hospital.

Acute stress disorder (ASD) encompasses a set of symptoms that can arise in individuals after exposure to a traumatic event. This study assessed the defense mechanisms used by victims of physical trauma who developed ASD.

Insights about the economic impact of chronic obstructive pulmonary disease readmissions post implementation of the hospital readmission reduction program.

Chronic obstructive pulmonary disease (COPD) affects over 12 million adults in the United States and is the third leading cause of 30-day readmissions. COPD is costly with almost $50 billion in direct costs annually. Total COPD costs can be up to double the identified direct costs because of comorbid disease and numerous indirect costs such as absenteeism. Acute exacerbations of COPD (AECOPD) are responsible for up to 70% of COPD-related healthcare costs; hospital readmissions alone account for over $15 billion annually. In this review, we aim to describe insights about the economic impact of COPD readmissions based on articles published over the last 18 months.

Pulmonary rehabilitation for patients with acute chronic obstructive pulmonary disease exacerbations: is the evidence strengthening?

This manuscript aims to review the most recent evidence about the benefits of early pulmonary rehabilitation commenced during an acute exacerbation in people with COPD (AECOPD).

Obesity in COPD: Revealed and Unrevealed Issues.

The interactions between obesity and chronic obstructive pulmonary disease (COPD) are being increasingly explored. In part, this is due to the globally increasing prevalence rates of obesity. The prevalence of obesity in COPD patients is variable, and it seems that obesity is more common in COPD patients compared with subjects who do not have COPD. However, further studies are encouraged in this area due to observed inconsistencies in the current data. In this review, we focus on the knowledge of the effects of obesity on dyspnea, pulmonary function, exercise capacity and exacerbation risk. Reduction of dyspnea is one of the main therapy targets in COPD care. There is still no consensus as to whether obesity has a negative or even a positive effect on dyspnea in COPD patients. It is hypothesized that obese COPD patients might benefit from favourable respiratory mechanics (less lung hyperinflation). However, despite less hyperinflation, obesity seems to have a negative influence on exercise capacity measured with weight-bearing tests. This negative influence is not seen with weight-supported exercise such as cycling. With respect to severe exacerbations, obesity seems to be associated with better survival. In summary, it is concluded that due to differences in study methodology and cohort selection, there are still too many knowledge gaps to develop guidelines for clinical practice. Further exploration is needed to get conclusive answers.

Efficacy and Safety of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis: An Update.

Idiopathic pulmonary fibrosis is a fatal form of progressive fibrosing interstitial pneumonia with limited treatment options. In recent years, its management has been transformed with the approval of two new antifibrotic drugs: nintedanib and pirfenidone. Nintedanib is a tyrosine kinase inhibitor that efficiently slows idiopathic pulmonary fibrosis progression and has an acceptable tolerability profile. This article reviews new available evidence on the long-term efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis. Data from extension trials indicate that nintedanib continues to slow disease progression for up to 3 years and is similarly effective in patients with mild and severe impairment of lung function. Treatment with nintedanib reduces the risk of acute exacerbations, and a combined analysis of data from clinical trials of nintedanib shows a trend towards a reduction in mortality. Nintedanib is well tolerated and has been shown to be safe for up to 51 months. Gastrointestinal events, mainly diarrhoea, are the main adverse events caused by the treatment. Currently available data confirm its safety profile in real-life clinical settings, with no new safety concerns identified in patients with comorbidities.

Corticosteroid plus β2-agonist in a single inhaler as reliever therapy in intermittent and mild asthma: a proof-of-concept systematic review and meta-analysis.

Current guidelines recommend a single inhaler maintenance and reliever therapy (SMART) regimen for moderate to severe asthma. However, evidence for the inhaled corticosteroid plus fast-onset-acting β2-agonist (ICS/FABA) as reliever therapy in management of intermittent and mild asthma patients is lacking.

Dual bronchodilator therapy for chronic obstructive pulmonary disease: evidence for the efficacy and Safety of fixed dose combination treatments in the setting of recent guideline updates.

Recent updates to the GOLD guidelines emphasize the use of combination LABA and LAMA bronchodilators for patients with chronic obstructive pulmonary disease with persistent dyspnea despite monotherapy or frequent exacerbations despite LAMA monotherapy. There are several commercially available LABA/LAMA fixed dose combination inhalers, which are likely to become the principle therapy for many patients with COPD.

Work-related asthma in a sample of subjects with established asthma.

To assess the impact of occupational exposure to irritants or sensitizers on the occurrence, recrudescence and worsening of asthma and to identify unrecognized cases of work related asthma (WRA) including Work-Exacerbated Asthma (WEA) and Occupational Asthma (OA), in a general asthma clinic population sample.

Biological effects of p38 MAPK inhibitor losmapimod does not translate to clinical benefits in COPD.

p38 mitogen-activated protein kinase (MAPK) expression is increased in chronic inflammatory disease. Losmapimod, a p38 MAPK inhibitor, has been developed as a potential anti-inflammatory therapy in COPD.

Intensive smoking diminishes the differences in quality of life and exacerbation frequency between the alpha-1-antitrypsin deficiency genotypes PiZZ and PiSZ.

Alpha-1-antitrypsin deficiency (AATD) is a rare genetic disorder that is associated with low levels of circulating alpha-1-antitrypsin in serum. In comparison to the genotype PiZZ, PiSZ usually leads to lower risk of emphysema, better lung function and better survival. The aim of this study was to analyze the relationship between cigarette smoking (packyears) and the AATD genotypes (PiZZ and PiSZ) concerning quality of life (SGRQ), transfer factor of the lung for carbon monoxide (TLCO), forced expiratory volume in one second (FEV1) and exacerbation rate.

Asthma and Pregnancy: Possible to prevent complications?- With Special reference to the impact of obesity and type of airwayinflammation

Background Asthma is a serious global health issue and the most prevalent chronic disorder among Danish pregnant women. Exacerbations of asthma during pregnancy have been associated with increased risk of adverse pregnancy and perinatal outcomes, and by that making asthma a potential serious medical condition during pregnancy. Monitoring of asthma every four to six weeks is recommended during pregnancy, although evidence is lacking that following this recommendation will improve pregnancy outcome and, not least, be beneficial for all pregnant women with asthma. Aim The overall aim of the present thesis was to gain more knowledge of the interaction between asthma and pregnancy. The specific research questions were to identify pregnancies with low risk of an exacerbation during pregnancy, to identify risk factors for an exacerbation during pregnancy, and to compare the adverse pregnancy and perinatal outcomes in women without asthma and women with asthma monitored closely as recommended during pregnancy. Methods In study I and II, determinants of pregnancies with low risk of an exacerbation and maternal pregnancy-related risk factors for an exacerbations were investigated in a large prospective cohort study with 1.283 women with asthma. The Management of Asthma during Pregnancy (MAP) was initiated in 2007, and all pregnant women referred to Hvidovre Hospital have since then received an invitation to participate. Women were followed-up every four weeks with assessment of asthma control and adjustment of medication if necessary. In study III, the potential differences in airway hyperresponsiveness and airway inflammation, in participants (n=50) from the MAP cohort, were investigated in a post-partum examination. In study IV, the effect of maternal asthma on obstetrical and perinatal outcomes was investigated in a large case-control study, with 938 cases i.e. women with asthma from the MAP cohort, and 2.778 controls i.e. women without asthma. Results No history of pre-pregnancy exacerbations, no prescribed controller medication, and clinically stable asthma at the first visit was determinants of pregnancies with a low risk of an asthma exacerbation during pregnancy (study I). Excessive gestational weight gain (GWG) in first trimester was associated with increased risk of an asthma exacerbation during pregnancy; furthermore, the impact of GWG was dose-dependent (Study II). In study III, women experiencing an asthma exacerbation during pregnancy had more pronounced airway hyperresponsiveness and were more often non-atopic. Finally, in study IV, the overall risk of adverse obstetrical and perinatal outcomes in women with asthma monitored closely during pregnancy was low. Conclusion Women with no history of pre-pregnancy exacerbations, no prescribed controller medication, and clinically stable asthma at the first visit have a very low risk of an exacerbation. Furthermore, excessive GWG, airway hyperresponsiveness and being non-atopic are risk factors for exacerbations of asthma during pregnancy. However, the overall risk of adverse obstetrical and perinatal outcomes in women with actively managed asthma during pregnancy is comparable to women without asthma

Fixed versus variable practice for teaching medical students the management of pediatric asthma exacerbations using simulation.

Simulation-based trainings represent an interesting approach to teach medical students the management of pediatric asthma exacerbations (PAEs). In this study, we compared two pedagogical approaches, training students once on three different scenarios of PAEs versus training students three times on the same scenario of PAE. Eighty-five third-year medical students, novice learners for the management of PAEs, were randomized and trained. Students were assessed twice, 1 week and 4 months after the training, on a scenario of PAE new to both groups and on scenarios used during the training. The main outcome was the performance score on the new scenario of PAE at 1 week, assessed on a checklist custom-designed for the study. All students progressed rapidly and acquired excellent skills. One week after the training, there was no difference between the two groups on all the scenarios tested, including the new scenario of PAE (median performance score (IQR) of 8.3 (7.4-10.0) in the variation group versus 8.0 (6.0-10.0) in the repetition group (p = 0.16)). Four months later, the performance of the two groups remained similar.

Caspase-1 deficiency reduces eosinophilia and interleukin-33 in an asthma exacerbation model.

Rhinovirus infections are common triggers of asthma exacerbations. Viruses can activate the inflammasome, resulting in processing and activation of caspase-1. This recruitment triggers production of interleukin (IL)-1β and IL-18, which have been implicated in asthma. Elucidating the involvement of the inflammasome and its compartments, such as caspase-1, in asthma exacerbations is warranted. Gene expression of caspase-1 was measured in rhinovirus-infected primary bronchial epithelial cells of asthmatic and healthy donors 24 h post-infection. In an in vivo exacerbation experiment C57BL/6 wild-type and caspase-1-/- mice were challenged with house dust mite followed by exposures to the viral mimic poly(I:C). General lung inflammatory parameters and levels of T-helper type 2 (Th2)-upstream cytokines IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 were assessed. Caspase-1 expression was elevated after rhinoviral infection exclusively in bronchial epithelial cells from asthmatics. In a translational mouse model of asthma exacerbation effects of caspase-1 on airway inflammation and Th2-upstream cytokines were explored. Caspase-1 deficient mice exhibited no alterations of general lung inflammatory parameters, but showed markedly reduced eosinophilia. Furthermore, the Th2-upstream cytokines IL-33, TSLP and IL-25 were reduced at exacerbation in mice lacking caspase-1. Rhinovirus infection increases bronchial epithelial caspase-1 in asthma. Caspase-1 may induce production of lung Th2-upstream cytokines and eosinophilia at exacerbations. Further targeting of caspase-1 signalling is warranted to explore its role in asthma exacerbations.

Mapping protective regions on a three-dimensional model of the Moraxella catarrhalis vaccine antigen, Oligopeptide Permease A.

A vaccine against Moraxella catarrhalis will reduce tremendous morbidity, mortality, and financial burden by preventing otitis media in children and exacerbations of COPD in adults. Oligopeptide permease A (OppA) is a candidate vaccine antigen that is 1) a nutritional virulence factor expressed on the bacterial cell surface during infection, 2) widely conserved among strains, 3) highly immunogenic, and 4) a protective antigen based on its capacity to induce protective responses in immunized animals. In the present study, we show that the antibodies to OppA following vaccination mediate accelerated clearance in animals following pulmonary challenge. To identify regions of OppA that bind protective antibodies, truncated constructs of OppA were engineered and studied to map regions of OppA with surface-accessible epitopes that bind high avidity antibodies following vaccination. Protective epitopes were located in the N- and C-terminus of the protein. Immunization of mice with constructs corresponding to these regions (T5 and T8) induced protective responses. Studies of overlapping peptide libraries of constructs T5 and T8 with OppA immune serum identified two discrete regions on each construct. These potentially protective regions were mapped on a three-dimensional computational model of OppA, where regions with solvent-accessible amino acids were identified as three potentially protective epitopes. In all, these studies revealed two regions with three specific epitopes in OppA that induce potentially protective antibody responses following vaccination. Detection of antibodies to these regions could serve to guide vaccine formulation and as a diagnostic tool for monitoring development of protective responses during clinical trials.

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study.

Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1.

The efficacy of topical hyaluronan in rhinosinusitis: a systematic review.

Rhinosinusitis is one of the most common inflammatory conditions of the nasal cavity and paranasal sinuses and is one of the most common causes of absence from work and for visits to the family doctor. The treatment strategy in both acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) is to reduce the severity of the symptoms, minimize the duration of the disease and prevent complications. Topical therapy has become an important tool in otolaryngologists’ armamentarium for rhinosinusitis treatment. Recently, topical hyaluronic acid (HA), the major component of many extracellular matrices that promotes tissue healing, including activation and moderation of the inflammatory responses, cell proliferation, migration and angiogenesis, has been proposed for ARS and CRS adjuvant tool. The aim of the study is to systematically review the published literature regarding all the therapeutic effects of HA on the ARS and CRS. Relevant published studies were found in PubMed, Google Scholar and Ovid, using a combined keyword search or medical subject headings. At the end of our study selection process, 5 relevant publications were included: 2 of them investigated the potential role of HA in reducing symptoms and preventing exacerbations of CRS in adult population, two of them in paediatric patients affected by upper respiratory tract infections and one of them in cystic fibrosis patients with bacterial rhinopharyngitis. Data deriving from the present review of 5 clinical studies showed that the use of topical HA represents a relevant therapeutic advance in rhinosinusitis to minimize symptoms and prevent reacutization with a significant improvement of their quality of life, as it avoids systemic side effects and increases local drug activity. Further studies on larger populations and with new specific nebulization devices for upper airway are needed to confirm these encouraging results.

Emergency Department Asthma Medication Delivery Program: An Initiative to Provide Discharge Prescriptions and Education.

Prescription fill rates for children being discharged from the emergency department (ED) after asthma exacerbations are low, placing the child at risk for additional ED visits or admissions for asthma. This article describes the implementation of an ED asthma prescription delivery service designed to improve pharmacy prescription capture and decrease ED revisit rates.

Evaluation of clinical variables according to follow-up times in COPD: results from ON-SINT cohort.

Background: COPD is a chronic disease traditionally associated with increased symptoms as lung function deteriorates. Follow-up times in previous cohort studies were limited to a few years. Interestingly, newer longer observational studies show a more comprehensive picture on disease progression over time. Therefore, the question on the relevancy of the follow-up time in cohort studies remains open. Methods: The ON-SINT study is an observational, retrospective, nationwide, real-life cohort study, in which patients diagnosed with COPD were recruited between December 2011 and April 2013 by primary care (PC) and secondary care (SC) physicians. Patients were evaluated at the inclusion visit and at the initial visit when the diagnosis of COPD was first established. Distribution of lung function decline over the years was studied comparing those cases with longer follow-up times, with the median of the distribution as the cutoff point. Results: The sample included 1214 patients of which 857 (70.6%) were recruited by PC and 357 (29.4%) by SC physicians. Median follow-up time was 6.26 years. Mean annual change in the complete cohort were -4.5 (222) ml year-1 for FVC and 5.5 (134) ml year-1 for FEV1. We confirm the variable distribution of FEV1 decline and found that longer follow-up periods reduce this variability. Of note, FEV1 decline was different between groups (shorter: 19.7 [180.4] vs longer: -9.7 [46.9]; p = 0.018). Further, our data revealed differences in the clinical presentation according to follow-up times, with special emphasis on dyspnea (OR: 1.035; 95%CI: 1.014-1.056), exacerbations (OR 1.172; 95%CI 1.045-1.315) and CAT scores (OR 1.047; 95%CI 1.019-1.075) being associated with longer follow-up times. Conclusions: This study describes the impact of follow-up periods on lung function variability, and reveals differences in clinical presentation according to follow-up times, with special emphasis on dyspnea, exacerbations and CAT scores.