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exacerbations - Top 30 Publications

Music as an Adjunct to Opioid-Based Analgesia.

Epidemic increases in opioid use in the USA and globally highlight the need for effective adjunctive therapies to opioid-based analgesia. Given the shortcomings of behavioral adjuncts to opioid-based pain treatment, an urgent need exists for pain-related behavioral interventions that resonate with broad patient populations, can be delivered confidentially in any environment, and can incorporate new content automatically. Understanding the potential for automated behavioral therapies like music therapy in modulating the experience of pain may unlock methods to transition patients to lower doses of pharmacologic therapy or provide alternatives to opioids during acute exacerbations of pain. This manuscript describes the neurologic mechanism of action, theoretical basis, and potential applications of personalized music as a smartphone-based mHealth intervention for acute and chronic pain management.

Mepolizumab for the treatment of severe eosinophilic asthma.

Published data on the pharmacology, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety of the interleukin-5 antagonist mepolizumab are reviewed.

Context Relevant Prediction Model for COPD Domain Using Bayesian Belief Network.

In the last three decades, researchers have examined extensively how context-aware systems can assist people, specifically those suffering from incurable diseases, to help them cope with their medical illness. Over the years, a huge number of studies on Chronic Obstructive Pulmonary Disease (COPD) have been published. However, how to derive relevant attributes and early detection of COPD exacerbations remains a challenge. In this research work, we will use an efficient algorithm to select relevant attributes where there is no proper approach in this domain. Such algorithm predicts exacerbations with high accuracy by adding discretization process, and organizes the pertinent attributes in priority order based on their impact to facilitate the emergency medical treatment. In this paper, we propose an extension of our existing Helper Context-Aware Engine System (HCES) for COPD. This project uses Bayesian network algorithm to depict the dependency between the COPD symptoms (attributes) in order to overcome the insufficiency and the independency hypothesis of naïve Bayesian. In addition, the dependency in Bayesian network is realized using TAN algorithm rather than consulting pneumologists. All these combined algorithms (discretization, selection, dependency, and the ordering of the relevant attributes) constitute an effective prediction model, comparing to effective ones. Moreover, an investigation and comparison of different scenarios of these algorithms are also done to verify which sequence of steps of prediction model gives more accurate results. Finally, we designed and validated a computer-aided support application to integrate different steps of this model. The findings of our system HCES has shown promising results using Area Under Receiver Operating Characteristic (AUC = 81.5%).

Chronic Respiratory Infection in Patients with Chronic Obstructive Pulmonary Disease: What Is the Role of Antibiotics?

Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD). The major objective of the management of these patients is the prevention and effective treatment of exacerbations. Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy. It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens. In some patients, systemic corticosteroids are also indicated to improve symptoms. In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence. It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy. Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition. Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations. Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations. There is a need to design long-term studies to evaluate these interventions in the natural history of the disease. The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions.

The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies.

Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting β2-agonists (ICS/LABA) significantly reduced asthma exacerbations, improved lung function, and reduced symptoms for patients with severe, uncontrolled asthma with blood eosinophil counts ≥300 cells/µL in the Phase III SIROCCO and CALIMA studies. To understand the efficacy and safety of benralizumab for patients with eosinophil-driven disease with blood eosinophil counts lower than 300 cells/µL, we evaluated the effect of applying an eosinophil cutoff of ≥150 cells/µL.

Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis.

Chronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs.

Age exacerbates abnormal protein expression in a mouse model of Down syndrome.

The Ts65Dn is a popular mouse model of Down syndrome (DS). It displays DS-relevant features of learning/memory deficits and age-related loss of functional markers in basal forebrain cholinergic neurons. Here we describe protein expression abnormalities in brain regions of 12-month-old male Ts65Dn mice. We show that the magnitudes of abnormalities of human chromosome 21 and non-human chromosome 21 orthologous proteins are greater at 12 months than at ∼6 months. Age-related exacerbations involve the number of components affected in the mechanistic target of rapamycin pathway, the levels of components of the mitogen-activated protein kinase pathway, and proteins associated with Alzheimer's disease. Among brain regions, the number of abnormalities in cerebellum decreased while the number in cortex greatly increased with age. The Ts65Dn is being used in preclinical evaluations of drugs for cognition in DS. Most commonly, drug evaluations are tested in ∼4- to 6-month-old mice. Data on age-related changes in magnitude and specificity of protein perturbations can be used to understand the molecular basis of changes in cognitive ability and to predict potential age-related specificities in drug efficacies.

Assessment of exhaled carbon monoxide in exacerbations of chronic obstructive pulmonary disease.

Introduction Exhaled carbon monoxide (eCO) has been widely implicated as a pulmonary biomarker in respiratory diseases. The aim of this study was to investigate whether the treatment of patients with severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) could be aided by monitoring the changes in eCO. Methods The levels of eCO along with routine clinical parameters were analyzed in 29 current smoker and 33 ex-smoker COPD patients, first at the time of hospital admission, and again at discharge following the standard treatment. Patients with AECOPD were also stratified according to sputum bacteria. Results At exacerbation, the levels of eCO were increased in current smokers compared to ex-smokers (6.0 [2.0-9.5] versus 1.0 [1.0-2.0] ppm, p < 0.001). Similarly, eCO levels were higher in smokers after treatment (7.0 [2.0-12.5] versus 1.0 [1.0-2.0] ppm, p < 0.001). Treatment of AECOPD did not affect eCO concentrations. The levels of eCO were not statistically different between bacterial and non-bacterial AECOPD either. Investigating a subgroup of current smoker patients (n = 15), there was a significant correlation between the levels of eCO and blood carboxyhemoglobin concentrations both at exacerbation and discharge. No associations were found between eCO and lung function or blood gas parameters. Conclusion Our results suggest that monitoring eCO during the treatment of AECOPD is of limited clinical value.

Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium.

International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium.

Chronic obstructive pulmonary disease concurrent with metabolic syndrome: Pathophysiological and clinical features.

Chronic obstructive pulmonary disease (COPD) still remains a serious public health problem, which is a common cause of disability and death in the able-bodied population. Furthermore, the number of patients with metabolic syndrome (MS) is steadily increasing worldwide. Recently, there is also an increase in the number of patients with COPD concurrent with MS, which is a mutually confounding risk factor for concomitant cardiovascular disease and adversely affects prognosis in these patients. Systemic subclinical inflammation is a common link between COPD and the components of MS. Systemic inflammation in patients with comorbidity is complemented by an inflammatory process in the abdominal visceral adipose tissue that serves as a source of proinflammatory adipokines (leptin, resistin, and tumor necrosis factor-α). Patients with COPD in the presence of MS components have in general higher ventilation needs, more obvious clinical manifestations of bronchopulmonary diseases, and more frequent COPD exacerbations and frequently require higher doses of inhaled glucocorticosteroids. As compared with normal-weight patients with COPD, obese patients with this condition have more limited physical activity and much more exercise intolerance. There are currently no practical recommendations for the management of patients with comorbidity; patients with COPD concurrent with MS need an individual therapeutic approach. It is important to elaborate a package of preventive measures to improve quality of life in patients, to reduce the incidence of systemic complications, and to achieve symptomatic improvements. Thus, to develop and implement practical guidelines for physicians and patients are an urgent issue.

The problem of obstructive sleep apnea syndrome in asthmatic patients.

Asthma and obstructive sleep apnea syndrome (OSAS) are one of the most common chronic respiratory diseases. These have common risk factors that include obesity, gastroesophageal reflux disease (GERD) and impaired nasal breathing (allergic rhinitis, sinusitis). At the same time, experimental evidence demonstrates common pathophysiological mechanisms of these diseases, such as involvement in the process of the respiratory tract, a systemic inflammatory response, and implementation of neuromechanical reflexes. Thus, there is an obvious synergism between these conditions, which affects symptoms, response to therapy, and prognosis. The available data allow discussion on whether there is a need to identify and treat OSAS in asthmatic patients. By keeping in mind the high incidence of OSAS in patients with severe asthma, it may be suggested that treatment for OSAS can reduce the number of exacerbations, improve the quality of life, and decline the number of obstinate asthma cases. It is very important for general practitioners to assess risk factors, such as body weight, nasal stuffiness, and GERD, and to utilize screening tools for more efficient use of healthcare resources. Considering the known positive effects of CPAP therapy in short-term studies, future investigations should focus on the impact of CPAP therapy on asthma symptoms in the long-term, as well as on the effects of asthma drugs on the course of OSAS.

A missed primary care appointment correlates with a subsequent emergency department visit among children with asthma.

Since the Affordable Care Act's implementation, emergency department (ED) visits have increased. Poor asthma control increases the risk of acute exacerbations and preventable ED visits. The Centers for Medicare and Medicaid Services support the reduction of preventable ED visits to reduce healthcare spending. Implementation of interventions to avoid preventable ED visits has become a priority for many healthcare systems yet little data exist examining children's missed asthma management primary care (PC) appointments and subsequent ED visits.

Predictors of re-exacerbation after an index exacerbation of chronic obstructive pulmonary disease in the REDUCE randomised clinical trial.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) compromise physical activity and quality of life and contribute significantly to health care costs. Systemic glucocorticoids benefit clinical outcome in AECOPD, and the REDUCE trial demonstrated noninferiority of a 5-day treatment course with prednisone compared with 14 days therapy regarding clinical outcome over 6 months of follow-up. Unexpectedly, we found an inverse correlation between circulating cortisol levels and exacerbation risk during a 6-month follow-up period.

Optimizing bronchodilation in the prevention of COPD exacerbations.

The natural disease course of chronic obstructive pulmonary disease (COPD) is often punctuated by exacerbations: acute events of symptom worsening associated with significant morbidity and healthcare resource utilization; reduced quality of life; and increased risk of hospitalization and death. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend that patients at risk of exacerbations (GOLD Groups C and D) receive a long-acting muscarinic antagonist (LAMA) or a long-acting β2-agonist (LABA)/LAMA combination, respectively, as preferred initial treatments. The latter recommendation is based on recent trial evidence demonstrating the superior efficacy of a fixed-dose LABA/LAMA over an inhaled corticosteroid (ICS)/LABA in exacerbation prevention. ICS in combination with a LABA is also indicated for prevention of exacerbations, but the use of ICS is associated with an increased risk of adverse events such as pneumonia, and offers limited benefits beyond those provided by LABA or LAMA monotherapy. In this review, we examine evidence from a number of pivotal studies of LABAs and LAMAs, administered as monotherapy or as part of dual or triple combination therapy, with a specific focus on their effect on exacerbations. We also discuss a new proposed treatment paradigm for the management of COPD that takes into account this recent evidence and adopts a more cautious approach to the use of ICS. In alignment with GOLD 2017, we suggest that ICS should be reserved for patients with concomitant asthma or in whom exacerbations persist despite treatment with LABA/LAMA.

Chronobiological approach to managing an exacerbation of chronic recurrent bacterial cystite.

To investigate the effects of complex therapy with and without phototherapy for an exacerbation of chronic recurrent bacterial cystitis in women at the peaks of chronobiological activity.

Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: A systematic literature review.

There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety ofomalizumab in the real-world management of allergic asthma.

Umeclidinium bromide versus placebo for people with chronic obstructive pulmonary disease (COPD).

People with chronic obstructive pulmonary disease (COPD) have poor quality of life, reduced survival, and accelerated decline in lung function, especially associated with acute exacerbations, leading to high healthcare costs. Long-acting bronchodilators are the mainstay of treatment for symptomatic improvement, and umeclidinium is one of the new long-acting muscarinic antagonists approved for treatment of patients with stable COPD.

Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis.

Antibiotic therapy for acute pulmonary exacerbations in people with cystic fibrosis is usually chosen based on the results of antimicrobial susceptibility testing of individual drugs. Combination antimicrobial susceptibility testing assesses the efficacy of drug combinations including two or three antibiotics in vitro and can often demonstrate antimicrobial efficacy against bacterial isolates even when individual antibiotics have little or no effect. Therefore, choosing antibiotics based on combination antimicrobial susceptibility testing could potentially improve response to treatment in people with cystic fibrosis with acute exacerbations. This is an updated version of a previously published review.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control.

Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease.

Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. Chronic obstructive pulmonary disease is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis.

Continuous glucose monitoring in a cystic fibrosis patient to predict pulmonary exacerbation?

Patients with cystic fibrosis (CF) experience a significant decline in pulmonary status before the diagnosis of cystic fibrosis related diabetes (CFRD). We hypothesized that hyperglycemia may be a factor in the decline of pulmonary function and increased frequency of pulmonary exacerbations. Long term continuous glucose monitoring (CGM) has not been reported in patients with CF and impaired glucose tolerance. We performed CGM for three months in a 17year old male with F508del and F553X CF mutations, baseline forced expiratory volume in 1s (FEV1) of 92% predicted, and impaired glucose tolerance to evaluate changes in glucose levels prior to the diagnosis of a pulmonary exacerbation. Results revealed elevated overnight, fasting and post-prandial glucose levels up to one week prior to diagnosis of a pulmonary exacerbation compared to baseline. In addition, mean glucose was elevated and the patient spent a greater percentage of time with interstitial glucose>140mg/dL up to one week prior to diagnosis of a pulmonary exacerbation. This emphasizes the hypothesis that hyperglycaemia may be a factor in pulmonary exacerbations in this population. This case study strengthens the evidence base to support larger longitudinal studies to understand the impact of glycaemic control and pulmonary function in patients with CF and glucose intolerance.

Heart Rate Recovery After 6-min Walking Test Predicts Acute Exacerbation in COPD.

Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR1) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR1 predicts acute exacerbations (AECOPD).

The effect of combining manual therapy with exercise for mild chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

Chronic obstructive pulmonary disease (COPD) is a major cause of disability and hospital admission. Current management strategies have not been successful in altering the loss of lung function typically seen as the disease progresses. A recent systematic review into the use of spinal manipulative therapy (SMT) in the management of COPD concluded that there was low level evidence to support the view that a combination of SMT and exercise had the potential to improve lung function more than exercise alone in people with moderate to severe COPD. The aim of this study is to investigate whether the combination of exercise and manual therapy (MT) that includes SMT produces sustainable improvements in lung function and exercise capacity in people with mild COPD.

Linear immunoglobulin A/G bullous dermatosis associated with ulcerative colitis.

Linear immunoglobulin (Ig)A/G bullous dermatosis (LAGBD) is an autoimmune bullous disease characterized by formation of subepidermal blisters and linear deposition of IgA and IgG antibodies along the basement membrane zone (BMZ). The association between linear IgA bullous dermatosis and ulcerative colitis (UC) is well recognized, but reports of UC-associated LAGBD are lacking. We have reported a 24-year-old man suffering from LAGBD associated with UC, which occurred before exacerbations of skin rash. A skin biopsy indicated a subepidermal blister with an infiltration of primarily neutrophils and eosinophils in the dermis. Direct immunofluorescence (IF) studies showed a linear deposition of IgA, IgG and C3c. Indirect IF of human skin revealed IgA and IgG anti-BMZ autoantibodies. Indirect IF of 1 M NaCl-split human skin demonstrated reactivity of IgA and IgG antibodies at the epidermal side. Immunoblotting showed that IgG antibodies reacted to the BP180 NC16a domain and 120-kDa linear IgA dermatosis-1, and enzyme-linked immunoassay detected IgG anti-BP230 antibodies. Administration of prednisolone and diaminodiphenyl sulfone (DDS) via the p.o. route improved skin lesions and bowel conditions. These results suggest that the bowel inflammation observed in UC may have a causative effect of initiation of the immune response to the skin and development of the bullous skin lesions in LAGBD. A combination of DDS and corticosteroid could be a recommended therapeutic option for patients with LAGBD with UC.

Clinically Promising Biomarkers in Cystic Fibrosis Pulmonary Exacerbations.

Cystic fibrosis is a complex genetic disease hallmarked by repetitive infectious exacerbations that leads to destruction of airway architecture, acute on chronic inflammatory changes, and deterioration in lung function. Predicting an exacerbation may help preempt some of these changes by the initiation of swift antibiotic and anti-inflammatory therapy. A search for biomarkers that could predict exacerbations or help guide duration of antibiotic therapy is being aggressively sought. In this review, we discuss the most recent and promising biomarkers that hopefully will assist in the future management of the CF patient.

Demyelination, strokes, and eculizumab: Lessons from the congenital CD59 gene mutations.

Neurological symptoms of patients with p.Cys89Tyr mutation in the CD59 gene include recurrent peripheral neuropathy resembling Guillain-Barré syndrome, characterized by sensory-motor demyelinating neuropathy with secondary axonal damage and moderate enhancement of the nerve roots on spine MRI, together with recurrent strokes and retinal involvement. Three additional mutations in CD59, leading to loss of function, have been described, and overall, 12/12 (100%) of patients with any mutation presented with neurological symptoms; 11/12 (92%) patients presented with recurrent peripheral neuropathy, 6/12 (50%) with recurrent strokes, and 1/12 (8%) with retinal involvement. We review the possible thrombophilic profile associated with the mutations. In these patients, excessive intravascular hemolysis saturates scavenger mechanisms resulting in free hemoglobin in plasma that irreversibly reacts with nitric oxide to form nitrate and methemoglobin, leading to arterial thrombosis. CD59 loss of function is also one of the major thrombophilic mechanisms in patients with paroxysmal nocturnal hemoglobinuria. We then describe the relationship with demyelination. The lack of CD59 allows uncontrolled complement amplification following low-level spontaneous-, viral-, or post viral-induced complement activation, resulting in severe demyelination in the peripheral nervous system. It is interesting, and certainly encouraging, that after 3 years, following 4 patients with Cys89Tyr mutations who are treated with eculizumab, no strokes occurred and non-permanent neurological insults underwent resolution without any new neurological exacerbations.

Defining asthma and assessing asthma outcomes using electronic health record data: a systematic scoping review.

There is currently no consensus on approaches to defining asthma or assessing asthma outcomes using electronic health record-derived data. We explored these approaches in the recent literature and examined the clarity of reporting.We systematically searched for asthma-related articles published between January 1, 2014 and December 31, 2015, extracted the algorithms used to identify asthma patients and assess severity, control and exacerbations, and examined how the validity of these outcomes was justified.From 113 eligible articles, we found significant heterogeneity in the algorithms used to define asthma (n=66 different algorithms), severity (n=18), control (n=9) and exacerbations (n=24). For the majority of algorithms (n=106), validity was not justified. In the remaining cases, approaches ranged from using algorithms validated in the same databases to using nonvalidated algorithms that were based on clinical judgement or clinical guidelines. The implementation of these algorithms was suboptimally described overall.Although electronic health record-derived data are now widely used to study asthma, the approaches being used are significantly varied and are often underdescribed, rendering it difficult to assess the validity of studies and compare their findings. Given the substantial growth in this body of literature, it is crucial that scientific consensus is reached on the underlying definitions and algorithms.

Older patients with late-stage COPD: their illness experiences and involvement in decision-making regarding mechanical ventilation and noninvasive ventilation.

Older patients with late-stage COPD: their illness experiences and involvement in decision-making regarding mechanical ventilation and noninvasive ventilation AIMS AND OBJECTIVES: The aim of this study was twofold: first, to explore the illness experiences of older patients' with late-stage chronic obstructive pulmonary disease; and second, to develop knowledge about how patients perceive their preferences to be taken into account in decision-making processes concerning mechanical ventilation and /or non-invasive ventilation.

Risk of pneumonia in obstructive lung disease: A real-life study comparing extra-fine and fine-particle inhaled corticosteroids.

Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD. The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used.

Primary ciliary dyskinesia presenting with spontaneous pneumothorax: Case report and review of the literature.

Primary ciliary dyskinesia (PCD) is an autosomal recessive heterogeneous group of conditions with variable clinical findings.