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exacerbations - Top 30 Publications

Targeting the interleukin-4 and interleukin-13 pathways in severe asthma: current knowledge and future needs.

Severe asthma is a heterogeneous disease that can be classified into phenotypes and endotypes based upon clinical or biological characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2) asthma. This article reviews the signaling pathway of IL-4 and IL-13 and highlights its targeted therapy in severe asthma.

Use of a Remote Inhaler Monitoring Device to Measure Change in Inhaler Use with Chronic Obstructive Pulmonary Disease Exacerbations.

Remote inhaler monitoring is an emerging technology that enables the healthcare team to monitor the time and location of a patient's inhaler use. We assessed the feasibility of remote inhaler monitoring for chronic obstructive pulmonary disease (COPD) patients and the pattern of albuterol inhaler use associated with COPD exacerbations.

Blood Eosinophilia Does Not Reflect Tissue Eosinophils nor Worsen Clinical Outcomes in COPD.

Home supply of emergency oral steroids and reduction in asthma healthcare utilization.

To determine if children with moderate-to-severe persistent asthma have decreased healthcare utilization after receiving a prescription and instructions to use an at home emergency supply of oral steroids during asthma exacerbations.

The Salford Lung Study: a pioneering comparative effectiveness approach to COPD and asthma in clinical trials.

The Salford Lung Study (SLS) of patients with asthma and chronic obstructive pulmonary disease (COPD) is a practical, community-based, randomized, open-label pragmatic study on the efficacy and safety of the once-daily dry powder inhaler that combines the inhaled corticosteroid fluticasone furoate (FF) with the long-acting beta2 agonist vilanterol (VI). The asthma component of the SLS is not yet reported but the COPD component, done over a 12-month period, found a statistically significant 8.4% reduction in COPD exacerbations when compared to usual care. No differences in adverse events, including serious adverse events and pneumonia, were noted. The importance of real-world findings, such as those found in the SLS COPD trial with inhaled FF/VI, is discussed in comparison to classical randomized controlled trials (RCTs) with inhaled FF/VI in COPD patients. The real-world, community-based pragmatic RCT like the SLS provides additional generalizable data with direct clinical applicability and potential usefulness in the development of practice guidelines. The results from the SLS, along with those of large and small RCTs, are supportive of the use of once-daily FF/VI in COPD maintenance therapy.

Associations between the psychological health of patients and carers in advanced COPD.

Anxiety and depression are highly prevalent in patients with COPD and their informal carers, and associated with numerous risk factors. However, few studies have investigated these in primary care or the link between patient and carer anxiety and depression. We aimed to determine this association and factors associated with anxiety and depression in patients, carers, and both (dyads), in a population-based sample.

Interleukin-22 attenuates double-stranded RNA-induced upregulation of PD-L1 in airway epithelial cells via a STAT3-dependent mechanism.

Double-stranded RNA derived from viruses induces host immune responses. PD-L1, also known as B7-H1, is an immune-checkpoint molecule associated with the escape of viruses from host immune systems, which plays a role in the persistence of viral infection, resulting in exacerbations of underlying diseases such as asthma and chronic obstructive pulmonary disease. Interleukin (IL)-22 is produced from various immune cells and has protective properties on mucosal tissue. The binding of IL-22 to IL-22 receptor induces STAT3 activation. We investigated the effect of IL-22 on the expression in airway epithelial cells in vitro and in mouse lungs in vivo after the stimulation with an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly I:C). Stimulation with poly I:C upregulated PD-L1 expression on BEAS-2B cells. This upregulation of PD-L1 was attenuated by IL-22 administration. STAT3 phosphorylation was induced by IL-22 and poly I:C. Treatment of cells with STAT3 siRNA abolished the effect of IL-22 on the poly I:C-induced upregulation of PD-L1. This upregulation of PD-L1 was also attenuated by IL-11, a cytokine inducing STAT3 phosphorylation, in BEAS-2B cells. In mouse lung cells in vivo, IL-22 suppressed poly I:C-induced upregulation of PD-L1. These results suggest that IL-22 attenuates virus-induced upregulation of PD-L1 in airway epithelial cells via a STAT3-dependent mechanism.

Development and validation of an LC tandem MS assay for the quantification of β-lactam antibiotics in the sputum of cystic fibrosis patients.

Antibiotic therapy is of vital importance for the control of infectious exacerbations in cystic fibrosis (CF) patients. However, very little is known regarding the fraction of systemically administered antibiotics reaching the lower respiratory tract secretions. We developed and validated a method to measure the concentrations of piperacillin, ceftazidime, meropenem and aztreonam in CF sputum, and present the validation data.

Can phage therapy solve the problem of recalcitrant chronic rhinosinusitis?

Chronic rhinosinusitis (CRS) affects 5-15% of the global population. In some patients, the infectious exacerbations of the disease are recalcitrant to medical treatment and surgery. These cases are probably associated with the presence of bacterial biofilms. Bacteriophage (phage) therapy seems to be a promising antibiofilm strategy. The efficacy of phage therapy in sinonasal infections has been demonstrated both in vitro and in animal models. In the past, phage preparations were also administered to humans with CRS with favorable outcomes and no significant side effects. Very recently, the safety and efficacy of phage therapy in otolaryngological infections has been demonstrated in pioneer Phase I/II clinical trials. This review addresses the potential of phage therapy to treat CRS. We also discuss issues that require further research.

Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort.

Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection.127 patients aged 40-85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year.Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755-0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition.

Characterisation of asthma subgroups associated with circulating YKL-40 levels.

The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined.We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups.Four YKL-40 clusters (C1-C4) were identified. C3 and C4 had high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction, and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and less airflow obstruction, but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-type 2 inflammatory pathways.Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.

Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study.

Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient(-1)·year(-1) for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.

Th17 cytokines: novel potential therapeutic targets for COPD pathogenesis and exacerbations.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways caused mainly by cigarette smoke exposure. COPD progression is marked by exacerbations of the disease, often associated with infections. Recent data show the involvement in COPD pathophysiology of interleukin (IL)-17 and IL-22, two cytokines that are important in the control of lung inflammation and infection. During the initiation and progression of the disease, increased IL-17 secretion causes neutrophil recruitment, leading to chronic inflammation, airways obstruction and emphysema. In the established phase of COPD, a defective IL-22 response facilitates pathogen-associated infections and disease exacerbations. Altered production of these cytokines involves a complex network of immune cells and dysfunction of antigen-presenting cells. In this review, we describe current knowledge on the involvement of IL-17 and IL-22 in COPD pathophysiology at steady state and during exacerbations, and discuss implications for COPD management and future therapeutic approaches.

Asthma exacerbations and socio-economic status in French adults with persistent asthma: a prospective cohort study.

Adults disadvantaged by poor socio-economic status (SES) are more severely affected by asthma compared to those with better SES. We aimed to determine whether the frequency of asthma exacerbations (AEx), as well as aspects related to AEx management, differed based on SES in patients treated with daily treatments.

Presence of atopy increases the risk of asthma relapse.

To describe the point prevalence of respiratory viruses/atypical bacteria using PCR and evaluate the impact of respiratory viruses/atypical bacteria and atopy on acute severity and clinical recovery in children with hospitalised and non-hospitalised asthma exacerbations.

Comparative features of Asthma with frequent or infrequent exacerbations: A longitudinal study of retrospective and prospective events.

A "frequent exacerbator phenotype" has been described, mostly in the population of patients with severe asthma. Further data are needed on such exacerbation-prone patients in milder asthma.

The role of human rhinovirus (HRV) species on asthma exacerbation severity in children and adolescents.

It is recognized that human rhinovirus (HRV) infection is an important factor in asthma exacerbations requiring hospitalization in children. However, previous studies have disagreed on the differential impact of various HRV species. We sought to assess the impact of HRV species on the severity of asthma exacerbations in children and adolescents. We also examined whether the effect of HRV species on severity was modified by age and gender.

Unique circumferential peripheral keratitis in relapsing polychondritis: A case report.

Relapsing polychondritis (RP) is a rare collagen disease characterized by inflammation and destruction of cartilage throughout the body. The paper details the clinical course of a case of RP with unique circumferential peripheral keratitis.

Nintedanib for Idiopathic Pulmonary Fibrosis.

To review the pharmacology, safety, and efficacy of nintedanib for the treatment of idiopathic pulmonary fibrosis (IPF).

Biologicals in the Treatment of Bronchial Asthma.

Biologicals are a therapeutic option for patients with severe asthma. Difficult asthma in patients with untreated comorbidities or persistent trigger factors is much more common than severe refractory asthma. Optimized medical treatment, adherence to medication, elimination of trigger factors and treatment of comorbidities are essential before escalating the therapy with a biological. A careful phenotyping of patient with severe asthma is necessary because all available biological are only effective in certain phenotypes of the disease. For patients with severe allergic asthma an antibody against IgE (Omalizumab) is available. For patients with severe asthma and eosinophilic inflammation the Interleukin (IL)-5 Antibodies Mepolizumab and Reslizumab have recently been approved. The most prominent effect of biological treatment is the reduction of acute exacerbations in these patients. Further antibodies against IL-5 receptor (Benralizumab) or against the IL-4 receptor alpha chain (Dupilumab) are in advanced clinical development.

A genome-by-environment interaction classifier for precision medicine: personal transcriptome response to rhinovirus identifies children prone to asthma exacerbations.

To introduce a disease prognosis framework enabled by a robust classification scheme derived from patient-specific transcriptomic response to stimulation.

Algorithm for the management of asthma in pregnant women: a protocol to optimize processes in healthcare.

Asthma is the most common chronic disease in pregnant women. Its evolution during pregnancy could improve, stay the same or worsen, especially in cases where there is a loss of clinical control. This can lead to maternal and fetal hypoxia with serious adverse perinatal outcomes. Areas covered: This article reviews physiological modifications in pregnancy, effects of pregnancy on asthma, and possible consequences on fetus development. Furthermore, it reviews evidence on assessment and both pharmacological and non-pharmacological management of asthma in pregnant and breastfeeding women as well as in acute exacerbations. Electronic databases, such as PUBMED, were searched for terms pregnan* or perinat* or obstet* and breastfeeding or asthma or wheeze, as well as a book published by the present authors. Expert commentary: A patient-centered multidisciplinary approach, where the respiratory specialists have a key role in assessing and achieving control, as well as the education interventions for self-monitoring and adherence are at least as important as adequate pharmacological treatment.

The EU project "United4Health": Results and experiences from automatic health status assessment in a Norwegian telemedicine trial system.

Introduction Patients with chronic obstructive pulmonary disease require help in daily life situations to increase their individual perception of security, especially under worsened medical conditions. Unnecessary hospital (re-)admissions and home visits by doctors or nurses shall be avoided. This study evaluates the results from a two-year telemedicine field trial for automatic health status assessment based on remote monitoring and analysis of a long time series of vital signs data from patients at home over periods of weeks or months. Methods After discharge from hospital treatment for acute exacerbations, 94 patients were recruited for follow-up by the trial system. The system supported daily measurements of pulse and transdermal peripheral capillary oxygen saturation at patients' homes, a symptom-specific questionnaire, and provided nurses trained to use telemedicine ("telenurses") with an automatically generated health status overview of all monitored patients. A colour code (green/yellow/red) indicated whether the patient was stable or had a notable deterioration, while red alerts highlighted those in most urgent need of follow-up. The telenurses could manually overwrite the status level based on the patients' conditions observed through video consultation. Results Health status evaluation in 4970 telemonitor datasets were assessed retrospectively. The automatic health status determination (subgroup of 33 patients) showed green status at 46% of the days during a one-month monitoring period, 28% yellow status, and 19% red status (no data reported at 7% of the days). The telenurses manually downrated approximately 10% of the red or yellow alerts. Discussion The evaluation of the defined real-time health status assessment algorithms, which involve static rules with personally adapted elements, shows limitations to adapt long-term home monitoring with adequate interpretation of day-to-day changes in the patient's condition. Thus, due to the given sensitivity and specificity of such algorithms, it seems challenging to avoid false high alerts.

Innovative Telemonitoring Enhanced Care Programme for Chronic Heart Failure (ITEC-CHF) to improve guideline compliance and collaborative care: protocol of a multicentre randomised controlled trial.

Chronic heart failure (CHF) is a life-threatening chronic disease characterised by periodic exacerbations and recurrent hospitalisations. In the management of CHF, patient compliance with evidence-based clinical guidelines is essential, but remains difficult practically. The objective of this study is to examine whether an Innovative Telemonitoring Enhanced Care Programme for CHF (ITEC-CHF) improves patients' compliance, and associated health and economic outcomes.

Hospitalization due to acute exacerbation of chronic pain: An intervention study in a university hospital.

Hospitalization as a result of acute exacerbation of complex chronic pain is a largely hidden problem, as patients are often admitted to hospital under a variety of specialities, and there is frequently no overarching inpatient chronic pain service dedicated to their management. Our institution had established an inpatient acute pain service overseen by pain physicians and staffed by specialist nurses that was intended to focus on the management of perioperative pain. We soon observed an increasing number of nurse-to-nurse referrals of non-surgical inpatients admitted with chronic pain. Some of these patients had seemingly intractable and highly complex pain problems, and consequently we initiated twice-weekly attending physician-led inpatient pain rounds to coordinate their management. From these referrals, we identified a cohort of 20 patients who were frequently hospitalized for long periods with exacerbations of chronic pain. We sought to establish whether the introduction of the physician-led inpatient pain ward round reduced the number and duration of hospitalizations, and costs of treatment.

A prospective, placebo controlled study on the humoral immune response to and safety of tetanus revaccination in myasthenia gravis.

To investigate the humoral immune response to and safety of a tetanus revaccination in patients with myasthenia gravis or Lambert-Eaton myasthenic syndrome.

The optimal approach to nutrition and cystic fibrosis: latest evidence and recommendations.

Cystic fibrosis (CF) is a progressive genetic disease that affects multiple organ systems. Therapy is directed to maintain and optimize nutritional status and pulmonary function, as these are key factors in survival. In this review, the most recent findings regarding nutritional management associated with pulmonary function and outcome will be explored.

Hepatitis C and pulmonary fibrosis.

Hepatitis C is one of the most important infectious agents worldwide. There are conflicting results regarding the relationship between pulmonary fibrosis and hepatitis C. It is thought that hepatitis C may play a role in the development or exacerbations of idiopathic pulmonary fibrosis, but no clear link between hepatitis C and pulmonary fibrosis development has been demonstrated yet to date. In the recent era, indirect effects of hepatitis C rather than a direct effect are more suspected on pulmonary fibrosis. These indirect effects could also been documented only by a few case-based studies.

Medical and Surgical Advancements in the Management of Cystic Fibrosis Chronic Rhinosinusitis.

The purpose of this review is to provide otolaryngologists with the most up-to-date advancements in both the medical and surgical management of CF-related sinus disease.

Estimating the effectiveness of pulmonary rehabilitation for COPD exacerbations: reduction of hospital inpatient days during the following year.

To study the short- and long-term results of pulmonary rehabilitation (PR) given in the Helsinki University Heart and Lung Center and to understand the hospital resources used to treat severe COPD exacerbations in the city of Helsinki.