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exacerbations - Top 30 Publications

Diabetes risks and outcomes in chronic obstructive pulmonary disease patients: Two nationwide population-based retrospective cohort studies.

The relationship between chronic obstructive pulmonary disease (COPD) and diabetes remains incompletely understood. This study evaluated diabetes risk and post-diabetes outcomes in COPD patients with and without exacerbations.

Validating the Concept of COPD Control: A Real-world Cohort Study from the United Kingdom.

The concept of Chronic Obstructive Pulmonary Disease (COPD) control has been developed to inform therapeutic decision-making. We explored the validity of a definition of COPD control in a representative population of patients with COPD in the United Kingdom. Electronic medical records and linked COPD questionnaire data from the Optimum Patient Care Research Database were used to characterize control status. Patients were aged ≥40 years, with spirometry-confirmed COPD, current or ex-smokers, and continuous records throughout the study period. Control was evaluated based on COPD stability and patients' (i) clinical features or (ii) COPD Assessment Test (CAT) score over a three-month baseline period and linked to time to first exacerbation. Of 2788 eligible patients, 2511 (90%) had mild/moderate COPD and 277 (10%) had severe/very severe COPD based on Body Mass Index, Obstruction, Dyspnoea, Exacerbations (BODEx) cut-off of 4. Within the mild/moderate cohort, 4.5% of patients were controlled at baseline according to clinical features and 21.5% according to CAT threshold of 10. Within the severe/very severe cohort, no patients were controlled at baseline according to the proposed clinical features and 8.3% were controlled according to CAT threshold of 20. Compared with uncontrolled patients, time to first exacerbation was longer for controlled patients with mild/moderate COPD but not for those with severe/very severe COPD. Lowering the BODEx threshold for severity classification to 2 increased the number of patients achieving control. CAT scores were not good predictors of the risk of future exacerbation. With the proposed definition, very few patients were defined as controlled.

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

Risk factors for totally implantable venous access device-associated complications in cystic fibrosis.

Candidaemia is an important nosocomial infection, seen frequently in immunocompromised and critically ill patients and increasingly recognised in cystic fibrosis (CF) patients with totally implantable venous access devices (TIVADs). This study aims to investigate the incidence and risk factors for the development of TIVAD-associated candidaemia and to assess the rate of TIVAD-related complications in CF patients.

Role of Vitamin D in reducing number of acute exacerbations in Chronic Obstructive Pulmonary Disease (COPD) patients.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic incompletely reversible poor airflow and air trapping and usually this debilitating disorder limits the outside activities of the patients depriving them of sunlight which is a rich source of Vitamin D. The objective of this study was to determine the effect of vitamin D supplementation in reducing number of acute exacerbation in COPD patients.

Values of procalcitonin and C-reactive proteins in the diagnosis and treatment of chronic obstructive pulmonary disease having concomitant bacterial infection.

To observe the changes in the levels of C-reactive protein (CRP) and procalcitonin (PCT) in serum of patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and to compare with the values of CRP in combination with PCT in the diagnosis and treatment of infective exacerbation of COPD.

A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations - The CORTICO steroid reduction in COPD (CORTICO-COP) study protocol.

The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects. Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome.

Efficacy and safety of tiotropium Respimat in the treatment of chronic obstructive pulmonary disease: systematic review.

Objective: To evaluate the efficacy and safety of tiotropium Respimat in the treatment of chronic obstructive pulmonary disease (COPD) according to the Cochrane systematic evaluation. Methods: The Cochrane Library, PubMed, EMbase, CNKI, VIP and CBM, Wanfang Data were searched(from the foundation date to Jan. 2016) for the randomized controlled trials (RCTs) of tiotropium Respimat in the treatment of patients with COPD. Two reviewers independently retrieved the RCTs according to the inclusion and exclusion criteria, assessed the methodological quality of the included trials.and performed statistical analysis on the data using RevMan 5.3 software. Results: Totally 11 RCTs on efficacy were finally included.The results of the combined analysis showed that FEV(1) was significantly improved in the tiotropium Respimat group than that in the placebo group[MD=0.12, 95%CI(0.10-0.14), P<0.000 01], while FEV(1) was similar between the tiotropium Respimat group and the tiotropium HandiHaler group[5 μg: MD=0.00, 95%CI(-0.04-0.04), P=0.94; 2.5 μg: MD=-0.04, 95%CI(-0.10-0.01), P=0.12; 10 μg: MD=0.02, 95%CI(-0.06-0.09), P=0.66]. FVC was significantly improved in the tiotropium Respimat group than that in the placebo group[MD=0.18, 95%CI(0.09-0.28), P=0.0002], while FVC was similar between the tiotropium Respimat group and the HandiHaler group[2.5 μg: MD=-0.06, 95%CI(-0.16-0.04), P=0.24; 5 μg: MD=-0.00, 95%CI(-0.08-0.08), P=1.00; 10 μg: MD=0.02, 95%CI(-0.14-0.19), P=0.78]. The risk of acute exacerbations was lower in the tiotropium Respimat group (5 μg / kg) than in the placebo group [OR=0.72, 95%CI(0.60-0.86), P=0.000 3]. It was similar in the tiotropium Respimat group (5 μg) and the HandiHaler group[OR=1.01, 95%CI(0.94-1.09), P=0.71]. The SGRQ total score of the tiotropium Respimat group (5 μg) was significantly different from that of the placebo group[MD=-3.6, 95%CI(-3.88--3.32), P<0.000 01]. C(max, ss) and AUC(0-6 h, ss) were also similar between the tiotropium Respimat group and the HandiHaler group[MD=0.2, 95%CI(-5.1-5.5), P=0.94]; MD=-1.01, 95%CI(-11.78-9.77), P=0.85]. Nine RCTs were included in the evaluation of the incident rates of adverse drug reactions(ADR). There was no significant difference between the tiotropium Respimat group HandiHaler group and the placebo group[RR=0.95, 95%CI(0.89-1.00), P=0.05], [OR=1.07, 95%CI(1.00-1.16), P=0.06]. Conclusions: The efficacy and safety of tiotropium Respimat was similar to tiotropium HandiHaler in the treatment of COPD. They can effectively improve the pulmonary function and clinical symptoms of patients. But the long-term efficacy and safety of tiotropium Respimat still need to be confirmed by higher quality and larger RCTs with long-term follow-up.

Isolation of Group 2 Innate Lymphoid Cells from Mouse Lungs.

The recently described group 2 innate lymphoid cells (ILC2) exert critical roles in type 2 immune responses, epithelial repair at mucosal tissues and metabolic homeostasis. ILC2 release large amounts of type 2 cytokines such as interleukin 4 (IL-4), IL-5, and IL-13, driving type 2 immunity such as the defense against helminths. However, if not tightly regulated ILC2 can trigger unwanted type 2 immunopathologies including allergic airway inflammation, airway hyper-responsiveness, and atopic dermatitis. Viral respiratory tract infections, archetypal triggers of type 1 immune responses, often give rise to pulmonary type 2 immunopathologies such as asthma and asthma exacerbations. Interestingly, pulmonary viral infections induce the release of IL-33, followed by induction of ILC2-mediated pulmonary type 2 immunopathology independent of the adaptive immune system. Due to their scarcity at steady state but also after infection and inflammation, pulmonary ILC2 are challenging to work with. In this chapter, we describe the detection and isolation procedure of pulmonary mouse ILC2 by flow cytometry and compare four distinct enzymatic mouse lung tissue processing protocols for optimized cell yield.

Effect of Pregnancy on Quantitative Medication Use and Relation to Exacerbations in Asthma.

The quantification of asthma medication reduction and its relation to an aggravation of asthma during pregnancy at an individual level are unclear.

Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis.

Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease. A systems-level description of airway surface liquid (ASL) homeostasis could accelerate development of such therapies. Accordingly, we developed a mathematical model to describe the dynamic coupling of ion and water transport to extracellular purinergic signaling. We trained our model from steady-state and time-dependent experimental measurements made using normal and cystic fibrosis (CF) cultured human airway epithelium. To reproduce CF conditions, reduced chloride secretion, increased potassium secretion, and increased sodium absorption were required. The model accurately predicted ASL height under basal normal and CF conditions and the collapse of surface hydration due to the accelerated nucleotide metabolism associated with CF exacerbations. Finally, the model predicted a therapeutic strategy to deliver nucleotide receptor agonists to effectively rehydrate the ASL of CF airways.

Estimating the Public Health Impact of Air Pollution for Informing Policy in the Twin Cities: A Minnesota Tracking Collaboration.

The Minnesota Department of Health and the Minnesota Pollution Control Agency used local air pollution and public health data to estimate the impacts of particulate matter and ozone on population health, to identify disparities, and to inform decisions that will improve health.

Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI.

Some environmental factors have been already associated to increased risk of multiple sclerosis (MS), but it is plausible that additional factors might play a role.

Asthma Exacerbations and Triggers in Children in TENOR: Impact on Quality of Life.

Data examining associations between asthma exacerbations, triggers, and asthma-related quality of life (QOL) in children with severe/difficult-to-treat asthma are unavailable.

Anxiety Contributes to Poorer Asthma Outcomes in Inner-City Black Adolescents.

The factors associated with poor asthma control, exacerbations, and health care utilization in black adolescents are complex and not well understood. Although psychological comorbidities such as anxiety are common in patients with asthma, these have not been studied in this population.

Nontypeable Haemophilus influenzae (NTHi) directly interfere with the regulation of E-cadherin in lung epithelial cells.

Loss of epithelial barriers characterized by reduction of E-cadherin is a hallmark of chronic obstructive pulmonary disease (COPD). We investigated the effects of nontypeable Haemophilus influenzae (NTHi) infections, associated with acute exacerbations of chronic bronchitis, on the regulation of E-cadherin in host cells. NTHi infection decreased E-cadherin mRNA and protein-levels in lung epithelial cells. E-cadherin reduction was mediated by activation of the fibroblast growth factor 2 (FGF2), the mammalian target of rapamycin (mTOR) and Slug. These data indicate that epithelial integrity and barrier function is disturbed by NTHi infection. Mainly, the destruction of cell-cell contacts is a prominent feature in NTHi infection.

Microbiome in lung explants of idiopathic pulmonary fibrosis: a case-control study in patients with end-stage fibrosis.

The microbiome has been proposed to play a role in the progression of idiopathic pulmonary fibrosis (IPF) based on bronchoalveolar lavage analyses, but the microbiome of lung tissue in IPF has not been explored. In a case-control study of lung explants analysed by 16S rRNA gene sequencing, we could not reliably detect bacterial DNA in basilar tissue samples from patients with either chronic or acute exacerbations of IPF, in contrast to control candidate-donor lungs or cystic fibrosis explants. Thus, our data do not indicate microbiome alterations in regions of IPF lung with advanced fibrosis.

Effectiveness of Healthcare Coordination in Patients with Chronic Respiratory Diseases.

Coordination of healthcare effectively prevents exacerbations and reduces the number of hospitalizations, emergency visits, and the mortality rate in patients with chronic respiratory diseases. The purpose of this study was to determine clinical effectiveness of ambulatory healthcare coordination in chronic respiratory patients and its effect on the level of healthcare services as an indicator of direct medical costs. We conducted a retrospective health record survey, using an online database of 550 patients with chronic respiratory diseases. There were decreases in breathing rate, heart rate, and the number of cigarettes smoked per day, and forced vital capacity (FVC) and forced expired volume in 1 s (FEV1) increased after the implementation of the coordinated healthcare structure. These benefits were accompanied by increases in the number of visits to the pulmonary outpatient clinic (p < 0.001), diagnostic costs (p < 0.001), and referrals to other outpatient clinics (p < 0.003) and hospitals (p < 0.001). The advantageous effects of healthcare coordination on clinical status of respiratory patients above outlined persisted over a 3-year period being reviewed.

In stable COPD, long-acting muscarinic antagonist plus long-acting beta-agonists resulted in less exacerbations, pneumonia and larger improvement in FEV 1 than long-acting beta-agonists plus inhaled corticosteroids.

Assessing the Impact of a Remote Digital Coaching Engagement Program on Patient Reported Outcomes in Asthma.

Low adherence and poor outcomes provide opportunity for digital coaching to engage patients with uncontrolled asthma in their care to improve outcomes.

Omalizumab in non-allergic asthma: A report of 13 cases.

There are limited data regarding the effectiveness of omalizumab in patients with non-allergic asthma.

Severity of Airflow Obstruction in Chronic Obstructive Pulmonary Disease (COPD): Proposal for a New Classification.

Current classifications of Chronic Obstructive Pulmonary Disease (COPD) severity are complex and do not grade levels of obstruction. Obstruction is a simpler construct and independent of ethnicity. We constructed an index of obstruction severity based on the FEV1/FVC ratio, with cut-points dividing the Burden of Obstructive Lung Disease (BOLD) study population into four similarly sized strata to those created by the GOLD criteria that uses FEV1. We measured the agreement between classifications and the validity of the FEV1-based classification in identifying the level of obstruction as defined by the new groupings. We compared the strengths of association of each classification with quality of life (QoL), MRC dyspnoea score and the self-reported exacerbation rate. Agreement between classifications was only fair. FEV1-based criteria for moderate COPD identified only 79% of those with moderate obstruction and misclassified half of the participants with mild obstruction as having more severe COPD. Both scales were equally strongly associated with QoL, exertional dyspnoea and respiratory exacerbations. Severity assessed using the FEV1/FVC ratio is only in moderate agreement with the severity assessed using FEV1 but is equally strongly associated with other outcomes. Severity assessed using the FEV1/FVC ratio is likely to be independent of ethnicity.

High usability of a smartphone application for reporting symptoms in adults with cystic fibrosis.

Introduction In cystic fibrosis, exacerbations impair lung function and health-related quality of life, increase healthcare costs and reduce survival. Delayed reporting of worsening symptoms can result in more severe exacerbations and worse clinical outcomes; therefore there is a need for a novel approach to facilitate the early identification and treatment of exacerbations in this population. This study investigated the usability of a smartphone application to report symptoms in adults with cystic fibrosis, and the observer agreement in clinical decision-making between senior clinicians interpreting smartphone application responses. Methods Adults with cystic fibrosis used the smartphone application weekly for four weeks. The application comprised 10 yes/no questions regarding respiratory symptoms and two regarding emotional well-being. Usability was measured with the System Usability Scale; Observer agreement was tested by providing a cystic fibrosis physician and a nurse practitioner with 45 clinical scenarios. For each scenario the clinicians, who were blinded to each other's responses, were asked to indicate whether or not they would: (i) initiate telephone contact, and/or (ii) request a clinic visit for the individual. Results Ten participants (five female), aged mean (SD) 33 (11) years, FEV1 49 (27)% predicted completed the study. The mean (SD) System Usability Scale score was 94 (6). There was perfect agreement between clinicians for initiating contact with the participant ( κ = 1.0, p < 0.001), and near-perfect for requesting a clinic visit ( κ = 0.86, p < 0.001). Discussion The use of a smartphone application for reporting symptoms in adults with cystic fibrosis has excellent usability and near-perfect agreement between senior clinicians when interpreting the application responses.

Role of atmospheric pollution on the natural history of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has an unpredictable course corresponding to various profiles: stability, physiological disease progression and rapid decline. A minority of patients experience acute exacerbations (AEs). A recent study suggested that ozone and nitrogen dioxide might contribute to the occurrence of AE. We hypothesised that outdoor air pollution might influence the natural history of IPF.

Epidemiology and impact of chronic bronchitis in chronic obstructive pulmonary disease.

Research on the association between chronic bronchitis and chronic obstructive pulmonary disease (COPD) exacerbations has led to discordant results. Furthermore, the impact of chronic bronchitis on mortality in COPD subjects is unclear.Within the Rotterdam Study, a population-based cohort study of subjects aged ≥45 years, chronic bronchitis was defined as having a productive cough for ≥3 months per year for two consecutive years. Linear, logistic regression and Cox proportional hazard models were adjusted for age, sex and pack-years.Out of 972 included COPD subjects, 752 had no chronic phlegm production (CB(-)) and 220 had chronic phlegm production, of whom 172 met the definition of chronic bronchitis (CB(+)). CB(+) subjects were older, more frequently current smokers and had more pack-years than CB(-) subjects. During a median 6.5 years of follow-up, CB(+) subjects had greater decline in lung function (-38 mL·year(-1), 95% CI -61.7--14.6; p=0.024). CB(+) subjects had an increased risk of frequent exacerbations (OR 4.0, 95% CI 2.7-5.9; p<0.001). In females, survival was significantly worse in CB(+) subjects compared to CB(-) subjects. Regarding cause-specific mortality, CB(+) subjects had an increased risk of respiratory mortality (hazard ratio 2.16, 95% CI 1.12-4.17; p=0.002).COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production.

More Than a Decade Follow-up in Severe or Difficult-to-Treat Asthma: TENOR II.

The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR I) study demonstrated high morbidity in patients with severe/difficult-to-treat asthma, despite standard-of-care treatment.

Hospital Procalcitonin Testing and Antibiotic Treatment of Patients Admitted for COPD Exacerbation.

Randomized trials suggest that assessment of serum procalcitonin (PCT) levels can be used to safely limit antibiotic use among patients hospitalized for exacerbations of COPD.

Pharmacokinetics of Azole Antifungals in Cystic Fibrosis.

Defects in mucociliary clearance predispose cystic fibrosis (CF) patients to airway colonization and infection by various fungi, especially Aspergillus fumigatus. Although the clinical significance of airway fungal colonization is not clear, several studies have suggested its association with worsening lung function and increased risk of CF exacerbations. Antifungal triazole agents have been used in CF patients with airway fungal colonization or infections with varying results. Limited pharmacokinetic studies to date have demonstrated high inter-subject variability of triazole levels among CF patients. This review discusses the basic principles of pharmacokinetics, the pharmacokinetic changes associated with CF and the effect of CF on the pharmacokinetic principles of azole antifungals. The inconsistent azole serum levels in CF patients may be associated with sub-therapeutic (thus risk of therapeutic failure and/or emergence of azole-resistant fungi) or supratherapeutic exposures (thus potential risk of azole toxicity), suggesting that therapeutic dose monitoring is necessary in CF patients.

The association of tidal EFL with exercise performance, exacerbations, and death in COPD.

Tidal expiratory flow limitation (EFLT) is frequently found in patients with COPD and can be detected by forced oscillations when within-breath reactance of a single-breath is ≥0.28 kPa·s·L(-1). The present study explored the association of within-breath reactance measured over multiple breaths and EFLT with 6-minute walk distance (6MWD), exacerbations, and mortality.

A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease.

Interleukin-1 receptor 1 (IL-1R1) inhibition is a potential strategy for treating patients with chronic obstructive pulmonary disease (COPD). MEDI8968, a fully human monoclonal antibody, binds selectively to IL-1R1, inhibiting activation by IL-1α and IL-1β. We studied the efficacy and safety/tolerability of MEDI8968 in adults with symptomatic, moderate-to-very severe COPD.