Search

Asthma is commonly reported in patients with a diagnosis of bronchiectasis. The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography–confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A. [ABSTRACT FROM AUTHOR]

· The microbiota in the lower airway of people with cystic fibrosis is resilient in the short and medium term. · Among the microbiota metrics studied at the start and after completion of treatment of a pulmonary exacerbation, the greatest shift was observed in community richness which decreased with treatment. · While lower community richness may suggest an increased risk of exacerbation, regression analysis highlighted that lung function was the most important predictor of future pulmonary exacerbations. · Complex microbiota data may provide some additional insights when used in combination with routine clinical measurements. Whether there is any benefit in integrating culture-independent molecular analysis of the lower airway microbiota of people with cystic fibrosis into clinical care is unclear. This study determined the longitudinal trajectory of the microbiota and if there were microbiota characteristics that corresponded with response to treatment or predicted a future pulmonary exacerbation. At least one sputum sample was collected from 149 participants enrolled in this prospective longitudinal multi-centre study and total bacterial density and microbiota community measurements were determined and compared with clinical parameters. In 114 participants with paired samples when clinically stable, ∼8 months apart, the microbiota remained conserved between timepoints, regardless of whether participants received acute intravenous antibiotic treatment or not. In 62 participants, who presented with an acute exacerbation, a decrease in community richness correlated best with patient response to antibiotic treatment. Analysis of baseline samples from 30 participants who exacerbated within 4 months of their stable sample being collected and 72 participants who remained stable throughout the study showed that community characteristics such as lower richness at baseline may be predictive of an exacerbation in addition to several clinical parameters. However, lasso regression analysis indicated that only lung function (p = 0.014) was associated with a future exacerbation. The airway microbiota remains stable over periods <1 year with modest shifts related to treatment apparent which might provide some additional insights to patient-level measurements. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought new insights into the immunologic intricacies of asthma. In this review, we discuss the epidemiology of asthma in patients infected with SARS-CoV-2 and the risk of severe infection. Type 2 inflammation had an overall protective effect against SARS-CoV-2 infection by various mechanisms summarized in this review. Asthma, intranasal, and inhaled corticosteroids decreased the angiotensin-converting enzyme 2 receptor, an important receptor for SARS-CoV-2 entry into host cells. We summarize the nuances of the treatment of type 2 inflammation despite its underlying protective effects. Research to date has shown that patients on various allergen immunotherapies and biologics do benefit from being vaccinated. [ABSTRACT FROM AUTHOR]

Objective: To determine whether school infrastructure is associated with health and academic outcomes among elementary school children with asthma. Methods: We conducted a retrospective cohort study of linked medical, academic, and facilities data from a large mid-Atlantic school district of the United States. All K-5 students with asthma who were enrolled under the state's Children's Health Insurance Program were included. We estimated associations of the infrastructure quality of the student's school, as assessed by an engineering firm in Summer 2011 and represented by the Facility Condition Index (FCI), with asthma health outcomes, absenteeism, and standardized test scores in math and reading in the 2 academic years thereafter. Results: A total of 6558 students were identified, the majority non-Hispanic Black, across 130 schools. Most schools (97/130, 75%) were in very poor or worse condition. In cluster-adjusted models accounting for demographics, grade, school-specific area deprivation, and inhaled corticosteroid use, a one standard deviation increase in FCI, corresponding to greater infrastructure deficiency, was associated with higher rates of asthma-related hospitalizations (incidence rate ratio [IRR] 1.16; 95% confidence interval [CI] 1.03, 1.32), more absenteeism (IRR 1.05; 95% CI 1.01, 1.08), and lower scores in math (mean difference [MD] -3.3; 95% CI -5.5, -1.2) and reading (MD -3.0; 95% CI -5.1, -0.9). There were no differences in rates of asthma-related emergency visits or steroid prescriptions. Conclusions: Children with asthma attending schools with poorer infrastructure had worse health and academic outcomes. Public policy emphasizing reinvestment in school infrastructure may be a potential means of addressing asthma disparities. [ABSTRACT FROM AUTHOR]

[Display omitted] The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤.037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤.046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10−12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUC training : 0.82 and AUC validation : 0.77). The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS. [ABSTRACT FROM AUTHOR]

• The impact of home vs hospital care is an important clinical question in the treatment of pulmonary exacerbations (PEx). • We assessed treatment responses for adults with CF treated for PEx with intravenous antibiotics at home, in the hospital, or both. • Compared to PEx treatment at home only, treatment in the hospital was associated with greater mean lung function, respiratory symptom, and weight improvements. In the STOP2 (Standardized Treatment of Pulmonary Exacerbations-2) study, intravenous (IV) antimicrobial treatment duration for adults with cystic fibrosis (CF) experiencing pulmonary exacerbations (PEx) was determined based on initial treatment response. The impact of home vs hospital care remains an important clinical question in CF. Our hypothesis was that STOP2 participants treated at home would have less improvement in lung function compared to those treated in the hospital. Treating clinicians determined PEx treatment location, which was a stratification factor for STOP2 randomization. Lung function, weight, and symptom recovery were evaluated by treatment location. Propensity scores and inverse probability treatment weighting were used to test for differences in clinical response by treatment location. In all, 33% of STOP2 participants received IV antimicrobials in the hospital only, 46% both in the hospital and at home, and 21% at home only. Mean (95% CI) ppFEV 1 improvement was significantly (p < 0.05) lower for those treated at home only, 5.0 (3.5, 6.5), compared with at home and in the hospital, 7.0 (5.9, 8.1), and in the hospital only, 8.0 (6.7, 9.4). Mean weight (p < 0.001) and symptom (p < 0.05) changes were significantly smaller for those treated at home only compared to those treated in the hospital only. Compared to PEx treatment at home only, treatment in the hospital was associated with greater mean lung function, respiratory symptom, and weight improvements. The limitations of home IV therapy should be addressed in order to optimize outcomes for adults with CF treated at home. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

7• Home spirometry can be used to track exacerbation recovery in cystic fibrosis. 7• Home spirometry demonstrated limited variability during periods of stability. 7• Oral antimicrobials are frequently used to treat cystic fibrosis exacerbations. 7• Events treated with oral antimicrobials showed minimal lung function recovery. 7• Oral agents may be less effective than IV antimicrobials at treating exacerbations. Retrospective studies indicate that more cystic fibrosis (CF) pulmonary exacerbations (PEx) are treated with oral (PO) than with intravenous (IV) antimicrobials despite little knowledge of the relative effects of PO treatment on lung function recovery or long-term impacts on lung disease progression. Previous studies have suggested that PO treatment may be associated with slower lung function recovery compared with IV treatment. We used longitudinal home spirometry data from the eICE study (NCT01104402) to compare PO versus IV antimicrobial treatment responses for PEx diagnosed by home spirometry and symptom assessment. Adolescent and adult eICE participants performed home spirometry twice weekly for one year. PEx were diagnosed by a protocol-defined algorithm of change in percent predicted forced expiratory volume in 1 second (ppFEV 1) and/or respiratory signs and symptoms. PO- and IV-treated PEx were grouped by initial ppFEV 1 drop magnitude. Group ppFEV 1 treatment responses were modeled with multivariate, repeat-measure linear regression. Of 87 qualifying PEx from 56 participants, 62 were PO-treated and 25 were IV-treated. The average drop from best ppFEV 1 to PEx start was 11.0 [95%CI: 8.5, 13.5] with similar treatment group means (p=0.72). Participants with IV-treated PEx averaged 0.72 [0.24, 1.20] ppFEV 1 /day greater response than those treated with PO, who experienced minimal ppFEV1 recovery. Many PO-treated participants who had <10 ppFEV 1 drop from baseline tended to worsen or show no ppFEV 1 improvement. These results suggest that, in this cohort, PO antimicrobial treatment of CF PEx were less effective than IVs at improving ppFEV 1 during treatment. [ABSTRACT FROM AUTHOR]

• Antibiotics with broad anaerobe coverage are used in ~ 1/4 of CF exacerbations. • Broad anaerobe coverage is used more often in patients with lower lung function. • Exacerbation outcomes did not differ between antibiotics with broad vs minimal anaerobe coverage. Obligate and facultative anaerobic bacteria are prevalent in cystic fibrosis (CF) airways. Increases in anaerobe relative abundance have been associated with CF pulmonary exacerbations (PEx); however, the impact of antibiotic treatment of anaerobes during PEx is unknown. We hypothesized that PEx treated with antibiotics with activity against anaerobes would improve outcomes compared to antibiotics without anaerobic activity. This was a single-center, retrospective study of people with CF, ages 6 years and older, treated with intravenous (IV) antibiotics for PEx. IV antibiotics were classified as either broad or minimal anaerobic activity. PEx treated with broad anaerobe coverage were propensity-score matched to PEx treated with minimal anaerobic coverage. The primary outcome, % of baseline % predicted forced expiratory volume in one second (ppFEV 1) recovered, was compared between antibiotic categories with a linear mixed model. The secondary outcome, time to next PEx, was assessed using a Prentice Williams Petersen model. 514 PEx from 182 patients were included. Broad anaerobe coverage was used in 27% of PEx, and was used more often for older patients (p < 0.001) with worse baseline ppFEV 1 (p < 0.001), and with Achromobacter (p < 0.001) or Burkholderia infections (p = 0.002). In the matched PEx, broad anaerobe coverage was not a significant predictor of % of baseline ppFEV 1 recovered (∆ppFEV 1 = -2.4, p = 0.09). Broad anaerobe coverage was also not a significant predictor of time to next PEx (HR 0.89, 95% CI 0.7-1.13, p = 0.35). In this single center, retrospective study, antibiotics with broad activity against anaerobes were not associated with improved outcomes of CF PEx. [ABSTRACT FROM AUTHOR]

Chronic Obstructive Pulmonary Disease (COPD) is a multifaceted respiratory disorder characterized by progressive airflow limitation and systemic implications. It has become increasingly apparent that COPD exerts its influence far beyond the respiratory system, extending its impact to various organ systems. Among these, the musculoskeletal system emerges as a central player in both the pathogenesis and management of COPD and its associated comorbidities. Muscle dysfunction and osteoporosis are prevalent musculoskeletal disorders in COPD patients, leading to a substantial decline in exercise capacity and overall health. These manifestations are influenced by systemic inflammation, oxidative stress, and hormonal imbalances, all hallmarks of COPD. Recent research has uncovered an intricate interplay between COPD and musculoskeletal comorbidities, suggesting that muscle and bone tissues may cross-communicate through the release of signalling molecules, known as "myokines" and "osteokines". We explored this dynamic relationship, with a particular focus on the role of the immune system in mediating the cross-communication between muscle and bone in COPD. Moreover, we delved into existing and emerging therapeutic strategies for managing musculoskeletal disorders in COPD. It underscores the development of personalized treatment approaches that target both the respiratory and musculoskeletal aspects of COPD, offering the promise of improved well-being and quality of life for individuals grappling with this complex condition. This comprehensive review underscores the significance of recognizing the profound impact of COPD on the musculoskeletal system and its comorbidities. By unravelling the intricate connections between these systems and exploring innovative treatment avenues, we can aspire to enhance the overall care and outcomes for COPD patients, ultimately offering hope for improved health and well-being. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Depression and anxiety worsen COPD and lead to greater respiratory symptom severity and health care utilization. Fear of physical sensations of anxiety (AS-P) is known to exacerbate respiratory symptoms. The current study investigated the unique contribution of AS-P in respiratory symptom exacerbations, emergency department visits, hospitalizations, and COPD-related functional health status, controlling for medical characteristics, depression, and anxiety. The sample included 535 adults with COPD (M age = 56.57; 58.1% male). Participants were recruited from a web-based panel of adults with chronic respiratory disease and completed an online battery of self-report measures. Consistent with hypotheses, AS-P significantly increased the likelihood of acute symptom exacerbations by 12% and respiratory-related emergency department visits and hospitalizations by 7% during the prior 12 month period. Additionally, AS-P demonstrated a unique, large effect (f 2 = 0.37) on COPD-related functional health status. Fear of physical sensations contributed to worse respiratory outcomes and health care utilization among adults with COPD. Screening for AS-P may effectively identify at-risk COPD patients, while reducing AS-P through targeted interventions may result in decreased symptom severity, functional limitations, and burden on the health care system. [ABSTRACT FROM AUTHOR]

The objective of this study was to analyse lung function decline over time in bronchiectasis, along with the factors associated with it. Spirometry was measured every year in this observational, prospective study in 849 patients from the Spanish Bronchiectasis Registry (RIBRON). The main outcome was the decline in the rate of forced expiratory volume during the first second (FEV1). To be included in this study, patients needed a baseline assessment and at least one subsequent assessment. FEV1 decline was analysed using a mixed-effects linear regression model adjusted for clinically significant variables. We recruited 849 bronchiectasis patients with at least two annual lung function measurements (follow-up range 1–4 years). A total of 2262 lung function tests were performed (mean 2.66 per patient, range 2–5). Mean baseline FEV1 was 1.78 L (standard deviation (SD) 0.76; 71.3% predicted). Mean age was 69.1 (SD 15.4) years; 543 (64% women. The adjusted rates of FEV1 decline were –0.98% predicted/year (95% confidence interval (CI) –2.41 to –0.69) and –31.6 (95% CI –44.4 to –18.8) mL. The annual FEV1 decline was faster in those patients with chronic bronchial infection by Pseudomonas aeruginosa (–1.37% (52.1 mL) vs –0.37% (–24.6 mL); p < 0.001), greater age, increased number of severe exacerbations in the previous year and higher baseline FEV1 value. In patients with bronchiectasis, the annual rate of FEV1 decline was –31.6 mL/year and it was faster in older patients and those with chronic bronchial infection by P. aeruginosa , increased number of previous severe exacerbations and higher baseline FEV1 value. [ABSTRACT FROM AUTHOR]

• Serum CRP and calprotectin levels are highly variable between individuals during stable clinic visits. • Serum CRP and calprotectin are capable of discriminating pulmonary exacerbation from stable clinic visits. • A step-wise algorithm that incorporates both absolute and fold-change cut-offs can increase the diagnostic performance of these biomarkers. Cystic fibrosis (CF) pulmonary exacerbations (PEx) remain underdiagnosed by CF clinicians. Serum C-reactive protein (CRP) and calprotectin are inflammatory biomarkers that have the potential to aid in the diagnosis of PEx. 19 subjects (56 stable, 46 PEx visits) from a longitudinal study were included and the diagnostic performance of absolute and fold-change CRP and calprotectin cut-offs to discriminate stable and PEx visits was assessed. Based on Youden's index, optimal absolute and fold-change thresholds to identify PEx were 9.5 mg/L (Sn 76%, Sp 73%; AUC 0.76) and 2.2-fold (Sn 50%, Sp 96%; AUC 0.78) for CRP and 8.1 mg/L (Sn 61%, Sp 79%; AUC 0.72) and 1.3-fold (Sn 57%, Sp 88%; AUC 0.74) for calprotectin. A step-wise algorithm was able to improve diagnostic performance (Sn 80%; Sp 88%). CRP and calprotectin could discriminate stable vs. PEx visits with good performance and appear promising as diagnostic biomarkers but further validation studies are required prior to implementing these diagnostic thresholds. [ABSTRACT FROM AUTHOR]

• HRQOL in children with CF at age 5-years is lower than healthy children. • Early life pulmonary exacerbations are associated with worse HRQOL at age 5-years. • Nutritional status and FEV 1 is positively associated with HRQOL at age 5-years. • Parent-proxy and child self-reports of HRQOL in CF are not interchangeable. The impact of early cystic fibrosis (CF) on health-related quality-of-life (HRQOL) in preschool children is poorly characterised, and data on relationships between HRQOL and health outcomes in young children with CF are limited. We aimed to characterise and compare parent-proxy and child-reported HRQOL and evaluate relationships with clinical outcomes at age 5-years. Subjects were participating in the multi-centre Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial investigating BAL-directed versus standard CF therapy. Children aged 5-years and their parents rated HRQOL using the Pediatric Quality of Life Inventory (PedsQL™) and Cystic Fibrosis Questionnaire-Revised (CFQ-R) questionnaires. PedsQL and CFQ-R questionnaires were completed by 141 primary caregivers and 135 and 130 children, respectively. There were no differences in HRQOL between children randomised to BAL-directed versus standard CF therapy. Children with CF rated worse HRQOL than healthy children and there was poor parent-child concordance across HRQOL domains. Nutritional status, CF-CT scan score, forced expiratory volume in 1-second (FEV 1), and pulmonary exacerbations correlated with HRQOL at age 5-years. FEV 1 z-scores positively correlated with parent-proxy HRQOL in CFQ-R Respiratory (p = 0.018), Physical (<0.001), Emotional (p = 0.007) subscales and PedsQL Total-score (p = 0.021), Physical (p = 0.019) domains. Pulmonary exacerbation rates were inversely associated with parent-proxy CFQ-R Respiratory (p = 0.004), Physical (p = 0.022), PedsQL Total (p = 0.009) and Physical (p = 0.009) scores. Parent-reported HRQOL is a meaningful clinical endpoint to evaluate interventions in young children. Parent and child HRQOL reports provide different, complementary information. A preschool version of the CFQ-R is needed to assess relationships between HRQOL and clinical outcomes in young children. [ABSTRACT FROM AUTHOR]

• We utilised a real life, case control study with 105 patients; 72 on LUM/IVA and 33 controls. • LUM/IVA demonstrated a large reduction in exacerbations with an incident rate ratio of 0.455 (95%CI; 0.306 – 0.676), p < 0.001. • prolonged the time to first exacerbation and reduced the rate of decline in ppFEV1 over 12 months. • Adverse events were common; chest tightness or dyspnoea was experienced by 55% and resulted in cessation of treatment in 32%. Lumacaftor/ivacaftor (LUM/IVA) improves outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with ppFEV1 > 40%. There is limited safety or efficacy data in patients with ppFEV1 < 40%. We determined whether LUM/IVA in patients with ppFEV1 < 40 would reduce the rate of pulmonary exacerbations. This was a case control study performed on patients > 12 years, homozygous for Phe508del CFTR mutation and with ppFEV1 < 40%. Control subjects were matched for age, sex and ppFEV1, and had mutations ineligible for LUM/IVA. We assessed the rate of pulmonary exacerbations requiring intravenous antibiotics, the mean rate of change in ppFEV1 over 12 months and all adverse events. Data was collected from 7 Australian CF centres on 105 patients; 72 on LUM/IVA and 33 controls. LUM/IVA demonstrated a large reduction in exacerbations with an incident rate ratio of 0.455 (95%CI; 0.306 – 0.676), p < 0.001 after adjusting for the number of exacerbations in the previous 12 months. LUM/IVA prolonged the time to first exacerbation and reduced the rate of decline in ppFEV1 over 12 months. Adverse events were common; chest tightness or dyspnoea was experienced by 55% and resulted in cessation of treatment in 32%. Treatment with LUM/IVA resulted in a substantially lower rate of pulmonary exacerbations, prolonged time to first exacerbation and slowed the rate of decline of ppFEV1 in participants with severe lung disease. Adverse reactions to LUM/IVA however were unacceptably frequent, and resulted in a very high discontinuation rate. [ABSTRACT FROM AUTHOR]

Objective: Written action plans for patients with chronic obstructive pulmonary disease (COPD) aim at early recognition of exacerbations and self-initiation of interventions. Previous research suggest underuse of COPD action plans. We wanted to 1) examine which factors clinicians in specialist healthcare perceived as influencing clinicians' use of written action plans in COPD-self management support and 2) propose a framework for understanding the factors affecting clinicians' use of action plans in routine practice.Methods: We performed a theory-driven retrospective qualitative study. Documentary data were collected to describe the COPD action plan in context. In-depth interviews with clinicians (n = 8) were carried out. Interview data were thematically analyzed, using a predetermined model for understanding behavior.Results: Our study revealed that a number of factors influenced clinicians' use of action plans, including their capabilities (knowledge and skills to identify "the right patient" and to individualize the plan template) and motivations (beliefs, reinforcements, and emotions s.a. frustration, fear, and distrust), together with organizational and social opportunities (resources, patient, and GP preferences).Conclusion: A multilevel understanding of factors that affect clinicians' use of action plans in self-management support is needed.Practice Implication: The proposed framework can be used to guide future initiatives to promote targeted self-management support. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and recurrent pulmonary exacerbations. Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration and augment innate immunity. We examined the safety and efficacy of aerosolized xylitol use for 2 weeks in subjects hospitalized with a pulmonary exacerbation of CF. In a 2-week study, 60 subjects with cystic fibrosis and FEV 1 > 30% predicted were enrolled to receive aerosolized 7% hypertonic saline (4 ml) or 15% xylitol (5 ml) twice a day for 14 days. Outcomes assessed included change from baseline in FEV 1 % predicted, change in sputum microbial density, revised CF quality of life questionnaire including the respiratory symptom score, time to next hospitalization for a pulmonary exacerbation, and frequency of adverse events. 59 subjects completed the study (one subject in the saline group withdrew before any study product administration). No significant differences were noted between the 2 arms in mean changes in lung function, sputum microbial density for Pseudomonas aeruginosa and Staphylococcus aureus , body weight, quality of life, and frequency of adverse events. Aerosolized hypertonic xylitol was well-tolerated among subjects hospitalized for CF pulmonary exacerbation. Future studies examining efficacy for long term use in patients with CF lung disease would be worthwhile. The clinical trial registration number for this study is NCT00928135. • The mean change in lung function was not different between the treatment groups. • Improvement in FEV 1 and FVC, BMI and WBC at treatment completion in both groups. • No difference in the median time to next exacerbation between the groups. • No difference in the incidence of adverse events between the groups. [ABSTRACT FROM AUTHOR]

Minority groups of African descent experience disproportionately greater asthma morbidity compared with other racial groups, suggesting that genetic variation from a common ancestry could influence exacerbation risk. We evaluated clinical trial measures in the context of self-reported race and genetic ancestry to identify risk factors for asthma exacerbations. One thousand eight hundred forty multiethnic subjects from 12 Asthma Clinical Research Network and AsthmaNet trials were analyzed for incident asthma exacerbations with Poisson regression models that included clinical measures, self-reported race (black, non-Hispanic white, and other), and estimates of global genetic African ancestry in a subgroup (n = 760). Twenty-four percent of 1840 subjects self-identified as black. Black and white subjects had common risk factors for exacerbations, including a history of 2 or more exacerbations in the previous year and FEV 1 percent predicted values, whereas chronic sinusitis, allergic rhinitis, and gastroesophageal reflux disease were only associated with increased exacerbation risk in black subjects. In the combined multiethnic cohort, neither race (P =.30) nor percentage of genetic African ancestry as a continuous variable associated with exacerbation risk (adjusted rate ratio [RR], 1.26 [95% CI, 0.94-1.70; P =.13]; RR per 1-SD change [32% ancestry], 0.97 [95% CI, 0.78-1.19; P =.74]). However, in 161 black subjects with genetic data, those with African ancestry greater than the median (≥82%) had a significantly greater risk of exacerbation (RR, 3.06 [95% CI, 1.09-8.6; P =.03]). Black subjects have unique risk factors for asthma exacerbations, of which global African genetic ancestry had the strongest effect. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a common condition responsible for substantial morbidity, mortality, and costs in the United States. The economic burden of COPD is driven primarily by hospitalizations, with 1 in 5 hospitalized patients experiencing a 30-day readmission. Bronchodilators, delivered via handheld inhalers or nebulizers, are the mainstay of therapy for COPD. However, differences in outcomes between short- and long-acting therapies are unclear. We examined real-world differences in 30-day readmission and exacerbation rates between Medicare beneficiaries with COPD treated with a nebulized long-acting beta 2 -agonist (arformoterol tartrate [ARF]) and beneficiaries treated with a nebulized short-acting beta 2 -agonist (SABA) for maintenance therapy after hospital discharge. Truven MarketScan Hospital Drug Database and Medicare files were probabilistically matched between 2009 and 2013 to identify beneficiaries who were aged ≥65 years and discharged from a hospital with a primary COPD diagnosis or a secondary COPD diagnosis and a primary diagnosis for another respiratory condition. Matching was performed by using COPD hospitalization date (±7 days) and source, length of stay (±1 day), discharge date and destination, and hospital region. After applying additional inclusion/exclusion criteria, 2 cohorts were created: nebulized ARF users (n = 953) and nebulized SABA users (n = 6939). Logistic regression analyses were used to examine 30-day readmission (all-cause and COPD related) and exacerbation rates. Odds ratios (ORs), 95% CIs, and P values were computed. On average, nebulized SABA users had more comorbidities than nebulized ARF users, including diabetes, atrial fibrillation, renal disease, musculoskeletal disease, myocardial infarction, and cognitive impairment (all, P < 0.0001). However, nebulized ARF users had a higher average COPD severity score than nebulized SABA users (49.5 v. 38.0; P < 0.001). COPD therapies at baseline were similar in both cohorts and included systemic corticosteroids (≥65%), short-acting bronchodilators (≥33%), and inhaled corticosteroids + long-acting beta 2 -agonists (30%). After adjusting for sociodemographic and hospital characteristics, concomitant medications, and case-mix, nebulized ARF users had 27% lower odds of an all-cause readmission (OR, 0.73; 95% CI, 0.59–0.92; P = 0.008) and 23% lower odds of a COPD-related readmission (OR, 0.77; 95% CI, 0.60–0.98; P = 0.032) at 30 days compared with users of a nebulized SABA. No difference was found in 30-day exacerbation rates between the cohorts. Nebulized ARF users had lower 30-day readmission rates, greater COPD severity, and fewer comorbidities than nebulized SABA users. In this population, maintenance treatment with ARF reduced costly COPD outcomes. [ABSTRACT FROM AUTHOR]

L'azithromycine est un macrolide de plus en plus utilisé pour ses propriétés anti-inflammatoires dans les pathologies bronchiques chroniques. Ce traitement peut être proposé à des patients atteints de dilatation des bronches, d'asthme et de bronchopneumopathie chronique obstructive sévère ayant eu plus de 3 exacerbations par an ou ayant eu une dégradation de leur fonction respiratoire malgré un traitement de fond optimal bien conduit. Malgré l'efficacité sur le nombre d'exacerbations, l'utilisation des macrolides au long cours doit faire l'objet de précaution du fait de ses toxicités cardiovasculaires, otologiques et de l'émergence de bactéries résistantes. De plus, les études restent insuffisantes pour établir la posologie optimale ainsi que la durée des traitements par azithromycine. Azithromycin is a macrolide widely used in chronic bronchial diseases due to its anti-inflammatory properties. This treatment is prescribed to patients with bronchiectasis, asthma and severe chronic obstructive pulmonary disease who present more than 3 exacerbations per year or a deterioration of respiratory function despite an optimal treatment. Macrolides decrease the number of exacerbation but azythromycine must be prescribed carefully. Indeed, it involves potential cardiovascular and otological toxicities and the emergence of resistant bacteria. In addition, studies remain insufficient to establish the optimal dosage and duration of azithromycine. [ABSTRACT FROM AUTHOR]

• The STOP-OB study collected respiratory symptom changes with exacerbation treatment. • Symptoms were collected by Chronic Respiratory Infection Symptom Score (CRISS). • >90% of subjects had a minimal clinically important CRISS change (11) by day 14. • Younger age and higher CRISS baselines were associated with greater CRISS response. • CRISS has good dynamic range and may be a useful endpoint in exacerbation studies. : Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822. : Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression. : Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041). : CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized. [ABSTRACT FROM AUTHOR]

Outdoor air pollution is increasingly identified as a contributor to respiratory and cardiovascular disease. Pro-inflammatory particles and gases are inhaled deep into the lungs, and are associated with impaired lung growth and exacerbations of chronic respiratory diseases. The magnitude of these effects are of interest to patients and families, and have been assessed in studies specific to CF. Using systematic review methodology, we sought to collate these studies in order to summarise the known effects of air pollution in cystic fibrosis, and to present information on decreasing personal air pollution exposures. [ABSTRACT FROM AUTHOR]

Background: Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined. Objective: We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function. Methods: NET protein complexes (DNA-elastase and histoneelastase complexes), cell-free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome. Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation. Results: Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001). This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P 5.002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P 5 .009) and dominance of Haemophilus species operational taxonomic units (P 5 .01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD. Conclusion: NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity. [ABSTRACT FROM AUTHOR]

It is necessary to evaluate the severity of asthma exacerbations for subjective symptoms and objective indicators. When patients cannot perform spirometry, oscillometry is a surrogate test. We assessed the usefulness of oscillometry for the evaluation of treatment responsiveness in patients with asthma exacerbations. The subjects included 21 consecutive patients with asthma exacerbations. Symptomatic responses, oscillometry, and spirometry (if possible) were assessed before and after treatment with corticosteroids and aminophylline. After treatment, all of the patients were allowed to return home and had no hospital visits. Oscillometry was feasible in all patients; however, spirometry could not be performed in 9 patients. Overall, there was a significant improvement in wheezing scores and oscillometric parameters, but not in FEV1 after treatment. The thresholds for a positive bronchodilator response in oscillometry were observed in 4 or more patients, while the minimal clinically important differences in FEV1 were observed in one patient. Oscillometry can detect improvements that cannot • Severity of asthma exacerbations should be evaluated subjectively and objectively. • When patients cannot perform spirometry, oscillometry is a surrogate test. • Oscillometry can detect improvements that cannot be detected by spirometry or wheezing. [ABSTRACT FROM AUTHOR]

Rhinoviruses (RVs) are the most common trigger for asthma exacerbations, and there are currently no targeted therapies for viral-induced asthma exacerbations. RV infection causes neutrophilic inflammation, which is often resistant to effects of glucocorticoids. IL-1 receptor antagonist (IL-1RA) treatment reduces neutrophilic inflammation in humans challenged with inhaled endotoxin and thus may have therapeutic potential for RV-induced asthma exacerbations. We sought to test the hypothesis that IL-1RA treatment of airway epithelium reduces RV-mediated proinflammatory cytokine production, which is important for neutrophil recruitment. Human bronchial epithelial cells from deceased donors without prior pulmonary disease were cultured at air-liquid interface and treated with IL-13 to approximate an asthmatic inflammatory milieu. Human bronchial epithelial cells were infected with human RV-16 with or without IL-1RA treatment. RV infection promoted the release of IL-1α and the neutrophil-attractant cytokines IL-6, IL-8, and CXCL10. Proinflammatory cytokine secretion was significantly reduced by IL-1RA treatment without significant change in IFN-β release or RV titer. In addition, IL-1RA reduced MUC5B expression after RV infection without impacting MUC5AC. These data suggest that IL-1RA treatment significantly reduced proinflammatory cytokines while preserving the antiviral response. These results provide evidence for further investigation of IL-1RA as a novel targeted therapy against neutrophil-attractant cytokine release in RV-induced airway inflammatory responses. [ABSTRACT FROM AUTHOR]

The primary goals of long-term disease management in non-cystic fibrosis bronchiectasis (NCFB) are to reduce the number of exacerbations, and improve quality of life. However, currently no therapies are licensed for this. Ciprofloxacin Dry Powder for Inhalation (Ciprofloxacin DPI) has potential to be the first long-term intermittent therapy approved to reduce exacerbations in NCFB patients. The RESPIRE programme consists of two international phase III prospective, parallel-group, randomized, double-blinded, multicentre, placebo-controlled trials of the same design. Adult patients with idiopathic or post-infectious NCFB, a history of ≥ 2 exacerbations in the previous 12 months, and positive sputum culture for one of seven pre-specified pathogens, undergo stratified randomization 2:1 to receive twice-daily Ciprofloxacin DPI 32.5 mg or placebo using a pocket-sized inhaler in one of two regimens: 28 days on/off treatment or 14 days on/off treatment. The treatment period is 48 weeks plus an 8-week follow-up after the last dose. The primary efficacy endpoints are time to first exacerbation after treatment initiation and frequency of exacerbations using a stringent definition of exacerbation. Secondary endpoints, including frequency of events using different exacerbation definitions, microbiology, quality of life and lung function will also be evaluated. The RESPIRE trials will determine the efficacy and safety of Ciprofloxacin DPI. The strict entry criteria and stratified randomization, the inclusion of two treatment regimens and a stringent definition of exacerbation should clarify the patient population best positioned to benefit from long-term inhaled antibiotic therapy. Additionally RESPIRE will increase understanding of NCFB treatment and could lead to an important new therapy for sufferers. Trial registration: The RESPIRE trials are registered in ClinicalTrials.gov , ID number NCT01764841 (RESPIRE 1; date of registration January 8, 2013) and NCT02106832 (RESPIRE 2; date of registration April 4, 2014). [ABSTRACT FROM AUTHOR]

Résumé L’asthme affecte environ 300 millions de personnes dans le monde. C’est un important problème de santé publique qui concerne tous les âges, du nourrisson aux personnes âgées. Depuis plus de 30 ans, on observe une forte augmentation de sa prévalence dans la plupart des pays du monde, à l’origine d’une forte morbidité et de coûts da santé élevés. La mise au point du global initiative for asthma 2015 (GINA) a pour but d’informer les pneumologues et tous les médecins susceptibles de prendre en charge un patient asthmatique. Elle est également destinée à tous les professionnels de santé et aux familles. Pour information, le lecteur est renvoyé à la mise au point du GINA 2015 « Diagnostic et prise en charge de l’asthme chez les enfants âgés de 5 ans et moins ». Compte tenu du volume des recommandations du GINA (28 pages), cette analyse concerne l’essentiel de ce que l’on doit savoir. Cette mise à jour 2015 aborde successivement : (i) ce que l’on sait sur l’asthme ; (ii) le diagnostic de la maladie ; (iii) l’évaluation de l’asthmatique ; (iv) la prise en charge de l’asthme ; (v) les exacerbations. Un glossaire des médicaments antiasthmatiques termine le guide. Asthma now affects about 300 million people our world. This important public health problem concerns people of all ages, from young infants to elderly people. Since more than 30 years, there has been an important increase in the prevalence of asthma in most parts of the world, and this has led to much more poor health and greater health expenditures. The updated Global initiative for asthma (GINA) 2015 is meant to be of interest to pneumologists and all physicians who are likely to treat asthmatic patients, but it is equally aimed at all health professionals and to patients’ families. Those with a particular interest are directed to the section of GINA 2015 on “Diagnosis and management of asthma in children less than 6 years of age”. Considering the large number of recommendations in GINA 2015 (28 pages), the present analysis concerns only the essence of what one should know. It considers in sequence: (i) much of what is known about asthma; (ii) the diagnosis of asthma; (iii) evaluation of the asthmatic; (iv) management of the asthmatic patient; and (v) asthma exacerbations. A glossary of anti-asthmatic drugs is given at the end of the document. [ABSTRACT FROM AUTHOR]

Despite current treatments, patients with myasthenia gravis (MG) experience unpredictable and inadequately controlled symptoms, lending to variability in the clinical and economic burden of disease. However, limited data are available on MG healthcare costs, and specifically, no data on patients initiating second-line therapy. Using claims data from the IBM® MarketScan® database, we assessed patient characteristics, healthcare resource utilization, and costs among MG patients initiating second-line therapy, and identified potential factors associated with high healthcare costs over a two-year follow-up period. We identified 1498 patients, of whom 49% and 31% received chronic steroids and non-steroidal immunosuppressants (NSISTs) as their second-line therapy, respectively. During follow-up, 49% experienced ≥1 MG exacerbation. Among all patients, mean all-cause total healthcare cost was $106,821 per patient during follow-up, with $88,040 and $18,780 attributed to medical and pharmacy costs, respectively. In a multivariable analysis, variables significantly associated with high cost included use of high-dose steroids, chronic intravenous immunoglobulin (IVIg, ≥6 cycles), and 1 and ≥ 4 (but not 2–3) MG exacerbations in the first year after second-line therapy initiation. Any number of exacerbations were associated with high cost in a univariable analysis. A stratified cost analysis showed that patients with >1 exacerbation, ≥1 treatment switch, and high-dose steroid use in this first year experienced $198,487, $114,037, and $79,752 mean MG-related total healthcare spend during follow-up, respectively. These data suggest that patients receiving chronic IVIg or NSISTs for MG experience significant economic burden. Disease characteristics including exacerbation and treatment history may be an indicator of future high costs. • Limited HCRU data exist on patients with MG initiating second-line therapy. • This was a real-world study of HCRU in MG patients initiating second-line therapy. • There are potential attributes associated with higher MG-related healthcare cost. • Exacerbation and treatment history may be indicators of future high costs. [ABSTRACT FROM AUTHOR]

Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ–induced epithelial cell signature and a tissue resident memory T-cell signature. Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ–induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell–associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Patients with asthma have a higher incidence of obstructive sleep apnea (OSA). However, the association between OSA and the exacerbation of severe asthma remains unclear. In this study, we aimed to investigate the prevalence of OSA in a cross-sectional study of asthma patients and to prospectively examine the significance of the effect of OSA on severe asthma exacerbations.Methods: One hundred and forty-six patients with asthma and 157 matched-controlled individuals were enrolled in this study. The patients with asthma were prospectively studied for one year, and exacerbation episodes were identified based on the patients' medical histories. Lung function and the percentages of eosinophils in induced sputum samples were determined, and the frequencies of severe asthma exacerbations during the previous year were evaluated in the group of patients with asthma.Results: The rates of OSA were 19.2% (28/146) among the patients with asthma and 9.6% (15/157) among the control individuals (p = 0.016). The frequency of severe asthma exacerbations was significantly higher among the asthma patients with OSA compared with those who did not have OSA (p < 0.001). The apnea-hypopnea index (AHI) correlated significantly with the number of severe asthma exacerbations (r = 0.507, 95% confidence interval [CI] 0.357-0.637, p < 0.001). Logistic regression analyses determined that the AHI was significantly associated with the occurrence of severe asthma exacerbations (odds ratio 1.322, 95% CI 1.148-1.523, p < 0.001).Conclusions: Patients with asthma had a high prevalence of OSA, which was an important factor associated with severe asthma exacerbations. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic disease in childhood and places a significant burden on public and private health systems. This retrospective cohort analysis utilised administrative healthcare claims data (US Clinformatics™ Multiplan database; compliant with the US Department of Health & Human Services Health Insurance Portability and Accountability Act) to characterise asthma exacerbations requiring intervention in a US paediatric patient population. Methods: Patients aged > 1-17 years with a recorded asthma diagnosis and receiving treatment were identified in the US Clinformatics™ Multiplan database over a 9-year period (2004-2012). Both incident and prevalent cases of asthma were included, with the most recently recorded asthma diagnosis designated as the index date. The 12-month period following the index date was analysed for asthma exacerbations, defined as an event requiring treatment with systemic corticosteroid or resulting in an asthma-related hospitalisation or emergency department visit. Results: Data from 734,114 children with asthma (41.5 % females, 58.5 % males) were analysed, of this cohort 34.4 % experienced ≥ 1 exacerbation during the follow-up period. The proportion who experienced ≥ 1 exacerbation increased from 28.9 % in 2004 to 36.3 % in 2012, based on the reported index date. Their mean annual exacerbation frequency was 1.4; 85.8 % of exacerbations were defined by systemic corticosteroids use. A consistent trend of increased exacerbation incidence in the fall and early winter was observed, in particular exacerbations defined by systemic corticosteroid use. A greater proportion of asthma-related hospitalisations were associated with younger age. Conclusions: Approximately one-third of children experienced ≥ 1 exacerbation in real-world clinical practice. A targeted treatment approach with a focus on those with a history of recurrent exacerbations is recommended to improve asthma control. This targeted approach could also minimise the frequent systemic corticosteroid exposure particularly at an early age when side effects of systemic corticosteroids are more pronounced. [ABSTRACT FROM AUTHOR]

Objective: Living in an area with a high density of livestock farms has been associated with adverse respiratory health effects in some studies. As patients with COPD and asthma already have a compromised respiratory function and chronic airway inflammation, they are expected to be at increased risk for adverse respiratory health effects. The objective of this study was to assess the association between livestock exposure and exacerbations in COPD and asthma. Methods: 899 COPD and 2546 asthma patients from 15 general practices in a rural area with a high livestock density and 933 COPD and 2310 asthma patients from 15 practices in a control area in the Netherlands were included. Occurrence of exacerbations was based on the pharmaceutical treatment of exacerbations in COPD and asthma patients using 2006-2012 prescription data of electronic medical records. Farm exposure was assessed by comparing the study area with the control area, and with individual exposure estimates in the study area using Geographic Information System data. Results: The exacerbation rate was higher in the study area compared with the control area in COPD (IRR: 1.28; 95%CI: 1.06-1.55), but not in asthma patients (IRR: 0.87; 95%CI: 0.72-1.05). In general, individual exposure estimates in the study area were not associated with exacerbations. COPD patients living within a 500m radius of up to12,499 chickens had a 36% higher exacerbation rate (IRR: 1.36; 95%CI: 1.03-1.79). Conclusions: Living in an area with a high livestock density is a risk factor for exacerbations in COPD patients. The environmental exposure responsible for this increased risk remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background/purpose: Evidence for the effectiveness of the new multidimensional GOLD (Global Initiative for Chronic Obstructive Lung Disease) classification is currently limited. The new classification has been validated in the United States and Europe, but validation in Asian patients is still lacking. We examined the abilities of the GOLD 2013 classification to predict clinical outcomes in Taiwanese patients with chronic obstructive pulmonary disease (COPD).Methods: Patients with COPD were recruited from January 2006 to December 2012 and followed up for exacerbation and mortality. The predictive abilities of various assessments were compared through logistic regression analysis using receiver operating curve (ROC) estimations and area under the curve (AUC).Results: A total of 471 patients with COPD were analyzed. The GOLD 2013 groups at high risk of exacerbation (C and D) experienced a higher average number of exacerbations per year (2.1 ± 3.1 vs. 0.3 ± 1.0, p < 0.001) than the low risk groups (A and B). The mortality rates were 10.1% in GOLD 2013 Group A, 14.1% in Group B, 4.0% in Group C, and 30.5% in Group D. The AUC values for GOLD 2013 and GOLD 2007 were 0.78 versus 0.67 (p < 0.001) for exacerbation, and 0.66 versus 0.61 (p = 0.15) for mortality.Conclusion: The GOLD 2013 classification has powerful ability to predict exacerbation, but poor ability to predict mortality. The prognostic validity of the GOLD 2013 classification to predict exacerbations was better than the GOLD 2007 classification. [ABSTRACT FROM AUTHOR]

Background: IgE sensitization to Aspergillus fumigatus and a positive sputum fungal culture result are common in patients with refractory asthma. It is not clear whether these patients would benefit from antifungal treatment. Objectives: We sought to determine whether a 3-month course of voriconazole improved asthma-related outcomes in patients with asthma who are IgE sensitized to A fumigatus. Methods: Asthmatic patients who were IgE sensitized to A fumigatus with a history of at least 2 severe exacerbations in the previous 12 months were treated for 3 months with 200 mg of voriconazole twice daily, followed by observation for 9 months, in a double-blind, placebo-controlled, randomized design. Primary outcomes were improvement in quality of life at the end of the treatment period and a reduction in the number of severe exacerbations over the 12 months of the study. Results: Sixty-five patients were randomized. Fifty-nine patients started treatment (32 receiving voriconazole and 27 receiving placebo) and were included in an intention-to-treat analysis. Fifty-six patients took the full 3 months of medication. Between the voriconazole and placebo groups, there were no significant differences in the number of severe exacerbations (1.16 vs 1.41 per patient per year, respectively; mean difference, 0.25; 95% CI, 0.19-0.31), quality of life (change in Asthma Quality of Life Questionnaire score, 0.68 vs 0.88; mean difference between groups, 0.2; 95% CI, -0.05 to -0.11), or any of our secondary outcome measures. Conclusion: We were unable to show a beneficial effect of 3 months of treatment with voriconazole in patients with moderate-to-severe asthma who were IgE sensitized to A fumigatus on either the rate of severe exacerbations, quality of life, or other markers of asthma control. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Mycology / Journal de Mycologie Médicale is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Introduction: Chronic obstructive pulmonary disease (COPD) is a very common disease of the respiratory system. An increasing number of clinical trials on Weijing formula in the management of acute exacerbations of COPD have been performed, but the evidence base remains unknown. However, the evidence base for it remains unknown. This review aimed to evaluate the efficacy and safety of Weijing formula in the treatment of COPD exacerbations by systematically summing up the evidence from all available trials. Methods: Four English language databases and 4 Chinese databases were searched to identify relevant randomized controlled trials from their respective inception up to June 2013. The electronic search was supplemented with a manual search. The Cochrane tool was used for the assessment of risk of bias in the included trials. The following outcomes were evaluated: (1) lung function; (2) arterial blood gases; (3) serum levels of inflammatory mediators; and (4) adverse events. Data were analyzed using STATA 12.0 software. Results: A total of 11 studies that compared Weijing formula combined with conventional Western medications with the same conventional Western medications alone were included. In general, the methodological quality of the included trials was relatively poor. Due to the poor quality of the available studies and obvious heterogeneity across studies, we did not perform any pooled analysis. The results of this systematic review indicate that, in general, the effects of Weijing formula combined with conventional Western medications were no worse than those of the same conventional Western medications alone. In most cases, compared with Western medications alone, the combined use of Weijing formula and Western medications could significantly improve PaO2, and lung function measured as FEV1, FEV1% predicted and FEV1/FVC ratio, and reduce PaCO2 and the serum levels of TNF-α and IL-8. No adverse events were reported in all included studies except one study. Conclusions: Within the limitations of this systematic review, we may conclude that compared with Western medications alone, the addition of Weijing formula seems to provide more benefits for patients with COPD exacerbations, without any serious adverse reactions being identified. There is encouraging evidence suggesting that Weijing formula in conjunction with Western medications may be a safe and effective treatment option for patients experiencing COPD exacerbations. However, further rigorously designed studies are warranted. [Copyright &y& Elsevier]

Objectives: Relapse management is a crucial component of multiple sclerosis (MS) care. High-dose corticosteroids (CSs) are used to dampen inflammation, which is thought to hasten the recovery of MS relapse. A diversity of mechanisms drive the heterogeneous clinical response to exogenous CSs in patients with MS. Preclinical research is beginning to provide important insights into how CSs work, both in terms of intended and unintended effects. In this article we discuss cellular, systemic, and clinical characteristics that might contribute to intended and unintended CS effects when utilizing supraphysiological doses in clinical practice. The goal of this article is to consider recent insights about CS mechanisms of action in the context of MS. Methods: We reviewed relevant preclinical and clinical studies on the desirable and undesirable effects of high-dose corticosteroids used in MS care. Results: Preclinical studies reviewed suggest that corticosteroids may act in unpredictable ways in the context of autoimmune conditions. The precise timing, dosage, duration, cellular exposure, and background CS milieu likely contribute to their clinical heterogeneity. Conclusion: It is difficult to predict when patients will respond favorably to CSs, both in terms of therapeutic response and tolerability profile. There are specific cellular, systemic, and clinical characteristics that might merit further consideration when utilizing CSs in clinical practice, and these should be explored in a translational setting. [ABSTRACT FROM AUTHOR]