Subsequent Exacerbation Research Articles

The Role of Environmental Controls in Managing Asthma in Lower-Income Urban Communities.

Children living in lower-income urban communities are at much greater risk of developing asthma, going to the emergency department for an asthma attack and being hospitalized for asthma than children living in upper- and middle-income communities. For many asthmatic children living in urban communities, especially those with greater morbidity, the allergic pathway is important in the etiology of the disease. The stages of developing allergic disease can be divided into the onset of allergic sensitization, development of allergic disease and subsequent exacerbations, and it is useful to consider the relevance of interventions at each of these stages. Indoor allergens and environmental exposures are a major contributor to allergic disease, particularly among lower socioeconomic status, urban, minority communities. These exposures include allergens, environmental tobacco smoke, combustion by-products, and mold, all of which can play an important role in asthma progression as well as morbidity. These exposures are often not found in isolation and thus these concomitant exposures need to be considered when conducting environmental interventions. There have been numerous studies looking at both primary and tertiary prevention strategies and the impact on allergic sensitization and asthma with varied results. While the outcomes of these studies have been mixed, what has emerged is the need for tertiary interventions to be targeted to the individual and to reduce all relevant exposures to which an asthmatic child is exposed and sensitized. In addition, effective intervention strategies must also consider other social determinants of asthma morbidity impacting low socioeconomic, urban communities.

Assessment of stability and fluctuations of cultured lower airway bacterial communities in people with cystic fibrosis

BackgroundRoutine clinical culture detects a subset of the cystic fibrosis (CF) airways microbiota based on culture-independent (molecular) methods. This study aimed to determine how extended sputum culture of viable bacteria changes over time in relation to clinical status and predicts exacerbations. MethodsSputa from patients at a baseline stable and up to three subsequent time-points were analysed by extended-quantitative culture; aerobe/anaerobe densities, ecological indexes and community structure were assessed together with clinical outcomes. ResultsEighty patients were prospectively recruited. Sputa were successfully collected and cultured at 199/267 (74.5%) study visits. Eighty-two sputa from 25 patients comprised a complete sample-set for longitudinal analyses. Bacterial density, ecological indexes and clinical outcomes were unchanged in 18 patients with three sequential stable visits. Conversely, in 7 patients who had an exacerbation, total bacterial and aerobe densities differed over four study visits (P < .001) with this difference particularly apparent between the baseline visit and completion of acute antibiotic treatment where a decrease in density was observed. Bacterial communities were more similar within than between patients but stable patients had the least variation in community structure over time. Using logistic regression in a further analysis, baseline features in 37 patients without compared to 15 patients with a subsequent exacerbation showed that clinical measures rather than bacterial density or ecological indexes were independent predictors of an exacerbation. ConclusionsGreater fluctuation in the viable bacterial community during treatment of an exacerbation than between stable visits was observed. Extended-quantitative culture did not provide prognostic information of a future exacerbation.

Dynamic changes in marines' reports of PTSD symptoms and problem alcohol use across the deployment cycle.

Posttraumatic stress disorder (PTSD) and alcohol misuse are commonly co-occurring problems in active-duty service members (SMs) and veterans. Unfortunately, relatively little is known about the temporal associations between these problems in the acute period following exposure to combat stressors. Discerning the temporal associations between these problems across the deployment cycle could inform prevention and treatment efforts. In this study, we examined the association between PTSD symptom severity and problem alcohol use in a large cohort of United States Marines (n = 758) evaluated prior to deployment and approximately 1, 5, and 8 months postdeployment. Results indicate that problem alcohol use was associated with a subsequent exacerbation of PTSD symptoms between the 1st and 2nd and 2nd and 3rd postdeployment assessments. PTSD symptom severity was associated with increased problem alcohol use between the 1st and 2nd postdeployment assessments. These findings suggest that problem drinking may lead to new onset or worsening of PTSD symptoms over time and that SMs with greater PTSD symptom severity upon returning from deployment may increase alcohol use in the weeks immediately following homecoming. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Faecal Microbiota Dynamics and their Relation to Disease Course in Crohn's Disease.

BackgroundMicrobial shifts have been associated with disease activity in Crohn’s disease [CD], but findings on specific taxa are inconsistent. This may be due to differences in applied methods and cross-sectional study designs. We prospectively examined the faecal microbiota in adult CD patients with changing or stable disease course over time.MethodsFaeces were collected at two time-points from 15 healthy control individuals [HCs], 35 CD patients who were in remission and who maintained remission [RRs], and 22 CD patients during remission and also during subsequent exacerbation [RAs]. The microbial composition was assessed by 16S rRNA [V4] gene sequencing.ResultsCompared with HCs, patients with CD had a lower microbial richness [p = 0.0002] and diversity [p = 0.005]. Moreover, the microbial community structure of a subset of patients, clustered apart from HCs, was characterized by low microbial diversity and Faecalibacterium abundance. Patients within this cluster did not differ with respect to long-term disease course compared with patients with a ‘healthy-appearing’ microbiota.Over time, microbial richness and diversity did not change in RR versus RA patients. Although the microbial community structure of both RR and RA patients was less stable over time compared with that of HCs, no differences were observed between the patient groups [p = 0.17]; nor was the stability impacted by Montreal classification, medication use, or surgery.ConclusionThe altered microbiota composition and stability in CD was neither associated with disease activity nor long-term disease course, questioning its involvement in the development of an exacerbation. The aberrant microbiota composition in a subset of CD patients warrants further exploration of a more microbiota-driven etiology in this group.

Streptococcal Infections and Exacerbations in PANDAS: A Systematic Review and Meta-analysis.

The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) hypothesis suggests an association between group A beta-hemolytic streptococcus (GABHS) infections and subsequent onset or exacerbation of neuropsychiatric symptoms, such as obsessive-compulsive disorder or tic disorders. We performed a systematic review and meta-analysis including longitudinal, prospective studies on exacerbations of neuropsychiatric symptoms associated with GABHS infections in children with PANDAS. We searched PubMed and EMBASE through August 14, 2017. Two independent reviewers extracted data and we used random-effects analysis to calculate rate ratios (RR). Three studies were included with a total of 82 PANDAS cases and 127 control children with obsessive-compulsive disorder or chronic tic disorder. PANDAS cases had a nonsignificantly increased RR of 2.33 [95% confidence interval [CI]: 0.63-8.70, P = 0.21, I = 28.3%] for exacerbations of neuropsychiatric symptoms in temporal proximity to a GABHS infection and no increased risk of GABHS infections (RR = 0.99, 95% CI: 0.56-1.73, P = 0.97, I = 45%) compared with the control children. However, PANDAS cases had an increased risk of neuropsychiatric exacerbations in general with a RR of 1.54 (95% CI: 1.12-2.11, P = 0.008, I = 0%) compared with the control children. The studies had methodologic heterogeneity, high risk of selection bias and differed concerning case definition and infection measures. Our findings did not show significant evidence concerning higher rates of temporally associated GABHS infections and exacerbations of neuropsychiatric symptoms in children with PANDAS. The included studies were small and limited by low GABHS rates and exacerbations. Future studies with large population sizes and routine evaluations are needed to thoroughly examine the PANDAS hypothesis.

Buy now, pay later: American military intervention and the strategic cost paradox

ABSTRACTThis paper explores the notion that US efforts to evade the political costs of war paradoxically contribute to the subsequent exacerbation of costs over time. Leaders seek to purchase political capital in the short term by limiting the costs and requirements of military operations, but in doing so cause strategic and political liabilities to mount in the long run. While identification of such behaviour is not new, insufficient attention has been devoted to explaining its causes, dynamics, and manifestations in relation to key decisions on and in war. Evidence derived from studies of recent American discretionary campaigns is analysed to advance an argument with respect to this pattern of self-defeating strategic behaviour.

Predicting Lung Healthiness Risk Scores to Identify Probability of an Asthma Attack

For asthma, monitoring of symptoms and progression of the disease while avoiding triggers and minimizing the frequency of attacks are the main objectives of care. Tracking and analyzing lung healthiness, symptoms, medications, level of interference with daily life activities provides a hint of the level of severity of asthma, and that is indeed a strong predictor of subsequent and future exacerbations. In a prior effort, we employed Text Classification method to classify asthma severity. However, asthma attack prediction depends on many other risk factors such as physiological measurements, patient behaviors and characteristics, environmental triggers, and personal risk scores. In this paper, we propose a method to forecast future asthma attacks using historical data linking the asthma severity level and the personalized risk scores of triggers. Specifically, we used the Additive Interaction Analysis of Exposures technique combined with the Long Short-Term Memory method to predict risk scores of respiratory and oxygen saturation. These risk scores are then used to forecast the probability of an asthma attack.

Dynamics of homeostasis and the outcome of sarcoidosis of the respiratory system in the treatment of corticosteroids

The outcome of sarcoidosis of the respiratory system is closely linked to the state of homeostasis and reactivity. Monitoring their status is possible through immunological, biochemical and hormonal studies. Within common medical institutions re-executing these studies is not always possible for a number of reasons. Therefore, the research for the availability and informative criteria of homeostasis and reactivity state was initiated at the end of XIXth century and continues until now. At the Department of Phthisiopulmonology of the First St.-Petersburg state medical University Academy I. P. Pavlov. University, new accessible and informative diagnostic criteria for estimation the state of homeostatic balance of the organism are developed. They are based on research of the general adaptation syndrome and the discovery of antistress types of adaptive reactions of the organism. In this regard, based on the leukogram evaluation following diagnostic criteria were developed and tested: leukocyte-lymphocytic index, types of adaptive reactions, entropy and redundancy of formed elements of white blood cells, extent of disturbance of homeostasis, indices of proliferation and differentiation of monocytes and reactivity types. Unfortunately, in the pulmonology clinics, they are used today only in single cases. The monitoring of homeostasis and reactivity indicators in patients with respiratory system sarcoidosis had a high working performance. It is established that in sarcoidosis the best treatment effect with corticosteroids with minimal residual changes of respiratory system took place in patients with the appropriate type of reactivity and normal range of other indicators. Pathological reactivity of an organism, especially hyporeactive and areactive types, are always accompanied by formation of pronounced residual sarcoidosis changes in the respiratory tract, which is the basis for the subsequent exacerbation (recurrence) of sarcoidosis.

Evaluation of Epstein-Barr virus-specific antibodies in Cypriot multiple sclerosis patients

Multiple Sclerosis (MS) is a chronic, demyelinating, inflammatory disease of the central nervous system (CNS) with a strong autoimmune component. Several genetic and environmental factors have been suggested to contribute in MS. The Epstein-Barr virus (EBV) is one pathogenic candidate proposed to be involved in the onset of MS and/or induction of subsequent exacerbations. The possible involvement of EBV in MS is highlighted by a number of national epidemiological studies showing a higher percentage of EBV seropositivity. This study aims to evaluate for the first time the seroprevalence of EBV in Cypriot MS patients. The serum of 133 MS patients and 101 healthy controls (HCs) was used to determine the positivity index of the EBV nuclear antigen-1 (EBNA-1) IgG, viral capsid antigen (VCA) IgG, and early antigen-D (EA-D) IgG, using ELISA. All MS patients were seropositive for both EBNA-1 IgG and VCA IgG as compared to 94.1% (Fisher’s exact test, p = 0.0059) and 93.1% (Fisher’s exact test, p = 0.0025) of HCs respectively. Furthermore, the positivity indexes of both antibodies were significantly higher in MS patients. There was no significant difference in the presence/absence of EA-D IgG between the two groups nor in the corresponding P.I. levels. The results obtained, revealing higher seropositivity of EBNA-1 IgG and VCA IgG in MS patients, seem to concur with previous findings of studies in other countries, thereby further asserting the theory of EBV involvement in MS.

First-episode schizophrenia is associated with a reduction of HERV-K methylation in peripheral blood

Human endogenous retroviruses (HERV) have been widely associated with schizophrenia etiology. Aberrant epigenetic processes may play a role in the etiology of schizophrenia. In this study, we tested whether schizophrenia patients at different stages of illness might present alterations in the levels of HERV-K methylation. We recruited 49 first-episode schizophrenia (FES) patients with 47 age- and sex-matched healthy controls (HCs), and 100 multi-episode schizophrenia (MES) patients with 50 age- and sex-matched HCs. Based on the Schedule for Deficit Schizophrenia, patients with MES were also divided into two subgroups: deficit (D-SCZ) and non-deficit schizophrenia (ND-SCZ). DNA methylation levels of HERV-K sequences were examined in peripheral blood leukocytes. We found significantly lower levels of HERV-K methylation in FES patients compared to HCs. Patients with MES and matched HCs had similar levels of HERV-K methylation. There was a significant positive correlation between chlorpromazine equivalent dosage and HERV-K methylation levels in MES patients, but not in FES individuals. No significant differences in HERV-K methylation levels between D-SCZ and ND-SCZ as well as HCs were found. Our results indicate lower HERV-K methylation levels at early stages of schizophrenia. This difference might normalize with subsequent exacerbations of schizophrenia, likely due to the effects of antipsychotics.

Prediction of Poor Prognosis After Severe Head Injury in Children Using Logistic Regression

Head trauma is one of the main causes of death in childhood and often leaves severe disability with serious neurological damage. Appropriate treatment must be provided immediately to improve outcomes. This study was performed to identify factors associated with a poor prognosis at an early stage of severe head injury in children. The subjects were registered in the Japan Neurotrauma Data Bank. They were 119 children (mean age, 8 years; male, 67.2%) with severe head injury registered during a period of 4 years (from July 1, 2004 to June 30, 2006 and from July 1, 2009 to June 30, 2011). Univariate and multivariate analyses were performed to examine relationships among factors and outcome 6 months after discharge. Logistic regression analysis was performed to develop models for poor prognosis and death. Outcome was evaluated based on the Glasgow Outcome Scale: 73 children (61.3%) had good recovery, 11 (9.2%) had moderate disability, 8 (6.7%) had severe disability, 4 (3.3%) were in a vegetative state, and 23 (19.3%) had died. Four factors were identified as predictors of a poor prognosis: serum glucose level greater than or equal to 200 mg/dL, Glasgow Coma Scale score on admission less than or equal to 5, presence of mydriasis, and presence of traumatic subarachnoid hemorrhage. Three factors were identified as predictors of death: serum glucose level greater than or equal to 200 mg/dL, Glasgow Coma Scale score on admission less than or equal to 5, and presence of mydriasis. Using these predictors, subsequent exacerbation may be predicted just after arrival at the hospital and appropriate treatment can be provided immediately.

The usefulness of soluble receptor for advanced glycation end-products in the identification of COPD frequent exacerbator phenotype.

IntroductionExacerbations of COPD (ECOPDs) are important events in the course of COPD, accelerating the rate of decline in lung function and increasing the mortality risk. A growing body of evidence suggests the significance of the “frequent exacerbator” phenotype. This phenotype seems to be associated with a more severe airflow limitation, symptoms, health-related quality of life impairment, and higher mortality. However, there is no described biomarker that would help to identify this group of patients.Patients and methodsPatients with COPD in “D” GOLD category were monitored for 3 years according to events of ECOPD. Serum samples were collected from the patients. Circulating level of plasma soluble receptor for advanced glycation end-products (sRAGE) was measured using commercially available high sensitivity kits. The receiver operating characteristic (ROC) curve analysis was used to assess the usefulness of sRAGE to identify frequent exacerbator phenotype. Log-rank test was used in the analysis of time to the subsequent exacerbation. Pearson (R) or Spearman’s rank (RS) correlation coefficients were used for correlation analysis.ResultsNineteen patients were enrolled. The area under the ROC curve (AUROC) for sRAGE for the identification of frequent exacerbator phenotype was 0.81. Analysis identified the cutoff point as 850.407 pg/mL, characterized by a sensitivity of 0.80 (95% CI: 0.28–1.0) and specificity of 0.93 (95% CI: 0.66–1.0). Additionally, in the group with sRAGE ≤850.407 pg/mL, we observed significantly shorter time to the subsequent exacerbation: median of 32 vs 105.5 days (P=0.03). Correlation analysis revealed significant negative correlation between sRAGE and the number of exacerbations requiring hospitalization during the whole time of follow-up (RS=−0.53; P=0.02) and significant positive correlation with FEV1 expressed as the percentage of reference value (R=0.6; P=0.006).ConclusionsRAGE seems to be useful in the identification of frequent exacerbator phenotype. This parameter may also be used in the prediction of time to ECOPD. Our findings should be confirmed in a sufficiently powered larger sample.

Impact of prompt versus delayed initiation of triple therapy post COPD exacerbation in a US-managed care setting.

It is unknown whether there is a benefit to initiating triple therapy (TT; inhaled corticosteroids combined with long-acting β2-agonists and long-acting muscarinic antagonists) promptly (within 30 days) following a chronic obstructive pulmonary disease (COPD)-related hospitalization or emergency-department (ED) visit compared with delaying treatment (31-180 days). This retrospective, observational study (GSK: HO-15-15256) used healthcare claims from a commercial and Medicare claims database (January 1, 2008-December 31, 2015). ≥40 years of age, diagnosed with COPD and no history of TT 12 months pre-index. Patients experiencing a COPD-related hospitalization or ED visit (index) who initiated TT ≤ 6 months following index were included (January 1, 2009-December 31, 2014). Patients initiating TT ≤ 30 or 31-180 days following index were included in the Prompt or Delayed cohorts, respectively. All-cause and COPD-related costs (total, medical and prescription), and exacerbations (severe and moderate) per patient per year were determined for 12 months post index. Outcomes were adjusted by cohort, weighted for a balanced distribution of baseline covariates between cohorts using inverse probability weights. Overall, 10,902 patients were identified (Prompt: n = 5701; Delayed: n = 5201). Total, medical and prescription all-cause costs were significantly higher in the Delayed versus Prompt cohorts (percent increase: 18.7%, 22.8% and 8.8%, respectively; all p < 0.0001). COPD-related total, medical and prescription costs were 49.3%, 66.3% and 10.3% higher in the Delayed versus Prompt cohorts, respectively (all p < 0.0001). Total and severe COPD-related exacerbation rates were 28.2% and 64.7% higher in the Delayed versus Prompt cohorts (p < 0.0001). Prompt use of TT following a COPD-inpatient or ED visit may reduce future costs and subsequent exacerbations compared with delaying the initiation of TT.

ИНЪЕКЦИОННАЯ ЭТАПНАЯ ТЕРАПИЯ ПО ЗАПАТЕНТОВАННОЙ ТЕХНОЛОГИИ

Treatment of hernia by the method of Dr. Koss is used in cases where conventional physiotherapy exercises are already late and therefore ineffective and surgery is inevitable. This can sometimes be the consequence of the rupture of the fibrous ring, when self healing is unrealistic.The industry of advanced medicine translates the treatment of intervertebral hernia into a kind of Assembly flow. This also applies to operational techniques. Alas, in this well-established scientific and technical chain there is a significant gap - it is the unavailability of their own doctor, who would control the whole process of healing from the very first moment of pain to the stage of their elimination and further, in dynamics, the prevention of possible subsequent exacerbations. The pa- tient goes from doctor to doctor, from therapist to neurologist, from neurologist to neurosurgeon. Some use “point” treatment options - only operation, only bone (manual therapy, osteopathy), only injections, only massage, etc., etc.Methodical in all stages of treatment, collegiality, doctoral acceptability and gramotnaya neurorehabilitation subsequently relieving the compression of nerve roots of an intervertebral hernia (whether nucleoplasty, other neurosurgical surgery or non-surgical method of treatment according to the method of the doctor Cossa), prevention of recurrent exacerbations, such as in other areas of the spine that is the problem which needs to be addressed to the attending doctor together with the patient.

Eosinophil counts in first COPD hospitalizations: a 1-year cost analysis in Quebec, Canada.

BackgroundExacerbations explain much of the cost of COPD. Higher blood eosinophil cell counts at admission for acute exacerbation of COPD increase the risk of subsequent exacerbations and hospitalizations. However, there is no literature on the economic burden of patients with this inflammatory profile. The objective of this study is to assess the cost of health-care service utilization according to different counts of blood eosinophils.MethodsThe observational retrospective cohort included all first hospitalizations for COPD exacerbation between April 2006 and March 2013. The eosinophilic group was defined by blood eosinophil counts on admission ≥200 cells/µL and/or ≥2% of the total white blood cell count. Study outcomes were: total costs (2016 Canadian dollars) (index hospitalization and 1-year follow-up), total index hospitalization costs, total 1-year costs (all-cause readmissions, ambulatory and emergency service use), and 1-year COPD-related costs (only cost for COPD after initial discharge). Sensitivity analyses were conducted to evaluate the impact of different eosinophil cut-offs on outcomes.ResultsIn total, 479 patients were included, 173 in the eosinophilic group (92 in the higher cut-off). The average total cost was $18,263 ($6,706 for the index hospitalization), without significant difference between groups (P=0.3). The average 1-year COPD-related cost was higher in the eosinophilic group ($3,667 vs $2,472, P=0.006), with an adjusted mean difference of $1,416. Analysis of data using the higher cut-off of ≥400 cells or ≥3% was associated with a slightly larger difference in 1-year COPD-related costs between groups ($4,060 vs $2,629, P=0.003), with an adjusted mean difference of $1,640.ConclusionA higher blood eosinophil cell count at admission for a first hospitalization is associated with an increase in total 1-year COPD-related costs.

PRS21 - ECONOMIC IMPACT OF DELAYING INITIATION WITH MULTIPLE INHALER MAINTENANCE TRIPLE THERAPY TREATMENT IN SPANISH COPD PATIENTS

GOLD guidelines recommend the use of inhaled triple therapy of ICS/LAMA/LABA to reduce the risk of future exacerbations in symptomatic chronic obstructive pulmonary disease (COPD) patients with a history of exacerbations. The aim of this study was to estimate COPD-related healthcare resource use and costs, and subsequent exacerbation rate of patients initiating an inhaled triple therapy with multiple inhalers (MITT) early (<30 days) versus late (31-180 days) following an exacerbation in a real-life clinical setting. Observational, longitudinal, retrospective study using electronic medical records from the Spanish database REDISS. Patients >40 years old with a confirmed COPD diagnosis and who were newly prescribed MITT within 180 days after an exacerbation that required hospitalization or emergency department (ED) visit between January 2013 and December 2015 were included. Patients were followed from index date (date of early or late MITT initiation) and followed for up to 12 months to assess COPD-related healthcare resource use (routine and emergency visits, hospitalizations tests, pharmacologic treatment), exacerbation rate and costs (€2017). 1,280 patients were included; mean age 73 years, 78% male, 41% had a severe/very severe lung function impairment. 61.6% patients initiated MITT early vs 38.4% late. There were no statistically significant differences in baseline characteristics of patients initiating early vs late. During follow-up, healthcare resource consumption was lower in early vs late group, especially primary care and ED visits, leading to lower costs (€1,861 vs €1,935; p<0.05). 28% patients in the early group experienced >1 exacerbation in the follow-up period vs 36.4% in the late group (p=0.002), with an exacerbation rate of 0.5 vs 0.6 per person year (p=0.022) respectively. COPD patients initiating MITT early (<30 days) after an exacerbation showed lower healthcare resource use and exacerbation rate, leading to lower associated costs.

Nebulised hypertonic saline for cystic fibrosis.

Background Impaired mucociliary clearance characterises lung disease in cystic fibrosis (CF). Hypertonic saline (HS) enhances mucociliary clearance in vitro and may lessen the destructive inflammatory process in the airways. Objectives To investigate the effects of nebulised HS in CF compared to placebo or other treatments for mucociliary clearance. Search methods We searched the Cochrane CF and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 31 July 2008. Selection criteria Controlled trials assessing HS compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity). Data collection and analysis Two authors independently reviewed all identified trials and data; and assessed trial quality. Main results Twelve trials (442 participants, aged 6 to 46 years) were included; five excluded and two await classification. In two placebo-controlled trials, HS (3% to 7%, 10 ml twice-a-day) significantly increased forced expiratory volume at one second (FEV1) at four weeks, mean difference (MD) 4.15 (95% CI 1.14 to 7.16); but not significantly after 48 weeks, MD 2.31 (95% CI -2.72 to 7.34). Two trials compared a similar dose of HS to recombinant deoxyribonuclease (RhDNAse). One three-week trial showed a non-significant difference, MD 1.60 (95% CI -7.96 to 11.16). However, in the second trial, after 12 weeks, RhDNAse led to a greater increase in FEV1 than HS (5 ml twice-daily), in participants with moderate to severe lung disease, MD 8.00 (95% CI 2.00 to 14.00). One 48-week placebo-controlled trial showed significant improvements in frequency of antibiotic use and quality of life; also that HS did not increase the concentration of Pseudomonas aeruginosa or Staphylococcus aureus. Authors' conclusions Treatment with 7% HS for 48 weeks showed a small improvement in FEV1 at four weeks; however, this was not sustained at 48 weeks (primary outcome measure of the only long-term trial). Unlike RhDNAse, HS can't, in the long term, be said to improve lung function. However, it did improve quality of life and reduce pulmonary exacerbations. Delivered following a bronchodilator, HS appears inexpensive and safe with no increased infection risk. We believe there is sufficient evidence to recommend using HS in CF; qualifying this we highlight that the only long-term trial failed to demonstrate a significant difference in its primary outcome (lung function) with improvements only in secondary outcomes.

PRS10 - The Epidemiology and Disease Burden of Severe Asthma in Japan Utilizing Multiple Data Sources

The aim of this presentation is to draw a whole picture of the epidemiology and burden of severe asthma (SA) by using data from three studies with different data sources in Japan. Three data sources (all GSK sponsored studies) were: medical records/claim data of the Kyoto University Hospital (HOSPITAL; HO1515492), health insurance claim database (CLAIM, population based; HO1616484), and Diagnosis Procedure Combination database (HO1617890; DPC, hospital based)]. Asthma patients ≥ 15 years of age were identified by International Classification of Disease, 10th revision codes and prescription data of asthma management. We assessed proportion of SA among persistent asthma (CLAIM, DPC), distribution of blood eosinophil count among SA (HOSPITAL), risk factors for exacerbations (HOSPITAL, CLAIM), asthma-related direct cost (HOSPITAL, CLAIM, DPC). An increasing proportion of SA among asthma patients was observed with 0.6-3.6% (15 to 65 years of age, CLAIM) and 6.6-13.4% (15 to 90+ years of age, DPC), and 34% of SA had a blood eosinophil count ≥300 cells/µl (HOSPITAL). Exacerbation history (HOSPITAL, CLAIM) and asthma severity (CLAIM) were associated with subsequent exacerbations. Large economic burden was shown among SA (HOSPITAL, CLAIM, DPC). We showed a more complete picture of the epidemiology and burden of SA. Combining different pieces of information from multiple data sources can be useful to complement limitations of each database and answer complex research questions.

Risk Factors for Asthma Exacerbation and Treatment Failure in Adults and Adolescents with Well-controlled Asthma during Continuation and Step-Down Therapy.

Although national and international guidelines recommend reduction of asthma controller therapy or "step-down" therapy in patients with well-controlled asthma, it is expected that some individuals may experience worsening of asthma symptoms or asthma exacerbations during step-down. Characteristics associated with subsequent exacerbations during step-down therapy have not been well defined. The effect of environmental tobacco smoke exposure on risk of treatment failure during asthma step-down therapy has not been reported. To identify baseline characteristics associated with treatment failure and asthma exacerbation during maintenance and guideline-based step-down therapy. The present analysis uses data collected from a completed randomized controlled trial of optimal step-down therapy in patients with well-controlled asthma taking moderate-dose combination inhaled corticosteroids/long-acting β-agonists. Participants were 12 years or older with physician-diagnosed asthma and were enrolled between December 2011 and May 2014. An emergency room visit in the previous year was associated with subsequent treatment failure (hazard ratio, 1.53; 95% confidence interval, 1.06-2.21). For every 10% increase in baseline forced expiratory volume in one second percent predicted, the hazard ratio of treatment failure was 14% lower (hazard ratio, 0.86; 95% confidence interval, 0.74-0.99). There was no difference in the risk of treatment failure between adults and children, nor was the duration of asthma associated with the risk of treatment failure. Age of asthma onset was not associated with an increased risk of treatment failure. Unexpected emergency room visit in the previous year was the only risk factor significantly associated with subsequent asthma exacerbations requiring systemic corticosteroids. Time to treatment failure or exacerbation did not differ in participants with and without self-report of environmental tobacco smoke exposure. The present findings can help clinicians identify adults and adolescents with asthma who are more likely to develop treatment failure and exacerbations and who may therefore require closer monitoring during asthma step-down treatment. Those with reduced pulmonary function, a history of exacerbations, and early-onset disease, even if otherwise well controlled, may require closer observation to prevent treatment failures and asthma exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT01437995).

Three patients with injection of intravitreal vascular endothelial growth factor inhibitors and subsequent exacerbation of chronic proteinuria and hypertension

Vascular endothelial growth factor (VEGF) receptor inhibition is a commonly used tool to prevent vascular proliferation in tumors and retinal diseases. The antiangiogenic effects of these drugs have made them potent adjunct therapies when given systemically for malignancies. They are also useful tools to ameliorate diminishing eyesight in retinopathy. Hypertension and proteinuria have been observed in systemic VEGF inhibitor therapy, with rarer presentations involving nephrotic-range proteinuria due to glomerulopathies. Pharmacokinetic studies have shown detectable blood levels of anti-VEGF inhibitors up to 30 days postintravitreal injection. Animal studies have also demonstrated binding of VEGF inhibitors in simian glomeruli 1 week after a single intravitreal injection. We report three patients who received intravitreal bevacizumab and/or aflibercept with worsening hypertension, proteinuria and renal injury. Data regarding emerging evidence of VEGF inhibitor nephrotoxicity after intravitreal injections are also presented. The clinical data and the existing literature are reviewed to support the hypothesis that intravitreal anti-VEGF agents may be unrecognized nephrotoxins. These agents are given to vulnerable patients with diabetes, hypertension and preexisting nephropathy and proteinuria. This case series is reported to spur further study of the systemic effects of intravitreal VEGF inhibitors.