Effect of Tooth Bleach on Dentin Fatigue Resistance in Situ.

BACKGROUND: Negative effects of bleaching on dentin have previously been reported in vitro. OBJECTIVE: The purpose of this study was to determine the effect of carbamide peroxide bleaching on dentin fatigue resistance using a clinically relevant in situ model. METHODS AND MATERIALS: Following research ethics board approval, 60 human teeth requiring extraction were collected. Sterilized human dentin specimens were cut (1.2x1.2x10 mm) and secured into customized bleaching trays to be used by study participants. Participants were randomly assigned to either bleach (10% carbamide peroxide, n=23) or control (gel without bleach, n=26) treatment groups. Treatment was applied to the bleaching trays and worn overnight by participants for 14 days. After treatment completion, dentin specimens were removed from the bleaching trays and subjected to fatigue testing (10 N, 3 mm/s, 2x105 cycles) while submerged in artificial saliva. Kaplan-Meier survival analysis was conducted to compare the number of cycles to failure during fatigue testing in both groups. A log rank test was run to determine if there were differences in the survival distribution between the two groups (α<0.05). RESULTS: The median number of cycles to failure was 352 ± 202 and 760 ± 644 for the bleach and control groups, respectively. The survival distributions for the two groups were significantly different (p=0.020). Dentin fatigue resistance was significantly lower in the bleach group compared to the control. CONCLUSIONS: Direct bleaching of human dentin using an at-home tray bleaching protocol in situ reduced dentin fatigue resistance. This has implications for tooth fracture risk and longevity.

Stability of hippocampal subfield volumes after trauma and relationship to development of PTSD symptoms.

BACKGROUND: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus' functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0. METHODS: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. RESULTS: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl - T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. CONCLUSION: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).

Statin use and lung cancer risk in chronic obstructive pulmonary disease patients: a population-based cohort study.

BACKGROUND: Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer. A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins. This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients. METHODS: We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA). We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose). To assess residual confounding, a negative control exposure was used to test the validity of our results. All exposure variables were time-dependent. RESULTS: The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female. There were 12,469 patients who received at least one statin prescription. Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73-1.00) in COPD patients, but this result not statistically significant. Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77-0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96-0.99). Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75-1.10). CONCLUSIONS: The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer. While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy.

Effects of long-term inhaled corticosteroid treatment on fragility fractures in older women: the Manitoba BMD registry study.

The effects of inhaled corticosteroids (ICS) on fracture risk in older women with chronic respiratory diseases are not well established. Our results indicate long-term ICS use in this population does not increase the risk of major osteoporotic fracture. This finding further elucidates the long-term safety of ICS in older women. INTRODUCTION: Inhaled corticosteroids (ICS) are frequently used in older women with chronic respiratory diseases. There is insufficient evidence regarding the association between long-term ICS use and the risk of fragility fractures in this population. METHODS: We used linked Manitoba health administrative databases and the provincial bone mineral density (BMD) registry (1996-2013) to identify women ≥ 40 years of age with asthma and/or chronic obstructive pulmonary disease (COPD) within 3 years preceding the baseline BMD test. We followed them until the first major osteoporotic fracture or end of study, whichever came first. ICS use, stratified by exposure tertiles, was measured within the 12-month period following the baseline BMD test (by total days and quantity, primary outcome), and over the entire follow-up period (by medication possession ratio (MPR) and average annual dose, secondary outcome). The hazard ratio of fracture with ICS use was estimated using a Cox proportional hazards model, controlling for baseline determinants of fracture. RESULTS: Of 6880 older women with asthma (38%) or COPD (62%), 810 (12%) experienced a major osteoporotic fracture over a mean follow-up of 7.7 years (SD = 3.9). ICS use at any tertile was not associated with an increased risk of fracture (dispensed days, p = 0.90; dispensed quantity, p = 0.67). Similarly, ICS use at any tertile during the entire follow-up period was not associated with an increased risk of fracture (MPR, p = 0.62; average annual dose, p = 0.58). CONCLUSION: Our findings do not support an increased risk of major osteoporotic fracture in older women with chronic respiratory diseases due to long-term ICS use.

Efficacy of once-daily tiotropium Respimat in adults with asthma at GINA Steps 2-5.

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4-5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2-5, a post hoc analysis of five double-blind trials (12-48-weeks; patients aged 18-75 years) investigated the effect of tiotropium Respimat, 5 µg or 2.5 µg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0-3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients' background treatment regimen. Baseline characteristics of patients (N = 2926) were balanced between treatments. Tiotropium Respimat showed consistent improvements in lung function across GINA steps; placebo-corrected peak FEV1(0-3h) improvements after tiotropium Respimat 5 µg and 2.5 µg were: Step 2 (Week 8), 135 mL (95% confidence interval: 84, 187) and 155 mL (103, 206); Step 3 (Week 24), 187 mL (139, 235) and 235 mL (187, 283); Step 4 (Week 24), 111 mL (63, 159) and 181 mL (35, 326); Step 5 (Week 24; 5 µg only), 164 mL (5, 323). Asthma control improved with tiotropium Respimat versus placebo, showing statistical significance (nominal P value) with tiotropium Respimat 5 µg at Step 4 (odds ratio 1.36 [1.03, 1.78]). Safety profiles were similar between treatments. In conclusion, tiotropium Respimat add-on therapy improves lung function, and may improve asthma control, in adults across disease severities.

Phenotyping and outcomes of hospitalized COPD patients using rapid molecular diagnostics on sputum samples.

BACKGROUND: Etiologies of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous. We phenotyped severe AECOPD based on molecular pathogen detection of sputum samples collected at hospitalization of COPD patients and determined their outcomes. METHODS: We phenotyped 72 sputum samples of COPD patients who were hospitalized with a primary diagnosis of AECOPD using a molecular array that detected common bacterial and viral respiratory pathogens. Based on these results, the patients were classified into positive or negative pathogen groups. The pathogen-positive group was further divided into virus or bacteria subgroups. Admission day 1 blood samples were assayed for N-terminal prohormone brain natriuretic peptide, CRP, and complete blood counts. RESULTS: A total of 52 patients had a positive result on the array, while 20 patients had no pathogens detected. The most common bacterial pathogen detected was Haemophilus influenzae and the most common virus was rhinovirus. The pathogen-negative group had the worse outcomes with longer hospital stays (median 6.5 vs 5 days for bacteria-positive group, P=0.02) and a trend toward increased 1-year mortality (P=0.052). The bacteria-positive group had the best prognosis, whereas the virus-positive group had outcomes somewhere in between the bacteria-positive and pathogen-negative groups. CONCLUSION: Molecular diagnostics on sputum can rapidly phenotype serious AECOPD into bacteria-, virus-, or pathogen-negative groups. The bacteria-positive group appears to have the best prognosis, while pathogen-negative group has the worst. These data suggest that AECOPD is a heterogeneous event and that accurate phenotyping of AECOPD may lead to novel management strategies that are personalized and more precise.

The effects of a CCR3 inhibitor, AXP1275, on allergen-induced airway responses in adults with mild-to-moderate atopic asthma.

BACKGROUND: CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. OBJECTIVE: This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. METHODS: Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind cross-over study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo. RESULTS: There was a significant increase in methacholine PC20 after 12 days of AXP1275 treatment compared to placebo (increase of 0.92 doubling doses versus 0.17 doubling doses, P = .01), but this protection was lost post-allergen challenge. There was no effect of AXP1275 on allergen-induced late asthmatic responses, or eosinophils in blood and sputum. The early asthmatic response and exhaled nitric oxide levels were slightly lower with AXP1275, but this did not reach statistical significance. The number of subjects who experienced treatment-emergent adverse events while receiving AXP1275 was comparable placebo. CONCLUSIONS & CLINICAL RELEVANCE: AXP1275 50 mg administered daily was safe and well tolerated, and there was no difference in the type, severity or frequency of treatment-emergent adverse events in subjects while receiving AXP1275 compared to placebo. AXP1275 increased the methacholine PC20 ; however, the low and variable exposure to APX1275 over a short treatment period may have contributed to poor efficacy on other outcomes.

The role of predictive coding in the pathogenesis of delirium.

Delirium and dementia represent an emerging global crisis in healthcare. Attempts have been made to identify the pathognomonic feature that would make delirium stand out from dementia but unfortunately the global neural dysfunction of both disorders has made the establishment of a direct measurement difficult. Modern conceptualisations of delirium have been influenced by the assessment tools used to assess, detect, and analyse its complex and transient nature. Recent publication of the DSM-V criteria for delirium has marginally altered the previous DSM-IV criteria with a focus upon inattention with vague terms such as consciousness downplayed. Such an alteration has been found to be restrictive and thus impact upon delirium case identification. Although these findings are approximating the empirical state of delirium as measured by validated instruments, a more refined neuroscientifically informed phenomenological framework is required in order to enhance the theoretical understanding of delirium assessment and resolve these challenges. One such application is the predictive coding (PC) model, also known as the hierarchical Bayesian inference model, to interpreting delirium pathophysiology. Therefore, the aims of this paper are to 1) propose the hypothesis that delirium pathophysiology can be explained in terms of the PC model, 2) support this hypothesis by applying this model to current methods of assessing delirium phenomenology, particularly attention, and 3) outline a future programme of research to test many of the parameters of this application.

Validated methods for identifying tuberculosis patients in health administrative databases: systematic review.

BACKGROUND: An increasing number of studies are using health administrative databases for tuberculosis (TB) research. However, there are limitations to using such databases for identifying patients with TB. OBJECTIVE: To summarise validated methods for identifying TB in health administrative databases. METHODS: We conducted a systematic literature search in two databases (Ovid Medline and Embase, January 1980-January 2016). We limited the search to diagnostic accuracy studies assessing algorithms derived from drug prescription, International Classification of Diseases (ICD) diagnostic code and/or laboratory data for identifying patients with TB in health administrative databases. RESULTS: The search identified 2413 unique citations. Of the 40 full-text articles reviewed, we included 14 in our review. Algorithms and diagnostic accuracy outcomes to identify TB varied widely across studies, with positive predictive value ranging from 1.3% to 100% and sensitivity ranging from 20% to 100%. CONCLUSIONS: Diagnostic accuracy measures of algorithms using out-patient, in-patient and/or laboratory data to identify patients with TB in health administrative databases vary widely across studies. Use solely of ICD diagnostic codes to identify TB, particularly when using out-patient records, is likely to lead to incorrect estimates of case numbers, given the current limitations of ICD systems in coding TB.

Impact of a COPD comprehensive case management program on hospital length of stay and readmission rates.

BACKGROUND: COPD accounts for the highest rate of hospital admissions among major chronic diseases. COPD hospitalizations are associated with impaired quality of life, high health care utilization, and poor prognosis and result in an economic and a social burden that is both substantial and increasing. AIM: The aim of this study is to determine the efficacy of a comprehensive case management program (CCMP) in reducing length of stay (LOS) and risk of hospital admissions and readmissions in patients with COPD. MATERIALS AND METHODOLOGY: We retrospectively compared outcomes across five large hospitals in Vancouver, BC, Canada, following the implementation of a systems approach to the management of COPD patients who were identified in the hospital and followed up in the community for 90 days. We compared numbers, rates, and intervals of readmission and LOS during 2 years of active program delivery compared to 1 year prior to program implementation. RESULTS: A total of 1,564 patients with a clinical diagnosis of COPD were identified from 2,719 hospital admissions during the 3 years of study. The disease management program reduced COPD-related hospitalizations by 30% and hospitalizations for all causes by 13.6%. Similarly, the rate of readmission for all causes showed a significant decline, with hazard ratios (HRs) of 0.55 (year 1) and 0.51 (year 2) of intervention (P<0.001). In addition, patients' mean LOS (days) for COPD-related admissions declined significantly from 10.8 to 6.8 (P<0.05). CONCLUSION: A comprehensive disease management program for COPD patients, including education, case management, and follow-up, was associated with significant reduction in hospital admissions and LOS.

Infection control and tuberculosis in health care workers: an assessment of 28 hospitals in South Africa.

SETTING: Twenty-eight public hospitals in the Free State Province, South Africa. OBJECTIVE: To examine the association between tuberculosis (TB) infection control (IC) scores in Free State hospitals and the incidence of TB disease among health care workers (HCWs) in 2012. DESIGN: A cross-sectional survey and mixed-methods analysis of TB IC policies, practices and infrastructure using a comprehensive, 83-item IC audit and observation tool. RESULTS: As the total IC score increased, the probability of TB in an HCW at that hospital decreased. When adjusted for other covariates in multivariate analysis, if the total score of a hospital increased by one unit, the odds of an HCW having TB decreased by 4.9% (95%CI 0.9-8.8). Significant associations were also seen for the personal protective equipment (PPE) score, where odds decreased by 11.5% (95%CI 1.8-20.1) for each unit increase in score. Administrative score, environmental score and miscellaneous score were not statistically significant in the multivariate model. CONCLUSIONS: These findings reaffirm that overall IC and PPE are essential to protect HCWs from acquiring TB. More attention to TB IC is required to protect the health care workforce and to stop the South African TB epidemic.

The safety of mepolizumab for the treatment of asthma.

INTRODUCTION: Asthma is an airway disease characterized by airway inflammation. It is associated with significant morbidity, mortality, and costs to the healthcare system and society. Interleukin-5 (IL-5) was identified for its role in eosinophil development, maturation, and survival in tissues, which has been related to disease severity and airway eosinophilia. Areas covered: In this review, we will present the pharmacokinetics and dynamics of mepolizumab in addition to efficacy and safety data. Expert Opinion: Mepolizumab is novel, new, first-in-class therapy targeting IL-5. It has been found to be particularly effective in the management of patients with asthma whose peripheral blood eosinophil count is at a well-defined cut point within the normative range. This easily available biomarker, along with a history of asthma exacerbations, has translated into a clinically significant reduction in asthma exacerbations and the dose of oral corticosteroids in patients who previously have been prednisone-dependent. The pivotal studies indicate that mepolizumab was well tolerated, with the most frequently reported adverse events being headache, nasopharyngitis, worsening of asthma, and local injection reactions. These study investigators did not report any deaths or anaphylaxis related to mepolizumab.

Ten-year trends in direct costs of asthma: a population-based study.

INTRODUCTION: There is little information on recent trends in the economic burden of asthma. Our objective was to estimate the excess costs of asthma and their trend in British Columbia, Canada, from 2002 to 2011. METHODS: A retrospective cohort of individuals aged 5-55 years was constructed from the provincial administrative health databases, consisting of patients with physician-diagnosed asthma and a propensity-score-matched comparison sample from the general population. Total direct medical costs were calculated as the sum of hospitalizations, outpatient visits and medication costs, adjusted to 2012 Canadian dollars ($). Excess costs were defined as the difference in costs between the asthma and comparison groups. RESULTS: A total of 341 457 individuals (mean age at entry 27.3, 54.1% female) were equally divided into the asthma and comparison groups. Excess costs in patients with asthma were $1028.0 (95% CI $982.7-$1073.4) per patient-year (PY). Medications contributed to the greatest share of excess costs ($471.7/PY), whereas hospitalization and outpatient costs were, respectively, $272.2/PY and $284.1/PY. Only $192.9/PY was attributable to asthma itself. There was a 2.9%/year increase in excess costs (P < 0.001), a combination of asthma-attributable costs declining by 0.8%/year while nonasthma excess costs increasing by 3.8%/year. The most dramatic trend was observed in asthma-related outpatient costs, which decreased by %6.6/year. CONCLUSIONS: A significant share of excess costs in asthma is not attributable to the disease itself. The pattern of costs changed significantly during the study period. The burden of comorbid conditions should be considered in developing evidence-based policies for management of patients with asthma.

A dual CysLT1/2 antagonist attenuates allergen-induced airway responses in subjects with mild allergic asthma.

BACKGROUND: The cysteinyl leukotrienes (cysLTs) play a key role in the pathophysiology of asthma. In addition to functioning as potent bronchoconstrictors, cysLTs contribute to airway inflammation through eosinophil and neutrophil chemotaxis, plasma exudation, and mucus secretion. We tested the activity of the dual cysLT1/2 antagonist, ONO-6950, against allergen-induced airway responses. METHODS: Subjects with documented allergen-induced early (EAR) and late asthmatic response (LAR) were randomized in a three-way crossover study to receive ONO-6950 (200 mg) or montelukast (10 mg) or placebo q.d. on days 1-8 of the three treatment periods. Allergen was inhaled on day 7 two hours postdose, and forced expiratory volume in 1 s (FEV1 ) was measured for 7 h following challenge. Sputum eosinophils and airway hyperresponsiveness were measured before and after allergen challenge. The primary outcome was the effect of ONO-6950 vs placebo on the EAR and LAR. RESULTS: Twenty-five nonsmoking subjects with mild allergic asthma were enrolled and 20 subjects completed all three treatment periods per protocol. ONO-6950 was well tolerated. Compared to placebo, ONO-6950 significantly attenuated the maximum % fall in FEV1 and area under the %FEV1 /time curve during the EAR and LAR asthmatic responses (P < 0.05) and allergen-induced sputum eosinophils. There were no significant differences between ONO-6950 and montelukast. CONCLUSIONS: Attenuation of EAR, LAR, and airway inflammation is consistent with cysLT1 blockade. Whether dual cysLT1/2 antagonism offers additional benefit for treatment of asthma requires further study.

Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study.

BACKGROUND: Asthma is a biologically heterogeneous disease and development of novel therapeutics requires understanding of pathophysiologic phenotypes. There is uncertainty regarding the stability of clinical characteristics and biomarkers in asthma over time. This report presents the longitudinal stability over 12 months of clinical characteristics and clinically accessible biomarkers from ADEPT. METHODS: Mild, moderate, and severe asthma subjects were assessed at 5 visits over 12 months. Assessments included patient questionnaires, spirometry, bronchodilator reversibility, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum. RESULTS: Mild (n = 52), moderate (n = 55), and severe (n = 51) asthma cohorts were enrolled from North America and Western Europe. For all clinical characteristics and biomarkers, group mean data showed no significant change from visit to visit. However, individual data showed considerable variability. FEV1/FVC ratio showed excellent reproducibility while pre-bronchodilator FEV1 and FVC were only moderately reproducible. Of note bronchodilator FEV1 reversibility showed low reproducibility, with the nonreversible phenotype much more reproducible than the reversible phenotype. The 7-item asthma control questionnaire (ACQ7) demonstrated moderate reproducibility for the combined asthma cohorts, but the uncontrolled asthma phenotype (ACQ7 > 1.5) was inconstant in mild and moderate asthma but stable in severe asthma. FENO demonstrated good reproducibility, with the FENO-low phenotype (FENO < 35 ppb) more stable than the FENO-high phenotype (FENO ≥ 35 ppb). Induced sputum inflammatory phenotypes showed marked variability across the 3 sputum samples taken over 6 months. CONCLUSIONS: The ADEPT cohort showed group stability, individual stability in some parameters e.g. low FEV1/FVC ratio, and low FENO, but marked individual variability in other clinical characteristics and biomarkers e.g. type-2 biomarkers over 12 months. This variability is possibly related to seasonal variations in climate and allergen exposure, medication changes and acute exacerbations. The implications for patient selection strategies based on clinical biomarkers may be considerable.

Saving in medical costs by achieving guideline-based asthma symptom control: a population-based study.

BACKGROUND: Asthma control is increasingly used as an outcome measure in asthma trials. Economic evaluations of asthma interventions require converting the impact of interventions on control to impact on resource use. The purpose of this study was to estimate the savings in direct costs by achieving asthma symptom control as defined in the Global Initiative for Asthma (GINA) 2014 management strategy. METHODS: Adolescents and adults with asthma were recruited through random digit dialing. Asthma control per GINA and the use of healthcare resources were assessed at baseline and three-monthly visits up to 1 year. We used regression models to associate costs, measured in 2012 Canadian dollars ($), with symptom control, adjusting for potential confounding variables. RESULTS: The final sample included 517 individuals (average age 48.9, 65.8% female) with mostly mild-moderate asthma contributing 2033 follow-up visits. In 598 (29.4%), 809 (39.8%), and 626 (30.8%) of visits, asthma was symptomatically controlled, partially controlled, or uncontrolled, respectively. The average 3-month costs of asthma were $134.5. Of these, 20.5% were attributable to inpatient care, 47.8% to outpatient care, and 31.5% to medication. Compared to controlled asthma, partially controlled asthma was associated with a nonsignificant increase of $9.5 (95% CI -$13.6 - $32.6) in adjusted 3-month costs and uncontrolled asthma with a statistically significant increase of $81.7 (95% CI $48.5 - $114.9). CONCLUSION: A substantial fraction of this population-based sample of largely mild-moderate asthmatics was symptomatically uncontrolled. Achieving symptom control was associated with a reduction in direct costs. The adjusted values from this study can be used to inform cost-effectiveness analyses of asthma treatments.

The global economic burden of asthma and chronic obstructive pulmonary disease.

Non-communicable diseases are now the number one cause of disabilities and loss of life expectancy. Among them, chronic respiratory conditions constitute a major class. The burden of chronic respiratory diseases is generally increasing across the globe, and asthma and chronic obstructive pulmonary disease (COPD) are among the main causes of mortality and morbidity. However, the direct and indirect costs of these conditions vary across jurisdictions. This article reports on recent estimates of the costs of asthma and COPD, with a focus on comparing disease burden across different regions. Overall, there is tremendous variation in per capita annual costs of asthma and COPD. However, the methodology of the cost-of-illness studies is also vastly different, making it difficult to associate differences in reported costs to differences in the true burden of asthma and COPD. Suggestions are provided towards improving the validity and comparability of future studies.

Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study.

BACKGROUND: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects. METHODS: Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy. RESULTS: Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts. CONCLUSIONS: The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.