Asthma Treatment Regimens Research Articles

APPaRENT 3: Asthma Patients' and Physicians' Perspectives on the Burden and Management of Asthma in Seven Countries.

Asthma management is strongly dependent on physician and patient beliefs and perceptions about the disease and its long-term treatment. The APPaRENT 3 study was conducted to explore factors influencing treatment choice and to understand patients' and physicians' attitudes and perspectives on the use of controller inhalers in regular versus flexible dosing for asthma management. This cross-sectional survey of patients with asthma and treating physicians was conducted in seven countries: Indonesia, Malaysia, Philippines, Thailand, Vietnam (patient survey only), Saudi Arabia, and the United Arab Emirates. Assessment was carried out through an online/face-to-face questionnaire, where patients' viewpoints were focused on their attitudes and beliefs about asthma and treatment adherence, whereas physicians' viewpoints were gathered on their attitudes and beliefs about asthma management, knowledge of and adherence to asthma treatment guidelines, and asthma treatment regimens. Overall, 1400 patients (mean age, 34years) and 599 physicians (mean age, 43years) were included in the survey. Physicians similarly prioritised symptom control (39%) and exacerbation reduction (40%) in moderate asthma, whereas patients prioritised symptom control (41%) over exacerbation reduction (22%). Although both groups (physicians, 86%; patients, 84%) perceived asthma as well-controlled, poor management was evident based on Asthma Control Test (ACT) scores (mean, 15.7; standard deviation, 4.14; 82% had an ACT score<20) and high symptom burden (39% reported nighttime awakenings or early mornings≥2 nights/week). Most patients (76%) with moderate asthma were prescribed regular dosing, with the most common treatment being inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) with as-needed inhaled short-acting β2-agonist (SABA; 20%). Among patients on maintenance and reliever therapy, 93% of patients received a separate inhaled reliever. Despite high symptom burden, patients overestimated their level of asthma control. Physicians prioritised controlling symptoms and reducing exacerbations as treatment goals for moderate asthma, often prescribing regular dosing with ICS/LABA with as-needed inhaled SABA.

AIM2 participates in house dust mite (HDM)-induced epithelial dysfunctions and ovalbumin (OVA)-induced allergic asthma in infant mice

Objective: Allergen sensitization and high rates of concomitant allergic diseases are characteristic of severe pediatric asthma. The present study was aimed to explore the mechanism of allergic asthma via bioinformatics and experiment investigation. Methods: The GSE27011 dataset contained the expression profiles of normal and pediatric asthma white blood cells was downloaded for analyzing the different expression genes and function enrichment. The allergic asthma model in infant mice was established by ovalbumin (OVA) stimulation. The cellular model was established by house dust mite (HDM)-stimulation in human bronchial epithelial cells. The absent in melanoma 2 (AIM2) knockdown was achieved by intranasal lentivirus injection or cell infection. The bronchoalveolar lavage fluid (BALF) was collected for cell counting and ELISA assessment of cytokines. Lung tissues were collected for HE staining and immunohistochemical (IHC) staining. Real-time PCR and immunoblotting were used for the determination of key gene expressions in mouse and cell models. Results: upregulation of AIM2 gene expression was observed in pediatric asthma patients based on GSE27011 and OVA-induced infant mouse allergic asthma model. AIM2 knockdown ameliorated OVA caused elevation in airway hyper-responsiveness (AHR), elevation in cell quantities (eosinophils, neutrophils, lymphocytes), and levels of cytokines (IL-4, IL-13, TNF-α, and OVA-specific IgE) in BALF. Moreover, AIM2 knockdown relieved OVA-caused histopathological alterations in mouse lungs, up-regulation of AIM2 levels, and NOD1 and receptor-interacting protein 2 (RIP2) protein levels, as well as p65 phosphorylation. In the cell model, AIM2 knockdown partially ameliorated HDM-induced epithelial dysfunctions by promoting cell viability, down-regulating inflammatory cytokines levels, and decreasing the protein levels of AIM2, NOD1, RIP2, and phosphorylated p65. Conclusion: AIM2 participates in HDM-induced epithelial dysfunctions and OVA-induced allergic asthma progression. AIM2 could be a promising target for pediatric allergic asthma treatment regimens, which warrants further in vivo investigations.

Derivation of asthma severity from electronic prescription records using British thoracic society treatment steps

Background:Asthma severity is typically assessed through a retrospective assessment of the treatment required to control symptoms and to prevent exacerbations. The joint British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) guidelines encourage a stepwise approach to pharmacotherapy, and as such, current treatment step can be considered as a severity categorisation proxy. Briefly, the steps for adults can be summarised as: no controller therapy (Step 0), low-strength Inhaled Corticosteroids (ICS; Step 1), ICS plus Long-Acting Beta-2 Agonist (LABA; Step 2), medium-dose ICS + LABA (Step 3), and finally either an increase in strength or additional therapies (Step 4). This study aimed to investigate how BTS/SIGN Steps can be estimated from across a large cohort using electronic prescription records, and to describe the incidence of each BTS/SIGN Step in a general population.Methods:There were 41,433,707 prescriptions, for 671,304 individuals, in the Asthma Learning Health System Scottish cohort, between 1/2009 and 3/2017. Days on which an individual had a prescription for at least one asthma controller (preventer) medication were labelled prescription events. A rule-based algorithm was developed for extracting the strength and volume of medication instructed to be taken daily from free-text data fields. Asthma treatment regimens were categorised by the combination of medications prescribed in the 120 days preceding any prescription event and categorised into BTS/SIGN treatment steps.Results:Almost 4.5 million ALHS prescriptions were for asthma controllers. 26% of prescription events had no inhaled corticosteroid prescriptions in the preceding 120 days (Step 0), 16% were assigned to BTS/SIGN Step 1, 7% to Step 2, 21% to Step 3, and 30% to Step 4. The median days spent on a treatment step before a step-down in treatment was 297 days, whereas a step-up only took a median of 134 days.ConclusionWe developed a reproducible methodology enabling researchers to estimate BTS/SIGN asthma treatment steps in population health studies, providing valuable insights into population and patient-specific trajectories, towards improving the management of asthma.

Characteristics of Oral Corticosteroid Users Among Persons with Asthma on GINA Step 3 Therapy and Above: A Cross-Sectional Study in Portuguese Community Pharmacies.

Oral corticosteroids (OCS) are frequently used in asthma management but have an important risk-profile. The aim of the study is to characterize and compare the sociodemographic and clinical characteristics, treatment regimen and asthma control between OCS users and non-users among the population of asthma patients (≥18 years) at GINA step 3 and above treated with a fixed combination of an inhaled corticosteroid and a long-acting beta-agonist (ICS/LABA). Cross-sectional study in Portuguese community pharmacies. Data was collected via paper-based interview delivered at the pharmacy (sociodemographic characteristics and asthma treatment regimen, namely ICS/LABA and OCS utilization), followed by a telephonic interview collecting smoking history, comorbidities, body mass index (BMI), history of exacerbations and asthma-related healthcare resource utilization (HCRU) in the previous 12 months, as well as asthma control using the Control of Allergic Rhinitis and Asthma Test (CARAT®). A total of 347 patients recruited in 98 pharmacies were included in the analysis. Of those, 328 had completed both questionnaires. A quarter of the individuals reported OCS use in the previous 12 months (OCS users), either as add-on therapy (6%) or exacerbation treatment (19%). Patients were mostly females (72%), with an average age of 59.5 years (SD=15.4). OCS users were significantly older and reported more frequently having conjunctivitis (25.9% vs 15.0%), osteoporosis (25.9% vs 13.4%), arthritis (14.6% vs 6.9%), and gastrointestinal disease (16.1% vs 8.1%). OCS users also reported greater urgent HCRU: unscheduled consultations (33.3% vs 9.3%) and emergency department (ED) visits (32.1% vs 12.1%). Both groups presented poor disease control (85.2% of OCS users vs 72.9% of non-OCS users). These results highlight the burden of OCS therapy to asthma patients and the need to improve asthma management, by adopting OCS sparing strategies in this subgroup of patients.

Beta-adrenergic and M-cholinergic receptor interactions characteristics in the pathogenesis of bronchial obstructive pulmonary diseases

Crosstalk between beta-2-adrenoceptor and M- cholinoreceptors in the airway plays one of the main role in the pathogenesis of bronchoobstructive diseases. The interaction of M3-cholinergic receptors and beta2-receptors in the lungs can be characterized as functional antagonism. M3 activation can lead to desensitization of beta2 receptors. Beta2 receptors also limit the action of M3 receptors in various ways. In this case, M2 cholinergic receptors act as autoreceptors. On the one hand, they limit bronchoconstriction caused by a change in the conformation of the M3 cholinergic receptor, and on the other hand, they are able to suppress the excessive bronchorelaxating effect that occurs when beta2 receptor is activated. Knowledge of the crosstalk mechanisms can help to understanad the pathogenesis of bronchial obstructive diseases, optimize existing treatment regimens for chronic obstructive disease (COPD) and bronchial asthma (BA)

Barriers of Asthma Care among Asthmatic Children in Saudi Arabia: Maternal Perspectives

Background Bronchial asthma is one of the most common chronic conditions among children. Despite the improvement in asthma treatment regimens, its prevalence and related morbidity are increasing, especially among underserved, minority children. There are barriers in the management of asthma, which may impact the quality of outcomes. The goal of this study is to explore these barriers. Methods A cross-sectional study was conducted on interview data collected through 2019 from mothers of children (aged 6 - 12 years) with asthma visiting, for convenience, a public shopping mall. The interviewees were randomly selected, because they met the inclusion criteria. Participants were considered if the mother answered “yes” to the following questions: Has your child had physician-diagnosed asthma? Is your child currently taking asthma medications of asthma? Two community nurses conducted the interviews. Data was obtained using administrative questionnaires. Data were analyzed using SPSS version 21.0 (IBM Inc., Chicago, IL, USA). Descriptive statistics of percentage, mean, frequency and standard deviation were applied for categorical and continuous variables. Results Three hundred mothers participated in this study. Their average age was 36.8 years, 55% were housekeepers by profession, and 34% had obtained less than high school education. The majority of children (61%) were males, 45% had moderate asthma, and 42% had mild asthma. The most frequent types of barriers identified by parents were environmental factors (67.7%), followed by health care providers (63%), the health care system (48%), and patient or family characteristics (43%). Mothers were specifically concerned about the use, safety, and long-term complications of medications, the impact of exercise limitation on their child’s quality of life, and their own quality of life. Conclusion This study showed several barriers against asthma care in Saudi Arabia, which mainly related to environmental or personal characteristics. This highlights the need to enhance current policies within the health care system in Saudi Arabia to overcome these barriers.

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

BE Chipps, T Haselkorn, K Rosen, DR Minks, BL Trzaskoma, AT Luskin. J Allergy Clin Immunol Pract. 2018;6(1):169–176.e2 To assess the impact of asthma triggers and exacerbations on asthma-specific quality of life in children. A 3-year observational study, The Epidemiology and Natural History of Asthma Outcomes and Treatment Regimens, included a cohort of 438 children aged 6 to 12 years with severe or difficult-to-treat asthma recruited from 283 sites in the United States. …

Provider use of a participatory decision-making style with youth and caregivers and satisfaction with pediatric asthma visits.

BackgroundWe conducted a randomized controlled trial to test the effectiveness of an asthma question prompt list with video intervention to engage the youth during clinic visits. We examined whether the intervention was associated with 1) providers including youth and caregiver inputs more into asthma treatment regimens, 2) youth and caregivers rating providers as using more of a participatory decision-making style, and 3) youth and caregivers being more satisfied with visits.MethodsEnglish- or Spanish-speaking youth aged 11–17 years with persistent asthma and their caregivers were recruited from four pediatric clinics and randomized to the intervention or usual care groups. The youth in the intervention group watched the video with their caregivers on an iPad and completed a one-page asthma question prompt list before their clinic visits. All visits were audiotaped. Generalized estimating equations were used to analyze the data.ResultsForty providers and their patients (n=359) participated in this study. Providers included youth input into the asthma management treatment regimens during 2.5% of visits and caregiver input during 3.3% of visits. The youth in the intervention group were significantly more likely to rate their providers as using more of a participatory decision-making style (odds ratio=1.7, 95% confidence interval=1.1, 2.5). White caregivers were significantly more likely to rate the providers as more participatory (odds ratio=2.3, 95% confidence interval=1.2, 4.4). Youth (beta=4.9, 95% confidence interval=3.3, 6.5) and caregivers (beta=7.5, 95% confidence interval=3.1, 12.0) who rated their providers as being more participatory were significantly more satisfied with their visits. Youth (beta=−1.9, 95% confidence interval=−3.4, −0.4) and caregivers (beta=−8.8, 95% confidence interval=−16.2, −1.3) who spoke Spanish at home were less satisfied with visits.ConclusionThe intervention did not increase the inclusion of youth and caregiver inputs into asthma treatment regimens. However, it did increase the youth’s perception of participatory decision-making style of the providers, and this in turn was associated with greater satisfaction.

Biomarkers and asthma management: analysis and potential applications

Asthma features a high degree of heterogeneity in both pathophysiology and therapeutic response, resulting in many asthma patients being treated inadequately. Biomarkers indicative of underlying pathological processes could be used to identify disease subtypes, determine prognosis and to predict or monitor treatment response. However, the newly identified as well as more established biomarkers have different applications and limitations. Conventional markers for type 2-high asthma, such as blood eosinophils, fraction of exhaled nitric oxide, serum IgE and periostin, feature limited sensitivity and specificity despite their significant correlations. More distinctive models have been developed by combining biomarkers and/or using omics techniques. Recently, a model with a positive predictive value of 100% for identification of type 2-high asthma based on a combination of minimally invasive biomarkers was developed. Individualisation of asthma treatment regimens on the basis of biomarkers is necessary to improve asthma control. However, the suboptimal properties of currently available conventional biomarkers limit its clinical utility. Newly identified biomarkers and models based on combinations and/or omics analysis must be validated and standardised before they can be routinely applied in clinical practice. The development of robust biomarkers will allow development of more efficacious precision medicine-based treatment approaches for asthma.

Corticosteroid phobia among parents of asthmatic children.

Özçeker D, Uçkun U, İslamova D, Tamay Z, Güler N. Corticosteroid phobia among parents of asthmatic children. Turk J Pediatr 2018; 60: 142-146. Asthma is one of the most prevalent chronic diseases among children. Its prevalence and morbidity have been rising in recent decades. Pediatric asthma causes a significant burden on families; allergen-avoidance measures, uncontrolled disease, and disease severity which are the major cost predictors of childhood asthma in Turkey. Inhaled corticosteroids (ICS) are considered as cornerstone medications in asthma management which reduce asthma morbidity and mortality. Our aim was to address corticosteroid phobia in caregivers of asthmatic children and its impact on asthma management. Five hundred caregivers of asthmatic children were interviewed using structured questionnaire in this study. Over fifty percent of the caregivers (56.8%), most of whom (82.6%) are already aware of using corticosteroids in their anti-asthma drug regimen, mentioned that they are afraid of using them. Almost one fourth of caregivers (24.8%) made either some changes in their treatment regimen or stopped using the drugs due to corticophobia. Of the caregivers 55.2% had no idea about the side effects of corticosteroids and only 12.6% of them mentioned that they were informed by their physicians about the effects of corticosteroids. Any change in asthma treatment regimen due to corticophobia was found to be related with poor asthma control level (p: 0.004). The impact of parental information about the effects and importance of steroids given by the physicians on better asthma control was found to be highly significant (p < 0.001). That`s why physicians and health care providers should spend enough time explaining the importance of adherence to treatment in asthma management, which may help in overcoming the fear of using ICS.

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

Data examining associations between asthmaexacerbations, triggers, and asthma-related quality of life (QOL)in children with severe/difficult-to-treat asthma are unavailable. To evaluate real-world data on relationships between asthma exacerbations, triggers, and QOL in children using data from TENOR (The Epidemiology and Natural History of Asthma Outcomes and Treatment Regimens), a 3-year observational study of patients with severe/difficult-to-treat asthma, including those aged 6 to 12 years. QOL was examined using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and defined exacerbations hierarchically (descending order of severity): hospitalization, emergency department visit, steroid burst, no exacerbation, using the highest value from months 6 and 12. One-way ANOVA was used to test for differences in PAQLQ domain scores at month 12 across exacerbation severity, total number of asthma exacerbations, and number of baseline asthma triggers. Mantel-Haenszel chi-square test was used to test the association between the number of triggers and exacerbation hierarchy. Greater severity of asthma exacerbations was associated with significantly (P < .001) lower mean PAQLQ domain scores, indicating poorer QOL. A higher number of asthma exacerbations was associated with significantly (P < .001) lower mean PAQLQ domain scores. PAQLQ scores were significantly lower with higher numbers of baseline triggers. Higher baseline number of asthma triggers was associated with greater severity (P= .05) and number of asthma exacerbations (P < .001). A higher number of asthma triggers at baseline was associated with greater asthma severity and number of asthma exacerbations and lower QOL in children with severe/difficult-to-treat asthma.

Introduction of a new paediatric asthma guideline: Effects on asthma control levels.

In 2008, a new national paediatric asthma management guideline based on the international Global Initiative for Asthma (GINA) guideline was launched in the Netherlands. We studied whether asthma control and treatment regimens improved after introduction of the guideline by comparing survey data before and after the guideline introduction. Two comparable groups of children (6-16 years) with asthma were included before (2004) and after (2013) the introduction of the guideline. Children, parents and paediatricians completed questionnaires about asthma symptoms, medication and healthcare use. Spirometry was performed. Data of 209 patients were analysed. Level of asthma control did not improve between 2004 and 2013 with a proportion of (partly) controlled asthmatics of 51% in 2004 and 59% in 2013 (p = 0.28). In 2013, paediatricians characterized 76% of children as (partly) controlled, while 59% of children was (partly) controlled according to GINA criteria (p < 0.05). Step-down treatment in controlled patients was more applied by paediatricians in 2013 compared to 2004 (from 8 to 40%, p < 0.05). Step-up treatment in uncontrolled patients did not improve. Asthma control did not improve after the introduction of the new guideline. Compared to 2004, an improvement was observed in step-down treatment in patients with controlled disease.

Clinical effectiveness of anticholinergic tiotropium bromide as an add-on therapy in patients with severe bronchial asthma: A randomized controlled trial

Background and Objectives: Severe asthma seen in substantial proportion of patients has been a poorly controlled disease, with recurring symptoms and exacerbations despite the use of inhaled glucocorticoids (ICS), long-acting beta-agonists (LABAs-2), leukotriene receptor antagonist (LTRA), and theophyllines. A potential alternative approach is addition of a second bronchodilator with an alternative mode of action, the anticholinergic tiotropium bromide. Hence, the present study was undertaken to evaluate clinical effectiveness of tiotropium bromide 18 mcg as add-on therapy in severe asthma patients. Methodology: A single-blinded randomized study was carried in patients with severe asthma. The patients were randomized into two groups. The study group received an addition of 18 mcg of tiotropium while both groups were continued on LABA and high dose ICS combination, theophyllines, and LTRA. Improvement in lung function (forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC], and peak expiratory flow rate [PEFR]), clinical symptoms, and quality of life were assessed by mini asthma quality of life questionnaire (mini-AQLQ) at 4, 8, and 12 weeks. Results: Seventy patients were included in the study, of which 63 completed the study period. Baseline characteristics were well matched between the groups. At the end of 12 weeks, the tiotropium group showed a mean improvement in FEV1 and FVC of 450 ml and 560 ml, respectively, as compared to the control group (P Conclusions: The addition of once-daily tiotropium to severe asthma treatment regimen including high-dose ICS plus LABA, theophyllines, and LTRA significantly improves lung functions and quality of life over 12 weeks of therapy.

Illness representations and cultural practices play a role in patient-centered care in childhood asthma: experiences of Mexican mothers

Objective: Patients’ cultural health beliefs and behaviors may conflict with biomedical healthcare values and practices potentially leading to non-adherence with asthma treatment regimens. To optimize shared decision-making, healthcare providers should understand and be sensitive to these cultural beliefs and behaviors and negotiate an asthma management plan acceptable to parents. The purpose of this study was to obtain the perspective of Mexican mothers regarding (1) their experiences of living with a child with asthma, (2) their understanding of the nature of asthma, and (3) how their cultural beliefs influence asthma management. Methods: A qualitative, phenomenological study design was employed to assess mothers’ lived experiences with and perceptions of their child’s asthma. Individual in-depth interviews were conducted with a purposeful sample of 20 Mexican mothers of children ages 5–17 years with asthma. An inductive, theory-driven, phenomenological analysis approach was used to elicit thematic findings. Results: Mothers expressed a symptomatic perception of asthma and limited understanding of the disease. Most believe the disease is present only when their child is symptomatic. Many are surprised and puzzled by the unpredictability of their child’s asthma attacks, which they report as sometimes “silent”. The inconsistency of triggers also leads to frustration and worry, which may reflect their concerns around daily controller medication use and preference for alternative illness management strategies. Conclusions: Our clinical encounters should be refocused to better understand the context of these families’ lives and the cultural lens through which they view their child’s asthma.

Design of a smartphone application to monitor stress, asthma symptoms, and asthma inhaler use

Design of a smartphone application to monitor stress, asthma symptoms, and asthma inhaler use

Physician-prescribed Asthma Treatment Regimen does not differ Between Smoking and Non-smoking Patients With Asthma in Seoul and Gyunggi province of Korea.

PurposeSmoking has detrimental effects on asthma symptom control and response to treatment and is prevalent among asthma patients in South Korea. The aim of this study is to determine the prevalence of smoking among asthma patients in South Korea and to compare the medication regimens of asthma patients who do and do not smoke.MethodsA cross-sectional survey was conducted from August 2010 to January 2011. Participating physicians (N=25) recorded demographic and clinical data on all asthma patients presenting during the study period (N=2,032), and then recruited a subset of patients (N=500) for the survey such that half were self-reported current smokers. Recruited patients were between the ages of 18 and 60.ResultsAmong presenting asthma patients, 17.3% were current smokers, 19.2% were former smokers, and 63.5% had never smoked. Within the analyzable study population (N=471), 212 patients reported smoking currently, 79 smoking formerly, and 180 never smoking. Among current and former smokers, 79.7% and 81.0%, respectively, were men, while women represented 80.5% of patients who had never smoked. Agreement was strong between physician-determined smoking status and patient-reported smoking status (κ=0.82; P<0.001). However, asthma medication regimens examined according to GINA treatment steps did not differ by smoking status. In addition, mean quality of life scores and level of asthma control did not differ by smoking status.ConclusionsIn South Korea, physicians are well aware of the smoking status of their patients. However, smoking status did not affect the prescribed medication regimens of this population of asthma patients.

Asthma characteristics among older adults: using the California health interview survey to examine asthma incidence, morbidity and ethnic differences

Objective: The purpose of this study was to examine the incidence, characteristics of asthma morbidity and care, and ethnic differences that exist in older adults with asthma in California. Methods: Data were from the 2009 California Health Interview Survey (CHIS). Characteristics of older adults (≥65 years) with and without asthma were compared using population-weighted estimates. Asthma-specific variables were compared among different ethnic groups. Multivariate analyses were preformed to determine factors associated with asthma status, asthma episodes/attacks, asthma symptom frequency and emergency department (ED) visits due to asthma. Results: Asthma was present in 8.1% of older adults, among which, 67.3% reported taking medication daily for asthma. Asthma symptoms were experienced every day by almost 20%, with over 34% of seniors with asthma having symptoms at least once per week. Despite having a lower frequency of asthma symptoms, Hispanics were 5.31 times more likely to visit the ED due to asthma than were Caucasians. Conclusions: The findings from the study showed that older adults with asthma had difficulty with asthma control. We recommend a focus on asthma education so that when symptoms do occur, options are available to avoid costly ED visits. Further research should focus on specific asthma management skills and adherence to asthma treatment regimen among ethnic groups.

Distinct apoptotic machinery and selective gene regulation by glucocorticoids in Th17 cells (P1294)

Abstract Glucocorticoids (GCs) are extensively used in the treatment of inflammatory disorders and surprisingly, are ineffective in suppressing Th17 responses. We sought to determine the mechanisms underlying the insensitivity of Th17 cells to GCs. We found that in vitro polarized murine Th1 and Th2 cells, but not Th17 cells, were sensitive to GC-induced apoptosis as determined by various apoptotic markers such as annexin-V staining. At the mRNA level, GCs suppressed IL-4 and IFN-γ, and unexpectedly IL-22 but not IL-17 (A and F). Despite the distinct GC responses, Th1, Th2, and Th17 cells showed similar levels of GC receptor (GR) isoforms. Using PCR array to survey 84 genes involved in apoptosis, we found significant differences in the apoptotic machinery between Th1 and Th17 cells. Th17 cells showed increased expression of anti-apoptotic survivin and Bfl-1 whereas Th1 cells showed increased expression of pro-apoptotic Bim, Fas ligand, caspase 1, and death receptor 5. GCs induced Bim in both Th1 and Th17 cells while the same treatment decreased the expression of Nod1 and Bcl-xL in Th1 but not Th17 cells. Altered apoptotic machinery and differences in genes regulated after GC treatment may underlie the inability of GCs to induce apoptosis in Th17 cells. These studies on the mechanisms underlying the selective insensitivity of Th17 cells to GCs may provide a basis for improved treatment regimens for severe asthma and other Th17-mediated disorders.

Dynamic visco-elastic buckling analysis of an in vitro airway model: prediction of circumferential and axial buckling mode numbers

The purpose of the research reported here was to elucidate the mechanism of formation of the various lobes observed in asthmatic airways by both theoretical and experimental analysis employing an in vitro airway model. The rationale is that the elucidated mechanism will facilitate the development of new diagnostic methods and treatment regimens for asthma. Lobe formation was analyzed on the basis of an assumption of cross-sectional buckling of the airway. Here, we propose a dynamic visco-elastic buckling model analysis of the airway for the prediction of circumferential and axial buckling mode numbers. The calculated circumferential buckling mode numbers were in reasonably good agreement with those measured in the dynamic buckling experiment using the in vitro airway model. The calculated axial buckling mode numbers were in qualitative agreement with those observed in the experiment. The non-dimensional parameters related to the remodeling and the consequent pathologies occurring in asthmatic airways were also shown, and the influence of changes in the non-dimensional parameters on the circumferential and axial buckling mode numbers was also calculated. The circumferential and axial buckling mode numbers decreased due to thickening and stiffening of the basement membrane. Thickening of the tissues surrounding the basement membrane and the increase in the mucus secreted in the airway lumen were modeled as an increase in the added mass on the basement membrane. The results of calculation showed that the circumferential and axial buckling mode numbers increased because of the thickening of the surrounding tissues and the increase in mucus secretion. We suggest that it may be possible to diagnose the severity of asthma by using the results of the calculation of the changes in the buckling mode numbers caused by the changes in the strength of the remodeling. The physiological reality of the in vitro airway model reported here is discussed using the non-dimensional parameters.

Measurement of Inhaled Corticosteroid Adherence in Inner-City, Minority Children with Persistent Asthma by Parental Report and Integrated Dose Counter

Parents often overreport adherence to asthma treatment regimens making accurate assessment of medication adherence in clinical practice difficult. This study was conducted to compare two adherence assessment methods clinicians may choose from when assessing patient inhaled corticosteroid (ICS) adherence: parental report and dose counter measurements of metered-dose inhaler (MDI) actuation. Participants included children (N = 50) with persistent asthma and their parents (N = 50). At enrollment, children received a new, marked ICS at the dose prescribed by their physician. Thirty days following enrollment, we measured ICS adherence by parental report and objectively, with a dose counter. Parental report overestimated ICS adherence when compared to dose counter. We found a statistically significant overall difference between parental report and objectively measured adherence. A dose counter that most ICS inhalers are equipped with may be a more reliable alternative measure of ICS adherence in a clinical practice setting.