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- Obesity and Asthma in Children: Current and Future Therapeutic Options. [JOURNAL ARTICLE]
- Paediatr Drugs 2014 Mar 7.
With the childhood prevalence of obesity and asthma increasing, it is important for pediatric professionals to appreciate that obesity modifies the diagnosis and management of asthma. These disease modifications present challenges to clinical management, including decreased responsiveness to controller therapy and decreased quality of life compared with normal-weight asthmatic children. While consensus guidelines do not currently suggest specific changes in asthma management for obese patients, management of some patients may be improved with consideration of the latest evidence. This article briefly summarizes what is known regarding the complex relationship between obesity and asthma in children, and discusses practical issues associated with the diagnosis and effective clinical management of asthma in obese children. On average, obese patients with asthma do not respond as well to inhaled corticosteroid therapy. Management approaches including weight loss and routine exercise are safe, and may improve important asthma outcomes. Asthma providers should learn to facilitate weight loss for their obese patients. In addition, pharmacologic interventions for weight loss in obese asthma, though not currently recommended, may soon be considered.
- Short-Term Effects of the Particulate Pollutants Contained in Saharan Dust on the Visits of Children to the Emergency Department due to Asthmatic Conditions in Guadeloupe (French Archipelago of the Caribbean). [Journal Article]
- PLoS One 2014; 9(3):e91136.
The prevalence of asthma in children is a significant phenomenon in the Caribbean. Among the etiologic factors aggravating asthma in children, environmental pollution is one of the main causes. In Guadeloupe, pollution is primarily transported by Saharan dust including inhalable particles.This study assesses, over one year (2011), the short-term effects of pollutants referred to as PM10 (PM10: particulate matter <10 µm) and PM2.5-10 (PM2.5-10: particulate matter >2.5 µm and <10 µm) contained in Saharan dust, on the visits of children aged between 5 and 15 years for asthma in the health emergency department of the main medical facility of the archipelago of Guadeloupe. A time-stratified case-crossover model was applied and the data were analysed by a conditional logistic regression for all of the children but also for sub-groups corresponding to different age classes and genders.The visits for asthma concerned 836 children including 514 boys and 322 girls. The Saharan dust has affected 15% of the days of the study (337 days) and involved an increase in the average daily concentrations of PM10 (49.7 µg/m3 vs. 19.2 µg/m3) and PM 2.5-10 (36.2 µg/m3 vs. 10.3 µg/m3) compared to days without dust. The excess risk percentages (IR%) for visits related to asthma in children aged between 5 and 15 years on days with dust compared to days without dust were, for PM10, ((IR %: 9.1% (CI95%, 7.1%-11.1%) versus 1.1%(CI95%, -5.9%-4.6%)) and for PM2.5-10 (IR%: 4.5%(CI95%, 2.5%-6.5%) versus 1.6% (CI95%, -1.1%-3.4%). There was no statistical difference in the IR% for periods with Saharan dust among different age group of children and between boys and girls for PM10 and PM2.5-10.The PM10 and PM2.5-10 pollutants contained in the Saharan dust increased the risk of visiting the health emergency department for children with asthma in Guadeloupe during the study period.
- Between-visit variability of small airway obstruction markers in patients with asthma. [JOURNAL ARTICLE]
- Eur Respir J 2014 Mar 6.
To the Editor:Clinical trials in patients with airway diseases often use forced expiratory volume in 1 s (FEV1) as the sole physiological outcome measure. However, FEV1 is thought to be insensitive to obstruction of the smaller airways, which may be particularly relevant in asthma (1). Putative markers of small airway obstruction include measures of airway resistance using impulse oscillometry (IOS) (2) and indices of ventilation heterogeneity derived from multiple-breath inert gas washout (MBW) (3). We recently showed that increased airway resistance at 5 Hz (R5) and 20 Hz (R20) is associated with worse asthma control and more frequent exacerbations (4), and Farah et al. (5) demonstrated that MBW parameters may be responsive to asthma therapy.In order to conduct clinical trials using these alternative outcome measures, it is necessary to be assured of their repeatability and stability over time. Moreover, an estimate of between-visit variability in the stable state is required so that sample size calculations can be performed. We therefore aimed to determine the between-visit variability of a range of IOS and MBW indices in a group of patients with asthma in the stable state. We investigated between-visit variability over two time intervals, namely 2 weeks and 3 months, in order to encompass the typical lengths.
- Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement. [JOURNAL ARTICLE]
- Eur Respir J 2014 Mar 6.
This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed.Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare.A positive response is defined by a fall in forced expiratory volume in 1 s ≥15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma.
- Impact of Prescription Patterns on Compliance With Follow-Up Visits at an Urban Teaching Primary Care Continuity Clinic. [JOURNAL ARTICLE]
- J Prim Care Community Health 2014 Mar 5.
Although limiting prescription refills is considered as a strategy to increase compliance with the treatment regimen and follow-up, no literature exists to support its effectiveness. We sought to investigate whether decreasing the number of prescription refills affects no-show rate at an urban teaching primary care continuity clinic in New York.Eight teaching attending physicians and 19 residents implemented a "new prescribing strategy" from February 9 to 22, 2012, which limited the number of refills only to cover until the next intended clinic visit. All adult patient visits were included if follow-up visits were requested to be scheduled within 3 months and prescriptions were given through an electronic prescription system. No-show rates for the first follow-up visits up to 120 days from the initial visits during the interventional period were compared with those during the baseline period (December 15-28, 2011).Two hundred twenty-one patients in the baseline period and 278 in the interventional period were included in the analysis. Median total supply of prescription was 6 and 3 months, respectively (P < .001). The no-show rates were not significantly different between the 2 periods (19.0% [42/221] vs 16.6% [46/278], P = .5). In multivariate regression analysis, the no-show rate did not change significantly during the interventional period compared with the baseline period (odds ratio [OR] 1.0; 95% confidence interval, 0.6-1.5; P = .8). Younger age (OR 1.03 per year, P = .008), male gender (OR 2.0, P = .003), Medicaid or Medicare insurance (OR 3.7, P = .01; OR 4.2, P = .02), and diagnosis of diabetes (OR 1.8, P = .04) or asthma (OR 2.0, P = .03) were associated with higher no-show rates.Reducing the number of refills did not significantly affect no-show rates in the immediate follow-up. Alternative strategies should be considered to minimize no-shows.
- Expression of genes related to anti-inflammatory pathways are modified among farmers' children. [Journal Article]
- PLoS One 2014; 9(3):e91097.
The hygiene hypothesis states that children exposed to higher loads of microbes such as farmers' children suffer less from allergies later in life. Several immunological mechanisms underpinning the hygiene hypothesis have been proposed such as a shift in T helper cell balance, T regulatory cell activity, or immune regulatory mechanisms induced by the innate immunity.To investigate whether the proposed immunological mechanisms for the hygiene hypotheses are found in farmers' children.We assessed gene expression levels of 64 essential markers of the innate and adaptive immunity by quantitative real-time PCR in white blood cells in 316 Swiss children of the PARSIFAL study to compare farmers' to non-farmers' expressions and to associate them to the prevalence of asthma and rhinoconjunctivitis, total and allergen-specific IgE in serum, and expression of Cε germ-line transcripts.We found enhanced expression of genes of the innate immunity such as IRAK-4 and RIPK1 and enhanced expression of regulatory molecules such as IL-10, TGF-β, SOCS4, and IRAK-2 in farmers' children. Furthermore, farmers' children expressed less of the TH1 associated cytokine IFN-γ while TH2 associated transcription factor GATA3 was enhanced. No significant associations between the assessed immunological markers and allergic diseases or sensitization to allergens were observed.Farmers' children express multiple increased innate immune response and immune regulatory molecules, which may contribute to the mechanisms of action of the hygiene hypothesis.
- Ethnic and gender differentials in non-communicable diseases and self-rated health in malaysia. [Journal Article]
- PLoS One 2014; 9(3):e91328.
This paper examines the ethnic and gender differentials in high blood pressure (HBP), diabetes, coronary heart disease (CHD), arthritis and asthma among older people in Malaysia, and how these diseases along with other factors affect self-rated health. Differentials in the prevalence of non-communicable diseases among older people are examined in the context of socio-cultural perspectives in multi-ethnic Malaysia.Data for this paper are obtained from the 2004 Malaysian Population and Family Survey. The survey covered a nationally representative sample of 3,406 persons aged 50 and over, comprising three main ethnic groups (Malays, Chinese and Indians) and all other indigenous groups. Bivariate analyses and hierarchical logistic regression were used in the analyses.Arthritis was the most common non-communicable disease (NCD), followed by HBP, diabetes, asthma and CHD. Older females were more likely than males to have arthritis and HBP, but males were more likely to have asthma. Diabetes and CHD were most prevalent among Indians, while arthritis and HBP were most prevalent among the Indigenous groups. Older people were more likely to report poor health if they suffered from NCD, especially CHD. Controlling for socio-economic, health and lifestyle factors, Chinese were least likely to report poor health, whereas Indians and Indigenous people were more likely to do so. Chinese that had HBP were more likely to report poor health compared to other ethnic groups with the same disease. Among those with arthritis, Indians were more likely to report poor health.Perceived health status and prevalence of arthritis, HBP, diabetes, asthma and CHD varied widely across ethnic groups. Promotion of healthy lifestyle, early detection and timely intervention of NCDs affecting different ethnic groups and gender with socio-cultural orientations would go a long way in alleviating the debilitating effects of the common NCDs among older people.
- Mitochondria in the center of human eosinophil apoptosis and survival. [Journal Article]
- Int J Mol Sci 2014; 15(3):3952-69.
Eosinophils are abundantly present in most phenotypes of asthma and they contribute to the maintenance and exacerbations of the disease. Regulators of eosinophil longevity play critical roles in determining whether eosinophils accumulate into the airways of asthmatics. Several cytokines enhance eosinophil survival promoting eosinophilic airway inflammation while for example glucocorticoids, the most important anti-inflammatory drugs used to treat asthma, promote the intrinsic pathway of eosinophil apoptosis and by this mechanism contribute to the resolution of eosinophilic airway inflammation. Mitochondria seem to play central roles in both intrinsic mitochondrion-centered and extrinsic receptor-mediated pathways of apoptosis in eosinophils. Mitochondria may also be important for survival signalling. In addition to glucocorticoids, another important agent that regulates human eosinophil longevity via mitochondrial route is nitric oxide, which is present in increased amounts in the airways of asthmatics. Nitric oxide seems to be able to trigger both survival and apoptosis in eosinophils. This review discusses the current evidence of the mechanisms of induced eosinophil apoptosis and survival focusing on the role of mitochondria and clinically relevant stimulants, such as glucocorticoids and nitric oxide.
- Lipid Profiles Alter from Pro-Atherogenic into Less Atherogenic and Proinflammatory in Juvenile Idiopathic Arthritis Patients Responding to Anti TNF-α Treatment. [Journal Article]
- PLoS One 2014; 9(3):e90757.
Dyslipidemia with higher inflammatory states, disease activity, and longer disease duration in juvenile idiopathic arthritis (JIA) patients seemed to increase the risks of atherosclerosis. Tumor necrosis factor- α (TNF-α) receptor blocking agent etanercept has been proven to be effective in JIA. However, data about the correlation of anti-inflammatory treatment on lipid profiles and atherogenic index in JIA patients remains limited. This study aimed to investigate the longitudinal changes on lipid profiles and atherogenic index in JIA patients after etanercept treatment.Twenty-three patients diagnosed with JIA (polyarticular type n = 7; oligoarticular type, n = 2; systemic type, n = 10, Enthesitis-related arthritis = 4) received treatment with etanercept during the period 2004-012 in a medical center. We measured their serum lipid profiles at baseline and 2, 4, 6, 12 months later, and determined whether there were differences in complete blood counts, inflammatory mediators, lipid levels and atherogenic indices between patients who had inactive disease (responders) and those who were poor responders (non-responders) to etanercept treatment.Analysis of dynamic change in total JIA patients before and after TNF inhibitor therapy showed modest increases in hemoglobin levels (P = 0.02) and decreases in WBC counts, Platelet and CRP levels progressively (p = 0.002, p = 0.006 and p = 0.006, respectively).Twelve of the 23 patients achieved inactive disease status (responders) after 12-months of treatment. In responders, compared to non-responders, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increased significantly (P = 0.007,P = 0.044,P<0.001), whereas triglyceride and atherogenic index (TC/HDL-C ratio) significantly decreased (P = 0.04, P = 0.01, respectively) after etanercept treatment.Disease severity was associated with triglyceride level, atherogenic index and was inversely associated with total cholesterol, HDL-C, and LDL-C levels and can be improved substantially by using anti TNF-α treatment. Such treatment may have a beneficial effect on the cardiovascular risk in patients with JIA.
- Clinical features of eosinophilic esophagitis. [Journal Article]
- Dig Dis 2014; 32(1-2):61-7.
Eosinophilic esophagitis (EoE) may affect individuals at any age with a predominance for Caucasian males. The clinical manifestation of EoE is strongly age dependent. While dysphagia and food impaction are typical lead symptoms in adults and adolescents, infants often present with unspecific symptoms such as feeding problems, abdominal pain and vomiting. Some EoE patients may also experience heartburn. Therefore, EoE should always be considered in cases of heartburn refractory to antireflux therapy. Concomitant allergic diseases such as asthma, rhinitis and eczema are prevalent. Peripheral eosinophilia and elevated total serum IgE values are found in up to 50 and 70% of cases, respectively. Endoscopic features of EoE are variable and none of them is pathognomonic. Frequent findings are mucosal edema, furrows, exudates and corrugated rings. These endoscopic abnormalities have high specificities (90-95%), but low sensitivities (15-48%). A novel grading and classification system for the endoscopic assessment of EoE has been proposed which includes fixed rings, exudates, furrows and edema as major features. This classification system demonstrated good interobserver agreement among pediatric and adult gastroenterologists, and presents a useful tool to standardize endoscopic assessments and to further investigate the relation between endoscopic manifestation, clinical activity and response to treatment in EoE. Long-term follow-up studies have shown that EoE is a chronic disease causing recurrent dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of disease, which stresses the importance of early diagnosis and consequent treatment of EoE. © 2014 S. Karger AG, Basel.