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Objectives: While asthma presents various clinical forms with different levels of severity, it is unclear whether asthma severities are a consequence of disease management or varied etiologies. We sought to investigate this question. Methods: This paper presents a cross-sectional study of 113,671 Israeli adolescents. Prevalence rates of mild and moderate-to-severe asthma over a 24-year period were calculated and multivariate regression models (outcomes: different asthma severity, reference: subjects without asthma) were performed to analyze associations with anthropometric indices and socio-demographic variables, in males and females separately. Results: The prevalence of mild asthma increased until birth years 1976-1980 and then steadily decreased. In contrast, the prevalence of moderate-to-severe asthma was relatively stable until birth years 1976-1980, then rose steeply until 1986-1990 and subsequently plateaued in the early 1990s. Obesity was positively associated with both mild and moderate-to-severe asthma in males (Odds Ratio (OR) [95%CIs]: 1.61 [1.37-1.89] and 1.63 [1.34-1.98], respectively) and females (1.54 [1.10-2.16] and 1.54 [1.20-1.98], respectively). Family size greater than three siblings was negatively associated with both mild and moderate-to-severe asthma in males (0.62 [0.56-0.68] and 0.59 [0.52-0.68]) and females (0.71 [0.60-0.83] and 0.73 [0.63-0.83]). In contrast, in males, underweight was only associated with mild asthma (1.54 [1.22-1.94]) but not with moderate-to-severe asthma. In females, overweight was only associated with moderate-to-severe asthma (1.21 [1.00-1.46]) and rural residence was only associated with mild asthma (1.26 [1.09-1.47]). Conclusions: The differences between mild and moderate-to-severe asthma enhance asthma phenotype characterization, with respect to secular trends and associated variables, and indicate varied etiologies. [ABSTRACT FROM AUTHOR]

Objective: To identify challenges that disadvantaged adults with asthma face in mitigating social and environmental factors associated with poor symptom control. Methods: Using a community-engaged approach, we partnered with a community health center in New Haven, CT to conduct in-person interviews and a written survey of asthmatic adults with poor symptom control. Using the constant comparative method, we analyzed participant interviews to establish emerging themes and identify common barriers to improved outcomes. Through a written survey utilizing clinically validated questions, we assessed information on access to medical care, asthma control, and selected social and environmental risk factors. Results: Twenty-one patients (mean age 47, 62% female, 71% Black, 95% insured by Medicaid) participated. The average Asthma Control Test (ACT) score was 11.6. Seventy-six percent of participants were currently employed and of those, 75% reported work-related symptoms. Among participants currently in housing, 59% reported exposure to domiciliary mice and 47% to mold. We identified three themes that summarize the challenges the study participants face: 1) Lack of knowledge about home and workplace asthma triggers; 2) Lack of awareness of legal rights or resources available to mitigate adverse conditions in the home or work environment; and 3) Fear of retaliation from landlords or employers, including threats of eviction, sexual assault, and job loss. Conclusion: Patients with poorly controlled asthma in a disadvantaged urban northeast community identified common barriers in both the domestic and work environments that impeded attainment of symptom control. These challenges may be best addressed through legal advocacy for those most at risk. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin (IL)‐17 is a major contributor to the pathogenesis of allergic asthma. Developmental endothelial locus‐1 (Del‐1) is an endothelial cell‐secreted protein known to inhibit IL‐17 expression. However, little is known about the association between Del‐1 and IL‐17 in the pathogenesis of allergic asthma. Using bronchoalveolar lavage fluid (BALF) and peripheral blood samples collected from allergic asthmatic patients and controls, we explored the role of Del‐1 in relation to IL‐17 in allergic asthma. We found that the negative correlation between Del‐1 and IL‐17 was significant in BALF of allergic asthmatics. Del‐1 treatment inhibited the expression of IL‐17, the differentiation of IL‐17‐secreting leukocytes and associated cytokines. Contrarily, IL‐17 levels were increased after treatment with anti‐Del‐1 mAb. Consistent with this, Del‐1 treatment led to downregulation of IL‐5, CCL5 and IL‐4, thus reducing secretion of eosinophil cationic protein. Furthermore, Del‐1 significantly downregulated the expression of ICAM‐1 and may have the potential to reduce leukocyte transendothelial migration. Our data demonstrate that Del‐1 can negatively regulate IL‐17 and its proinflammatory function, thereby limiting airway inflammation in allergic asthmatics, and suggest Del‐1 as a potential candidate for prevention and treatment of allergic asthma. [ABSTRACT FROM AUTHOR]

Abstract: Background: Treatment non‐adherence is a challenge to achieve asthma control. However, few prospective studies were done for exploring asthma patient adherence in real world. Objectives: To evaluate treatment adherence and causes of non‐adherence in a large asthma Chinese population. To analyze newly‐diagnosed patients' adherence first time. Methods: About 1582 asthma patients' data were collected from 12 study centers in China from February, 2012 to October, 2012. Disease and treatment information of subjects were collected were at first clinic visit, at 4, 12, and 24 weeks after that, follow‐up phone calls were carried out for recording subjects' treatment adherence based on their self‐reports. Subjects who reported non‐adherence were additionally asked to choose the primary non‐adherence cause from a list of nine potential causes. Results: Treatment adherence rate of all subjects markedly decreased from 83.3% at week 4 to 42.0% at week 24 after the first clinic visit. Significantly, at week 24, good treatment adherence rate in newly‐diagnosed patients was lower than those patients with asthma history (22.9% vs. 63.9%, P < .001). Newly‐diagnosed patients were three times more likely to become non‐adherence than those patients with asthma history. Female patients had lower treatment adherence rate than male patients (38.3% vs. 45.6%, P = .006). Subjects in 30‐39 year age group had the worst treatment adherence (27.3%). The most commonly chosen cause for non‐adherence was “relief of symptoms after short‐term controller medication use” (43.8%). Conclusions: Asthma patients' treatment adherence could be improved by improving patient education, doctor/patient partnership, and level of medical service in Chinese population. [ABSTRACT FROM AUTHOR]

Cytomegalovirus ( CMV) IgG antibodies have been associated with inflammaging and immunosenescence. We aimed to assess the presence of CMV DNA in the blood of adult and elderly patients with bronchial asthma to establish potential association of CMV DNAemia with asthma and asthma characteristics. Eighty-five elderly asthmatics, 74 younger asthma patients, and 114 age-matched controls were recruited. The CMV DNA was detected using commercial artus assay in 10.7% of asthma patients, but was negative in all control individuals. The secondary assay identified CMV DNA in 41.5% of asthmatics and 13.3% of control subjects ( P < .001). Presence of CMV DNA was associated with an increased risk of asthma and CMV DNA copy numbers correlated with some asthma traits, including respiratory parameters and exhaled breath nitric oxide. We conclude that CMV infection is associated with asthma and may contribute to the pathogenesis of asthmatic inflammation. [ABSTRACT FROM AUTHOR]

The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab. Moreover, since 2010, bronchial thermoplasty has been successfully introduced for a limited number of patients. This is a nonpharmacologic endoscopic procedure which is considered a promising therapy, even though several aspects still need to be clarified. Despite the increasing availability of new therapies, one of the major problems of each treatment is still the identification of the most suitable patients. This sudden abundance of therapeutic options, sometimes partially overlapping with each other, increases the importance to identify new biomarkers useful to guide the clinician in selecting the most appropriate patients and treatments, without forgetting the drug-economic aspects seen in elevated direct cost of new therapies. The aim of this review is, therefore, to update the clinician on the state of the art of therapies available for refractory asthma and, above all, to give useful directions that will help understand the different choices that sometimes partially overlap and to dispel the possible doubts that still exist. [ABSTRACT FROM AUTHOR]

Increased ambient concentration of particulate matters are considered as one of major causes for increased prevalence or exacerbation of asthma or asthma like symptoms. Recently, possible temporal variation in risks of PM on mortality has been suggested. We investigated short-term effect of both PM 10 and PM 2.5 on asthma hospitalization, and assessed temporal variation of PM risks in Seoul, Korea, 2003–2011. Generalized additive model was used to estimate PM risks on asthma hospitalization with consideration by long-term trend, influenza epidemic, day of week, meteorological factors. To assess temporal variation of PM risks, year-round PM risks were estimated. Stratified analysis by season and age-group were also conducted. Estimated RRs of PM on asthma hospitalization by an increase of 10㎍/㎥were 1.0084 (95% CI: 1.0041–1.0127) and 1.0156 (95% CI: 1.0055–1.0259) respectively with 7-days lag periods (lag06). PM 2.5 had stronger effect than PM 10 for all age group. Elderly group was most affected by PM. For the analysis of temporal variation of PM risks, we found increasing trend in total population and the elderly group. In the season-specific analysis, we also found increasing trend in winter for PM 10 , and in spring for PM 2.5 . PM 10 and PM 2.5 has adverse effect on asthma hospitalization with evidence suggesting temporal variation in PM risks. Further research will be needed to confirm the temporal variation of PM risk on asthma hospitalization, and to identify casual factors affecting this temporal variation. This study results could be evidentiary materials for establishing valid public health policies to reduce health burden or economic burden of asthma. [ABSTRACT FROM AUTHOR]

Linker for activation of T cells (LAT) is a key adaptor in the T cell receptor (TCR) signaling pathway. The expression of LAT is lower in asthmatic patients than that in healthy people, but there is little knowledge about the mechanism underlying this phenomenon. This study was aimed to determine whether LAT-PLC-γ1 interaction was involved in the development of asthma. It was shown that the phosphorylation of PLC-γ1 decreased in the asthmatic mouse model and Th2 cell differentiated CD4+ T cells. In addition, depleted endogenous PLC-γ1 promoted CD4+ T cells to differentiate into IL-4-Productor. It was therefore concluded that the low level of LAT-PLC-γ1 interaction was associated with Th2 polarized differentiation, and this may contribute to the etiology of asthma. [ABSTRACT FROM AUTHOR]

Background Hyperpolarised ³He MRI provides a way to visualise regional pulmonary functional abnormalities that in asthma are thought to be related to airway morphological abnormalities. However, the exact aetiology of ventilation defects in asthma is not well understood. Objective To better understand the determinants of ventilation defects in asthma, we evaluated wellestablished clinical as well as ³He MRI and X-ray CT airway measurements in healthy subjects and subjects with asthma. Methods Thirty-four subjects (n=26 subjects with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography, fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a region-of-interest proximal to ventilation defects. For subjects who consented to CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3rd to 5th generation airway wall area and wall thickness per cent and lumen area. Results Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of ³He ventilation defects prior to bronchoprovocation and nine subjects with asthma had no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with asthma with defects were older (p=0.01) with worse forced expiratory volume in 1 s (FEV1)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of methacholine that reduced FEV1 by 20% ( p=0.008) and wall thickness per cent (p=0.02) compared with subjects with asthma without defects. There was a moderate correlation for wall area per cent with ventilation defect per cent (r=0.43, p=0.04). Conclusions Subjects with asthma with ³He ventilation defects were older with significantly worse airway hyperresponsiveness, inflammation and airway remodelling but similar FEV1 as subjects with asthma without defects; hyperpolarised ³He ventilation abnormalities were spatially and quantitatively related to abnormally remodelled airways. [ABSTRACT FROM AUTHOR]

In the majority of cases, asthma and chronic obstructive pulmonary disease (COPD) are two clearly distinct disease entities. However, in some patients there may be significant overlap between the two conditions. This constitutes an important area of concern because these patients are generally excluded from randomised controlled trials (mostly because of smoking history in the case of asthma or because of significant bronchodilator reversibility in the case of COPD). As a result, their pathobiology, prognosis and response to therapy are largely unknown. This may lead to suboptimal management and can limit the development of more personalised therapeutic options. Emerging genetic and molecular information coupled with new bioinformatics capabilities provide novel information that can pave the way towards a new taxonomy of airway diseases. In this paper we question the current value of the terms 'asthma' and 'COPD' as still useful diagnostic labels; discuss the scientific and clinical progress made over the past few years towards unravelling the complexity of airway diseases, from the definition of clinical phenotypes and endotypes to a better understanding of cellular and molecular networks as key pathogenic elements of human diseases (so-called systems medicine); and summarise a number of ongoing studies with the potential to move the field towards a new taxonomy of airways diseases and, hopefully, a more personalised approach to medicine, in which the focus will shift from the current goal of treating diseases as best as possible to the so-called P4 medicine, a new type of medicine that is predictive, preventive, personalised and participatory. [ABSTRACT FROM AUTHOR]

Abstract: The etiology of status asthmaticus (SA), a complication of severe asthma, is unknown. Fungal exposure, as measured by fungal atopy, is a major risk factor for developing asthma, but the relationship of fungi in SA per se has not previously been reported. In this five patient retrospective case series study, lower respiratory tract cultures were performed on bronchoalveolar lavage or tracheal aspirate fluid, comparing standard clinical laboratory cultures with a specialized technique in which respiratory mucus was removed prior to culture. We show that mucolytic treatment allows an increased detection of fungal growth, especially yeast, from the lower airways of all SA patients. We also demonstrate that inhalation of the yeast Candida albicans readily induces asthma-like disease in mice. Our observations suggest that SA may represent a fungal infectious process, and support additional prospective studies utilizing anti-fungal therapy to supplement conventional therapy, broad-spectrum antibiotics and high-dose glucocorticoids, which can promote fungal overgrowth. [Copyright &y& Elsevier]

Adherence in asthma is an important cause for concern. Although nearly 50% of asthma patients are considered poorly adherent to therapeutic advices, adherence is still difficult to assess, understand and improve despite major medical consequences. In this review, we revisited the literature of the last 10 years related to adherence in severe asthma. The concepts have changed and 'compliance' is usually replaced by 'adherence'. Assessment of adherence is addressing ethical issues, but provides important insight into difficult-to-treat asthma. Different tools have been used but none is routinely recommended. Health-related outcomes (poor control, exacerbations, hospitalizations, lung function decline), which are clearly associated with severe asthma, are often worsened by non-adherence with consequences also on patient related outcomes (quality of life). The potential behaviour associated with non-adherence and all other related factors including easy-to-recognize psychological traits can help for patient's future management. Therapeutic educational interventions have been recognized with a scientifically proven efficiency even though evolution and improvements are needed. A multidisciplinary approach is required in severe asthma. Therapeutic adherence for a given patient is always a prerequisite to any other aspects when addressing severe asthma phenotypes. Severe asthma should be considered only in those who still experienced poor asthma outcomes despite optimal adherence. At a glance, poor adherence and severe asthma should be considered antinomic. Better understanding of the causes and customised management are potential future directions. [ABSTRACT FROM AUTHOR]

Bakers are frequently exposed to various irritant chemicals during work which can induce respiratory problems. In this study, pulmonary function tests and self-reported respiratory and allergic symptoms in bakers were compared with matched control subjects. The frequency of respiratory and allergic symptoms was evaluated in a sample of 58 Iranian bakers and 58 control subjects using a questionnaire. Pulmonary function tests (PFT) were also measured in all participants. All respiratory symptoms were significantly higher in bakers than control croup (p<0.05 to p<0.005). All allergic symptoms in bakers were also significantly greater than control group (p<0.05 to p<0.005). In addition, all respiratory (except sputum) and allergic (except urticaria) symptoms were significantly higher in bakers compared to rest period (p<0.05 to p<0.01) during work. Most PFT values except MEF25 were also significantly lower in bakers than control subjects (p<0.05 to p<0.001). These results showed that bakers have a higher frequency of work related respiratory symptoms and to a lesser extend allergic symptoms particularly during the work period. PFT values were also significantly reduced among bakers. [ABSTRACT FROM AUTHOR]

The article presents the key points related to the management of acute asthma among children in primary care. Topics discussed include the number of children under asthma treatment in Great Britain, its features that parents need to consider, and the requirement for asthma patients to have a personalised asthma action plan.

The author reflects on the study conducted by C. D. Thomson and colleagues regarding asthma in children. The author states that there had been no evidence in the relationship of dietary selenium levels with asthma which was tackled in the study and the effect of nutritional antioxidants to the development of asthma in children. An overview of the occurrence of allergic asthma in children is presented.

The article focuses on the clinical importance of asthma control. It is difficult to find out the accurate assessment of asthma control because disease variability requires assessment of a variety of outcomes such as day and night symptoms, need for rescue medication and impairment of daily activities. For avoiding these problems, several tools have been developed including the Asthma Control Test (ACT), the Asthma Control Questionnaire (ACQ) and the Asthma Control Scoring System.