Some but not all of this difference can be explained by factors such as a higher incidence of low birth weight LBW among blacks; however, even conditional on LBW, blacks have a higher incidence of asthma than others.
All LBW children in these zip codes, regardless of race, have a higher incidence of asthma. Our results point to the importance of residential segregation and neighborhoods in explaining persistent racial health disparities. Residential segregation and racial gaps in childhood asthma, " Journal of Health Economics,. Development of the American Economy. Economic Fluctuations and Growth. International Finance and Macroeconomics. International Trade and Investment. Responses to infection then may vary depending on the characteristics of asthmatic inflammation, and there is the implication that treatment with high doses of ICS may increase susceptibility to viral infection in asthma.
This is an area of great interest and could have significant implications for individually tailored IFN augmentation treatments. Dysregulated type II immune responses are seen in a large proportion of asthmatics, especially those with childhood-onset disease. The mechanisms of impaired IFN responses and how they relate to the type II inflammatory responses typically seen in asthmatics is also of considerable interest in the current literature. Contoli et al. This resulted in increased RV replication in the cultures This study demonstrates that a type II immune cytokine environment alone is sufficient to dampen innate immune responses in BECs.
In contrast, Herbert et al. It was found that SOCS1 protein expression was increased in the airway epithelium from asthmatic adults measured in bronchial biopsy specimens, and the presence of SOCS1 correlated with a greater severity of atopy and airway hyper-responsiveness Therefore, increased levels of SOCS1 were shown to impair IFN induction in asthmatic patients through its nuclear localization, but this was specific for only antiviral immunity, as inflammatory mediators were not affected. This is a novel study revealing a possible mechanism for impaired IFN responses in asthmatics.
Jackson et al.
IL was strongly induced by RV infection of primary bronchial cells in vitro. IL has also been suggested as a link between innate immune activation and type II immune responses in asthma. In mice, Tashiro et al. Another emerging and important link between activation of the innate immune response in asthma and acquired type II immune responses that are driven by T helper type 2 TH2 cells are innate lymphoid cells ILCs. These are non-T, non-B lymphocytes that can be activated rapidly in response to external stimuli without the need for a specific antigen—antibody interaction.
The role for ILC2s in asthma is currently under intense investigation. In a pioneering study, Duerr et al. In turn, Lynch et al.
This was shown to be through the downregulation of viperin and IRAK1 in plasmacytoid dendritic cells in vivo and in vitro , leading to a state of TLR7 hyper-responsiveness While overall very few in number, elevated numbers of ILC2s have been previously found in the peripheral blood of allergic asthmatics.
The investigators found that the frequencies of ILC2s were increased in asthmatics 0. These studies provide exciting links between innate anti-viral responses and the type II cytokine inflammatory conditions seen in asthma and are summarized in Figure 1.http://kick-cocoa.info/components/fylusyta/fyze-sentire-le-chiamate.php
Asthma Research Papers
If a type II cytokine environment suppresses IFN responses, and IFN responses are able to suppress ILC2s, then in asthma there could be a positive cycle feeding into an exaggerated pro-inflammatory cytokine response, as well as a perpetuation of viral replication. This could provide insights into what happens during a viral infection and exacerbations leading to worsened asthmatic inflammation. The asthmatic airway is suggested to be deficient in the production of interferons in response to rhinovirus infection. This contributes to increased viral replication.
IL is induced by rhinovirus infection and activates type 2 innate lymphoid cells ILC2s , which in turn release type II cytokines and pro-inflammatory cytokines such as IL-6 and granulocyte macrophage colony-stimulating factor GM-CSF. BECs have been recognized as having an important contribution to the innate immune response but are thought to have a limited contribution to adaptive immune responses.
Asthma Research Papers - tuzysreisimill.ml
Zissler et al. The prevention of asthma or modifying the risk of its development in utero would clearly be enormously beneficial to society and for those suffering from asthma throughout their lives. Vitamin D has long been implicated in the pathogenesis of asthma and immunity, and two important trials sought to determine if vitamin D3 supplementation could influence the development of asthma in early childhood.
The first trial, which was based in Europe, recruited women at 24 weeks and followed children to age 3 Women were randomized to receive the usual supplement of IU or vitamin D at IU, with the primary aim being that supplementation would reduce persistent wheeze at age 3 years.
The second trial reported in the same journal was a larger US study in three centers and followed children to age 3 but recruited women whose children were at high risk of asthma Interestingly, most of the effect appeared to occur in the first 1—2 years and then may have waned. In both studies, those who received extra supplementation were more likely to be vitamin D sufficient. The results seen in both trials were similar, and it is possible that the trials were underpowered to detect such a complex outcome, though as a consequence the case that vitamin D supplementation will modify asthma risk remains unproven.
The risk of developing early life asthma is complex and it has been known for some time that this risk is modified by gender, with a heightened risk in boys that switches to girls at puberty The complexity of early life asthma was illustrated by a cross-sectional US epidemiological survey that further emphasized the importance of gender In singleton live births that were followed by questionnaire at 6 months and then yearly until age 9, the investigators found The strong association between paternal asthma and risk in boys is certainly emphasized as well as confirming the role of other previously described environmental and social factors.
These studies emphasize that for boys, paternal inherited factors appear to play an important role in developing persistent asthma and what those factors are should be further investigated. The close association between asthma and allergy to dust mites in childhood has led to numerous interventions to reduce the impact of this exposure on asthma. The advent of sublingual immunotherapy has revised academic interest in desensitization, opening this up as a therapy to more individuals with less disruption and potentially less risk compared to subcutaneously administered protocols of desensitization.
Virchow et al.
The impact of severe asthma on patients’ autonomy: A qualitative study
Subjects were randomized to receive either placebo or two doses of sublingual HDM; the primary outcome was a reduction in time to first moderate to severe exacerbation. Both of the doses reduced the risk of asthma exacerbation hazard ratio 0. While the effect seen was modest, it does demonstrate that chronic allergen exposure plays a direct role in exacerbation risk and, if reduced, modifies asthma.
Exacerbations of asthma in children continue to occur despite treatment and are more likely in those with more severe disease and a history of previous exacerbations An interesting phenomenon that has been seen with these exacerbations has been a rise that occurs when children first return to school from their summer holidays that has been attributed to the combined effects of allergen exposure and the exacerbation triggered by a viral infection. An intervention that disrupts this interaction therefore could have an important effect on improving asthma care.
This was proposed by Teach et al. Before the fall seasons of and , children were enrolled, were randomized, and were analyzed.
Subjects received omalizumab a monoclonal antibody against immunoglobulin E [IgE] that has been shown to reduce asthma exacerbation frequency , a boost in their ICS dose, or placebo. The fall in exacerbation rate was significantly lower in the omalizumab versus placebo arms In a pre-specified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo 6.
Omalizumab was also more effective in those who were defined as having more severe disease requiring treatment during the run-in phase. This trial for the first time accurately identified that children with more severe disease — including a history of serious exacerbations despite regular ICS treatment — will benefit from more intense treatment of their asthma, directly reducing their susceptibility to virus-induced exacerbations of asthma.
One of the most revealing studies to come from was the longitudinal follow-up of the childhood asthma management project CAMP cohort. This original study took children aged 5—12 years with chronic mild to moderate asthma and treated them for 5 years with inhaled budesonide, nedocromil, or placebo The interventions at the time failed to influence lung function growth.
A paper by McGeachie et al. In persons without lung disease, forced expiratory volume in 1 second FEV1 reaches its maximal level in late adolescence or early adulthood usually around 20 years of age and remains stable for several years, a period known as the plateau of lung function, before gradually declining, usually after 25 years Impaired lung function at enrollment and male sex were the most significant predictors of abnormal longitudinal patterns of lung function growth and decline.
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This study clearly emphasizes the enormous long-term effect childhood asthma can have on lung function throughout life. It makes the case that identifying and following those with abnormal spirometric trajectories may be important to identify those at risk of adult lung disease, though it is sobering that we still do not have an intervention that has been shown to alter these outcomes.
The advantage in asthma of using medications that are inhaled is that the drug can be delivered to the affected airway, the site of disease, while minimizing off-target side effects. Therefore, systems that more effectively deliver therapy throughout the airways, especially ICS, may be more effective. In addition, a small-particle aerosol that remains suspended in the air for longer should provide an advantage for dis-coordinated patients by improving lung deposition of the drug and reducing the dependence on correct inhaler technique. With these advantages in mind, Hodgson et al. Despite the lower dose of ICS, the ciclesonide arm demonstrated fewer acute exacerbations, with an adjusted rate ratio of 0.
Finally, there was the example of applying technology to deliver corticosteroids to the airways more effectively. Vogelmeier et al. Biologic agents represent a major innovation in the treatment of chronic immune-mediated disease and have led to important advances in the management of rheumatoid arthritis, inflammatory bowel disease, and, since the advent of omalizumab, severe asthma. It has demonstrated promising efficacy in the treatment of allergic rhinitis and nasal polyposis, eczema, and asthma with elevated blood eosinophils In their publication, however, Wenzel et al.
Patients were randomly assigned to receive subcutaneous dupilumab mg or mg every 2 weeks or every 4 weeks, or placebo, over a week period. The best effect was seen with biweekly dosing and little difference was seen between mg and mg doses. The effect size appeared slightly greater in those with elevated blood eosinophils, but significant improvements were seen in all patients. The greatest change in FEV1 compared with placebo was observed at week 12 with doses every 2 weeks in the mg group mean change 0. These changes were sustained to week In addition, subjects demonstrated reductions in annualized rates of exacerbation in the overall population 70— Dupilumab offers perhaps the most promise of any of the current biological agents proposed for managing severe asthma.
It appears to have favorable effects on important co-morbidities such as chronic sinusitis, nasal polyposis, and atopic dermatitis. A second-generation monoclonal antibody to IgE, ligelizumab, has been developed and this demonstrates significantly greater in vitro binding affinity than does omalizumab In a small proof-of-concept trial, 37 mild atopic asthmatics were randomized to receive ligelizumab, omalizumab, or placebo Ligelizumab attenuated the effect of allergen challenge threefold more effectively than did omalizumab and fold better than did placebo.