The vast majority of patients with asthma have rhinitis, and rhinitis is a major independent risk factor for asthma in cross-sectional and longitudinal studies. The relationships between rhinitis and ...asthma can be viewed under the concept that the 2 conditions are manifestations of one syndrome, the chronic allergic respiratory syndrome, in 2 parts of the respiratory tract. At the low end of the syndrome's severity spectrum, rhinitis appears to be the sole manifestation, although pathologic abnormalities in the lower airways are already present. At the higher end, rhinitis is worse, and the lower airways disease becomes clinically evident. Once manifested, the 2 conditions track in parallel in terms of severity. This parallel relationship is influenced by many interactions between the nasal and the lower airways: some interactions stem from the fact that the nasal passages play a major homeostatic role by conditioning inhaled air, but perhaps even more important is the bidirectional interaction that results from the systemic inflammation that is produced after local allergic reactions. Successful management of the chronic allergic respiratory syndrome requires an integrated view of the airways and an understanding of their interactions. (J Allergy Clin Immunol 2003;111:1171-83.)
Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.
To test whether omalizumab treatment to reduce IgE would ...shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma.
In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression.
RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84).
In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).
Abstract Background Allergic rhinitis affects 10 to 40% of the population. It reduces quality of life, school and work performance, and is a frequent reason for office visits in general practice. ...Medical costs are large but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma – ARIA guidelines in 2010 prompting its update. Objective To provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patient values and preferences, and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides updated and new recommendations about the pharmacological treatment of allergic rhinitis. It specifically addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or their combination. The ARIA guideline panel provides specific recommendations for the choice of treatment, the rationale for the choice, and discusses specific considerations that clinicians and patients may want to review in order to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of allergic rhinitis may improve patients’ quality of life, school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a TH 2 pattern of mucosal ...cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy.
Background Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, ...the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy. Objectives Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy. Results The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation. Conclusions Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.
Background Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. Objective We sought to compare (1) omalizumab with placebo and (2) ...omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school. Methods A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations ( clincaltrials.gov # NCT01430403 ). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-α responses to rhinovirus in PBMCs were examined. Results Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio OR, 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-α responses to rhinovirus, and within the omalizumab group, greater IFN-α increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms. Conclusions Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.
Humans have populations of innate-like T lymphocytes with an invariant TCR α-chain that recognize nonpeptide Ags, including invariant NKT (iNKT) cells and mucosal-associated invariant T (MAIT) cells. ...iNKT cell involvement in human asthma is controversial, whereas there has been little analysis of MAIT cells. Using peripheral blood cells from 110 participants from the Urban Environment and Childhood Asthma (URECA) birth cohort study, these cells were analyzed for number and function. We determined whether iNKT cell or MAIT cell frequency at 1 y is correlated with the cytokine polarization of mainstream CD4
T cells and/or the development of asthma by age 7 y. Dust samples from 300 houses were tested for iNKT cell antigenic activity. Our results show that a higher MAIT cell frequency at 1 y of age was associated with a decreased risk of asthma by age 7 y. The frequency of MAIT cells was associated with increased production of IFN-γ by activated CD4
T cells from the URECA cohort. iNKT cell antigenic activity in bedroom dust samples was associated with higher endotoxin concentration and also with reduced risk of asthma. In conclusion, MAIT cell frequency at 1 y may reflect the tendency of the immune system toward Th1 responses and is associated with protection from asthma. Additionally, iNKT cell antigenic activity may be a marker of houses with increased microbial exposures and therefore also with protection from asthma.
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