Allergic rhinitis Greiner, Alexander N, MD; Hellings, Peter W, MD; Rotiroti, Guiseppina, MD ...
The Lancet (British edition),
12/2011, Volume:
378, Issue:
9809
Journal Article
Peer reviewed
Summary Allergic rhinitis is a very common disorder that affects people of all ages, peaking in the teenage years. It is frequently ignored, underdiagnosed, misdiagnosed, and mistreated, which not ...only is detrimental to health but also has societal costs. Although allergic rhinitis is not a serious illness, it is clinically relevant because it underlies many complications, is a major risk factor for poor asthma control, and affects quality of life and productivity at work or school. Management of allergic rhinitis is best when directed by guidelines. A diagnostic trial of a pharmacotherapeutic agent could be started in people with clinically identified allergic rhinitis; however, to confirm the diagnosis, specific IgE reactivity needs to be recorded. Documented IgE reactivity has the added benefit of guiding implementation of environmental controls, which could substantially ameliorate symptoms of allergic rhinitis and might prevent development of asthma, especially in an occupational setting. Many classes of drug are available, effective, and safe. In meta-analyses, intranasal corticosteroids are superior to other treatments, have a good safety profile, and treat all symptoms of allergic rhinitis effectively. First-generation antihistamines are associated with sedation, psychomotor retardation, and reduced academic performance. Only immunotherapy with individually targeted allergens has the potential to alter the natural history of allergic rhinitis. Patients' education is a vital component of treatment. Even with the best pharmacotherapy, one in five affected individuals remains highly symptomatic, and further research is needed in this area.
Seasonal allergic rhinitis (SAR) caused by Japanese cedar pollen (JCP; ie, sugi-pollinosis) is the most common disease in Japan and has been considered a national affliction. More than one third of ...all Japanese persons have sugi-pollinosis, and this number has significantly increased in the last 2 decades. In our opinion the reason why sugi-pollinosis became a common disease in the last half century is the increased number of cedar pollens, with global climate change and forest growth caused by the tree-planting program of the Japanese government after World War II playing substantial roles; dust storms containing small particulate matter from China might also contribute to the increased incidence of sugi-pollinosis. To help minimize their symptoms, many Japanese wear facemasks and eyeglasses at all times between February and April to prevent exposure to JCP and aerosol pollutants. Forecasts for JCP levels typically follow the weather forecast in mass media broadcasts, and real-time information regarding JCP levels is also available on the Internet. Because a large amount of JCP is produced over several months, it can induce severe symptoms. Japanese guidelines for allergic rhinitis recommend prophylactic treatment with antihistamines or antileukotrienes before the start of JCP dispersion. Additionally, sublingual immunotherapy will be supported by health insurance in the summer of 2014. However, many patients with sugi-pollinosis do not find satisfactory symptom relief with currently available therapies. Collaboration between scientists and pharmaceutical companies to produce new therapeutics for the control of sugi-pollinosis symptoms is necessary.
Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT).
We sought to ...define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells DC2s) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy.
Transcriptomes and proteomes of monocyte-derived DCs polarized toward DCs driving the differentiation of TH1 cells (DC1s), DC2s, or DCs driving the differentiation of regulatory T cells (DCreg cells) profiles were compared by using genome-wide cDNA microarrays and label-free quantitative proteomics, respectively. Markers differentially regulated in DC2s and DCreg cells were assessed by means of quantitative PCR in PBMCs from 80 patients with grass pollen allergy before and after 2 or 4 months of sublingual AIT in parallel with rhinoconjunctivitis symptom scores.
We identified 20 and 26 new genes/proteins overexpressed in DC2s and DCreg cells, respectively. At an individual patient level, DC2-associated markers, such as CD141, GATA3, OX40 ligand, and receptor-interacting serine/threonine-protein kinase 4 (RIPK4), were downregulated after a 4-month sublingual AIT course concomitantly with an upregulation of DCreg cell–associated markers, including complement C1q subcomponent subunit A (C1QA), FcγRIIIA, ferritin light chain (FTL), and solute carrier organic anion transporter family member 2B1 (SLCO2B1), in the blood of clinical responders as opposed to nonresponders. Changes in such markers were better correlated with clinical benefit than alterations of allergen-specific CD4+ T-cell or IgG responses.
A combination of 5 markers predominantly expressed by blood DCs (ie, C1Q and CD141) or shared with lymphoid cells (ie, FcγRIIIA, GATA3, and RIPK4) reflecting changes in the balance of regulatory/proallergic responses in peripheral blood can be used as early as after 2 months to monitor the early onset of AIT efficacy.
Summary
Background
Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in industrialized countries. This highly debilitating ...condition poses a considerable burden to both the individual and society at large. The pathophysiology of atopic dermatitis is complex, encompassing both genetic and environmental risk factors.
Methods
This is a narrative review based on a systematic literature search.
Conclusions
Dysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise in preventing atopic dermatitis, such as the early use of emollients in high‐risk infants. This may have broader implications in terms of halting the progression to atopic comorbidities including food allergy, hay fever and asthma.
What's already known about this topic?
Atopic dermatitis is a common and highly debilitating chronic inflammatory skin disorder.
Immune dysregulation plays a key role, but recent evidence has shifted the focus to skin barrier disruption as the key precursor.
Loss‐of‐function mutations in the filaggrin gene are the strongest known genetic risk factor, but there are numerous environmental and immunological factors that influence the disease manifestation and course.
The current therapeutic armamentarium is limited to simple lipid‐based barrier‐enhancing emollients, topical anti‐inflammatory agents and systemic immunosuppressive therapies.
What does this study add?
We review how defects in structural epidermal proteins and environmental factors converge to impair skin barrier function, resulting in increased susceptibility to atopic dermatitis.
We explore the impact of the defective skin barrier on immune responses and the skin microbiome, highlighting how the complex interplay between the skin barrier and immune activation determines the response to environmental factors such as allergens and microbes.
We outline emerging strategies for treating and preventing atopic dermatitis.
Linked Comment: Silverberg. Br J Dermatol 2019; 180:447–448.
The Poaceae family comprises over 12 000 wind‐pollinated species, which release large amounts of pollen into the atmosphere. Poaceae pollen is currently regarded as the leading airborne biological ...pollutant and the chief cause of pollen allergy worldwide. Sensitization rates vary by country, and those variations are reviewed here. Grass pollen allergens are grouped according to their protein structure and function. In Poaceae, although species belonging to different subfamilies are characterized by distinct allergen subsets, there is a considerable degree of cross‐reactivity between many species. Cross‐reactivity between grass pollen protein and fresh fruit pan‐allergens is associated with the appearance of food allergies. The additional influence of urban pollution may prompt a more severe immunological response. The timing and the intensity of the pollen season are governed by species genetics, but plant phenology is also influenced by climate; as a result, climate changes may affect airborne pollen concentrations. This article reviews the findings of worldwide research which has highlighted the major impact of climate change on plant phenology and also on the prevalence and severity of allergic disease.
Background Sensitization to profilins and other cross-reacting molecules might hinder proper specific immunotherapy (SIT) prescription in polysensitized patients with pollen-related allergic rhinitis ...(AR). In these patients, component-resolved diagnosis (CRD) might modify SIT prescription by improving the identification of the disease-eliciting pollen sources. Objectives We sought to measure the effect of CRD on SIT prescription in children with pollen-related AR. Methods Children (n = 651) with moderate-to-severe pollen-related AR were recruited between May 2009 and June 2011 in 16 Italian outpatient clinics. Skin prick test (SPT) reactivity to grass, cypress, olive, mugwort, pellitory, and/or Betulaceae pollen was considered clinically relevant if symptoms occurred during the corresponding peak pollen season. IgE sensitization to Phl p 1, Phl p 5, Bet v 1, Cup a 1, Art v 1, Ole e 1, Par j 2, and Phl p 12 (profilin) was measured by using ImmunoCAP. SIT prescription was modeled on SPT responses first and then remodeled considering also CRD according to GA2 LEN–European Academy of Allergology and Clinical Immunology guidelines and the opinions of 14 pediatric allergists. Results No IgE to the respective major allergens was detected in significant proportions of patients with supposed clinically relevant sensitization to mugwort (45/65 69%), Betulaceae (146/252 60%), pellitory (78/257 30%), olive (111/390 28%), cypress (28/184 15%), and grass (56/568 10%). IgE to profilins, polcalcins, or both could justify 173 (37%) of 464 of these SPT reactions. After CRD, the SPT-based decision on SIT prescription or composition was changed in 277 (42%) of 651 or 315 (48%) of 651 children according to the European or American approach, respectively, and in 305 (47%) of 651 children according to the opinion of the 14 local pediatric allergists. Conclusions In children with pollen-related AR, applying CRD leads to changes in a large proportion of SIT prescriptions as opposed to relying on clinical history and SPT alone. The hypothesis that CRD-guided prescription improves SIT efficacy deserves to be tested.
Background
Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time ...periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus.
Methods
A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus.
Results
The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for ‘pollen season’, ‘high pollen season’ (or ‘peak pollen period’) and ‘high pollen days’.
Conclusion
This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.
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