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The Journal of Allergy and Clinical... Jan 2023Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear.
OBJECTIVE
We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD.
METHODS
As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence.
RESULTS
Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings.
CONCLUSIONS
SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.
Topics: Adult; Animals; Humans; Child; Dermatitis, Atopic; Quality of Life; Bayes Theorem; Desensitization, Immunologic; Pyroglyphidae; Hypersensitivity; Asthma; Allergens; Sublingual Immunotherapy; Dermatophagoides pteronyssinus; Eczema
PubMed: 36191689
DOI: 10.1016/j.jaci.2022.09.020 -
Expert Review of Clinical Immunology Jan 2018Atopic dermatitis (AD) is a chronic relapsing skin disease, characterized by flare-up due to the exposure to allergens in patients sensitized to them. Currently, therapy... (Review)
Review
Atopic dermatitis (AD) is a chronic relapsing skin disease, characterized by flare-up due to the exposure to allergens in patients sensitized to them. Currently, therapy of AD is mainly based on symptomatic treatment and avoidance of irritating/allergenic factors, house dust mites being particularly important. Allergen immunotherapy (AIT) is suggested to be the only etiologic treatment, to modify the natural history of the disease. Areas covered: The aim of this review is investigating the putative role of AIT in AD through the evaluation of the most recent scientific literature. Several studies have been conducted since 1970, with promising results in improving the clinical outcome of AD, but they often lack the necessary scientific rigorousness. Moreover, heterogeneity of the studies makes it very difficult to compare and to analyze data in a systematic review or meta-analysis. Expert commentary: As a result of the above-mentioned limitations, the treatment of AD with causative aeroallergen can nowadays be suggested only as an add-on therapy in selected patients who are non-responsive to the traditional therapy.
Topics: Animals; Antigens, Dermatophagoides; Dermatitis, Atopic; Desensitization, Immunologic; Humans; Hypersensitivity; Pyroglyphidae
PubMed: 29110542
DOI: 10.1080/1744666X.2018.1401469 -
Frontiers in Immunology 2023To systematically evaluate the clinical efficacy and safety of sublingual immunotherapy for allergic rhinitis (AR) and provide evidence for clinical treatment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To systematically evaluate the clinical efficacy and safety of sublingual immunotherapy for allergic rhinitis (AR) and provide evidence for clinical treatment.
METHODS
A literature search was performed on the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Web of Science, Cochrane Library, and Embase database. Data from randomized controlled trials (RCTs) of sublingual immunotherapy for AR were screened and extracted from the establishment of those databases to November 2022. Subsequently, a network meta-analysis was performed using a statistical software R 4.2.
RESULTS
Totally 22 RCTs that met the inclusion and exclusion criteria and screened from 1,164 literature were included. A total of 4,941 AR patients were involved in the 22 trials, as well as five interventions including placebo, pharmacotherapy, subcutaneous immunotherapy_dust mite, sublingual immunotherapy_dust mite, and sublingual immunotherapy_ grass mix plus pollen extract. The results of network meta-analysis showed that, based on symptom scores after different interventions for AR, the most effective treatments for AR were in order as follows: sublingual immunotherapy_dust mite, subcutaneous immunotherapy_dust mite, sublingual immunotherapy_ grass mix plus pollen extract, placebo, and pharmacotherapy. Importantly, sublingual immunotherapy had fewer adverse reactions and higher safety.
CONCLUSION
Sublingual immunotherapy_dust mite for AR has the best efficacy, whereas traditional medicine has the worst. More high-quality studies with a large sample and multiple centers are needed to verify this conclusion in the future, so as to further provide more reliable evidence-based medical evidence for the clinical treatment options of AR patients.
Topics: Animals; Humans; Sublingual Immunotherapy; Network Meta-Analysis; Rhinitis, Allergic; Pyroglyphidae; Plant Extracts
PubMed: 37063866
DOI: 10.3389/fimmu.2023.1144816 -
The Cochrane Database of Systematic... Aug 2015Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important... (Review)
Review
BACKGROUND
Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important allergic component to their disease, which may provide an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house dust mite, pollen extract) under the tongue to induce immune tolerance. However, it is not clear whether the sublingual delivery route is safe and effective in asthma.
OBJECTIVES
To assess the efficacy and safety of sublingual immunotherapy compared with placebo or standard care for adults and children with asthma.
SEARCH METHODS
We identified trials from the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/) and reference lists of all primary studies and review articles. The search is up to date as of 25 March 2015.
SELECTION CRITERIA
We included parallel randomised controlled trials (RCTs), irrespective of blinding or duration, that evaluated sublingual immunotherapy versus placebo or as an add-on to standard asthma management. We included both adults and children with asthma of any severity and with any allergen-sensitisation pattern. We included studies that recruited participants with asthma, rhinitis, or both, providing at least 80% of trial participants had a diagnosis of asthma.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results for included trials, extracted numerical data and assessed risk of bias, all of which were cross-checked for accuracy. We resolved disagreements by discussion.We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs) using study participants as the unit of analysis; we analysed continuous data as mean differences (MDs) or standardised mean differences (SMDs) using random-effects models. We rated all outcomes using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) and presented results in the 'Summary of findings' table.
MAIN RESULTS
Fifty-two studies met our inclusion criteria, randomly assigning 5077 participants to comparisons of interest. Most studies were double-blind and placebo-controlled, but studies varied in duration from one day to three years. Most participants had mild or intermittent asthma, often with co-morbid allergic rhinitis. Eighteen studies recruited only adults, 25 recruited only children and several recruited both or did not specify (n = 9).With the exception of adverse events, reporting of outcomes of interest to this review was infrequent, and selective reporting may have had a serious effect on the completeness of the evidence. Allocation procedures generally were not well described, about a quarter of the studies were at high risk of bias for performance or detection bias or both and participant attrition was high or unknown in around half of the studies.One short study reported exacerbations requiring a hospital visit and observed no adverse events. Five studies reported quality of life, but the data were not suitable for meta-analysis. Serious adverse events were infrequent, and analysis using risk differences suggests that no more than 1 in 100 are likely to suffer a serious adverse event as a result of treatment with SLIT (RD 0.0012, 95% confidence interval (CI) -0.0077 to 0.0102; participants = 2560; studies = 22; moderate-quality evidence).Within secondary outcomes, wide but varied reporting of largely unvalidated asthma symptom and medication scores precluded meaningful meta-analysis; a general trend suggested SLIT benefit over placebo, but variation in scales meant that results were difficult to interpret.Changes in inhaled corticosteroid use in micrograms per day (MD 35.10 mcg/d, 95% CI -50.21 to 120.42; low-quality evidence), exacerbations requiring oral steroids (studies = 2; no events) and bronchial provocation (SMD 0.69, 95% CI -0.04 to 1.43; very low-quality evidence) were not often reported. This led to many imprecise estimates with wide confidence intervals that included the possibility of both benefit and harm from SLIT.More people taking SLIT had adverse events of any kind compared with control (OR 1.70, 95% CI 1.21 to 2.38; low-quality evidence; participants = 1755; studies = 19), but events were usually reported to be transient and mild.Lack of data prevented most of the planned subgroup and sensitivity analyses.
AUTHORS' CONCLUSIONS
Lack of data for important outcomes such as exacerbations and quality of life and use of different unvalidated symptom and medication scores have limited our ability to draw a clinically useful conclusion. Further research using validated scales and important outcomes for patients and decision makers is needed so that SLIT can be properly assessed as clinical treatment for asthma. Very few serious adverse events have been reported, but most studies have included patients with intermittent or mild asthma, so we cannot comment on the safety of SLIT for those with moderate or severe asthma. SLIT is associated with increased risk of all adverse events.
Topics: Adult; Animals; Asthma; Child; Humans; Pollen; Pyroglyphidae; Randomized Controlled Trials as Topic; Sublingual Immunotherapy
PubMed: 26315994
DOI: 10.1002/14651858.CD011293.pub2 -
The Cochrane Database of Systematic... Sep 2020Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important allergic component to their disease, which may provide an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house dust mite, pollen extract) under the tongue to induce immune tolerance. Fifty-two studies were identified and synthesised in the original Cochrane Review in 2015, but questions remained about the safety and efficacy of sublingual immunotherapy for people with asthma.
OBJECTIVES
To assess the efficacy and safety of sublingual immunotherapy compared with placebo or standard care for adults and children with asthma.
SEARCH METHODS
The original searches for trials from the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, WHO ICTRP, and reference lists of all primary studies and review articles found trials up to 25 March 2015. The most recent search for trials for the current update was conducted on 29 October 2019.
SELECTION CRITERIA
We included parallel randomised controlled trials, irrespective of blinding or duration, that evaluated sublingual immunotherapy versus placebo or as an add-on to standard asthma management. We included both adults and children with asthma of any severity and with any allergen-sensitisation pattern. We included studies that recruited participants with asthma, rhinitis, or both, providing at least 80% of trial participants had a diagnosis of asthma. We selected outcomes to reflect recommended outcomes for asthma clinical trials and those most important to people with asthma. Primary outcomes were asthma exacerbations requiring a visit to the emergency department (ED) or admission to hospital, validated measures of quality of life, and all-cause serious adverse events (SAEs). Secondary outcomes were asthma symptom scores, exacerbations requiring systemic corticosteroids, response to provocation tests, and dose of inhaled corticosteroids (ICS).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results for included trials, extracted numerical data, and assessed risk of bias, all of which were cross-checked for accuracy. Any disagreements were resolved by discussion. We analysed dichotomous data as odds ratios (ORs) or risk differences (RDs) using study participants as the unit of analysis; we analysed continuous data as mean differences (MDs) or standardised mean differences (SMDs) using random-effects models. We considered the strength of evidence for all primary and secondary outcomes using the GRADE approach.
MAIN RESULTS
Sixty-six studies met the inclusion criteria for this update, including 52 studies from the original review. Most studies were double-blind and placebo-controlled, varied in duration from one day to three years, and recruited participants with mild or intermittent asthma, often with comorbid allergic rhinitis. Twenty-three studies recruited adults and teenagers; 31 recruited only children; three recruited both; and nine did not specify. The pattern of reporting and results remained largely unchanged from the original review despite 14 further studies and a 50% increase in participants studied (5077 to 7944). Reporting of primary efficacy outcomes to measure the impact of SLIT on asthma exacerbations and quality of life was infrequent, and selective reporting may have had a serious effect on the completeness of the evidence; 16 studies did not contribute any data, and a further six studies could only be included in a post hoc analysis of all adverse events. Allocation procedures were generally not well described; about a quarter of the studies were at high risk of performance or detection bias (or both); and participant attrition was high or unknown in around half of the studies. The primary outcome in most studies did not align with those of interest to the review (mostly asthma or rhinitis symptoms), and only two small studies reported our primary outcome of exacerbations requiring an ED or hospital visit; the pooled estimate from these studies suggests SLIT may reduce exacerbations compared with placebo or usual care, but the evidence is very uncertain (OR 0.35, 95% confidence interval (CI) 0.10 to 1.20; n = 108; very low-certainty evidence). Nine studies reporting quality of life could not be combined in a meta-analysis and, whilst the direction of effect mostly favoured SLIT, the effects were often uncertain and small. SLIT likely does not increase SAEs compared with placebo or usual care, and analysis by risk difference suggests no more than 1 in 100 people taking SLIT will have a serious adverse event (RD -0.0004, 95% CI -0.0072 to 0.0064; participants = 4810; studies = 29; moderate-certainty evidence). Regarding secondary outcomes, asthma symptom and medication scores were mostly measured with non-validated scales, which precluded meaningful meta-analysis or interpretation, but there was a general trend of SLIT benefit over placebo. Changes in ICS use (MD -17.13 µg/d, 95% CI -61.19 to 26.93; low-certainty evidence), exacerbations requiring oral steroids (studies = 2; no events), and bronchial provocation (SMD 0.99, 95% CI 0.17 to 1.82; low-certainty evidence) were not often reported. Results were imprecise and included the possibility of important benefit or little effect and, in some cases, potential harm from SLIT. More people taking SLIT had adverse events of any kind compared with control (OR 1.99, 95% CI 1.49 to 2.67; high-certainty evidence; participants = 4251; studies = 27), but events were usually reported to be transient and mild. Lack of data prevented most of the planned subgroup and sensitivity analyses.
AUTHORS' CONCLUSIONS
Despite continued study in the field, the evidence for important outcomes such as exacerbations and quality of life remains too limited to draw clinically useful conclusions about the efficacy of SLIT for people with asthma. Trials mostly recruited mixed populations with mild and intermittent asthma and/or rhinitis and focused on non-validated symptom and medication scores. The review findings suggest that SLIT may be a safe option for people with well-controlled mild-to-moderate asthma and rhinitis who are likely to be at low risk of serious harm, but the role of SLIT for people with uncontrolled asthma requires further evaluation.
Topics: Adolescent; Adult; Animals; Asthma; Child; Disease Progression; Hospitalization; Humans; Placebos; Pollen; Pyroglyphidae; Quality of Life; Randomized Controlled Trials as Topic; Rhinitis, Allergic; Sublingual Immunotherapy
PubMed: 32926419
DOI: 10.1002/14651858.CD011293.pub3 -
Allergy and Asthma Proceedings Sep 2017A clinical history of allergic symptoms and a skin-prick test with house-dust mite crude extracts are standard diagnostic procedures for Dermatophagoides pteronyssinus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A clinical history of allergic symptoms and a skin-prick test with house-dust mite crude extracts are standard diagnostic procedures for Dermatophagoides pteronyssinus allergy. Specific immunoglobulin E (IgE) responses to Der p 1 and Der p 2 allergens have been used for the diagnosis of D. pteronyssinus allergy; however, evaluation of the diagnostic performance of Der p 1 and Der p 2 specific IgE (sIgE) produced inconsistent findings. We sought to evaluate the diagnostic accuracy of Der p 1 sIgE and Der p 2 sIgE measurement in the diagnosis of D. pteronyssinus allergy by performing a systematic review and meta-analysis of previously published studies.
METHODS
Several medical literature electronic data bases were searched for related literature published through August 1, 2016. A bivariate model was used to pool estimates of sensitivity, specificity, diagnostic odds ratio, and area under the summary receiver operating curves as the main diagnostic measures.
RESULTS
Eight studies, which involved 1095 patients, were included in our analysis. The pooled estimates of sensitivity, specificity, and diagnostic odds ratio for Der p 1 were 0.84, 0.97, and 166.57, respectively. The combined results for Der p 2 were a sensitivity of 0.87, specificity of 1.00, and a diagnostic odds ratio of 17342.35. The areas under the summary receiver operating curves for Der p 1 sIgE and Der p 2 sIgE were 0.94 and 0.98, respectively.
CONCLUSION
Our results supported the use of Der p 1 and Der p 2 sIgE in the diagnosis of D. pteronyssinus allergy. Both displayed good diagnostic performance and would be useful in a clinical setting in the accurate diagnosis of dust mite allergy.
Topics: Allergens; Animals; Antibody Specificity; Antigens, Dermatophagoides; Arthropod Proteins; Cysteine Endopeptidases; Dermatophagoides pteronyssinus; Humans; Hypersensitivity; Immunoglobulin E; Odds Ratio; Publication Bias; ROC Curve; Regression Analysis; Reproducibility of Results; Sensitivity and Specificity; Skin Tests
PubMed: 28814355
DOI: 10.2500/aap.2017.38.4073 -
International Forum of Allergy &... Jul 2017Although the preventive efficacy of allergen immunotherapy (AIT) in the onset of new allergen sensitizations has been asserted by many reviews, position papers, and... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although the preventive efficacy of allergen immunotherapy (AIT) in the onset of new allergen sensitizations has been asserted by many reviews, position papers, and consensus conferences, the evidence available is from only 3 studies. The objective of this work was a systematic review to evaluate the preventive efficacy of AIT in the onset of new allergen sensitizations. The end-point was the risk difference (RD) in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy.
METHODS
Computerized bibliographic searches of MEDLINE, EMBASE, and the Cochrane Library (until November 30th, 2016) were done. Random-effects and fixed-effects model meta-analyses were performed. Randomized controlled trials or observational studies comparing children treated with AIT with house dust mite (HDM) to subjects who did not receive AIT, with a long-term observation period (at least 3 years including treatment and follow-up) have been included.
RESULTS
Eight studies totaling 721 children (390 treated with AIT and 331 with pharmacotherapy) met the inclusion criteria. The risk of bias was high. Low evidence supports the conclusion that AIT prevents the onset of new allergen sensitizations, with 3 of 8 studies reporting a reduction in the onset of new sensitizations in patients treated with AIT vs pharmacotherapy. Our meta-analysis found no difference between AIT and pharmacotherapy, with high heterogeneity (RD, -0.10; 95% confidence interval [CI], -0.31 to 0.11; p = 0.32; I = 91.4%).
CONCLUSION
The data of this systematic review do not support a preventive effect in the onset of new allergen sensitizations, in children treated with AIT in comparison with those treated with pharmacotherapy.
Topics: Animals; Anti-Allergic Agents; Antigens, Dermatophagoides; Child; Desensitization, Immunologic; Humans; Hypersensitivity; Immunization; Pyroglyphidae; Randomized Controlled Trials as Topic
PubMed: 28544523
DOI: 10.1002/alr.21946 -
The Cochrane Database of Systematic... Jan 2015Eczema is an inflammatory skin disease that tends to involve skin creases, such as the folds of the elbows or knees; it is an intensely itchy skin condition, which can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eczema is an inflammatory skin disease that tends to involve skin creases, such as the folds of the elbows or knees; it is an intensely itchy skin condition, which can relapse and remit over time. As many as a third of people with eczema who have a positive test for allergy to house dust mite have reported worsening of eczema or respiratory symptoms when exposed to dust.
OBJECTIVES
To assess the effects of all house dust mite reduction and avoidance measures for the treatment of eczema.
SEARCH METHODS
We searched the following databases up to 14 August 2014: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 8), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), and the GREAT database. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant studies. We handsearched abstracts from international eczema and allergy meetings.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of any of the house dust mite reduction and avoidance measures for the treatment of eczema, which included participants of any age diagnosed by a clinician with eczema as defined by the World Allergy Organization. We included all non-pharmacological and pharmacological interventions that sought to reduce or avoid exposure to house dust mite and their allergenic faeces. The comparators were any active treatment, no treatment, placebo, or standard care only.
DATA COLLECTION AND ANALYSIS
Two authors independently checked the titles and abstracts identified, and there were no disagreements. We contacted authors of included studies for additional information. We assessed the risk of bias using Cochrane methodology.
MAIN RESULTS
We included seven studies of 324 adults and children with eczema. Overall, the included studies had a high risk of bias. Four of the seven trials tested interventions with multiple components, and three tested a single intervention. Two of the seven trials included only children, four included children and adults, and one included only adults. Interventions to reduce or avoid exposure to house dust mite included covers for mattresses and bedding, increased or high-quality vacuuming of carpets and mattresses, and sprays that kill house dust mites.Four studies assessed our first primary outcome of 'Clinician-assessed eczema severity using a named scale'. Of these, one study (n = 20) did not show any significant short-term benefit from allergen impermeable polyurethane mattress encasings and acaricide spray versus allergen permeable cotton mattress encasings and placebo acaricide spray. One study (n = 60) found a modest statistically significant benefit in the Six Area, Six Sign Atopic Dermatitis (SASSAD) scale over six months (mean difference of 4.2 (95% confidence interval 1.7 to 6.7), P = 0.008) in favour of a mite impermeable bedding system combined with benzyltannate spray and high-filtration vacuuming versus mite permeable cotton encasings, water with a trace of alcohol spray, and a low-filtration vacuum cleaner. The third study (n = 41) did not compare the change in severity of eczema between the two treatment groups. The fourth study (n = 86) reported no evidence of a difference between the treatment groups.With regard to the secondary outcomes 'Participant- or caregiver-assessed global eczema severity score' and the 'Amount and frequency of topical treatment required', one study (n = 20) assessed these outcomes with similar results being reported for these outcomes in both groups. Four studies (n = 159) assessed 'Sensitivity to house dust mite allergen using a marker'; there was no clear evidence of a difference in sensitivity levels reported between treatments in any of the four trials.None of the seven included studies assessed our second primary outcome 'Participant- or caregiver-assessed eczema-related quality of life using a named instrument' or the secondary outcome of 'Adverse effects'.We were unable to combine any of our results because of variability in the interventions and paucity of data.
AUTHORS' CONCLUSIONS
We were unable to determine clear implications to inform clinical practice from the very low-quality evidence currently available. The modest treatment responses reported were in people with atopic eczema, specifically with sensitivity to one or more aeroallergens. Thus, their use in the eczema population as a whole is unknown. High-quality long-term trials of single, easy-to-administer house dust mite reduction or avoidance measures are worth pursuing.
Topics: Acaricides; Adolescent; Adult; Animals; Bedding and Linens; Child; Child, Preschool; Dust; Eczema; Elbow; Environmental Exposure; Household Work; Humans; Knee; Middle Aged; Pyroglyphidae; Randomized Controlled Trials as Topic; Respiratory Hypersensitivity; Young Adult
PubMed: 25598014
DOI: 10.1002/14651858.CD008426.pub2 -
The Cochrane Database of Systematic... Feb 2016Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant allergen. A high quality systematic review has not previously assessed the efficacy and safety of this treatment.
OBJECTIVES
To assess the effects of specific allergen immunotherapy (SIT), including subcutaneous, sublingual, intradermal, and oral routes, compared with placebo or a standard treatment in people with atopic eczema.
SEARCH METHODS
We searched the following databases up to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), Web of Science™ (from 2005), the Global Resource of EczemA Trials (GREAT database), and five trials databases. We searched abstracts from recent European and North American allergy meetings and checked the references of included studies and review articles for further references to relevant trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of specific allergen immunotherapy that used standardised allergen extracts in people with AE.
DATA COLLECTION AND ANALYSIS
Two authors independently undertook study selection, data extraction (including adverse effects), assessment of risk of bias, and analyses. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified 12 RCTs for inclusion in this review; the total number of participants was 733. The interventions included SIT in children and adults allergic to either house dust mite (10 trials), grass pollen, or other inhalant allergens (two trials). They were administered subcutaneously (six trials), sublingually (four trials), orally, or intradermally (two trials). Overall, the risk of bias was moderate, with high loss to follow up and lack of blinding as the main methodological concern.Our primary outcomes were 'Participant- or parent-reported global assessment of disease severity at the end of treatment'; 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'; and 'Adverse events, such as acute episodes of asthma or anaphylaxis'. SCORing Atopic Dermatitis (SCORAD) is a means of measuring the effect of atopic dermatitis by area (A); intensity (B); and subjective measures (C), such as itch and sleeplessness, which we used.For 'Participant- or parent-reported global assessment of disease severity at the end of treatment', one trial (20 participants) found improvement in 7/9 participants (78%) treated with the SIT compared with 3/11 (27%) treated with the placebo (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.02 to 7.96; P = 0.04). Another study (24 participants) found no difference: global disease severity improved in 8/13 participants (62%) treated with the SIT compared with 9/11 (81%) treated with the placebo (RR 0.75, 95% CI 0.45 to 1.26; P = 0.38). We did not perform meta-analysis because of high heterogeneity between these two studies. The quality of the evidence was low.For 'Participant- or parent-reported specific symptoms of eczema, by subjective measures', two trials (184 participants) did not find that the SIT improved SCORAD part C (mean difference (MD) -0.74, 95% CI -1.98 to 0.50) or sleep disturbance (MD -0.49, 95% CI -1.03 to 0.06) more than placebo. For SCORAD part C itch severity, these two trials (184 participants) did not find that the SIT improved itch (MD -0.24, 95% CI -1.00 to 0.52). One other non-blinded study (60 participants) found that the SIT reduced itch compared with no treatment (MD -4.20, 95% CI -3.69 to -4.71) and reduced the participants' overall symptoms (P < 0.01), but we could not pool these three studies due to high heterogeneity. The quality of the evidence was very low.Seven trials reported systemic adverse reactions: 18/282 participants (6.4%) treated with the SIT had a systemic reaction compared with 15/210 (7.1%) with no treatment (RR 0.78, 95% CI 0.41 to 1.49; the quality of the evidence was moderate). The same seven trials reported local adverse reactions: 90/280 participants (32.1%) treated with the SIT had a local reaction compared with 44/204 (21.6%) in the no treatment group (RR 1.27, 95% CI 0.89 to 1.81). As these had the same study limitations, we deemed the quality of the evidence to also be moderate.Of our secondary outcomes, there was a significant improvement in 'Investigator- or physician-rated global assessment of disease severity at the end of treatment' (six trials, 262 participants; RR 1.48, 95% CI 1.16 to 1.88). None of the studies reported our secondary outcome 'Parent- or participant-rated eczema severity assessed using a published scale', but two studies (n = 184), which have been mentioned above, used SCORAD part C, which we included as our primary outcome 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'.Our findings were generally inconclusive because of the small number of studies. We were unable to determine by subgroup analyses a particular type of allergen or a particular age or level of disease severity where allergen immunotherapy was more successful. We were also unable to determine whether sublingual immunotherapy was associated with more local adverse reactions compared with subcutaneous immunotherapy.
AUTHORS' CONCLUSIONS
Overall, the quality of the evidence was low. The low quality was mainly due to the differing results between studies, lack of blinding in some studies, and relatively few studies reporting participant-centred outcome measures. We found limited evidence that SIT may be an effective treatment for people with AE. The treatments used in these trials were not associated with an increased risk of local or systemic reactions. Future studies should use high quality allergen formulations with a proven track record in other allergic conditions and should include participant-reported outcome measures.
Topics: Adult; Allergens; Animals; Child; Dermatitis, Atopic; Dermatophagoides farinae; Dermatophagoides pteronyssinus; Desensitization, Immunologic; Humans; Randomized Controlled Trials as Topic
PubMed: 26871981
DOI: 10.1002/14651858.CD008774.pub2 -
Pediatric Allergy and Immunology :... Nov 2015Dust mite sensitization plays a controversial role in the development of atopic dermatitis. Despite a lack of evidence for its efficacy, dust mite avoidance is commonly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dust mite sensitization plays a controversial role in the development of atopic dermatitis. Despite a lack of evidence for its efficacy, dust mite avoidance is commonly recommended for the prevention and treatment of atopic dermatitis. We aimed to evaluate whether dust mite avoidance strategies reduce the risk of developing atopic dermatitis in high-risk infants compared to randomized controls.
METHODS
Studies were obtained by searching MEDLINE, PubMed, Scopus, The Cochrane Library, and The Global Resource of Eczema Trials databases. We included randomized, controlled trials of high-risk infants treated with a dust mite avoidance intervention and assessed for atopic dermatitis. Data were extracted independently by two reviewers using predefined criteria.
RESULTS
Seven randomized controlled trials met our inclusion criteria (total n = 3040). Studies were largely unblinded but otherwise of reasonable quality. Three trials utilizing a dust mite avoidance approach but not additional interventions were combined in a meta-analysis. Dust mite avoidance provided no benefit in the prevention of atopic dermatitis (relative risk (RR) = 1.08, 95% confidence interval (CI) = 0.78-1.49, I(2) = 73%).
CONCLUSIONS
Dust mite avoidance strategies alone or in combination with additional allergen avoidance modalities do not decrease the risk of developing atopic dermatitis and, given the current state of the evidence, should not be recommended for this purpose. The utility of dust mite avoidance for the treatment of atopic dermatitis or for the prevention and treatment of asthma or seasonal rhinoconjunctivitis are outside the scope of this review.
Topics: Allergens; Animals; Antigens, Dermatophagoides; Dermatitis, Atopic; Environmental Exposure; Humans; Models, Statistical; Primary Prevention; Pyroglyphidae; Treatment Outcome
PubMed: 26235650
DOI: 10.1111/pai.12452