The local sensitizing patterns for allergic rhinitis (AR) vary globally, while house dust mite (HDM) was a common aeroallergen responsible, causing perennial nasal symptoms. The efficacies of AR are evaluated by assessing changes in individual and total nasal symptom score by means of visual analogue scale, medication score, and quality of life (QoL) using rhinoconjunctivitis quality of life questionnaire (RQLQ), following treatment. The safety profile is usually assessed as incidence or prevalence of adverse effects (AEs). Allergen specific immunotherapy (AIT), including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), is the only etiological treatment available for AR, while selective immunomodulator is also available for perennial allergic rhinitis (PAR). There are relatively few AIT trials on HDM-induced AR, and although it is not clear whether SCIT or SLIT is better in this respect, while promising evidence of efficacy for SLIT has been confirmed. To our knowledge, no meta-analysis has been reported of SCIT for HDM-induced PAR. Thus, we performed a meta-analysis of appropriate studies studying the efficacy and safety of HDM-SCIT in patients with HDM-induced PAR.

Studies are required before incorporating egg-oral-immunotherapy (OIT) into clinical practice. The Spanish-Society of Pediatric-Allergy-Asthma and ClinicalImmunology (SEICAP) conducted a multicenter-randomized-controlled study assessing effectiveness and safety of OIT using pasteurized-egg-white (PEW) in egg-allergic-children.

One-hundred-one egg-allergic children (6-9 years) were randomized for one year: 25 to an egg-free-diet (CG) and 76 to OIT (target-dose 3.3g PEWproteins), PI (30% weekly plus 5% daily increments) or PII (only 30% weekly-increments) build-up patterns. Egg skin-prick-test, sIgE and sIgG4 serum levels, PEW double-blind placebo-controlled-food-challenge (DBPCFC) and adverse-dosing-reactions (DARs) were evaluated in all patients from inclusion (T0) until completing one year of follow-up (T12). At T12, egg-allergic control patients could start OIT. Effectiveness and safety of OIT and the effect of the build-up pattern were analyzed.

At T12, 4/25(16.0%) CG patients passed the PEW DBPCFC vs. 64/76(84.2%) OIT that reached total desensitization (p=.000); 12 egg-allergic-control patients started OIT. Finally 72/88(81.81%) patients reached total desensitization, 96.15% PI vs.75.80% on PII (p=.01). Induction period (121.12±91.43, median 98.00 days) resulted longer in patients on PII build-up-pattern, those with allergic-asthma, minor threshold-dose or higher egg-sIgE (p<.05). Most patients (89.06%) developed DARs: 74.53% mild; 21.90% moderate and 3.5% requiring adrenaline. Moderate reactions and those requiring adrenaline were more frequent in patients with allergic-asthma, PII pattern or higher egg sIgE serum antibody levels (p<.05).

PEW OIT is an effective treatment for children with persistent egg allergy. A 30% weekly plus 5% daily increment pattern could be more effective and safer than one with only 30% weekly increments.

We recently described that oral immunotherapy (OIT)-induced gastrointestinal symptoms were associated with peripheral eosinophilic responses (termed OITIGER).

To identify treatment outcomes after dose modification and risk factors for developing OITIGER.

Treatment modifications in patients with OITIGER (n = 65) including cumulative dose reductions or treatment suspension were individualized and based on the severity of symptoms and an associated absolute eosinophil count (AEC, eosinophils/μL) of more than 900. Multivariate analysis for risk factors associated with OITIGER was performed in milk-OIT subjects.

Treatment modifications reduced the cumulative daily dosage load by a median of 50% (interquartile range, 50%-67%) in 43 of 65 (66.1%) patients, deferred dose increases in 2 of 65 (3.1%) patients, or temporarily suspended treatment in 18 of 65 (27.7%) patients. Two patients (3.1%) had no treatment intervention. Symptoms and eosinophilia abated on dosage modification, allowing for resumption of dose increases (n = 34) or reinitiation of treatment (n = 9) after a median of 29 (interquartile range, 20-56) and 19 (interquartile range, 17-44) days, respectively. OITIGER reoccurred during treatment in 10 of 54 (18.5%) patients, which resolved after further dose modification. In long-term follow-up (>3-26 months), 31 of 32 patients were asymptomatic with stable AECs. Patients with OITIGER had a higher OIT failure rate (P = .004) and were less likely to reach full desensitization (P < .001), as compared with asymptomatic patients (n = 684). Multivariate analysis identified several risk factors for OITIGER: starting dose more than 120 mg (P < .001; odds ratio, 7.14), second-month dose more than 4-fold over the starting dose (P = .037; odds ratio, 2.18), and baseline AEC more than 600/μL (P = .002; odds ratio, 3.2).

OITIGER is transient or reversible in most subjects, and its occurrence is related to OIT starting dose, its rate of increase, and baseline AECs.

Allergen immunotherapy (AIT) with mold extracts has been performed for many years but the final demonstration of its clinical efficacy is still missing, due to the small number of studies and their inconsistent results.

To systematically review efficacy and safety of AIT for the treatment of respiratory allergies to molds.

The primary outcomes were safety and reduction of symptoms (Symptom Score, SS) and medication use (Medication Score, MS) in patients treated with AIT compared to controls. The strength of the evidence was graded based on the risk of bias, consistency and magnitude of effect, according to the GRADE Working Group’s guide.

Medline, Web of Science and the Cochrane Library (through September 2017)supplemented with manual searches of reference lists.

Randomized studies of intervention comparing AIT to placebo/pharmacotherapy. Studies not reporting on our outcome of interest or without a control population were excluded.

Nine studies (168 children, 99 adults; median sample size, 27) met the inclusion criteria. The risk of bias was moderate-to-high in all but one study. Low strength evidence supports the assumption that AIT is effective in reducing symptoms and medication use, with only 4 out of 9 studies reporting higher benefit of AIT vs. comparators. The highest benefit of AIT compared to pharmacotherapy/placebo was reported in studies with a longer follow-up (SMD for MS from -3.96 to -3.97 in favor of AIT) and low-risk of bias (VAS for SS: 66,3±13 in AIT group; 186,6±39 in comparators; p<0.05). No difference was reported with respect to study sample size, route of administration, age of participants. Generalised adverse reactions were reported in 12.5% of participants treated with sublingual immunotherapy, and 37.2% of participants treated with subcutaneous immunotherapy.

Low strength evidence suggests that mold AIT is efficacious for the treatment of respiratory allergies. High-quality studies with an adequate sample size are needed.

In this review, we sought to outline many of the recent evidences about the available clinical trials in which biologic agents [i.e. omalizumab (OMA)] were associated as add-on to allergen-specific immunotherapy (AIT).

The available literature shows that OMA may be a valuable option as add-on to AIT for respiratory allergy, or food desensitization, especially in the escalation or build-up phases, in which adverse events are more commonly expected. The encouraging data for hymenoptera venom allergy remain limited to case reports, and no structured clinical trial is available.

Over the past decade, studies of OMA used with AIT have shown promising results. Today, big randomized, double-blind, placebo-controlled trials are needed to better select those patients who would benefit from the addition of OMA (or other biologic agents) to AIT, as well as optimal dosing schedules, optimal duration of treatments and, finally, adequate evaluation about pharmacoeconomic aspects.

Cat allergy can manifest as allergic rhinitis, conjunctivitis and/or asthma. With widespread cat ownership and exposure, cat allergy has emerged as a major cause of morbidity. Cat allergen immunotherapy is a potential disease modifying treatment for patients with cat allergy. We examine evidence on the effectiveness, cost-effectiveness and safety of cat allergen immunotherapy and consider the clinical contexts in which it should be prescribed.

The European Association of Allergy and Clinical Immunology systematic reviews on allergic rhinitis and asthma along with the accompanying guidelines on allergic rhinitis were used as primary sources of evidence. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are most common routes of administration for allergen immunotherapy (AIT). A limited number of high-quality studies related to cat dander have shown mixed results in improvements in ocular and nasal symptoms, asthma symptoms, peak expiratory flow rate and medication use scores with subcutaneous immunotherapy. Two studies examining cat dander and cat-related allergy response with sublingual immunotherapy have shown mixed results in terms of symptomatic response. One randomized trial examining intralymphatic immunotherapy has shown a positive symptom response and a favourable safety profile. Although studies have reported mixed results regarding safety of SCIT, adverse events have been reported more commonly with SCIT than SLIT.

There is a limited body of high-quality evidence on the effectiveness and safety of cat AIT and no high-quality data on its cost-effectiveness. The available evidence on effectiveness is mixed based on studying a limited array of immunological, physiological and patient-reported outcome measures. Based on this evidence and extrapolating on the wider evidence base in AIT, it is likely that some patients may benefit from this modality of treatment, particularly those with moderate-to-severe disease who are inadequately controlled on allergen avoidance measures and pharmacotherapy and those who are monosensitized to Felix Domesticus 1. Further evidence is, however, required from larger trials before more definitive advice can be offered.

Partially hydrolyzed cow’s milk protein-based formula (pHF) possesses low allergenicity. Here, we investigate the safety and efficacy of oral immunotherapy using pHF for children with cow’s milk protein allergy (CMPA).

A randomized, double-blind, controlled single-center trial was conducted to evaluate the efficacy and safety of pHF oral immunotherapy in children with CMPA

Participants were randomized into double-blind pHF-pHF and extensively hydrolyzed cow’s milk protein-based formula (eHF)-pHF groups. During this phase, the pHF-pHF group received pHF and the eHF-pHF group received eHF. During the open phase, all participants received pHF. The primary end point was a change in thresholds between baseline and the end of the first phase. Secondary end points were changes in thresholds between baseline and the end of the second phase, and casein-specific immunoglobulin (Ig)E, IgG4, and basophil activation.

Twenty-five children, aged 1-9 years, were randomized into pHF-pHF and eHF-pHF groups. The threshold between baseline and the end of the first phase was significantly elevated in the pHF-pHF group (p = 0.048), but not in the eHF-pHF group. The threshold between other phases did not change significantly in either group. There were significant decreases in casein-specific IgE antibody levels between baseline and the second phase in the eHF-pHF group (p = 0.014). No participants suffered systemic allergic reactions requiring adrenaline or systemic corticosteroids after receiving the formulas.

The results of this trial suggest that, in children with CMPA, tolerance to cow’s milk might be safely enhanced by intake of pHF, relative to that of eHF.

The development of methods to predict the clinical effectiveness of sublingual immunotherapy (SLIT) for allergic diseases is a crucial matter. We sought to determine whether whole saliva, which is the first body component that contacts allergen extracts during SLIT, is associated with the clinical effectiveness of SLIT in Japanese cedar pollinosis.

Blood monocytes or monocytic THP-1 cells were cultured in the presence or absence of either whole saliva or pure saliva with or without treatments including filtration and blockade of TLR2 and/or TLR4 signaling. IL-10 levels in the supernatants were then measured. Whole saliva-induced IL-10 production by THP-1 cells was compared between asymptomatic and disease-onset patients during peak pollen dispersal after SLIT.

Both monocytes and THP-1 cells produced substantial amounts of IL-10 in response to whole saliva. IL-10 production was significantly reduced in response to pure saliva and 0.2 μm-filtered saliva. Simultaneous treatment with polymyxin B and TL2.1, a neutralizing antibody against TLR2, also reduced IL-10 production. IL-10 levels produced by THP-1 cells in response to whole saliva collected prior to SLIT were significantly higher in asymptomatic patients determined by symptom-medication scores than disease-onset patients following SLIT. Such differences were not seen in saliva collected 3 months after the initiation of SLIT or saliva collected during peak pollen dispersal.

Our results provide a basis for why the sublingual route is effective and preferable in allergen immunotherapy. Saliva-induced IL-10 levels produced by THP1 cells may be a predictive marker for clinical remission after SLIT.

Allergic rhinitis (AR) is an IgE-mediated inflammatory disease of the nasal mucosa with well described local immune responses during allergen exposure. The frequent association of AR with general extra-nasal symptoms and other allergic conditions, such as conjunctivitis and asthma, however, support a more systemic disease impact. In addition to acute elevation of soluble inflammatory mediators in periphery blood, a growing number of studies have reported changes in circulating blood cells after specific nasal allergen challenge or environmental allergen exposure. These findings imply an involvement of specific blood leukocyte subsets, thrombocytes and recently, erythrocytes. This review summarizes the circulating blood cell dynamics associated with allergen exposure in AR subjects reported so far. Additionally, the impact of therapy, particularly allergen-specific immunotherapy (AIT), the only currently available causal treatment reducing AR-related symptoms, is further considered in this context.

Subcutaneous immunotherapy (SCIT) is an effective treatment for allergic disease such as allergic rhinitis and asthma. Reported adherence rates to SCIT have been low, ranging between 50% and 89%. This study sought to evaluate compliance to SCIT in an urban “safety net,” tertiary care center, and to evaluate for disparities in compliance based upon insurance and socioeconomic status.

A retrospective chart review of SCIT patients between 2003 and 2016 was performed. Demographic data, insurance carriers, and comorbidities were collected. Compliance was evaluated on treatment adherence (percentage of injections administered/scheduled appointments). Statistical analysis was performed using R statistical software. Linear regression analysis was performed to compare compliance to the variables, asthma, duration of therapy, payor, and age. Analysis of variance was used to compare mean compliance between payor groups.

Two hundred five patients met our inclusion criteria and 28 were excluded. Insurance composition was Medicaid (67, 33%), Medicare (18, 9%), Health Safety Net (HSN) in Massachusetts (33, 16%), and commercial payors (82, 42%). Linear regression demonstrated that age, duration of therapy, and asthma status were not related to the percentage of missed doses ( P > .05). Payor status was statistically predictive of missed doses ( P = .02). When comparing average percentage of missed immunotherapy shots, Medicaid patients missed the most 34.2%, followed by Medicare 24.4%, commercial insurance 19.9%, and HSN in Massachusetts 18.5% ( P ≤ .02).

In a cohort of patients at a tertiary care “safety-net” center serving a low-income population, compliance to SCIT was found to be overall high but lower in the Medicaid population.

This multicenter randomized placebo-controlled double-blind clinical trial investigated which maintenance dose shows the optimal benefit-risk ratio for subcutaneous immunotherapy with a Dermatophagoides pteronyssinus allergoid preparation.

To evaluate four maintenance doses of the allergoid preparation versus placebo.

The late-phase reaction of the intracutaneous test was chosen as efficacy parameter and minimal dose of fluticasone required for asthma control.

A total of 146 adults with bronchial asthma were randomized. After subcutaneous immunotherapy, reductions in swelling size were greatest with 10,000 therapeutic units (TU). The 18,000 TU group showed the highest percentage of patients with fluticasone dose reduced to 0 μg/day