Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy.

Background: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year.

Objective: We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response.

Differential induction of allergen-specific IgA responses following timothy grass subcutaneous and sublingual immunotherapy.

Introduction: There is no detailed comparison of allergen-specific immunoglobulin responses following sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT).

Objective: We sought to compare nasal and systemic timothy grass pollen (TGP)-specific antibody responses during 2 years of SCIT and SLIT and 1 year after treatment discontinuation in a double-blind, double-dummy, placebo-controlled trial.

Methods: Nasal fluid and serum were obtained yearly (per-protocol population, n = 84).

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy.

Background: Allergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance.

Objective: We sought to evaluate the role of circulating CXCR5PD-1 T follicular helper (cT) and T follicular regulatory (T) cells following grass pollen subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) and the accompanying changes in their chromatin landscape.

Methods: Phenotype and function of cT cells were initially evaluated in the grass pollen-allergic (GPA) group (n = 28) and nonatopic healthy controls (NAC, n = 13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively.

EAACI Allergen Immunotherapy User's Guide.

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well-defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites.

Nasal allergen-neutralizing IgG antibodies block IgE-mediated responses: Novel biomarker of subcutaneous grass pollen immunotherapy.

Background: Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells.

Objective: We sought to determine whether SCIT induces nasal allergen-specific IgG antibodies with inhibitory activity that correlates closely with clinical response.

Methods: In a cross-sectional controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergic patients (with seasonal allergic rhinitis [SAR]), and 12 nonatopic control subjects.

Duration of Allergen Immunotherapy for Long-Term Efficacy in Allergic Rhinoconjunctivitis.

Rationale: Subcutaneous and sublingual immunotherapy are effective for allergic rhinitis. An important question is whether allergen immunotherapy provides a sustained clinical effect after treatment cessation. In view of potential side effects, cost and the necessary patient commitment, long-term benefit is an important consideration for the recommendation of immunotherapy over standard pharmacotherapy.

Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial.

Importance: Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment.

Objective: To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up.

Pathogenesis of rhinitis.

Rhinitis is a heterogeneous condition that has been associated with inflammatory responses as in allergic rhinitis but can also occur in the absence of inflammation such as in so-called idiopathic (previously 'vasomotor') rhinitis. Allergic rhinitis affects approximately one in four of the population of westernized countries and is characterized by typical symptoms of nasal itching, sneezing, watery discharge and congestion. The intention of this review is to illustrate key concepts of the pathogenesis of rhinitis.

Long-Term Effect of Sublingual and Subcutaneous Immunotherapy in Dust Mite-Allergic Children With Asthma/Rhinitis: A 3-Year Prospective Randomized Controlled Trial.

Background And Objective: Specific allergen immunotherapy is the only treatment modality that might change the natural course of allergic diseases in childhood. We sought to prospectively compare the long-term clinical and immunological effects of sublingual (SLIT) and subcutaneous (SCIT) immunotherapy compared with pharmacotherapy alone.

Methods: In this single-center, prospective randomized controlled trial, 48 children with mild persistent asthma with/without rhinitis, monosensitized to house dust mites (HDMs) were followed for 3 years.

Protocol for a randomised, double-blind, placebo-controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes.

Background: Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined.

Severe Persistent Allergic Rhinitis. Inflammation but No Histologic Features of Structural Upper Airway Remodeling.

Rationale: Increases in airway smooth muscle, extracellular matrix, and vascularity are prominent features of airway remodeling in asthma, whereas the extent of such remodeling in patients with persistent allergic rhinitis (PAR) is unknown.

Objectives: To test the hypothesis that upper airway remodeling is a feature of PAR.

Methods: Total nasal symptoms scores, nasal biopsies, and Th1 and Th2 cytokines from nasal lavage were assessed in subjects with severe PAR (n = 46) and healthy control subjects (n = 19).

Effect of grass pollen immunotherapy on clinical and local immune response to nasal allergen challenge.

Rationale: Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments.

Objective: To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study.

Methods: We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a nonatopic control group (n = 14).

Local and systemic effects of cat allergen nasal provocation.

Background: Cat allergen is widely distributed in homes and schools; allergic sensitization is common.

Objective: To develop a model of cat allergen nasal challenge to establish dose-response and time-course characteristics and investigate local and systemic biomarkers of allergic inflammation.

Methods: Nineteen cat-allergic individuals underwent titrated nasal challenge, range 0.

Allergen immunotherapy for house dust mite: clinical efficacy and immunological mechanisms in allergic rhinitis and asthma.

Introduction: There is an increasing prevalence of atopic diseases such as allergic rhinitis and asthma with house dust mite (HDM) being the common allergen that is highly associated with allergic rhinitis and asthma. Allergen avoidance and pharmacotherapy are part of treatment but it has proved difficult to change the course of HDM-related allergic diseases. Allergen immunotherapy (AIT) has been in use for the past century and has been shown to be effective in the treatment of allergic respiratory disease.

Risk factors for persistence of asthma in children: 10-year follow-up.

Objective: Risk factors related to the outcome of childhood asthma are not yet well established. We aimed to investigate the long-term outcome for children with asthma to determine the risk factors in predicting persistence of disease.

Methods: Sixty-two children with asthma were evaluated retrospectively at the end of a 10-year follow-up.

Sublingual immunotherapy in children with allergic rhinoconjunctivitis mono-sensitized to house-dust-mites: a double-blind-placebo-controlled randomised trial.

Background: Although sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficient treatment in children with seasonal allergic rhinitis (AR), there is little evidence on the efficacy of SLIT with house-dust-mite (HDM) extract in children with isolated perennial AR.

Objectives: We sought to assess the clinical efficacy and safety of HDM-SLIT in children with isolated allergic rhinitis-conjunctivitis mono-sensitized to HDM without asthma symptoms.

Methods: Twenty-two children (aged 5-10 years) with perennial AR and conjunctivitis symptoms mono-sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae were enrolled.

Impact of inhaled corticosteroids on the natural history of asthma in children.

Asthma is a heterogeneous disorder with a variable course. It begins very early in life and of different phenotypes. Mainstay treatment for asthma is corticosteroids as controller therapy and guidelines recommends the add-on and step-up or step-down strategies.

Reduced T-bet in addition to enhanced STAT6 and GATA3 expressing T cells contribute to human allergen-induced late responses.

Background: T-bet and GATA-3 are transcriptional factors involved in Th1 and Th2 cell differentiation, although their concomitant roles at protein levels in target organs during human allergic disease have not been assessed.

Objectives: We investigated the expression of T-bet and GATA-3 in nasal and cutaneous models of Th2 (grass-pollen allergen) and a cutaneous model of Th1 (PPD) responses in man.

Methods: Nasal biopsies were obtained at 8 h and skin biopsies at 8 and 48 h after allergen and PPD challenges, respectively, from 10 allergic rhinitics and 6 non-atopic controls.

Long-term clinical and immunological effects of allergen immunotherapy.

Purpose Of Review: The present review updates current findings on long-term clinical and immunological outcomes after cessation of allergen immunotherapy for allergic respiratory disease.

Recent Findings: Recent studies have shown that allergen immunotherapy has sustained disease-modifying effects that persist for years after discontinuation. This is in contrast to the effects of antiallergic drugs that do not induce tolerance to offending allergens.

Neonatal BCG vaccination induces IL-10 production by CD4+ CD25+ T cells.

To determine the optimal time of Bacillus Calmette-Guerin (BCG) vaccination for induction of Th1 immunity, we measured the interferon (IFN)-γ and interleukin (IL)-10 secretion in purified protein derivative (PPD)-stimulated peripheral blood mononuclear cell (PBMC) cultures in newborns vaccinated at birth or 2nd month of life. Moreover, role of CD4(+) CD25(+) T cells was studied by depletion assay at 8th month. Nineteen term and healthy newborns were randomized into two groups: Group I composed of 10 newborns vaccinated with BCG at birth and the remaining 9 (group II) at 2nd month of life.

Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial.

Background: In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated.

Objectives: To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM).

Methods: In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n=16), SCIT (n=16) or pharmacotherapy alone (n=16).

No association between tuberculin skin test and atopy in a bacillus Calmette-Guérin vaccinated birth cohort.

Previously, an inverse association was suggested between mycobacterial infection and atopy. We aimed to determine the association between tuberculin skin test (TST) and allergic manifestations in a birth cohort where all infants were vaccinated with bacillus Calmette-Guérin (BCG) at birth. Newborns were enrolled randomly and prospectively followed up for a period of 5 yr.

Clinical and immunologic features of pediatric patients with common variable immunodeficiency and respiratory complications.

Background: Common variable immunodeficiency (CVID) is the term used to describe a heterogeneous group of B-cell deficiency syndromes characterized by hypogammaglobulinemia, impaired antibody production, and recurrent bacterial infections.

Objectives: To determine the clinical manifestations and perform an immunological analysis of pediatric CVID patients suffering from respiratory complications.

Methods: The records of 10 patients with CVID who were followed up from 1992 to 2005 (6 males and 4 females) with a median (interquartile range) age of 13.