Allergen Valency, Dose, and FcεRI Occupancy Set Thresholds for Secretory Responses to Pen a 1 and Motivate Design of Hypoallergens.

Ag-mediated crosslinking of IgE-FcεRI complexes activates mast cells and basophils, initiating the allergic response. Of 34 donors recruited having self-reported shrimp allergy, only 35% had significant levels of shrimp-specific IgE in serum and measurable basophil secretory responses to rPen a 1 (shrimp tropomyosin). We report that degranulation is linked to the number of FcεRI occupied with allergen-specific IgE, as well as the dose and valency of Pen a 1.

Chitinase 3-like-1 regulates both visceral fat accumulation and asthma-like Th2 inflammation.

Rationale: Obesity, especially truncal obesity, is a risk factor for asthma incidence, prevalence, and severity. Chitinase 3-like-1 (Chi3l1) is an evolutionarily conserved moiety that plays a critical role in antipathogen and Th2 responses. However, the mechanisms that underlie the association between asthma and obesity and the role(s) of Chi3l1 in fat accumulation have not been defined.

High sputum total adiponectin is associated with low odds for asthma.

Objective: Adipose tissue produces adiponectin, an anti-inflammatory protein. High systemic total adiponectin is associated with a low risk for incident asthma but the association with lung adiponectin is not known. Our objective was to evaluate the association between sputum total adiponectin and asthma.

Body mass index is a stronger predictor than the metabolic syndrome for future asthma in women. The longitudinal CARDIA study.

Rationale: It is hypothesized that the metabolic syndrome explains the association between body mass index (BMI) and asthma in adults.

Objectives: Our objective was to longitudinally compare the relative strengths of the associations of the metabolic syndrome and BMI with incident asthma in adults.

Methods: We included 4,619 eligible participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort followed over 25 years.

Adult-onset asthma becomes the dominant phenotype among women by age 40 years. the longitudinal CARDIA study.

Rationale: Although asthma is usually considered to originate in childhood, adult-onset disease is being increasingly reported.

Objectives: To contrast the proportion and natural history of adult-onset versus pediatric-onset asthma in a community-based cohort. We hypothesized that asthma in women is predominantly of adult onset rather than of pediatric onset.

Effect of allergen inhalation on airway oxidant stress, using exhaled breath condensate 8-isoprostane, in mild asthma.

Objective: Exhaled breath condensate (EBC) 8-isoprostane concentrations are increased in asthma, but it is not known if they acutely change following bronchoprovocation. The objective of this study was to evaluate EBC 8-isoprostane concentrations following allergen-induced bronchoprovocation in asthma.

Methods: This comparison study included eight mild atopic asthmatics and six controls.

Low serum adiponectin predicts future risk for asthma in women.

Rationale: Our previous cross-sectional study showed that serum adiponectin is inversely associated with asthma among women. However, it is not known if serum adiponectin predicts future development of asthma or if asthma affects subsequent serum adiponectin concentrations among women.

Objectives: To determine longitudinal association between serum adiponectin and incident asthma among women.

Cigarette smoke suppresses Bik to cause epithelial cell hyperplasia and mucous cell metaplasia.

Rationale: Aberrant regulation of airway epithelial cell numbers in airways leads to increased mucous secretions in chronic lung diseases such as chronic bronchitis. Because the Bcl-2 family of proteins is crucial for airway epithelial homeostasis, identifying the players that reduce cigarette smoke (CS)-induced mucous cell metaplasia can help to develop effective therapies.

Objectives: To identify the Bcl-2 family of proteins that play a role in reducing CS-induced mucous cell metaplasia.

Anti-IgE therapy results in decreased myeloid dendritic cells in asthmatic airways.

Anti-IgE treatment of intermittent to mild-persistent asthma in a cohort of seven volunteers resulted in improved allergen-induced airway hyperreactivity and a significant reduction in the number of airway myeloid dendritic cells.

Do electronic health records affect the patient-psychiatrist relationship? A before & after study of psychiatric outpatients.

Background: A growing body of literature shows that patients accept the use of computers in clinical care. Nonetheless, studies have shown that computers unequivocally change both verbal and non-verbal communication style and increase patients' concerns about the privacy of their records. We found no studies which evaluated the use of Electronic Health Records (EHRs) specifically on psychiatric patient satisfaction, nor any that took place exclusively in a psychiatric treatment setting.

Roles for the High Affinity IgE Receptor, FcεRI, of Human Basophils in the Pathogenesis and Therapy of Allergic Asthma: Disease Promotion, Protection or Both?

The role of basophils, the rarest of blood granulocytes, in the pathophysiology of allergic asthma is still incompletely understood. Indirect evidence generated over many decades is consistent with a role for basophils in disease promotion. Recent improvements in procedures to purify and analyze very small numbers of human cells have generally supported this view, but have also revealed new complexities.

Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy.

Background: Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair, reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, FcepsilonRI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the FcepsilonRI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined.

Classification of hypersensitivity pneumonitis: a hypothesis.

Background: Regardless of the causative antigen, hypersensitivity pneumonitis (HP) is usually classified as 'acute', 'subacute' or 'chronic'. Considerable confusion still surrounds this classification because there are no widely accepted criteria to distinguish the various stages. The objective of this study was to determine whether the current classification of HP truly reflects categories of patients with distinct clinical features.

Effect of specific allergen inhalation on serum adiponectin in human asthma.

Background: Adiponectin is associated with asthma. The direction of this association is not known in humans. In mice, this association is bidirectional: allergen inhalation affects serum adiponectin, and exogenous adiponectin administration affects asthma.

Expression of the proapoptotic protein Bax is reduced in bronchial mucous cells of asthmatic subjects.

The present studies were designed to determine whether our findings in mice showing that the Bcl-2-associated protein X (Bax), which plays a role in the resolution of allergen-induced mucous cell metaplasia, can be applied to asthma in humans. Immunostaining of autopsy tissues from mild and severe asthmatic subjects showed a significant reduction in the percentage of Bax-positive mucous cells compared with those from nonasthmatic controls. To exclude the possibility that postmortem changes may have affected Bax expression, Bax mRNA levels in airway epithelial cells obtained from nonsmoking asthmatic subjects were compared with those from nonasthmatic controls.

A comparison of inflammatory mediators released by basophils of asthmatic and control subjects in response to high-affinity IgE receptor aggregation.

Background: In human blood basophils, cross-linking the high-affinity IgE receptor Fc epsilonRI with multivalent antigen activates a signaling pathway leading to secretion of inflammatory mediators and cytokine production. Basophils are known to play an important role in the pathogenesis of asthma but there has been no comprehensive examination of the effectors these cells produce. Here a study of the transcription and release of a selection of chemokines and cytokines from basophils was undertaken.

Histamine release from the basophils of control and asthmatic subjects and a comparison of gene expression between "releaser" and "nonreleaser" basophils.

Most human blood basophils respond to FcepsilonRI cross-linking by releasing histamine and other inflammatory mediators. Basophils that do not degranulate after anti-IgE challenge, known as "nonreleaser" basophils, characteristically have no or barely detectable levels of the Syk tyrosine kinase. The true incidence of the nonreleaser phenotype, its relationship (if any) to allergic asthma, and its molecular mechanism are not well understood.

Characterization of myeloid and plasmacytoid dendritic cells in human lung.

Dendritic cells (DCs) are bone marrow-derived mononuclear cells that play a central role in the initiation of immune responses. Because human lung DCs have been incompletely characterized, we enumerated and phenotyped mononuclear cell populations from excess lung tissue obtained at surgery. Myeloid DCs (MDCs) were identified as CD1c(+)CD11c(+)CD14(-)HLA-DR(+) cells and comprised approximately 2% of low autofluorescent (LAF) mononuclear cells.

Effect of electronic charting on the patient-psychiatrist relationship.

The impending implementation of an electronic medical record (EMR) within Behavioral Health facilities at the University of New Mexico (UNM) offers a unique opportunity to study the effects of EMR usage on a psychiatric patient population. A pre-test and post-test design using a satisfaction survey will test for changes to the patient-psychiatrist relationship before and after implementation. To date, 48 subjects have participated in the pre-implementation portion of the study.

Emotional responses to APO E genotype disclosure for Alzheimer disease.

The purpose of our study is to assess the emotional responses to disclosing APO E genotype to asymptomatic older adults at increased risk for Alzheimer disease (AD). This is a longitudinal cohort study of volunteer subjects who were aged 50 years or over, asymptomatic for (AD), had a family history of AD, passed a psychological assessment, and participated in pre- and post-test genetic counseling and three follow-up visits over 10 months. We analyzed responses by three emotional constructs: depressed, worried, and relieved.

Needs and opportunities for research in hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) develops after inhalation of many different environmental antigens, causing variable clinical symptoms that often make diagnosis uncertain. The prevalence of HP is higher than recognized, especially its chronic form. Mechanisms of disease are still incompletely known.

Immune response to hepatitis B vaccine in asthmatic children.

Asthma is a disease that demonstrates chronic Th2 lymphocyte-mediated pulmonary inflammation. We hypothesized that cytokines produced by asthmatic lung inflammation bias the immune response to antigens administered systemically toward a Th2 response, as assessed by serum IgE antibody and lymphocyte-secreted IL-4 and IL-5. We also hypothesized that treatment of asthmatic children with local anti-inflammatory agents reduces this cytokine-mediated Th2 influence.