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Inhaled corticosteroids (ICSs) constitute the most commonly prescribed therapies for asthma. They are effective, but there are up to 24% of asthma patients who do not achieve significant improvement with them. ICSs produce treatment responses in six clinical phenotypes: lung function, bronchodilator response, airway responsiveness, symptoms, need for oral steroids, and frequency of emergency department visits or need for hospitalization. For the past 15 years and in an escalating prevalence of asthma, researchers have considered these phenotypes to be guided by separate mechanisms. Clemmer et al propose a move away from the focus on single phenotypes to a more holistic approach. They suggest that there is a corticosteroid responsiveness endophenotype that modulates the asthma disease process, is latent in ICS-untreated patients, and is active in ICS-treated patients. Under this hypothesis, the corticosteroid responsiveness endophenotype influences the asthma disease process to produce ...

Allergic reaction to drugs is a serious and often underserved public health concern. In 2013, the National Institute of Allergy and Infectious Diseases (NIAID) Division of Allergy, Immunology and Transplantation convened a workshop on the issue. Representatives from several NIH institutes and from the FDA joined experts in drug allergy for a day-long discussion. Wheatley et al present a summary of the topics and recommendations ( J Allergy Clin Immunol 2015; 136(2): 262-271 ). The authors define “drug allergy” as any adverse drug reaction (ADR) that has a proven immunologic mechanism, including but not limited to IgE-mediated disease. There are currently no systematic epidemiologic studies of drug allergy. Most of the epidemiologic data on adverse drug reactions (ADRs) at this point relies on clinical diagnosis. With few specific diagnostic tests, physician-based assessment remains the gold standard for phenotyping the reactions. ADRs are categorized as type A or type B. Type A reacti...

While means of measurement and estimates differ, in the past ten to fifteen years the prevalence of peanut allergy may have as much as tripled in countries such as the United States. This translates to nearly 100,000 new cases a year in the United States and United Kingdom. Fleischer et al. highlight emerging evidence that supports early, rather than delayed, peanut introduction in the period of complementary food introduction in infants, including many of those considered to be at high risk for peanut allergy. ( J Allergy Clin Immunol 2015; 136(2): 258-261 ) In the Learning Early About Peanut Allergy (LEAP) trial, 640 infants between the ages of four and eleven months, who were considered to be at high-risk because of egg allergy and/or severe eczema, were randomized to consume peanut at least 6 grams of peanut protein three times a week or to completely avoid peanut for the first five years of life. Five hundred and forty-two of these infants had a negative skin prick test (SPT) res...

The house dust mite (HDM) is present in human habitats around the globe, and it is a significant factor in allergic rhinitis and allergic asthma. Sensitization to mite allergens in early life compromises lung function and leads to wheezing in children, and it associates with poorer outcomes in a patient’s respiratory health in the long term. Calderón et al review the epidemiology of HDM allergy and the effect of HDM allergens on the human immune system ( J Allergy Clin Immunol 2015; 136(1): 38-48 ). Both assessing prevalence of HDM sensitivity and controlling a patient’s exposure to the allergen pose challenges. Prevalence data for HDM sensitization vary according to targeted population: from estimating 65 million to 130 million people in the global general population may be affected to as many as 50% of those with asthma. In addition, results vary within geographic locations, meaning studies have found significant differences in prevalence within a given country or region. In terms o...

Psoriasis is a chronic immune-mediated inflammatory skin disease with a global incidence of approximately 2%. The extent of the affected body surface area and degree of erythema, induration, and scaling in four areas define its severity, and approximately 25% of patients have moderate-to-severe disease. Genome-wide association studies have linked variants in the gene for the IL-23 receptor and the p19 subunit of IL-23 to psoriasis susceptibility. IL-23 induces differentiation of T H 17 cells and T H 22 cells. The former are a primary cellular source of proinflammatory cytokines, including IL-17, and the latter are a primary source of IL-22. Both interleukins can mediate the development of the epidermal hyperplasia and tissue inflammation that occurs in psoriasis. Krueger et al present the first-in-human proof-of-concept study to evaluate the clinical and biological effects of BI 655066 in patients with moderate-to-severe psoriasis. BI 655066 is a novel, fully human IgG 1 mAb selective...

Little is known about the mechanisms regulating the persistence of chronic asthma. Because many allergens are perennially present, it has been difficult to ascertain whether persistence depends on this proximity. Studies of patients with occupational asthma have shown they experience symptoms for years after occupational exposure has ended. Christianson et al developed a mouse model in which asthma persisted for six months after allergen exposure ceased. They then used a combination of immunologic, genetic, microarray, and pharmacologic approaches to identify the factors contributing to symptom persistence ( J Allergy Clin Immunol 2015; 136(1):59-68 ). The authors found increased ILC2 levels characterize chronic asthma. In addition, IL-33-driven ILC2s prove to be an essential factor. The blockade of epithelial IL-33 led to a complete resolution of airway hyperactivity and a significant reduction of airway inflammation. They found IL-13, a product of ILC2s, can induce production of IL-...

It is acknowledged that key events that determine risk for the development of allergic disease frequently occur years before manifestation of symptoms. Recent culture-based studies, in combination with population-wide bacterial metagenomic data, suggest that parallel bacterial interactions may contribute to disease development. Holt reviews these and related issues of immune competence in infancy ( J Allergy Clin Immunol 2015; 136(1): 15-22 ). A number of factors specific to  infancy can contribute to disease development. Prospective tracking of postnatal IgE titres in serum samples collected over the first five years of life strongly suggests IgE antibody production against aeroallergens rarely begins before the age of six months. Airway mucosal dendritic cells (AMDC) transmit aeroallergen-specific signals from the airway mucosal surface to the central immune system and program the balance between the Th2 and T regulatory cell components of the immunological memory that results. T...