clair088

Inhaled corticosteroids (ICSs) are the mainstay of treatment of asthma. However, a considerable proportion of asthmatic patients do not respond to ICSs based on lung function, or other clinical outcomes, or both. Therefore, biomarkers relevant to the underlying pathophysiologic process, the response to treatment, or both would be useful in personalizing care of asthmatic patients. This need led Cowan et al to follow up from an original study of a 2 phase trial consisting of a steroid-naïve phase 1 and a 28-day trial of ICSs (phase 2) during which fraction of exhaled nitric oxide (F ENO ) values, eosinophil counts, and urinary bromotyrosine (BrTyr) levels were measured in asthmatic patients ( J Allergy Clin Immunol 2015; 135(4): 877-883 ). Over the last decade, F ENO values and sputum eosinophil counts have been used as biomarkers of airway inflammation and predictors of steroid responsiveness. F ENO values are correlated with airway eosinophilia and associated with airway hyper-resp...

The relationship between overweight/obesity and asthma phenotype in children remains inadequately defined. Several large epidemiologic studies have demonstrated that obesity increases the risk of physician-diagnosed asthma and is associated with greater asthma-related health utilization and asthma that is more problematic and difficult to control. This discrepancy regarding the impact of obesity suggests that more in-depth and novel assessments of lean and obese asthmatic children may be required. Specifically, few studies have addressed how obese patients perceive and report asthma symptoms. This led Lang et al to determine the qualitative differences in symptoms between lean and overweight/obese children with early-onset, atopic asthma ( J Allergy Clin Immunol 2015; 135(4): 886-893 ). The authors conducted a cross-sectional analytic study of lean and overweight/obese 10-17 year old children with persistent, early-onset asthma. Participants provided a complete history, qualitative an...

Severe asthma is characterized by difficulty to achieve disease control despite high-dose inhaled glucocorticoids plus long acting β 2 –agonists (LABAs) or oral corticosteroids (OCSs). In 2011, the Innovative Medicine Initiative (IMI) published an international consensus statement in which a more accurate definition of severe asthma was proposed. In this statement, a clear distinction was made between “difficult to control asthma” and “severe refractory asthma.” In patients with difficult to control asthma, the lack of asthma control is due to other factors than asthma itself, such as nonadherence to treatment or incorrect inhalation technique. On the other hand, in patients with severe refractory asthma, the disease remains uncontrolled despite addressing and removing all possible factors that might aggravate the underlying disease. Hekking et al sought to estimate the prevalence of severe refractory asthma as defined by the IMI consensus ( J Allergy Clin Immunol 2015; 135(4): 896-902...

In addition to having a nonfunctional NADPH oxidase, activated phagocytes from patients with chronic granulomatous disease (CGD) and gp91phox-/- mice (modeling X-linked CGD) lack oxidant production from mitochondria, as reported by authors Fernandez-Boyanapalli et al ( http://www.jacionline.org/article/S0091-6749%2814%2901576-0/abstract ) . Specifically, neutrophils and monocytes from blood, as well as recruited neutrophils and macrophages from inflamed tissues of CGD mice, failed to produce mitochondrial oxidants when activated. Deficient mitochondrial oxidant production was shown to contribute to impaired bactericidal activity against Staphylococcus aureus and Burkholderia cepacia in vitro. Importantly, the researchers demonstrated that mitochondrial oxidant production was restored (see Figure) following short-term treatment of CGD mice with pioglitazone, a PPAR? agonist approved for treatment of type 2 diabetes. Pioglitazone is known to induce metabolic changes that mimic “starvatio...

Psoriasis, a chronic immune-mediated inflammatory skin disease, affects approximately 2% of the global population. Eighty to ninety percent of patients have plaque psoriasis, and the extent of the affected surface areas of the body and the degree of redness, hardening, and scaling of the skin define its severity. In addition to its negative effect on well-being and quality of life, moderate-to-severe psoriasis has comorbidities including increased risk of heart disease and stroke. Approximately 25% of psoriasis patients have moderate-to-severe disease. Genome-wide association studies have previously linked a variant in the genes for the IL-23 receptor and the p19 subunit of IL-23, or IL-23A, to psoriasis susceptibility. BI 655066 is a fully-human IgG 1 mAb selective for IL-23A. In this phase I proof-of-concept study, Krueger et al evaluated the results of administering a single-rising-dose of BI 655066 to patients with moderate-to-severe plaque psoriasis ( J Allergy Clin Immunol 2015 ...

The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review by Konradsen et al, research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components ( J Allergy Clin Immunol 2015; 135: 616-625 ). Exposure to allergens ...

Recent years have seen a tremendous acceleration of knowledge in the field of glycobiology, revealing many intricacies and functional contributions that were previously poorly appreciated or even unrecognized. This review by Bochner and Zimmermann highlights several topics relevant to glycoimmunology in which mammalian and pathogen-derived glycans displayed on glycoproteins and other scaffolds are recognized by specific glycan-binding proteins (GBPs), leading to a variety of proinflammatory and anti-inflammatory cellular responses ( J Allergy Clin Immunol 2015; 135: 598-608 ). Their main focus is on 2 families of GBPs, sialic acid–binding immunoglobulin-like lectins (siglecs) and selectins, which are involved in multiple steps of the immune response, including distinguishing pathogens from self, cell trafficking to sites of inflammation, fine-tuning of immune responses leading to activation or tolerance, and regulation of cell survival. Importantly for the clinician, accelerated rates ...