Practical Guidance for Prevention and Management of Glucocorticoid-Induced Osteoporosis for the Allergist/Immunologist.

Osteoporosis is a silent disorder with dire consequences, and glucocorticoid use remains the most common iatrogenic cause illustrated by the fact that 30% to 50% of subjects on such long-term therapy experience fractures (Oimomi M, Nakamichi T, Ohara T, Sakai M, Igaki N, Hata F, et al. Fructose-related glycation. Diabetes Res Clin Pract 1989;7:137-9; Reid IR. Glucocorticoid osteoporosis--mechanisms and management. Eur J Endocrinol 1997;137:209-17). By directly affecting bone quality while actively used, glucocorticoids increase the risk of fracture that is independent of a subject's bone density status at the time (Weinstein RS. True strength. J Bone Miner Res 2000;15:621-5). A large number of subjects seen in an allergy and immunology clinic have asthma, chronic rhinosinusitis, or other chronic inflammatory diseases, necessitating the use of these medications and placing them at higher risk for this disease. Data on the effects of both oral and inhaled glucocorticoids on fracture risk are presented. This review concretizes the importance of osteoporosis, its pathophysiology, and provides practical guidelines to prevent and treat it. Management recommendations are tailored to 2 different age groups. The first group consists of children, adolescents, and adults 40 years or younger with a focus on attaining peak bone mass. The second group consists of adults 40 years or older where the use of imaging modalities and Fracture Risk Assessment Tool scores helps triage subjects into fracture risk categories. Those at moderate to high risk require bone-sparing medications. Universal preventive measures for both groups are reviewed. Complicated and severe cases may need additional expertise by an endocrinologist or rheumatologist.

Mechanisms of non-type 2 asthma.

Non-type 2 inflammation (Non-T2)-mediated asthma is difficult to define due to lack of signature biomarkers. It exists in the absence of T2-high or eosinophilic inflammation and includes neutrophilic and paucigranulocytic subtypes. Several cell types and cytokines, including Th1, Th17, IL-6, and IL-17, contribute to mechanisms of non-T2 asthma. Neutrophil extracellular traps (NETs) and inflammasome activation likely play a role in severe neutrophilic asthma. Several mechanisms lead to uncoupling of airway hyperresponsiveness and remodeling from airway inflammation in paucigranulocytic asthma. Recent research on transcriptomics and proteomics in non-T2 asthma is discussed in this review. Investigations of specific drug therapies for non-T2 asthma have been disappointing, and remain an important area for future clinical studies.

Cardiovascular and Diabetic Medications That Cause Bradykinin-Mediated Angioedema.

Medication-induced angioedema is a bradykinin-mediated process that results from increased production or decreased degradation of bradykinin. These reactions are documented for several cardiac medications including blockers of the renin-angiotensin-aldosterone system (RAAS). Other cardiovascular and diabetes medications further increase the risk of medication-induced angioedema, particularly with concomitant use of RAAS inhibitors. Dipeptidyl peptidase IV inhibitors are a class of oral diabetic agents that affect bradykinin and substance P degradation and therefore can lead to angioedema. Neprilysin inhibitors are a separate class of cardiac medications, which includes sacubitril, and can lead to drug-induced angioedema especially when used in combination with RAAS inhibitors. This article discusses the proposed mechanisms by which these medications cause angioedema and how medication-induced angioedema differs from mast cell-mediated angioedema. It also details how to recognize medication-induced angioedema and the treatment options available.