Association Between Aspirin-Exacerbated Respiratory Disease and Atherosclerotic Cardiovascular Disease: A Retrospective Review of US Claims Data.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) consists of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). Asthma is associated with increased risk of atherosclerotic cardiovascular diseases (ASCVD). However, there is lack of data on association between AERD and ASCVD. OBJECTIVE: To investigate the relationship between AERD and subsequent risk of ASCVD. METHODS: An algorithm to find patients with AERD was generated and validated through chart review at our home institution. This algorithm was applied to a national insurance claims database to obtain data for a retrospective cohort study. Demographic and comorbidity data were obtained for propensity matching. Several methods of analysis were performed on the data. RESULTS: A total of 571 patients met criteria for AERD; 3909 met criteria for asthma, CRSwNP, and no allergy to aspirin or NSAIDs (group 1); and 75,050 met criteria for asthma, CRS without nasal polyps, and no allergy to aspirin or NSAIDs (group 2). After covariate adjustment, AERD was significantly associated with ASCVD, including severe ASCVD, over groups 1 and 2 regardless of asthma severity. CONCLUSION: Patients with AERD are at higher risk of ASCVD than patients with asthma and CRSwNP or CRS without nasal polyps, underscoring the need for early ASCVD screening and a consideration for aspirin desensitization or use of a nonaspirin antiplatelet agent in the setting of AERD and comorbid ASCVD.

SCIT Versus SLIT: Which One Do You Recommend, Doc?

Allergic rhinitis is a prevalent condition that has a significant impact on the quality of life of many patients. When initial therapy fails to control the symptoms, allergen immunotherapy (AIT) has been suggested as an option by the Joint Task Force on Practice Parameters. The 2 main forms of AIT are via subcutaneous and sublingual routes, called subcutaneous immunotherapy and sublingual immunotherapy, respectively. There is debate about which is the better option for patients with each method offering its own pros and cons. We present 2 patients with allergic rhinitisAR that were deemed good candidates for AIT and explore current evidence for both subcutaneous immunotherapy and sublingual immunotherapy. The advantages and disadvantages of each method are discussed with the goal of providing a framework for the physician when deciding on AIT for their patients. In addition, we explore the use of AIT in patients with asthma and atopic dermatitis as potential patient populations that may benefit from the treatment. We use the discussion to provide recommendations regarding which method of AIT is best suited for both our patients.

Interleukin-4/interleukin-13 versus interleukin-5: a comparison of molecular targets in biologic therapy for the treatment of severe asthma.

PURPOSE OF REVIEW: Asthma is a chronic, inflammatory disorder of the airways caused by a complex interplay of various biologic mechanisms. Several monoclonal antibody therapies targeting interleukin (IL)-4/IL-13 and IL-5 cytokine pathways have been developed for the treatment of severe eosinophilic asthma. As individuals can display biomarkers and clinical features characteristic of several asthma phenotypes, selection of anoptimal biologic can be difficult. RECENT FINDINGS: Dupilumab, a monoclonal antibody that binds to the α subunit of the IL-4 receptor (IL-4Rα) and has been approved for the treatment of adults with severe atopic dermatitis, has been shown in recent phase 3 trials to also have significant clinical benefits in the asthmatic population irrespective of baseline eosinophil counts. SUMMARY: As monoclonal antibodies targeting either IL-4 or IL-13 cytokines individually have failed to demonstrate significant clinical benefits, biologics that target cytokine receptors may be more efficacious compared to those that target cytokines. Furthermore, inhibition of the IL-4/IL-13 signaling cascades may disrupt a broader Th2 inflammatory response compared to a more selective impairment of eosinophil proliferation and activity via blockage of the IL-5 pathway. Future research with independently funded, head-to-head trials of approved biologics is needed to elucidate a favorable therapeutic option.

Asthma versus chronic obstructive pulmonary disease, the Dutch versus British hypothesis, and role of interleukin-5.

PURPOSE OF REVIEW: Asthma and COPD represent heterogeneous disorders with broad ranging impact on patients and health systems. This review focuses on evidence for early attempts at understanding their pathogenesis by the British and Dutch hypotheses. It also addresses the role of eosinophils, IL-5, and biologics targeting these pathways in asthma and COPD. RECENT FINDINGS: Among asthma and COPD patients, clusters exist based on phenotypic and biologic markers allowing for further understanding of endotypes. Recent studies suggest the role of eosinophils and optimal therapies for each condition may be different. SUMMARY: Although patients with ACOS or overlap symptoms may be an exception, overall there appears to be more evidence supporting that asthma and COPD are distinct processes. Targeting eosinophils with anti-IL-5 therapy appears to be an exciting pathway in the properly selected patient with asthma and recent data also supports its use in COPD.

Biologic Therapy in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is common worldwide. The predominant cause in most COPD is environmental exposure to toxicants. The inflammatory processes in COPD are multifactorial, complex, and interacting, leading to many potential therapeutic targets. Although most typically associated with neutrophilic/macrophagic inflammation (type 1), it is now known that COPD can also be associated with eosinophilic inflammation (type 2), particularly in exacerbations. Accordingly, there is an active program of investigation of highly selective biologic therapeutic agents in the management of COPD. This review summarizes clinical trials of the use of these novel agents in the management of COPD.

Biologic therapy in the management of asthma.

PURPOSE OF REVIEW: Current asthma management relies on inhaled corticosteroids, but some asthma is not well controlled with inhaled steroids alone or in combination with long-acting bronchodilators or leukotriene pathway inhibitors. The field of biologic therapy has grown dramatically in the past two decades, with current availability of three molecules, with two distinct and highly selective approaches to interfering with the allergic and eosinophilic airway inflammation common to most asthma. This review summarizes current and future options for incorporating biologic therapy into the overall management of asthma. RECENT FINDINGS: Two new biologic agents have been recently introduced in the United States market, supported by well controlled, randomized clinical trials. These trials have provided insight into the types of patients who are most likely to benefit from these novel agents. SUMMARY: In asthma patients with frequent exacerbations, the addition of a biologic agent targeting the interleukin-5 pathway, or immunoglobulin E, can significantly reduce exacerbations and improve asthma control. The clinical predictors of utility of specific agents overlap with one another, highlighting the importance of clinical judgment in the overall management of this complex disorder.

Acute methotrexate toxicity seen as plaque psoriasis ulceration and necrosis: A diagnostic clue.

In addition to the well-known signs of methotrexate toxicity, rare cutaneous side effects have been described. These cutaneous signs may provide a diagnostic clue into the diagnosis of toxicity as well as facilitate early and aggressive therapy. We describe the case of a 37-year-old male, with a diagnosis of psoriasis, who developed characteristic signs and symptoms of acute methotrexate toxicity after receiving an unknown amount of intravenous methotrexate. The patient experienced a distinct change in the morphology of his existing psoriatic plaques, which became ulcerated and necrotic in the week following the methotrexate injection. Shortly after the development of cutaneous erosions, the patient developed pancytopenia, which ultimately led to his death. Ulceration and necrosis of cutaneous psoriasis plaques may serve as a herald for the impending development of life-threatening pancytopenia in patients with acute methotrexate toxicity.