Efficacy and Safety of a Polypill to Reduce Cardiovascular Events: A Review of Clinical Trials.

ABSTRACT: Cardiovascular disease continues to be the leading cause of mortality globally. Modifiable risk factors, such as hypertension and dyslipidemia, can be managed through lifestyle and pharmacotherapy treatments to reduce the risk of primary and secondary major cardiovascular events in patients with elevated risk. Despite effective and available medications to manage and mitigate cardiovascular risk factors, control rates of hypertension and dyslipidemia are suboptimal, and greater efforts are needed to reduce cardiovascular event rates worldwide. A polypill containing several classes of medications proven to lower cardiovascular risk in a single-dose form has been associated with improved medication adherence over multiple single-ingredient medications and may lead to reduced cardiovascular events. The goal of this article is to review available data from clinical trials assessing the efficacy and safety of polypills compared with placebo or usual care for cardiovascular risk reduction. Three databases were searched (PubMed/MEDLINE, CINAHL, and ScienceDirect) for randomized trials that compared a single polypill with usual care or placebo and reported major adverse cardiovascular events for each study group. A total of 6 trials were selected for inclusion. Several polypill formulations were compared with placebo or usual care with multiple single-ingredient medications in study populations consisting of both primary and secondary prevention patients. Overall, the polypill seems to be associated with reduced major adverse cardiovascular event and comparable safety with usual care treatment with an added benefit of improved adherence over multiple single-ingredient medications. The polypill has potential to be a cost-effective intervention to reduce the global burden of cardiovascular disease.

With Current Safety and Efficacy Data, Should Statins Be Made Available as Nonprescription Over-the-Counter Drugs?

PURPOSE OF REVIEW: Statins inhibit the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the liver and reduce atherosclerotic cardiovascular disease (ASCVD) risk by enhancing low-density lipoprotein (LDL) clearance from the circulation. In this review, we discuss their efficacy, safety, and real-world utilization to make a case for reclassifying statins as nonprescription over-the-counter drugs to improve access and availability with the overarching goal of increasing statin utilization in patients most likely to benefit from this class of therapy. RECENT FINDINGS: Statin efficacy for reducing risk in primary and secondary ASCVD prevention populations as well as their safety and tolerability has been thoroughly investigated in large-scale clinical trials over the past 3 decades. Despite the overwhelming scientific evidence, statins are underutilized even among those at the highest ASCVD risk. We propose a nuanced approach to use statins as nonprescription drugs that leverages a multi-disciplinary clinical model. It integrates lessons learned from experiences outside the USA with a proposed Food and Drug Administration rule change that allows nonprescription drug products with an additional condition for nonprescription use.

Predictors of faculty narrative evaluation quality in medical school clerkships.

INTRODUCTION: Narrative approaches to assessment provide meaningful and valid representations of trainee performance. Yet, narratives are frequently perceived as vague, nonspecific and low quality. To date, there is little research examining factors associated with narrative evaluation quality, particularly in undergraduate medical education. The purpose of this study was to examine associations of faculty- and student-level characteristics with the quality of faculty member's narrative evaluations of clerkship students. METHODS: The authors reviewed faculty narrative evaluations of 50 students' clinical performance in their inpatient medicine and neurology clerkships, resulting in 165 and 87 unique evaluations in the respective clerkships. The authors evaluated narrative quality using the Narrative Evaluation Quality Instrument (NEQI). The authors used linear mixed effects modelling to predict total NEQI score. Explanatory covariates included the following: time to evaluation completion, number of weeks spent with student, faculty total weeks on service per year, total faculty years in clinical education, student gender, faculty gender, and an interaction term between student and faculty gender. RESULTS: Significantly higher narrative evaluation quality was associated with a shorter time to evaluation completion, with NEQI scores decreasing by approximately 0.3 points every 10 days following students' rotations (p = .004). Additionally, women faculty had statistically higher quality narrative evaluations with NEQI scores 1.92 points greater than men faculty (p = .012). All other covariates were not significant. CONCLUSIONS: The quality of faculty members' narrative evaluations of medical students was associated with time to evaluation completion and faculty gender but not faculty experience in clinical education, faculty weeks on service, or the amount of time spent with students. Findings advance understanding on ways to improve the quality of narrative evaluations which are imperative given assessment models that will increase the volume and reliance on narratives.

Diagnostic Yield of Cardiac Biomarker Testing in Predicting Cardiac Disease and Multisystem Inflammatory Syndrome in Children in the Pandemic Era.

OBJECTIVES: This study aimed to assess whether elevations in cardiac biomarkers are associated with pediatric cardiac diagnoses in the era of COVID-19 and multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: This single-center retrospective study analyzed children with a troponin drawn in the emergency department or inpatient unit between April 21 and December 31, 2020. The primary outcome was the presence of a cardiac diagnosis or MIS-C. Relationships among demographics, complaint, cardiac diagnostics, and cardiac biomarkers were analyzed. RESULTS: Four hundred eighty-six patients (mean ± SD; age 13.1 ± 7.8 years; 46.7% women) met inclusion criteria, for whom a cardiac diagnosis (excluding MIS-C) was made in 27 (5.6%) patients, with MIS-C diagnosed in 14 (2.9%) patients. The sensitivity and specificity of an elevated initial high-sensitivity troponin T (hsTropT) value (>14 ng/L) in predicting the composite outcome of a cardiac diagnosis or MIS-C were 54% and 89%, respectively. Four percent of patients with negative initial troponin values were found to have a cardiac diagnosis or MIS-C. Multivariable regression analysis demonstrated that elevated hsTropT (>14 ng/L; odds ratio [OR] [95% confidence interval]: 4.9 [1.70-14.0]) and elevated N-terminal pro B-type natriuretic peptide values (>500 pg/mL; 6.4 [2.01-20.1]) were associated with increased odds of a cardiac diagnosis or MIS-C. CONCLUSIONS: Children with elevated cardiac biomarkers have increased odds of a cardiac diagnosis or MIS-C and warrant workup regardless of indication for testing. Although a negative hsTropT may reassure providers, further investigation is critical in developing algorithms to reliably exclude cardiac disease.

Home blood pressure monitoring to improve hypertension control: a narrative review of international guideline recommendations.

Home blood pressure monitoring (HBPM) is a convenient way to assess out-of-office blood pressure control and is recommended by numerous international guidelines to aid clinicians in the diagnosis and management of essential hypertension. Although available guidelines recommend the use of HBPM in patients receiving antihypertensive medication, their specific recommendations regarding optimal monitoring schedule, duration, and clinician interpretation of home blood pressure readings may differ among guidelines. Purpose: The purpose of this article is to review available international hypertension guideline recommendations related to the use of HBPM to improve hypertension control among patients receiving antihypertensive therapy. We also briefly highlight clinical trials that have shown improved blood pressure control using HBPM to intensify antihypertensive therapy and provide a practical guide for implementing HBPM to improve hypertension control. Results: Eleven international guidelines were identified and reviewed. In total, recommendations relating to which HBPM to use, number of measurements per day, and how to interpret home blood pressure values were largely in agreement among available guidelines. Conclusion: Clinicians recommending HBPM to their patients with hypertension should utilise a standardised HBPM protocol, based on available guideline recommendations.

Distinguishing Features of Patients Evaluated for Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: Given the significant overlap of multisystem inflammatory syndrome in children (MIS-C) with other common childhood illnesses presenting to the emergency department, extensive workup of this syndrome has become necessary. Nevertheless, little has been published on the factors differentiating MIS-C from other conditions in the acute care setting. We investigated differences in presentation and laboratory studies between suspected versus confirmed MIS-C patients. METHODS: This was a retrospective cohort study on patients 21 years or younger undergoing investigation for possible MIS-C at a single institution between April 21 and July 1, 2020. The primary outcome was diagnosis of MIS-C or an alternative final diagnosis. Clinical features and laboratory findings from initial presentation were collected and analyzed. RESULTS: A total of 106 patients (median, 4 years; 55.7% male) were included, of whom 17 (16%) of 106 met the criteria for MIS-C. Multisystem inflammatory syndrome in children patients were significantly more likely to report a coronavirus disease 2019 exposure (odds ratio (OR), 13.17 [3.87-44.9]), have gastrointestinal symptoms (OR, 3.81 [1.02-14.19]), and have a significantly higher odds of having abnormal laboratory values including high-sensitivity troponin T (OR, 13 [4.0-42.2]), N-terminal B-type natriuretic peptide (OR, 8.4 [2.3-30.1]), D-dimer (OR, 13 [1.6-103]), and ferritin (OR, 7.8 [2.2-27.2]). There were also differences between groups in inflammatory markers: C-reactive protein (median, 134.45 mg/L vs 12.6 mg/L; P < 0.05) and procalcitonin (1.71 ng/mL vs 0.14 ng/mL; P < 0.001). CONCLUSIONS: Higher elevations in key laboratory studies may help to distinguish between MIS-C patients and non-MIS-C patients presenting to the emergency department.

School Social Worker Voice during COVID-19 School Disruptions: A National Qualitative Analysis.

The novel coronavirus (COVID-19) pandemic has created unprecedented impacts on our schools and society, requiring school social workers (SSWs) to attend to layered and cascading effects for students and their families. This study presents rich qualitative data from a national survey of SSWs about their personal and professional roles supporting students, families, and staff members as schools shifted to remote instruction. Findings indicate that SSWs are highly concerned about a lack of basic needs resources, including food, housing, and mental health support for students and families. SSWs highlighted the unequal effects of school closures for families without technology and Internet access as well as the difficulties providing services during the pandemic. Recovery policies should target resources to schools with the highest needs while prioritizing food, housing, mental health, and access to tools for online learning. SSWs also need additional and refined professional support to overcome their isolated roles in schools and bolster their ability to deliver online services effectively.

Role of Bempedoic Acid in Dyslipidemia Management.

Statins remain the preferred agent to reduce low-density lipoprotein cholesterol (LDL-C) and lower atherosclerotic cardiovascular disease (ASCVD) risk. Additional nonstatin agents are recommended to further lower LDL-C among patients at high-risk of ASCVD or those with heterozygous familial hypercholesterolemia, despite statin therapy. Patients unable to tolerate recommended doses of statin therapy due to adverse effects, including statin-associated muscle symptoms, may also require additional nonstatin agents to lower LDL-C and ASCVD risk. Bempedoic acid is a first-in-class, once-daily oral agent, recently approved as monotherapy and in combination with ezetimibe, as an adjunct to maximally tolerated statin therapy in patients with ASCVD or heterozygous familial hypercholesterolemia who require additional LDL-C lowering. Its novel mechanism is reported to avoid adverse muscle symptoms associated with statins. The effectiveness and safety of bempedoic acid and bempedoic acid/ezetimibe combination have been reported in multiple phase 2 and 3 trials. In this review, we report the lipid-lowering effects associated with bempedoic acid, and the safety profile from multiple clinical trials. Based on available data, bempedoic acid significantly lowers LDL-C and other atherogenic lipoprotein measures, and high-sensitivity C-reactive protein when added to background lipid-lowering therapy in patients with and without statin intolerance. Overall safety of bempedoic acid seems to be comparable to placebo, except for increased serum uric acid and tendon rupture. Ongoing clinical trials assessing the long-term safety and cardiovascular outcomes will provide additional insight into the role of bempedoic acid as an adjunct lipid-lowering medication.

PCSK9 Inhibitors in Secondary Prevention-An Opportunity for Personalized Therapy.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is the primary cause of ASCVD and reducing LDL-C levels with statin therapy significantly reduces ASCVD risk; however, significant residual risk remains. Two monoclonal antibodies (mAbs), alirocumab and evolocumab, that target proprotein convertase subtilisin/kexin-type 9 (PCSK9), reduce LDL-C levels by up to 60% when used in combination with statins and significantly reduce the risk of recurrent ASCVD events in both stable secondary prevention and acute coronary syndrome populations. Prespecified analyses of recent randomized controlled trials have shed light on how best to prioritize these therapies to maximize their value in select high-risk groups. These data have also informed recent clinical practice guidelines and scientific statements resulting in an expanded role for PCSK9-mAbs compared with previous guidelines, albeit there are notable differences between these recommendations. Ongoing research is exploring the long-term safety of PCSK9-mAbs and their role in the acute setting and patients without prior myocardial infarction or stroke. Novel therapies that inhibit PCSK9 synthesis via small interfering RNA, such as inclisiran, are also in development and may reduce LDL-C levels similar to PCSK9-mAbs, but with less frequent administration. Nonetheless, the PCSK9-mAbs are a breakthrough therapy and warrant consideration in very high-risk patients who are most likely to benefit. Such a personalized approach can help to ensure cost-effectiveness and maximize their value.

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty.

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Initial Response to Transcranial Magnetic Stimulation Treatment for Depression Predicts Subsequent Response.

This study provides support for the hypothesis that treatment response to an initial course of repetitive transcranial magnetic stimulation (rTMS) for depression predicts the magnitude of response to a subsequent course of rTMS in the setting of symptom relapse.

Role of lipoprotein(a) in atherosclerotic cardiovascular disease: A review of current and emerging therapies.

Lipoprotein(a), or Lp(a), is structurally like low-density lipoprotein (LDL) but differs in that it contains glycoprotein apolipoprotein(a) [apo(a)]. Due to its prothrombotic and proinflammatory properties, Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Lp(a) levels are genetically determined, and it is estimated that 20%-25% of the global population has an Lp(a) level ≥50 mg/dL (or ≥125 nmol/L). Diet and lifestyle interventions have little to no effect on Lp(a) levels. Lipoprotein apheresis is the only approved treatment for elevated Lp(a) but is time-intensive for the patient and only modestly effective. Pharmacological approaches to reduce Lp(a) levels and its associated risks are of significant interest; however, currently available lipid-lowering therapies have limited effectiveness in reducing Lp(a) levels. Although statins are first-line agents to reduce LDL cholesterol levels, they modestly increase Lp(a) levels and have not been shown to change Lp(a)-mediated ASCVD risk. Alirocumab, evolocumab, and inclisiran reduce Lp(a) levels by 20-25%, yet the clinical implications of this reduction for Lp(a)-mediated ASCVD risk are uncertain. Niacin also lowers Lp(a) levels; however, its effectiveness in mitigating Lp(a)-mediated ASCVD risk remains unclear, and its side effects have limited its utilization. Recommendations for when to screen and how to manage individuals with elevated Lp(a) vary widely between national and international guidelines and scientific statements. Three investigational compounds targeting Lp(a), including small interfering RNA (siRNA) agents (olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen), are in various stages of development. These compounds block the translation of messenger RNA (mRNA) into apo(a), a key structural component of Lp(a), thereby substantially reducing Lp(a) synthesis in the liver. The purpose of this review is to describe current recommendations for screening and managing elevated Lp(a), describe the effects of currently available lipid-lowering therapies on Lp(a) levels, and provide insight into emerging therapies targeting Lp(a).

DARE Training: Teaching Educators How to Revise Internal Medicine Residency Lectures by Using an Anti-racism Framework.

Introduction: Systemic inequities and provider-held biases reinforce racism and further disparities in graduate medical education. We developed the Department of Medicine Anti-Racism and Equity Educational Initiative (DARE) to improve internal medicine residency conferences. We trained faculty and residents to serve as coaches to support other faculty in delivering lectures. The training leveraged a best-practices checklist to revise existing lectures. Methods: We recruited internal medicine faculty and residents to serve as DARE coaches, who supported educators in improving lectures' anti-racism content. During the training, coaches watched a videotaped didactic presentation that we created about health equity and anti-racism frameworks. DARE coaches then participated in a workshop where they engaged in case-based learning and small-group discussion to apply the DARE best-practices checklist to sample lecture slides. To assess training effectiveness, coaches completed pre- and posttraining assessments in which they edited different sample lecture slides. Our training took 1 hour to complete. Results: Thirty-four individuals completed DARE training. Following the training, the sample slides were significantly improved with respect to diversity of graphics (p < .001), discussion of research participant demographics (p < .001), and discussion of the impact of racism/bias on health disparities (p = .03). After DARE training, 23 of 24 participants (96%) endorsed feeling more prepared to bring an anti-racist framework to lectures and to support colleagues in doing the same. Discussion: Training residents and faculty to use DARE principles in delivering internal medicine lectures is an innovative and effective way to integrate anti-racism into internal medicine residency conferences.

An Anti-Racism and Equity Initiative Improves Residency Educational Conferences.

Background: Graduate medical education curricula may reinforce systemic inequities and bias, thus contributing to health disparities. Curricular interventions and evaluation measures are needed to increase trainee awareness of bias and known inequities in health care. Objective: This study sought to improve the content of core noontime internal medicine residency educational conferences by implementing the Department of Medicine Anti-Racism and Equity (DARE) educational initiative. Methods: DARE best practices were developed from available anti-racism and equity educational materials. Volunteer trainees and faculty in the department of medicine of a large urban academic medical center were recruited and underwent an hourlong training to utilize DARE best practices to coach faculty on improving the anti-racist and equity content of educational conferences. DARE coaches then met with faculty to review the planned 2021-2022 academic year (AY) lectures and facilitate alignment with DARE best practices. A rubric was created from DARE practices and utilized to compare pre-intervention (AY21) and post-intervention (AY22) conferences. Results: Using the DARE best practices while coaching increased the anti-racism and equity content from AY21 to AY22 (total rubric score mean [SD] 0.16 [1.19] to 1.38 [1.39]; P=.001; possible scores -4 to +5), with 75% (21 of 28) of AY22 conferences showing improvement. This included increased diversity of photographs, discussion of the racial or ethnic makeup of research study participants, appropriate use of race in case vignettes, and discussion of the impact of racism or bias on health disparities. Conclusions: Training coaches to implement DARE best practices improved the anti-racism and equity content of existing noontime internal medicine residency educational conferences.

Preferred Language Mediates Association Between Race, Ethnicity, and Delayed Presentation in Critically Ill Patients With COVID-19.

Which social factors explain racial and ethnic disparities in COVID-19 access to care and outcomes remain unclear. OBJECTIVES: We hypothesized that preferred language mediates the association between race, ethnicity and delays to care. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective cohort study of adults with COVID-19 consecutively admitted to the ICU in three Massachusetts hospitals in 2020. MAIN OUTCOME AND MEASURES: Causal mediation analysis was performed to evaluate potential mediators including preferred language, insurance status, and neighborhood characteristics. RESULTS: Non-Hispanic White (NHW) patients (157/442, 36%) were more likely to speak English as their preferred language (78% vs. 13%), were less likely to be un- or under-insured (1% vs. 28%), lived in neighborhoods with lower social vulnerability index (SVI) than patients from racial and ethnic minority groups (SVI percentile 59 [28] vs. 74 [21]) but had more comorbidities (Charlson comorbidity index 4.6 [2.5] vs. 3.0 [2.5]), and were older (70 [13.2] vs. 58 [15.1] years). From symptom onset, NHW patients were admitted 1.67 [0.71-2.63] days earlier than patients from racial and ethnic minority groups (p < 0.01). Non-English preferred language was associated with delay to admission of 1.29 [0.40-2.18] days (p < 0.01). Preferred language mediated 63% of the total effect (p = 0.02) between race, ethnicity and days from symptom onset to hospital admission. Insurance status, social vulnerability, and distance to the hospital were not on the causal pathway between race, ethnicity and delay to admission. CONCLUSIONS AND RELEVANCE: Preferred language mediates the association between race, ethnicity and delays to presentation for critically ill patients with COVID-19, although our results are limited by possible collider stratification bias. Effective COVID-19 treatments require early diagnosis, and delays are associated with increased mortality. Further research on the role preferred language plays in racial and ethnic disparities may identify effective solutions for equitable care.

An update on dapagliflozin for chronic kidney disease.

Dapagliflozin is an oral agent for type 2 diabetes mellitus (T2DM) belonging to the sodium/glucose cotransporter 2 inhibitor (SGLT2-I) class of antihyperglycemic medications. In clinical trials, dapagliflozin has also been shown to reduce cardiovascular and major renal events. In the DAPA-CKD trial, dapagliflozin significantly reduced the composite renal outcome in patients with chronic kidney disease (CKD). Dapagliflozin represents a new pharmacologic option for reducing CKD progression in patients with and without diabetes.

Pharmacist-Led Programs to Increase Statin Prescribing: A Narrative Review of the Literature.

Statins are lipid-lowing medications shown to reduce cardiovascular events and are recommended for specific patient populations at elevated risk of atherosclerotic cardiovascular disease (ASCVD). Despite the demonstrated efficacy of statins for reducing ASCVD risk, and guidance on which populations should receive statin therapy, a substantial portion of eligible patients are not prescribed statin therapy. Pharmacists have attempted to increase the number of eligible patients receiving appropriate statin therapy through a variety of interventions and across several clinical settings. In this article, we highlight multiple studies evaluating the effectiveness of pharmacist-led interventions to improve statin use. A total of seven studies were selected for this narrative review, demonstrating the effectiveness and barriers of different statin-initiation programs delivered by pharmacists to increase statin use in eligible patients. Among the interventions assessed, a combination of provider communicating and statin prescribing through collaborative drug therapy management (CDTM) appear to the be the most useful at increasing statin use. Pharmacists can significantly improve statin use rates among eligible patients through multiple intervention types and across different clinical settings. Further studies should evaluate continued statin adherence and clinical outcomes among patients served by pharmacists.

Medical residents and attending physicians' perceptions of feedback and teaching in the United States: a qualitative study.

PURPOSE: Residents and attendings agree on the importance of feedback to resident education. However, while faculty report providing frequent feedback, residents often do not perceive receiving it, particularly in the context of teaching. Given the nuanced differences between feedback and teaching, we aimed to explore resident and attending perceptions of feedback and teaching in the clinical setting. METHODS: We conducted a qualitative study of internal medicine residents and attendings from December 2018 through March 2019 at the Massachusetts General Hospital to investigate perceptions of feedback in the inpatient clinical setting. Residents and faculty were recruited to participate in focus groups. Data were analyzed using thematic analysis to explore perspectives and barriers to feedback provision and identification. RESULTS: Five focus groups included 33 total participants in 3 attending (n=20) and 2 resident (n=13) groups. Thematic analysis of focus group transcripts identified 7 themes which organized into 3 thematic categories: (1) disentangling feedback and teaching, (2) delivering high-quality feedback, and (3) experiencing feedback in the group setting. Residents and attendings highlighted important themes in discriminating feedback from teaching. They indicated that while feedback is reactive in response to an action or behavior, teaching is proactive and oriented toward future endeavors. CONCLUSION: Confusion between the critical concepts of teaching and feedback may be minimized by allowing them to each have their intended impact, either in response to prior events or aimed toward those yet to take place.

The Environmental Microbiome, Allergic Disease, and Asthma.

The environmental microbiome represents the entirety of the microbes and their metabolites that we encounter in our environments. A growing body of evidence supports the role of the environmental microbiome in risk for and severity of allergic diseases and asthma. The environmental microbiome represents a ubiquitous, lifelong exposure to non-self antigens. During the critical window between birth and 1 year of life, interactions between our early immune system and the environmental microbiome have 2 consequences: our individual microbiome is populated by environmental microbes, and our immune system is trained regarding which antigens to tolerate. During this time, a diversity of exposures appears largely protective, dramatically decreasing the risk of developing allergic diseases and asthma. As we grow older, our interactions with the environmental microbiome change. While it continues to exert influence over the composition of the human microbiome, the environmental microbiome becomes increasingly a source for antigenic stimulation and infection. The same microbial exposure protective against disease development may exacerbate disease severity. Although much has been learned about the importance of the environmental microbiome in allergic disease, much more remains to be understood about these complicated interactions between our environment, our microbiome, our immune system, and disease.