Daniel Rotrosen

Asthma in the inner city: The perspective of the National Institute of Allergy and Infectious Diseases

Since 1991, the National Institute of Allergy and Infectious Diseases (NIAID) has funded four consecutive research initiatives to investigate the problem of high asthma prevalence, morbidity and mortality in poor urban communities. The multi-site studies conducted under these initiatives have identified key risk factors for asthma morbidity and novel interventions to improve asthma control. NIAID focuses its asthma and allergy programs on understanding the interaction of the immune system with allergens and infectious agents and identifying genetic and epigenetic elements that influence the immune system. A key goal in this field is to define mechanisms of immune system deviation and immune tolerance and apply this knowledge to generate improvements in asthma care and allergen immunotherapy. A related goal is to further understand the environmental, social, and immunological elements that impact on the development of inner-city asthma through in-depth characterization and longitudinal follow-up of inner-city children from the time of birth. In the past 5 years, NIH budgetary constraints have imposed many challenges for the academic research community. Despite these constraints, NIAID has maintained its support of a highly productive asthma and allergy research program.

The Immune Tolerance Network at 10 years: tolerance research at the bedside

Immune tolerance-inducing therapies reprogramme immune cells to eliminate pathogenic immune responses while preserving protective immunity. The Immune Tolerance Network (ITN), sponsored by the US National Institutes of Health, was established in 1999 to evaluate new tolerance-inducing therapies and carry out mechanistic studies using a unique interactive approach in partnership with industry, academia and foundations. Ten years later, the ITN has carried out approximately 36 clinical trials and tolerance studies examining innovative tolerogenic approaches in the settings of allergy, autoimmune diseases and organ transplantation. ITN investigators have published more than 80 original research papers based on this work. This Timeline article summarizes the progress and challenges of clinical research in the ITN.

Ascorbic acid in human neutrophils

The uptake and distribution of ascorbic acid and the effect of extracellular glucose on ascorbic acid transport were investigated in human neutrophils. Freshly isolated neutrophils contained 1.0-1.4 mmol ascorbic acid/L, at least 94% of which was present unbound in the cytosol. Intracellular ascorbic acid was found only in the reduced form. The presence of physiologic amounts of ascorbic acid in the extracellular buffer led to the accumulation of millimolar concentrations of ascorbic acid intracellularly. Accumulation was mediated by a high- and a low-affinity transport activity. The high-affinity transport activity had an apparent Km of 2-5 mumol/L whereas the low-affinity transport activity had an apparent Km of 6-7 mmol/L. Glucose inhibited the uptake and accumulation of ascorbic acid by both transport activities in a concentration-dependent fashion. Glucose-induced inhibition of both ascorbic acid transport activities was completely reversible.

Immunology research: challenges and opportunities in a time of budgetary constraint.

There have been enormous advances in the field of immunology over the past 3 decades, and those advances have had a positive effect on many subspecialties of medicine. Opportunities for even more notable advances remain. However, present and projected budget constraints for the National Institutes of Health have created formidable challenges. This commentary addresses the opportunities and challenges for the field of immunology during a period of restricted budgets.

Ascorbic acid accumulation in plated human neutrophils

Ascorbic acid uptake was investigated in isolated, plated human neutrophils using high‐performance liquid chromatography with coulometric electrochemical detection. Freshly isolated neutrophils contained 1.3 mM ascorbic acid and accumulated significantly greater amounts when physiologic concentrations of the vitamin were present in the extracellular buffer. In several different buffers uptake was dependent on the presence of calcium and magnesium. Under these conditions, scintillation spectrometry of [14C]ascorbic acid in conjunction with high‐performance liquid chromatography was suited for measuring ascorbic acid transport.

Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel

BackgroundFood allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.ObjectivesPrompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.ResultsThe addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider’s office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.ConclusionsGuidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

Addendum guidelines for the prevention of peanut allergy in the United States.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases In 2015, findings from the landmark Learning Early About Peanut Allergy (LEAP) study—the first randomized trial to study early allergen introduction as a preventive strategy—showed that early introduction of peanut-containing foods to infants at high risk of developing peanut allergy was safe and led to an 81 percent relative reduction in the subsequent development of peanut allergy.

Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases–sponsored expert panel

BackgroundFood allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.ObjectivesPrompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy.ResultsThe addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider’s office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation.ConclusionsGuidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy.

The Benefits of New Guidelines to Prevent Peanut Allergy

* Abbreviations: AAP — : American Academy of Pediatrics EP — : expert panel LEAP — : Learning Early About Peanut Allergy NIAID — : National Institute of Allergy and Infectious Diseases sIgE — : serum food-specific IgE antibody SPT — : skin prick test Peanut allergy appears to have tripled in prevalence in the United States since 1997 and now affects 1% to 2% of children.1 The high prevalence, severity, and life-long persistence of peanut allergy have generated intense interest in prevention strategies. Initially, such strategies focused on allergen avoidance, but a key observation, the 10-fold higher rate of peanut allergy among Jewish children in the United Kingdom compared with Israeli children of similar ancestry, suggested an alternative approach.2 A notable difference between these populations was the almost complete lack of peanut ingestion in the first year of life in the United Kingdom compared with substantial consumption among Israeli infants. Based on this observation, the National Institutes of Health–sponsored Learning Early About Peanut Allergy (LEAP) trial randomized 640 infants between 4 and 11 months of age with severe eczema and/or egg allergy to consume or avoid peanut-containing foods until 60 months of age.3 The study excluded infants with large (>4 mm) positive skin prick tests (SPTs) to peanut, assuming many were already allergic, and stratified the enrolled infants as having no peanut SPT wheal or having one that was 1 to 4 mm in diameter. In the intention-to-treat population with negative SPT ( n = 530), the prevalence of peanut allergy at 60 months of age was 13.7% in the avoidance group versus 1.9% in the consumption group ( P < .001; 86.1% relative risk reduction), and among those in the SPT positive group ( n = 98), the prevalence of peanut allergy was 35.3% in the avoidance group and … Address correspondence to Scott H. Sicherer, MD, Department of Pediatrics, Mount Sinai Hospital, Box 1198, 1 Gustave L Levy Pl, New York, NY 10029. E-mail: scott.sicherer{at}mssm.edu

Clinical trial data access: Opening doors with TrialShare

The need for improved access to clinical trial data is widely recognized to ensure complete information is in the public domain, to honor the commitment of research subjects, and to empower and engage analytic talent across the worldwide biomedical community. Open access to patient-level data from clinical trials enables data transparency, fosters data sharing, and catalyzes research innovation. As noted by Ross andKrumholzm ‘‘A wall surrounds much. clinical research data, sequestering knowledge, impeding the free flow of information, and obscuring a clear view of the totality of evidence relevant to many research questions and clinical decisions.’’ Mello et al stress the benefits of data transparency, which range from improving reporting accuracy to improving patient safety, as well as speeding innovation. Long-term benefits of data sharing include improvements in future clinical trial design, generation of new research hypotheses and research grant applications, and identification of targets for future drug development. Indeed, the National Institute on Drug Abuse Treatment Clinical Trials Network Data Share Project recently documented 13 published examples of secondary use of public data sets fromNational Institute onDrugAbuse–sponsored clinical trials, illustrating the potential to promote additional research and new insights from completed studies. Immune Tolerance Network (ITN) TrialShare, a novel portal for viewing and analyzing complete data sets from ITN trials, demonstrates this commitment through open access and userfriendly analytic tools. ITN TrialShare integrates data display from laboratory outputs, biomarker outcomes, and clinical and demographic attributes across a wide range of immunologic diseases and interventions, including the recent Learning Early About Peanut Allergy (LEAP) and LEAP-ON studies. This has