Results From a National Survey of Asthma Provider Beliefs and Practices Regarding Exercise and Asthma: A Work Group Report of the AAAAI Committee on Sports, Exercise, and Fitness.

BACKGROUND: National Heart, Lung, and Blood Institute guidelines recommend regular physical activity (PA) for patients with asthma. Health care provider (HCP) counseling represents an effective approach to optimizing patient PA. However, current exercise rates among asthma patients are suboptimal, which suggests that counseling may be improved. OBJECTIVE: To understand PA counseling behaviors among HCPs who manage asthma. METHODS: A voluntary 36-item survey assessing self-reported awareness of PA recommendations and current clinical practices was sent to 979 randomly selected HCP members of the American Academy of Allergy, Asthma & Immunology (AAAAI). RESULTS: The overall response rate was 9.3% (91 of 979). Respondents were physicians (100%) and allergists/immunologists (96%) who reported an average of 18.1 ± 12.3 years in independent practice. Over half (58%) reported personally engaging in 150 min/wk or more of moderate to strenuous PA. Eighty percent of participants were unaware of specific PA guidelines for patients with asthma, yet 66% acknowledged evidence for improved asthma outcomes with moderate exercise. A large majority of respondents believed that patients with asthma (97%) and severe asthma (84%) should pursue exercise. Whereas 90% of respondents support incorporating exercise counseling into asthma care, only 69% regularly counsel asthma patients about PA. Barriers cited included limited time, lack of knowledge regarding how and where to refer patients for exercise, and other medical priorities. Potential facilitators of PA included increasing practitioner education and patient-directed posters in waiting areas. CONCLUSIONS: Health care providers recognized PA as an important component of asthma care but were often unaware of specific guidelines. Promoting PA counseling may require using a time-efficient approach to implement counseling at each asthma patient encounter.

An International, Retrospective Study of Off-Label Biologic Use in the Treatment of Hypereosinophilic Syndromes.

BACKGROUND: Treatment of hypereosinophilic syndrome (HES) often requires the use of immunomodulators with substantial side effect profiles. The emergence of biologics offers an alternative treatment modality. OBJECTIVE: To examine real-world practice data to describe the safety and consequences of various biologics suspected to directly or indirectly affect eosinophilic inflammation for the treatment of HES. METHODS: Retrospective data from 13 centers were collected via an online Research Electronic Data Capture repository. Inclusion criteria included (1) peripheral eosinophil count of 1,500/mm3 or greater without a secondary cause; (2) clinical manifestations attributable to the eosinophilia; and (3) having received mepolizumab (anti-IL-5), benralizumab (afucosylated anti-IL-5 receptor α), omalizumab (anti-IgE), alemtuzumab (anti-CD52), dupilumab (anti-IL-4 receptor α), or reslizumab (anti-IL-5) outside a placebo-controlled clinical trial. RESULTS: Of the 151 courses of biologics prescribed for 121 patients with HES, 59% resulted in improved HES symptoms and 77% enabled tapering of other HES medications. Overall, 105 patients were receiving daily systemic glucocorticoids at the time of a biologic initiation and were able to reduce the glucocorticoid dose by a median reduction of 10 mg of daily prednisone equivalents. Biologics were generally safe and well-tolerated other than infusion reactions with alemtuzumab. Thirteen of 24 patients had clinical improvement after switching biologics and nine patients responded to increasing the dose of mepolizumab after a lack of response to a lower dose. CONCLUSIONS: Biologics may offer a safer treatment alternative to existing therapies for HES, although the optimal dosing and choice for each subtype of HES remain to be determined. Limitations of this study include its retrospective nature and intersite differences in data collection and availability of each biologic.

Delayed-Onset ADA1 (ADA) Deficiency Not Detected by TREC Screen.

A 9-month-old boy presented to a community pediatrician with a recent history of failure to thrive. Workup revealed neutropenia and lymphopenia. Subsequent admission for fever and pneumonia revealed an absolute neutrophil count of 860 and absolute lymphocyte count of 214. Lymphopenia affected all lymphocyte subsets and his naïve and memory CD4+ T-cell ratio was inverted for age. Immunoglobulin levels were normal for age, and tetanus and diphtheria antibody titers were protective. The profound lymphopenia raised suspicion for severe combined immunodeficiency (SCID), despite a normal newborn screening by T-cell receptor excision circle analysis. He did not have a previous history of recurrent fevers or infections, had attended day care, and had received all age-appropriate vaccines. He subsequently was diagnosed with Pneumocystis jirovecii pneumonia, adenovirus upper respiratory infection, and rotaviral diarrhea. An enzyme assay revealed absent adenosine deaminase (ADA) activity and elevated erythrocyte deoxyadenosine nucleotides. With genetic sequencing, 2 pathogenic variants in the ADA gene were confirmed. Acute management of ADA-SCID is aimed at restoration of enzyme activity, followed by curative therapy. The patient is currently on immunoglobulin therapy and recombinant ADA (Revcovi), with an excellent immune response, while awaiting sibling hematopoietic cell transplant from a matched sibling. Hypomorphic ADA variants can present with delayed-onset SCID, and some of these patients are missed by SCID newborn screening. A careful review of a complete blood cell count might offer clues and promote confirmatory diagnostic investigation.

Allergy/Immunology Trainee Experiences During the COVID-19 Pandemic: AAAAI Work Group Report of the Fellows-in-Training Committee.

As a result of the coronavirus disease 2019 (COVID-19) global pandemic, medical trainees have faced unique challenges and uncertainties. To capture the experiences of allergy and immunology fellows throughout the United States and Canada during this time, a 17-item electronic questionnaire was distributed to 380 fellow-in-training (FIT) members of the American Academy of Allergy, Asthma, and Immunology enrolled in US and Canadian allergy/immunology fellowship programs. Voluntary and anonymous responses were collected from April 15 to May 15, 2020. In addition to summary statistics, categorical data were compared using χ2 tests (Fisher's exact). Responses were obtained from FITs across all years of training and primary specialties (Internal Medicine, Pediatrics, and Medicine-Pediatrics) with a response rate of 32.6% (124 of 380). Reassignment to COVID-19 clinical responsibilities was reported by 12% (15 of 124) of FITs, with the largest proportion in the US northeast region. A majority of FITs used telehealth (95%) and virtual learning (82%) during the pandemic. Overall, 21% (25 of 120) of FITs expressed concern about potentially lacking clinical experience for independently practicing allergy and immunology. However, FITs using telehealth reported lower concern compared with those who did not (18.4% [21 of 114] vs 66.7% [4 of 6]; P = .01). The survey shows that allergy and immunology trainee experiences have varied considerably since the COVID-19 outbreak. Notably, the adoption of telehealth and virtual learning was commonly reported, and optimization of these virtual experiences will be helpful. Even outside of pandemics, training on the use of telemedicine may be a sound strategy in preparation for future health care delivery and unexpected events.

Sudden Cardiac Arrest in a Young Patient With Severe Pectus Excavatum.

We report a case of sudden cardiac arrest in the setting of ventricular fibrillation in a previously healthy 19-year-old male. Chest imaging demonstrated severe pectus excavatum with Pectus Severity Index of 22.7. Extensive workup was unrevealing for other cardiopulmonary etiologies, including conduction and structural abnormalities. The patient was scheduled for a Ravitch procedure and was discharged on a wearable defibrillator vest for temporary protection against ventricular arrhythmias. Later, the patient underwent subcutaneous implantable cardioverter defibrillator placement. Sudden cardiac arrest as an initial presentation of pectus excavatum is a rare entity scarcely discussed in medical literature. In this patient-centered focused review, we explore this unique case and offer our management approach amid the lack of concrete guidelines.

Aberrant "Barbed-Wire" Nuclear Projections of Neutrophils in Trisomy 18 (Edwards Syndrome).

We discuss the significance of neutrophils with increased, aberrant nuclear projections mimicking "barbed-wire" in a newborn child with trisomy 18 (T18). Increased, aberrant nuclear projections have been previously reported in trisomy of the D group of chromosomes (chromosomes 13, 14, and 15), and we report similar findings in a patient with T18. The peripheral blood smear showed relative neutrophilia with the majority (37%) of neutrophils showing two or more thin, rod-shaped or spike-shaped, and often pedunculated aberrant nuclear projections. The number of projections ranged from 2 to 6 per cell, averaged 2 per affected neutrophil, and ranged in length from 0.22 µm to 0.83 µm. This case confirms that the morphologic finding described is not restricted to trisomy of one of the chromosomes in group D, as implied in the literature.

Expression pattern of id proteins in medulloblastoma.

Inhibitor of DNA binding or inhibitor of differentiation (Id) proteins are up regulated in a variety of neoplasms, particularly in association with high-grade, poorly differentiated tumors, while differentiated tissues show little or no Id expression. The four Id genes are members of the helix-loop-helix (HLH) family of transcription factors and act as negative regulators of transcription by binding to and sequestering HLH complexes. We tested the hypothesis that Id proteins are overexpressed in medulloblastoma by performing immunohistochemistry using a medulloblastoma tissue microarray with 45 unique medulloblastoma and 11 normal control cerebella, and antibodies specific for Id1, Id2, Id3, and Id4. A semi-quantitative staining score that took staining intensity and the proportion of immunoreactive cells into account was used. Id1 was not detected in normal cerebella or in medulloblastoma cells, but 78 % of tumors showed strong Id1 expression in endothelial nuclei of tumor vessels. Id2 expression was scant in normal cerebella and increased in medulloblastoma (median staining score: 4). Id3 expression was noted in some neurons of the developing cerebellar cortex, but it was markedly up regulated in medulloblastoma (median staining score: 12) and in tumor endothelial cells. Id4 was not expressed in normal cerebella or in tumor cells. Id2 or Id3 overexpression drove proliferation in medulloblastoma cell lines by altering the expression of critical cell cycle regulatory proteins in favor of cell proliferation. This study shows that Id1 expression in endothelial cells may contribute to angiogenic processes and that increased expression of Id2 and Id3 in medulloblastoma is potentially involved in tumor cell proliferation and survival.