All That Wheezes Is Not Asthma.

Wheezing is a high pitched, whistling sound generated when air flows through narrowed airways and is often equated with asthma. However, wheezing may be a presenting symptom of various other conditions including structural lesions of the airways, foreign body aspiration, pulmonary infections as well as cardiac causes. Underlying etiology of wheezing may also vary with age. Detailed history, physical examination, and laboratory investigations are often required to identify the underlying etiology of wheezing. Additional studies may sometimes be needed to accurately identify the underlying etiology such as pulmonary function test or spirometry, chest radiography (chest X-ray), and bronchoscopy. This review article discusses the common causes of wheezing encountered in clinical practice. [Pediatr Ann. 2024;53(5):e189-e194.].

Audiological and Speech and Language Characteristics of a Case with Hunter's Syndrome.

Hearing loss is a common manifestation of Hunter's syndrome, with reported rates ranging from 67.3 to 94%. The aim is to highlight the audiological profile and pathophysiology of mixed hearing loss in individuals with hunter's syndrome. A 7.6-year-old male child was brought to the department of audiology with a complaint of not responding to name call and regression in the speech and language skills. Detailed audiological showed severe to profound mixed hearing loss. REELS and 3DLAT results showed RLA to be 9 to 10 months and ELA to be 6 to 7 months. Owing to the progressive nature and high prevalence of hearing loss in hunter's syndrome, this case report highlights the importance of middle ear evaluation in the pediatric hearing assessment apart from OAE and ABR. Speech- language therapy must be considered with a focus on functional communication.

Increased mortality in infants with abnormal T-cell receptor excision circles.

BACKGROUND: T-Cell Receptor Excision Circles based newborn screening (TREC-NBS) allows for early detection of T-cell lymphopenia in infants with primary immunodeficiency disorders (PIDD). The utility of abnormal TREC-NBS in infants without PIDD is not well studied. We sought to evaluate the association of abnormal TREC-NBS with mortality. METHODS: 365,207 TREC-NBS from October 2011 to December 2014 were reviewed. 467 newborns had abnormal screens and did not meet the criteria for a PIDD diagnosis. Cases were matched to controls (1:3) based on gestational age, birth weight, neonatal intensive care unit status (NICU), and race. Data were obtained through NBS, birth and death certificates records from the Michigan Department of Health and Human Services (MDHHS) databases. RESULTS: Infants with abnormal TREC-NBS had higher mortality even when PIDD was ruled-out. Transient abnormal TREC-NBS was not associated with higher mortality, but unresolved or late abnormal TREC-NBS was associated with higher mortality. Infants with late abnormal TREC-NBS had severe prematurity, lower birth weight, lower Apgar scores, and higher percentage of congenital anomalies. CONCLUSION: Infants with abnormal TREC-NBS may be at a higher risk of morbidity and mortality and should be carefully followed, especially if discharged home before a repeat screen can be completed. IMPACT: This study explores the risk factors and mortality for newborns with secondary T-cell lymphopenia captured on T-Cell Receptor Excision Circles based newborn screening (TREC-NBS). Abnormal TREC-NBS allows for prompt life-saving interventions for primary immunological conditions such as Severe Combined Immunodeficiency (SCID), but can also be associated with non-immunologic conditions. Unresolved and late abnormal TREC-NBS is associated with higher mortality even without primary immunodeficiency, likely detected in infants with more severe prematurity, lower birth weight, and congenital anomalies. TREC-NBS positive infants with secondary T-cell lymphopenia require special attention and close monitoring.

Use of activity trackers to improve blood pressure in young people at risk for cardiovascular disease: a pilot randomized controlled trial.

BACKGROUND: Promoting physical activity among young individuals with cardiovascular disease (CVD) risk factors such as hypertension, diabetes, or chronic kidney disease can lower systolic blood pressure (BP). We sought to determine whether a 6-month intervention using a physical activity tracker was feasible and effective, compared with usual care. METHODS: Participants were recruited at a single academic medical center. Those aged 8-30 years were randomized in a 2:1 ratio to either the intervention (use of a Fitbit physical activity tracker coupled with feedback regarding the participant's step count) or usual care. The primary feasibility outcomes were screening-to-enrollment ratio and 6-month retention rates; the primary clinical outcome was a change in systolic BP from 0-6 months. RESULTS: Sixty-three participants were enrolled (57% male; mean age: 18 ± 4 years). The screening-to-enrollment ratio was 1.8:1. Six-month retention was 62% in the intervention group and 86% in the control group (p = 0.08). Mean change in systolic BP in the intervention group was not significantly different from the control group at 6 months (- 2.3 mmHg; 95% CI - 6.5, 1.8 vs. 3.0 mmHg; 95% CI - 2.5, 8.4, respectively, p = 0.12). CONCLUSIONS: Among children and young adults at elevated CVD risk, the use of a physical activity tracker coupled with tailored feedback regarding their step count progress was feasible but not sustained over time. Physical activity tracker use did not have a statistically significant effect on BP after 6 months. Augmented strategies to mitigate risk in young patients at high risk for early-onset CVD should be explored. This trial is registered at ClinicalTrials.gov (NCT03325426).

Adaptation and Validation of Overall Assessment of the Speaker's Experience of Stuttering for Adults in Kannada (OASES-A-K).

INTRODUCTION: Psychosocial aspects of stuttering may affect the quality of life of a person who stutters (PWS). Further, the social stigma and experiences of PWS may vary globally. The WHO-ICF guidelines recommend quality of life as an essential component in the assessment of individuals who stutter. However, the availability of linguistically and culturally appropriate tools is often a challenge. Thus, the current study adapted and validated the OASES-A for Kannada-speaking adults who stutter. METHOD: The original English version of OASES-A was adapted to Kannada using a standard reverse translation process. The adapted version was administered on 51 Kannada-speaking adults with very mild to very severe stuttering. The data were analyzed for item characteristics, reliability, and validity assessment. RESULTS: The results revealed floor and ceiling effects for six and two items, respectively. The mean overall impact score indicated a moderate impact of stuttering. Further, the impact score for section II was relatively higher when compared to the data from other countries. The reliability and validity analyses showed good internal consistency and test-retest reliability for OASES-A-K. CONCLUSION: The findings of the current research suggest that OASES-A-K is a sensitive and reliable tool to assess the impact of stuttering in Kannada-speaking PWS. The findings also highlight cross-cultural differences and the need for research in this direction.

Non-infectious Pulmonary Complications in Children with Primary Immunodeficiency.

Primary immune deficiency (PID) is a large group of diseases characterized by defective immune function, leading to recurrent infections, and immune dysregulation. Clinical presentations, severity, and complications differ for each disease, based on the components of the immune system that are impacted. When patients with PID present with respiratory symptoms, infections should be initially suspected, investigated, and promptly managed. However, non-infectious complications of PID also frequently occur and can lead to significant morbidity and mortality. They can involve both the upper and lower respiratory systems, resulting in various presentations that mimic infectious diseases. Thus, clinicians should be able to detect these conditions and make an appropriate referral to an immunologist and a pulmonologist for further management. In this article, we use case-based scenarios to review the differential diagnosis, investigation, and multidisciplinary treatment of non-infectious pulmonary complications in patients with primary immune deficiencies.

Positive Newborn Screening for Severe Combined Immunodeficiency: What Should the Pediatrician Do?

Severe combined immunodeficiency (SCID) is a group of diseases characterized by low T-cell count and impaired T-cell function, resulting in severe cellular and humoral immune defects. If not diagnosed and treated promptly, infants affected by this condition can develop severe infections which will result in death. Delayed treatment can markedly reduce the survival outcome of infants with SCID. T-cell receptor excision circle (TREC) levels are measured on newborn screening to promptly identify infants with SCID. It is important for primary care providers and pediatricians to understand the approach to managing infants with positive TREC-based newborn screening as they may be the first contact for infants with SCID. Primary care providers should be familiar with providing anticipatory guidance to the family in regard to protective isolation, measures to minimize the risk of infection, and the coordination of care with the SCID coordinating center team of specialists. In this article, we use case-based scenarios to review the principles of TREC-based newborn screening, the genetics and subtypes of SCID, and management for an infant with a positive TREC-based newborn screen.

Comparison of the Nitric Oxide Synthase Interactomes and S-Nitroso-Proteomes: Furthering the Case for Enzymatic S-Nitrosylation.

Aims: S-nitrosylation of proteins is the main mechanism through which nitric oxide (NO) regulates cellular function and likely represents the archetype redox-based signaling system across aerobic and anaerobic organisms. How NO generated by different nitric oxide synthase (NOS) isoforms leads to specificity of S-nitrosylation remains incompletely understood. This study aimed to identify proteins interacting with, and whose S-nitrosylation is mediated by, human NOS isoforms in the same cellular system, thereby illuminating the contribution of individual NOSs to specificity. Results: Of the hundreds of proteins interacting with each NOS, many were also S-nitrosylated. However, a large proportion of S-nitrosylated proteins (SNO-proteins) did not associate with NOS. Moreover, most NOS interactors and SNO-proteins were unique to each isoform. The amount of NO produced by each NOS isoform was unrelated to the numbers of SNO-proteins. Thus, NOSs promoted S-nitrosylation of largely distinct sets of target proteins. Different signaling pathways were enriched downstream of each NOS. Innovation and Conclusion: The interactomes and SNOomes of individual NOS isoforms were largely distinct. Only a small fraction of SNO-proteins interacted with their respective NOS. Amounts of S-nitrosylation were unrelated to the amount of NO generated by NOSs. These data argue against free diffusion of NO or NOS interactions as being necessary or sufficient for S-nitrosylation and favor roles for additional enzymes and/or regulatory elements in imparting SNO-protein specificity. Antioxid. Redox Signal. 39, 621-634.

Association of Wildfire Air Pollution With Clinic Visits for Psoriasis.

This cross-sectional study examines whether clinic visits and online search interest for psoriasis were associated with wildfire air pollution after a delayed lag period.

Discordances between pediatric and adult thresholds in the diagnosis of hypertension in adolescents with CKD.

BACKGROUND: Adolescents with chronic kidney disease (CKD) are a unique population with a high prevalence of hypertension. Management of hypertension during the transition from adolescence to adulthood can be challenging given differences in normative blood pressure values in adolescents compared with adults. METHODS: In this retrospective analysis of the Chronic Kidney Disease in Children Cohort Study, we compared pediatric versus adult definitions of ambulatory- and clinic-diagnosed hypertension in their ability to discriminate risk for left ventricular hypertrophy (LVH) and kidney failure using logistic and Cox models, respectively. RESULTS: Overall, among 363 adolescents included for study, the prevalence of systolic hypertension was 27%, 44%, 12%, and 9% based on pediatric ambulatory, adult ambulatory, pediatric clinic, and adult clinic definitions, respectively. All definitions of hypertension were statistically significantly associated with LVH except for the adult ambulatory definition. Presence of ambulatory hypertension was associated with 2.6 times higher odds of LVH using pediatric definitions (95% CI 1.4-5.1) compared to 1.4 times higher odds using adult definitions (95% CI 0.8-3.0). The c-statistics for discrimination of LVH was statistically significantly higher for the pediatric definition of ambulatory hypertension (c=0.61) compared to the adult ambulatory definition (c=0.54), and the Akaike Information Criterion was lower for the pediatric definition. All definitions were associated with progression to kidney failure. CONCLUSION: Overall, there was not a substantial difference in pediatric versus adult definitions of hypertension in predicting kidney outcomes, but there was slightly better risk discrimination of the risk of LVH with the pediatric definition of ambulatory hypertension.

Anaphylaxis in Children and Adolescents.

Anaphylaxis is an acute, potentially life-threatening systemic hypersensitivity reaction. Classically, anaphylaxis is an immunoglobulin (Ig) E-mediated reaction; however, IgG or immune complex complement-related immunologic reactions that lead to degranulation of mast cells can also cause anaphylaxis. Food allergy is the most common cause of anaphylaxis, followed by drugs. Patients with anaphylaxis commonly present with symptoms involving skin or mucous membranes, followed by respiratory and gastrointestinal symptoms. Epinephrine is the drug of choice for treating anaphylaxis. Patients and caregivers should be educated on the use of epinephrine autoinjectors with periodic review of symptoms and emergency action plan for anaphylaxis.

Pediatric Inner-City Asthma.

Inner-city children with asthma are known to have high disease mortality and morbidity. Frequently, asthma in this high-risk population is difficult to control and more severe in nature. Several factors, including socioeconomic hardship, ability to access to health care, adherence to medication, exposure to certain allergens, pollution, crowd environment, stress, and infections, play an important role in the pathophysiology of inner-city asthma. Comprehensive control of home allergens and exposure to tobacco smoke, the use of immune based therapies, and school-based asthma programs have shown promising results in asthma control in this population.

Contact Dermatitis in Children.

Contact dermatitis (CD) is commonly encountered in the pediatric population. Allergic and irritant are the two forms of CD and both cause significant clinical problems in children, but they are often underrecognized. The skin lesions in CD may be polymorphic and closely mimic other common pediatric skin diseases. The diagnosis usually requires patch testing after obtaining a detailed history and performing a physical examination. Metals, fragrances, and certain preservatives are the most common causative agents in children. This article discusses the pathophysiology, diagnosis, and management of this common skin condition in the pediatric population. [Pediatr Ann. 2021(5):e198-e205.].

Treatment for Severe Asthma in Children: What About Biologics?

Asthma is the most common pulmonary disease in children age 5 to 17 years. Asthma is characterized by chronic airway inflammation and heterogeneous clinical phenotypes. A small proportion of patients (approximately 5% to 10%) diagnosed with severe asthma are unable to achieve asthma control even with intensive therapy. Severe asthma in children is characterized by poor asthma control, uncontrolled symptoms, poor quality of life, disrupted school-related activities and increased risk of exacerbations, health care use, and morbidities due to asthma. Several new biologic agents targeting the mediators of asthma inflammation that are now approved are likely to improve asthma outcomes in children with severe asthma. This article outlines the various biologic agents currently approved for use in children. [Pediatr Ann. 2021;50(5):e206-e213.].

Allergic Broncho-Pulmonary Aspergillosis.

Allergic broncho-pulmonary aspergillosis (ABPA) is an immunologically mediated lung disease that usually occurs in people with a diagnosis of asthma or cystic fibrosis. It is a noninvasive lung disease caused by colonization of the airways with Aspergillus fumigatus. In people who are susceptible, Aspergillus leads to an exaggerated immune response and ultimately pulmonary inflammation and lung damage. Patients with ABPA typically present with poorly controlled asthma, recurrent pulmonary infiltrates, and bronchiectasis. Diagnosis of ABPA is established based on a combination of clinical manifestations as well as laboratory and radiological evaluations. Delay in diagnosis can result in airway destruction and pulmonary fibrosis, which may result in significant morbidity and mortality. This article discusses the clinical characteristics, diagnosis, and management of patients with ABPA. It aims to serve as a tool for pediatricians to aid in early recognition of this debilitating disease and consider referral, facilitating early diagnosis and treatment. [Pediatr Ann. 2021;50(5):e214-e221.].

Approach to Children with Hives.

Urticaria (or hives) is a pruritic and erythematous skin rash. Angioedema commonly occurs with urticaria. The term "chronic urticaria" is used when hives are present for more than 6 weeks. Acute urticaria is common in children, whereas chronic urticaria is rare. Causes of urticaria can be identified in many cases of acute urticaria with a thorough medical history. Laboratory evaluation may be needed to confirm the etiology of acute urticaria. Chronic urticaria is often idiopathic. Clinicians should avoid universal allergy testing for food allergens or aeroallergens in chronic urticaria as it usually does not help in identifying the cause, can lead to false-positive results, and unnecessary avoidance of allergens or foods. Urticarial vasculitis should be considered for lesions that are painful, present for more than 48 hours, leave scars/hyperpigmentation, or present with systemic symptoms such as fever, weight loss, and arthritis. Skin biopsy should be considered for suspected urticarial vasculitis. [Pediatr Ann. 2021(5):e191-e197.].

Azithromycin in the Successful Management of COVID-19: A Family Physician's Perspective.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), causing coronavirus disease-19 (COVID-19), has been responsible for approximately 75 million cases and 1.6 million deaths globally as of December 22, 2020. Currently, no treatment modalities or management options have been recommended by the National Institutes of Health (NIH) prior to patient hospitalization and supplemental oxygen requirement. This poses a unique challenge for outpatient primary care physicians, who are often tasked with initial care of patients early on in their disease course. During the pandemic, our family practice provided medical care to approximately 2,000 families located in the surrounding Brooklyn community. With only telemedicine at our disposal, our clinic was tasked with treating patients presenting remotely who may or may not have had COVID-19 - a large clinical diagnosis was made given the absence of in-person testing. Often co-administered, Azithromycin was considered a supportive agent that may or may not have increased the benefit of hydroxychloroquine. However, Azithromycin may perform well on its own for various reasons as it has been shown to have antiviral activity against other RNA viruses, anti-inflammatory properties, and antiviral effects within bronchial epithelial cells. Azithromycin has also shown efficacy as an add-on treatment for reducing asthma exacerbations - pertinent to the pro-inflammatory pulmonary conditions in COVID-19 progression - and may even prevent or treat bacterial co-infection in patients with SARS-COV-2. In order to investigate the association between Azithromycin and the COVID-19 disease process, our clinical study retrospectively identified patients who were prescribed Azithromycin (500 mg on day one + 250 mg on days two to five) during the peak months of the COVID-19 pandemic in New York City from March 2020 through May 2020. All patients prescribed Azithromycin with suspicion of COVID-19 infection were interviewed via telephone regarding their constellation of symptoms, compliance with the prescribed antibiotic for the intended course, symptom duration prior to and following antibiotic course initiation, as well as any further complications of their illness, if present. Ultimately, the majority of the patients who were interviewed over the phone concluded that a full course of Azithromycin helped improve their symptoms during their infection with COVID-19. Outcomes and complications in patients treated with Azithromycin were noteworthy in that there were no reports of pulmonary complications or deterioration of pulmonary function after treatment (e.g., no shortness of breath, wheezing, dyspnea, etc.), although some patients did experience residual coughing and nasal discharge post-treatment. We believe further study of this treatment in the setting of experimental, randomized controlled trials may reveal the benefits of Azithromycin in terms of reducing infection severity, length, and limiting the incidence of complications in patients with COVID-19.

Reducing acetylated tau is neuroprotective in brain injury.

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.