The Role of Secreted Frizzled-related Protein-1 in Allergic Asthma.

Although allergic asthma is a highly prevalent chronic inflammatory condition, the underlying pathogenesis driving T-helper cell type 2 inflammation is not well understood. Wnt/ß-catenin signaling has been implicated, but the influence of individual members of the pathway is not clear. We hypothesized that SFRP-1 (secreted frizzled-related protein-1), a Wnt signaling modulator, plays an important role in the development of allergic inflammation in asthma. Using an in vivo house dust mite asthma model, SFRP-1-/- mice were sensitized, and their BAL fluid was collected to evaluate airway inflammation. SFRP-1-/- mice exhibited less inflammation with reduced cellular infiltration and concentration of IL-5 in bronchoalveolar lavage fluid compared with wild-type (WT) mice. Similar findings were observed in WT mice treated with SFRP-1 inhibitor, WAY316606. Alveolar macrophages from sensitized SFRP-1-/- mice demonstrated reduced alternative polarization compared with WT, indicating that macrophages could mediate the alteration in inflammation seen in these mice. These findings suggest that SFRP-1 is an important potentiator of asthmatic airway inflammation.

Wingless/integrase-1 signaling in allergic asthma and pediatric lung diseases.

PURPOSE OF REVIEW: To provide an update on the current understanding of the role of wingless/integrase-1 (Wnt) signaling in pediatric allergic asthma and other pediatric lung diseases. RECENT FINDINGS: The Wnt signaling pathway is critical for normal lung development. Genetic and epigenetic human studies indicate a link between Wnt signaling and the development and severity of asthma in children. Mechanistic studies using animal models of allergic asthma demonstrate a key role for Wnt signaling in allergic airway inflammation and remodeling. More recently, data on bronchopulmonary dysplasia (BPD) pathogenesis points to the Wnt signaling pathway as an important regulator. SUMMARY: Current data indicates that the Wnt signaling pathway is an important mediator in allergic asthma and BPD pathogenesis. Further studies are needed to characterize the roles of individual Wnt signals in childhood disease, and to identify potential novel therapeutic targets to slow or prevent disease processes.

Asthma among hospitalized patients with COVID-19 and related outcomes.

BACKGROUND: Several underlying conditions have been associated with severe acute respiratory syndrome coronavirus 2 illness, but it remains unclear whether underlying asthma is associated with worse coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: Given the high prevalence of asthma in the New York City area, our objective was to determine whether underlying asthma was associated with poor outcomes among hospitalized patients with severe COVID-19 compared with patients without asthma. METHODS: Electronic heath records were reviewed for 1298 sequential patients 65 years or younger without chronic obstructive pulmonary disease who were admitted to our hospital system with a confirmed positive severe acute respiratory syndrome coronavirus 2 test result. RESULTS: The overall prevalence of asthma among all hospitalized patients with COVID-19 was 12.6%, yet a higher prevalence (23.6%) was observed in the subset of 55 patients younger than 21 years. There was no significant difference in hospital length of stay, need for intubation, length of intubation, tracheostomy tube placement, hospital readmission, or mortality between patients with and without asthma. Observations between patients with and without asthma were similar when stratified by obesity, other comorbid conditions (ie, hypertension, hyperlipidemia, and diabetes), use of controller asthma medication, and absolute eosinophil count. CONCLUSIONS: Among hospitalized patients 65 years or younger with severe COVID-19, asthma diagnosis was not associated with worse outcomes, regardless of age, obesity, or other high-risk comorbidities. Future population-based studies are needed to investigate the risk of developing COVID-19 among patients with asthma once universal testing becomes readily available.

Severe respiratory viral infections in children with history of asymptomatic or mild COVID-19.

IMPORTANCE: The spectrum of complications of COVID-19 in children, including the effect of COVID-19 on later viral infection, is not known. OBJECTIVE: To examine the features of children hospitalized for respiratory illness with history of prior COVID-19. DESIGN: Retrospective observational case series at a single pediatric quaternary medical center in New York City. Data were obtained from review of medical records. PARTICIPANTS: Children with prior mild or asymptomatic COVID-19 and no known risk factors for severe respiratory disease, who were hospitalized at our center for acute respiratory illness from October 2020 to May 2021, were reviewed. MAIN OUTCOMES AND MEASURES: Co-morbidities, history of prior COVID-19 symptoms, respiratory viral panel findings, acuity of illness, degree of respiratory decompensation based on support and interventions required, duration of hospitalization, and overall clinical course were assessed from the medical record. RESULTS: This study included 5 patients (median age, 4 years; age range: 0.8-9 years; 4 [80%] male). All had positive COVID-19 serology, 1 (20%) had mild symptoms, while the others had no symptoms of prior Sars-CoV-2 infection, 3 (60%) had asthma, and the remaining had no co-morbidities. All were admitted between April and May 2021. Two were re-admitted for respiratory symptoms in the subsequent 3 months. CONCLUSIONS AND RELEVANCE: This case series describes a possible association between severe lower respiratory tract infection and prior mild COVID-19 in children. Larger cohort studies describing the respiratory effects of prior COVID-19 in children are needed.

Cheyne-Stokes Respiration in a 17-Year-Old Boy Awaiting Heart Transplantation.

Cheyne-Stokes respiration is a pattern of alternating central apnea and hyperpnea. It is well described in adults with congestive heart failure, but not in children. We report the case of a 17-year-old boy whose systolic heart failure was complicated by Cheyne-Stokes respiration. He was given supportive therapy until heart transplant, after which his Cheyne-Stokes respiration clinically resolved. Clinicians should be aware of this uncommon condition in pediatric and adolescent patients who have advanced heart failure and irregular breathing.

Post Splenectomy Outcome in ß-Thalassemia.

OBJECTIVES: To evaluate changes in annual blood transfusion requirements and complications after splenectomy in patients with ß-thalassemia. METHODS: Forty post-splenectomy ß-thalassemic patients aged 8-33 y, receiving regular blood transfusions and chelation therapy were included and non transfusion dependant patients were excluded from this retrospective cross-sectional study. Details about their surgery, transfusion requirements, and platelet levels were recorded on a standard proforma. All patients underwent a B-mode and color-coded duplex sonography of the hepatoportal system during the study period. RESULTS: The average ferritin level in the year prior to the study was 4432 mcg/L (range 480-12,200 mcg/L). The annual blood transfusion requirement in the first year and 5 y post splenectomy [mean ± SD (138.41 ± 90.38 ml/kg/y); (116 ± 41.44 ml/kg/y)] were significantly different from requirements before splenectomy [(mean ± SD) 294.85 ± 226 ml/kg/y; p value <0.001]. There was a significant rise in platelet counts within 24 h post splenectomy with a mean rise of 4,51,000/mm(3) (p value < 0.001). During the follow up period, infections were noted in 50 % of patients, with malaria (18.75 %) being the most common. Doppler study of the portal system in one case showed portal vein thrombosis. CONCLUSIONS: A significant sustained fall in annual blood transfusion requirement and a rise in platelet counts occurred post-splenectomy. Increase in annual blood transfusion requirement should be investigated to find the cause.