Pulmonary manifestations of childhood-onset primary Sjogren's syndrome (SS) masquerading as reactive airways disease in a male patient and review of interstitial lung disease associated with SS.

Background: Sjogren's syndrome (SS) is a rare chronic autoimmune disease involving exocrine glands presenting with sicca syndrome, recurrent parotitis and other extraglandular stigmata. SS is well characterized in the adult population with classification criteria; however, primary SS presenting in childhood is poorly defined and rare in males. Recurrent parotitis is the most common presenting symptom in children with primary SS; however, clinical phenotype in children appears more variable than in adults.

Severe asthma in children: Description of a large multidisciplinary clinical cohort.

Background: Children with severe asthma have substantial morbidity and healthcare utilization. Pediatric severe asthma is a heterogeneous disease, and a multidisciplinary approach can improve the diagnosis and management of these children.

Methods: We reviewed the electronic health records for patients seen in the Severe Asthma Clinic (SAC) at UPMC Children's Hospital of Pittsburgh between August 2012 and October 2019.

Baseline Features of the Severe Asthma Research Program (SARP III) Cohort: Differences with Age.

Background: The effect of age on asthma severity is poorly understood.

Objectives: The objective of this study was to compare the baseline features of severe and nonsevere asthma in the Severe Asthma Research Program (SARP) III cohort, and examine in cross section the effects of age on those features.

Methods: SARP III is a National Institutes of Health/National Heart Lung Blood Institute multisite 3-year cohort study conducted to investigate mechanisms of severe asthma.

Inflammatory and Comorbid Features of Patients with Severe Asthma and Frequent Exacerbations.

Rationale: Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.

Objectives: To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.

Methods: Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed.

Chronic Esophageal Foreign Body Presenting as Wheezing and Cough in a Toddler.

The presentation, evaluation, and management of chronic esophageal foreign bodies are not well described in pediatric patients. Many patients present with ill-defined respiratory symptoms, making diagnosis challenging. We report on a 2-year-old girl who presented with several months of worsening cough and wheezing unresponsive to medical management.

Vitamin D and asthma.

Vitamin D deficiency and asthma are common conditions that share risk factors such as African American ethnicity, inner-city residence, and obesity. This review provides a critical examination of current experimental and epidemiologic evidence of a causal association between vitamin D status and asthma or asthma morbidity, including potential protective mechanisms such as antiviral effects and enhanced steroid responsiveness. Because most published epidemiologic studies of vitamin D and asthma or asthma morbidity are observational, a recommendation for or against vitamin D supplementation as preventive or secondary treatment for asthma is not advisable and must await results of ongoing clinical trials.

Airway molecular phenotypes in pediatric asthma.

Purpose Of Review: The review discusses what is known regarding airway molecular phenotypes in pediatric asthma, specifically biomarkers that have been studied and their relation to the various clinical phenotypes of asthma.

Recent Findings: Pediatric asthma is a complex and heterogeneous disease that consists of several clinical phenotypes. There have been numerous studies investigating inflammatory markers that would increase our understanding of the underlying pathogenesis of asthma as well as facilitate the discovery of therapies for these patients.

T(H)17 cells in asthma and inflammation.

Background: The chronic airway disease asthma causes significant burden to patients as well as the healthcare system with limited options for prevention or cure. Inadequate treatment strategies are most likely due to the complex heterogeneous nature of asthma. Furthermore, the severe asthma phenotype is characterized by the lack of a response to standard medication, namely, corticosteroids.

Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program.

Background: Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to school-age children with persistent asthma across a wide range of severities.

Objectives: This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity.

Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%-15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA.

Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells.

The innate immune functions of human airways include mucociliary clearance and antimicrobial peptide activity. Both functions may be affected by changes in epithelial ion transport. Interleukin-17A (IL-17A), which has a receptor at the basolateral membrane of airway epithelia, is a T cell cytokine that has been shown to increase mucus secretion and antimicrobial peptide production by human bronchial epithelial (HBE) cells.

Requirement of IL-17RA in Con A induced hepatitis and negative regulation of IL-17 production in mouse T cells.

Th17 cells, a subset of T cells involved in autoimmunity and host defense against extracellular Gram-negative infection, express both IL-17A and IL-17F. Both IL-17A and IL-17F can signal via the IL-17RA; however, IL-17F does so at a 1- to 2-log higher concentration than IL-17A. In this study, we show that the IL-17F homodimer via IL-17RA is a negative regulator of IL-17 production in T cells and suggest a mechanism whereby IL-17RA on T cells serves as an autocrine/paracrine regulator of IL-17 synthesis in T cells.

IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.

Emerging evidence supports the concept that T helper type 17 (T(H)17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the T(H)17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony-stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury.

Interleukin-17 in pulmonary host defense.

Interleukin (IL)-17A and IL-17F are produced by a novel class of effector alphabeta T cells called Th17 cells as well as gammadelta T cells. alphabeta IL-17-producing T cells are controlled by the transcription factor RORgammat and develop independent of GATA-3, T-bet, Stat 4, and Stat 6. Effector molecules produced by these cells include IL-17A, IL-17F, and IL-22.

Th17 cells and mucosal host defense.

Th17 cells are a new lineage of T-cells that are controlled by the transcription factor RORgammat and develop independent of GATA-3, T-bet, Stat 4 and Stat 6. Novel effector molecules produced by these cells include IL-17A, IL-17F, IL-22, and IL-26. IL-17RA binds IL-17A and IL-17F and is critical for host defense against extracellular planktonic bacteria by regulating chemokine gradients for neutrophil emigration into infected tissue sites as well as host granulopoiesis.

Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F.

The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease.