Contribution of caregiver and child anxiety and depressive symptoms to child asthma-related quality of life.

BACKGROUND: Depression and anxiety negatively affect asthma-related quality of life (QoL). Yet, little is known regarding mood and asthma-related factors that best uniquely explain asthma-related QoL in children. OBJECTIVE: This cross-sectional study evaluated the unique variance explained by caregiver and child depressive and anxiety symptom severity in child asthma-related QoL, apart from that explained by demographics and asthma control. METHODS: Children aged 7 to 17 years with asthma (n = 205) and their caregivers with major depressive disorder were included. A 3-stage hierarchical linear regression analysis was conducted with the Pediatric Asthma Quality of Life Questionnaire total scores considered as the outcome. Predictors included demographic characteristics (stage 1); asthma control assessed by the Asthma Control Test (stage 2); and caregiver depression and anxiety (Hamilton Rating Scale for Depression and the Spielberger State/Trait Anxiety Scale) and child depression and anxiety (Children's Depression Inventory and the Screen for Child Anxiety-Related Disorders) (stage 3). RESULTS: Demographic characteristics accounted for only 5.5% of the Pediatric Asthma Quality of Life Questionnaire scores. Asthma control significantly increased variance explained in QoL to 32.6%, whereas caregiver and child depression and anxiety symptoms significantly increased variance explained to 42.6%. Child anxiety was found to uniquely explain the largest proportion of variance in QoL (rs2 = 0.584). CONCLUSION: After adjusting variance in QoL for demographic characteristics and asthma control, caregiver and child depression and anxiety measures significantly increased the proportion of variance explained in a child's asthma-related QoL. In addition to better asthma control, child and caregiver depression and anxiety should be addressed to increase child asthma-related QoL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02809677.

Autoimmunity in people with cystic fibrosis.

Cystic fibrosis (CF) clinicians may see patients who have difficult-to-manage symptoms that do not have a clear CF-related etiology, such as unusual gastrointestinal (GI) complaints, vasculitis, or arthritis. Alterations in immunity, inflammation and intraluminal dysbiosis create a milieu that may lead to autoimmunity, and the CF transmembrane regulator protein may have a direct role as well. While autoantibodies and other autoimmune markers may develop, these may or may not lead to organ involvement, therefore they are helpful but not sufficient to establish an autoimmune diagnosis. Autoimmune involvement of the GI tract is the best-established association. Next steps to understand autoimmunity in CF should include a more in-depth assessment of the community perspective on its impact. In addition, bringing together specialists in various fields including, but not limited to, pulmonology, gastroenterology, immunology, and rheumatology, would lead to cross-dissemination and help define the path forward in basic science and clinical practice.

Egg Introduction during Infancy is Associated with Lower Fat Mass Index in Females at Early Adolescence.

BACKGROUND: Egg consumption may play an important role in early-life growth given their high-quality protein, essential fatty acids, and micronutrients. OBJECTIVES: Study objectives were to examine the longitudinal associations of infant age at egg introduction with obesity outcomes in early childhood, middle childhood (mid-childhood), and early adolescence. METHODS: We used existing data from 1089 mother-child dyads from Project Viva to estimate age at egg introduction through a questionnaire completed by mothers at ∼1 y postpartum (mean ± SD, 13.3 ± 1.2 mo). Outcome measures included height and weight (early childhood, mid-childhood, and early adolescence), body composition including total fat mass, trunk fat mass, and lean mass (mid-childhood and early adolescence), and plasma adiponectin and leptin (early and mid-childhood and early adolescence). We defined childhood obesity as sex- and age-specific BMI ≥ 95th percentile. We estimated the associations of infant age at egg introduction with risk of obesity using multivariable logistic regression and multivariable linear regression models for BMI-z-score, body composition measures, and adiposity hormones; adjusted for maternal prepregnancy BMI and sociodemographics. RESULTS: Among females, those introduced to egg by the 1-y survey had a lower total fat mass index (confounder-adjusted mean difference, -1.23 kg/m2; 95% CI: -2.14, -0.31), and trunk fat mass index (confounder-adjusted mean difference, -0.57 kg/m2; 95% CI: -1.01, -0.12) in early adolescence compared to those not introduced (reference group). However, no associations between infant age at egg introduction and risk of obesity were observed among males (confounder-adjusted odd ratio [aOR], 1.97; 95% CI: 0.90, 4.30) or females (aOR, 0.68; 95% CI: 0.38, 1.24) across all ages. Egg introduction in infancy was associated with lower plasma adiponectin among females (confounder-adjusted mean difference, -1.93 µg/mL; 95% CI: -3.70, -0.16) in early childhood only. CONCLUSIONS: Egg introduction during infancy among females is associated with lower total fat mass index in early adolescence and plasma adiponectin in early childhood. This trial was registered at clinicaltrials.gov as NCT02820402.

Frequency of Infant Egg Consumption and Risk of Maternal-Reported Egg Allergy at 6 Years.

BACKGROUND: Recent research suggests that early egg introduction during infancy may help to prevent egg allergy development. However, the infant egg consumption frequency that is sufficient to induce this immune tolerance remains uncertain. OBJECTIVES: We examined the associations between the infant egg consumption frequency and maternal-reported child egg allergy at 6 y. METHODS: We analyzed data of 1252 children from the Infant Feeding Practices Study II (2005-2012). Mothers reported the frequency of infant egg consumption at 2, 3, 4, 5, 6, 7, 9, 10, and 12 mo old. Mothers reported the status of their child's egg allergy at the 6-y follow-up. We used Fisher exact test, Cochran-Armitage Trend Test, and log Poisson regression models to compare 6-y egg allergy risk by the frequency of infant egg consumption. RESULTS: The risk of maternal-reported egg allergy at 6 y significantly (P-trend = 0.004) decreased with infant egg consumption frequency at 12 mo: 2.05% (11/537) for infants not consuming eggs, 0.41% (1/244) for those consuming eggs <2 times per wk, and 0.21% (1/471) for those consuming eggs ≥2 times per wk. A similar but nonsignificant trend (P-trend=0.109) was observed for egg consumption at 10 mo (1.25%, 0.85%, and 0%, respectively). After adjusting for socioeconomic confounders, breastfeeding, complementary food introduction, and infant eczema, infants who consumed eggs ≥2 times per wk at 12 mo had a significantly lower RR of maternal-reported egg allergy at 6 y (confounder-adjusted RR: 0.11; 95% CI: 0.01, 0.88; P = 0.038), whereas those who consumed <2 times per wk (confounder-adjusted RR: 0.21; 95% CI: 0.03, 1.67; P = 0.141) did not have a significantly lower risk than those who did not consume eggs at all. CONCLUSIONS: Consumption of eggs ≥2 times per wk in late infancy is associated with a reduced risk of developing egg allergy later in childhood.

PEGylated Recombinant Adenosine Deaminase Maintains Detoxification and Lymphocyte Counts in Patients with ADA-SCID.

PURPOSE: Metabolic detoxification with enzyme replacement therapy (ERT) promotes immune recovery in patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (ADA-SCID). Elapegademase is a PEGylated recombinant bovine ADA ERT developed to replace the now-discontinued bovine-derived pegademase. This study was a 1-way crossover from pegademase to elapegademase in 7 patients with ADA-SCID to assess efficacy and safety outcomes for elapegademase. METHODS: After once-weekly pegademase dosage was adjusted to achieve therapeutic metabolic detoxification and trough ADA activity, patients transitioned to a bioequivalent dose of elapegademase. Maintenance of metabolic detoxification and adequate ADA activity were evaluated periodically. RESULTS: One patient withdrew after 2 doses of an early elapegademase formulation due to injection-site pain caused by EDTA. The 6 remaining patients completed 71-216 weeks of elapegademase therapy with a formulation that did not contain EDTA. In these patients, elapegademase improved ADA activity compared with pegademase and maintained metabolic detoxification. Total lymphocyte counts increased for all completer patients from between 1.2- and 2.1-fold at the end of study compared with baseline. Elapegademase had a comparable safety profile to pegademase; no patient developed a severe infectious complication. Three patients had transient, non-neutralizing antibodies to pegademase, elapegademase, and/or polyethylene glycol ≤ 47 weeks of treatment without effect on trough plasma ADA activity or trough erythrocyte deoxyadenosine nucleotide levels. CONCLUSION: Elapegademase was safe, well tolerated, achieved stable trough plasma ADA activity with weekly dosing, was effective in maintaining metabolic detoxification, and was associated with maintenance or improvements in lymphocyte counts compared with pegademase therapy in patients with ADA-SCID.

The Impact of Caregiver Depression on Child Asthma Outcomes: Pathways and Mechanisms.

BACKGROUND: Depression is common in caregivers of children with asthma and is associated with poor outcomes in their child. No prior studies have longitudinally examined caregiver depression remission as a predictor of improvement in child asthma control. OBJECTIVE: This 2-site study examined whether the proportion of time a caregiver was in depression remission predicted subsequent child asthma control at exit. METHOD: Caregivers (n = 205) with current major depressive disorder and their children, ages 7 to 17, with persistent asthma were observed every 4 weeks for 52 weeks. Caregiver depressive symptoms were measured using the 17-item Hamilton Rating Scale for Depression (HRSD). Child asthma was assessed with the (Childhood) Asthma Control Test (cACT/ACT) and spirometry, and depression with the Children's Depression Inventory (CDI). Linear regression analyses were conducted with change in cACT/ACT, CDI, and forced expiratory volume in 1 second (FEV1)% predicted as outcomes and proportion of time the caregiver was in remission (HRSD score ≤ 7) as the predictor. Multilevel mediation analyses examined the role of child depressive symptoms and asthma controller medication adherence. RESULTS: Children were, on average, 54.1% female and 11 years old. Caregiver proportion of time in HRSD-assessed remission of depression was a significant predictor of improvement in cACT/ACT, CDI, and FEV1% predicted. Child CDI score, but not medication adherence, mediated the relationship between caregiver HRSD scores and child asthma control scores. CONCLUSIONS: Improvement in caregiver depression positively influences child asthma outcomes partially through improvement in child depressive symptom severity. Caregiver depression screening and treatment might lead to improvement in child asthma outcomes.

Delayed egg introduction beyond infancy and increased egg allergy risk in childhood.

AIM: Egg is a major food allergen in childhood. Recent studies suggest that early introduction of allergenic foods can decrease the risk of developing egg allergy. The impact of early egg introduction in the general population is unclear. We examined associations between age of infant egg introduction and childhood egg allergy outcomes in a general population. METHODS: The study population consisted of 1217 neonates from Project Viva, a longitudinal pre-birth cohort in eastern Massachusetts area, USA. Mothers reported age of infant egg introduction and child egg allergy using questionnaires and specific IgE to egg white was assayed. We estimated associations between age of infant egg introduction and egg allergy outcomes using Log-binomial regression models, adjusting for socio-demographics and health confounders. RESULTS: Egg allergy at 2 years was significantly higher (8.0% vs. 1.4%, P < 0.0001) in children who had delayed egg introduction beyond infancy, compared with children who were introduced to egg during infancy (adjusted relative risk or aRR 7.58; 95% CI 3.08, 18.61). At 12 years, the risk of egg allergy remained significantly higher (3.9% vs. 1.1%, P = 0.048) in children with delayed egg introduction compared with children introduced to egg during infancy (aRR 4.07; 95% CI 1.20, 13.87). CONCLUSIONS: Infants with delayed introduction of eggs after 12 months had increased risk of egg allergy in childhood (2 years) and the relationship persisted in early adolescence (12 years). Our findings suggest that introduction to eggs before 12 months could contribute to the prevention of egg allergy.

Infant age at egg introduction and malnutrition-related child growth in the United States.

To evaluate the relationship between infant age of egg introduction and malnutrition-related growth outcomes in the United States, we analysed secondary data of 1716 mother-child dyads in the Infant Feeding Practices Study II and its Year 6 Follow-Up Study. Malnutrition-related growth outcomes included body mass index z-score (BMIZ), obesity (weight-for-height z-score [WHZ] ≥3 or BMIZ ≥ 2), WHZ, wasting (WHZ < -2), height-for-age z-score (HAZ), and stunting (HAZ < -2). Infant age at egg introduction was analysed as a continuous variable. We used generalised estimating equations to estimate the mean difference in continuous outcomes and relative risk [RR]) for binary outcomes, adjusting for related maternal and child confounders. We also explored interactions with child sex, maternal race/ethnicity, maternal educational level, ever breastfeeding, and formula feeding. In the total sample, a later infant age at egg introduction was associated with a lower mean difference in HAZ (confounder-adjusted mean difference = -0.08, 95% confidence interval [CI]: -0.12 to -0.03 per month) and a higher risk of stunting (confounder-adjusted RR = 1.17, 95% CI: 1.03-1.33 per month) at 6 years. The associations between infant age at egg introduction and 12-month growth outcomes differed by child sex. Among females but not among males, later introduction of eggs was associated with a lower mean WHZ (-0.06 [-0.12 to 0.00] per month) at 12 months. Later egg introduction during infancy was associated with a lower mean HAZ and a higher risk of stunting in 6-year-old children. Besides this, it was associated with a lower WHZ among females at 12 months.

Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees.

Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.

A pilot school-based health center intervention to improve asthma chronic care in high-poverty schools.

OBJECTIVE: To test the feasibility and effectiveness of a multifaceted intervention administered through school-based health centers (SBHCs) to improve asthma control for children in high-poverty schools with not well controlled asthma. METHODS: Students 4-14 years old with persistent asthma were enrolled from three SBHCs. The centers' advanced practice providers received training on evidence-based asthma guidelines. Students randomized to the intervention received directly observed therapy of their asthma controller medication, medication adjustments as needed by the centers' providers, and daily self-management support. Students randomized to usual care were referred back to their primary care provider (PCP) for routine asthma care. RESULTS: We enrolled 29 students. Students in the intervention group received their controller medication 92% of days they were in school. Ninety-four percent of follow-up assessments were completed. During the study, 11 of 12 intervention students had a step-up in medication; 2 of 15 usual care students were stepped up by their PCP. Asthma Control Test scores did not differ between groups, although there were significant improvements from baseline to the 7 month follow-up within each group (both p < .01). Both FEV1% predicted and FEV1/FVC ratio significantly worsened in the usual care group (both p = .001), but did not change in the intervention group (p = .76 and .28 respectively). CONCLUSIONS: Our pilot data suggest that a multifaceted intervention can be feasibly administered through SBHCs in communities with health disparities. Despite the small sample size, spirometry detected advantages in the intervention group. Further study is needed to optimize the intervention and evaluate outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03032744.

Respiratory Infections in Patients with Primary Immunodeficiency.

Recurrent and life-threatening respiratory infections are nearly universal in patients with primary immunodeficiency diseases (PIDD). Early recognition, aggressive treatment, and prophylaxis with antimicrobials and immunoglobulin replacement have been the mainstays of management and will be reviewed here with an emphasis on respiratory infections. Genetic discoveries have allowed direct translation of research to clinical practice, improving our understanding of clinical patterns of pathogen susceptibilities and guiding prophylaxis. The recent identification of inborn errors in type I interferon signaling as a basis for life-threatening viral infections in otherwise healthy individuals suggests another targetable pathway for treatment and/or prophylaxis. The future of PIDD diagnosis will certainly involve early genetic identification by newborn screening before onset of infections, with early treatment offering the potential of preventing disease complications such as chronic lung changes. Gene editing approaches offer tremendous therapeutic potential, with rapidly emerging delivery systems. Antiviral therapies are desperately needed, and specific cellular therapies show promise in patients requiring hematopoietic stem cell transplantation. The introduction of approved therapies for clinical use in PIDD is limited by the difficulty of studying outcomes in rare patients/conditions with conventional clinical trials.

Candida Glabrata Lymphadenitis Following Infliximab Therapy for Inflammatory Bowel Disease in a Patient With Chronic Granulomatous Disease: Case Report and Literature Review.

Chronic granulomatous disease (CGD) is an inborn error of immunity caused by inactivating genetic mutations in any one of the components of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Phagocytic cell reactive oxygen species generation is impaired in the absence of a functional NADPH oxidase complex. As a result, patients with CGD are at high risk of developing deep-seated infections with certain bacteria and fungi. Additionally, aberrant inflammation and granuloma formation may occur in multiple organs including the bowels, with inflammatory bowel disease seen as a common inflammatory complication of CGD. Traditionally, TNF-α inhibitors are considered effective biological therapies for moderate-to-severe inflammatory bowel disease. While limited case series and reports of patients with CGD have shown improvement in fistula healing with use of TNF-α inhibitors, several patients have developed severe, even fatal, infections with CGD-related pathogens while on TNF-inhibitor therapy. In this case report, we describe an adolescent male with X-linked CGD and steroid-refractory colitis with perirectal fistula and abscesses, who was initiated on treatment with infliximab, a TNF-α inhibitor. Following his first two infliximab doses, the patient developed a Candida glabrata lymphadenitis and associated ulcerating oropharyngeal lesions, requiring hospitalization and therapy with amphotericin B for resolution. We compare our patient's case to prior reports of infliximab use in CGD-related inflammatory bowel disease.

Eosinophilic Esophagitis.

Eosinophilic esophagitis is a recently defined condition that has dramatically increased in prevalence in the last several decades. It may occur at any age, but the clinical presentation in young children is often more vague than the classic solid food dysphagia and food impacting that are the major presenting symptoms of eosinophilic esophagitis in adults and adolescents. Successful therapies exist, including medications and dietary modifications, but disease typically recurs when the intervention is discontinued.

Multivariate Association of Child Depression and Anxiety with Asthma Outcomes.

BACKGROUND: Pediatric asthma is associated with increased health services utilization, missed school days, and diminished quality of life. Children with asthma also report more frequent depressive and anxiety symptoms than children without asthma, which may further worsen asthma outcomes. OBJECTIVE: The current study investigated the relationship between depressive and anxiety symptoms and 4 asthma outcomes (asthma control, asthma severity, lung function, and asthma-related quality of life) in children (N = 205) with moderate to severe persistent asthma. METHODS: The data were analyzed using a canonical correlation analysis, a multivariate framework that allows examination of all variables of interest in the same model. RESULTS: We found a statistically significant relationship between symptoms of depression and anxiety and asthma outcomes (1 - Λ = .372; P < .001). A large effect size suggests that 37.2% of variance is shared between depression and anxiety symptoms and 4 asthma outcomes (particularly asthma control and asthma-related quality of life) in the overall sample. Among girls (vs. boys), asthma control (measured by the Asthma Control Test) emerged as a stronger contributor to asthma outcomes compared with boys. CONCLUSIONS: These results suggest that psychiatric symptoms, especially anxiety, are associated with poor asthma-related quality of life, and more negative perception of asthma control in girls compared with boys (with no observed sex difference in physiological lung function). Clinicians should consider incorporating questions about psychiatric symptoms as part of routine asthma management, and focus patient education on unique differences in which boys and girls perceive their asthma symptoms.

Twist2 is NFkB-responsive when p120-catenin is inactivated and EGFR is overexpressed in esophageal keratinocytes.

Esophageal squamous cell carcinoma (ESCC) is among the most aggressive and fatal cancer types. ESCC classically progresses rapidly and frequently causes mortality in four out of five patients within two years of diagnosis. Yet, little is known about the mechanisms that make ESCC so aggressive. In a previous study we demonstrated that p120-catenin (p120ctn) and EGFR, two genes associated with poor prognosis in ESCC, work together to cause invasion. Specifically, inactivation of p120ctn combined with overexpression of EGFR induces a signaling cascade that leads to hyperactivation of NFkB and a resultant aggressive cell type. The purpose of this present study was to identify targets that are responsive to NFkB when p120ctn and EGFR are modified. Using human esophageal keratinocytes, we have identified Twist2 as an NFkB-responsive gene. Interestingly, we found that when NFkB is hyperactivated in cells with EGFR overexpression and p120ctn inactivation, Twist2 is significantly upregulated. Inhibition of NFkB activity results in nearly complete loss of Twist2 expression, suggesting that this potential EMT-inducing gene, is a responsive target of NFkB. There exists a paucity of research on Twist2 in any cancer type; as such, these findings are important in ESCC as well as in other cancer types.

Loss of p120ctn causes EGFR-targeted therapy resistance and failure.

Epidermal growth factor receptor (EGFR) plays a vital role in cell division and survival signaling pathways. EGFR is activated in nearly every cancer type, and its high expression in tumors is correlated with poor patient outcome. Altogether, EGFR is a prime candidate as a therapeutic target. While targeted EGFR therapy is initially effective in 75% of patients, a majority of patients relapse within the first year due to poorly understood mechanisms of resistance. p120-catenin (p120ctn) has recently been implicated as a biomarker for EGFR therapy. In previous studies, we demonstrated that p120ctn is a tumor suppressor and its loss is capable of inducing cancer. Furthermore, p120ctn down-regulation synergizes with EGFR overexpression to cause a highly invasive cell phenotype. The purpose of this present study was to investigate whether p120ctn down-regulation induced EGFR therapeutic resistance. Using human esophageal keratinocytes, we have found that EGFR-targeting compounds are toxic to cells overexpressing EGFR. Interestingly, these therapies do not cause toxicity in cells with EGFR overexpression and decreased p120ctn expression. These data suggest that decreased p120ctn causes resistance to EGFR therapy. We believe these findings are of utmost importance, as there is an unmet need to discover mechanisms of EGFR resistance.

Current and Future Monoclonal Antibodies in the Treatment of Atopic Dermatitis.

Atopic dermatitis is a common immunologic skin disease. Mild atopic dermatitis can be managed with emollients and topical therapies such as low potency topical steroids, which have a favorable safety profile. Severe atopic dermatitis, in contrast, is a challenging disease to treat. Topical therapies are typically inadequate for control of severe atopic dermatitis. When topical therapies fail, the mainstay of therapy for severe atopic dermatitis has traditionally been phototherapy or off-label use of systemic immunosuppressant treatment, yet systemic immunosuppressants all have significant potential toxicities, drug interactions, and contraindications, requiring close monitoring. Targeted biologics are therefore attractive treatment options for topical therapy-refractory cases of atopic dermatitis, with the potential to offer effective, safer treatment of uncontrolled atopic dermatitis. Dupilumab, as the only biologic therapy currently FDA-approved for atopic dermatitis, is effective for many patients, but there is need for continuing study of additional biologic therapies to address the needs of diverse patients with uncontrolled atopic dermatitis.

The role of neutrophils in host defense and disease.

Neutrophils, the most abundant circulating leukocyte, are critical for host defense. Granulopoiesis is under the control of transcriptional factors and culminates in mature neutrophils with a broad armamentarium of antimicrobial pathways. These pathways include nicotinamide adenine dinucleotide phosphate oxidase, which generates microbicidal reactive oxidants, and nonoxidant pathways that target microbes through several mechanisms. Activated neutrophils can cause or worsen tissue injury, underscoring the need for calibration of activation and resolution of inflammation when infection has been cleared. Acquired neutrophil disorders are typically caused by cytotoxic chemotherapy or immunosuppressive agents. Primary neutrophil disorders typically result from disabling mutations of individual genes that result in impaired neutrophil number or function, and provide insight into basic mechanisms of neutrophil biology. Neutrophils can also be activated by noninfectious causes, including trauma and cellular injury, and can have off-target effects in which pathways that typically defend against infection exacerbate injury and disease. These off-target effects include acute organ injury, autoimmunity, and variable effects on the tumor microenvironment that can limit or worsen tumor progression. A greater understanding of neutrophil plasticity in these conditions is likely to pave the way to new therapeutic approaches.

Comorbid Obesity and Depressive Symptoms in Childhood Asthma: A Harmful Synergy.

BACKGROUND: Overweight/obesity (OV/OB) and depression have each been separately associated with worsened childhood asthma severity and control. Pathways by which these factors may jointly affect childhood asthma have not been elucidated. OBJECTIVE: To examine the interrelationship of OV/OB and depressive symptoms with childhood asthma and explore associated psychobiologic pathways. The present study investigated whether comorbid OV/OB and depressive symptoms are associated with impaired baseline lung function and increased airway resistance during emotional stress, and to assess whether such effects may be mediated by autonomic nervous system (ANS) dysregulation, specifically through predominance of vagal over sympathetic reactivity (vagal bias). METHODS: A total of 250 children with asthma, aged 7 to 17, were assessed for OV/OB using body mass index, depressive symptoms using the Children's Depression Inventory (CDI), and asthma severity using National Asthma Education and Prevention Program Expert Panel Report 3 criteria. Baseline pulmonary function (forced expiratory volume in 1 second [FEV1]) was assessed. The film "E.T. the Extra-Terrestrial" was used in a laboratory paradigm to evoke emotional stress/arousal. Airway resistance (Rint) was measured before and after the film to determine changes in airway function. ANS reactivity was assessed by measuring parasympathetic/vagal and sympathetic reactivity throughout the film. RESULTS: In OV/OB children with asthma, depressive symptoms predicted lower baseline FEV1 (ß = -0.67, standard error [SE] = 0.24, P = .008), CDI predicted vagal bias under emotion stress/arousal (ß = 0.27, SE = 0.09, P = .009), and vagal bias predicted increased Rint (ß = 3.55, SE = 1.54, P = .023). CONCLUSION: This study is the first to link OV/OB and depressive symptoms in their relationship to childhood asthma. In OV/OB children with asthma, depression may potentiate airway compromise, mediated by vagal bias. Use of antidepressant and anticholinergic therapies should be studied in this subgroup of patients.