Volunteerism Addressing Environmental Disparities in Allergy (VAEDIA): The presidential initiative to combat environmental injustice in allergy and immunology-a Work Group Report of the AAAAI VAEDIA task force.

Many vulnerable people lose their health or lives each year as a result of unhealthy environmental conditions that perpetuate medical conditions within the scope of allergy and immunology specialists' expertise. While detrimental environmental factors impact all humans globally, the effect is disproportionately more profound in impoverished neighborhoods. Environmental injustice is the inequitable exposure of disadvantaged populations to environmental hazards. Professional medical organizations such as the American Academy of Allergy, Asthma & Immunology (AAAAI) are well positioned to engage and encourage community outreach volunteer programs to combat environmental justice. Here we discuss how environmental injustices and climate change impacts allergic diseases among vulnerable populations. We discuss pathways allergists/immunologists can use to contribute to addressing environmental determinants by providing volunteer clinical service, education, and advocacy. Furthermore, allergists/immunologists can play a role in building trust within these communities, partnering with other patient advocacy nonprofit stakeholders, and engaging with local, state, national, and international nongovernmental organizations, faith-based organizations, and governments. The AAAAI's Volunteerism Addressing Environmental Disparities in Allergy (VAEDIA) is the presidential task force aiming to promote volunteer initiatives by creating platforms for discussion and collaboration and by funding community-based projects to address environmental injustice.

Prebirth effects of climate change on children's respiratory health.

PURPOSE OF REVIEW: To date, there is no evidence that humanity will implement appropriate mitigation measures to avoid the catastrophic impact of climate change on the planet and human health. Vulnerable populations such as pregnant women and children will be the most affected. This review highlights epidemiologic data on climate change-related prenatal environmental exposures affecting the fetus and children's respiratory health. RECENT FINDINGS: Research on outcomes of prenatal exposure to climate change-related environmental changes and pediatric pulmonary health is limited. In addition to adverse pregnancy outcomes known to affect lung development, changes in lung function, increased prevalence of wheezing, atopy, and respiratory infections have been associated with prenatal exposure to increased temperatures, air pollution, and maternal stress. The mechanisms behind these changes are ill-defined, although oxidative stress, impaired placental functioning, and epigenetic modifications have been observed. However, the long-term impact of these changes remains unknown. SUMMARY: The detrimental impact of the climate crisis on pediatric respiratory health begins before birth, highlighting the inherent vulnerability of pregnant women and children. Research and advocacy, along with mitigation and adaptation measures, must be implemented to protect pregnant women and children, the most affected but the least responsible for the climate crisis.

An Examination of the Intersection of Climate Change, the Physician Specialty Workforce, and Graduate Medical Education in the U.S.

Issue: As U.S. healthcare systems plan for future physician workforce needs, the systemic impacts of climate change, a worldwide environmental and health crisis, have not been factored in. The current focus on increasing the number of trained physicians and optimizing efficiencies in healthcare delivery may be insufficient. Graduate medical education (GME) priorities and training should be considered in order to prepare a climate-educated physician workforce. Evidence: We used a holistic lens to explore the available literature regarding the intersection of future physician workforce needs, GME program priorities, and resident education within the larger context of climate change. Our interinstitutional, transdisciplinary team brought perspectives from their own fields, including climate science, climate and health research, and medical education to provide recommendations for building a climate-educated physician workforce. Implications: Acknowledging and preparing for the effects of climate change on the physician workforce will require identification of workforce gaps, changes to GME program priorities, and education of trainees on the health and societal impacts of climate change. Alignment of GME training with workforce considerations and climate action and adaptation initiatives will be critical in ensuring the U.S. has a climate-educated physician workforce capable of addressing health and healthcare system challenges. This article offers a number of recommendations for physician workforce priorities, resident education, and system-level changes to better prepare for the health and health system impacts of climate change.

Climate change and global issues in allergy and immunology.

The steady increase in global temperatures, resulting from the combustion of fossil fuels and the accumulation of greenhouse gases (GHGs), continues to destabilize all ecosystems worldwide. Although annual emissions must be halved by 2030 and reach net zero by 2050 to limit some of the most catastrophic impacts associated with a warming planet, the world's efforts to curb GHG emissions fall short of the commitments made in the 2015 Paris Agreement. To this effect, July 2021 was recently declared the hottest month ever recorded in 142 years. The ramifications of these changes for global temperatures are complex and further promote outdoor air pollution, pollen exposure, and extreme weather events. Besides worsening respiratory health, air pollution promotes atopy and susceptibility to infections. The effects of GHGs on pollen affect the frequency and severity of asthma and allergic rhinitis. Changes in temperature, air pollution, and extreme weather events exert adverse multisystemic health effects and disproportionally affect disadvantaged and vulnerable populations. This review article is an update for allergists and immunologists about the health impacts of climate change that are already evident in our daily practices. It is also a call to action and advocacy, including to integrate climate change-related mitigation, education, and adaptation measures to protect our patients and avert further injury to our planet.

Pulmonary Manifestations of Immunodeficiency and Immunosuppressive Diseases Other than Human Immunodeficiency Virus.

Immune deficiencies may alter normal lung function and protective mechanisms, resulting in a myriad of pulmonary manifestations. Primary immunodeficiencies involve multiple branches of the immune system, and defects may predispose to recurrent upper and lower respiratory infections by common pathogens; opportunistic infections; and autoimmune, inflammatory, and malignant processes that may result in interstitial pneumonias. Secondary immunodeficiencies may result from neoplasms or their treatment, organ transplant and immunosuppression, and from autoimmune diseases and their treatments. Primary and secondary immunodeficiencies and their pulmonary manifestations may be difficult to diagnose and treat. A multidisciplinary approach to evaluation is essential.

Changes in intestinal Toll-like receptors and cytokines precede histological injury in a rat model of necrotizing enterocolitis.

It is unclear whether the broad inflammatory response shown in neonatal necrotizing enterocolitis (NEC) is the cause or the effect of tissue injury. Toll-like receptors (TLRs) on intestinal dendritic, mononuclear, and epithelial cells recognize bacterial ligands and damaged tissues, thus activating the inflammatory response. The present study aimed to determine whether active TLR signaling would precede histological injury in NEC. Newborn rat pups were divided into four groups: dam fed, dam fed-hypoxic, formula fed, and formula fed-hypoxic (NEC). The ileal tissues were evaluated for NEC scores at 24, 48, 72, and 120 h. Quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry were used to measure and localize intestinal TLRs. Cytokines were assessed by a multispot cytokine array. Among the four groups, ileal injury was seen only after 72 h of formula feeding and hypoxia. We found selective induction of mRNA levels in NEC compared with dam-fed controls for TLR2 > TLR4 > TLR1 = TLR3, TLR7, and TLR9 > TLR6 (P < 0.01); TLR5 was downregulated (P < 0.01). All TLR changes started at 48 h, before any histological evidence of NEC. Both Th1-type cytokines (IFN-gamma, IL-1beta, TNF-alpha, and KC/GRO) and Th2-type cytokines (IL-4, IL-5 and IL-13) were significantly increased in NEC but also in nondamaged formula-fed rat ileum. In conclusion, the intestinal expression of TLRs and cytokines precedes histological injury in the experimental NEC.

The emerging role of immune dysfunction in mitochondrial diseases as a paradigm for understanding immunometabolism.

Immunometabolism aims to define the role of intermediary metabolism in immune cell function, with bioenergetics and the mitochondria recently taking center stage. To date, the medical literature on mitochondria and immune function extols the virtues of mouse models in exploring this biologic intersection. While the laboratory mouse has become a standard for studying mammalian biology, this model comprises part of a comprehensive approach. Humans, with their broad array of inherited phenotypes, serve as a starting point for studying immunometabolism; specifically, patients with mitochondrial disease. Using this top-down approach, the mouse as a model organism facilitates further exploration of the consequences of mutations involved in mitochondrial maintenance and function. In this review, we will discuss the emerging phenotype of immune dysfunction in mitochondrial disease as a model for understanding the role of the mitochondria in immune function in available mouse models.

Cytochrome c Oxidase Activity Is a Metabolic Checkpoint that Regulates Cell Fate Decisions During T Cell Activation and Differentiation.

T cells undergo metabolic reprogramming with major changes in cellular energy metabolism during activation. In patients with mitochondrial disease, clinical data were marked by frequent infections and immunodeficiency, prompting us to explore the consequences of oxidative phosphorylation dysfunction in T cells. Since cytochrome c oxidase (COX) is a critical regulator of OXPHOS, we created a mouse model with isolated dysfunction in T cells by targeting a gene, COX10, that produces mitochondrial disease in humans. COX dysfunction resulted in increased apoptosis following activation in vitro and immunodeficiency in vivo. Select T cell effector subsets were particularly affected; this could be traced to their bioenergetic requirements. In summary, the findings presented herein emphasize the role of COX particularly in T cells as a metabolic checkpoint for cell fate decisions following T cell activation, with heterogeneous effects in T cell subsets. In addition, our studies highlight the utility of translational models that recapitulate human mitochondrial disease for understanding immunometabolism.

Global Climate Change and Children's Health.

Rising global temperature is causing major physical, chemical, and ecological changes across the planet. There is wide consensus among scientific organizations and climatologists that these broad effects, known as climate change, are the result of contemporary human activity. Climate change poses threats to human health, safety, and security. Children are uniquely vulnerable to these threats. The effects of climate change on child health include physical and psychological sequelae of weather disasters, increased heat stress, decreased air quality, altered disease patterns of some climate-sensitive infections, and food, water, and nutrient insecurity in vulnerable regions. Prompt implementation of mitigation and adaptation strategies will protect children against worsening of the problem and its associated health effects. This technical report reviews the nature of climate change and its associated child health effects and supports the recommendations in the accompanying policy statement on climate change and children's health.

Clinical experience with linezolid for the treatment of nocardia infection.

Linezolid is an oxazolidinone that has activity against most gram-positive bacteria, including in vitro activity against all Nocardia species and strains. We describe 6 clinical cases of nocardiosis that were successfully treated with linezolid. Two patients had underlying X-linked chronic granulomatous disease, and 2 patients were receiving chronic corticosteroid therapy. Four of 6 patients had disseminated disease, and 2 of these 4 patients had multiple brain abscesses. Four patients primarily received monotherapy; for the fifth patient, linezolid was added to a failing multiple-drug regimen, and, for the sixth patient, it was used as part of combination therapy. All 6 patients were successfully treated, although 1 patient had a presumed relapse of central nervous system infection after premature discontinuation of the drug. Linezolid appears to be an effective alternative for the treatment of nocardiosis.

Dysanaptic growth of lung and airway in children with post-infectious bronchiolitis obliterans.

RATIONALE: Post-infectious bronchiolitis obliterans (PBO) is a rare form of chronic obstructive lung disease associated with small airway fibrosis following a severe insult to the lower respiratory tract. It has been suggested that PBO is a non-progressive disease. However, evidence supporting this statement is limited. In this case series, we sought to determine the changes of pulmonary function tests (PFT) over time in children with PBO. METHODS: Seven children with PBO, ages 6-15 years old, were retrospectively studied between 1994 and 2012. Spirometry and lung volumes tests were performed in accordance with American Thoracic Society (ATS) guidelines and were monitored over time. The average rate of change was calculated using generalized linear mixed models. RESULTS: The median baseline values for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio and forced expiratory flow 25%-75% (FEF25%-75%) were 57%, 50%, 87% and 29%, respectively. FVC increased at a rate of 1.8% per year (P = 0.008). There was no significant change in FEV1 over time (P = 0.112). However, the FEV1/FVC ratio decreased by 2.6% per year (P < 0.001). CONCLUSION: PFT in childhood PBO was characterized by significant airway obstruction. Over time, FVC (lung parenchyma) increased and FEV1 (airway) remained stable, but FEV1/FVC ratio declined more than expected, suggesting a mismatch in the growth of the airway and lung parenchyma (dysanaptic growth). Further studies in larger populations are needed to validate these observations.

Sleep disordered breathing in children with mitochondrial disease.

A retrospective chart review study was performed to determine the presence of sleep disordered breathing (SDB) in children with primary mitochondrial disease (MD). The symptoms, sleep-related breathing, and movement abnormalities are described for 18 subjects (ages 1.5 to 18 years, 61% male) with MD who underwent polysomnography in our pediatric sleep center from 2007 to 2012. Of the 18 subjects with MD, the common indications for polysomnography were excessive somnolence or fatigue (61%, N = 11), snoring (44%, N = 8), and sleep movement complaints (17%, N = 3). Polysomnographic measurements showed SDB in 56% (N = 10) (obstructive sleep apnea in 60% (N = 6), hypoxemia in 40% (N = 4), and sleep hypoventilation in 20% (N = 2)). There was a significant association between decreased muscle tone and SDB (P: 0.043) as well as obese and overweight status with SDB (P = 0.036). SDB is common in subjects with MD. Early detection of SDB, utilizing polysomnography, should be considered to assist in identification of MD patients who may benefit from sleep-related interventions.

Effect of perinatal antiretroviral drug exposure on hematologic values in HIV-uninfected children: An analysis of the women and infants transmission study.

BACKGROUND: With the increasing use of antiretroviral (ARV) drugs to prevent mother-to-child transmission of human immunodeficiency virus (HIV), large numbers of infants are exposed, with possible consequent toxicity. METHODS: Hematologic values in 1820 uninfected HIV- and ARV-exposed children were compared with those in 351 ARV-unexposed children from the Women and Infants Transmission Study. Hemoglobin concentrations and platelet, neutrophil, lymphocyte, and CD4+ and CD8+ cell counts were analyzed at birth and ages 2, 6, 12, 18, and 24 months. Multivariate analysis was conducted age 0-2 and 6-24 months, with adjustment for multiple cofactors. RESULTS: Hemoglobin concentrations and neutrophil, lymphocyte, and CD4+ cell counts were significantly lower at age 0-2 months in infants exposed to ARV drugs than in those who were not. At 6-24 months, differences in hemoglobin concentrations and neutrophil counts were no longer significant, whereas differences in platelet, lymphocyte, and CD4+ cell counts persisted and CD8+ cell counts became significantly lower. In comparison with ARV monotherapy, combination therapy was associated with larger decreases in neutrophil, lymphocyte, and CD8+ cell counts at age 0-2 months but with only differences in CD8+ cell counts at age 6-24 months. Clinically significant abnormalities were rare and did not differ by exposure to ARV drugs. CONCLUSION: Infants exposed to ARV drugs have small but significant differences in several hematologic parameters for the first 24 months of life. These results indicate the need for long-term follow-up of uninfected infants with ARV exposure.