SARS-CoV-2 pandemic effect on pediatric asthma health care utilization in an urban hospital.

Background: The "September epidemic" is a well-described phenomenon of increased pediatric asthma-related health care utilization from August to September each year. The coronavirus disease 2019 (COVID-19) pandemic has brought about significant changes in health care utilization, warranting an investigation into its impact on the September epidemic. Objective: Our aim was to identify the impact of COVID-19 in asthma-related health care utilization, specifically in the September epidemic. Methods: Our study involved a retrospective analysis of data from a Children's Hospital in New York City. We compared the change in asthma-related health care utilization during August and September 2020 with the average change in utilization during the same period in 2017-2019 and 2021-2022. Stratified analyses based on age and sex were conducted by using chi-square tests to determine variations in health care utilization. Results: During September 2020, there was a marked reduction in emergency department (ED) visits related to asthma, with only a 6% rise from the preceding month. This stands in contrast to the observed increases from 89% to 193% in the other years studied (P < .05 for all). This pattern was seen in both sexes and in children under 13 years old (P < .05). No significant variation was found for those older than 13 years (P > .05). Conclusions: Despite an overall reduction in health care utilization over the first year of the COVID-19 pandemic, the decline in ED visits related to asthma during the September epidemic was significantly more pronounced. These results suggest that there may be remediable risk factors contributing to the September epidemic that can be used to guide future interventions for managing pediatric asthma.

A Geneticist Transcribing the Chemical Language of Bacteria.

The study of quorum sensing, bacterial cell-to-cell communication mediated by the production and detection of small molecule signals, has skyrocketed since its discovery in the last third of the 20th century. Building from early investigations of bacterial bioluminescence, the process has been characterized to control a numerous and growing number of group behaviors, including virulence and biofilm formation. Bonnie Bassler has made key contributions to the understanding of quorum sensing, leading interdisciplinary efforts to characterize key signaling pathway components and their respective signaling molecules across a range of gram-negative bacteria. This review highlights her work in the field, with a particular emphasis on the chemical contributions of her work.

Effect of Early Infant Lactobacillus rhamnosus GG Supplementation in Preventing Viral Respiratory Illness.

The role of early probiotic supplementation in infants for the prevention of respiratory viral illnesses is unclear. We examined the association of Lactobacillus rhamnosus GG (LGG) supplementation during the first 6 months of life with the frequency and severity of viral illnesses during the first 24 months of life. We conducted a secondary analysis of data from the randomized controlled Trial of Infant Probiotic Supplementation (n = 184). Parents reported the number of respiratory viral illnesses, and a composite severity score was created based on symptoms. A negative binomial regression model and a mixed-effects linear regression model assessed for differences in the number of episodes and severity of episodes between treatment groups, respectively. There was no significant difference in the incidence rate of viral illness episodes or symptom severity between treatment groups. Daily supplementation with LGG in early infancy does not decrease the number or severity of viral illnesses during the first 2 years of life.

Associations between sleep, obesity, and asthma in urban minority children.

STUDY OBJECTIVES: Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and pulmonary function on polysomnography in children with asthma. METHODS: We conducted a retrospective chart review on 448 7- to 18-year-old children with asthma who had undergone polysomnography testing between 1/2007-12/2011 to elucidate the association between spirometry variables, body-mass index, and polysomnography parameters, adjusting for asthma and antiallergic medications. RESULTS: Obese children had poorer sleep architecture and more severe gas exchange abnormalities compared to healthy weight children. Multivariate analysis revealed an independent association of body-mass index with sleep efficiency, with more light and less deep sleep in both obese and healthy-weight children, and with baseline oxygen saturation and oxygen nadir in obese children. In obese children, forced vital capacity was independently associated with less deep sleep (time in N3 sleep) as well as with oxygen nadir, while among healthy-weight children, forced expiratory volume directly correlated but forced vital capacity inversely correlated with deep sleep. In obese children, inhaled corticosteroid was associated with baseline oxygen saturation, and montelukast was associated with lower end-tidal carbon dioxide. In healthy-weight children, inhaled corticosteroid was associated with arousal awakening index, and montelukast was associated with light sleep. Antiallergic medications were not independently associated with polysomnography parameters. CONCLUSIONS: Pulmonary function, body-mass index, and asthma medications have independent and differing influences on sleep architecture and gas exchange polysomnography parameters in obese and healthy-weight children with asthma. Asthma medications are associated with improved gas exchange in obese children and improved sleep architecture in healthy-weight children with asthma. CITATION: Conrad LA, Nandalike K, Rani S, Rastogi D. Associations between sleep, obesity, and asthma in urban minority children. J Clin Sleep Med. 2022;18(10):2377-2385.

Child Interstitial Lung Disease in an Infant with Surfactant Protein C Dysfunction due to c.202G>T Variant (p.V68F).

For newborns suspected having childhood interstitial lung disease (ChILD), the sequencing of genes encoding surfactant proteins is recommended. However, it is still difficult to interpret the clinical significance of those variants found. We report a full-term born female infant who presented with respiratory distress and failure to thrive at 2 months of age and both imaging and lung biopsy were consistent with ChILD. Her genetic test was initially reported as a variant of unknown significance in surfactant protein C (c.202G > T, p.V68F), which was modified later as likely pathogenic after reviewing a report of the same variant as causing ChILD. The infant was placed on noninvasive ventilation and treated with IV Methylprednisolone, Hydroxychloroquine, and Azithromycin but did not show significant clinical and radiological improvement underwent tracheostomy and is awaiting lung transplantation at 8 months of age. The challenges interpreting the genetic results are discussed.

Increased Heart Rate Variability Response Among Infants with Reported Rhinorrhea and Watery Eyes: A Pilot Study.

INTRODUCTION: Previously, we found that reported infant rhinorrhea and watery eyes without a cold (RWWC) predicted school age exercise-induced wheeze, emergency department visits, and hospitalizations. These findings were independent of allergic sensitization, and we theorized that increased parasympathetic tone underlay the association. We also reported that increased heart-rate variability (HRV) in infants predicted wheeze in 2-3 year-olds. In a convenience sample of children participating in a birth cohort study, we tested the hypothesis that infants with RWWC would have elevated HRV, indicating increased parasympathetic tone. METHODS: RWWC symptoms since birth were queried for 3-month-old children. At 4-months, HRV was assessed (root mean square of successive differences [RMSSD]) during a standardized infant-mother still-face paradigm, which included 2 minutes of mother/child play immediately followed by 2 minutes of the mother maintaining a still-face. RESULTS: Among participants (n=38), RWWC was common for girls (32%) and boys (21%). The children with the greatest decrease in RMSSD between play and still-face challenge (lowest tertile) had a higher prevalence of RWWC as compared with children in the higher tertiles (50% vs 16%, P=0.045). In a logistic regression model controlling for sex, age and time between HRV and RWWC assessment, children with greater decrease in HRV between play and still-face (lowest tertile) had greater odds of having RWWC (odds ratio=6.0, P=0.029). CONCLUSION: In this relatively small study, we demonstrated greater decreases in HRV in response to a stressor among children with reported RWWC, suggesting that these children might have increased parasympathetic tone and/or overall greater vagal reactivity.

Antibiotic Adjuvant Activity Revealed in a Photoaffinity Approach to Determine the Molecular Target of Antipyocyanin Compounds.

Infections with Pseudomonas aeruginosa are a looming threat to public health. New treatment strategies are needed to combat this pathogen, for example, by blocking the production of virulence factors like pyocyanin. A photoaffinity analogue of an antipyocyanin compound was developed to interrogate the inhibitor's molecular mechanism of action. While we sought to develop antivirulence inhibitors, the proteomics results suggested that the compounds had antibiotic adjuvant activity. Unexpectedly, we found that these compounds amplify the bactericidal activity of colistin, a well-characterized antibiotic, suggesting they may represent a first-in-class antibiotic adjuvant therapy. Analogues have the potential not only to widen the therapeutic index of cationic antimicrobial peptides like colistin, but also to be effective against colistin-resistant strains, strengthening our arsenal to combat P. aeruginosa infections.

Defining pediatric asthma: phenotypes to endotypes and beyond.

Asthma is the most common chronic pediatric lung disease that has traditionally been defined as a syndrome of airway inflammation characterized by clinical symptoms of cough and wheeze. Highlighting the complex and heterogeneous nature of asthma, this review summarizes recent advances in asthma classification that are based on pathobiology, and thereby directly addresses limitations of existent definitions of asthma. By reviewing and contrasting clinical and mechanistic features of adult and childhood asthma, the review summarizes key biomarkers that distinguish childhood asthma subtypes. While atopy and its severity are important features of childhood asthma, there is evidence to support the existence of a childhood asthma endotype distinct from the atopic endotype. Although biomarkers of non-atopic asthma are an area of future research, we summarize a clinical approach that includes existing measures of airway-specific and systemic measures of atopy, co-existing morbidities, and disease severity and control, in the definition of childhood asthma, to empower health care providers to better characterize asthma disease burden in children. Identification of biomarkers of non-atopic asthma and the contribution of genetics and epigenetics to pediatric asthma burden remains a research need, which can potentially allow delivery of precision medicine to pediatric asthma. IMPACT: This review highlights asthma as a complex and heterogeneous disease and discusses recent advances in the understanding of the pathobiology of asthma to demonstrate the need for a more nuanced definitions of asthma. We review current knowledge of asthma phenotypes and endotypes and put forth an approach to endotyping asthma that may be useful for defining asthma for clinical care as well as for future research studies in the realm of personalized medicine for asthma.

Report of prenatal maternal demoralization and material hardship and infant rhinorrhea and watery eyes.

BACKGROUND: Previously, we found that reported infant rhinorrhea and watery eyes without a cold (RWWC) predicted school age exercise-induced wheezing, emergency department visits, and respiratory-related hospitalizations for asthma. These findings appeared independent of infant wheezing and allergy. Overall, we theorize that prenatal material hardship and psychosocial distress can induce infant dysregulation in the autonomic nervous system leading to infant RWWC and school age exercise-induced wheezing. OBJECTIVE: To test the hypotheses that indicators of prenatal stress and measures of maternal demoralization, which can alter infant autonomic nervous system responses, would predict infant RWWC. METHODS: In a prospective birth cohort of urban children (n = 578), pregnant women were queried in the third trimester about material hardship and maternal demoralization using validated instruments. Child RWWC was queried every 3 months in infancy. RESULTS: Notably, 44% of the mothers reported not being able to afford at least one of the basic needs of daily living during pregnancy, and children of those mothers were more likely to have infant RWWC (P < .001). The children had an increased risk of RWWC with increasing maternal demoralization during pregnancy (P < .001). In models controlling for sex, race and ethnicity, maternal asthma, maternal allergy, smoker in the home (pre- or postnatal), prenatal pesticide exposure, and older siblings, RWWC was predicted by mother's report of material hardship (relative risk, 1.22; P = .021) and maternal demoralization (relative risk, 1.14; P = .030). CONCLUSION: These results suggest an association between material hardship and psychological distress during pregnancy and RWWC in infancy, further supporting a link between infant autonomic dysregulation and RWWC.

Vaping associated lung injury: A potentially life-threatening epidemic in US youth.

BACKGROUND: The Center for Disease Control (CDC) has identified a national outbreak in the United States of over 2600 cases of e-cigarette or vaping product use-associated lung injury (EVALI), including 60 deaths as of January 2020. We describe our experience in six adolescents. MATERIAL AND METHODS: We identified all pediatric patients diagnosed with EVALI by CDC guidelines over a 6-month period at our health system. Clinical presentation, hospital course, and imaging were reviewed. RESULTS: Six patients were identified (three males, three females; median age 18.5 years). Presenting symptoms varied, including constitutional, gastrointestinal, neurologic, and respiratory complaints with pulmonary symptomatology becoming the dominant feature of the illness. Three patients required intensive care unit-level care, one of whom expired 36 days after presentation. Three had bronchoalveolar lavage, two with evidence of lipid-laden macrophages. Four had pulmonary function testing with various results. Admission chest radiographs in all revealed bibasilar interstitial infiltrate which rapidly progressed. Five patients had computed tomography chest imaging demonstrating: confluent pulmonary infiltrates with subpleural sparing (n = 2), generalized ground-glass opacities (n = 1), patchy ground-glass opacities (n = 1) and a reticulonodular pattern (n = 1). Brain magnetic resonance imaging (MRI) obtained in two patients was normal in one and showed a focal signal abnormality in the corpus callosum in one. CONCLUSION: We describe the clinical course and radiologic findings of EVALI in our adolescent patients and present a new finding in the brain not yet described in the literature. Given the diversity of presenting symptoms, a high level of suspicion for EVALI is necessary for patients reporting vaping product use regardless of the presence of pulmonary complaints. Brain MRI should be strongly considered in patients with neurologic symptoms.

The Pseudomonas aeruginosa product pyochelin interferes with Trypanosoma cruzi infection and multiplication in vitro.

BACKGROUND: Bacteria are sources of numerous molecules used in treatment of infectious diseases. We investigated effects of molecules produced by 26 Pseudomonas aeruginosa strains against infection of mammalian cell cultures with Trypanosoma cruzi, the aetiological agent of Chagas disease. METHODS: Vero cells were infected with T. cruzi in the presence of wild-type P. aeruginosa supernatants or supernatants of mutants with defects in the production of various virulence, quorum sensing and iron acquisition factors. Quantification of T. cruzi infection (percentage of infected cells) and multiplication (number of amastigotes per infected cell) was performed and cell viability was determined. RESULTS: Wild-type P. aeruginosa products negatively affected T. cruzi infection and multiplication in a dose-dependent manner, without evident toxicity for mammalian cells. PvdD/pchE mutation (loss of the P. aeruginosa siderophores pyoverdine and pyochelin) had the greatest impact on anti-T. cruzi activity. Negative effects on T. cruzi infection by pure pyochelin, but not pyoverdine, or other P. aeruginosa exoproducts studied, were quantitatively similar to the effects of benznidazole, the current standard therapy against T. cruzi. CONCLUSIONS: The P. aeruginosa product pyochelin showed promising activity against T. cruzi and might become a new lead molecule for therapy development.

Global H-NS counter-silencing by LuxR activates quorum sensing gene expression.

Bacteria coordinate cellular behaviors using a cell-cell communication system termed quorum sensing. In Vibrio harveyi, the master quorum sensing transcription factor LuxR directly regulates >100 genes in response to changes in population density. Here, we show that LuxR derepresses quorum sensing loci by competing with H-NS, a global transcriptional repressor that oligomerizes on DNA to form filaments and bridges. We first identified H-NS as a repressor of bioluminescence gene expression, for which LuxR is a required activator. In an hns deletion strain, LuxR is no longer necessary for transcription activation of the bioluminescence genes, suggesting that the primary role of LuxR is to displace H-NS to derepress gene expression. Using RNA-seq and ChIP-seq, we determined that H-NS and LuxR co-regulate and co-occupy 28 promoters driving expression of 63 genes across the genome. ChIP-PCR assays show that as autoinducer concentration increases, LuxR protein accumulates at co-occupied promoters while H-NS protein disperses. LuxR is sufficient to evict H-NS from promoter DNA in vitro, which is dependent on LuxR DNA binding activity. From these findings, we propose a model in which LuxR serves as a counter-silencer at H-NS-repressed quorum sensing loci by disrupting H-NS nucleoprotein complexes that block transcription.

The Role of Environmental Controls in Managing Asthma in Lower-Income Urban Communities.

Children living in lower-income urban communities are at much greater risk of developing asthma, going to the emergency department for an asthma attack and being hospitalized for asthma than children living in upper- and middle-income communities. For many asthmatic children living in urban communities, especially those with greater morbidity, the allergic pathway is important in the etiology of the disease. The stages of developing allergic disease can be divided into the onset of allergic sensitization, development of allergic disease and subsequent exacerbations, and it is useful to consider the relevance of interventions at each of these stages. Indoor allergens and environmental exposures are a major contributor to allergic disease, particularly among lower socioeconomic status, urban, minority communities. These exposures include allergens, environmental tobacco smoke, combustion by-products, and mold, all of which can play an important role in asthma progression as well as morbidity. These exposures are often not found in isolation and thus these concomitant exposures need to be considered when conducting environmental interventions. There have been numerous studies looking at both primary and tertiary prevention strategies and the impact on allergic sensitization and asthma with varied results. While the outcomes of these studies have been mixed, what has emerged is the need for tertiary interventions to be targeted to the individual and to reduce all relevant exposures to which an asthmatic child is exposed and sensitized. In addition, effective intervention strategies must also consider other social determinants of asthma morbidity impacting low socioeconomic, urban communities.

C. elegans avoids toxin-producing Streptomyces using a seven transmembrane domain chemosensory receptor.

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator-prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic acid, which is sensed by SRB-6. This behavioral adaptation represents an important strategy for the nematode, which utilizes specialized sensory organs and a chemoreceptor that is tuned to recognize the bacteria. These findings provide a window into the molecules and organs used in the coevolutionary arms race between predator and potential prey.