Endotypes of difficult-to-control asthma in inner-city African American children

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6–17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population

ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed

An ostomy self-management telehealth intervention for cancer survivors: Technology-related findings from a randomized controlled trial

Background: An Ostomy Self-management Telehealth (OSMT) intervention by nurse educators and peer ostomates can equip new ostomates with critical knowledge regarding ostomy care. A telehealth technology assessment aim was to measure telehealth engineer support requirements for telehealth technology–related (TTR) incidents encountered during OSMT intervention sessions held via a secure cloud-based videoconferencing service, Zoom for Healthcare. Objective: This paper examines technology-related challenges, issues, and opportunities encountered in the use of telehealth in a randomized controlled trial intervention for cancer survivors living with a permanent ostomy. Methods: The Arizona Telemedicine Program provided telehealth engineering support for 105 OSMT sessions, scheduled for 90 to 120 minutes each, over a 2-year period. The OSMT groups included up to 15 participants, comprising 4-6 ostomates, 4-6 peer ostomates, 2 nurse educators, and 1 telehealth engineer. OSMT-session TTR incidents were recorded contemporaneously in detailed notes by the research staff. TTR incidents were categorized and tallied. Results: A total of 97.1% (102/105) OSMT sessions were completed as scheduled. In total, 3 OSMT sessions were not held owing to non–technology-related reasons. Of the 93 ostomates who participated in OSMT sessions, 80 (86%) completed their OSMT curriculum. TTR incidents occurred in 36.3% (37/102) of the completed sessions with varying disruptive impacts. No sessions were canceled or rescheduled because of TTR incidents. Disruptions from TTR incidents were minimized by following the TTR incident prevention and incident response plans. Conclusions: Telehealth videoconferencing technology can enable ostomates to participate in ostomy self-management education by incorporating dedicated telehealth engineering support. Potentially, OSMT greatly expands the availability of ostomy self-management education for new ostomates. Trial Registration: ClinicalTrials.gov NCT02974634; https://clinicaltrials.gov/ct2/show/NCT02974634 ©Ronald S Weinstein, Michael J Holcomb, Julia Mo, Peter Yonsetto, Octavio Bojorquez, Marcia Grant, Christopher S Wendel, Nancy J Tallman, Elizabeth Ercolano, Zuleyha Cidav, Mark C Hornbrook, Virginia Sun, Ruth McCorkle, Robert S Krouse.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Endotypes of difficult-to-control asthma in inner-city African American children.

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6-17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population