Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Prehospital Pediatric Emergency Training Using Augmented Reality Simulation: A Prospective, Mixed Methods Study.

OBJECTIVE: Pediatric emergencies are high-stakes yet low-volume clinical encounters for emergency medical services (EMS) clinicians, necessitating innovative approaches to training. We sought to explore the acceptability, usability, and ergonomics of a novel augmented reality (AR) software for EMS crisis management training. METHODS: This was a prospective, mixed-methods study employing qualitative and quantitative analyses. We enrolled emergency medical technicians (EMTs) and paramedics at a municipal fire service in Northern California. We ran the Chariot Augmented Reality Medical simulation software (Stanford Chariot Program, Stanford University, Stanford, CA) on the ML1 headset (Magic Leap, Inc., Plantation, FL), which enabled participants to view an AR image of a patient overlaid with real-world training objects. Participants completed a simulation of a pediatric hypoglycemia-induced seizure and cardiac arrest. Participants subsequently engaged in structured focus group interviews assessing acceptability, which we coded and thematically analyzed. We evaluated the usability of the AR system and ergonomics of the ML1 headset using previously validated scales, and we analyzed findings with descriptive statistics. RESULTS: Twenty-two EMS clinicians participated. We categorized focus group interview statements into seven domains after an iterative thematic analysis: general appraisal, realism, learning efficacy, mixed reality feasibility, technology acceptance, software optimization, and alternate use cases. Participants valued the realism and the mixed reality functionality of the training simulation. They reported that AR could be effective for practicing pediatric clinical algorithms and task prioritization, building verbal communication skills, and promoting stress indoctrination. However, participants also noted challenges with integrating AR images with real-world objects, the learning curve required to adapt to the technology, and areas for software improvement. Participants favorably evaluated the ease of use of the technology and comfortability of wearing the hardware; however, most participants reported that they would need technical support. CONCLUSION: Participants positively evaluated the acceptability, usability, and ergonomics of an AR simulator for pediatric emergency management training, and participants identified current technological limitations and areas for improvement. AR simulation may serve as an effective training adjunct for prehospital clinicians.

Inhaled endotoxin induces a systemic neutrophil response without affecting cardiovascular measures in a randomized cross-over exposure study.

OBJECTIVE: The gram-negative bacterial cell wall component endotoxin (lipopolysaccharide, LPS) is a key component of particulate matter (PM). PM exposure is associated with cardiovascular morbidity and mortality. However, the contribution of individual components of PM to acute and chronic cardiovascular measures is not clear. This study examines whether systemic inflammation induced by LPS inhalation causes acute changes in cardiovascular physiology measures. MATERIALS AND METHODS: In this double blinded, placebo-controlled crossover study, fifteen adult volunteers underwent inhalation exposure to 20,000 EU Clinical Center Reference Endotoxin (CCRE). Peripheral blood and induced sputum neutrophils were obtained at baseline and six hours post-exposure. Blood pressure, measures of left ventricular function (ejection fraction (LVEF) and global longitudinal strain (LVGLS)), and indices of endothelial function (flow mediated dilation (FMD) and velocity time integral during hyperemia (VTIhyp)) were measured before and after treatment. Wilcoxon sign-rank tests and linear mixed models were used for statistical analysis. RESULTS: In comparison with normal saline, LPS inhalation resulted in significant increases in peripheral blood and sputum neutrophils but was not associated with significant alterations in blood pressure, LVGLS, LVEF, FMD, or VTIhyp. DISCUSSION AND CONCLUSIONS: In healthy adults, systemic inflammation after LPS inhalation was not associated with acute changes in cardiovascular physiology. Larger studies are needed to investigate the effects of other PM components on inflammation induced cardiovascular dysfunction.

Environmental justice and allergic disease: A Work Group Report of the AAAAI Environmental Exposure and Respiratory Health Committee and the Diversity, Equity and Inclusion Committee.

Environmental justice is the concept that all people have the right to live in a healthy environment, to be protected against environmental hazards, and to participate in decisions affecting their communities. Communities of color and low-income populations live, work, and play in environments with disproportionate exposure to hazards associated with allergic disease. This unequal distribution of hazards has contributed to health disparities and is largely the result of systemic racism that promotes segregation of neighborhoods, disinvestment in predominantly racial/ethnic minority neighborhoods, and discriminatory housing, employment, and lending practices. The AAAAI Environmental Exposure and Respiratory Health Committee and Diversity, Equity and Inclusion Committee jointly developed this report to improve allergy/immunology specialists' awareness of environmental injustice, its roots in systemic racism, and its impact on health disparities in allergic disease. We present evidence supporting the relationship between exposure to environmental hazards, particularly at the neighborhood level, and the disproportionately high incidence and poor outcomes from allergic diseases in marginalized populations. Achieving environmental justice requires investment in at-risk communities to increase access to safe housing, clean air and water, employment opportunities, education, nutrition, and health care. Through policies that promote environmental justice, we can achieve greater health equity in allergic disease.

IL-1 receptor antagonist attenuates proinflammatory responses to rhinovirus in airway epithelium.

BACKGROUND: Rhinoviruses (RVs) are the most common trigger for asthma exacerbations, and there are currently no targeted therapies for viral-induced asthma exacerbations. RV infection causes neutrophilic inflammation, which is often resistant to effects of glucocorticoids. IL-1 receptor antagonist (IL-1RA) treatment reduces neutrophilic inflammation in humans challenged with inhaled endotoxin and thus may have therapeutic potential for RV-induced asthma exacerbations. OBJECTIVE: We sought to test the hypothesis that IL-1RA treatment of airway epithelium reduces RV-mediated proinflammatory cytokine production, which is important for neutrophil recruitment. METHODS: Human bronchial epithelial cells from deceased donors without prior pulmonary disease were cultured at air-liquid interface and treated with IL-13 to approximate an asthmatic inflammatory milieu. Human bronchial epithelial cells were infected with human RV-16 with or without IL-1RA treatment. RESULTS: RV infection promoted the release of IL-1α and the neutrophil-attractant cytokines IL-6, IL-8, and CXCL10. Proinflammatory cytokine secretion was significantly reduced by IL-1RA treatment without significant change in IFN-ß release or RV titer. In addition, IL-1RA reduced MUC5B expression after RV infection without impacting MUC5AC. CONCLUSIONS: These data suggest that IL-1RA treatment significantly reduced proinflammatory cytokines while preserving the antiviral response. These results provide evidence for further investigation of IL-1RA as a novel targeted therapy against neutrophil-attractant cytokine release in RV-induced airway inflammatory responses.

Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: A randomized controlled trial.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses. OBJECTIVE: We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis. METHODS: We conducted a double-blind parallel design trial in patients with cat allergy. A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks, followed by 52 weeks of observation. Nasal allergen challenge (NAC), skin testing, and blood and nasal samples were obtained throughout the study. RESULTS: At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as area under the curve [AUC0-1h] and as peak score [Peak0-1h] during the first hour after NAC) were significantly reduced in patients receiving tezepelumab/SCIT compared to SCIT alone. At week 104, one year after stopping treatment, the primary end point TNSS AUC0-1h was not significantly different in the tezepelumab/SCIT group compared to SCIT alone, while TNSS Peak0-1h was significantly lower in those receiving combination treatment versus SCIT. Transcriptomic analysis of nasal epithelial samples demonstrated that treatment with the combination of SCIT/tezepelumab, but neither monotherapy, caused persistent downregulation of a gene network related to type 2 inflammation that was associated with improvement in NAC responses. CONCLUSIONS: Inhibition of TSLP augments the efficacy of SCIT during therapy and may promote tolerance after a 1-year course of treatment. (ClinicalTrials.gov NCT02237196).

Assessment of Pregnancy-Related Telehealth Interventions in the United States: A 10-Year Scoping Review.

Introduction: Telehealth use in obstetrics has been demonstrated to improve efficiency, access to care, and pregnancy outcomes. Despite reported successful implementation of these programs, information regarding the program variations and its impact on health care costs and outcomes are scarce. Methods: This is a scoping review of pregnancy-related telehealth studies to understand the current landscape of pregnancy-related telehealth interventions as well as to subset those that are used in high-risk pregnancies. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework to guide this review. Results: A total of 70 articles were included in this scoping review. Of those, 53 (75.7%) studies included a pregnant population and 17 (24.3%) studies focused on a rural and/or urban population. Most studies (n = 56; 80%) included some form of synchronous interaction between provider and participant. Patient outcomes included maternal/infant health outcomes (n = 41; 44.1%), patient satisfaction (n = 9; 9.7%), and attendance/compliance (n = 5; 5.4%). Provider-level outcomes included knowledge change (n = 11; 11.8%) and self-efficacy (n = 3; 3.2%). Other outcomes included assessment of costs and patient/provider feasibility and acceptability of the intervention. Overall, there has been a growing trend in articles published on pregnancy-related telehealth studies since 2011, with 2018 having the most publications in a single year. Conclusion: This review suggests a steadily growing body of literature on pregnancy-related telehealth interventions; however, more research is needed to better understand outcomes of telehealth for pregnancy-related care, especially related to patient satisfaction, health disparities, and cost-benefit.

Race-specific spirometry equations may overestimate asthma control in Black children and adolescents.

BACKGROUND: A growing body of evidence suggests that use of race terms in spirometry reference equations underestimates disease burden in Black populations, which may lead to disparities in pulmonary disease outcomes. Data on asthma-specific health consequences of using race-adjusted spirometry are lacking. METHODS: We performed a secondary analysis of 163 children from two observational asthma studies to determine the frequencies of participants with ppFEV1 < 80% (consistent with uncontrolled asthma) or ppFEV1 ≥ 80% using race-specific (GLI-African American or Caucasian) vs. race-neutral (GLI-Global) spirometry and their alignment with indicators of asthma control (Asthma Control Test™, ACT). Comparisons of mean ppFEV1 values were conducted using Wilcoxon matched-pairs signed-rank tests. Two group comparisons were conducted using Wilcoxon rank-sum tests. RESULTS: Data from 163 children (100 Black, 63 White) were analyzed. Mean ppFEV1 was 95.4% (SD 15.8) using race-specific spirometry and 90.4% (16.3) using race-neutral spirometry (p < 0.0001). Among 54 Black children with uncontrolled asthma (ACT ≤ 19), 20% had ppFEV1 < 80% using race-specific spirometry compared to 40% using race-neutral spirometry. In Black children with controlled asthma (ACT > 19), 87% had ppFEV1 ≥ 80% using race-specific compared to 67% using race-neutral spirometry. Children whose ppFEV1 changed to ≤ 80% with race-neutral spirometry had lower FEV1/FVC compared to those whose ppFEV1 remained ≥ 80% [0.83 (0.07) vs. 0.77 (0.05), respectively; p = 0.04], suggesting greater airway obstruction. Minimal changes in alignment of ppFEV1 with ACT score were observed for White children. CONCLUSIONS: Use of race-specific reference equations in Black children may increase the risk of inappropriately labeling asthma as controlled.

Wildfire smoke exposure and early childhood respiratory health: a study of prescription claims data.

Wildfire smoke is associated with short-term respiratory outcomes including asthma exacerbation in children. As investigations into developmental wildfire smoke exposure on children's longer-term respiratory health are sparse, we investigated associations between developmental wildfire smoke exposure and first use of respiratory medications. Prescription claims from IBM MarketScan Commercial Claims and Encounters database were linked with wildfire smoke plume data from NASA satellites based on Metropolitan Statistical Area (MSA). A retrospective cohort of live infants (2010-2016) born into MSAs in six western states (U.S.A.), having prescription insurance, and whose birthdate was estimable from claims data was constructed (N = 184,703); of these, gestational age was estimated for 113,154 infants. The residential MSA, gestational age, and birthdate were used to estimate average weekly smoke exposure days (smoke-day) for each developmental period: three trimesters, and two sequential 12-week periods post-birth. Medications treating respiratory tract inflammation were classified using active ingredient and mode of administration into three categories:: 'upper respiratory', 'lower respiratory', 'systemic anti-inflammatory'. To evaluate associations between wildfire smoke exposure and medication usage, Cox models associating smoke-days with first observed prescription of each medication category were adjusted for infant sex, birth-season, and birthyear with a random intercept for MSA. Smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications (1-12 weeks: hazard ratio (HR) = 1.094 per 1-day increase in average weekly smoke-day, 95%CI: (1.005,1.191); 13-24 weeks: HR = 1.108, 95%CI: (1.016,1.209)). Protective associations were observed during gestational windows for both lower respiratory and systemic anti-inflammatory medications; it is possible that these associations may be a consequence of live-birth bias. These findings suggest wildfire smoke exposure during early postnatal developmental periods impact subsequent early life respiratory health.

Changes in Arkansans' attitudes toward pharmacist involvement and regulation of medical cannabis following its availability in Arkansas.

BACKGROUND: Pharmacists are likely to encounter questions from patients regarding medical cannabis (MC). This serves as an opportunity for pharmacists to provide reliable medical information about MC dosing, drug interactions, and impact on preexisting health conditions. OBJECTIVES: This study examined changes in perceptions of the Arkansan community toward MC regulation and pharmacist involvement in MC dispensing after MC products became available in Arkansas. METHODS: A longitudinal, self-administered online survey was conducted in February 2018 (baseline) and September 2019 (follow-up). Baseline participants were recruited through Facebook posts, emails, and printed flyers. Participants from the baseline survey (N = 1526) were invited to participate in the follow-up survey. Paired t tests were used to determine changes in responses, and multivariable regression analysis was used to identify factors associated with follow-up perceptions. RESULTS: Participants (n = 607, response rate 39.8%) started the follow-up survey, resulting in 555 usable surveys. The largest group of participants was 40-64 year old (40.9%). The majority were female (67.9%), white (90.6%), and reported past 30-day cannabis use (83.1%). Compared to baseline, participants preferred less regulatory control of MC. They were also less likely to agree that pharmacists helped improve MC-related patient safety. Participants favoring less MC regulation were more likely to report 30-day cannabis use and perceived cannabis to have low health risk. Past 30-day cannabis use was also significantly associated with disagreement that pharmacists improve patient safety and are well-trained to provide MC counseling. CONCLUSION: After MC product availability, Arkansans' attitudes changed toward less MC regulation and less agreement with the pharmacist's role in improving MC safety. These findings call for pharmacists to better promote their role in public health safety and demonstrate their knowledge concerning MC. Pharmacists should advocate for an expanded, active consultant role in dispensaries to improve safety of MC use.

Caribbean Latinx with moderate-severe asthma bear greater asthma morbidity than other Latinx.

BACKGROUND: Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization. OBJECTIVES: This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups. METHODS: Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [C&D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and C&D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (C&D [n = 56] and PR [n = 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression. RESULTS: CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas C&D only had increased odds of exacerbations compared to OHL. PR compared to C&D had greater odds of ED/UC and health care utilization. CONCLUSIONS: CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.

Utilization of Remote Patient Monitoring Within the United States Health Care System: A Scoping Review.

Introduction: Limited information exists on the landscape of studies and policies for remote patient monitoring (RPM) in the United States. Methods: We conducted a scoping review to assess (1) for which adult patient populations and health care needs is RPM being used and (2) the landscape of national- and state-level reimbursement policies for RPM. This study was guided by the Arksey and O'Malley methodological framework for scoping reviews and the Joanna Briggs Institute Manual for Evidence Synthesis. Results: A total of 399 articles were included in our final sample: 268 study articles and 131 articles of gray literature (e.g., websites, legislative bills). RPM-related articles rose drastically from 2015 to 2021, and the vast majority of articles were peer-reviewed journal articles. Of the study articles, prospective cohort studies were the most common study method, with m-health/smart watches being the most common RPM modality. RPM was found to be most commonly tested within patients with cardiovascular diseases, and the most common outcomes measured were usability and feasibility. Gray literature found 36 U.S. state Medicaid programs had reimbursement policies for RPM in 2021; however, 28 of those had at least one restriction on reimbursement (e.g., limited to specific providers). Conclusions: Despite the rapid growth in the literature on RPM and the adoption of reimbursement policies, retrospective, population-level studies, large randomized controlled trials, studies with a focus on additional favorable outcomes (e.g., quality of life), and studies evaluating trends in RPM reimbursement policies are lacking in the current literature.

Stressful Life Events and Near-term Suicidal Risk in a Clinical Population.

The present study examined 22 specific stressful life events (SLEs) in relation to recent and prospective suicidal thoughts and behaviors (STBs). The effect of assessment method (self-report vs. chart-based ratings) and inpatient/outpatient status was also investigated. Past 3-month STBs and SLEs were assessed for 1,058 psychiatric patients; 696 completed one-month follow-up assessments. SLEs were common, with 684 participants (64.7%) reporting at least one. Total number of SLEs correlated with recent and prospective STB. A higher incidence of SLE's was found with self-report vs. chart-based measures (on 20 SLEs) and inpatients vs. outpatients (on 7 SLEs). SLEs of interpersonal rejection and loss, homelessness and academic failure offered elevated risk. In sum, SLEs are common and associated with STBs in psychiatric patients. SLEs of interpersonal rejection and loss, homelessness and academic failure may merit increased clinical attention.

World Trade Center dust induces nasal and neurological tissue injury while propagating reduced olfaction capabilities and increased anxiety behaviors.

Objective: Previous in vitro and in vivo World Trade Center particulate matter (WTCPM) exposure studies have provided evidence of exposure-driven oxidative/nitrative stress and inflammation on respiratory tract and aortic tissues. What remains to be fully understood are secondary organ impacts due to WTCPM exposure. This study was designed to test if WTC particle-induced nasal and neurologic tissue injury may result in unforeseen functional and behavioral outcomes.Material and Methods: WTCPM was intranasally administered in mice, evaluating genotypic, histopathologic, and olfaction latency endpoints.Results: WTCPM exposure was found to incite neurologic injury and olfaction latency in intranasally (IN) exposed mice. Single high-dose and repeat low-dose nasal cavity insults from WTCPM dust resulted in significant olfaction delays and enduring olfaction deficits. Anxiety-dependent behaviors also occurred in mice experiencing olfaction loss including significant body weight loss, increased incidence and time spent in hind stretch postures, as well as increased stationary time and decreased exploratory time. Additionally, WTCPM exposure resulted in increased whole brain wet/dry ratios and wet whole brain to body mass ratios that were correlated with exposure and increased exposure dose (p<0.05).Discussion: The potential molecular drivers of WTCPM-driven tissue injury and olfaction latency may be linked to oxidative/nitrative stress and inflammatory cascades in both upper respiratory nasal and brain tissues.Conclusion: Cumulatively, these data provide evidence of WTCPM exposure in relation to tissue damage related to oxidative stress-driven inflammation identified in the nasal cavity, propagated to olfactory bulb tissues and, potentially, over extended periods, to other CNS tissues.

Development of a screening protocol to identify persons who are responsive to wood smoke particle-induced airway inflammation with pilot assessment of GSTM1 genotype and asthma status as response modifiers.

BACKGROUND: We are currently screening human volunteers to determine their sputum polymorphonuclear neutrophil (PMN) response 6- and 24-hours following initiation of exposure to wood smoke particles (WSP). Inflammatory responders (≥10% increase in %PMN) are identified for their subsequent participation in mitigation studies against WSP-induced airways inflammation. In this report we compared responder status (<i>N</i> = 52) at both 6 and 24 hr time points to refine/expand its classification, assessed the impact of the GSTM1 genotype, asthma status and sex on responder status, and explored whether sputum soluble phase markers of inflammation correlate with PMN responsiveness to WSP. RESULTS: Six-hour responders tended to be 24-hour responders and vice versa, but 24-hour responders also had significantly increased IL-1beta, IL-6, IL-8 at 24 hours post WSP exposure. The GSTM1 null genotype significantly (<i>p</i> &lt; 0.05) enhanced the %PMN response by 24% in the 24-hour responders and not at all in the 6 hours responders. Asthma status enhanced the 24 hour %PMN response in the 6- and 24-hour responders. In the entire cohort (not stratified by responder status), we found a significant, but very small decrease in FVC and systolic blood pressure immediately following WSP exposure and sputum %PMNs were significantly increased and associated with sputum inflammatory markers (IL-1beta, IL-6, IL-8, and PMN/mg) at 24 but not 6 hours post exposure. Blood endpoints in the entire cohort showed a significant increase in %PMN and PMN/mg at 6 but not 24 hours. Sex had no effect on %PMN response. CONCLUSIONS: The 24-hour time point was more informative than the 6-hour time point in optimally and expansively defining airway inflammatory responsiveness to WSP exposure. GSTM1 and asthma status are significant effect modifiers of this response. These study design and subject parameters should be considered before enrolling volunteers for proof-of-concept WSP mitigation studies.

Impact of the COVID-19 pandemic on the clinical training of last year medical students in Mexico: a cross-sectional nationwide study.

BACKGROUND: The COVID-19 pandemic has brought unprecedented changes to medical education. However, no data are available regarding the impact the pandemic may have on medical training in Mexico. The aim of our study was to evaluate and identify the medical school students' perceptions of the changes in their clinical training due to the pandemic in Mexico. METHODS: This was a cross-sectional study where a previous validated online survey was translated and adapted by medical education experts and applied to senior medical students from March to April of 2021. The 16-item questionnaire was distributed online combining dichotomous, multiple-choice, and 5-point Likert response scale questions. Descriptive and multivariate analyses were performed to compare the student's perceptions between public and private schools. RESULTS: A total of 671 responses were included in the study period. Most participants were from public schools (81%) and female (61%). Almost every respondent (94%) indicated it was necessary to obtain COVID-19 education, yet only half (54%) received such training. Students in private schools were less likely to have their clinical instruction canceled (53% vs. 77%, p = 0.001) and more likely to have access to virtual instruction (46% vs. 22%, p = 0.001) when compared to students from public schools. Four out of every five students considered their training inferior to that of previous generations, and most students (82%) would consider repeating their final year of clinical training. CONCLUSIONS: The impact of the COVID-19 on medical education in Mexico has been significant. Most final-year medical students have been affected by the cancellation of their in-person clinical instruction, for which the majority would consider repeating their final year of training. Efforts to counterbalance this lack of clinical experience with virtual or simulation instruction are needed.

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.

Isolation of Rickettsia rickettsii in Rocky Mountain Spotted Fever Outbreak, Panama.

We report new cases of Rocky Mountain spotted fever in patients from Kinkantu, Ngäbe-Bugle indigenous comarca, Panama. We isolated Rickettsia rickettsii in cell culture after intraperitoneal inoculation of guinea pigs with tissues from a deceased patient. Our results indicate that Rocky Mountain spotted fever is emerging in this region.

Airway IL-1ß associates with IL-5 production following dust mite allergen inhalation in humans.

BACKGROUND: Preclinical studies implicate interleukin (IL)-1ß as a key mediator of asthma and have shown the efficacy of IL-1 antagonism for treatment of allergic airway inflammation; human studies in this area are lacking. OBJECTIVES: Our aim was to study the relationship of airway IL-1ß to features of acute allergen-induced asthma exacerbation in humans. METHODS: Dust mite-allergic adults with mild asthma underwent inhalation challenge with Dermatophagoides farinae. Fractional exhaled nitric oxide (FeNO), induced sputum and peripheral blood samples were obtained pre- and 24 h post-challenge. Spirometry was performed before and throughout the challenge at 10-min intervals, and allergen responsiveness was defined by a 20% fall in Forced Expiratory Volume in 1 s (FEV1). Sputum samples were analyzed for inflammatory cells, cytokines and chemokines. Multiple linear regression was employed to test the association between sputum IL-1ß concentration and biomarkers of T helper type 2 (T2)-dominant inflammation. RESULTS: Fourteen volunteers underwent inhaled allergen challenge. Allergen responsive volunteers showed a greater positive change in IL-1ß in sputum following allergen challenge compared to non-responders. Higher pre-challenge sputum IL-1ß was associated with greater increase in sputum IL-5 (p = 0.004), sputum eosinophils (p = 0.001) and blood IL-5 (p = 0.003) following allergen challenge. Allergen-induced sputum IL-1ß production was significantly associated with sputum and blood IL-5 (p < 0.001 and p = 0.007, respectively), sputum IL-4 (p = 0.001), IL-13 (p = 0.026), eosinophils (p = 0.008) and FeNO (p = 0.03). CONCLUSIONS: The positive association between production of IL-1ß and biomarkers of T2 inflammation, particularly IL-5, in humans is consistent with work in animal models that demonstrates a link between IL-1ß and the pathophysiology of allergic asthma. The role of IL-1ß in human asthma warrants further study.

Validation of an app-based portable spirometer in adolescents with asthma.

OBJECTIVES: Objective measurements of asthma impairment could aid teens in recognition of changes in asthma status over time. Ready access to a conventional spirometer is not realistic outside of the clinical setting. In this proof-of-concept study, we compared the performance of the VitalFlo mobile spirometer to the nSpire KoKo® sx1000 spirometer for accuracy in measuring Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC) in adolescents with asthma. METHODS: Two hundred forty pulmonary function measurements were collected from 48 adolescents with persistent asthma from the University of North Carolina's pediatric allergy and pulmonology subspecialty clinics. Participants performed spirometry with the nSpireKoKo® sx1000 spirometer and the VitalFlo spirometer during their clinic visits. 119 simulated FVC maneuvers were conducted on both devices to standardize measurements. Pearson correlations, Bland-Altman procedure, and two-sample comparison tests were performed to assess the relationship between the two spirometers. RESULTS: VitalFlo measurements were significantly highly correlated with nSpireKoKo® spirometer values for FEV1, (r2=0.721, [95% CI, 0.749 ± 0.120], P < 0.001) and moderately for FVC (r2= 0.617, [95% CI, 0.640 ± 0.130], P < 0.001) measurements. There were no statistically significant differences of the mean FEV1 (M = 0.00764, SD = 0.364, t(59)=0.16, P = 0.87) and FVC measurements (M = 0.00261, SD = 0.565, t(59)=0.036, P = 0.97.) between the VitalFlo and nSpireKoKo® systems. Both devices demonstrated significantly high correlation when comparing the automated FVC (r2 = 0.997, [95% CI, 1.00 ± 0.00974], P < 0.001) measurements. Bland-Altman plots did not demonstrate significant bias between devices for both FEV1 (0.00764 L) and FVC (0.00261 L) measurements. CONCLUSIONS: Lung function measurements from the VitalFlo mobile spirometer were comparable to a commercially-available spirometer commonly used in clinical settings. This validated app-based spirometer for home use has the potential to improve asthma self-management.