"Black People Like Me": A virtual conference series to engage underserved patients with asthma in patient centered outcomes research.

BACKGROUND: In response to racial inequity in asthma, asthma-related research among diverse patients is vital. However, people from historically marginalized groups are underrepresented in clinical and patient-centered outcomes research (PCOR). The "Black People Like Me" (BPLM) virtual conference series was developed to: (1) engage Black patients with asthma and their caregivers in education and discussions about asthma, and (2) encourage involvement in PCOR. Education about COVID-19 and COVID-19 vaccination was also incorporated. METHODS: The Project Advisory Group consisting of Black patients, clergy, physicians, and a program evaluator met monthly to develop BPLM. The program consisted of free one-hour virtual sessions held monthly for 6 months. BPLM was promoted through the Allergy & Asthma Network website, emails, social media, and personal contacts with a recruitment goal of ≥ 100 Black patients with asthma or caregivers. Program evaluations, interactive polling questions during each session, and participant pre- and post-session tests were conducted. RESULTS: Sessions averaged 658 participants including Black patients, family members, caregivers, Black clergy, health care providers, and other concerned community. Overall, 77% of participants strongly agreed with satisfaction with the sessions. Pre- and post-tests demonstrated that participants exhibited growth in knowledge regarding asthma risk, PCOR, and PCOR research opportunities for patients, exhibited preexisting and sustained knowledge regarding COVID-19 vaccination and side effects, and demonstrated an increased sense of empowerment during healthcare visits. CONCLUSIONS: BPLM demonstrated that a virtual platform can successfully engage Black communities. Incorporating clergy and religious organizations was critical in developing the trust of the Black community towards BPLM.

Corticosteroid exposure and cumulative effects in patients with eczema: Results from a patient survey.

BACKGROUND: Individuals with eczema may have substantial lifetime corticosteroid exposure, increasing the risk of corticosteroid-related side effects. OBJECTIVE: To conduct a patient survey evaluating corticosteroid exposure and its cumulative effects in individuals with eczema. METHODS: The multinational online survey was conducted between November 5, 2020, and January 11, 2021. Participants were aged 18 years or older and a patient (n = 1889) or a caregiver of a child (n = 271) diagnosed with having eczema by a medical professional. RESULTS: All participants reported using corticosteroids. Average duration of topical corticosteroid (TCS) use was 15.3 years in adults and 3.6 years in children; 75% used TCS 1 to 2 times a day and 50% applied TCS 15 to 30 days/mo. Frequency and duration could not be determined by varying prescription TCS potencies. Oral corticosteroid use was reported by 36% of the participants (23% for eczema), with a lifetime average of 8.4 courses in adults and 8.1 courses in children. Corticosteroids for non-eczema atopic conditions were reported by 49% of the participants. In participants using TCS, 83% of adults and 64% of children experienced worsening symptoms over time. Development of new symptoms and conditions increased with a greater number of corticosteroid treatments and longer duration of TCS use but may have been owing to eczema progression. Symptoms consistent with topical steroid withdrawal syndrome after TCS discontinuation were reported by many participants. CONCLUSION: Reported substantial corticosteroid exposure throughout their lifetime eczema experience placed participants at risk of negative outcomes. Corticosteroids are a critical component of eczema treatment for many patients. However, careful corticosteroid prescribing practices and monitoring are needed to avoid side effects. When possible, corticosteroid-sparing strategies should be explored.

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.

COVID-19 pandemic impact on telehealth use and perceptions for atopic and respiratory disease: Survey results.

Background: Telehealth use increased during the coronavirus disease 2019 (COVID-19) pandemic to provide patient care while deferring to social distancing recommendations. Objective: Health-care provider and patient surveys were conducted to assess the impact of COVID-19 on the use and perception of telehealth visits for atopic and respiratory diseases. Methods: Health-care provider (N = 200) and patient (N = 200) surveys were conducted in the United States between September and October, 2020, and January, 2021. The participants were required to have used telehealth before or after March 1, 2020, the cutoff date selected to represent the start of the COVID-19 pandemic. Results: Before the pandemic, 40% of the health-care provider participants were conducting telehealth visits, which increased to 100% after the pandemic started. The average time spent per telehealth visit with patients increased from 13 to 16 minutes. A higher percentage of family medicine physicians/pediatricians had access to most monitoring tools than allergy/dermatology specialists both before the pandemic and after the pandemic started. Practice expenses reportedly increased after the pandemic started for 42% of participants. Before the pandemic, 27% of the patient participants used telehealth, which increased to 94% after the pandemic started. Ratings of "good" or "excellent" for the overall telehealth experience by the health-care provider participants improved from 44% before to 60% after the pandemic started, and by the patient participants improved from 77% to 88%. The willingness by the health-care provider participants to recommend telehealth to colleagues improved from 73% before to 83% after the pandemic started. The willingness by the patient participants to use telehealth again dropped slightly, from 94% to 89%. Conclusion: Telehealth visits for atopic and respiratory diseases increased during the COVID-19 pandemic. Telehealth experiences were overall positive, particularly for the patients.

Impact of Social Determinants on the Burden of Asthma and Eczema: Results from a US Patient Survey.

INTRODUCTION: Little is known about how patients with asthma and eczema perceive their medical care and burden of disease. A survey was conducted to evaluate the perceptions among the general patient population with asthma and/or eczema regarding disease and treatment burden and barriers to adequate care. METHODS: An online survey was completed by market research panelists in the USA between March 24, 2020 and April 6, 2020. Eligible participants were at least 18 years of age and endorsed a diagnosis of asthma and/or eczema. Survey responses are described for all participants, by designated racial/ethnic groups, and by income level. RESULTS: In all, 841 participants completed the survey (asthma, n = 554; eczema, n = 398; both, n = 111; White, n = 421; Black, n = 252; Hispanic, n = 95; low income [less than $15,000/year], n = 99; higher income [at least $15,000/year], n = 713). More Black and Hispanic participants than White participants, and more participants with low income than higher income, endorsed health literacy as a barrier (e.g., filling out official documents, understanding written materials). Participants with low income were less likely than participants with higher income to have an asthma action plan (42% vs 53%, respectively) and to discuss asthma control with their healthcare provider (54% vs 69%). Black and Hispanic participants were more likely than White participants to have an emergency department visit (52% and 49% vs 31%, respectively) or hospitalization (31% and 39% vs 16%) for asthma within the last 12 months. Participants reporting low income indicated that they experienced eczema symptoms more frequently than participants with higher income; 35% of low-income participants vs 15% of higher-income participants reported that they had not tried any eczema treatments. Participants in all racial/ethnic and income-level groups reported that their asthma or eczema impacted their lifestyle and daily activities. CONCLUSION: More effective and culturally informed communication and education strategies to improve health information uptake and shared decision-making are needed to reduce the burdens of disease and treatment in highly impacted populations.

Disparities in asthma and eczema outcomes have been described in various populations. However, little is known about how these patient populations perceive their disease management or disease burden. A survey of 841 adults across diverse demographic groups in the USA with asthma and/or eczema was conducted to evaluate overall perceived disease burden and to specifically understand burden experiences by marginalized populations. In general, all participants indicated that asthma and eczema have a negative physical, emotional, and social impact on their lives. Some participants who identified as Black or Hispanic, and those with low income (less than $15,000/year), indicated greater difficulties in filling out paperwork or understanding written materials related to their condition than White participants or those with higher incomes. Black and Hispanic participants tended to receive asthma care in the emergency department or urgent care more than White participants and had more emergency department visits and hospitalizations than White Participants. Participants with low income were less likely to discuss their asthma management with their doctor than those with higher incomes and also indicated potential undertreatment of eczema. These results indicate that Black, Hispanic, or low-income patients may experience barriers to health equity. These barriers include lack of effective communication methods and materials to meet the needs of all patients, as well as the overall lack of quality healthcare access. These challenges must be addressed to overcome social disparities in health.

Needs assessment: knowledge of self-management of asthma for children with co-morbid physical and intellectual disabilities: brief report.

OBJECTIVES: The main goal of this study was to conduct a needs assessment to ascertain professionals' and parents' knowledge of and perceptions about education for self-management of asthma for children with physical and intellectual disabilities (IDs). Another goal was to understand needs for education of children with IDs about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus) and other infectious diseases. METHODS: Surveys, presented in the RedCap system, were administered online. Respondents (n = 498) were recruited through sites and listservs for children with disabilities and individuals with asthma. Respondents answered eight questions about knowledge and education for self-management of asthma for children with physical disabilities and IDs. Respondents answered four questions pertaining to management of coronavirus for children with IDs. RESULTS: Respondents' indicated that it would be easier to educate youth with mild or moderate versus severe levels of disabilities. Children with IDs may not receive the education they need to manage their asthma. When comparing those in different occupations, teachers reported lower knowledge for educating children with IDs about asthma management and coronavirus. CONCLUSIONS: Doctors and nurses can develop programs for children with physical disabilities and IDs. Programming for youth with severe impairments is needed and perhaps developmentally appropriate programming for youth with IDs will improve education of youth and, concomitantly improve their self-management of asthma and potentially quality of life. Educating teachers is critical specifically about asthma triggers, how to involve youth in self-care, and how to educate children with IDs about coronavirus.Abbreviations:U.S.: United States;IDs: intellectual disabilities.

Cannabis attitudes and patterns of use among followers of the Allergy & Asthma Network.

BACKGROUND: Cannabis use in patients with allergy/asthma, a high-risk group for adverse effects to cannabis, is unknown. OBJECTIVE: To determine the patterns of use and attitudes toward cannabis in patients with allergy/asthma. METHODS: An anonymous online survey on cannabis attitudes and use was conducted through the Adult Allergy & Asthma Network. The Asthma Control Test assessed asthma burden. Cluster analyses determined group phenotypes and factor analyses condensed cannabis subjective effects into similar response patterns. RESULTS: A total of 88 of 489 respondents (18.0%) currently use cannabis with most at the age of less than 50 years old, of female sex, and of White race. Of the noncannabis users (N = 401), 2.5% reported cannabis allergy. Cluster analysis revealed that a liberal attitude toward cannabis was associated with current cannabis use (P < .001). Among current cannabis users, 40.9% of their physicians inquired on cannabis use; only 37.5% of users wanted to discuss cannabis. In addition, 65.9% used cannabis for medical or medical/recreational purposes. Cannabinoids used were tetrahydrocannabinol (33.0%), cannabidiol (19.3%), or both (47.7%). Smoked and vaped cannabis were reported by 53.4% and 35.2%, respectively. Furthermore, 51 cannabis users (58.0%) reported current asthma with 39.2% uncontrolled; of these, 50% smoked cannabis. Compared with current participants with asthma not using cannabis, those currently using cannabis experienced similar levels of asthma control, quality of life, and frequency of asthma exacerbations. Positive effects were endorsed more than negative effects to cannabis (P < .001). Moreover, 19.3% of cannabis users reported coughing that was associated with smoking cannabis (P < .001). CONCLUSION: Cannabis was used by less than 20% of the respondents with positive effects more frequent than negative effects. Half of cannabis users with uncontrolled asthma smoke cannabis, but only a minority of the physicians inquire about its use.

Usefulness of harmonica playing to improve outcomes in patients with chronic obstructive pulmonary disease.

Pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) includes a multidisciplinary approach of exercise and pursed-lip diaphragmatic breathing. Pursed-lip diaphragmatic breathing reduces alveolar collapse during exhalation, and diaphragmatic breathing improves inspiratory pressures. Harmonica playing has maneuvers similar to those taught in pursed-lip diaphragmatic breathing, with diaphragmatic breathing to create musical tones. Hence, we designed a trial to determine whether patients with COPD would benefit from harmonica playing. COPD patients who completed pulmonary rehabilitation at least 6 months prior were eligible for this trial. Patients attended 12 weeks of harmonica training sessions for 2 hours a week and were encouraged to practice at home. Participants completed pre- and postspirometry testing, maximum inspired and expired pressure (PImax, PEmax) testing, and 6-minute walk tests. Eleven of the 14 participants completed the 12-week trial. PImax and PEmax increased by an average of 15.4 ± 12.0 cm H2O (P = 0.0017) and 14.4 ± 14.0 cm H2O (P = 0.0061), respectively. Additionally, 6-minute walk distance increased by approximately 60 m (61 ± 78, P = 0.03). This pilot study showed that a 12-week harmonica program significantly improved PImax, PEmax, and 6-minute walk distance in COPD patients after rehabilitation. Larger-scale harmonica studies are warranted to evaluate this program's adjunctive potential benefit to formal pulmonary rehabilitation.

Development of a novel clinical staging model for cirrhosis using the Nationwide Inpatient Sample.

Scoring systems such as Model for End-stage Liver Disease (MELD) and Child-Pugh are often used by clinicians to determine prognosis in patients with cirrhosis. Since clinical complications are important in determining cirrhosis outcomes, our goal was to use these to develop a novel prognostic staging model. Data from the Nationwide Inpatient Sample (NIS), years 2003-2011, were queried for records of patients over the age of 18 with cirrhosis excluding patients with prior or inpatient liver transplantation. The primary outcome was inpatient mortality with focus on cirrhosis-related complications: non-bleeding esophageal varices, variceal hemorrhage, ascites, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS). Of 59 862 903 hospitalizations, 824 783 (1.4%) with cirrhosis were identified. Overall mortality was 7% with two-thirds (66%) of deaths occurring in patients with a decompensating event, defined as variceal hemorrhage, ascites, HE, SBP, and/or HRS. Overall mortality rates decreased from 2003 to 2011 (9.0-6.0%), in both compensated and decompensated groups. Mortality was higher in patients with variceal haemorrhage (OR 1.56; p<0.05), HE (OR 1.75; p<0.05), SBP (OR 2.64; p<0.05) and HRS (OR 9.10; p<0.05) compared with patients with no complications. HRS had the highest mortality, whether alone or in combination with another event such as HE (OR 12.40; p<0.05) or SBP (OR 12.64; p<0.05). Cirrhosis inpatient outcomes are related to the severity of liver disease, with more severe complications such as HE, SBP, and HRS having the most significant effect on inpatient mortality, and are utilised in this novel four-stage clinical model.

Office Spirometry in Primary Care for the Diagnosis and Management of COPD: National Lung Health Education Program Update.

The use of office spirometry was recommended by the National Lung Health Education Program (NLHEP) consensus conference in 1999 for detection and management of COPD. Since that time, spirometry utilization has increased, but its role in the diagnosis of COPD is still evolving. This update reviews the role of spirometry for screening and case finding in COPD as well as for asthma. Spirometry has been used for disease management in patients with airway obstruction, with varying results. The diagnostic criteria for COPD using spirometry have also evolved in the past 17 years, with differences arising between the Global Initiative for Chronic Obstructive Lung Disease and NLHEP recommendations. More sophisticated spirometers as well as new reference equations are widely available. Standardization guidelines from the American Thoracic Society/European Respiratory Society published in 2005 provide a robust framework for performing and interpreting spirometry, but clinicians still need hands-on training and meaningful feedback to perform high-quality spirometry in the office setting.

Recombinant proteins of Zaire ebolavirus induce potent humoral and cellular immune responses and protect against live virus infection in mice.

Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death. Questions remain with regard to the few survivors of infection, who manage to mount an effective adaptive immune response. These questions concern the humoral and cellular components of this response, and whether such a response can be elicited by an appropriate prophylactic vaccine. The data reported herein describe the production and evaluation of a recombinant subunit Ebola virus vaccine candidate consisting of insect cell expressed Zaire ebolavirus (EBOV) surface glycoprotein (GP) and the matrix proteins VP24 and VP40. The recombinant subunit proteins are shown to be highly immunogenic in mice, yielding both humoral and cellular responses, as well as highly efficacious, providing up to 100% protection against a lethal challenge with live virus. These results demonstrate proof of concept for such a recombinant non-replicating vaccine candidate in the mouse model of EBOV which helps to elucidate immune correlates of protection and warrants further development.

Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P < 0.0001). Vaccination also decreased signs of pneumonic plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 µg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection.

Phase I/II randomized double-blind study of the safety and immunogenicity of a nonadjuvanted vero cell culture-derived whole-virus H9N2 influenza vaccine in healthy adults.

Studies on candidate pandemic vaccines against avian influenza viruses have focused on H5N1, but viruses of other subtypes, such as A/H9N2, are also considered to have pandemic potential. We investigated the safety and immunogenicity of two immunizations with one of five different antigen doses (ranging from 3.75 to 45 µg of hemagglutinin antigen) of a nonadjuvanted whole-virus G9 lineage H9N2 influenza virus vaccine in healthy adults aged 18 to 49 years. The antibody responses were measured by hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays. To investigate a hypothesis that previous exposure to H2N2 viruses in subjects born in or before 1968 might prime for more robust antibody responses to H9N2 vaccination than that in subjects born after 1968, a post hoc age-stratified analysis of antibody responses was done. Both vaccinations in all dose groups were safe and well tolerated. No vaccine-related serious adverse events were reported, and the majority of the adverse reactions were rated as mild. The rates of injection site reactions were lower in the 3.75-µg- and 7.5-µg-dose groups than those in the higher-dose groups; the rates of systemic reactions were similar across all dose groups. The seroprotection rates among the different dose groups 21 days after the second immunization ranged from 52.8% to 88.9% as measured by HI assay, from 88.7% to 98.1% or 82.7% to 96.2% as measured by MN assay (MN titer cutoffs, 1:40 and 1:80, respectively), and from 94.2% to 100% as measured by SRH assay. Higher antibody responses were not induced in subjects born in or before 1968. These data indicate that a nonadjuvanted whole-virus H9N2 vaccine is well tolerated and immunogenic in healthy adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01320696.).

Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses.

Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal. Importance: Three related viruses belonging to the genus Alphavirus cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV). Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the surface proteins of all three viruses. In this report we demonstrate in both mice and macaques that this combined vaccine is safe, generates a strong immune response, and protects against aerosol challenge with the viruses that cause Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis.

Validation of Rules of Two™ as a paradigm for assessing asthma control.

Assessing asthma control at each patient encounter is an essential task to determine pharmacologic requirements. Rules of Two (Ro2) was created from the original 1991 National Asthma Education Program guidelines to determine the need for controller therapy. This study determined the degree of agreement between Ro2 and the Expert Panel Report (EPR-3) definition of "in control" asthma and compared that value with the Asthma Control Test (ACT) in a group of asthmatics for the purpose of validating this tool. Patients with documented asthma were randomized to complete Ro2 or ACT prior to being assessed for asthma control by certified asthma educators using an EPR-3 template. Assessments occurred in either a specialty asthma clinic or at a local health fair. Patients were also queried for their personal assessment of asthma control. The primary statistical methodology employed was the degree of agreement (kappa) between each survey tool and the EPR-3 template. Of 150 patients, 72% did not have their asthma in control, based on the EPR-3 template. Ro2 identified 58% of patients not in control of their asthma, whereas ACT identified 36%, with kappa scores of 0.41 for Ro2 and 0.37 for ACT compared with the EPR-3 template. These were not significantly different. Of the 150 patients, 75% considered their asthma in control based on self-assessments, with a kappa of 0.23. In 14 of 73 ACT questionnaires, scores were not added or were misadded. Eliminating evaluation of static lung function significantly improved both kappa scores of Ro2 and ACT. In conclusion, Ro2 identifies patients with uncontrolled asthma as well as ACT and may be useful to the primary assessing clinician in determining asthma control.

Venezuelan equine encephalitis virus replicon particle vaccine protects nonhuman primates from intramuscular and aerosol challenge with ebolavirus.

There are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. Previously, a replicon vaccine based on Venezuelan equine encephalitis virus (VEEV) demonstrated protective efficacy against Marburg virus in nonhuman primates. Here, we report the protective efficacy of Sudan virus (SUDV)- and Ebola virus (EBOV)-specific VEEV replicon particle (VRP) vaccines in nonhuman primates. VRP vaccines were developed to express the glycoprotein (GP) of either SUDV or EBOV. A single intramuscular vaccination of cynomolgus macaques with VRP expressing SUDV GP provided complete protection against intramuscular challenge with SUDV. Vaccination against SUDV and subsequent survival of SUDV challenge did not fully protect cynomolgus macaques against intramuscular EBOV back-challenge. However, a single simultaneous intramuscular vaccination with VRP expressing SUDV GP combined with VRP expressing EBOV GP did provide complete protection against intramuscular challenge with either SUDV or EBOV in cynomolgus macaques. Finally, intramuscular vaccination with VRP expressing SUDV GP completely protected cynomolgus macaques when challenged with aerosolized SUDV, although complete protection against aerosol challenge required two vaccinations with this vaccine.

Designing and testing broadly-protective filoviral vaccines optimized for cytotoxic T-lymphocyte epitope coverage.

We report the rational design and in vivo testing of mosaic proteins for a polyvalent pan-filoviral vaccine using a computational strategy designed for the Human Immunodeficiency Virus type 1 (HIV-1) but also appropriate for Hepatitis C virus (HCV) and potentially other diverse viruses. Mosaics are sets of artificial recombinant proteins that are based on natural proteins. The recombinants are computationally selected using a genetic algorithm to optimize the coverage of potential cytotoxic T lymphocyte (CTL) epitopes. Because evolutionary history differs markedly between HIV-1 and filoviruses, we devised an adapted computational technique that is effective for sparsely sampled taxa; our first significant result is that the mosaic technique is effective in creating high-quality mosaic filovirus proteins. The resulting coverage of potential epitopes across filovirus species is superior to coverage by any natural variants, including current vaccine strains with demonstrated cross-reactivity. The mosaic cocktails are also robust: mosaics substantially outperformed natural strains when computationally tested against poorly sampled species and more variable genes. Furthermore, in a computational comparison of cross-reactive potential a design constructed prior to the Bundibugyo outbreak performed nearly as well against all species as an updated design that included Bundibugyo. These points suggest that the mosaic designs would be more resilient than natural-variant vaccines against future Ebola outbreaks dominated by novel viral variants. We demonstrate in vivo immunogenicity and protection against a heterologous challenge in a mouse model. This design work delineates the likely requirements and limitations on broadly-protective filoviral CTL vaccines.

Severe exercise-induced hypoxemia.

Exercise training is an essential component of pulmonary rehabilitation and is associated with improved function and other important outcomes in persons with chronic lung disease. A subset of pulmonary rehabilitation patients experience hypoxemia that may occur or worsen with exercise. For the purpose of this review, severe exercise-induced hypoxemia is defined as an S(pO(2)) of < 89% during exercise, despite use of supplemental oxygen delivered at up to 6 L/min. There is a paucity of evidence and clinical guidelines that address assessment and management of this important manifestation of chronic lung disease. This review presents background of this topic and suggests strategies for assessment, management, and safety measures for patients with severe exercise-induced hypoxemia.

A cell culture-derived influenza vaccine provides consistent protection against infection and reduces the duration and severity of disease in infected individuals.

BACKGROUND: Current knowledge of the consistency of protection induced by seasonal influenza vaccines over the duration of a full influenza season is limited, and little is known about the clinical course of disease in individuals who become infected despite vaccination. METHODS: Data from a randomized double-blind placebo-controlled clinical trial undertaken in healthy young adults in the 2008-2009 influenza season were used to investigate the weekly cumulative efficacy of a Vero cell culture-derived influenza vaccine. In addition, the duration and severity of disease in vaccine and placebo recipients with cell culture-confirmed influenza infection were compared. RESULTS: Vaccine efficacy against matching strains was consistently high (73%-82%) throughout the study, including the entire period of the influenza season during which influenza activity was above the epidemic threshold. Vaccine efficacy was also consistent (68%-83%) when calculated for all strains, irrespective of antigenic match. Vaccination also ameliorated disease symptoms when infection was not prevented. Bivariate analysis of duration and severity showed a significant amelioration of myalgia (P = .003), headache (P = .025), and fatigue (P = .013) in infected vaccinated subjects compared with placebo. Cough (P = .143) and oropharyngeal pain (P = .083) were also reduced in infected vaccinated subjects. CONCLUSIONS: A Vero cell culture-derived influenza vaccine provides consistently high levels of protection against cell culture-confirmed infection by seasonal influenza virus and significantly reduces the duration and severity of disease in those individuals in which infection is not prevented. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT00566345.