The influence of body mass index on airway resistance in children with sickle cell disease: A longitudinal study based on impulse oscillometry.

BACKGROUND: Impulse oscillometry (IOS) is an effective tool for assessing airway mechanics and diagnosing obstructive airway disease (OAD) in children with sickle cell disease (C-SCD). Obesity is known to be associated with OAD, and untreated OAD often leads to hypoxia-related complications in C-SCD. Considering the increasing prevalence of obesity in C-SCD, it is important to explore the influence of body mass index (BMI) on OAD in this disease population. METHODS: A longitudinal retrospective chart review was conducted on 55 C-SCD (161 IOS observations) and 35 non-SCD asthmatic children (C-Asthma) (58 observations), primarily to investigate the association between BMI and airway resistance in C-SCD and C-Asthma. We conducted generalized linear mixed models (GLMM), adjusted for pharmacotherapies, to demonstrate the influence of BMI on total (R5), central (R20), and peripheral (R5-20) airway resistance and reactance (X5, resonant frequency (Fres)). We further compared age, BMI, and IOS indices between C-SCD and C-Asthma using the Mann-Whitney test. RESULTS: Age and BMI were not statistically different between the two groups. In C-SCD, BMI was associated with R5 (GLMM t-statistics:3.75, 95%CI:1.01,3.27, p-value<0.001*) and R20 (t-statistics:4.01, 95%CI:1.04,1.15, p-value<0.001*), but not with R5-20 or airway reactance. In asthmatics, BMI was not associated with IOS estimates except Fres (t-statistics: 3.93, 95%CI: -0.06, -0.02, p-value<0.001*). C-SCD demonstrated higher airway resistances (R5 and R20) and reactance (Fres) compared to C-Asthma (Mann-Whitney: p-values<0.05). CONCLUSION: BMI significantly influenced total and central airway resistance in C-SCD. While higher airway resistances reflected increased OAD in C-SCD than asthmatics, higher Fres perhaps indicated progressive pulmonary involvement in C-SCD.

The influence of pediatricians' recommendation on caregivers' COVID-19 vaccine acceptance for children: A nationwide cross-sectional survey study from USA.

Background: The influence of pediatricians on parental acceptance of COVID-19 vaccine for children has not been well studied. We designed a survey to estimate the impact of pediatricians' recommendations on caregivers' vaccine acceptance while accounting for participants' socio-demographic and personal characteristics. The secondary objectives were to compare childhood vaccination rates among different age groups and categorize caregivers' concerns about vaccinating young (under-five) children. Overall, the study aimed to provide insight into potential pro-vaccination strategies that could integrate pediatricians to alleviate parental vaccine hesitancy. Methods: We conducted an online cross-sectional survey study using Redcap, in August 2022. We enquired COVID-19 vaccination status of the children in the family (≥five years). The survey questionnaire included socio-demographic and personal characteristics: age, race, sex, education, financial status, residence, healthcare worker, COVID-19 vaccination status and side effects, children's influenza vaccination status, and pediatricians' recommendations (1-5 scale). Logistic regression and neural network models were used to estimate the influence of socio-demographic determinants on children's vaccine status and build predictors' ranking. Results: The participants (N = 2,622) were predominantly white, female, middle-class, and vaccinated against COVID-19 (89%). The logistic regression model was significant vs. the null (likelihood-ratio χ2 = 514.57, p < 0.001, pseudo-R2 = .440). The neural network model also demonstrated strong prediction ability with a correct prediction rates of 82.9% and 81.9% for the training and testing models, respectively. Both models identified pediatricians' recommendations, self-COVID-19 vaccination status, and post-vaccination side effects as dominant predictors of caregivers' vaccine acceptance. Among the pediatricians, 70.48% discussed and had an affirmative opinion about COVID-19 vaccine for children. Vaccine acceptance was lower for children aged 5-8 years compared to older age groups (9-12 and 13-18 years), and acceptance varied significantly among the three cohorts of children (χ2 = 65.62, p < 0.001). About half of the participants were concerned about inadequate availability of vaccine safety information for under-five children. Conclusions: Pediatricians' affirmative recommendation was significantly associated with caregivers' COVID-19 vaccine acceptance for children while accounting for participants' socio-demographic characteristics. Notably, vaccine acceptance was lower among younger compared to older children, and caregivers' uncertainty about vaccine safety for under-five children was prevalent. Thus, pro-vaccination strategies might incorporate pediatricians to alleviate parental concerns and optimize poor vaccination rate among under-five children.

The Upsurge of Impact Factors in Pediatric Journals Post COVID-19 Outbreak: A Cross-Sectional Study.

Background: Impact factor (IF) is a quantitative tool designed to evaluate scientific journals' excellence. There was an unprecedented upsurge in biomedical journals' IF in 2020, perhaps contributed by the increased number of publications since the COVID-19 outbreak. We conducted a cross-sectional study (2018-2020) to analyze recent trends in standard bibliometrics (IF, Eigenfactor, SNIP) of pediatric journals. We also estimated reference and publication counts of biomedical journals since publication volume determines the number of citations offered and IF. Methods: Various bibliometrics of pediatric journals and reference/publication volumes of biomedical journals were compared between 2020 vs. 2019 and 2019 vs. 2018. We also compared open access (OA) and subscription journals' trends. Finally, we estimated IF changes in the journals of a different specialty, pulmonology. Results: The study included 164 pediatric and 4,918 biomedical journals (OA = 1,473, subscription = 3,445). Pediatric journals' IFs had increased significantly in 2020 [median (IQR) = 2.35 (1.34)] vs. 2019 [1.82 (1.22)] (Wilcoxon: p-value < 0.001). IFs were unchanged between 2018 and 2019. Eigenfactor remained stable between 2018 and 2020, while SNIP increased progressively. Reference/publication volumes of biomedical journals escalated between 2018 and 2020, and OA journals experienced faster growth than subscription journals. IFs of pulmonary journals also increased considerably in 2020 vs. 2019. Conclusions: We report an upsurge in pediatric journals' IF, perhaps contributed by a sudden increase in publication numbers in 2020. Therefore, considering this limitation, IF should be cautiously used as the benchmark of excellence. Unlike IF, Eigenfactor remained stable between 2018 and 2020. Similar changes in IF were also observed among the journals of another specialty, pulmonology.

The Influence of COVID-19 on Influenza and Respiratory Syncytial Virus Activities.

Background: Respiratory viral diseases have considerably declined since the COVID-19 outbreak, perhaps through influence by nonpharmaceutical interventions. We conducted a cross-sectional study using the CDC database to compare the pre- vs. post-pandemic flu activity (incidence) between the US states. Our secondary objectives were to estimate the association between flu activity and flu vaccination rates and compare the national trends of flu and RSV activities since the pandemic outbreak. Methods: We estimated the difference between pre-pandemic (April 2019-March 2020) and post-pandemic (April 2020-March 2021) flu activity between individual states using the Wilcoxon signed-rank test. The association between flu activity and immunization rates was also measured. Finally, parallel time trend graphs for flu and RSV activities were illustrated with a time series modeler. Results: The median (IQR) pre-pandemic flu activity was 4.10 (1.38), higher than the post-pandemic activity (1.38 (0.71)) (p-value < 0.001). There was no difference between pre-pandemic (45.50% (39.10%)) and post-pandemic (45.0% (19.84%)) flu vaccine acceptance (p-value > 0.05). Flu activity and vaccination rates were not associated (p-value > 0.05). Flu activity has declined since the COVID-19 outbreak, while RSV made a strong comeback in June 2021. Conclusion: Flu activity has significantly diminished throughout the pandemic while a sudden upsurge in RSV is a public health concern indicative of possible resurgence of other viruses. Flu vaccine acceptance neither changed during the pandemic nor influenced the diminished Flu activity.

The Influence of Sociodemographic Heterogeneity on the Perceptions of COVID-19: A Countrywide Survey Study in the USA.

Background: Sociodemographic factors such as age, race, education, family income, and sex have been reported to influence COVID-related perceptions, reflected by knowledge, stress, and preventive behavior. We conducted a US-based survey to estimate the difference in COVID-related perceptions among diverse sociodemographic groups and the influence of sociodemographic heterogeneity on COVID-related perceptions. Methods: The survey enquired about sociodemographic parameters and relevant information to measure knowledge, stress, and preventive behavior. COVID-perception scores among sociodemographic subgroups were compared with ANOVA (Bonferroni). The general linear model (GLM) was used to estimate the association among sociodemographic factors and COVID-related perceptions. Results: Females (75%) and White participants (78%) were the predominant (N = 3734). Females, White participants, wealthy, and educated participants demonstrated better knowledge, while participants of minority races, younger ages, low incomes, and females experienced high stress. Females, African-Americans, and educated participants better adopted preventive behaviors. Race, family income, and sex were the highest contributors to the predictive model. Sociodemographic determinants had statistically significant associations with knowledge (F-score = 7.72, p < 0.001; foremost predictor: race), stress (F-score = 16.46, p < 0.001; foremost predictor: income), and preventive behavior (GLM: F-score = 7.72, p < 0.001, foremost predictor: sex). Conclusion: Sociodemographic heterogeneity significantly influenced COVID-related perceptions, while race, family income, and sex were the strongest determinants of COVID-related perceptions.

Sociodemographic predictors of COVID-19 vaccine acceptance: a nationwide US-based survey study.

OBJECTIVES: Acceptance of COVID-19 vaccination is attributable to sociodemographic factors and their complex interactions. Attitudes towards COVID-19 vaccines in the United States are changing frequently, especially since the launch of the vaccines and as the United States faces a third wave of the pandemic. Our primary objective was to determine the relative influence of sociodemographic predictors on COVID-19 vaccine acceptance. The secondary objectives were to understand the reasons behind vaccine refusal and compare COVID-19 vaccine acceptance with influenza vaccine uptake. STUDY DESIGN: This was a nationwide US-based survey study. METHODS: A REDCap survey link was distributed using various online platforms. The primary study outcome was COVID-19 vaccine acceptance (yes/no). Sociodemographic factors, such as age, ethnicity, gender, education, family income, healthcare worker profession, residence regions, local healthcare facility and 'vaccine launch' period (pre vs post), were included as potential predictors. The differences in vaccine acceptance rates among sociodemographic subgroups were estimated by Chi-squared tests, whereas logistic regression and neural networks computed the prediction models and determined the predictors of relative significance. RESULTS: Among 2978 eligible respondents, 81.1% of participants were likely to receive the vaccine. All the predictors demonstrated significant associations with vaccine acceptance, except vaccine launch period. Regression analyses eliminated gender and vaccine launch period from the model, and the machine learning model reproduced the regression result. Both models precisely predicted individual vaccine acceptance and recognised education, ethnicity and age as the most important predictors. Fear of adverse effects and concern with efficacy were the principal reasons for vaccine refusal. CONCLUSIONS: Sociodemographic predictors, such as education, ethnicity and age, significantly influenced COVID-19 vaccine acceptance, and concerns of side-effects and efficacy led to increased vaccine hesitancy.

Perceived Stress, Knowledge, and Preventive Behaviors in Indian versus US-based Participants During COVID-19: A Survey Study.

Rationale: India and the USA, the worst affected countries by COVID-19, experienced very different pandemic courses. By 2020, COVID-19 cases had steadily declined in India, whereas the fight continued in the US. The people of India and the USA perhaps perceived threats very differently, influenced by their knowledge, available healthcare facilities, and social security. We conducted an online survey study to compare COVID-related perceptions between Indian participants (IND-P) and US-based participants (US-P). Methods: COVID-related perceptions such as stress, knowledge, and preventive behaviors were measured with specific questionnaires, and normalized scores were computed. T-tests were used to compare the perception scores, while the Kruskal-Wallis-H (KWH) tests were used to compare socioeconomic distributions between participants from two countries. Generalized linear model (GLM) adjusted for sociodemographic confounders estimated the association between the country of residence and COVID-perception. Results: The IND-P (N = 242) were younger and male-dominated compared with the US-P (N = 531) (age: KWH = 97.37, p < 0.0001, gender: KWH = 140.38, p < 0.0001). Positive attitudes toward preventive guidelines were associated with higher perceived risk and stress (r = 0.35, p < 0.001, and r = 0.21, p < 0.001, respectively) but not with the knowledge (r = -0.05, p = 0.14). Compared with the US-P, the IND-P had lower knowledge (5.19 ± 1.95 vs. 7.82 ± 1.35; t-test: p < 0.0001), higher stress (7.01 ± 1.51 vs. 6.07 ± 1.61; t-test: p < 0.0001), and better adherence to preventive guidelines (8.84 ± 1.30 vs. 8.34 ± 2.09; t-test: p = 0.0006). GLM demonstrated a significant association between the country and COVID-perception scores. Conclusion: The IND-P experienced higher stress and perceived threat during COVID-19 than the US-P, perhaps due to a lack of faith in the healthcare system and insecurity. Despite lower knowledge, the IND-P had better acceptance of preventive guidelines than the US-P.

Predictors of Diffusing Capacity in Children With Sickle Cell Disease: A Longitudinal Study.

Background: Gas exchange abnormalities in Sickle Cell Disease (SCD) may represent cardiopulmonary deterioration. Identifying predictors of these abnormalities in children with SCD (C-SCD) may help us understand disease progression and develop informed management decisions. Objectives: To identify pulmonary function tests (PFT) estimates and biomarkers of disease severity that are associated with and predict abnormal diffusing capacity (DLCO) in C-SCD. Methods: We obtained PFT data from 51 C-SCD (median age:12.4 years, male: female = 29:22) (115 observations) and 22 controls (median age:11.1 years, male: female = 8:14), formulated a rank list of DLCO predictors based on machine learning algorithms (XGBoost) or linear mixed-effect models, and compared estimated DLCO to the measured values. Finally, we evaluated the association between measured or estimated DLCO and clinical outcomes, including SCD crises, pulmonary hypertension, and nocturnal desaturation. Results: Hemoglobin-adjusted DLCO (%) and several PFT indices were diminished in C-SCD compared to controls. Both statistical approaches ranked FVC (%), neutrophils (%), and FEF25-75 (%) as the top three predictors of DLCO. XGBoost had superior performance compared to the linear model. Both measured and estimated DLCO demonstrated a significant association with SCD severity: higher DLCO, estimated by XGBoost, was associated with fewer SCD crises [beta = -0.084 (95%CI: -0.13, -0.033)] and lower TRJV [beta = -0.009 (-0.017, -0.001)], but not with nocturnal desaturation (p = 0.12). Conclusions: In this cohort of C-CSD, DLCO was associated with PFT estimates representing restrictive lung disease (FVC, TLC), airflow obstruction (FEF25-75, FEV1/FVC, R5), and inflammation (neutrophilia). We used these indices to estimate DLCO, and show association with disease outcomes, underscoring the prediction models' clinical relevance.

Changes in Flavor Preference in a Cohort of Long-Term Electronic Cigarette Users.

Rationale: The use of electronic cigarettes (e-cigarettes) has rapidly increased in the United States, and thousands of e-cigarette flavors are available. However, there remains a dearth of evidence on e-cigarette flavor use patterns among older e-cigarette users.Objectives: This longitudinal study examined changes in flavor use patterns in long-term e-cigarette users, assessed self-reported adverse reactions, and evaluated users' anticipated reactions to possible U.S. Food and Drug Administration e-cigarette flavor regulatory scenarios.Methods: The study population was 383 adult participants who completed two online e-cigarette surveys in 2012-2014 (baseline survey) and in 2017-2019 (follow-up survey). In both surveys, participants were asked, "Thinking about your preferred liquid, what is the name of this liquid flavor?" and to list all flavors used in the past 30 days. Flavor preference was classified using the Penn State Three-Step Flavor Classification method. Participants reported adverse events (open-ended description) with the associated flavor. Regulatory scenarios were presented, and participants selected perceived actions from among a list of 15 options.Results: Participants' age averaged 44 ± 12 years; 86% were exclusive e-cigarette users, and 13% reported "poly-use" (i.e., e-cigarette and other tobacco product use). E-cigarette flavor preference migration occurred in all demographic groups: only 36-44% maintained a preference for their original flavor. Preference for tobacco and menthol or mint decreased over time (40% baseline vs. 22% follow-up); preference for fruit remained stable (23% baseline and follow-up), but chocolate/candy or other sweets preference significantly increased (16% baseline vs. 29% follow-up), and other flavors increased slightly. Migration to sweet flavors was more noticeable in younger adults (18-45 yr); exclusive e-cigarette users preferred sweet flavors more commonly than poly-users did (31% vs. 19%). Flavor-associated adverse reactions, mainly respiratory irritations, were reported by 26 (6.9%) participants. Nearly 50% of the participants reported that they would "find a way" to buy their preferred flavor or add flavoring agents themselves if nontobacco flavors were banned.Conclusions: Flavor migration toward sweet flavors occurred in long-term e-cigarette users, a trend most pronounced in younger and exclusive e-cigarette users. The anticipated maintenance of access to flavors despite regulation suggests an element of e-cigarette-related dependence that requires further evaluation. This information could help clinicians understand the health impacts of e-cigarette flavors, develop appropriate strategies for smoking cessation, and inform the U.S. Food and Drug Administration to plan future regulation of e-cigarette flavors.

Diagnostic value of spirometry vs impulse oscillometry: A comparative study in children with sickle cell disease.

BACKGROUND: Spirometry is conventionally used to diagnose airway diseases in children with sickle cell disease (C-SCD). However, spirometry is difficult for younger children to perform, is effort dependent, and it provides limited information on respiratory mechanics. Impulse oscillometry (IOS) is an effort-independent pulmonary function test (PFT), which measures total airway resistance (R5Hz) and reactance (AX). IOS could be advantageous without certain limitations of spirometry. AIM: To compare the accuracy of IOS vs spirometry in making the diagnosis of asthma and assessing age-related pulmonary changes in C-SCD. STUDY DESIGN: Retrospective chart review. SUBJECT SELECTION: Fifty-six C-SCD and thirty-six controls (asthmatics without SCD) followed at Penn State with PFTs obtained during the initial pulmonary evaluation. METHODOLOGY: We grouped C-SCD into asthmatics and non-asthmatics based on pre-referral diagnosis and compared PFTs between two groups. Receiver operating characteristic (ROC) curve analyses and machine learning tools (XGBoost and artificial neural network) were used to rank the spirometry and IOS measures based on their ability to predict a diagnosis of asthma. Robust linear regression was used to analyze association among height/age with various PFT measures. RESULTS: Both ROC and XGBoost indicated that FEF25-75 %, forced expiratory volume in 1 second (FEV1)/forced vital capacity, and R5Hz(%) were the top three predictors for asthma diagnosis. R5Hz(%) and AX had superior bronchodilator response (BDR) than FEV1. IOS parameters had significant association with height/age in C-SCD (possibly due to the stiff lungs) but not in controls. CONCLUSION: IOS had advantages over spirometry in C-SCD because it is feasible in early childhood, provides insights into the pulmonary mechanics, and is more sensitive to detect BDR.

Association between pulmonary function and left ventricular volume and function in duchenne muscular dystrophy.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is characterized by absence of the subsarcolemmal protein dystrophin, present in skeletal muscles and cardiomyocytes. We hypothesized that progressive respiratory and left ventricular (LV) insufficiencies in DMD could be parallel and interrelated phenomena. METHODS: We conducted a retrospective chart review of 27 patients with DMD. Our primary objective was to compare the rates of decline between pulmonary function test (PFT) measures (forced expiratory volume in the first second, forced vital capacity, peak expiratory flow rate, maximal inspiratory/expiratory pressure) and echocardiographic estimates of LV end-diastolic volume and LV ejection fraction. RESULTS: The rates of decline/year of PFTs and LV estimates were not significantly different. Pulmonary function test measures of ventilatory efficiency and strength had strong intercorrelations. Pulmonary function tests and LV estimates had weak but statistically significant correlations. DISCUSSION: A comparable rate of decline in PFTs and LV indices in DMD provides evidence for concurrently progressive deterioration in respiratory and LV functions. Muscle Nerve, 2019.

The association of nocturnal hypoxia and an echocardiographic measure of pulmonary hypertension in children with sickle cell disease.

BACKGROUND: Pulmonary hypertension (PH) is multifactorial in origin and may develop early in children with sickle cell disease (C-SCD). Potential etiologies are hemolysis-induced endothelial dysfunction, left ventricular (LV) dysfunction, and chronic hypoxia. Nocturnal hypoxia (NH) in C-SCD is known to be a sequela of obstructive sleep apnea (OSA). The primary objective of this study is to correlate polysomnographic evidence NH with echocardiographic measures of PH in C-SCD. METHODS: We performed a retrospective chart review of 20 C-SCD (Hemoglobin SS), who had polysomnography and echocardiogram performed within a narrow time interval, and 31% of them had pre-existing cardiac conditions. Tricuspid regurgitant jet velocity (TRJV) ≥ 2.5 m/s was considered as an indicator of PH. RESULTS: Twenty-five percent of the subjects had NH. Forty percent of C-SCD, predominantly male, had evidence of PH based on an elevated TRJV. Children with NH compared to non-NH had significantly worse baseline hypoxemia (p < 0.001), higher TRJV (p = 0.005), and higher LV end-diastolic diameters (p = 0.009). The severity of NH was influenced by OSA. However, PH was not associated with OSA or duration of hydroxyurea therapy. CONCLUSION: Our study indicates that NH is associated with PH in C-SCD, and that screening for NH may help to identify C-SCD with higher morbidity risk.

The Association Between Female Smoking and Childhood Asthma Prevalence-A Study Based on Aggregative Data.

Aims: Socioeconomic and environmental factors influence childhood asthma prevalence across the world. In-depth epidemiological research is necessary to determine the association between asthma prevalence and socio-environmental conditions, and to develop public health strategies to protect the asthmatic children against the environmental precipitators. Our research was based on aggregative data and sought to compare the asthma prevalence between children of two different age-groups across the world and to identify the association among the key socio-environmental conditions with increased childhood asthma prevalence. Method: We included forty countries with available data on various socio-environmental conditions (2014-2015). Childhood asthma prevalence of two different age groups (6-7 and 13-14 years) were obtained from global asthma report 2014. Because of significant diversities, the selected countries were divided into two groups based on human developmental index (HDI), a well-recognized parameter to estimate the overall socioeconomic status of a country. Robust linear regression was conducted using childhood asthma prevalence as the dependent variable and female smoking prevalence, tertiary school enrollment (TSE), PM10 (particulate matter ≤10 µm in diameter) and gross domestic product (GDP) as predictors. Results: Asthma prevalence was not different between two age groups. Among all predictors, only female smoking prevalence (reflecting maternal smoking) was associated with asthma prevalence in the countries with lower socio-economic conditions (HDI), but not in the higher HDI group. The results were unchanged even after randomization. Conclusions: Childhood asthma prevalence did not change significantly with age. Female smoking may have a positive correlation with childhood asthma prevalence in lower HDI countries.

Flexible Bronchoscopy Under Bronchoscopist-Administered Moderate Sedation Versus General Anesthesia: A Comparative Study in Children.

Background: Flexible bronchoscopy (FB) can be performed under bronchoscopist administered moderate sedation (BAMS) with a midazolam/fentanyl combination or general anesthesia (GA). However, the outcome of BAMS has not been well established in children. Currently, most of the centers prefer FB under GA. Both techniques have their advantages and disadvantages with implications for safety, complications, and diagnostic yield. The primary objective of our study was to evaluate the safety, time efficiency, and cost-effectiveness of FB under BAMS as compared with FB under GA in a similar setting. Methods: We performed a retrospective chart review to compare BAMS versus GA for FB in children. We recruited BAMS children (n = 295) from University of Florida (UF) Health Shands Children's Hospital, and GA children (n = 100) from Penn State Children's Hospital (PSHCH). Both the groups had similar indications, complexities, and procedural environments. Comparisons of various time-intervals including preprocedure time, sedation-induction time, scope time, and post-procedure time among different BAMS versus GA age-groups were the primary outcomes. The secondary outcomes were the determination of the rates of complications, the dosages of sedative/anesthetic, cost-effectiveness, and sedation patterns under BAMS. Results: FB under BAMS required significantly higher preprocedure times and sedation-induction times (P < 0.001** and P < 0.001** respectively) but shorter scope and post-procedure times compared with the GA group times (P < 0.001** and P < 0.001** respectively). Younger children had a deeper level of sedation for an extended period under BAMS. The costs for the sedation services and the complication rates were lower in the BAMS group compared with the GA group. Conclusion: Our study demonstrated the feasibility of BAMS in children. FB under BAMS had an advantage of lower cost and fewer procedural complications compared with FB under GA. Despite that, the safety of BAMS could not be conclusively established from this retrospective study. Moreover, BAMS can potentially compromise the diagnostic yield because the bronchoscopist is also responsible for monitoring sedation and managing the airway.

Socioeconomic and Environmental Predictors of Asthma-Related Mortality.

The prevalence of asthma-related mortality (ARM) varies significantly among different countries, possibly influenced by various socioeconomic and environmental conditions (SEC). In-depth epidemiological research is necessary to understand the causal relationship between different SECs and ARM and to develop public health strategies to reduce the global burden of asthma. Our research aimed to identify the key SECs which may be attributed to ARM worldwide and to study the relationship between ARM and asthma prevalence. We included twenty-two countries with available data on SECs (2014-2015) and divided them into four groups: Asia, Africa, Europe, and Miscellaneous (Australia and North and South America). Tertiary school enrollment (TSE), gross domestic product (GDP), air pollution index, and male and female smoking prevalence rates were analyzed as predictors of ARM, using multiple linear regression. We found that ARM and asthma prevalence had an inverse relationship and developing countries compared to developed countries experienced higher ARM despite having lower asthma prevalence. Asian and African countries, compared to Europe and Miscellaneous countries, experienced poorer SECs, possibly associated with higher ARM. Among SECs, TSE and GDP had strongest association with ARM. In conclusion, lack of education and uneven distribution of resources may have an influence on the increased ARM in developing countries.

Effect of laparotomy on respiratory muscle activation pattern.

Muscular tone of the abdominal wall is important in maintaining transdiaphragmatic pressures and its loss can lead to decreased lung volumes. Patients who are status postlaparotomy are at risk of developing atelectasis. The compensatory role of respiratory muscle activity in postlaparotomy is not well studied. Normally, inspiratory muscles are active during inspiration and passive during expiration to allow for lung recoil. However, electrical activities of the inspiratory muscles continue during early expiratory phase to prevent rapid loss of lung volume. This activity is known as post-inspiratory inspiratory activity (PIIA). In this study, we hypothesized that laparotomy will elicit an increase in PIIA, which is enhanced by respiratory chemical loading. Experiments were conducted in cats under three different conditions: intact abdomen (n = 3), open abdomen (n = 10), and post abdominal closure (n = 10) during eupnea and hypercapnia (10% CO2). Electromyography (EMG) activities of the diaphragm and parasternal muscles were recorded and peak EMG amplitude, PIIA time, and area under the curve were measured. Intraesophageal pressure was also obtained. PIIA was significantly higher under open abdominal conditions in comparison to intact abdomen during eupnea. Our data indicates that PIIA is increased during open abdomen and may be an important compensatory mechanism for altered respiratory mechanics induced by laparotomy. Also, PIIA remained elevated after abdominal closure. However, under hypercapnia, PIIA was significantly higher during intact abdomen in comparison to open abdomen, which is thought to be due to respiratory muscle compensation under chemical loading.

Bioassay of salmeterol in children using methacholine challenge with impulse oscillometry.

BACKGROUND: Bronchoprovocation with methacholine (MC) is the most sensitive method of determining bioequivalence of inhaled bronchodilators. FEV1 is used to determine the endpoint, but many children cannot perform spirometry reproducibly. The purpose of this study was to determine whether MC, using impulse oscillometry (IOS) as the endpoint, can differentiate between two doses of salmeterol (SM). METHODS: This was a single-blind, randomized study of 10 subjects with mild stable asthma, ages 4-11 years. None were taking a long-acting ß-agonist but most were on low-dose inhaled corticosteroid. On one study day, MC was performed 1 hr after one inhalation from each of two separate Advair 100/50 Diskus (100 µg salmeterol treatment). On a second day, MC was performed after one inhalation from Advair Diskus and one inhalation from Flovent Diskus 100 (50 µg salmeterol treatment). The provocative concentration of methacholine causing a 40% increase in total airway resistance (PC40 R5 ) was calculated. RESULTS: The reduction in R5 (bronchodilator effect) was 15.5% and 18.4% for 50 and 100 µg, respectively (NS). After MC (bronchoprotective effect), the geometric mean (95%CI) PC40 R5 (mg/ml) was 2.4 (1.3-4.4) during screening, 22.9 (8.5-61.6) after 50 µg SM and 47.0 (25.2-87.8) after 100 µg SM (P = 0.051 for 50 vs. 100 using a linear mixed effects model). No adverse effects were observed. CONCLUSIONS: MC with IOS endpoint will be a useful method for determining bioequivalence of a generic inhaler in children. Seventy-two subjects will be required to achieve 80% power to assess bioequivalence of SM. Pediatr Pulmonol. 2016;51:570-575. © 2015 Wiley Periodicals, Inc.

Nonprescription racemic epinephrine for asthma.

BACKGROUND: Inhaled racepinephrine (RE) (Asthmanefrin) became available in September 2012 as a nonprescription treatment for bronchospasm based on a 1986 US Food and Drug Administration rule. It contains 11.25 mg RE in 0.5 mL and is delivered by a handheld electronic nebulizer. In 2001, we conducted a pilot study that was never published. Now that the product is promoted as a replacement for epinephrine chlorofluorocarbon metered-dose inhaler (Primatene), we provide the results of that study. Methacholine challenge was used as a bioassay. OBJECTIVE: To determine the dose of RE that is equivalent to nebulized albuterol. METHODS: Four subjects, 18 to 45 years old, with mild stable asthma completed the pilot study. Methacholine challenge was performed on the first screening day, without pretreatment, and then on different days, 15 minutes after 1.25 mg albuterol and 2.5, 5, 10, and 20 mg RE delivered by a Pari LC Plus nebulizer. The end point was the provocative concentration of methacholine that caused a 20% decrease in FEV1. Data were log transformed and analyzed by an ANOVA for repeated measures. RESULTS: There was a significant dose response for RE. The geometric mean provocative concentration of methacholine that caused a 20% decrease in FEV1 was 44 mg/mL (95% CI, 23-85 mg/mL) after albuterol, and 10.2 mg/mL (95% CI, 3.5-30 mg/mL) after the 10-mg dose of RE (approximate nonprescription dose) (P = .001). There were no adverse effects. CONCLUSION: RE provides less bronchoprotection from methacholine than does albuterol and may be less effective in treating acute bronchospasm.

Ivacaftor Therapy in CF Patients: Single Center Experience.

Ivacaftor is the first novel cystic fibrosis pharmaceutical that acts at the molecular level to potentiate cystic fibrosis transmembrane conductance regulator (CFTR) function and was first approved for clinical use in 2012. We are sharing our single center experience of five patients: four from pediatric age group and one adult patient. All patients had both subjective and objective improvements in their health. Despite established lung disease, our patients had significant improvement in both their FEV1 (forced expiratory volume in 1 second) and FEF25-75 and BMI (body mass index). Larger studies demonstrated only 6.7% improvement in mean FEV1 after starting Ivacaftor therapy but their patient population had normal lung function to begin with. In contrast our case series demonstrates that, in patients with established lung disease and diminished lung function, Ivacaftor can be expected to result in much higher recovery in lung function. Mean FEV1 improved by 35% in our case series. Ivacaftor is extremely expensive, costing $300,000 per patient per year requiring lifelong therapy, hence requiring prior authorizations from most third-party payers in the USA. The knowledge shared from our experience will be useful for other clinicians to petition healthcare policymakers on behalf of their patients.