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.

Opioid prescription and risk of atrial fibrillation in younger veterans.

BACKGROUND: Opioids may play a part in the development of atrial fibrillation (AF). Understanding the relationship between opioid exposure and AF can help providers better assess the risk and benefits of prescribing opioids. OBJECTIVE: To assess the incidence of AF as a function of prescribed opioids and opioid type. DESIGN: We performed unadjusted and adjusted time-updated Cox regressions to assess the association between opioid exposure and incident AF. PARTICIPANTS: The national study sample was comprised of Veterans enrolled in the Veterans Health Administration (VHA) who served in support of post-9/11 operations. MAIN MEASURES: The main predictor of interest was prescription opioid exposure, which was treated as a time-dependent variable. The first was any opioid exposure (yes/no). Secondary was opioid type. The outcome, incident AF, was identified through ICD-9-CM diagnostic codes at any primary care visit after the baseline period. KEY RESULTS: A total of 609,763 veterans (mean age: 34 years and 13.24% female) were included in our study. Median follow-up time was 4.8 years. Within this cohort, 124,395 veterans (20.40%) were prescribed an opioid. A total of 1,455 Veterans (0.24%) were diagnosed with AF. In adjusted time-updated Cox regressions, the risk of incident AF was higher in the veterans prescribed opioids (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.38-1.57). In adjusted time-updated Cox regressions, both immunomodulating and nonimmunomodulating opioid type was associated with increased risk of incident AF (HR: 1.40; 95% CI: 1.25-1.57 and HR: 1.49; 95% CI: 1.39-1.60), compared to no opioid use, respectively. CONCLUSIONS: Our findings suggest opioid prescription may be a modifiable risk factor for the development of AF.

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.

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.