SPECT/CT to quantify early small airway disease and its relationship to clinical symptoms in smokers with normal lung function: a pilot study.

Introduction: Smokers frequently display respiratory symptoms despite the fact that their pulmonary function tests (PFTs) can be normal. Quantitative lung ventilation single-photon emission computed tomography (SPECT/CT) can provide a quantification of lung ventilatory homogeneity and could prove useful as an early marker of airway disease in smokers. We measured the effects of smoking on regional ventilation distribution in subjects with normal lung function and evaluated whether ventilation distribution in these subjects is related to lung function tests results and clinical symptoms. Methods: Subjects without any history of respiratory disease were prospectively recruited and separated in two groups: active smokers (AS: ≥10 cigarettes/day and history of ≥15 pack-years) and never smokers (NS: lifetime exposure of <5 cigarettes). All subjects performed PFTs (which had to be normal, defined as z-score values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC) residual volume and diffusion capacity (DLCO) all falling between -1.65 and +1.65) and underwent SPECT/CT with Technegas, which generated subject- specific ventilation heterogeneity maps. The area under the compensated coefficient of variation (CV) density curve for CV values > 40%, (AUC-CV40%) was used as the measure of ventilation heterogeneity. Results: 30 subjects were recruited (15 per group). Subjects in the AS group displayed higher dyspnea levels (1 [1-2] vs. 0 [0-1] units on mMRC scale, p < 0.001). AUC- CV40% was significantly higher in the AS group (0.386 ± 0.106 vs. 0.293 ± 0.069, p = 0.004). AUC-CV40% was significantly correlated to FEV1 (rho = -0.47, p = 0.009), DLCO (rho = -0.49, p = 0.006), CAT score (rho = 0.55, p = 0.002) and mMRC score (rho = 0.54, p = 0.002). Subjects with mMRC >0 had higher AUC-CV40% values than those without dyspnea (0.289 ± 0.071 vs. 0.378 ± 0.102, p = 0.006), while FEV1 and DLCO were not different between those groups. ROC analyses showed that the AUC for AUC-CV40% in identifying subjects with mMRC score >0 was 0.78 (95%CI 0.61-0.95, p = 0.009), which was significantly higher than that of FEV1 and DLCO. Discussion: In smokers with normal lung function, ventilatory inhomogeneities can be quantified using SPECT/CT. AUC-CV40% values are related to lung function decline and to respiratory symptomatology, suggesting a potential role for this marker in the evaluation of symptomatic smokers.

Cystic fibrosis-related diabetes onset can be predicted using biomarkers measured at birth.

PURPOSE: Cystic fibrosis (CF), caused by pathogenic variants in the CF transmembrane conductance regulator (CFTR), affects multiple organs including the exocrine pancreas, which is a causal contributor to cystic fibrosis-related diabetes (CFRD). Untreated CFRD causes increased CF-related mortality whereas early detection can improve outcomes. METHODS: Using genetic and easily accessible clinical measures available at birth, we constructed a CFRD prediction model using the Canadian CF Gene Modifier Study (CGS; n = 1,958) and validated it in the French CF Gene Modifier Study (FGMS; n = 1,003). We investigated genetic variants shown to associate with CF disease severity across multiple organs in genome-wide association studies. RESULTS: The strongest predictors included sex, CFTR severity score, and several genetic variants including one annotated to PRSS1, which encodes cationic trypsinogen. The final model defined in the CGS shows excellent agreement when validated on the FGMS, and the risk classifier shows slightly better performance at predicting CFRD risk later in life in both studies. CONCLUSION: We demonstrated clinical utility by comparing CFRD prevalence rates between the top 10% of individuals with the highest risk and the bottom 10% with the lowest risk. A web-based application was developed to provide practitioners with patient-specific CFRD risk to guide CFRD monitoring and treatment.

Comparison of a closed system and an open system for blood collection in feline donors.

OBJECTIVES: This research aimed to evaluate the performance of a closed blood collection system and to compare it with an open system in terms of feasibility, tolerability by the donor, quality of blood collected and bacterial contamination. METHODS: Eight feline blood donors were prospectively and randomly subjected to both collection methods. Heart rate (HR), respiratory rate (RR) and blood pressure (BP) were evaluated before sedation, after sedation and after blood collection. The duration of the donation, the formation of a hematoma, and the degree of hemolysis and packed cell volume (PCV) of each blood unit were evaluated. Aliquot samples were aseptically collected from each unit and tested for bacterial contamination by culture and PCR on days 0, 14 and 28 of storage. RESULTS: There was no significant difference between collection methods for HR and RR at any time point. Before sedation, the mean systolic BP was significantly higher with the closed system (closed 169 mmHg, open 137 mmHg; P = 0.003). The average duration of collection was significantly shorter with the closed system (closed 3 mins 10 s, open 8 mins; P = 0.035); however, the prevalence of a successful blood collection with a single venipuncture and hematoma formation were not significantly different between systems. The mean unit PCV was significantly higher with the open system (closed 31%, open 34%; P = 0.026). On bacterial culture, 15/16 units were negative at all time points (closed 7; open 8). Using PCR, 5/16 units were positive for Ralstonia species for at least one time point (closed 3; open 2). CONCLUSIONS AND RELEVANCE: Our designed closed system appears to be well adapted to feline blood collection and was well tolerated by the donors, performing similarly to an open system, and could represent a valuable clinical device for the development of a feline blood bank, namely feline blood storage.

Benefits of 1-Year Lifestyle Modification Program on Exercise Capacity and Diastolic Function Among Coronary Artery Disease Men With and Without Type 2 Diabetes.

BACKGROUND: To assess the benefits of a 1-year lifestyle modification program on exercise capacity and diastolic function in men with left ventricular (LV) diastolic dysfunction (LVDD) and coronary artery disease (CAD), according to glucose tolerance status. METHODS: Fifty-three men (62 ± 8 years; BMI: 27.3 ± 3.5 kg/m2) with LVDD and CAD were enrolled in a 1-year lifestyle modification program based on dietary management and increased physical activity. Patients were classified by using a 75 grams oral glucose tolerance test as having normal glucose tolerance (n = 16), prediabetes (n = 23), or type 2 diabetes mellitus (T2DM) (n = 14). Cardiac morphology and function, visceral fat, and cardiac fat depots were measured using magnetic resonance imaging, whereas exercise capacity [cardiorespiratory fitness (CRF)] (VO2peak) was assessed with a maximal treadmill test. RESULTS: The 1-year lifestyle modification program was associated with reductions in body weight, and visceral and cardiac fat levels (all P < 0.05). CRF increased by 13% (24.9 ± 4.1 vs. 28.2 ± 4.8 mL O2/kg/min, P < 0.0001). Moreover, half of patients (53%) improved LV diastolic function in response to the lifestyle intervention. Multiple regression analyses revealed that age (partial R2 = 26.9, P < 0.0001) and presence of T2DM (partial R2 = 5.9, P = 0.04) were the stronger predictors of change in diastolic function, while favorable change in LV remodeling index was the best predictor of improvement in LV diastolic function after the lifestyle intervention (R2 = 21.9, P = 0.002). CONCLUSIONS: Irrespective of glucose tolerance status, a 1-year lifestyle modification program in men with LVDD and CAD is associated with significant improvements in exercise capacity and LV diastolic function in more than half of patients.

Longitudinal Changes in Cholesterol Efflux Capacities in Patients With Coronary Artery Disease Undergoing Lifestyle Modification Therapy.

BACKGROUND: Our objective was to identify the determinants of high-density lipoprotein cholesterol efflux capacity (HDL-CEC) changes in patients with coronary artery disease who participated in a lifestyle modification program aimed at increasing physical activity levels and improving diet quality. METHODS AND RESULTS: A total of 86 men with coronary artery disease aged between 35 and 80 years participated in a 1-year lifestyle modification program that aimed to achieve a minimum of 150 minutes of aerobic physical activity weekly and improve diet quality. HDL-CECs were measured before and after the 1-year intervention using 3H-cholesterol-labeled J774 and HepG2 cells. Visceral, subcutaneous, and cardiac adipose tissue levels were assessed before and after the intervention using magnetic resonance imaging. Lipoprotein particle size and concentrations were measured by proton nuclear magnetic resonance spectroscopy and a complete lipoprotein-lipid profile was obtained. At baseline, the best correlate of HDL-CECs were apolipoprotein AI (R2=0.35, P<0.0001) and high-density lipoprotein cholesterol (R2=0.21, P<0.0001) for J774-HDL-CECs and HepG2-HDL-CECs, respectively. Baseline and longitudinal changes in HDL-CECs were associated with several lipoprotein size and concentration indices, although high-density lipoprotein cholesterol was the best predictor of longitudinal changes in J774-HDL-CECs (R2=0.18, P=0.002) and apolipoprotein AI was found to be the best predictor of longitudinal changes in HepG2 cholesterol efflux capacities (R2=0.21, P=0.002). CONCLUSIONS: Results of this study suggest that increases in high-density lipoprotein cholesterol and apolipoprotein AI levels typically observed in patients with coronary artery disease undergoing healthy lifestyle modification therapy may be indicative of higher plasma concentrations of functional high-density lipoprotein particles.

Impact of a 1-year lifestyle modification program on plasma lipoprotein and PCSK9 concentrations in patients with coronary artery disease.

BACKGROUND: Patients with coronary artery disease (CAD) are characterized by an impaired cardiometabolic risk profile including high levels of atherogenic apolipoprotein (apo) B-containing lipoprotein levels. Genetic studies have highlighted a critical role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipoprotein metabolism and CAD risk. OBJECTIVE: To determine whether improving dietary quality and increasing physical activity levels improve parameters of the cardiometabolic risk profile such as plasma apoB and PCSK9 levels in patients with CAD. METHODS: We recruited 86 men aged between 39 and 80 years (82 of them on statins) undergoing coronary artery bypass graft (CABG) surgery. These patients participated in a 1-year lifestyle modification program aiming at achieving a minimum of 150 minutes/week of physical activity and improving diet quality by following dietary guidelines. We used magnetic resonance imaging to measure visceral adipose tissue and a modified Bruce protocol to measure fitness levels before and after the intervention. RESULTS: Plasma apoB and low-density lipoprotein cholesterol levels were not modified by the intervention (-3.0%, P = .08 and 1.3%, P = .56, respectively), whereas non-HDL cholesterol decreased by 4.5% (P = .04) and triglycerides by 13% (P = .002). In contrast, PCSK9 levels increased by 5.2% after the intervention (P = .05). HDL cholesterol and apolipoprotein A-I levels also increased (+12%, P < .0001 and + 6%, P < .0001, respectively). PCSK9 levels increased with improvements in fitness (r = 0.23, P = .04) and visceral fat mobilization (r = -0.23, P = .04). CONCLUSION: In post-CABG patients, a lifestyle modification program lead to significant improvements in some parameters of the lipoprotein profile but unexpectedly increased plasma PCSK9 levels.

Assessing and targeting key lifestyle cardiovascular risk factors at the workplace: Effect on hemoglobin A1c levels.

PURPOSE: Despite the key role played by lifestyle habits in the epidemic of type 2 diabetes (T2D), nutritional quality and physical activity are not systematically considered in clinical practice. The project was conducted to verify whether assessing/targeting lifestyle habits could reduce hemoglobin A1c (HbA1c) levels of employees. METHODS: The intervention consisted of a 3-month competition among teams of five employees to favor peer-based support in the adoption of healthier lifestyle habits (Eat better, Move more, and Quit smoking) (n = 900). A comprehensive cardiometabolic/cardiorespiratory health assessment was conducted before and after the contest (nutrition/physical activity questionnaires, blood pressure, anthropometric measurements, lipid profile, HbA1c, fitness). HbA1c levels were used to identify individuals with prediabetes (5.7%-6.4%) or T2D (≥6.5%). RESULTS: At baseline, 51% of the employees had increased HbA1c levels (≥5.7%). The HbA1c levels were associated with waist circumference, independently of body mass index. Subjects with prediabetes showed a higher waist circumference as well as a more deteriorated cardiometabolic profile compared to workers with normal HbA1c levels. After the intervention, employees with elevated HbA1c significantly reduced their HbA1c levels. CONCLUSION: Results suggest that assessing/targeting key lifestyle correlates of the cardiometabolic profile represents a relevant approach to target abdominal obesity and fitness with a significant impact on HbA1c levels.

Evaluation of eyedrop administration by inexperienced patients after cataract surgery.

PURPOSE: To evaluate efficacy and safety of eyedrop administration after cataract surgery and to identify predictors of better technique in patients without previous eyedrop experience. SETTING: Department of Ophthalmology, McGill University, Jewish General Hospital, Montreal, Quebec, Canada. DESIGN: Prospective cross-sectional study. METHODS: Eyedrop-naïve postoperative cataract patients were consecutively recruited the day after cataract surgery. Data were collected using a standardized self-reporting questionnaire and a chart review and by videotaping patients administering the drops in the operated eye. Two independent observers objectively evaluated the instillation technique. Predictors were assessed using odds ratios (ORs) from a logistic regression model. RESULTS: The study enrolled 54 patients. Subjectively, 17 patients (31%) reported difficulty instilling the eyedrops. Sixty-nine percent reported always washing their hands before using the drops, 42% believed that they never missed their eye when instilling drops, and 58.3% believed they never touched their eye with the bottle tip. Objectively, 50 patients (92.6%) showed an improper administration technique, including missing the eye (31.5%), instilling an incorrect amount of drops (64.0%), contaminating the bottle tip (57.4%), or failing to wash hands before drop instillation (78.0%). A better performance score was significantly associated with having received instructions on how to use drops (OR, 11.99; P=.011). CONCLUSIONS: Postoperative cataract patients inexperienced with eyedrop use showed a poor instillation technique by failing to wash hands, contaminating bottle tips, missing the eye, and using an incorrect amount of drops. There was a large discrepancy between the patients' perceptions and the observed technique of drop administration. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.