Supplementary Material for: Chronic Obstructive Pulmonary Disease and Cardiac Repolarization: Data from a Randomized Controlled Trial

<b><i>Background:</i></b> Altered cardiac repolarization is a risk factor for sudden cardiac death and seems to be increased in chronic obstructive pulmonary disease (COPD) patients. <b><i>Objective:</i></b> Lung volume reduction surgery (LVRS) has been shown to improve breathing mechanics and lung function in patients with severe COPD and emphysema and possibly also improve altered cardiac repolarization. <b><i>Methods:</i></b> Thirty patients scheduled for LVRS were randomized to LVRS or to the control group. We investigated the treatment effect 3 months after LVRS on measures of cardiac repolarization and dispersion of repolarization (QTc interval, QT dispersion) derived from electrocardiography. Univariable and multivariable analyses were used to identify possible confounders influencing the treatment effect. <b><i>Results:</i></b> LVRS<b> </b>was associated with an improvement in lung function (mean ± SD residual volume/total lung capacity of -9 ± 11% and forced expiratory volume in 1 s of +30 ± 29%). LVRS did not significantly reduce QTc (median -5.3 ms, 95% confidence interval, CI -15.5 to 3.7, p = 0.214) and QT dispersion (median -3.0 ms, 95% CI -13.0 to 7.0, p = 0.536) compared to the control group. No significant association between change in QTc and change in QT dispersion, respectively, and change in possible confounders was found. <b><i>Conclusion:</i></b> LVRS seems to have no effect on cardiac repolarization in patients with COPD. Thus, lung hyperinflation seems not to be a causal mechanism for altered cardiac repolarization in COPD patients

Supplementary Material for: Breath Analysis in Real Time by Mass Spectrometry in Chronic Obstructive Pulmonary Disease

<b><i>Background:</i></b> It has been suggested that exhaled breath contains relevant information on health status. <b><i>Objectives:</i></b> We hypothesized that a novel mass spectrometry (MS) technique to analyze breath in real time could be useful to differentiate breathprints from chronic obstructive pulmonary disease (COPD) patients and controls (smokers and nonsmokers). <b><i>Methods:</i></b> We studied 61 participants including 25 COPD patients [Global Initiative for Obstructive Lung Disease (GOLD) stages I-IV], 25 nonsmoking controls and 11 smoking controls. We analyzed their breath by MS in real time. Raw mass spectra were then processed and statistically analyzed. <b><i>Results:</i></b> A panel of discriminating mass-spectral features was identified for COPD (all stages; n = 25) versus healthy nonsmokers (n = 25), COPD (all stages; n = 25) versus healthy smokers (n = 11) and mild COPD (GOLD stages I/II; n = 13) versus severe COPD (GOLD stages III/IV; n = 12). A blind classification (i.e. leave-one-out cross validation) resulted in 96% sensitivity and 72.7% specificity (COPD vs. smoking controls), 88% sensitivity and 92% specificity (COPD vs. nonsmoking controls) and 92.3% sensitivity and 83.3% specificity (GOLD I/II vs. GOLD III/IV). Acetone and indole were identified as two of the discriminating exhaled molecules. <b><i>Conclusions:</i></b> We conclude that real-time MS may be a useful technique to analyze and characterize the metabolome of exhaled breath. The acquisition of breathprints in a rapid manner may be valuable to support COPD diagnosis and to gain insight into the disease

Supplementary Material for: Evaluation of the Utility of in utero Treatment of Twin Anemia-Polycythemia Sequence

<b><i>Objective:</i></b> The aim of this study is to evaluate the interest in the in utero treatment of twin anemia-polycythemia sequence (TAPS). <b><i>Methods:</i></b> The obstetrical and neonatal data on all cases of TAPS followed up in our institution between 2006 and 2013 were reviewed. Statistical analyses were conducted using Bayesian methods. <b><i>Results:</i></b> Twenty cases of TAPS were included. Laser therapy or intrauterine transfusion (IUT) was performed on the donor twin in 9 cases. Eleven cases were included in the ‘nontreated' group (managed expectantly or diagnosed at birth). The gestational age at diagnosis was lower in the group with treated TAPS [difference (diff) = -22.20 days (-57.13, 14.28), probability (Pr) (diff >0) = 10.6%]. The rate of preterm premature rupture of membranes was higher in the group with treated TAPS [diff = 22.5% (-14, 57), Pr (diff >0) = 89%], but overall mortality was similar. The interval between diagnosis and delivery was longer [diff = 44.37 days (9.41, 77.90), Pr (diff >0) = 99.2%], the TAPS resolution rate was higher [diff = 49.9% (12, 81), Pr (diff >0) = 99.4%], and the neonatal transfusion rate was lower [diff = -30.5% (-60, 0), Pr (diff >0) = 2.6%] in the treated group. <b><i>Conclusion:</i></b> In utero treatment for TAPS is associated with a higher resolution rate of TAPS and a longer time between diagnosis and birth, but overall mortality is the same as with expectant management

Supplementary Material for: Predictors of the Overlap Syndrome and Its Association with Comorbidities in Patients with Chronic Obstructive Pulmonary Disease

<b><i>Background:</i></b> The occurrence of both chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in an individual patient has been described as ‘overlap syndrome', which has been associated with poor prognosis. Little is known about the possible predictors of the overlap syndrome and its association with comorbidities contributing to impaired outcome. <b><i>Objectives:</i></b> This study aimed to evaluate the prevalence and possible predictors of the overlap syndrome and its association with comorbidities in a cohort of COPD patients. <b><i>Methods:</i></b> Individuals with COPD (GOLD stages I-IV, risk groups A-D) were recruited from outpatient clinics. Information on age, gender, body mass index (BMI), smoking status, Epworth sleepiness scale (ESS), COPD assessment test, comorbidities, medications and exacerbations in the past year was collected and a spirometry was performed. Participants underwent a nocturnal polygraphy using the ApneaLink™ device at home. An apnea-hypopnea index (AHI) >10 per hour was considered to indicate OSA. <b><i>Results:</i></b> We enrolled 177 COPD patients (112 men) with a mean age of 64 years (range 42-90), of whom 35 (20%) had an ESS score above 10. During nocturnal polygraphy, 33 patients (19%) had evidence of OSA. In multivariate analysis, BMI and pack years were positively associated with AHI, independent of other significant AHI determinants from univariate analysis. Arterial hypertension and diabetes were more common in patients with the overlap syndrome. <b><i>Conclusions:</i></b> Almost 20% of COPD patients also have OSA. BMI and smoking history seem to be predictors of the overlap syndrome, and these patients may be more often affected by hypertension and diabetes