Association between Sleep Disordered Breathing and Neonatal Outcomes in Nulliparous Individuals.

OBJECTIVE: Our objective was to determine whether objectively measured sleep-disordered breathing (SDB) during pregnancy is associated with an increased risk of adverse neonatal outcomes in a cohort of nulliparous individuals. STUDY DESIGN: Secondary analysis of the nuMom2b sleep disordered breathing substudy was performed. Individuals underwent in-home sleep studies for SDB assessment in early (6-15 weeks' gestation) and mid-pregnancy (22-31 weeks' gestation). SDB was defined as an apnea-hypopnea index ≥5 events/h at either time point. The primary outcome was a composite outcome of respiratory distress syndrome, transient tachypnea of the newborn, or receipt of respiratory support, treated hyperbilirubinemia or hypoglycemia, large-for-gestational age, seizures treated with medications or confirmed by electroencephalography, confirmed sepsis, or neonatal death. Individuals were categorized into (1) early pregnancy SDB (6-15 weeks' gestation), (2) new onset mid-pregnancy SDB (22-31 weeks' gestation), and (3) no SDB. Log-binomial regression was used to calculate adjusted risk ratios (RR) and 95% confidence intervals (CIs) representing the association. RESULTS: Among 2,106 participants, 3% (n = 75) had early pregnancy SDB and 5.7% (n = 119) developed new-onset mid-pregnancy SDB. The incidence of the primary outcome was higher in the offspring of individuals with early (29.3%) and new onset mid-pregnancy SDB (30.3%) compared with individuals with no SDB (17.8%). After adjustment for maternal age, chronic hypertension, pregestational diabetes, and body mass index, new onset mid-pregnancy SDB conferred increased risk (RR = 1.43, 95% CI: 1.05, 1.94), where there was no longer statistically significant association between early pregnancy SDB and the primary outcome. CONCLUSION: New onset, mid-pregnancy SDB is independently associated with neonatal morbidity. KEY POINTS: · Sleep disordered breathing (SDB) is a common condition impacting pregnancy with known maternal risks.. · Objectively defined SDB in pregnancy was associated with a composite of adverse neonatal outcomes.. · New onset SDB in mid pregnancy conferred statistically significant increased risk..

Prospective Correlation of Risk of Obstructive Sleep Apnea With Severe Clinical Features of Thyroid Eye Disease.

PURPOSE: To evaluate the association between risk of obstructive sleep apnea (OSA) and severity of thyroid eye disease (TED) using a validated OSA screening tool. METHODS: A prospective, observational cohort study was performed. New adult TED patients were offered OSA screening with the Snoring Tired Observed Pressure (STOP)-Bang survey during their initial evaluation. Clinical examination and treatment for TED were standard of care and utilized the International Thyroid Eye Disease Society Vision Inflammation Strabismus Appearance system. At the conclusion of the study period, analysis was performed correlating maximum severity of TED signs and symptoms between high- and low-risk OSA groups. Multivariate logistic and linear regression analyses were also performed to analyze the association between the numerical STOP-Bang score and maximum severity of the potentially actionable clinical features of TED (compressive optic neuropathy, vertical prism deviation, horizontal prism deviation, exophthalmos, vertical fissure height). RESULTS: Eighty-five patients met inclusion criteria. Twenty-eight percent were at high risk of OSA (STOP-Bang score of 3 or higher). When comparing the low- and high-risk cohorts, increased risk of OSA was significantly associated with the development of TED compressive optic neuropathy (p = 0.014), conjunctival injection (p = 0.027), chemosis (p = 0.013), upper eyelid edema (p = 0.024), lower eyelid edema (p = 0.003), eyelid erythema (p = 0.037), and vertical strabismus (p = 0.047). In the multivariate regression analyses, higher STOP-Bang scores correlated with increased risk of TED compressive optic neuropathy (p = 0.006), vertical strabismus (p = 0.019), and higher subjective diplopia scores (p = 0.045). CONCLUSIONS: Increased risk of OSA, as determined by the STOP-Bang survey, is associated with increased severity of multiple clinical features of TED, including TED compressive optic neuropathy and strabismus.

Predictors of sleep-disordered breathing in pregnancy.

BACKGROUND: Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES: The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN: Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS: Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION: Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.

Objectively measured short sleep duration and later sleep midpoint in pregnancy are associated with a higher risk of gestational diabetes.

BACKGROUND: Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes. OBJECTIVE: Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. STUDY DESIGN: This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks' gestation. They were asked to wear a wrist actigraphy monitor and complete a daily sleep log for a period of 7 consecutive days. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (<7 h/night), late sleep midpoint (midpoint between sleep onset and sleep offset >5 am), and top quartile of minutes of wake time after sleep onset and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes mellitus. We used χ2 tests to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. RESULTS: In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11-4.53; and odds ratio, 2.58; 95% confidence interval, 1.24-5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01-4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13-4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes. CONCLUSION: Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women.

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

NuMoM2b Sleep-Disordered Breathing study: objectives and methods.

OBJECTIVE: The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes. STUDY DESIGN: NuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations that was conducted across 8 sites with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing. A standardized level 3 home sleep test was performed between 6(0)-15(0) weeks' gestation (visit 1) and again between 22(0)-31(0) weeks' gestation (visit 3). Scoring of tests was conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met "urgent referral" criteria that were based on threshold levels of apnea hypopnea indices, oxygen saturation levels, or electrocardiogram abnormalities but were not notified of test results otherwise. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing are preeclampsia, gestational hypertension, gestational diabetes mellitus, fetal growth restriction, and preterm birth. RESULTS: Objective data were obtained at visit 1 on 3261 women, which was 88.1% of the studies that were attempted and at visit 3 on 2511 women, which was 87.6% of the studies that were attempted. Basic characteristics of the substudy cohort are reported in this methods article. CONCLUSION: The substudy was designed to address important questions regarding the relationship of sleep-disordered breathing on the risk of preeclampsia and other outcomes of relevance to maternal and child health.

Pulmonary hyperinflation and left ventricular mass: the Multi-Ethnic Study of Atherosclerosis COPD Study.

BACKGROUND: Left ventricular (LV) mass is an important predictor of heart failure and cardiovascular mortality, yet determinants of LV mass are incompletely understood. Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) may contribute to changes in intrathoracic pressure that increase LV wall stress. We therefore hypothesized that residual lung volume in COPD would be associated with greater LV mass. METHODS AND RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited smokers 50 to 79 years of age who were free of clinical cardiovascular disease. LV mass was measured by cardiac magnetic resonance. Pulmonary function testing was performed according to guidelines. Regression models were used to adjust for age, sex, body size, blood pressure, and other cardiac risk factors. Among 119 MESA COPD Study participants, the mean age was 69±6 years, 55% were male, and 65% had COPD, mostly of mild or moderate severity. Mean LV mass was 128±34 g. Residual lung volume was independently associated with greater LV mass (7.2 g per 1-SD increase in residual volume; 95% confidence interval, 2.2-12; P=0.004) and was similar in magnitude to that of systolic blood pressure (7.6 g per 1-SD increase in systolic blood pressure; 95% confidence interval, 4.3-11; P<0.001). Similar results were observed for the ratio of LV mass to end-diastolic volume (P=0.02) and with hyperinflation measured as residual volume to total lung capacity ratio (P=0.009). CONCLUSIONS: Pulmonary hyperinflation, as measured by residual lung volume or residual lung volume to total lung capacity ratio, is associated with greater LV mass.

Dual-tasking alleviated sleep deprivation disruption in visuomotor tracking: an fMRI study.

Effects of dual-responding on tracking performance after 49-h of sleep deprivation (SD) were evaluated behaviorally and with functional magnetic resonance imaging (fMRI). Continuous visuomotor tracking was performed simultaneously with an intermittent color-matching visual detection task in which a pair of color-matched stimuli constituted a target and non-matches were non-targets. Tracking error means were binned time-locked to stimulus onset of the detection task in order to observe changes associated with dual-responding by comparing the error during targets and non-targets. Similar comparison was made with fMRI data. Our result showed that despite a significant increase in the overall tracking error post SD, from 20 pixels pre SD to 45 pixels post SD, error decreased to a minimum of about 25 pixels 0-6s after dual-response. Despite an overall reduced activation post SD, greater activation difference between targets and non-targets was found post SD in task-related regions, such as the left cerebellum, the left somatosensory cortex, the left extrastriate cortex, bilateral precuneus, the left middle frontal gyrus, and the left motor cortex. Our results suggest that dual-response helps to alleviate performance impairment usually associated with SD. The duration of the alleviation effect was on the order of seconds after dual-responding.

Objectively assessed sleep-disordered breathing during pregnancy and infant birthweight.

BACKGROUND: Sleep-disordered breathing (SDB) in pregnancy is associated with adverse maternal outcomes. The relationship between SDB and infant birthweight is unclear. This study's primary aim is to determine if objectively measured SDB in pregnancy is associated with infant birthweight. METHODS: We measured SDB objectively in early (6-15 weeks' gestation) and mid (22-31 weeks' gestation) pregnancy in a large cohort of nulliparous women. SDB was defined as an Apnea-Hypopnea Index ≥5 and in secondary analyses we also examined measures of nocturnal hypoxemia. We used a modified Poisson regression approach to estimate relative risks (RR) of large-for-gestational-age (LGA: >90th percentile for gestational age) and small-for-gestational-age (SGA: <10th percentile for gestational age) birthweights. RESULTS: The prevalence of early-pregnancy SDB was nearly 4%. The incidence of mid-pregnancy SDB was nearly 6.0%. The prevalence of LGA and SGA was 7.4% and 11.9%, respectively. Early-pregnancy SDB was associated with a higher risk of LGA in unadjusted models (RR 2.2, 95% CI 1.3-3.5) but not BMI-adjusted models (aRR 1.0, 95% CI 0.6-1.8). Mid-pregnancy SDB was not associated with SGA or LGA. Mid-pregnancy nocturnal hypoxemia (% of sleep time <90% oxygen saturation) and increasing nocturnal hypoxemia from early to mid-pregnancy were associated with a higher risk of LGA in BMI-adjusted models. SDB and nocturnal hypoxemia were not associated with SGA. CONCLUSIONS: SDB in pregnancy was not associated with an increased risk of LGA or SGA birthweight, independent of BMI. Some measures nocturnal hypoxemia were associated with an increase in LGA risk, independent of BMI. ClinicalTrials.gov Registration number NCT02231398.

Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea.

BACKGROUND: Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea (OSA). We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA. The effects of continuous positive airway pressure (CPAP) therapy on endothelial function and repair capacity were assessed. METHODS AND RESULTS: Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied. Proteins that regulate basal endothelial nitric oxide (NO) production (endothelial NO synthase [eNOS] and phosphorylated eNOS) and inflammation (cyclooxygenase-2 and inducible NOS) and markers of oxidative stress (nitrotyrosine) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy. Vascular reactivity was measured by flow-mediated dilation. Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity. Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59% and 94%, respectively, in patients with OSA compared with control subjects. Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects, whereas inducible NOS expression was 56% greater. Expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine, cyclooxygenase-2, and inducible NOS significantly decreased in patients who adhered to CPAP > or = 4 hours daily. Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects, and both significantly increased in patients who adhered to CPAP > or = 4 hours daily. CONCLUSIONS: OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity. Effective CPAP therapy is associated with the reversal of these alterations.

The variable response-stimulus interval effect and sleep deprivation: an unexplored aspect of psychomotor vigilance task performance.

STUDY OBJECTIVES: The Psychomotor Vigilance Task (PVT) contains variable response-stimulus intervals (RSI). Our goal is to investigate the effect of RSI on performance to determine whether sleep deprivation affects the ability to attend to events across seconds and whether this effect is independent of impairment in sustaining attention across minutes, as measured by time on task. DESIGN: A control group following their normal sleep routines and 3 groups exposed to 54 hours of total sleep deprivation performed a 10-minute PVT every 6 hours for 9 total test runs. SETTING: Sleep deprivation occurred in a sleep laboratory with continuous behavioral monitoring; the control group took the PVT at home. SUBJECTS: Eighty-four healthy sleepers (68 sleep deprivation, 16 controls; 22 women; aged 18-35 years). MEASUREMENTS AND RESULTS: Across groups, as the RSI increased from 2 to 10 seconds, mean RT was reduced by 69 milliseconds (main effect of RSI, P < 0.001). There was no interaction between the sleep deprivation and RSI effects. As expected, there was a significant interaction of sleep deprivation and time on task for mean RT (P = 0.002). Time on task and RSI effects were independent. Parallel analyses of percentage of lapses and percentage of false starts produced similar results. CONCLUSIONS: We demonstrate that the cognitive mechanism of attention responsible for response preparation across seconds is distinct from that for maintaining attention to task performance across minutes. Of these, only vigilance across minutes is degraded by sleep deprivation. Theories of sleep deprivation should consider how this pattern of spared and impaired aspects of attention may affect real-world performance.

Sleep disordered breathing in patients with acutely decompensated heart failure.

OBJECTIVE: The purpose of this study is to systematically characterize sleep disordered breathing (SDB) during acute heart failure (HF) decompensation. BACKGROUND: SDB, both Cheyne-Stokes breathing (CSB) and obstructive sleep apnea, is common in stable congestive HF patients, but its presence and characteristics in decompensated HF is unknown. METHODS: Eighteen men and 11 women (mean age 57+/-17 years, plasma brain-natriuretic peptide 1660+/-1179pg/ml, left ventricular ejection fraction 20+/-6%) admitted with decompensated systolic HF without other active cardiorespiratory morbidity underwent echocardiography and overnight bedside polysomnography within 48h of admission. Ten patients underwent follow-up polysomnography just before or immediately after hospital discharge. RESULTS: Twenty-eight of 29 patients demonstrated an apnea+hypopnea index (AHI)>5 events/h (mean AHI 41+/-29/h); 22 patients had an AHI>15/h. SDB was predominantly CSB (central events 39+/-29/h; obstructive events 2+/-2/h, p<0.001). Time in CSB was 51+/-33% of total sleep time (TST); nadir oxygen saturation (SaO2) was 81+/-10%. SDB was similar on admission vs. follow-up polysomnography (mean AHI 44+/-39/h vs. 38+/-31/h; CSB 53+/-38% vs. 46+/-37% TST). Follow-up polysomnography showed a higher nadir SaO2 than admission (84+/-11% vs. 79+/-12%, p=0.05), but TST with SaO2<90% was not reduced. CONCLUSIONS: CSB is common and severe in patients hospitalized with decompensated HF. Acute treatment of HF does not consistently improve CSB. The effect of CSB on ventricular function and prognosis in decompensated HF remains to be demonstrated.

Quantification of single-breath underestimation of lung volume in emphysema.

The extent to which a single breath measurement represents available gas dilutional as well as compressible thoracic volume in emphysema patients has not been quantified. We therefore measured single breath (TLCSB) and rebreathe helium dilution (TLCRB), and plethysmographic lung volume (TLCpleth), in fifty-five outpatients with clinical and radiographic emphysema, and in twenty-one normal controls. Among emphysema patients, TLCSB increasingly underestimated both TLCpleth and TLCRB as FEV1% predicted decreased (p for interaction=0.001 for both) by a mean of 1.7 l for TLCRB (p<0.001) and 2.2l for TLCpleth (p<0.001). In contrast, TLCRB underestimated TLCpleth by a mean of 0.5l (p<0.001) regardless of FEV1% (p for interaction=0.25). TLCSB, TLCRB, and TLCpleth showed strong agreement among normal subjects. We conclude that TLCSB underestimates available gas dilutional and compressible lung volume as physiologic emphysema severity increases. In contrast, TLCRB and TLCpleth show closer agreement which is unaffected by physiologic emphysema severity.

Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers: the Emphysema and Cancer Action Project (EMCAP) Study.

RATIONALE: Basic science research suggests a causal role for endothelial dysfunction in chronic obstructive pulmonary disease (COPD). Clinical studies examining endothelial function are lacking, particularly early in the disease. Flow-mediated dilation (FMD) is a physiologic measure of endothelial reactivity to endogenous nitric oxide. OBJECTIVES: We hypothesized that lower FMD among former smokers would be associated with lower post-bronchodilator FEV(1), higher percentage of emphysema using computed tomography (CT) and lower diffusing capacity. METHODS: We measured FMD, pulmonary function, and CT percentage of emphysema in a random sample of 107 cotinine-confirmed former smokers in the ongoing EMCAP study. FMD was defined as percentage change in the brachial artery diameter with reactive hyperemia. Generalized additive models were used to adjust for potential confounders and assess linearity. MEASUREMENTS AND MAIN RESULTS: Mean age of participants was 71 +/- 5 years, 46% were female, and pack-years averaged 48 +/- 26. Mean FMD was 3.8 +/- 3.1%; mean post-bronchodilator FEV(1), 2.3 +/- 0.8 L; and mean CT percentage of emphysema, 26 +/- 10%. A 1 SD decrease in FMD was associated with a 132-ml (95% confidence interval, 16-248 ml; P = 0.03) decrement in post-bronchodilator FEV(1) and a 2.6% (95% confidence interval, 0.5-4.7%; P = 0.02) increase in CT percentage of emphysema in fully adjusted models. These associations were linear across the spectrum from normality to disease, independent of smoking history, and also significant among participants without COPD. Associations with diffusing capacity were consistent but nonsignificant (P = 0.09). The FMD-FEV(1) association was entirely attributable to percentage of emphysema. CONCLUSIONS: Impaired endothelial function, as measured by FMD, was associated with lower FEV(1) and higher CT percentage of emphysema in former smokers early in COPD.

Reproducibility and validity of a handheld spirometer.

BACKGROUND: Handheld spirometers have several advantages over desktop spirometers, but worries persist regarding reproducibility and validity of data from handheld spirometers. We undertook an independent examination of the EasyOne handheld spirometer. METHODS: The laboratory testing included reproducibility and validity testing with a waveform generator. We used standard American Thoracic Society waveforms for in-line testing, calibration adaptor testing, and testing during compression of the mouthpiece. The clinical testing involved repeated tests with 24 spirometry-naïve volunteers and comparison to spirometry results from laboratory (volume-sensing dry rolling seal) spirometer. RESULTS: The EasyOne exceeded standard thresholds for acceptability with the American Thoracic Society waveforms. In-line testing yielded valid results from the EasyOne. Between the EasyOne and the reference spirometer readings the mean +/- SD difference was 0.03 +/- 0.23 L for forced vital capacity (FVC) and -0.06 +/- 0.09 L for forced expiratory volume in the first second (FEV(1)). The calibration adaptor showed no appreciable problems. Extreme compression of the mouthpiece reduced the measured values. In clinical testing the coefficients of variation and limits of agreement were, respectively, 3.3% and 0.24 L for FVC, 2.6% and 0.18 L for FEV(1), and 1.9% and 0.05 for the FEV(1)/FVC ratio. The EasyOne readings were lower than those from the reference spirometer; the differences were: -0.12 L for FVC, -0.17 L for FEV(1), and -0.02 for FEV(1)/FVC. The limits of agreement were within criteria for FVC but not for the FEV(1), possibly due to a training effect. CONCLUSION: The EasyOne spirometer yielded generally reproducible results that were generally valid, compared to the values from the laboratory spirometer. The use of the EasyOne in clinical, occupational, and research settings seems justified.

Sleep disruption as a predictor of quality of life among patients in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS).

Study Objectives: Sleep quality is poor among patients with chronic obstructive pulmonary disease (COPD), and studies show that sleep disturbance is associated with low overall quality of life in this population. We evaluated the impact of patient-reported sleep quality and sleep apnea risk on disease-specific and overall quality of life within patients with COPD enrolled in the SPIROMICS study, after accounting for demographics and COPD disease severity. Methods: Baseline data from 1341 participants [892 mild/moderate COPD (FEV1 ≥ 50% predicted); 449 severe COPD (FEV1 < 50%)] were used to perform three nested (blocks) regression models to predict quality of life (Short Form-12 mental and physical components and St. George's Respiratory Questionnaire). Dependent measures used for the nested regressions included the following: Block1: demographics and smoking history; Block 2: disease severity (forced expiratory volume 1 s; 6 min walk test); Block 3: risk for obstructive sleep apnea (OSA; Berlin questionnaire); and Block 4: sleep quality (Pittsburgh Sleep Quality Index [PSQI]). Results: Over half of participants with COPD reported poor sleep quality (Mean PSQI 6.4 ± 3.9; 50% with high risk score on the Berlin questionnaire). In all three nested regression models, sleep quality (Block 4) was a significant predictor of poor quality of life, over and above variables included in blocks 1-3. Conclusions: Poor sleep quality represents a potentially modifiable risk factor for poor quality of life in patients with COPD, over and above demographics and smoking history, disease severity, and risk for OSA. Improving sleep quality may be an important target for clinical interventions. Clinical Trial: SPIROMICS. Clinical Trial URL: http://www2.cscc.unc.edu/spiromics/. Clinical Trial Registration: ClinicalTrials.gov NCT01969344.

Association Between Sleep-Disordered Breathing and Hypertensive Disorders of Pregnancy and Gestational Diabetes Mellitus.

OBJECTIVE: To estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM). METHODS: In this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models. RESULTS: Three thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM. CONCLUSION: There is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM.