Sean Hesselbacher

Cross-Sectional Analysis of the Utility of Pulmonary Function Tests in Predicting Emphysema in Ever-Smokers

Emphysema is largely an under-diagnosed medical condition that can exist in smokers in the absence of airway obstruction. We aimed to determine the sensitivity and specificity of pulmonary function tests (PFTs) in assessing emphysema using quantitative CT scans as the reference standard. We enrolled 224 ever-smokers (current or former) over the age of 40. CT of thorax was used to quantify the low attenuation area (% emphysema), and to measure the standardized airway wall thickness. PFTs were used individually and in combination to predict their ability to discriminate radiographic emphysema. Significant emphysema (>7%) was detected in 122 (54%) subjects. Twenty six (21%) emphysema subjects had no evidence of airflow obstruction (FEV1/FVC ratio <70%), while all subjects with >23% emphysema showed airflow obstruction. The sensitivity and specificity of spirometry for detecting radiographic emphysema were 79% and 75%, respectively. Standardized airway wall thickness was increased in subjects with airflow obstruction, but did not correlate with emphysema severity. In this cohort of lifetime ever-smokers, PFTs alone were inadequate for diagnosing emphysema. Airway wall thickness quantified by CT morphometry was associated with airflow limitation, but not with emphysema indicating that the heterogeneous nature of lung disease in smokers may represent distinct phenotypes.

Clinical and Immunological Factors in Emphysema Progression. Five-Year Prospective Longitudinal Exacerbation Study of Chronic Obstructive Pulmonary Disease (LES-COPD).

RATIONALE Cross-sectional studies of T-cell responses to self-antigens correlate with baseline emphysema severity. OBJECTIVES We investigated whether clinical and/or immunological factors could predict disease progression, such as emphysema, FEV1, and 6-minute-walk distance (6MWD), in former and active smokers in a 5-year prospective study. METHODS We recruited 224 ever smokers over 40 years of age and with greater than a 15 pack-year smoking history. MEASUREMENTS AND MAIN RESULTS Repeated spirometry, 6MWD, and peripheral blood T-cell cytokine responses to lung elastin fragments were measured. Baseline and repeat chest computed tomography (CT) scans (34 to 65 mo apart) were used to quantify emphysema progression. Of the 141 ever-smokers with baseline and repeat CT scans, the mean (SD) annual rate of change in percent emphysema was +0.46 (0.92), ranging from -1.8 to +4.1. In multivariable analyses, the rate of emphysema progression was greater in subjects who had lower body mass index (BMI) (+0.15 per 5-unit decrease in BMI; 95% confidence interval, +0.03 to +0.29). In active smokers, increased IFN-γ and IL-6 T-cell responses had a positive association with the annual rate of emphysema progression. Male sex and IL-6 T-cell responses to elastin fragments were significantly associated with annual 6MWD decline, whereas IL-13 was associated with an increase in annual 6MWD. CONCLUSIONS The rate of emphysema progression quantified by CT scans among ever-smokers was highly variable; clinical factors and biomarkers explained only some of the variability. Aggressive clinical care that targets active smokers with autoreactive T cells and low BMI may temporize progression of emphysema.

The NAMES assessment: a novel combined-modality screening tool for obstructive sleep apnea

PurposeObstructive sleep apnea (OSA) remains underdiagnosed, despite our understanding of its impact on general health. Current screening methods utilize either symptoms or physical exam findings suggestive of OSA, but not both. The purpose of this study was to develop a novel screening tool for the detection of OSA, the NAMES assessment (neck circumference, airway classification, comorbidities, Epworth scale, and snoring), combining self-reported historical factors with physical exam findings.MethodsSubjects were adults without previously diagnosed OSA, referred to a community sleep center for suspicion of OSA. General health, Epworth Sleepiness Scale (ESS), and Berlin questionnaires were completed, and a physical exam focusing on modified Friedman (MF) grade, body mass index (BMI), and neck circumference (NC) was performed prior to polysomnography. OSA was defined by a respiratory disturbance index ≥15. Each variable was dichotomized, and cutoff values were determined for the NAMES tool in a pilot group of 150 subjects. The NAMES score was calculated from NC, MF, comorbidities, ESS, and loud snoring values. The performances of the NAMES, Berlin questionnaire, and ESS screening tests in predicting OSA were then compared in a validation group of 509 subjects.ResultsIn the pilot population, the cutoff value for the composite NAMES tool was calculated at ≥3 points. In the validation group, NAMES demonstrated similar test characteristics to the Berlin questionnaire, and sensitivity was better than that seen with the Epworth scale. The addition of BMI and gender to the tool improved screening characteristics.ConclusionsThe NAMES assessment is an effective, inexpensive screening strategy for moderate to severe OSA.

Body Mass Index, Gender, and Ethnic Variations Alter the Clinical Implications of the Epworth Sleepiness Scale in Patients with Suspected Obstructive Sleep Apnea§

Introduction: The Epworth Sleepiness Scale (ESS) is often used in the evaluation of obstructive sleep apnea (OSA), though questions remain about the influence gender, ethnicity, and body morphometry have in the responses to this questionnaire. The aim of this study was to examine differences in ESS scores between various demographic groups of patients referred for polysomnography, and the relationship of these score to sleep-disordered breathing Methods: Nineteen hundred consecutive patients referred for polysomnographic diagnosis of OSA completed questionnaires, including demographic data and ESS. OSA was determined based on a respiratory disturbance index (RDI) ≥15 by polysomnography. Results: In this high risk population for OSA, the ESS was 10.7 ± 5.6. The highest ESS scores were seen in obese males; non-obese females and non-obese Caucasian males scored the lowest. ESS was weakly correlated with RDI (r = 0.17, P < 0.0001). The sensitivity of ESS for the diagnosis of OSA was 54% and the specificity was 57%. The positive (PPV) and negative (NPV) predictive values were 64% and 47%, respectively. In obese subjects, the sensitivity and specificity were 55% and 53%, compared with 47% and 63% in non-obese subjects. In obese, Hispanic males, the sensitivity, specificity, and PPV were 59%, 54%, and 84%, respectively. In non-obese, Caucasian females, the sensitivity, specificity, and NPV were 43%, 59%, and 72%. Conclusions: The ESS appears to be affected by many factors, including gender, ethnicity, and body morphometry. The ability of the ESS to predict OSA is modest, despite a significant correlation with the severity of OSA. The test characteristics improve significantly when applied to select populations, especially those at risk for OSA.

Autoreactive T Cells in Human Smokers is Predictive of Clinical Outcome

Cross-sectional studies have suggested a role for activation of adaptive immunity in smokers with emphysema, but the clinical application of these findings has not been explored. Here we examined the utility of detecting autoreactive T cells as a screening tool for emphysema in an at-risk population of smokers. We followed 156 former and current (ever)-smokers for 2 years to assess whether peripheral blood CD4 T cell cytokine responses to lung elastin fragments (EFs) could discriminate between those with and without emphysema, and to evaluate the relevance of autoreactive T cells to predict changes during follow-up in lung physiological parameters. Volunteers underwent baseline complete phenotypic assessment with pulmonary function tests, quantitative chest CT, yearly 6-min walk distance (6MWD) testing, and annual measurement of CD4 T cell cytokine responses to EFs. The areas under the receiver operating characteristic curve to predict emphysema for interferon gamma (IFN-γ), and interleukin 6 (IL-6) responses to EFs were 0.81 (95% CI of 0.74–0.88) and 0.79 (95% CI of 0.72–0.86) respectively. We developed a dual cytokine enzyme-linked immunocell spot assay, the γ-6 Spot, using CD4 T cell IFN-γ and IL-6 responses and found that it discriminated emphysema with 90% sensitivity. After adjusting for potential confounders, the presence of autoreactive T cells was predictive of a decrease in 6MWD over 2 years (decline in 6MWD, −19 m per fold change in IFN-γ; P = 0.026, and −26 m per fold change in IL-6; P = 0.003). In support of the human association studies, we cloned CD4 T cells with characteristic T helper (Th)1 and Th17 responses to EFs in the peripheral blood of ever-smokers with emphysema, confirming antigenicity of lung elastin in this population. These findings collectively suggest that the EF-specific autoreactive CD4 T cell assay, γ-6 Spot, could provide a non-invasive diagnostic tool with potential application to large-scale screening to discriminate emphysema in ever-smokers, and predict early relevant physiological outcomes in those at risk.

Self-reported sleep bruxism and nocturnal gastroesophageal reflux disease in patients with obstructive sleep apnea: relationship to gender and ethnicity.

Study Objectives : Nocturnal bruxism is associated with gastroesophageal reflux disease (GERD), and GERD is strongly associated with obstructive sleep apnea (OSA). Gender and ethnic differences in the prevalence and clinical presentation of these often overlapping sleep disorders have not been well documented. Our aim was to examine the associations between, and the symptoms associated with, nocturnal GERD and sleep bruxism in patients with OSA, and to examine the influence of gender and ethnicity. Methods : A retrospective chart review was performed of patients diagnosed with OSA at an academic sleep center. The patients completed a sleep questionnaire prior to undergoing polysomnography. Patients with confirmed OSA were evaluated based on gender and ethnicity. Associations were determined between sleep bruxism and nocturnal GERD, and daytime sleepiness, insomnia, restless legs symptoms, and markers of OSA severity in each group. Results : In these patients with OSA, the prevalence of nocturnal GERD (35%) and sleep bruxism (26%) were higher than the general population. Sleep bruxism was more common in Caucasians than in African Americans or Hispanics; there was no gender difference. Nocturnal GERD was similar among all gender and ethnic groups. Bruxism was associated with nocturnal GERD in females, restless legs symptoms in all subjects and in males, sleepiness in African Americans, and insomnia in Hispanics. Nocturnal GERD was associated with sleepiness in males and African Americans, insomnia in females, and restless legs symptoms in females and in Caucasians. Conclusion : Patients with OSA commonly have comorbid sleep bruxism and nocturnal GERD, which may require separate treatment. Providers should be aware of differences in clinical presentation among different ethnic and gender groups.

Sleep Habits of Elementary and Middle School Children in South Texas

Background. Sleep difficulties, including insufficient sleep and inadequate sleep hygiene, have been prevalent among children. Sleep deprivation can lead to poor grades, sleepiness, and moodiness. We undertook this study to assess the prevalence of sleep abnormalities among elementary and middle school students in South Texas and how the groups compare with one another. Method. After approval from the appropriate school district for a sleep education program, a baseline survey was taken of elementary and middle school students, using the Childrens Sleep Habit Questionnaire-Sleep Self-Report Form, which assessed the domains of bedtime resistance, sleep onset delay, sleep anxiety, sleep duration, night awakening, and daytime sleepiness. Results. The survey was completed by 499 elementary and 1008 middle school children. Trouble sleeping was reported by 43% in elementary school, compared with 29% of middle school children. Fifty percent of middle school children did not like sleeping, compared with 26% in elementary school. Bedtime resistance, sleep onset delay, and nighttime awakening were more common among elementary school students. Daytime sleepiness was more common among the middle school children when compared to elementary school children. Conclusions. Sleep abnormalities are present in elementary school children with changes in sleep habits into middle school.

Resolution of Sleepwalking Behavior after Initiation of Sodium Oxybate in a Patient with Narcolepsy Type 2

A 44-year-old male veteran with long-standing excessive daytime sleepiness was diagnosed with Narcolepsy Type 2. The patient was unable to tolerate effective doses of methylphenidate, due to mood disturbances, or modafinil, due to adverse gastrointestinal effects. Although the patient also reported an ongoing history of sleepwalking with potentially injurious behaviors, a cautious trial of sodium oxybate was initiated. The combination of sodium oxybate and low dose methylphenidate resulted in significant improvement in patient-reported subjective daytime sleepiness. Additionally, self-report of the sleepwalking behaviors markedly improved. This case shows that patients with narcolepsy and sleepwalking may still safely benefit from a cautious trial of sodium oxybate.