Comorbid insomnia and sleep apnea: characterization of the syndrome and understanding its associations with comorbid sleep conditions.

PURPOSE: Obstructive sleep apnea (OSA) is traditionally associated with excessive daytime sleepiness. Insomnia is characterized by hyperarousal, and is seen as a predominant feature in a subgroup of patients with OSA. The aim of this study was to describe the prevalence of comorbid insomnia and sleep apnea (COMISA) in a sleep apnea population and to characterize its features. METHODS: This was a chart review of patients who underwent overnight polysomnography (PSG). All patients completed questionnaires with the Epworth Sleepiness Scale (ESS), and symptoms of insomnia and other sleep-related comorbidities. Patients with OSA on the PSG were included. RESULTS: A total of 296 patients with OSA were included, of which 80% reported at least 1 major symptom of insomnia: 57% reported sleep onset insomnia, 68% sleep maintenance insomnia, and 48% had early morning awakenings. COMISA (OSA plus 2 or more major symptoms of insomnia) was seen in 63%. These patients were more likely to report an abnormal ESS score, gastroesophageal reflux (GER), and restless legs (RL) than those without; no difference was seen in self-reported sleep bruxism. Among the patients with COMISA, 85% reported at least 1 representative symptom of psychophysiological insomnia (PPI); each of the 5 PPI symptoms was present in at least 40% of patients with COMISA. CONCLUSIONS: Insomnia is extremely prevalent in our population of patients with OSA, accompanied by daytime sleepiness and symptoms of PPI, GER, and RL. Further study is needed to determine the interactions between symptoms and OSA treatments in these patients.

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.

Gender and age influence the effects of slow-wave sleep on respiration in patients with obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is influenced by sleep architecture with rapid eye movement (REM) sleep having the most adverse influence, especially in women. There is little data defining the influence of slow-wave sleep (SWS) on OSA. We wished to study the influence of SWS on OSA and identify differences attributable to gender and/or age, if any. METHODS: Retrospective study of polysomnography (PSG) records of adult patients referred for diagnostic PSG. Records were excluded if they underwent split night or positive airway pressure titration studies, had <180 min of total sleep time (TST) and/or <40% sleep efficiency, or had SWS <5 min and/or <1% of TST. The apnea-hypopnea index (AHI) recorded during SWS was compared with that measured during other non-rapid eye movement (NREM) sleep and during REM sleep. The REM-SWS difference in AHI was measured, and compared between genders. RESULTS: Records from 239 patients were included. The mean AHI in all subjects was 17.7 ± 22.6. The SWS AHI was 6.8 ± 18.9, compared to the REM AHI of 24.9 ± 25.8, and NREM AHI of 15.8 ± 22.8. Females had significantly higher SWS by percentage, and lower NREM AHI (P < 0.0001) and SWS AHI (P = 0.03). Among patients with OSA (AHI ≥5), the difference between REM AHI and SWS AHI was greater in women than in men (34.2 ± 27.4 vs. 21.6 ± 26.0, P = 0.006). CONCLUSIONS: The upper airway appears to be less susceptible to OSA during SWS than during REM and other NREM sleep. This may be related to phase-specific influences on both dynamic upper airway control as well as loop gain. Gender and age appear to modify this effect.

Experience With Adaptive Servo-Ventilation Among Veterans in the Post-SERVE-HF Era.

Background: The sleep medicine community has struggled to identify the ideal role for adaptive servo-ventilation (ASV) therapy following a study that found increased mortality in patients with central sleep apnea (CSA) and heart failure with reduced ejection fraction who used ASV therapy. We aimed to identify characteristics of patients who benefit from ASV therapy. Methods: We performed a record review of all patients treated with ASV therapy at the Hampton Veterans Affairs Medical Center in Virginia from January 1, 2015, to April 30, 2020. Clinical and polysomnographic characteristics of patients adherent to therapy were compared with those that were not adherent. Results: Our cohort of 31 patients was entirely male with a mean age of 67.2 years, body mass index of 34.0, and Epworth Sleepiness Scale score of 10.9. Primary CSA was initially diagnosed in 3 patients (10%), comorbid obstructive sleep apnea (OSA) and CSA in 9 (29%), and primary OSA in 19 (61%). Seventeen patients (55%) met minimal adherence criteria with ASV therapy. The obstructive apnea-hypopnea index (AHI), as a proportion of the total pretreatment AHI, was higher in adherent patients (81.5%) vs nonadherent patients (46.7%) (P = .02). The median residual AHI was lower in the adherent group, both as absolute values (1.7 vs 4.7 events/h; P = .004) and as a percentage of the pretreatment AHI (3.1% vs 10.2%; P = .002). Conclusions: Patients using ASV devices regularly have a larger component of obstructive sleep-disordered breathing and obtain greater objective benefit from ASV than those that do not. This understanding may help to identify patients that will most benefit from this debated form of therapy.

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

PURPOSE: Obstructive 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. METHODS: Subjects 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. RESULTS: In 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. CONCLUSIONS: The NAMES assessment is an effective, inexpensive screening strategy for moderate to severe OSA.

The Prevalence of Anxiety and Depression Symptoms in Obstructive Sleep Apnea.

Objectives Mood disorders are common in obstructive sleep apnea (OSA), though the interactions are not well-understood. The objective of this study was to evaluate the relationship between anxiety and depression with OSA.  Methods Patients who presented to the sleep center underwent polysomnography (PSG). Records were included if the sleep study showed OSA (Apnea-Hypopnea Index (AHI) ≥5 events/hour). All patients completed an Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS). A score of 8 or higher on the respective portion of the HADS was abnormal. Results A total of 45 records were included, with 28 scoring positive for anxiety and 29 positive for depression. Patients with anxiety had lower AHI (median (interquartile ratio)) than those without (21.4 (9.6-41.3) vs. 50.5 (25.1-94.3); p=0.0076). The peripheral oxygen saturation (SpO2) nadir (80 (74-84)% vs. 65 (57-76)%; p=0.0007) and time with SpO2 <90% (11 (6-12) minutes vs. 36 (13-68) minutes; p=0.0002) were less abnormal in patients with anxiety. The anxiety score on the HADS weakly correlated with AHI (r = -0.29). Patients with depression were not significantly different than those without depression in AHI, SpO2 nadir, and time with SpO2 <90%. Conclusions Symptoms of anxiety and depression are both prevalent in patients with OSA. There is an inverse relationship between OSA severity and the presence of anxiety, suggesting that comorbid anxiety may prompt sleep evaluation in less severe disease. Depression symptoms did not demonstrate a similar relationship with OSA severity.

A Study to Assess the Relationship between Attention Deficit Hyperactivity Disorder and Obstructive Sleep Apnea in Adults.

The association between obstructive sleep apnea (OSA) and attention deficit hyperactivity disorder (ADHD) is well-established in children. However, there is a paucity of literature regarding this association in adults. The aim of this study was to determine if ADHD is more common in adult patients with OSA. All patients referred to a sleep center for sleep evaluation were administered the Adult ADHD Self-Report Scale and diagnostic polysomnogram. The ADHD screen is considered positive if 4 of 6 questions in part A of the screening questionnaire were answered abnormally. The study population consisted of 194 participants, predominantly male (62%), Caucasian (54%), and Hispanic (44%). OSA was identified in 160 (83%) of participants, with 116 (60%) having moderate to severe OSA. The ADHD screen was positive in 37 (19%) of participants. There was no significant association between the severity of OSA and presence of ADHD symptoms. Patients with OSA who screened positive for ADHD had higher Epworth Sleepiness Scale scores than those that did not. These data suggest that ADHD is more prevalent in patients with OSA, but do not demonstrate a relationship between OSA severity and ADHD symptoms. Interestingly, sleepiness is more prominent in patients with ADHD.

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.

Use of sodium bicarbonate and blood gas monitoring in diabetic ketoacidosis: A review.

Diabetic ketoacidosis (DKA) is a severe and too-common complication of uncontrolled diabetes mellitus. Acidosis is one of the fundamental disruptions stemming from the disease process, the complications of which are potentially lethal. Hydration and insulin administration have been the cornerstones of DKA therapy; however, adjunctive treatments such as the use of sodium bicarbonate and protocols that include serial monitoring with blood gas analysis have been much more controversial. There is substantial literature available regarding the use of exogenous sodium bicarbonate in mild to moderately severe acidosis; the bulk of the data argue against significant benefit in important clinical outcomes and suggest possible adverse effects with the use of bicarbonate. However, there is scant data to support or refute the role of bicarbonate therapy in very severe acidosis. Arterial blood gas (ABG) assessment is an element of some treatment protocols, including society guidelines, for DKA. We review the evidence supporting these recommendations. In addition, we review the data supporting some less cumbersome tests, including venous blood gas assessment and routine chemistries. It remains unclear that measurement of blood gas pH, via arterial or venous sampling, impacts management of the patient substantially enough to warrant the testing, especially if sodium bicarbonate administration is not being considered. There are special circumstances when serial ABG monitoring and/or sodium bicarbonate infusion are necessary, which we also review. Additional studies are needed to determine the utility of these interventions in patients with severe DKA and pH less than 7.0.

Development and validation of a tool to assess knowledge of healthy lifestyles in early grade school children.

OBJECTIVE: Healthy habits during childhood has been of prime importance. We aimed to gather baseline information about health habits from children in kindergarten and first grade (typically ages 5-7). Our objectives were to validate the questionnaire in assessing health habits, as well as the electronic audience response system, iClicker (MPS, Gordonsville, VA), in this age group. RESULTS: The questionnaire completed by 75 kindergarteners and 66 first graders. For the first graders, questions involving healthy choices were answered correctly 78% of the time (range 8-94%) and had 84% agreement on repeat testing (range 64-93%). Questions on diabetes were answered correctly 79% of the time (range 65-94%) and had 85% agreement on repeat testing. Crohnbach's alpha was calculated to determine the reliability of the questionnaire: on the revised kindergarten questionnaire, this ranged from 0.79 to 0.81 on Day 1 and 0.84-0.97 on Day 5; for the first graders, this ranged 0.79-0.81 on Day 1 and 0.84-0.97 on Day 5. Both kindergarteners and first graders answered the simplest of the basic knowledge questions correctly > 80% of the time, with acceptable test-retest agreement. Additionally, these children demonstrated acceptable understanding of the use of the iClicker classroom response system.

Single injection of P-selectin or P-selectin glycoprotein ligand-1 monoclonal antibody blocks neointima formation after arterial injury in apolipoprotein E-deficient mice.

BACKGROUND: Emerging data suggest that P-selectin, by controlling adhesion of white blood cells, may be important in limiting the response to vascular injury. METHODS AND RESULTS: We tested the hypothesis that transient inhibition of P-selectin with either anti-P-selectin monoclonal antibody (mAb) or anti-P-selectin glycoprotein ligand-1 (PSGL-1) mAb would reduce neointima formation in the setting of carotid denudation injury in atherosclerosis-prone apolipoprotein E-/- mice. Neointima formation at 28 days was reduced significantly, by 50% or 80%, by a single injection on the day of injury of 100 or 200 microg P-selectin mAb RB 40.34 and by 55% by a single injection of 100 microg PSGL-1 mAb 4RA10 (P< or =0.005). In addition, there was a significant reduction in neointimal macrophage content. CONCLUSIONS: These findings demonstrate that transient P-selectin or PSGL-1 blockade at the time of arterial injury significantly limits plaque macrophage content and neointima formation in a dose-dependent manner after carotid denudation injury in apolipoprotein E-/- mice.

Rosiglitazone reduces the accelerated neointima formation after arterial injury in a mouse injury model of type 2 diabetes.

BACKGROUND: Hyperglycemia (HG) and hyperinsulinemia (HI) may be factors enhancing the atherosclerotic complications of diabetes. We hypothesized that specific feeding of C57BL/6 apolipoprotein (apo) E-/- mice would alter their metabolic profiles and result in different degrees of neointima (NI) formation. We additionally hypothesized that an insulin-sensitizing agent (rosiglitazone) would prevent the development of type 2 diabetes and reduce neointima formation after carotid wire injury measured at 28 days. METHODS AND RESULTS: Fasting glucose and insulin levels were elevated in the Western diet (WD) group, with a trend toward higher insulin levels and euglycemia in the fructose diet (FD)--fed mice. NI formation was exaggerated in the WD group compared with the FD or chow control groups. In the WD mice given rosiglitazone, glucose and insulin levels remained normal and NI formation was significantly reduced, as was NI macrophage content. CONCLUSIONS: These findings demonstrate that apoE-/- mice fed a WD develop type 2 diabetes with an exaggerated NI response to injury. FD mice maintain euglycemia but develop insulin resistance, with an intermediate degree of NI growth compared with chow diet controls. Rosiglitazone prevents the development of hyperglycemia and hyperinsulinemia and normalizes the insulin release profile in the apoE-/-, WD-fed mouse and significantly reduces NI formation by 65% after carotid wire injury while reducing macrophage infiltration. These data support the hypothesis that type 2 diabetes in the setting of elevated cholesterol accelerates the response to vascular injury and suggest that agents that improve insulin sensitivity may have therapeutic value in reducing restenosis in type 2 diabetes.

Sleep Quality and Vigilance Differ Among Inpatient Nurses Based on the Unit Setting and Shift Worked.

OBJECTIVES: Sleepiness in nurses has been shown to impact patient care and safety. The objectives of this study are to measure sleep quality, sleepiness, fatigue, and vigilance in inpatient nurses and to assess how setting (intensive care unit versus the general floor) and shift worked (day versus night) affect these measures. METHODS: Nurses from both the ICU and floor were included in the study. Participants completed questionnaires assessing self-reported sleep quality (Pittsburgh Sleep Quality Index, PSQI), sleepiness (Stanford Sleepiness Scale and Epworth Sleepiness Scale, ESS), and fatigue (Fatigue Severity Scale, FSS). Vigilance was measured by means of the psychomotor vigilance test (PVT), before and after a 12-hour duty shift. RESULTS: The ESS was abnormal in 22% of all nurses, the FSS was abnormal in 33%, and the global PSQI was abnormal in 63%. More ICU nurses than floor nurses reported abnormal sleep quality (component 5) on the PSQI. Sleep medication use (PSQI component 6) was higher in night shift nurses. The FSS was greater in night shift nurses. On preshift PVT testing, day-shift nurses overall provided faster mean reaction time (RT) than night-shift nurses. ICU nurses working the day shift made more than twice as many total errors and false starts than day shift floor nurses. Floor nurses demonstrated a significant decrease from preshift to postshift in the mean of the fastest 10% RT. CONCLUSIONS: Our data indicate that a significant number of inpatient nurses have impaired sleep quality, excessive sleepiness, and abnormal fatigue, which may place them at a greater risk of making medical errors and harming patients; these problems are especially pronounced in night shift workers. PVT results were inconsistent, but floor and day shift nurses performed better on some tasks than ICU and night shift nurses.

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 Children's 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.

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.

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.

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 (FEV(1)/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.