Publications by authors named "Chitra Lal"

26 Publications

  • Page 1 of 1

Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management.

Ann Am Thorac Soc 2021 05;18(5):757-768

Case Western Reserve University, Cleveland, Ohio.

Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.
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http://dx.doi.org/10.1513/AnnalsATS.202006-696FRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086534PMC
May 2021

A population-based estimate of the health care burden of obstructive sleep apnea using a STOP-BAG questionnaire in South Carolina.

J Clin Sleep Med 2021 03;17(3):367-374

Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Study Objectives: Population based estimates of obstructive sleep apnea (OSA) frequency and health impact are incomplete. The aim of this study was to determine the prevalence of risk factors for physician and sleep study diagnosed OSA among individuals in a state-based surveillance program.

Methods: Using questions inserted into the 2016 (n = 5,564) and 2017 (n = 10,884) South Carolina Behavioral Risk Factor Surveillance System of the Centers for Disease Control and Prevention, we analyzed the prevalence of physician diagnosed OSA and associated comorbidities. The validated STOP-BANG questionnaire without neck circumference (STOP-BAG) defined populations at moderate risk (score 3-4) and high risk (score 5-7). Statistical analysis using weighted prevalence and means and their 95% confidence intervals (CI) thus reflect population estimates of disease burden.

Results: The population-based prevalence of physician diagnosed OSA in South Carolina was 9.7% (95% CI: 9.0-10.4). However, the populations with moderate risk (18.5%, 95% CI: 17.3-19.8) and high risk (25.5%, 95% CI: 23.9-27.1) for OSA, as determined by the STOP-BAG questionnaire, were much higher. Compared to those at low risk for OSA, those at high risk were more often diagnosed with coronary heart disease, stroke, asthma, skin cancer, other cancers, chronic obstructive pulmonary disease, arthritis, depression, kidney disease, and diabetes (all P < .001).

Conclusions: OSA is common and strongly associated with major comorbidities. As such, this public health crisis warrants more diagnostic and therapeutic attention. The STOP-BAG questionnaire provides a public health platform to monitor this disease.
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http://dx.doi.org/10.5664/jcsm.8860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927332PMC
March 2021

Emerging Treatments for COPD: Evidence to Date on Revefenacin.

COPD 2020 02 13;17(1):112-119. Epub 2019 Dec 13.

Division of Pulmonary, and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA.

Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death in the United States. Due to the substantial public health burden of COPD, there has been a lot of interest in developing new drug therapies, directed at improving the symptomatology and quality of life in COPD patients. Revefenacin is the first once daily nebulized long acting muscarinic antagonist for COPD treatment. It offers an advantage over other nebulized bronchodilators, as once daily administration may improve patient compliance. Revefenacin has a rapid onset of action, is long acting and significantly improves lung function (FEV1) in patients with COPD. It can play a major role in the management of COPD, especially in patients who have difficulty mastering inhaler techniques and those with low baseline FEV1 who may have difficulty generating flow with an inhaler. This manuscript is a review on revefenacin and outlines the pharmacologic profile and the clinical trials which have evaluated it's the efficacy and safety. The authors also discuss their own perspective on the potential role of revefenacin in COPD management.
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http://dx.doi.org/10.1080/15412555.2019.1702010DOI Listing
February 2020

Prevalence of self-reported sleep problems amongst adults with obstructive airway disease in the NHANES cohort in the United States.

Sleep Breath 2020 Sep 13;24(3):985-993. Epub 2019 Sep 13.

Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB 816, MSC 630, Charleston, SC, 29425, USA.

Rationale: Sleep and respiratory problems are common in adults in the USA. However, sleep problems often remain undiagnosed in patients with obstructive airway diseases (OADs). This study was designed to examine the association between sleep problems and different categories of OAD amongst US adults.

Methods: We conducted an observational, cross-sectional study using a nationally representative sample of the US civilian non-institutionalized population from 2007 to 2008 National Health and Nutritional Examination Survey (NHANES). A total of 3204 study participants aged ≥35 years were stratified into four groups, using a self-reported history of asthma and data from spirometry: asthma-COPD overlap (ACO) (n = 70, 2.2%), asthma (n = 168, 5.2%), chronic obstructive pulmonary disease (COPD) (n = 412, 12.8%), and those without any OAD (normal) (n = 2554, 79.7%). After characterizing the baseline demographics and health status of the four groups, multivariate logistic regression analysis was performed to estimate the likelihood of sleep problems in adults after adjusting for age, gender, body mass index, smoking, alcohol, obstructive sleep apnea syndrome (OSAS), depression, and diabetes. The index sample was the normal group. Sleep problems were defined as any complaints which affect or involve sleep.

Results: The participants with COPD were older (62.0 ± 11.7 years) as compared to ACO (59.1 ± 11.3 years), asthma (53.6 ± 11.3), and normal groups (53.8 ± 12.1) (p < 0.0001). Comparing baseline characteristics between the four groups, there were significant associations between OAD status and sleep problems including inadequate sleep, sleep-onset insomnia, snoring, frequent trouble sleeping, nocturnal arousals, early morning awakenings, fatigue, daytime sleepiness, use of prescription medication for sleep, leg jerks, leg cramps, difficulty in concentration, and difficulty in remembering things when tired. The multivariate logistic regression models evaluating the prevalence of sleep problems in individual OADs showed a stronger association between asthma and sleep problems as compared to COPD and ACO and sleep disorders.

Conclusion: All OADs are associated with a higher prevalence of sleep problems. There is a stronger association between asthma and sleep problems as compared to COPD and ACO. We speculate that the nocturnal burden of asthma contributes to sleep problems. Our results suggest that adults with OAD should be aggressively screened for sleep problems.
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http://dx.doi.org/10.1007/s11325-019-01941-0DOI Listing
September 2020

Evaluating fluticasone furoate + vilanterol for the treatment of chronic obstructive pulmonary disease (COPD).

Expert Opin Pharmacother 2019 Jun 14;20(9):1075-1085. Epub 2019 Apr 14.

a Pulmonary, Critical Care, Allergy and Sleep Medicine , Medical University of South Carolina , Charleston , SC , USA.

Introduction: Inhaled corticosteroid/long-acting β-2 agonists (ICS/LABA) combination inhalers have been a lifeline for a generation of chronic obstructive pulmonary disease (COPD) and asthma patients. Fluticasone furoate and Vilanterol (FF/VI) as a once-daily ICS/LABA combination have an extensive clinical trial and real-world data to support its use in COPD patients. Areas covered: The authors provide pharmacological profiles of fluticasone furoate, vilanterol and the FF/VI fixed dose combination. Salient clinical trials evaluating efficacy and safety of the FF/VI combination, and studies demonstrating the impact on COPD exacerbation risk and mortality are also discussed. Expert opinion: ICS/LABA combinations provide bronchodilation and decrease the frequency of COPD exacerbations. Individualizing treatment of each COPD patient based on unique phenotypes will maximize chances of therapeutic responsiveness. Asthma-COPD overlap (ACO), patients with sputum and/or blood eosinophilia, patients with a brisk bronchodilator response, and patients with frequent exacerbations are more likely to show a therapeutic response to ICS than populations who have none of these features. FF/VI will likely remain a popular ICS/LBA combination to treat COPD, as a once-daily inhaled therapy delivered via the Ellipta device popular with COPD patients, with extensive clinical trial and real-world data to support its use.
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http://dx.doi.org/10.1080/14656566.2019.1603292DOI Listing
June 2019

Proteomic biomarkers of cognitive impairment in obstructive sleep apnea syndrome.

Sleep Breath 2019 Mar 2;23(1):251-257. Epub 2018 Jul 2.

Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB Suite 816, MSC 630, Charleston, SC, 29425, USA.

Purpose: There are currently no biomarkers that are associated with cognitive impairment (CI) in patients with obstructive sleep apnea syndrome (OSAS). This pilot study performed an exploratory plasma proteomic analysis to discover potential biomarkers and explore proteomic pathways that differentiate OSAS subjects with and without CI.

Methods: Participants were selected from a cohort of women within 5 years of menopause not on hormone replacement therapy between the ages of 45-60 years. The Berlin questionnaire was used to select OSAS participants who then completed the MCFSI (Mail-In Cognitive Function Screening Instrument) to measure cognition. Six subjects with the highest MCFSI scores (≥ 5 denoting CI) were compared to six with normal scores. Proteomic analysis was done by Myriad RBM using a targeted ELISA for 254 serum proteins. Pathway analysis of differentially expressed proteins was performed using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) software.

Results: Distinct proteomic signatures were seen in OSAS subjects with CI as compared to those without CI. Proteins including insulin, prostasin, angiopoietin-1, plasminogen activator inhibitor 1, and interleukin-1 beta were overexpressed in OSAS subjects with CI. Proteins underexpressed in CI participants included cathepsin B, ceruloplasmin, and adiponectin. Pathway analysis revealed prominence of insulin-regulated vascular disease biomarkers.

Conclusions: Proteomic biomarkers in participants with cognitive impairment suggest roles for insulin, and vascular signaling pathways, some of which are similar to findings in Alzheimer's disease. A better understanding of the pathogenic mechanisms of CI in OSAS will help focus clinical trials needed in this patient population.
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http://dx.doi.org/10.1007/s11325-018-1693-8DOI Listing
March 2019

Down syndrome and pediatric obstructive sleep apnea surgery: A national cohort.

Laryngoscope 2018 08 27;128(8):1963-1969. Epub 2017 Dec 27.

Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, U.S.A.

Objectives/hypothesis: To analyze the trend of sleep surgeries in pediatric patients with Down syndrome (DS) and obstructive sleep apnea (OSA), and to compare this to nonsyndromic (NS) children with OSA.

Study Design: Retrospective cohort database analysis.

Methods: Analysis of the 1997 to 2012 editions of the Kid's Inpatient Database was conducted. Using International Classification of Diseases, Ninth Revision codes, all patients with OSA were identified, and subsequently, subgroups of NS children and children with DS were identified. Trends of the number and types of sleep surgeries were analyzed.

Results: A total of 48,301 and 2,991 sleep surgeries were identified in the NS and DS groups, respectively, during the study period. Tonsillectomy with adenoidectomy was the most common procedure in both groups, but the proportion of tonsillectomy with adenoidectomy decreased over time (P < .01). The proportion of palatal surgery and tracheostomy also decreased significantly, whereas there was an increase in the proportion of lingual tonsillectomies, tongue-base reduction procedures, and supraglottoplasties performed in both groups over time. The relative rates of change in these procedures were higher in the DS population.

Conclusions: Tonsillectomy with adenoidectomy remains the most commonly performed procedure, although there was a significant increase in other sleep surgeries performed (lingual tonsillectomy, tongue-base reduction, and supraglottoplasty) between the two study periods, especially in children with DS.

Level Of Evidence: 2c. Laryngoscope, 1963-1969, 2018.
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http://dx.doi.org/10.1002/lary.27063DOI Listing
August 2018

A review of current and developing fixed-dose LABA/LAMA combinations for treating COPD.

Expert Opin Pharmacother 2017 Dec 15;18(17):1833-1843. Epub 2017 Nov 15.

a Pulmonary, Critical Care, Allergy and Sleep Medicine , Medical University of South Carolina , Charleston , SC , USA.

Introduction: The current GOLD (Global Initiative for Chronic Obstructive Lung Disease) recommendations suggest using long acting β2 agonists (LABA) and long acting muscarinic antagonists (LAMA) in combination for group B COPD patients with persistent symptoms, group C COPD patients with further exacerbations on LAMA therapy alone and for group D COPD patients with or without combination with inhaled corticosteroids (ICS). Thus, there is a lot of interest in developing LABA/LAMA combinations for maintenance therapy of chronic stable COPD. Areas covered: Many LABA/LAMA combinations have successfully been approved through carefully designed pivotal clinical trials. The current clinical use of LABA/LAMA combinations in COPD will continue to evolve as new trials with and without inhaled corticosteroids are completed. Expert opinion: Combining different classes of bronchodilators in a single inhaler is an attractive concept that can potentially improve patient adherence to therapy. Because LABA/LAMA combinations are the preferred treatment option for preventing COPD exacerbations in the updated GOLD guidelines for COPD, they will be clinically used. Future treatment of COPD should revolve around a personalized approach based on characterization of the COPD phenotype.
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http://dx.doi.org/10.1080/14656566.2017.1403583DOI Listing
December 2017

Sleep-disordered Breathing and Cognitive Impairment: A Subtle but Important Association.

Authors:
Chitra Lal

Ann Am Thorac Soc 2017 11;14(11):1636-1637

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina.

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http://dx.doi.org/10.1513/AnnalsATS.201708-648EDDOI Listing
November 2017

Pulmonary Embolism in Transit Before Pulseless Electrical Activity Arrest.

Am J Med Sci 2017 Oct 6;354(4):436-437. Epub 2017 Mar 6.

Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.amjms.2017.03.004DOI Listing
October 2017

Assessment of weight gain following adenotonsillectomy in children with Down syndrome.

Int J Pediatr Otorhinolaryngol 2017 Sep 27;100:103-106. Epub 2017 Jun 27.

Medical University of South Carolina, Department of Otolaryngology - Head and Neck Surgery, United States.

Introduction: Adenotonsillectomy (T&A) has been associated with postoperative weight gain in children. The purpose of this study is to determine whether a similar association exists in children with Down syndrome (DS).

Methods: The medical records of 311 DS patients were reviewed. Subjects were classified into either a control group or surgical group based on whether they had undergone adenotonsillectomy (T&A). Subjects were excluded if they only had one recorded BMI. Cases were analyzed in a pairwise fashion to maximize available data. 113 total patients with DS were identified: 84 (74.3%) in the control group and 29 (25.7%) in the T&A group. Height, weight, BMI, and Z-score data were compared between the control and T&A groups at 6-month intervals over a 24-month period.

Results: Children with DS who underwent T&A were comparable by demographics to children with DS who did not undergo T&A. Mean weight gain at 24 months for the T&A group was 8.07 ± 5.66 kg compared with 5.76 ± 13.20 kg in controls. The median Z-score at 24 months for the T&A group was 1.11 (0.10-1.88) compared with 1.17 (0.80-1.75) in controls. Children undergoing T&A had a stable median Z-score change of 0.09 at 24 months (p = 0.861, compared to baseline) while children who did not undergo T&A had a significantly increased median Z-score of 0.52 (p = 0.035, compared to baseline). Despite this, there were no significant intergroup differences between weight change, BMI, nor Z-score at any interval (p > 0.05).

Conclusions And Relevance: Children with DS did not have an increased rate of weight gain or increased BMI after T&A. BMI Z-scores were shown to stabilize over 24 months in the T&A group and increase in the control group. While this suggests that T&A provides an added benefit of weight control in patients with DS, the results should be interpreted with caution due to the small sample size and the fact that not all patients had complete follow up across a 24-month period.
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http://dx.doi.org/10.1016/j.ijporl.2017.06.029DOI Listing
September 2017

Meta-Analysis of Cardiovascular Outcomes With Continuous Positive Airway Pressure Therapy in Patients With Obstructive Sleep Apnea.

Am J Cardiol 2017 Aug 1;120(4):693-699. Epub 2017 Jun 1.

Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Continuous positive airway pressure (CPAP) is the main treatment of OSA. The present study explores the impact of CPAP on cardiovascular outcomes. A systematic search of electronic databases for randomized controlled trials comparing CPAP with medical therapy alone in patients with OSA who reported cardiovascular outcomes of interest was performed. The main outcome was major adverse cardiac events. Other outcomes included cardiac mortality, myocardial infarction, angina pectoris, stroke, and transient ischemic attack. Fixed effect model was used in all analyses except for subgroup analysis in which the random effect DerSimonian and Laird's model was used. Four randomized controlled trials with a total of 3,780 patients were included. Compared with medical therapy alone, CPAP use was not associated with reduced risk of major adverse cardiac events (relative risk [RR] 0.94, 95% confidence interval [CI] 0.78 to 1.15, p = 0.93, I = 0%) except in the subgroup that wore CPAP >4 hours (RR 0.70, 95% CI 0.52 to 0.94, p = 0.02, I = 0%). Furthermore, no reduction in the risk of cardiac mortality (RR 1.14, 95% CI 0.66 to 1.97, p <0.36, I = 2%), myocardial infarction (RR 0.96, 95% CI 0.64 to 1.44, p <0.15, I = 47%), angina pectoris (RR 1.16, 95% CI 0.9 to 1.50, p <0.51, I = 0%), stroke (RR 1.01, 95% CI 0.73 to 1.38, p <0.0.86, I = 0%), and transient ischemic attack (RR 1.36, 95% CI 00.69 to 2.68, p <0.24, I = 30%) was observed. Subgroup analysis of CPAP adherence in regards to cardiac outcomes showed that CPAP use is not associated with decreased risk of heart failure (RR 0.91, 95% CI 0.50 to 1.66, p <0.55, I = 0%). In conclusion, compared with medical therapy alone, utilization of CPAP in patients with OSA is not associated with improved cardiac outcomes except in patients who wore it for >4 hours.
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http://dx.doi.org/10.1016/j.amjcard.2017.05.042DOI Listing
August 2017

Spotlight on fluticasone furoate/umeclidinium/vilanterol in COPD: design, development, and potential place in therapy.

Int J Chron Obstruct Pulmon Dis 2017 30;12:135-140. Epub 2016 Dec 30.

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA.

COPD is characterized by persistent airflow obstruction caused by exposure to irritants including cigarette smoke, dust, and fumes. According to the latest GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines, a combination of inhaled corticosteroids, long-acting β agonists, and long-acting muscarinic receptor antagonists can be used for group D COPD patients who are at high risk for exacerbations. Umeclidinium/fluticasone furoate/vilanterol is one such triple-combination therapy currently under development with some completed and several ongoing clinical trials. This review paper summarizes the pharmacologic profiles of these medications and highlights findings from clinical trials, including safety and efficacy data, while speculating on the role of this therapy in current treatment for COPD.
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http://dx.doi.org/10.2147/COPD.S114273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221559PMC
October 2017

Impact of obstructive sleep apnea syndrome on cognition in early postmenopausal women.

Sleep Breath 2016 May 18;20(2):621-6. Epub 2015 Sep 18.

Department of Neurosciences, Medical University of South Carolina, Charleston, USA.

Purpose: Obstructive sleep apnea syndrome (OSAS) has a higher prevalence in postmenopausal women who are not on hormone replacement therapy (HRT), as compared to premenopausal women. Cognitive impairment (CI) is associated with OSAS and the early postmenopausal state. We hypothesized that compared to postmenopausal women at low risk for OSAS, postmenopausal women at high risk for OSAS would report worse cognitive function.

Methods: Early postmenopausal women not on HRT between the ages of 45 and 60 years, within 5 years of natural menopause, were enrolled. Participants completed a REDCap survey which collected information on demographics and risk factors, Berlin questionnaire to screen subjects for OSAS risk, and the Mail-In Cognitive Function Screening Instrument (MCFSI) score which was used to assess CI.

Results: Of 381 respondents, 127 were omitted due to missing/duplicate data or not meeting inclusion criteria. One hundred fifty-four women were classified as high risk for OSAS (OSAS+), and 100 were classified as low risk for OSAS (OSAS-). OSAS- women reported lifetime smoking, lifetime drinking, and recreational drug use more often than OSAS+ women, while OSAS+ women reported a depression diagnosis more often. The mean MCFSI score in the OSAS+ group was significantly higher (worse cognition) than in the OSAS- group after controlling for covariates (5.59, 95 % CI 5.08-6.11 vs. 4.29, 95 % CI 3.64-4.93, p < 0.05).

Conclusion: Early postmenopausal women at high risk for OSAS report more CI than those at low risk for OSAS. Future studies should identify biomarkers of this CI and define the degree of reversibility of CI with OSAS treatment.
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http://dx.doi.org/10.1007/s11325-015-1261-4DOI Listing
May 2016

Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle.

Neuroreport 2015 Sep;26(14):814-9

Departments of aNeurosciences bPulmonary, Critical Care, Allergy and Sleep Medicine, College of Medicine, Medical University of South Carolina, Charleston, South Carolina Departments of cBehavioral Sciences dObstetrics and Gynecology, Endocrinology eAnatomy and Neurobiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.

Mental rotation is a visuospatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional MRI. Ten premenopausal women were tested on a 3D mental rotation task during the early follicular and late follicular phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the late follicular than the early follicular phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuospatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.
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http://dx.doi.org/10.1097/WNR.0000000000000429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549195PMC
September 2015

Interrelationship between sleep-disordered breathing and sarcoidosis.

Chest 2015 Oct;148(4):1105-1114

Pulmonary and Critical Care Medicine, Albany Medical College, Albany, NY.

Sleep-disordered breathing (SDB) has a high prevalence in sarcoidosis. This high prevalence may be the result of increased upper airways resistance from sarcoidosis of the upper respiratory tract, corticosteroid-induced obesity, or parenchymal lung involvement from sarcoidosis. OSA is a form of SDB that is particularly common in patients with sarcoidosis. Sarcoidosis and SDB share many similar symptoms and clinical findings, including fatigue, gas exchange abnormalities, and pulmonary hypertension (PH). Sarcoidosis-associated fatigue is a common entity for which stimulants may be beneficial. Sarcoidosis-associated fatigue is a diagnosis of exclusion that requires an evaluation for the possibility of OSA. Hypercapnia is unusual in a patient with sarcoidosis without severe pulmonary dysfunction and, in this situation, should prompt evaluation for alternative causes of hypercapnia, such as SDB. PH is usually mild when associated with OSA, whereas the severity of sarcoidosis-associated PH is related to the severity of sarcoidosis. PH caused by OSA usually responds to CPAP, whereas sarcoidosis-associated PH commonly requires the use of vasodilators. Management of OSA in sarcoidosis is problematic because corticosteroid treatment of sarcoidosis may worsen OSA. Aggressive efforts should be made to place the patient on the lowest effective dose of corticosteroids, which involves early consideration of corticosteroid-sparing agents. Because of the significant morbidity associated with SDB, early recognition and treatment of SDB in patients with sarcoidosis may improve their overall quality of life.
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http://dx.doi.org/10.1378/chest.15-0584DOI Listing
October 2015

Sleep-disordered breathing in Down syndrome.

Chest 2015 Feb;147(2):570-579

Department of Pediatrics, Division of Developmental-Behavioral Pediatrics, Medical University of South Carolina, Charleston, SC.

OSA is associated with significant adverse outcomes with far-reaching health-care implications. OSA is much more common and severe in patients with Down syndrome (DS) than in the general population, yet there is a striking lack of literature in this area. In this review article, we have summarized the current state of knowledge and presented the available data on OSA in DS. The higher prevalence and severity of OSA in patients with DS may be related to unique upper airway anatomic features as well as increased risk for obesity, hypothyroidism, gastroesophageal reflux disease, and generalized hypotonia. Although many of the manifestations of OSA in patients with DS are similar to those seen in the general population, the relative morbidity is significantly higher. For individuals with DS who already face cognitive challenges, the added impact of OSA on cognitive function may hinder their ability to function independently and reach their full potential. Screening and evaluation for OSA should be done in children and adults with DS. Treatment of OSA in DS involves the use of CPAP, upper airway surgery, and dental appliances, along with weight-reduction strategies, nasal steroids, and oral leukotriene modifiers as adjunctive treatments. The treatment plan should be individualized for each patient with DS, taking into account age, comorbid conditions, and barriers to treatment adherence. Future research should aim to better characterize OSA, further evaluate neurocognitive outcomes, and evaluate the efficacy of treatments in patients with DS.
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http://dx.doi.org/10.1378/chest.14-0266DOI Listing
February 2015

Aclidinium bromide plus formoterol for the treatment of chronic obstructive pulmonary disease.

Expert Opin Pharmacother 2015 Feb;16(3):427-34

Medical University of South Carolina, Allergy and Sleep Medicine, Department of Pulmonary, Critical Care , 96 Jonathan Lucas Street, CSB 812, Msc 630, Charleston, SC 29425 , USA +1 843 792 7776 ; +1 843 876 2057 ;

Introduction: Drugs that target dynamic hyperinflation such as long-acting β-2 agonists and long-acting antimuscarinic antagonists form a cornerstone of chronic obstructive pulmonary disease (COPD) management. The idea of combining these two medications in a single formulation, which may potentially improve patient compliance, is novel and attractive.

Areas Covered: The pharmacologic profiles of aclidinium bromide and formoterol fumarate are discussed. However, studies to define drug interactions and alterations in the pharmacodynamics and pharmacokinetics of the fixed dose combination (FDC) of aclidinium bromide/formoterol fumarate in large populations remain unpublished. Results of Phase II and two Phase III pivotal trials, ACLIFORM/COPD and AUGMENT COPD, evaluating the FDC are discussed.

Expert Opinion: Initial data for the aclidinium/formoterol inhaler appears to be promising for impacting the lung function. To define if this benefit translates into improved long-term outcomes of decreased exacerbation frequency, improved quality of life and decreased disease-specific mortality are important. The introduction of this combination will likely have a significant impact on the prescribing habits of physicians across the world.
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http://dx.doi.org/10.1517/14656566.2015.1000861DOI Listing
February 2015

Impact of medications on cognitive function in obstructive sleep apnea syndrome.

Sleep Breath 2015 Sep 8;19(3):939-45. Epub 2015 Jan 8.

Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB Suite 812, Msc 630, Charleston, SC, 29425, USA,

Purpose: Medications can impact cognitive function. Obstructive sleep apnea syndrome (OSAS) is associated with cognitive impairment. There is currently a paucity of data evaluating the impact of medications on sleep architecture and cognition in untreated OSAS. Our objective was to evaluate the impact of obstructive sleep apnea syndrome (OSAS) and medications on cognition by a screening questionnaire called the Mail-In Cognitive Function Screening Instrument (MCFSI).

Methods: We conducted a retrospective chart review on consecutive adults (age > 18 years) with OSAS seen in Medical University of South Carolina Sleep Clinic between January 1, 2012 and May 8, 2013, for whom the Mail-In Cognitive Function Screening Instrument (MCFSI) score was available and who were not on continuous positive airway pressure (CPAP). The correlation between different medications, sleep study variables, and MCFSI scores was studied.

Results: Univariate analysis revealed that many medications had significant correlations with MCFSI scores, including antidepressants (p = 0.05), antipsychotics (p = 0.01), anxiolytics (p = 0.005), statins (p = 0.077) and narcotics (p = 0.006). The mean percentage of rapid eye movement (REM) sleep (p = 0.04) and Epworth Sleepiness Scale (p = 0.01) were also significantly correlated with MCFSI scores. Multivariate analysis revealed that Epworth Sleepiness Scale and use of antipsychotics, narcotics, and anxiolytics correlated with higher MCFSI scores (worse cognition) and conversely that statin use was associated with improved cognition.

Conclusions: Medications have a significant impact on cognitive function in OSAS. Thus, medication use should be considered in future studies of cognitive function in patients with OSAS.
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http://dx.doi.org/10.1007/s11325-014-1105-7DOI Listing
September 2015

Effect of obstructive sleep apnea treatment on mail-in cognitive function screening instrument.

Am J Med Sci 2014 Sep;348(3):215-8

Departments of Internal Medicine (BCB) and Pulmonary, Critical Care, Allergy and Sleep Medicine (CS, CL), Medical University of South Carolina (MUSC), Charleston, South Carolina.

Background: Obstructive sleep apnea syndrome (OSAS) may be associated with cognitive impairment (CI). The goal of this study was to evaluate the impact of risk factors and continuous positive airway pressure (CPAP) on a screening tool for cognitive function.

Methods: The Mail-In Cognitive Function Screening Instrument (MCFSI) is a self-administered test designed to identify CI in the Alzheimer's Disease Cooperative Study. It was administered to 88 consecutive patients with OSAS attending the Medical University of South Carolina Sleep Clinic. An MCFSI score ≥5 was considered abnormal.

Results: Data were analyzed on 61 patients after excluding missing and duplicate data. The MCFSI score was abnormal in 15 patients (25%). African Americans were more likely to be CPAP-noncompliant. Female gender and smoking were associated with abnormal MCFSI scores. CPAP-compliant patients were more likely to have normal MCFSI scores, although the difference was not statistically significant (P = 0.06).

Conclusions: CPAP-compliant patients showed a trend toward lower MCFSI scores. There may be gender and racial differences in CI related to OSAS, predisposing certain groups to worse morbidity. Appropriate treatment and compliance with CPAP could improve CI in OSAS. Larger studies with multivariate analyses are needed to identify relationships between individual OSAS and CI risk factors.
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http://dx.doi.org/10.1097/MAJ.0000000000000233DOI Listing
September 2014

Parasitic diseases of the pleura.

Am J Med Sci 2013 May;345(5):385-9

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Parasitic infections are prevalent in certain parts of the world and may cause pleural involvement, which often goes unrecognized. Common parasites involving the pleura include Entamoeba histolytica, Echinococcus granulosus and Paragonimus westermani. Amebiasis can cause empyema with "anchovy sauce" pus, reactive pleural effusions and bronchopleural fistula with hydropneumothorax. Echinococcosis may result in pleural thickening, pneumothorax, secondary pleural hydatidosis and pleural effusions. Paragonimiasis may cause chylous and cholesterol pleural effusions, pleural thickening and pneumothorax. Less commonly, pulmonary eosinophilia, or Loeffler's syndrome, caused by Ascaris lumbricoides, Ancylostoma duodenale and Necator americanus and tropical pulmonary eosinophilia caused by Wuchereria bancrofti and Brugia malayi may involve the pleura. This article provides a comprehensive review of parasitic infections involving the pleura. A high index of suspicion in the appropriate clinical setting is required to facilitate prompt diagnosis and treatment of these diseases.
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http://dx.doi.org/10.1097/MAJ.0b013e318266e984DOI Listing
May 2013

Neurocognitive impairment in obstructive sleep apnea.

Chest 2012 Jun;141(6):1601-1610

Division of Neurology, Department of Neurosciences, Medical University of South Carolina, Charleston, SC.

Obstructive sleep apnea syndrome (OSAS) is a common disorder with far-reaching health implications. One of the major consequences of OSAS is an impact on neurocognitive functioning. Several studies have shown that OSAS has an adverse effect on inductive and deductive reasoning, attention, vigilance, learning, and memory. Neurocognitive impairment can be measured objectively with tests such as the Wechsler Adult Intelligence Scale-Revised, the Psychomotor Vigilance Task, the Steer Clear Performance Test, and tests of repetitive finger tapping. In children, OSAS may cause attention-deficit hyperactivity disorder in addition to behavioral problems and learning disabilities. Risk factors for cognitive impairment include increasing age, male sex, apolipoprotein E ε4 allele positivity, current cigarette smoking, obesity, hypertension, diabetes mellitus, metabolic syndrome, Down syndrome, hypothyroidism, significant alcohol consumption, stroke, and the use of psychoactive medications. At a cellular level, OSAS likely causes cognitive impairment through intermittent hypoxia, hormonal imbalance, and/or systemic inflammation, either independently or via the resultant endothelial dysfunction that occurs. Excessive daytime sleepiness should be measured and minimized in all studies of neurocognitive impairment. Recent studies have used functional and structural neuroimaging to delineate the brain areas affected in patients with OSAS with neurocognitive dysfunction. A common finding in several of these studies is decreased hippocampal volume. Other affected brain areas include the frontal and parietal lobes of the brain, which show focal reductions in gray matter. These changes can be reversed at least partially with the use of CPAP, which highlights the importance of early recognition and treatment of OSAS. The currently available data in this field are quite limited, and more research is needed.
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http://dx.doi.org/10.1378/chest.11-2214DOI Listing
June 2012

Unilateral pulmonary artery aplasia in a pregnant patient.

Case Rep Med 2011 7;2011:806723. Epub 2011 Apr 7.

Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, CSB 812, MSC 630, Charleston, SC 29425, USA.

Unilateral pulmonary artery aplasia is a rare anomaly. Case reports of this condition in pregnant patients are even more uncommon and the best approach to management of such patients is still unclear. We report a patient who presented with a history of dyspnea, chest pain, and hemoptysis. Imaging established the diagnosis in a newly pregnant female. Management of the pulmonary artery aplasia patient in pregnancy requires prospective evaluation of pulmonary hypertension.
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http://dx.doi.org/10.1155/2011/806723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087430PMC
July 2011
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