The promise of compassion-based therapy as a novel intervention for adolescent PTSD.

In this review, we summarize current evidence for compassion-based approaches for PTSD and the potential for their application to the adolescent PTSD population. Exposure to traumatic events is common in adolescence and PTSD remains a public health crisis. Accessibility, willingness, and engagement are significant barriers to established treatments for PTSD, with attrition rates as high as 50 %. Compassion-based therapies provide potential solutions to treatment obstacles by providing a non-threatening, transdiagnostic option unburdened by aspects of current trauma treatment which may be associated with treatment resistance (e.g., exposure, trauma narrative, induction of fear). Compassion-based approaches are intuitive for trauma treatment, as compassion activates the self-soothing system, thereby disarming the fear system and promoting affect regulation. Compassion-based treatments demonstrate reductions across a substantial range of PTSD symptoms in adults, however, in adolescents extant literature is sparse, with cross-sectional studies suggesting self-compassion is inversely associated with trauma-related psychopathology. Understanding the impact of compassion-based approaches on adolescent PTSD is warranted as the adolescent developmental period may be a particularly opportune time for this approach. Evaluation of the impact of compassion-based treatment on adolescent PTSD in clinical populations via randomized-controlled studies and comparison of its relative efficacy to current evidence-based practices is warranted.

Association of neighborhood gentrification with prostate cancer and immune markers in African American and European American men.

BACKGROUND: Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer and serum proteome-defined inflammation and immune function in a diverse cohort. METHODS: The case-control study included 769 cases [405 African American (AA), 364 European American (EA) men] and 1023 controls (479 AA and 544 EA), with 219 all-cause and 59 prostate cancer-specific deaths among cases. Geocodes were linked to a neighborhood gentrification index (NGI) derived from US Census data. Cox and logistic regression, and MANOVA, were used to determine associations between NGI, as continuous or quintiles (Q), and outcomes. RESULTS: Adjusting for individual socioeconomic status (SES), continuous NGI was positively associated with prostate cancer among all men (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.14). AA and low-income men experienced the highest odds of prostate cancer when residing in tracts with moderate gentrification, whereas EA men experienced reduced odds of regional/metastatic cancer with increased gentrification in SES-adjusted analyses. Continuous NGI also associated with mortality among men presenting with localized disease and low-income men in SES-adjusted Cox regression analyses. NGI was not associated with serum proteome-defined chemotaxis, inflammation, and tumor immunity suppression. CONCLUSIONS: Findings show that neighborhood gentrification associates with prostate cancer and mortality in this diverse population albeit associations were heterogenous within subgroups. The observations suggest that changing neighborhood socioeconomic environments may affect prostate cancer risk and outcome, likely through multifactorial mechanisms.

Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors.

Importance: The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood. Objective: To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer. Design, Setting, and Participants: This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003. Participants were recruited through the University of Maryland Medical Center, with additional collection sites at Baltimore-area hospitals. Data analysis was performed from March 1 through December 1, 2022. Exposure: Year 2000 census tract-level socioeconomic deprivation measured via neighborhood deprivation index (NDI) as a standardized score, with Black and White race being ascertained through self-report. Main Outcome and Measures: The primary outcome was tissue DNA methylation using genome-wide measurements. The secondary outcome was tissue gene expression. Results: Participants included 185 women with breast cancer (110 Black [59.5%], 75 White [40.5%]). Mean (SD) age at surgery was 56.0 (14.1) years. Neighborhood deprivation was higher for Black women than for White women (Mean [SD] NDI, 2.96 [3.03] for Black women and -0.54 [1.91] for White women; difference, -3.50; 95% CI, -4.22 to -2.79; P < .001). In unstratified analysis, 8 hypomethylated CpG sites were identified as associated with the NDI, including sites in 2 tumor suppressor genes, LRIG1 and WWOX. Moreover, expression of the 2 genes inversely correlated with neighborhood deprivation. In the race-stratified analysis, the negative correlation between the LRIG1 gene body CpG site cg26131019 and the NDI remained significant in Black women. A neighborhood deprivation-associated decrease in gene expression was also observed for LRIG1 and WWOX in tumors from Black women. Conclusions and Relevance: In this study, high neighborhood deprivation was associated with differences in tissue DNA methylation and gene expression among Black women. These findings suggest that continued investment in public health interventions and policy changes at the neighborhood level may help to remedy biological alterations that could make minoritized populations more susceptible to chronic diseases.

Predicting emergency department visits among children with asthma in two academic medical systems.

Objective: To develop and validate a predictive algorithm that identifies pediatric patients at risk of asthma-related emergencies, and to test whether algorithm performance can be improved in an external site via local retraining.Methods: In a retrospective cohort at the first site, data from 26 008 patients with asthma aged 2-18 years (2012-2017) were used to develop a lasso-regularized logistic regression model predicting emergency department visits for asthma within one year of a primary care encounter, known as the Asthma Emergency Risk (AER) score. Internal validation was conducted on 8634 patient encounters from 2018. External validation of the AER score was conducted using 1313 pediatric patient encounters from a second site during 2018. The AER score components were then reweighted using logistic regression using data from the second site to improve local model performance. Prediction intervals (PI) were constructed via 10 000 bootstrapped samples.Results: At the first site, the AER score had a cross-validated area under the receiver operating characteristic curve (AUROC) of 0.768 (95% PI: 0.745-0.790) during model training and an AUROC of 0.769 in the 2018 internal validation dataset (p = 0.959). When applied without modification to the second site, the AER score had an AUROC of 0.684 (95% PI: 0.624-0.742). After local refitting, the cross-validated AUROC improved to 0.737 (95% PI: 0.676-0.794; p = 0.037 as compared to initial AUROC).Conclusions: The AER score demonstrated strong internal validity, but external validity was dependent on reweighting model components to reflect local data characteristics at the external site.

Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. Objective: To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. Design, Setting, and Participants: This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Interventions: Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Main Outcomes and Measures: Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Results: Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. Conclusions and Relevance: In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. Trial Registration: ClinicalTrials.gov Identifier: NCT02941809.

Association of Neighborhood Deprivation With Prostate Cancer and Immune Markers in African American and European American Men.

Importance: Neighborhood variables may be factors in the excessive burden of prostate cancer among African American men. Objective: To examine associations between neighborhood deprivation, circulating immune-oncology markers, and prostate cancer among African American and European American men. Design, Setting, and Participants: A case-control study was conducted between January 1, 2005, and January 1, 2016. Participants included men with prostate cancer and age- and race-frequency-matched population controls. Participants were recruited at the Baltimore Veterans Affairs Medical Center and University of Maryland Medical Center; controls were obtained through the Maryland Motor Vehicle Administration database. National Death Index follow-up was performed through December 31, 2020, and data analysis was conducted from February 1, 2022, through October 31, 2022. Exposures: 2000 Census-tract Neighborhood Deprivation Index as a standardized score. Main Outcomes and Measures: Primary outcomes included prostate cancer, all-cause mortality, and disease-specific mortality. Secondary outcomes included the National Comprehensive Cancer Network risk score and serum proteomes for 82 immune-oncology markers with pathway annotation. Results: Participants included men with prostate cancer (n = 769: 405 African American, 364 European American men) and age- and race-frequency-matched population controls (n = 1023: 479 African American, 544 European American men). The median survival follow-up was 9.70 years (IQR, 5.77 years), with 219 deaths. Among 884 African American men, mean (SD) age at recruitment was 63.8 (7.6) years; mean (SD) age at recruitment among 908 European American men was 66.4 (8.1) years. In the multivariable logistic regression analysis with individual socioeconomic status adjustment, neighborhood deprivation was associated with 55% increased odds of prostate cancer among African American men (odds ratio [OR], 1.55; 95% CI, 1.33-1.81), but was not associated with the disease among European American men. Residing in the most-deprived vs least-deprived neighborhoods corresponded to 88% higher disease odds (OR, 1.88; 95% CI, 1.30-2.75) among all men and an approximate 3-fold increase among African American men (OR, 3.58; 95% CI, 1.72-7.45), but no association was noted among European American men. In Cox proportional hazard regression analyses, socioeconomic status-adjusted neighborhood deprivation was associated with an increased all-cause mortality only among African American men (hazard ratio [HR], 1.28; 95% CI, 1.08-1.53), whereas it was associated with metastatic disease and a 50% increased hazard of a prostate cancer-specific death among all men (HR, 1.50; 95% CI, 1.07-2.09). In analyses restricted to controls, neighborhood deprivation was associated with increased activity scores of serum proteome-defined chemotaxis, inflammation, and tumor immunity suppression. Conclusions and Relevance: The findings of this study suggest that deprived neighborhood residency may increase the risk of African American men for prostate cancer and a related mortality, potentially through its association with systemic immune function and inflammation.

Social Determinants of Emergency Department Visits in Mild Compared to Moderate and Severe Asthma.

BACKGROUND: Social determinants of health (SDH) influence emergency department (ED) use among children with asthma. We aimed to examine if SDH were more strongly associated with ED use among children with moderate/severe compared to mild asthma. METHODS: This study utilized the 2016-2019 data from the National Survey of Children's Health. Children with asthma ages 0-17 years (N = 9937) were included in the analysis. Asthma severity and all-cause ED use in the past year were reported by caregivers. The association between patient factors and ED visits was evaluated using ordinal logistic regression. RESULTS: Based on the study sample, 29% of children with asthma had moderate/severe asthma. In the mild group, 30% visited the ED at least once in the past 12 months, compared to 49% in the moderate/severe group. SDH associated with ED visits included race/ethnicity, insurance coverage, and parental educational attainment, but the strength of these associations did not vary according to asthma severity. CONCLUSIONS: In a nationally representative data set, SDH were equally predictive of ED use regardless of children's asthma severity. Interventions to reduce ED use among children with asthma should be considered for children with any severity of asthma, especially children in socially disadvantaged groups at higher risk of ED utilization.

Reduction of Motion Artifacts in Functional Connectivity Resulting from Infrequent Large Motion.

Introduction: Subject head motion is an ongoing challenge in functional magnetic resonance imaging, particularly in the estimation of functional connectivity. Infants (1-month old) scanned during nonsedated sleep often have occasional but large movements of several millimeters separated by periods with relatively little movement. This results in residual signal changes even after image realignment and can distort estimates of functional connectivity. A new motion correction technique, JumpCor, is introduced to reduce the effects of this motion and compared to other existing techniques. Methods: Different approaches for reducing residual motion artifacts after image realignment were compared both in actual and simulated data: JumpCor, regressing out the estimated subject motion, and regressing out the average white matter, cerebrospinal fluid (CSF), and global signals and their temporal derivatives. Results: Motion-related signal changes resulting from infrequent large motion were significantly reduced both by regressing out the estimated motion parameters and by JumpCor. Furthermore, JumpCor significantly reduced artifacts and improved the quality of functional connectivity estimates when combined with typical preprocessing approaches. Discussion: Motion-related signal changes resulting from occasional large motion can be effectively corrected using JumpCor and to a certain extent also by regressing out the estimated motion. This technique should reduce the data loss in studies where participants exhibit this type of motion, such as sleeping infants.

The impact of childhood maltreatment on adaptive emotion regulation strategies.

OBJECTIVE: Childhood maltreatment is a potent known risk factor for psychopathology, accounting for nearly 30% of the risk for mental illness in adulthood. One mechanism by which maltreatment contributes to psychopathology is through impairments in emotion regulation. However, the impact of childhood maltreatment on adaptive regulation strategies remains unclear, particularly across positive and negative emotions. METHODS: Using Mechanical Turk, we recruited a cross-sectional sample of 207 adults (21-69 years) with and without childhood maltreatment exposure to complete an emotion regulation task where they were shown positive and negative emotional pictures and were instructed to reappraise or accept their emotions, alongside a non-instruction comparison condition. Participants rated their emotional intensity following each image, as well as perceived effectiveness of each strategy at the end of each block. We first investigated the impact of image valence and strategy use on the intensity of post-image emotions, followed by interacting both maltreatment exposure and severity with valence and strategy. FINDINGS: Surprisingly, maltreated individuals showed significantly higher emotional intensity compared to non-maltreated individuals, specifically toward positive images (F(2,194.6) = 5.01, p < 0.01). When examining strategy, the use of acceptance to regulate negative emotions was equally effective across all levels of maltreatment severity (F(2,194.6) = 15.93, p < 0.001), while reappraisal was effective only at lower maltreatment levels. CONCLUSION: These findings suggest that experiences of childhood maltreatment exert differential impacts on the ability to regulate positive and negative emotions using key adaptive regulation strategies, which has implications for both psychopathology risk and treatment interventions.

Pediatric Primary Care Relationships and Non-Urgent Emergency Department Use in Children.

OBJECTIVE: Non-urgent emergency department (ED) use contributes to healthcare costs and disrupts continuity of care. Factors influencing patient/guardian decision-making in non-urgent situations are poorly understood. We sought to determine the association of patient/guardian - primary care provider (PCP) relationship with non-urgent ED usage and explore related factors. METHODS: In an urban practice, we recruited 218 parent-child pairs and administered a survey with the PCP relationship (PDRQ-9), caregiver knowledge of office resources, and care-seeking behavior. We performed a 12-month retrospective chart review to document non-urgent ED visits. We evaluated the association of PDRQ9 and non-urgent ED usage by regression analysis. RESULTS: Mean child age was 7.0 ± 5 years, and 32.6% of children had at least one non-urgent ED visit. Mean PDRQ9 score was 39.8 ± 7.3 and was not associated with non-urgent ED use (P = .46). Lower child age (P < .001) and shorter time coming to the PCP practice (P < .001) were both associated with increased non-urgent ED use. Only 36.4% reported usually going to their PCP when they are sick. Knowledge of office resources was limited, and when prompted with acute, non-urgent medical scenarios, in 4 of 5 scenarios, 50% or more of participants chose to go to the ED over communicating with or going to their PCP. CONCLUSIONS: We did not find an association between patient-doctor relationship strength and non-urgent ED usage. Many patients/guardians were unaware of the practice's resources and selected the ED as first choice for acute, non-urgent medical scenarios. Additional work is needed to determine interventions to reduce non-urgent ED use.

Patterns of Health Insurance Coverage and Lung Disease Progression in Adolescents and Young Adults with Cystic Fibrosis.

Rationale: Health insurance coverage has been implicated as a socioeconomic factor affecting clinical outcomes in patients with cystic fibrosis (CF), but evidence for this is mixed and varies by age.Objectives: Focusing on adolescents and young adults with CF, we examined how multiyear patterns of health insurance coverage were associated with lung function decline and related outcomes.Methods: We used data from the 2000 to 2015 CF Foundation Patient Registry to classify patients in three cohorts (ages 12-17 yr, adolescents; 18-23 yr, transitioning to adulthood; and 24-29 yr, young adults) according to health insurance coverage, as follows: continuous private, continuous public, intermittent public, and coverage gaps. The primary outcome was the percentage predicted forced expiratory volume in 1 second (FEV1pp), which was modeled using mixed-effects regression. Additional outcomes included outpatient visits, hospital days for pulmonary exacerbation treatment, bacterial colonization, and body mass index. Outcomes were assessed over a 6-year period (e.g., ages 12-17 yr), whereas exposures were assessed over the prior 6 years (e.g., ages 6-11 yr).Results: The three cohorts included 3,365, 2,800, and 1,807 patients, respectively. The highest rate of FEV1pp decline was found in the middle cohort, with the annual decline being steeper among patients with continuous public (-3.1/yr; 95% confidence interval [CI], -3.3 to -2.8) or intermittent public (-2.4/yr; 95% CI, -2.6 to -2.2) coverage compared with patients with continuous private coverage (-2.1/yr; 95% CI, -2.2 to -2.0). These differences were not explained by differences in outpatient care utilization.Conclusions: During the transition to adulthood, use of public insurance was associated with accelerated lung function decline among patients with CF. The role of insurance as a causal factor in this decline or proxy for other socioeconomic characteristics should be explored in further studies.

Asthma deaths in North Carolina: 1999-2016.

Introduction: Despite the significant decline in overall death rates in the U.S. over the past decade, many asthma deaths could have been avoided. Eastern North Carolina (N.C.) is an economically challenged region with significant health disparities and a high prevalence of asthma. Objective: The primary purpose of this project was to examine trends of asthma deaths across N.C. and identify counties in the state with the highest mortality rates over an 18-year period. Methods: CDC WONDER was used to query and evaluate age-adjusted asthma mortality rates from 1999 to 2016 among residents in N.C., greater than 1 year of age. Asthma death data were derived from death certificates using ICD-10 underlying cause-of-death codes J45 (asthma) and J46 (status asthmaticus). The Join point regression program was used to test statistical significance in age-adjusted rates for the U.S. and N.C. over the entire study period. Results: N.C. experienced a total of 2,066 decedents assigned as the underlying cause of deaths for an overall death rate of 12.5 per 1,000,000 persons. Death rates were highest among females (14.6 deaths per 1,000,000) and black or African Americans (24.7 per 1,000,000). Discussion: Overall asthma mortality rates in N.C. decreased. However, several rural and impoverished counties in eastern N.C. with a large percent of blacks or African-Americans, had the highest asthma death rates in the state. Conclusion: Healthcare providers should remain highly cognizant to provide optimal asthma management, education, and follow-up with asthma patients to help avoid unnecessary asthma related deaths.

Bedside Ultrasound Versus Chest Radiography for Detection of Pulmonary Edema: A Prospective Cohort Study.

OBJECTIVES: Chest radiography has been the preferred imaging study to assess pulmonary congestion. However, chest radiography interpretation is influenced by the level of expertise and high interobserver variability. Lung ultrasound (US) may produce more objective findings through evaluation of vertical comet tail artifacts known as B-lines, which are created by a decrease in the ratio of alveolar air to fluid pulmonary content. Few studies have directly compared chest radiography to bedside US against a reference standard for the diagnosis of pulmonary edema. This study compared the sensitivity and specificity of bedside US and chest radiography in diagnosing pulmonary edema. METHODS: This prospective observational cohort study involved adult patients presenting to the emergency department of an urban tertiary hospital with dyspnea. The primary outcome was the presence or absence of pulmonary edema, as indicated by B-lines on a bedside lung US examination or radiologist-interpreted chest radiography. Patients underwent a US examination within about 1 hour of chest radiography. The final diagnosis from the discharge summary served as the reference standard. RESULTS: Ninety-nine patients were enrolled; 32.3% had congestive heart failure, and 40.4% had chronic obstructive pulmonary disease. Bedside US showed significantly higher sensitivity (96%) compared to chest radiography (65%; P < .001). Of 18 patients with negative radiographic findings and a discharge diagnosis of pulmonary edema, 16 (89%) had positive US findings (P < .001). CONCLUSIONS: Bedside US has the potential to identify pulmonary edema more accurately than chest radiography. As current practice within the United States uses chest radiography, reflecting American College of Cardiology Foundation/American Heart Association guidelines for management of heart failure, the results of this study warrant further evaluation.

Association of Prenatal Maternal Depression and Anxiety Symptoms With Infant White Matter Microstructure.

Importance: Maternal depression and anxiety can have deleterious and lifelong consequences on child development. However, many aspects of the association of early brain development with maternal symptoms remain unclear. Understanding the timing of potential neurobiological alterations holds inherent value for the development and evaluation of future therapies and interventions. Objective: To examine the association between exposure to prenatal maternal depression and anxiety symptoms and offspring white matter microstructure at 1 month of age. Design, Setting, and Participants: This cohort study of 101 mother-infant dyads used a composite of depression and anxiety symptoms measured in mothers during the third trimester of pregnancy and measures of white matter microstructure characterized in the mothers' 1-month offspring using diffusion tensor imaging and neurite orientation dispersion and density imaging performed from October 1, 2014, to November 30, 2016. Magnetic resonance imaging was performed at an academic research facility during natural, nonsedated sleep. Main Outcomes and Measures: Brain mapping algorithms and statistical models were used to evaluate the association between maternal depression and anxiety and 1-month infant white matter microstructure as measured by diffusion tensor imaging and neurite orientation dispersion and density imaging findings. Results: In the 101 mother-infant dyads (mean [SD] age of mothers, 33.22 [3.99] years; mean age of infants at magnetic resonance imaging, 33.07 days [range, 18-50 days]; 92 white mothers [91.1%]; 53 male infants [52.5%]), lower 1-month white matter microstructure (decreased neurite density and increased mean, radial, and axial diffusivity) was associated in right frontal white matter microstructure with higher prenatal maternal symptoms of depression and anxiety. Significant sex × symptom interactions with measures of white matter microstructure were also observed, suggesting that white matter development may be differentially sensitive to maternal depression and anxiety symptoms in males and females during the prenatal period. Conclusions and Relevance: These data highlight the importance of the prenatal period to early brain development and suggest that the underlying white matter microstructure is associated with the continuum of prenatal maternal depression and anxiety symptoms.

Progression of Polysomnographic Abnormalities in Mucolipidosis II (I-Cell Disease).

ABSTRACT: Mucolipidosis II (Inclusion cell or I-cell disease) is an autosomal recessive lysosomal storage disorder clinically comparable to the mucopolysaccharidoses (MPS), characterized by progressive respiratory and neurologic deterioration. Sleep problems, especially obstructive sleep apnea (OSA) and disrupted sleep architecture, are observed in other lysosomal storage diseases but have not been described in mucolipidosis II. We report the progression of polysomnographic abnormalities in a child with mucolipidosis II, demonstrated by worsening sleep-related hypoventilation, OSA, and sleep state fragmentation despite advancing PAP therapy. Background slowing and reduction in spindle activity on limited EEG may reflect progressive CNS disease affecting thalamic neurons.

Relationship of sleep to pulmonary function in mucopolysaccharidosis II.

OBJECTIVE: To study the sleep characteristics, pulmonary function, and their relationships in an enzyme naive population of patients with mucopolysaccharidoses (MPS) II (Hunter syndrome). STUDY DESIGN: The analyzed subjects (30 patients with MPS II with a median age of 9 years) had been enrolled in an MPS II natural history study and a phase I/II enzyme replacement clinical study in which they underwent standard polysomnography including spirometry and plethysmography, if cooperative. Descriptive statistics and nonparametric correlation were performed for demographic, sleep, and pulmonary function variables. RESULTS: Median apnea-hypopnea index was 6.4, with obstructive sleep apnea observed in 27/30 subjects. Sleep architecture was characterized by diminished rapid-eye movement sleep duration (median 13%), and decline in sleep efficiency and slow-wave sleep duration in older individuals. Oxygen desaturation below 90% occurred in 26/30 subjects, and hypoventilation above 50 Torr occurred in 11/23 subjects with accurate end-tidal carbon dioxide recordings. Of 15 subjects with reliable spirometry, median forced expiratory volume in 1 second was below 80% predicted in 12/15 subjects. Forced expiratory volume in 1 second in percent-predicted was inversely related to apnea-hypopnea index and increase from baseline end-tidal carbon dioxide (P=.023, rs=-0.58), (P<.001, rs=-0.82). CONCLUSION: Sleep in MPS II is characterized by obstructive sleep apnea, altered sleep architecture, and impaired gas exchange. Sleep disruption is related to daytime pulmonary function, thus both systems should be evaluated when sleep abnormalities are suspected.

Respiratory manifestations in mucopolysaccharidoses.

Mucopolysaccharidoses (MPS) are a group of inherited, metabolic diseases caused by deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAG). Loss of enzyme activity results in cellular accumulation of GAG fragments leading to the progressive multi-system manifestations. MPS are classified into seven clinical types based on eleven known lysosomal enzyme deficiencies of GAG metabolism. Respiratory involvement is seen in most MPS types with recurrent respiratory infections, upper and lower airway obstruction, tracheomalacia, restrictive lung disease, and sleep disturbances. Patients with airway obstruction are at high risk for anaesthetic complications. In this review, we present the respiratory manifestations in various MPS types and stages, evaluation of respiratory involvement, and treatment options for the progressive respiratory failure that occurs in MPS patients.