Examining the Longitudinal Relationship Between Metacognitive Beliefs and Psychological Distress in an Adolescent Population: A Preliminary Analysis.

Adolescence is a period marked by significant vulnerability to the onset of mental health concerns. Within adults, the metacognitive model of psychological disorders advocates for the involvement of metacognitive beliefs in the onset, and maintenance, of psychopathology. The current study aimed to assess the applicability of the metacognitive model in adolescence by exploring the relationship, as well as the trajectory, between metacognitive beliefs and psychological distress. The longitudinal prospective cohort study investigated data from a community-based sample of participants aged 12 to 13. Self-report assessment measures of metacognitive beliefs, psychological distress, and somatic distress are reported across four time-points. Baseline assessments are reported for 70 participants, which reduced to 53 participants at time-point four. Correlational analyses demonstrated a significant relationship between overall metacognition, as well as negative metacognitive beliefs, and psychological distress at each of the four time-points. Generalised Estimating Equations found a significant association between metacognitive predictors and psychological distress over the four time-points. These results indicate that negative metacognitive beliefs, positive metacognitive beliefs, metacognitive beliefs related to superstition, punishment, and responsibility, low perceived levels of cognitive confidence and cognitive self-consciousness predict psychological distress over 12 months in adolescents aged 12 to 13. The strongest longitudinal correlational structure was found for the model of negative metacognitive beliefs and psychological distress. These findings provide preliminary evidence for the positive linear relationship between metacognitive beliefs and psychological distress in adolescence. The study provides an important contribution to understanding the role of metacognitive beliefs in the aetiology and perpetuation of psychological distress in adolescence.

Treatment response with ketamine in chronic suicidality: An open label functional connectivity study.

BACKGROUND: Ketamine has recently been proposed as a treatment option for suicidality. Whilst its mechanism of action has been explored at molecular levels, the effect on the brain at the organ level remains unclear. Here we investigate immediate post-treatment and prolonged large-scale resting-state neural network changes to elucidate the neuronal underpinnings associated with ketamine's therapeutic effects. METHODS: Twenty-eight adults (aged 22-72 years) participated in the Oral Ketamine Trial On Suicidality, which is an open-label trial of weekly sub-anaesthetic doses of oral ketamine over 6 weeks. MRI was acquired at baseline, post-treatment, and follow-up. Functional connectivity changes at post-treatment and follow-up were examined using seed based and independent component analysis. RESULTS: The seed-based connectivity analysis revealed significantly reduced connectivity at post-treatment from the right hippocampus to both right and left superior frontal gyrus, from the left anterior parahippocampus to right superior frontal gyrus, left superior frontal gyrus, right middle frontal gyrus, and left frontal operculum cortex. Compared with baseline, the ICA showed reduced anterior default mode network connectivities to bilateral posterior cingulate cortex, middle and anterior cingulate cortex, lingual gyrus, and cuneus and increased connectivity of the frontoparietal network to the right superior parietal lobule at post-treatment. LIMITATIONS: Open label pilot study. CONCLUSIONS: We have shown sub-anaesthetic doses of ketamine alters connectivity in networks which have been shown to be aberrantly hyper-connected in numerous psychiatric conditions. These neurocircuitry changes are supported by significant reductions in suicide ideation. Our results provide support for the use of ketamine as a treatment for suicidality.

Sex differences in fronto-limbic white matter tracts in youth with mood disorders.

AIMS: Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders. METHODS: Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self-report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto-limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors. RESULTS: Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed. CONCLUSIONS: Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.

Elucidating the neural correlates of emotion recognition in children with sub-clinical anxiety.

BACKGROUND: The pervasiveness of subclinical anxiety in children, highlights the need to identify its neurobiological underpinnings to better inform interventions. Given the now well-established link between aberrant emotion processing and anxiety disorders and yet limited neurobiologically-informed research in this area, this study examined the neural correlates of emotion recognition (ER) in children with sub-clinical anxiety. METHOD: Ninety children (aged 9-11 years) with sub-clinical anxiety, completed an emotion recognition task whilst undergoing functional magnetic resonance imaging. The ER task required participants to match shapes and match emotional faces in the context of shape distractors. Participants also completed the Spence Children's Anxiety Scale (SCAS). RESULTS: Greater blood oxygenation level dependent (BOLD) changes associated with ER were observed in the lateral occipital cortex, middle frontal gyrus, superior middle frontal gyrus, inferior frontal gyrus, superior parietal lobule, inferior parietal lobule, superior temporal gyrus, and middle temporal gyrus symmetrically. The clusters also included posterior cingulate cortex, insula, hippocampus, amygdala and cerebellum during matching emotions than those matching shapes. Females showed greater BOLD changes associated with ER than males in the right middle frontal gyrus. The BOLD changes associated with ER in the right middle frontal gyrus and right insula were greater in children with SCAS subscale (physical injury fear) scores in the normal range than those with elevated scores. DISCUSSION: The findings in this study implicate the right middle frontal gyrus and insula as key regions in the neurobiological underpinnings of sub-clinical anxiety as they relate to attention impairments in anxious children. CONCLUSION: The results of this study indicate there are gender differences in young participants during emotion processing and provides a neurobiological target for attention impairments in anxious children.

Six-week oral ketamine treatment for chronic suicidality is associated with increased grey matter volume.

Chronic suicidality has been associated with neuronal atrophy in cortico-striato-limbic regions and is thought to be mediated via a glutamatergic imbalance. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been posited to exert anti-suicidal effects by promoting neurogenesis via modulation of glutamatergic transmission. This voxel-based morphometry study examined the effect of ketamine on whole brain grey matter in adults with chronic suicidality. Grey matter in the periaqueductal grey, nucleus accumbens, putamen, caudate, and thalamus was significantly increased following 6 weeks of low dose oral ketamine treatment. These results support the notion that ketamine rapidly enhances synaptic plasticity within striato-limbic regions.

Can measures of sleep quality or white matter structural integrity predict level of worry or rumination in adolescents facing stressful situations? Lessons from the COVID-19 pandemic.

INTRODUCTION: COVID-19 has resulted in major life changes to the majority of the world population, particularly adolescents, with social-distancing measures such as home-based schooling likely to impact sleep quality. Increased worry is also likely considering the substantial financial, educational and health concerns accompanying COVID-19. White matter (WM) integrity has been shown to be associated with anxiety and depression symptoms, including worry, as well being closely associated with sleep quality. This study aimed to investigate the associations between pre-COVID sleep quality, WM structural integrity and levels of worry and rumination about COVID. METHODS: N = 30 adolescent participants from Queensland, Australia, completed diffusion tensor imaging (DTI) scanning pre-COVID, the Pittsburgh Sleep Quality Index (PSQI) pre and during COVID, and 9 items designed to measure 3 constructs, perceived impact of COVID, general worry, and COVID-specific worry and rumination. RESULTS: Sleep quality (PSQI total) was significantly poorer during COVID compared with pre-COVID. Sleep onset latency measured pre-COVID was significantly associated with COVID-specific worry and rumination. While the structural integrity of a number of WM tracts (measured pre-COVID) were found to be significantly associated with COVID-specific worry and rumination. Follow-up regression analysis using a model including pre-COVID sleep onset latency, structural integrity of the posterior limb of the internal capsule (PLIC), gender and change in PSQI explained a significant 47% of the variance in COVID-specific worry and rumination. CONCLUSIONS: These findings suggest that adolescents with poor sleep quality and perturbed WM integrity may be at risk of heightened reactivity to future stressful events and interventions should focus on improving sleep onset latency.

The role of adolescent sleep quality in the development of anxiety disorders: A neurobiologically-informed model.

In a series of cognitive and neuroimaging studies we investigated the relationships between adolescent sleep quality, white matter (WM) microstructural integrity and psychological distress. Collectively these studies showed that during early adolescence (12-14 years of age), sleep quality and psychological distress are significantly related. Sleep quality and the microstructure of the posterior limb of the internal capsule (PLIC), a WM tract that provides important connectivity between the cortex, thalamus and brain stem, were also shown to be significantly correlated as too were social connectedness and psychological distress. Longitudinally the uncinate fasciculus (UF), a WM tract that provides bidirectional connectivity between the amygdala and executive control centers in the Prefrontal cortex (PFC), was observed to be undergoing continued development during this period and sleep quality was shown to impact this development. Sleep latency was also shown to be a significant predictor of worry endured by early adolescents during future stressful situations. The current review places these findings within the broader literature and proposes an empirically supported model based in a theoretical framework. This model focuses on how fronto-limbic top-down control (or lack thereof) explains how poor sleep quality during early adolescence plays a crucial role in the initial development of anxiety disorders, and possibly in the reduced ability of anxiety disorder sufferers to benefit from cognitive reappraisal based therapies. While the findings outlined in these studies highlight the importance of sleep quality for WM development and in mitigating psychological distress, further research is required to further explicate the associations proposed within the model to allow causal inferences to be made.

Short strides to important findings: A short interval longitudinal study of sleep quality, psychological distress and microstructure changes to the uncinate fasciculus in early adolescents.

BACKGROUND: Developmental studies have shown adolescence is a period of ongoing white matter (WM) development, reduced sleep quality and the onset of many mental disorders. Findings indicate the WM development of the uncinate fasciculus (UF), a WM tract suggested to play a key role in mental disorders, continues throughout adolescence. While these studies provide valuable information, they are limited by long intervals between scans (1 to 4 years) leaving researchers and clinicians to infer what may be occurring between time-points. To allow inferences to be made regarding the impact that sleep quality may be having on WM development, longitudinal studies with much shorter between-scan intervals are required. METHODS: The current study reports longitudinal data of self-reported sleep quality (PSQI), diffusion tensor imaging (DTI) measures of WM development and psychological distress (K10) for n = 64 early adolescents spanning the first twelve months (four time-points; Baseline, 4, 8, & 12 months) of the Longitudinal Adolescent Brain Study (LABS) study currently underway at the Thompson Institute. RESULTS: Generalised Estimating Equation analysis showed a significant relationship between sleep quality and psychological distress over the four time-points. Reduced radial diffusivity and increased fractional anisotropy of the UF is also reported with increasing age suggesting that ongoing myelination is occurring. Adding sleep quality to the model, however, negatively impacted this myelination process. CONCLUSION: These findings represent an important step towards elucidating how sleep, psychological distress and maturation of the UF may co-develop during early adolescence.

Fluid Balance Predicts Need for Intubation in Subjects With Respiratory Failure Initiated on High-Flow Nasal Cannula.

BACKGROUND: High-flow nasal cannula (HFNC) has gained widespread use for acute hypoxemic respiratory failure on the basis of recent publications that demonstrated fewer intubations and perhaps lower mortality in certain situations. However, a subset of patients initiated on HFNC for respiratory failure ultimately do require intubation. Our goal was to identify patient-level features predictive of this outcome. METHODS: This was a retrospective cohort study of subjects with hypoxemic respiratory failure treated with HFNC. Individuals were described as having succeeded (if weaned from HFNC) or failed (if they required intubation). A variety of easily measurable variables were evaluated for their ability to predict intubation risk, analyzed via a multivariate logistic regression model. RESULTS: Of a total of 74 subjects, 42 succeeded and 32 failed. The mean ± SD net fluid balance in the first 24 h after HFNC initiation was significantly lower in the success group versus the failure group (-33 ± 80 mL/h vs 72 ± 117 mL/h; P < .01). An adjusted model found only fluid balance and the previously described respiratory rate (breathing frequency [f]) to oxygenation (ROX) index ([[Formula: see text]/[Formula: see text]]/f) at 12 h as significant predictors of successful weaning (negative fluid balance adjusted odds ratio 0.77 [95% CI 0.62-0.96] for -10 mL/h increments [P = .02]; ROX adjusted OR 1.72 [1.15-2.57], P < .01). CONCLUSIONS: A negative fluid balance while on HFNC discriminated well between those who required intubation versus those who were successfully weaned.

Associations between sleep quality and psychological distress in early adolescence.

Background: Although numerous studies have reported an association between sleep quality and mental health, few have focused on this association exclusively in early adolescence. Targeting this age group is vital as many mental illnesses first emerge during adolescence and remain a significant burden throughout life. Method: In the current study n = 60 participants aged 12 years completed the Pittsburgh Sleep Quality Index (PSQI) and Kessler Psychological Distress Scale (K10). Results: Consistent with previous findings, bivariate correlations revealed significant positive linear relationships between K10 total score and (i) PSQI total score; (ii) sleep quality; (iii) daytime dysfunction; and (iv) sleep disturbance. However, contrary to previous findings, there was no significant correlation between K10 scores and sleep duration. Conclusion: The association between sleep quality and psychological distress in early adolescents provides some important clues about the role that sleep may play in predicting the onset of anxiety and depressive disorders. Longitudinal studies should be undertaken to investigate age-related changes in sleep and psychological distress.

Investigating the association between sleep quality and diffusion-derived structural integrity of white matter in early adolescence.

INTRODUCTION: Poor sleep quality has been linked to reduced neural connectivity through decreased white matter (WM) structural integrity. WM tract development has been shown to continue throughout adolescence with studies reporting positive correlations between diffusion-derived estimates of structural integrity and reduced sleep quality in adult samples. Few studies have investigated this relationship exclusively within a sample of young adolescents. METHODS: N = 51 participants aged 12 years (M = 151.5 months, SD = 4 months) completed a self-report questionnaire which included the Pittsburgh Sleep Quality Index (PSQI) and underwent Diffusion Tensor Imaging (DTI) as part of their baseline assessment in the Longitudinal Adolescent Brain Study (LABS) being undertaken in Queensland, Australia. Fractional anisotropy (FA) were extracted using Tract-Based Spatial Statistics (TBSS) to investigate associations between sleep quality and WM integrity across the brain. RESULTS: Significant correlations were found between the posterior limb of the internal capsule and the PSQI total sleep quality and sleep latency scores. There was also a significant difference in sleep duration between male and female participants. CONCLUSION: These findings provide an important insight of the impact that sleep may have on early adolescent WM development. Ongoing longitudinal assessment of sleep on WM development across adolescence is likely to provide further important information about how WM maturation relates to variations in sleep quality as circadian rhythm changes occur during middle and late adolescence.

Development of a National Academic Boot Camp to Improve Fellowship Readiness.

Background: Pulmonary and critical care medicine (PCCM) fellowship requires a high degree of medical knowledge and procedural competency. Gaps in fellowship readiness can result in significant trainee anxiety related to starting fellowship training.Objective: To improve fellowship readiness and alleviate anxiety for PCCM-bound trainees by improving confidence in procedural skills and cognitive domains.Methods: Medical educators within the American Thoracic Society developed a national resident boot camp (RBC) to provide an immersive, experiential training program for physicians entering PCCM fellowships. The RBC curriculum is a 2-day course designed to build procedural skills, medical knowledge, and clinical confidence through high-fidelity simulation and active learning methodology. Separate programs for adult and pediatric providers run concurrently to provide unique training objectives targeted to their learners' needs. Trainee assessments include multiple-choice pre- and post-RBC knowledge tests and confidence assessments, which are scored on a four-point Likert scale, for specific PCCM-related procedural and cognitive skills. Learners also evaluate course material and educator effectiveness, which guide modifications of future RBC programs and provide feedback for individual educators, respectively.Results: The American Thoracic Society RBC was implemented in 2014 and has grown annually to include 132 trainees and more than 100 faculty members. Mean knowledge test scores for participants in the 2019 RBC adult program increased from 55% (±14% SD) on the pretest to 72% (±11% SD; P < 0.001) after RBC completion. Similarly, mean pretest scores for pediatric course attendees increased from 54% (±13% SD) to 62% (±19% SD; P = 0.17). Specific content domains that improved by 10% or more between pre- and posttests included airway management, bronchoscopy, pulmonary function testing, and code management for adult course participants, and airway management, pulmonary function testing, and extracorporeal membrane oxygenation for pediatric course participants. Trainee confidence also significantly improved across all procedural and cognitive domains for adult trainees and in 10 of 11 domains for pediatric course attendees. Course content for the 2019 RBC was overwhelmingly rated as "on target" for the level of learner, with <4% of respondents indicating any specific session was "much too basic" or "much too advanced."Conclusion: RBC participation improved PCCM-bound trainee knowledge, procedural familiarity, and confidence. Refinement of the RBC curriculum over the past 7 years has been guided by educator and course evaluations, with the ongoing goal of meeting the evolving educational needs of rising PCCM trainees.

Investigating the links between adolescent sleep deprivation, fronto-limbic connectivity and the Onset of Mental Disorders: a review of the literature.

The importance of sleep for mental health has been known for some time. Although it was initially suggested that mental health conditions negatively impact sleep, it is now widely understood that this association is bidirectional. Adolescence is a period where people are at an increased risk of being sleep deprived largely due to a late shift in the circadian rhythm around puberty combined with early school start times. This combination may lead to adolescents being at an increased risk of mental health problems. Adolescence is also a period of continued brain development with white matter maturation continuing in the frontal brain regions throughout adolescence and into early adulthood. White matter development involves myelination of axons that link areas of grey matter and is integral for communication speed and efficiency. Studies have demonstrated that sufficient sleep is required for myelination to occur. The uncinate fasciculus (UF) is one of the last white matter tracts to be myelinated with this process occurring throughout adolescence and running between the amygdala in the limbic system and the orbitofrontal (OFC) and medial prefrontal cortices (mPFC). Recent studies have shown that connectivity between the amygdala and OFC is important for an individual's ability to exert top-down executive control over amygdala based automatic emotional responses to experiences perceived as threatening. The current literature review provides an overview of these mechanisms and concludes by proposing a model of adolescent sleep deprivation leading to potential life-long mental health issues through the moderating impact of reduced UF development.

Modeling risk for developing drug resistant bacterial infections in an MDR-naive critically ill population.

PURPOSE: To create a model predictive of an individual's risk of developing a de novo multidrug-resistant (MDR) infection while in the intensive care unit (ICU). METHODS: This is a case-control study in which 189 ICU patients diagnosed with their first infection with an MDR organism were compared on the basis of demographic, past medical and clinical variables to randomly selected ICU patients without such an infection, era-matched in a 2:1 ratio. A prediction tool was derived using multivariate logistic regression. RESULTS: Five features remained predictive of developing an infection with a drug-resistant pathogen: hospitalization within a year [adjusted odds ratio (OR) 2.14], chronic hemodialysis (3.86), underlying oxygen-dependent pulmonary disease (1.86), endotracheal intubation within 24 h (2.46) and reason for ICU admission (respiratory failure 2.89, non-respiratory failure, non-shock presentation 1.85). Using a scoring system (0-7 points) based on the adjusted OR, risk categories were derived (low: 0-2 points, intermediate: 3-4 points and high risk: 5-7 points). The negative predictive value at a score cutoff of 2 is excellent (88.9%). CONCLUSIONS: A clinical prediction rule comprised of five easily measured ICU variables reasonably discriminates between patients who will develop their first MDR infection versus those who will not.

Developing an innovative online medication calculator for patients with Parkinson's disease who are nil by mouth.

Missed Parkinson's disease (PD) medications when patients are admitted to hospital are associated with increased -morbidity and mortality. Swallowing difficulties in hospitalised PD patients are common and should prompt clinicians to -consider conversion of a patient's PD medications to a non-oral form - this is, however, recognised as a challenging area with potential for error. Northumbria Healthcare NHS Foundation Trust's PD service set out to address this patient safety issue through the development of an innovative online medication -calculator (pdmedcalc.co.uk). This article summarises the development process underpinning the calculator, presents numerical data on the usage of the calculator and presents survey data -relating to user experiences of the calculator. Lastly, we highlight how user feedback has been used to refine subsequent iterations of the calculator and how use of the calculator has rapidly spread beyond our trust because of it being freely accessible online.

The Pre-Eclampsia Ontology: A Disease Ontology Representing the Domain Knowledge Specific to Pre-Eclampsia.

Pre-eclampsia (PE) is a clinical syndrome characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation, and is a leading cause of maternal and perinatal morbidity and mortality. Previous studies have gathered abundant data about PE such as risk factors and pathological findings. However, most of these data are not semantically structured. Clinical data on PE patients are often generated with semantic heterogeneity such as using disparate terminology to describe the same phenomena. In clinical studies, interoperability of heterogenic clinical data is required in various situations. In such a situation, it is necessary to develop an interoperable and standardized semantic framework to research the pathology of PE more comprehensively and to achieve interoperability of heterogenic clinical data of PE patients. In this study, we developed an ontology representing clinical features, treatments, genetic factors, environmental factors, and other aspects of the current knowledge in the domain of PE. We call this pre-eclampsia ontology "PEO". To achieve interoperability with other ontologies, the core structure of PEO was compliant with the hierarchy of the Basic Formal Ontology (BFO). The PEO incorporates a wide range of key concepts and terms of PE from clinical and biomedical research in structuring the knowledge base that is specific to PE; therefore, PEO is expected to enhance PE-specific information retrieval and knowledge discovery in both clinical and biomedical research fields.

The pain interactome: connecting pain-specific protein interactions.

Understanding the molecular mechanisms associated with disease is a central goal of modern medical research. As such, many thousands of experiments have been published that detail individual molecular events that contribute to a disease. Here we use a semi-automated text mining approach to accurately and exhaustively curate the primary literature for chronic pain states. In so doing, we create a comprehensive network of 1,002 contextualized protein-protein interactions (PPIs) specifically associated with pain. The PPIs form a highly interconnected and coherent structure, and the resulting network provides an alternative to those derived from connecting genes associated with pain using interactions that have not been shown to occur in a painful state. We exploit the contextual data associated with our interactions to analyse subnetworks specific to inflammatory and neuropathic pain, and to various anatomical regions. Here, we identify potential targets for further study and several drug-repurposing opportunities. Finally, the network provides a framework for the interpretation of new data within the field of pain.

Cataloging the biomedical world of pain through semi-automated curation of molecular interactions.

The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie 'pain', a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can facilitate rapid curation of molecular interactions to create a custom database. Database URL: •••

Effects of allergic phenotype on respiratory symptoms and exacerbations in patients with chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) guidelines make no recommendations for allergy diagnosis or treatment. OBJECTIVES: To determine whether an allergic phenotype contributes to respiratory symptoms and exacerbations in patients with COPD. METHODS: Two separate cohorts were analyzed: National Health and Nutrition Survey III (NHANES III) and the COPD and domestic endotoxin (CODE) cohort. Subjects from NHANES III with COPD (n = 1,381) defined as age > 40 years, history of smoking, FEV1/FVC < 0.70, and no diagnosis of asthma were identified. The presence of an allergic phenotype (n = 296) was defined as self-reported doctor diagnosed hay fever or allergic upper respiratory symptoms. In CODE, former smokers with COPD (n = 77) were evaluated for allergic sensitization defined as a detectable specific IgE to perennial allergens. Bivariate and multivariate models were used to determine whether an allergic phenotype was associated with respiratory symptoms and exacerbations. MEASUREMENTS AND MAIN RESULTS: In NHANES III, multivariate analysis revealed that individuals with allergic phenotype were more likely to wheeze (odds ratio [OR], 2.1; P < 0.01), to have chronic cough (OR, 1.9; P = 0.01) and chronic phlegm (OR, 1.5; P < 0.05), and to have increased risk of COPD exacerbation requiring an acute doctor visit (OR, 1.7; P = 0.04). In the CODE cohort, multivariate analysis revealed that sensitized subjects reported more wheeze (OR, 5.91; P < 0.01), more nighttime awakening due to cough (OR, 4.20; P = 0.03), increased risk of COPD exacerbations requiring treatment with antibiotics (OR, 3.79; P = 0.02), and acute health visits (OR, 11.05; P < 0.01). An increasing number of sensitizations was associated with a higher risk for adverse health outcomes. CONCLUSIONS: Among individuals with COPD, evidence of an allergic phenotype is associated with increased respiratory symptoms and risk of COPD exacerbations.