Poly(4-vinylpyridine) and Poly(methacrylic acid) Particle Architectures for pH-Responsive and Mechanochromic Opal Films.

While stimuli-responsive structural colors are commonly found in nature, mimicking these in artificial materials is challenging. Dynamically switchable and tunable coloration, however, is in high demand in widespread fields of applications, including advanced display and monitoring technologies, smart sensing, and anticounterfeiting. This work reports a scalable protocol for the synthesis of tailor-made core-shell particles and subsequent processing to opal films with iridescent, pH-responsive, and mechanochromic structural color. Novel monodisperse core-shell architectures based on hard polystyrene core particles are synthesized via stepwise emulsion polymerization in a starved-feed mode. The incorporation of 4-vinylpyridine and methacrylic acid as functional comonomers in the soft particle shell facilitates pH-responsive swelling and deswelling. Mechanically stable and well-ordered colloidal crystal films are obtained by the self-assembly of the particles during processing with the powerful melt-shear organization technique. Thereby obtained opal films show Bragg-scattering at the colloidal crystalline structure and exhibit brilliant green-turquoise to blue-violet reflection colors, dependent on the angle of view and illumination. Upon changes in the pH value or mechanical deformation, the reflected wavelength shifts by more than 100 nm, leading to intriguing changes in the visible structural color. Excellent reversibility is achieved by the subsequent application of a convenient UV cross-linking strategy, corroborating the high application potential of these advanced functional materials.

Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae.

PURPOSE: Olfactory dysfunction (OD) commonly accompanies coronavirus disease 2019 (COVID-19). We investigated the kinetics of OD resolution following SARS-CoV-2 infection (wild-type and alpha variant) and its impact on quality of life, physical and mental health. METHODS: OD prevalence was assessed in an ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and an observational cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up). Co-occurrence of OD with other symptoms and effects on quality of life, physical and mental health were analyzed by multi-dimensional scaling, association rule mining and semi-supervised clustering. RESULTS: Both in the ambulatory COVID-19 survey study (72%) and the observational ambulatory and hospitalized cohort (41%) self-reported OD was frequent during acute COVID-19. Recovery from self-reported OD was slow (survey: median 28 days, observational cohort: 90 days). By clustering of the survey data, we identified a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorders (median recovery: 90 days) but low frequency of post-acute fatigue, respiratory or neurocognitive symptoms. This smell and taste disorder cluster was characterized by a high rating of physical performance, mental health, and quality of life as compared with convalescents affected by prolonged fatigue or neurocognitive complaints. CONCLUSION: Our results underline the heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype is characterized by good clinical, physical, and mental recovery and may pose a minor challenge for public health. STUDY REGISTRATION: ClinicalTrials.gov: NCT04661462 (survey study), NCT04416100 (observational cohort).

Undiagnosed chronic respiratory disorders in symptomatic patients with initially suspected and excluded coronary artery disease: insights from a prospective pilot study.

Background: Chronic respiratory diseases represent the third-leading cause of death on a global scale. Due to mutual symptoms with cardiovascular diseases and potential inappropriate attribution of symptoms, pulmonary diseases often remain undiagnosed. Therefore, we aimed to evaluate the prevalence of chronic respiratory disorders among symptomatic patients in whom suspected coronary artery disease (CAD) was ruled out. Methods: After CAD was excluded by invasive coronary angiography (ICA), 50 patients with chest pain or dyspnea were prospectively enrolled in this study. All patients underwent lung function testing, including spirometry and diffusion measurements. At baseline and the 3-month follow-up, standardized assessments of symptoms (CCS chest pain, mMRC score, CAT score) were performed. Results: Chronic respiratory disease was diagnosed in 14% of patients, with a prevalence of 6% for chronic obstructive ventilation disorders. At 3-month follow-up, patients with normal lung function tests revealed a substantial improvement in symptoms (mean mMRC 0.70 to 0.33, p = 0.06; median CAT 8 to 2, p = 0.01), while those with pulmonary findings showed non-significant alterations or unchanged symptoms (mean mMRC 1.14 to 0.71, p = 0.53; median CAT 6 to 6, p = 0.52). Conclusion: A substantial proportion of patients with an initial suspicion of coronary artery disease was diagnosed with underlying chronic respiratory diseases and exhibited persistent symptoms.

COVID-19 and its continuing burden after 12†months: a longitudinal observational prospective multicentre trial.

Background: Recovery trajectories from coronavirus disease 2019 (COVID-19) call for longitudinal investigation. We aimed to characterise the kinetics and status of clinical, cardiopulmonary and mental health recovery up to 1 year following COVID-19. Methods: Clinical evaluation, lung function testing (LFT), chest computed tomography (CT) and transthoracic echocardiography were conducted at 2, 3, 6 and 12 months after disease onset. Submaximal exercise capacity, mental health status and quality of life were assessed at 12 months. Recovery kinetics and patterns were investigated by mixed-effect logistic modelling, correlation and clustering analyses. Risk of persistent symptoms and cardiopulmonary abnormalities at the 1-year follow-up were modelled by logistic regression. Findings: Out of 145 CovILD study participants, 108 (74.5%) completed the 1-year follow-up (median age 56.5 years; 59.3% male; 24% intensive care unit patients). Comorbidities were present in 75% (n=81). Key outcome measures plateaued after 180 days. At 12 months, persistent symptoms were found in 65% of participants; 33% suffered from LFT impairment; 51% showed CT abnormalities; and 63% had low-grade diastolic dysfunction. Main risk factors for cardiopulmonary impairment included pro-inflammatory and immunological biomarkers at early visits. In addition, we deciphered three recovery clusters separating almost complete recovery from patients with post-acute inflammatory profile and an enrichment in cardiopulmonary residuals from a female-dominated post-COVID-19 syndrome with reduced mental health status. Conclusion: 1 year after COVID-19, the burden of persistent symptoms, impaired lung function, radiological abnormalities remains high in our study population. Yet, three recovery trajectories are emerging, ranging from almost complete recovery to post-COVID-19 syndrome with impaired mental health.

Persistent somatic symptoms are key to individual illness perception at one year after COVID-19 in a cross-sectional analysis of a prospective cohort study.

OBJECTIVE: Subjective illness perception (IP) can differ from physician's clinical assessment results. Herein, we explored patient's IP during coronavirus disease 2019 (COVID-19) recovery. METHODS: Participants of the prospective observation CovILD study (ClinicalTrials.gov: NCT04416100) with persistent somatic symptoms or cardiopulmonary findings one year after COVID-19 were analyzed (n = 74). Explanatory variables included demographic and comorbidity, COVID-19 course and one-year follow-up data of persistent somatic symptoms, physical performance, lung function testing, chest computed tomography and trans-thoracic echocardiography. Factors affecting IP (Brief Illness Perception Questionnaire) one year after COVID-19 were identified by regularized modeling and unsupervised clustering. RESULTS: In modeling, 33% of overall IP variance (R2) was attributed to fatigue intensity, reduced physical performance and persistent somatic symptom count. Overall IP was largely independent of lung and heart findings revealed by imaging and function testing. In clustering, persistent somatic symptom count (Kruskal-Wallis test: η2 = 0.31, p < .001), fatigue (η2 = 0.34, p < .001), diminished physical performance (χ2 test, Cramer V effect size statistic: V = 0.51, p < .001), dyspnea (V = 0.37, p = .006), hair loss (V = 0.57, p < .001) and sleep problems (V = 0.36, p = .008) were strongly associated with the concern, emotional representation, complaints, disease timeline and consequences IP dimensions. CONCLUSION: Persistent somatic symptoms rather than abnormalities in cardiopulmonary testing influence IP one year after COVID-19. Modifying IP represents a promising innovative approach to treatment of post-COVID-19 condition. Besides COVID-19 severity, individual IP should guide rehabilitation and psychological therapy decisions.

Pulmonary recovery from COVID-19 in patients with metabolic diseases: a longitudinal prospective cohort study.

The severity of coronavirus disease 2019 (COVID-19) is related to the presence of comorbidities including metabolic diseases. We herein present data from the longitudinal prospective CovILD trial, and investigate the recovery from COVID-19 in individuals with dysglycemia and dyslipidemia. A total of 145 COVID-19 patients were prospectively followed and a comprehensive clinical, laboratory and imaging assessment was performed at 60, 100, 180, and 360 days after the onset of COVID-19. The severity of acute COVID-19 and outcome at early post-acute follow-up were significantly related to the presence of dysglycemia and dyslipidemia. Still, at long-term follow-up, metabolic disorders were not associated with an adverse pulmonary outcome, as reflected by a good recovery of structural lung abnormalities in both, patients with and without metabolic diseases. To conclude, dyslipidemia and dysglycemia are associated with a more severe course of acute COVID-19 as well as delayed early recovery but do not impair long-term pulmonary recovery.

Enhancing Clinical Diagnosis for Patients With Persistent Pulmonary Abnormalities After COVID-19 Infection: The Potential Benefit of 68 Ga-FAPI PET/CT.

PATIENTS AND METHODS: Six post COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual-tracer PET/CT with 18 F-FDG and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga-FAPI-46 in the involved lung was compared with a control group of 9 non-COVID-19 patients. Clinical data and PET/CT imaging were collected and analyzed. RESULTS: PET/CT revealed in all 6 pulmonary impaired patients the reduced glucose avidity on 18 F-FDG and clear positivity on 68 Ga-FAPI-46 PET/CT in comparison to the control group. CONCLUSIONS: Enhancing fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may improve noninvasive clinical diagnostic performance in patients with long-term CT abnormalities after severe COVID-19. Although this study shows promising results, additional studies in larger populations are required to establish a general diagnostic guideline.

Chest CT of Lung Injury 1 Year after COVID-19 Pneumonia: The CovILD Study.

Background The long-term pulmonary sequelae of COVID-19 is not well known. Purpose To characterize patterns and rates of improvement of chest CT abnormalities 1 year after COVID-19 pneumonia. Materials and Methods This was a secondary analysis of a prospective, multicenter observational cohort study conducted from April 29 to August 12, 2020, to assess pulmonary abnormalities at chest CT approximately 2, 3, and 6 months and 1 year after onset of COVID-19 symptoms. Pulmonary findings were graded for each lung lobe using a qualitative CT severity score (CTSS) ranging from 0 (normal) to 25 (all lobes involved). The association of demographic and clinical factors with CT abnormalities after 1 year was assessed with logistic regression. The rate of change of the CTSS at follow-up CT was investigated by using the Friedmann test. Results Of 142 enrolled participants, 91 underwent a 1-year follow-up CT examination and were included in the analysis (mean age, 59 years ± 13 [SD]; 35 women [38%]). In 49 of 91 (54%) participants, CT abnormalities were observed: 31 of 91 (34%) participants showed subtle subpleural reticulation, ground-glass opacities, or both, and 18 of 91 (20%) participants had extensive ground-glass opacities, reticulations, bronchial dilation, microcystic changes, or a combination thereof. At multivariable analysis, age of more than 60 years (odds ratio [OR], 5.8; 95% CI: 1.7, 24; P = .009), critical COVID-19 severity (OR, 29; 95% CI: 4.8, 280; P < .001), and male sex (OR, 8.9; 95% CI: 2.6, 36; P < .001) were associated with persistent CT abnormalities at 1-year follow-up. Reduction of CTSS was observed in participants at subsequent follow-up CT (P < .001); during the study period, 49% (69 of 142) of participants had complete resolution of CT abnormalities. Thirty-one of 49 (63%) participants with CT abnormalities showed no further improvement after 6 months. Conclusion Long-term CT abnormalities were common 1 year after COVID-19 pneumonia. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leung in this issue.

Investigating phenotypes of pulmonary COVID-19 recovery: A longitudinal observational prospective multicenter trial.

Background: The optimal procedures to prevent, identify, monitor, and treat long-term pulmonary sequelae of COVID-19 are elusive. Here, we characterized the kinetics of respiratory and symptom recovery following COVID-19. Methods: We conducted a longitudinal, multicenter observational study in ambulatory and hospitalized COVID-19 patients recruited in early 2020 (n = 145). Pulmonary computed tomography (CT) and lung function (LF) readouts, symptom prevalence, and clinical and laboratory parameters were collected during acute COVID-19 and at 60, 100, and 180 days follow-up visits. Recovery kinetics and risk factors were investigated by logistic regression. Classification of clinical features and participants was accomplished by unsupervised and semi-supervised multiparameter clustering and machine learning. Results: At the 6-month follow-up, 49% of participants reported persistent symptoms. The frequency of structural lung CT abnormalities ranged from 18% in the mild outpatient cases to 76% in the intensive care unit (ICU) convalescents. Prevalence of impaired LF ranged from 14% in the mild outpatient cases to 50% in the ICU survivors. Incomplete radiological lung recovery was associated with increased anti-S1/S2 antibody titer, IL-6, and CRP levels at the early follow-up. We demonstrated that the risk of perturbed pulmonary recovery could be robustly estimated at early follow-up by clustering and machine learning classifiers employing solely non-CT and non-LF parameters. Conclusions: The severity of acute COVID-19 and protracted systemic inflammation is strongly linked to persistent structural and functional lung abnormality. Automated screening of multiparameter health record data may assist in the prediction of incomplete pulmonary recovery and optimize COVID-19 follow-up management. Funding: The State of Tyrol (GZ 71934), Boehringer Ingelheim/Investigator initiated study (IIS 1199-0424). Clinical trial number: ClinicalTrials.gov: NCT04416100.

A spark of hope: histopathological and functional recovery after critical COVID-19.

BACKGROUND: There are substantial concerns about fibrotic and vascular pulmonary sequelae after coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS).AQ1 Histopathology reports of lung biopsies from COVID-19 survivors are scarce. CASE: We herein report results of functional and histopathological studies in a 70 year-old man undergoing a co-incidental tumor lobectomy six months after long-term mechanical ventilation for COVID-19 pneumonia. CONCLUSION: Despite several unfavorable risk factors, this case presentation shows a completed pulmonary recovery process within a few months.

Phenotyping of Acute and Persistent Coronavirus Disease 2019 Features in the Outpatient Setting: Exploratory Analysis of an International Cross-sectional Online Survey.

BACKGROUND: Long COVID, defined as the presence of coronavirus disease 2019 (COVID-19) symptoms ≥28 days after clinical onset, is an emerging challenge to healthcare systems. The objective of the current study was to explore recovery phenotypes in nonhospitalized individuals with COVID-19. METHODS: A dual cohort, online survey study was conducted between September 2020 and July 2021 in the neighboring European regions Tyrol (TY; Austria, n = 1157) and South Tyrol (STY; Italy, n = 893). Data were collected on demographics, comorbid conditions, COVID-19 symptoms, and recovery in adult outpatients. Phenotypes of acute COVID-19, postacute sequelae, and risk of protracted recovery were explored using semi-supervised clustering and multiparameter least absolute shrinkage and selection operator (LASSO) modeling. RESULTS: Participants in the study cohorts were predominantly working age (median age [interquartile range], 43 [31-53] years] for TY and 45 [35-55] years] for STY) and female (65.1% in TY and 68.3% in STY). Nearly half (47.6% in TY and 49.3% in STY) reported symptom persistence beyond 28 days. Two acute COVID-19 phenotypes were discerned: the nonspecific infection phenotype and the multiorgan phenotype (MOP). Acute MOP symptoms encompassing multiple neurological, cardiopulmonary, gastrointestinal, and dermatological symptoms were linked to elevated risk of protracted recovery. The major subset of individuals with long COVID (49.3% in TY; 55.6% in STY) displayed no persistent hyposmia or hypogeusia but high counts of postacute MOP symptoms and poor self-reported physical recovery. CONCLUSIONS: The results of our 2-cohort analysis delineated phenotypic diversity of acute and postacute COVID-19 manifestations in home-isolated patients, which must be considered in predicting protracted convalescence and allocating medical resources.

Porous Mixed-Metal Oxide Li-Ion Battery Electrodes by Shear-Induced Co-assembly of Precursors and Tailored Polymer Particles.

Due to their various applications, metal oxides are of high interest for fundamental research and commercial usage. Per applications as catalysts or electrochemical devices, the tailored design of metal oxides featuring a high specific surface area and additional functionalities is of the utmost importance for the performance of the resulting materials. We report a new method for preparing free-standing films consisting of hierarchically porous metal oxides (titanium and niobium based) by combining emulsion polymerization and shear-induced monodisperse particle self-assembly in the presence of sol-gel precursors. After thermal treatment, the resulting porous materials can be used as electrodes in Li-ion batteries. The titanium and niobium sol-gel precursors were partially immobilized to the surface of organic core-interlayer particles featuring hydroxyl groups to obtain hybrid organic-inorganic particles through the melt-shear organization process. Free-standing particle-based films, in analogy to elastomeric opal films and colloidal crystals, can be prepared in a convenient one-step preparation process. After thermal treatment, ordered pores are obtained, while the pristine metal oxide precursor shell can be converted to the (mixed) metal oxide matrix. Heat treatment under CO2 leads to mixed-TiNb oxide/carbon hybrid materials. The highly porous derivative structure enhances electrolyte permeation. When tested as Li-ion battery electrodes, it shows a specific capacity of 335 mAh·g-1 at a rate of 10 mA·g-1. After 1000 cycles at 250 mA·g-1, the electrodes still provided a specific capacity of 191 mAh·g-1.

Embedding Photoacids into Polymer Opal Structures: Synergistic Effects on Optical and Stimuli-Responsive Features.

Opal films with their vivid structural colors represent a field of tremendous interest and obtained materials offer the possibility for many applications, such as optical sensors or anti-counterfeiting materials. A convenient method for the generation of opal structures relies on the tailored design of core-interlayer-shell (CIS) particles. Within the present study, elastomeric opal films were combined with stimuli-responsive photoacids to further influence the optical properties of structurally colored materials. Starting from cross-linked polystyrene (PS) core particles featuring a hydroxy-rich and polar soft shell, opal films were prepared by application of the melt-shear organization technique. The photoacid tris(2,2,2-trifluoroethyl) 8-hydroxypyrene-1,3,6-trisulfonate (TFEHTS) could be conveniently incorporated during freeze-drying the particle dispersion and prior to the melt-shear organization. Furthermore, the polar opal matrix featuring hydroxylic moieties enabled excited-state proton transfer (ESPT), which is proved by spectroscopic evaluation. Finally, the influence of the photoacid on the optical properties of the 3-dimensional colloidal crystals were investigated within different experimental conditions. The angle dependence of the emission spectra unambiguously shows the selective suppression of the photoacid's fluorescence in its deprotonated state.

COPD exacerbations are related to poor air quality in Innsbruck: A retrospective pilot study.

BACKGROUND: Triggers of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are diverse, potentially including airborne pollutants. OBJECTIVES: To analyze whether daily air pollution levels correlate with AECOPD frequency. METHODS: In this retrospective pilot-study, AECOPD frequency was recorded between 2010 and 2016 at the University Hospital of Innsbruck's emergency department and correlated with daily air quality parameters. Data was compared to pulmonary embolism (PE) frequency, a disease not directly involving the airways. RESULTS: In total, 669 AECOPD and 857 PE events were registered. Days with AECOPD revealed significantly higher concentrations of CO and SO2, whereas days with PE displayed an elevation of NO. Higher frequencies of AECOPD during winter months correlated with higher CO and SO2 levels, disclosing a seasonal trend, while no such pattern was observed for PE. CONCLUSION: Air pollution is linked to AECOPD frequency, however, prospective studies are needed to confirm this possible, underrecognized trigger of AECOPD.

Dye-Loaded Mechanochromic and pH-Responsive Elastomeric Opal Films.

In this work, the preparation and fabrication of elastomeric opal films revealing reversible mechanochromic and pH-responsive features are reported. The core-interlayer-shell (CIS) particles are synthesized via stepwise emulsion polymerization leading to hard core (polystyrene), crosslinked interlayer (poly(methyl methacrylate-co-allyl methacrylate), and soft poly(ethyl acrylate-co-butyl acrylate-co-(2-hydroxyethyl) methacrylate) shell particles featuring a size of 294.9 ± 14.8 nm. This particle architecture enables the application of the melt-shear organization technique leading to elastomeric opal films with orange, respectively, green brilliant reflection colors dependent on the angle of view. Moreover, the hydroxyl moieties as part of the particle shell are advantageously used for subsequent thermally induced crosslinking reactions enabling the preparation of reversibly tunable mechanochromic structural colors based on Bragg's law of diffraction. Additionally, the CIS particles can be loaded upon extrusion or chemically by a postfunctionalization strategy with organic dyes implying pH-responsive features. This convenient protocol for preparing multi-responsive, reversibly stretch-tunable opal films is expected to enable a new material family for anti-counterfeiting applications based on external triggers.

Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial.

BACKGROUND: After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking. METHODS: In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT). RESULTS: Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time. CONCLUSION: A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities >100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.

Persisting alterations of iron homeostasis in COVID-19 are associated with non-resolving lung pathologies and poor patients' performance: a prospective observational cohort study.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is frequently associated with hyperinflammation and hyperferritinemia. The latter is related to increased mortality in COVID-19. Still, it is not clear if iron dysmetabolism is mechanistically linked to COVID-19 pathobiology. METHODS: We herein present data from the ongoing prospective, multicentre, observational CovILD cohort study (ClinicalTrials.gov number, NCT04416100), which systematically follows up patients after COVID-19. 109 participants were evaluated 60 days after onset of first COVID-19 symptoms including clinical examination, chest computed tomography and laboratory testing. RESULTS: We investigated subjects with mild to critical COVID-19, of which the majority received hospital treatment. 60 days after disease onset, 30% of subjects still presented with iron deficiency and 9% had anemia, mostly categorized as anemia of inflammation. Anemic patients had increased levels of inflammation markers such as interleukin-6 and C-reactive protein and survived a more severe course of COVID-19. Hyperferritinemia was still present in 38% of all individuals and was more frequent in subjects with preceding severe or critical COVID-19. Analysis of the mRNA expression of peripheral blood mononuclear cells demonstrated a correlation of increased ferritin and cytokine mRNA expression in these patients. Finally, persisting hyperferritinemia was significantly associated with severe lung pathologies in computed tomography scans and a decreased performance status as compared to patients without hyperferritinemia. DISCUSSION: Alterations of iron homeostasis can persist for at least two months after the onset of COVID-19 and are closely associated with non-resolving lung pathologies and impaired physical performance. Determination of serum iron parameters may thus be a easy to access measure to monitor the resolution of COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04416100.

Current symptom-based risk scores for stable coronary artery disease evaluation are not applicable in COPD patients.

BACKGROUND: Cardiovascular diseases are arguably the most important comorbidity in patients with COPD. Despite an increased prevalence of coronary artery disease (CAD) in COPD patients, there are no dedicated diagnostic recommendations. OBJECTIVES: We investigated whether COPD patients receive adequate primary evaluation of CAD despite overlapping symptoms. METHODS: In total, 302 patients with COPD who underwent invasive coronary angiography (ICA) were retrospectively matched (for age, body mass index and cardiovascular risk factors) with 302 patients without functional lung diseases. Quality and onset of symptoms prior to ICA were documented, and individual patients' pretest probabilities according to European Society of Cardiology (ESC) guidelines were calculated. Endpoints were delay of ICA referral after symptom onset and clinical outcome, defined as subsequent revascularisation. RESULTS: Mean delay between symptom onset and ICA was 19.9±22.0 months in COPD patients compared to 8.3±12.7 months in the control group (p<0.0001). COPD patients had a lower rate of typical chest pain (25.2% versus 38.1%, p=0.0009), and dyspnoea only (18.2% versus 26.8%, p=0.015). Sub-analysis of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades revealed an incremental delay with increasing COPD severity: GOLD 1: 16.1±17.3 months; GOLD 2: 17.6±22.1 months; GOLD 3: 20.1±21.3 months; and GOLD 4: 24.2±23.4 months. Overall significant CAD prevalence (>70% stenosis) was 35.3%; the revascularisation rate increased with higher pretest probability for the control group but decreased for patients with COPD GOLD 1-4. CONCLUSION: Patients with COPD are insufficiently evaluated for CAD due to overlapping symptoms. Current CAD risk scores for stable chest pain appear inappropriate for patients with COPD.

Identification of ALK in Thinness.

There is considerable inter-individual variability in susceptibility to weight gain despite an equally obesogenic environment in large parts of the world. Whereas many studies have focused on identifying the genetic susceptibility to obesity, we performed a GWAS on metabolically healthy thin individuals (lowest 6th percentile of the population-wide BMI spectrum) in a uniquely phenotyped Estonian cohort. We discovered anaplastic lymphoma kinase (ALK) as a candidate thinness gene. In Drosophila, RNAi mediated knockdown of Alk led to decreased triglyceride levels. In mice, genetic deletion of Alk resulted in thin animals with marked resistance to diet- and leptin-mutation-induced obesity. Mechanistically, we found that ALK expression in hypothalamic neurons controls energy expenditure via sympathetic control of adipose tissue lipolysis. Our genetic and mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.