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Purpose: We aimed to explore the effect of multiple pre- and postnatal exposures on optic nerve status in young adults due to this critical period for development., Methods: We analysed peripapillary retinal nerve fibre layer (RNFL) status and macular thickness at age 18 years in the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000 ) cohort in relation to several exposures., Results: Of the 269 participants (median (IQR) age, 17.6 (0.6) years; 124 boys), 60 participants whose mothers had smoked during pregnancy had a thinner RNFL: adjusted mean difference -4.6 μm (95% CI -7.7; -1.5 μm, p = 0.004) compared with participants whose mothers had not smoked during pregnancy. A total of 30 participants who were exposed to tobacco smoke both during foetal life and childhood had thinner RNFL: -9.6 μm (-13.4; -5.8 μm, p < 0.001). Smoking during pregnancy was also associated with a macular thickness deficit: -4.7 μm (-9.0; -0.4 μm, p = 0.03). Higher indoor concentrations of particulate matter 2.5 (PM2.5) was associated with thinner RNFL: -3.6 μm (-5.6; -1.6 μm, p < 0.001) and a macular deficit: -2.7 μm (-5.3; -0.1 μm, p = 0.04) in the crude analyses, but not in the adjusted analyses. No difference was found among participants who smoked at age 18 years compared with non-smokers on RNFL or macular thickness., Conclusions: We found that exposure to smoking during early life was associated with a thinner RNFL and macula at age 18 years. The absence of an association between active smoking at 18 years suggests that the vulnerability of the optic nerve is highest during prenatal life and early childhood., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective: To investigate the frequency and duration of hypo- and hyperglycemia, assessed by continuous glucose monitoring (CGM) during and after major surgery, in departments with implemented diabetes care protocols., Summary Background Data: Inadequate glycemic control in the perioperative period is associated with serious adverse events, but monitoring currently relies on point blood glucose measurements, which may underreport glucose excursions., Methods: Adult patients without (A) or with diabetes [non-insulin-treated type 2 (B), insulin-treated type 2 (C) or type 1 (D)] undergoing major surgery were monitored using CGM (Dexcom G6), with an electrochemical sensor in the interstitial fluid, during surgery and for up to 10 days postoperatively. Patients and health care staff were blinded to CGM values, and glucose management adhered to the standard diabetes care protocol. Thirty-day postoperative serious adverse events were recorded. The primary outcome was duration of hypoglycemia (glucose <70 mg/dL). Clinicaltrials.gov: NCT04473001., Results: Seventy patients were included, with a median observation time of 4.0 days. CGM was recorded in median 96% of the observation time. The median daily duration of hypoglycemia was 2.5 minutes without significant difference between the 4 groups (A-D). Hypoglycemic events lasting ≥15 minutes occurred in 43% of all patients and 70% of patients with type 1 diabetes. Patients with type 1 diabetes spent a median of 40% of the monitoring time in the normoglycemic range 70 to 180 mg/dL and 27% in the hyperglycemic range >250 mg/dL. Duration of preceding hypo- and hyperglycemia tended to be longer in patients with serious adverse events, compared with patients without events, but these were exploratory analyses., Conclusions: Significant duration of both hypo- and hyperglycemia was detected in high proportions of patients, particularly in patients with diabetes, despite protocolized perioperative diabetes management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: New-onset postoperative atrial fibrillation (POAF) is associated with several cardiovascular complications and higher mortality. Several pathophysiological processes such as hypoxia can trigger POAF, but these are sparsely elucidated, and POAF is often asymptomatic. In patients undergoing major gastrointestinal cancer surgery, we aimed to describe the frequency of POAF as automatically estimated and detected via wireless repeated sampling monitoring and secondarily to describe the association between preceding vital sign deviations and POAF., Method: Patients ≥60 years of age undergoing major gastrointestinal cancer surgery were continuously monitored for up to 4 days postoperatively. Electrocardiograms were obtained every minute throughout the monitoring period. Clinical staff were blinded to all measurements. As for the primary outcome, POAF was defined as 30 consecutive minutes or more detected by a purpose-built computerized algorithm and validated by cardiologists. The primary exposure variable was any episode of peripheral oxygen saturation (Spo2) <85% for >5 consecutive minutes before POAF., Results: A total of 30,145 hours of monitoring was performed in 398 patients, with a median of 92 hours per patient (interquartile range [IQR], 54-96). POAF was detected in 26 patients (6.5%; 95% confidence interval [CI], 4.5-9.4) compared with 14 (3.5%; 95% CI, 1.94-5.83) discovered by clinical staff in the monitoring period. POAF was followed by 9.4 days hospitalization (IQR, 6.5-16) versus 6.5 days (IQR, 2.5-11) in patients without POAF. Preceding episodes of Spo2 <85% for >5 minutes (OR, 1.02; 95% CI, 0.24-4.00; P = .98) or other vital sign deviations were not significantly associated with POAF., Conclusions: New-onset POAF occurred in 6.5% (95% CI, 4.5-9.4) of patients after major gastrointestinal cancer surgery, and 1 in 3 cases was not detected by the clinical staff (35%; 95% CI, 17-56). POAF was not preceded by vital sign deviations., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Background: The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood., Methods: We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one-month-old healthy neonates from the COPSAC 2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6 years. Principal component analyses were used to describe the airway cytokine and chemokine composition., Results: A neonatal airway immune profile particularly characterized by enhanced IL-1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune-associated markers, including IL-1β and CXCL8, showed trend of association with development of early asthma endpoints., Conclusions: Development of early asthma endpoints and inhalant allergy during the first 6 years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre- and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Transcutaneous measurements of CO 2 and O 2 ([Formula: see text], [Formula: see text]) are noninvasive and allow for continuous monitoring in adults with exacerbation of COPD, but substantial accuracy issues may exist. We investigated agreement between results of arterial blood gas analysis and transcutaneous measurements of CO 2 and O 2 in patients with COPD., Methods: Adult subjects were monitored after acute admission to a respiratory intermediate care unit or ICU due to exacerbation of COPD and with ongoing noninvasive ventilation or immediately following extubation. Monitored variables were continuous transcutaneous measurement and simultaneous routine arterial blood gas analysis. Agreement between measurements was assessed by calculating bias with 95% limits of agreement for single-point estimates of [Formula: see text] versus [Formula: see text] and versus [Formula: see text], and for changes in transcutaneous measurements between 2 time points ([Formula: see text] and [Formula: see text]). We considered limits of agreement within ± 7.5 mm Hg to be acceptable., Results: A total of 57 transcutaneous measurements were made in 20 subjects for comparison with concurrent arterial blood gas analysis at 36 time points. The bias (limits of agreement) for [Formula: see text] and [Formula: see text] was 2.5 mm Hg (-10.6 to 15.6 mm Hg) and 11.2 mm Hg (-28.2 to 50.6 mm Hg), respectively. The bias for [Formula: see text] and [Formula: see text] was 2.3 mm Hg (-3.8 to 8.3 mm Hg) and -5.3 mm Hg (-37.5 to 27 mm Hg), respectively., Conclusions: [Formula: see text] and [Formula: see text] did not accurately reflect results from arterial blood gas analyses in this study of mostly hypercapnic subjects. Agreement between changes in CO 2 during the monitoring period was acceptable, however, and transcutaneous monitoring may be used for continuous monitoring of [Formula: see text] in conjunction with arterial blood gas analysis for reference., Competing Interests: This work was supported in part by the Innovation Fund Denmark (8056-00055B); the Danish Cancer Society (R150-A9865-16-S48); Copenhagen Center for Health Technology (CACHET); Radiometer; A.P. Møller Foundation; Bispebjerg and Frederiksberg Hospital; Rigshospitalet; and the Technical University of Denmark. The WARD-project has received grants from the Innovation Fund Denmark, the Novo Nordic Foundation, the Danish Cancer Society, Steno Diabetes Center Denmark, Copenhagen Center for Health Technology, Radiometer, A.P. Møller Foundation as well as internal institutional funding. Drs Meyhoff and Aasvang are co-founders of a start-up company, WARD247 ApS, with the aim of pursuing the regulatory and commercial activities of the WARD-project. WARD247 ApS has finalized terms for license agreement for any WARD-project software and patents. There are currently no patents pending or filed. None of the above entities have influence on the study design, conduct, analysis or reporting., (Copyright © 2021 by Daedalus Enterprises.)

Objective. Wireless sensors for continuous monitoring of vital signs have potential to improve patient care by earlier detection of deterioration in general ward patients. We aimed to assess agreement between wireless and standard (wired) monitoring devices in patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Approach. Paired measurements of vital signs were recorded with 15 min intervals for two hours. The primary outcome was agreement between wireless and standard monitor measurements using the Bland and Altman method to calculate bias with 95% limits of agreement (LoA). We considered LoA of less than ±5 beats min -1 (bpm) acceptable for heart rate (HR), whereas agreement of peripheral oxygen saturation (SpO 2 ), respiratory rate (RR), and blood pressure (BP) were acceptable if within ±3%-points, ±3 breaths min -1 (brpm), and ±10 mmHg, respectively. Main results. 180 sample-pairs of vital signs from 20 with AECOPD patients were recorded for comparison. The wireless versus standard monitor bias was 0.03 (LoA -3.2 to 3.3) bpm for HR measurements, 1.4% (LoA -0.7% to 3.6%) for SpO 2 , -7.8 (LoA -22.3 to 6.8) mmHg for systolic BP and -6.2 (LoA -16.8 to 4.5) mmHg for diastolic BP. The wireless versus standard monitor bias for RR measurements was 0.75 (LoA -6.1 to 7.6) brpm. Significance. Commercially available wireless monitors could accurately measure HR in patients admitted with AECOPD compared to standard wired monitoring. Agreement for SpO 2 were borderline acceptable while agreement for RR and BP should be interpreted with caution., (© 2021 Institute of Physics and Engineering in Medicine.)

Background: Asthma-like symptoms in young children are orchestrated by the local airway immune response, but current knowledge largely relies on in vitro airway models. Azithromycin has been shown to reduce the duration of episodes with asthma-like symptoms, but efficacy may depend on the individual child's immune response., Objectives: To investigate in vivo upper airway immune mediator levels during episodes with asthma-like symptoms in young children and their ability to predict the clinical response to azithromycin treatment., Methods: A total of 535 children aged 0-3 years from the Copenhagen Prospective Studies of Asthma in Childhood-2010 mother-child cohort were examined for immune mediator levels in samples of nasal epithelial lining fluid during episodes with asthma-like symptoms as well as in the asymptomatic state. In a sub-study, children with recurrent asthma-like symptoms were randomized to either a 3-day course of oral azithromycin (10 mg/kg; n = 32) or placebo (n = 38). In the current study, we compared the pretreatment immune mediator levels with the clinical response to treatment with azithromycin in an exploratory post hoc analysis., Results: The immune mediator concentrations during vs outside episodes were significantly upregulated for IFN-ɣ (ratio 1.73), TNF-α (ratio 2.05), IL-1β (ratio 1.45), IL-10 (ratio 1.97), while CCL22 (ratio 0.65) was downregulated. Low levels of TNF-α and IL-10 and high levels of CCL22 predicted better treatment response to azithromycin (P-values < .05)., Conclusion: Upper airway immune mediator levels were altered during episodes of asthma-like symptoms, and levels of TNF-α, CCL22, and IL-10 may predict the response to azithromycin treatment., (© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Rationale: Experimental evidence suggests that CDHR3 (cadherin-related family member 3) is a receptor for rhinovirus (RV)-C, and a missense variant in this gene (rs6967330) is associated with childhood asthma with severe exacerbations., Objectives: To determine whether rs6967330 influences RV-C infections and illnesses in early childhood., Methods: We studied associations between rs6967330 and respiratory infections and illnesses in the COPSAC 2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) and COAST (Childhood Origins of Asthma Birth Cohort Study) birth cohorts, where respiratory infections were monitored prospectively for the first 3 years of life. Nasal samples were collected during acute infections in both cohorts and during asymptomatic periods in COAST and analyzed for RV-A, RV-B, and RV-C, and other common respiratory viruses., Measurements and Main Results: The CDHR3 asthma risk allele (rs6967330-A) was associated with increased risk of respiratory tract illnesses (incidence risk ratio [IRR] = 1.14 [95% confidence interval, 1.05-1.23]; P = 0.003). In particular, this variant was associated with risk of respiratory episodes with detection of RV-C in COPSAC 2010 (IRR = 1.89 [1.14-3.05]; P = 0.01) and in COAST (IRR = 1.37 [1.02-1.82]; P = 0.03) children, and in a combined meta-analysis (IRR = 1.51 [1.13-2.02]; P = 0.006). In contrast, the variant was not associated with illnesses related to other viruses (IRR = 1.07 [0.92-1.25]; P = 0.37). Consistent with these observations, the CDHR3 variant was associated with increased detection of RV-C, but not of other viruses during scheduled visits at specific ages., Conclusions: The CDHR3 asthma risk allele is associated specifically with RV-C illnesses in two birth cohorts. This clinical evidence supports earlier molecular evidence indicating that CDHR3 functions as an RV-C receptor, and raises the possibility of preventing RV-C infections by targeting CDHR3.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Wheezy episodes in young children are often triggered by viral and bacterial respiratory tract infections, but there is little evidence supporting the hypothesis that symptom duration depends on the specific microbial trigger., Objective: We sought to investigate whether the duration of wheezy episodes in young children depends on the microbial trigger., Methods: Two hundred eighty-three children from the Copenhagen Prospective Study on Asthma in Childhood2000 at-risk birth cohort were prospectively examined for common airway pathogenic bacteria and viruses during acute wheezy episodes in the first 3 years of life. Findings were related to symptomatic duration of episodes, as monitored in daily diary cards from birth., Results: Eight hundred thirty-seven samples were investigated for viruses, bacteria, or both. Both viruses and bacteria were identified in 55% of episodes, bacteria were identified exclusively in 31% of episodes, and viruses were identified exclusively in 10% of episodes. The median duration of acute symptoms was 9 days (interquartile range, 5-16 days), and duration was independent of bacterial or viral species., Conclusions: The duration of wheezy episodes was independent of pathogenic airway bacterial or viral species. This suggests that symptom burden from infections is dependent on other factors, such as environmental exposures or host factors. The common term viral wheeze seems inappropriate in view of the finding of pathogenic bacteria in 86% of wheezy episodes., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)