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Scholarship addressing public and community engagement in tenure and promotion often invokes Ernest Boyer's landmark 1990 report, "Scholarship Reconsidered: Priorities of the Professoriate," and goes on to lament the lack of progress made in the three decades that have followed. This review intervenes: We synthesize extant scholarship on community-engaged scholarship and public engagement (CES&PE) in appointment, tenure, and promotion (APT); lay out three central challenges to the advancement of CES&PE; review the strategies institutions and individuals have leveraged to advance more equitable and effective processes; and caution against potential inadvertent, damaging consequences of reforms focused solely on CES&PE. We argue not only that recognition for CES&PE in APT is essential for fulfilling the institutional missions of universities for the public good, but also that it is essential to advancing diversity, equity, inclusion, and justice on college and university campuses.

The SARS-CoV-2 pandemic and the emergence of novel virus variants have had a dramatic impact on public health and the world economy, underscoring the need for detailed studies that explore the high efficacy of additional vaccines in animal models. In this study, we confirm the pathogenicity of the SARS-CoV-2/Leiden_008 isolate (GenBank accession number MT705206.1) in K18-hACE2 transgenic mice. Using this isolate, we show that a vaccine consisting of capsid virus-like particles (cVLPs) displaying the receptor-binding domain (RBD) of SARS-CoV-2 (Wuhan strain) induces strong neutralizing antibody responses and sterilizing immunity in K18-hACE2 mice. Furthermore, we demonstrate that vaccination with the RBD-cVLP vaccine protects mice from both a lethal infection and symptomatic disease. Our data also indicate that immunization significantly reduces inflammation and lung pathology associated with severe disease in mice. Additionally, we show that the survival of naïve animals significantly increases when sera from animals vaccinated with RBD-cVLP are passively transferred, prior to a lethal virus dose. Finally, the RBD-cVLP vaccine has a similar antigen composition to the clinical ABNCOV2 vaccine, which has shown non-inferiority to the Comirnaty mRNA vaccine in phase I-III trials. Therefore, our study provides evidence that this vaccine design is highly immunogenic and confers full protection against severe disease in mice.

BackgroundCoronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis.MethodsWe analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression.ResultsIn 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome.ConclusionsMortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.

BackgroundPatients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes.MethodsThe European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage.ResultsAmong 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2-7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage.ConclusionsThis study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic.

Background: In observational studies, high levels of desphospho-uncarboxylated matrix gla protein (dp-ucMGP) that result from vitamin K deficiency were consistently associated with poor clinical outcomes during COVID-19. Vitamin K-activated matrix gla protein (MGP) is required to protect against elastic fibre degradation, and a deficiency may contribute to pathology. However, intervention trials assessing the effects of vitamin K supplementation in COVID-19 are lacking. Methods: This is a single-centre, phase 2, double-blind, randomised, placebo-controlled trial investigating the effects of vitamin K2 supplementation in 40 hospitalised COVID-19 patients requiring supplemental oxygen. Individuals were randomly assigned in a 1:1 ratio to receive 999 mcg of vitamin K2—menaquinone-7 (MK-7)—or a placebo daily until discharge or for a maximum of 14 days. Dp-ucMGP, the rate of elastic fibre degradation quantified by desmosine, and hepatic vitamin K status quantified by PIVKA-II were measured. Grade 3 and 4 adverse events were collected daily. As an exploratory objective, circulating vitamin K2 levels were measured. Results: Vitamin K2 was well tolerated and did not increase the number of adverse events. A linear mixed model analysis showed that dp-ucMGP and PIVKA-II decreased significantly in subjects that received supplementation compared to the controls (p = 0.008 and p = 0.0017, respectively), reflecting improved vitamin K status. The decrease in dp-ucMGP correlated with higher plasma MK-7 levels (p = 0.015). No significant effect on desmosine was found (p = 0.545). Conclusions: These results demonstrate that vitamin K2 supplementation during COVID-19 is safe and decreases dp-ucMGP. However, the current dose of vitamin K2 failed to show a protective effect against elastic fibre degradation.

Abstract Background Increased airway wall thickness (AWT) and parenchymal lung destruction both contribute to airflow limitation. Advances in computed tomography (CT) post-processing imaging allow to quantify these features. The aim of this Dutch population study is to assess the relationships between AWT, lung function, emphysema and respiratory symptoms. Methods AWT and emphysema were assessed by low-dose CT in 500 male heavy smokers, randomly selected from a lung cancer screening population. AWT was measured in each lung lobe in cross-sectionally reformatted images with an automated imaging program at locations with an internal diameter of 3.5 mm, and validated in smaller cohorts of patients. The 15th percentile method (Perc15) was used to assess the severity of emphysema. Information about respiratory symptoms and smoking behavior was collected by questionnaires and lung function by spirometry. Results Median AWT in airways with an internal diameter of 3.5 mm (AWT3.5) was 0.57 (0.44 - 0.74) mm. Median AWT in subjects without symptoms was 0.52 (0.41-0.66) and in those with dyspnea and/or wheezing 0.65 (0.52-0.81) mm (p3.5 and emphysema independently explained 31.1%and 9.5%of the variance in FEV1%predicted, respectively, after adjustment for smoking behavior. Conclusions Post processing standardization of airway wall measurements provides a reliable and useful method to assess airway wall thickness. Increased airway wall thickness contributes more to airflow limitation than emphysema in a smoking male population even after adjustment for smoking behavior.

Erratum for hard copy: On page 105 the year of the internal South Sudanese civil war should be 2013, not 1913.

In this work, authors provide a proof-of-concept study showing that deubiquitinating enzyme inactivation in MERS-CoV leads to attenuation in mice, and protection against a lethal challenge.

Fossil fuels are the primary contributor to global climate change, and efforts to reach net-zero emissions will require a dramatic curtailment of their extraction and use. However, fossil fuels fund public services at all levels of government, and research has not assessed whether clean energy sources can provide similar scales of revenue. In this paper, we analyze a novel dataset that we have assembled on how fossil fuels and renewable energy contribute to local governments in 79 US counties across 10 states. Revenues from fossil fuels far outweigh renewables in aggregate terms, providing more than $1000 per capita annually in dozens of counties. However, wind and solar in some states generate more local public revenue than fossil fuels per unit of primary energy production. In most counties that depend heavily on fossil fuels for local revenues, solar—but not wind—has the technical potential to replace existing fossil fuel revenues, but this would require dedicating implausibly large portions of developable land (in some cases, more than half) to solar. For counties with less reliance on fossil fuels, wind and solar can more plausibly replace fossil fuel revenue streams. This finding suggests that while renewable energy will provide new revenue streams for communities, fossil fuel–dependent regions will need to build new tax bases well beyond wind and solar, develop other sources of revenue, or risk a decline in public service provision.

In a moment when the "value" of postsecondary education has been repeatedly called into question, this study responds by identifying long-term effects of the undergraduate experience with particular attention to the general education curriculum. Specifically, it draws on 559 written responses from a wide range of alumni to identify which elements of their undergraduate education are still most salient. Of these elements, coursework emerged as most important for alumni, who cited its contributions to their development of self-understanding, interpersonal skills, career preparation, and intellectual skills such as critical thinking. Alumni also indicated that perceptions of coursework shifted with time so that courses that did not seem useful at graduation ultimately provided valuable preparation for their lives and careers. In negative accounts, alumni described a lack of guidance through curricular requirements. This study demonstrates an approach that can yield more nuanced and complex information about the general education curriculum's long-term effects by including respondent writing as a supplement to the data gathered through closed-entry surveys. Analyzing what college alumni write about their undergraduate education proves not only to be a promising approach for understanding how to improve general education curricula more effectively, but to also further evidence for proclaiming the importance of general education.

Critical language awareness offers one approach to communal "justicing," an iterative and collective process that can address inequities in the disciplinary infrastructure of Writing Studies. We demonstrate justicing in the field's pasts, policies, and publications; offer a model of communal revision; and invite readers to become agents of communal justicing.

This essay examines how local draughtsmen using their visual expertise shaped natural historical knowledge production in colonial Indonesia in the early nineteenth century. The persons at the core of this essay are Tsing Wang Ho and Pieter van Oort, both draughtsmen who worked for the Natuurkundige Commissie voor Nederlandsch-Indië (Committee of Natural History of the Netherlands Indies). By zooming in on the Committee’s fieldwork in Java in the 1830s, this essay highlights that producing scientific drawings of animals and plants was a challenging endeavour. Despite detailed instructions from Europe and the logistical support of the colonial government in Batavia, the success of the Committee’s fieldwork also depended on local visual and natural expertise. By shifting the analytical focus from European draughtsmen and naturalists to local visual and natural expertise, this essay offers readers glimpses on a cross-cultural learning process which, in the long run, reshaped the visual repertoire on which taxonomic and biodiversity research has since then built on.

Introduction Consensus is lacking on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM). For future studies, the CONNECT consortium (the COllaborative Neonatal Network for the first European CPAM Trial)—an international collaboration of specialised caregivers—has established consensus on a core outcome set of outcome parameters concerning respiratory insufficiency, surgical complications, mass effect and multifocal disease. These outcome parameters have been incorporated in the CONNECT trial, a randomised controlled trial which, in order to develop evidence-based practice, aims to compare conservative and surgical management of patients with an asymptomatic CPAM.Methods and analysis Children are eligible for inclusion after the CPAM diagnosis has been confirmed on postnatal chest CT scan and they remain asymptomatic. On inclusion, children are randomised to receive either conservative or surgical management. Subsequently, children in both groups are enrolled into a standardised, 5-year follow-up programme with three visits, including a repeat chest CT scan at 2.5 years and a standardised exercise tolerance test at 5 years.The primary outcome is exercise tolerance at age 5 years, measured according to the Bruce treadmill protocol. Secondary outcome measures are molecular genetic diagnostics, validated questionnaires—on parental anxiety, quality of life and healthcare consumption—, repeated imaging and pulmonary morbidity during follow-up, as well as surgical complications and histopathology. This trial aims to end the continuous debate surrounding the optimal management of asymptomatic CPAM.Ethics and dissemination This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Centre Rotterdam, The Netherlands, has approved this protocol (MEC-2022–0441). Results will be disseminated through peer-reviewed scientific journals and conference presentations.Trial registration number NCT05701514.

This paper presents a rail network vulnerability analysis to identify which links within the Dutch rail network are most vulnerable to winter weather. A vulnerability index was developed to measure rail vulnerability during winter weather based on switch-related disruptions, integrating both node and link components into a probabilistic measure of vulnerability. The analysis looked at disruption data for 379 Dutch stations during the years 2007-2017. Links in dense population areas, which operate a high number of switches, are most susceptible to winter disturbances. Particularly, three main railway stations (Utrecht, Amersfoort and Zwolle) are the most critical locations within the network in terms of extreme winter conditions and disruptions. In addition, we developed two scenarios to analyse implications of different railway switch reduction strategies on rail vulnerability. The proposed rail vulnerability index can be a useful tool to define operational strategies to reduce the vulnerability of the Dutch railway network. Decreasing the number of switches at station areas appears to be more effective for reducing railway vulnerability than decreasing the number of switches throughout the entire network.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Background. The Netherlands was the third country to adopt the lung allocation score (LAS) for national allocation of donor lungs in April 2014. Evaluations of the introduction of the LAS in the United States and Germany showed mainly beneficial effects, including increased survival after transplantation. Methods. Data for transplant candidates from 2010 to 2019 were retrieved from the Dutch Transplant Foundation database. Diagnosis categories and outcomes were compared between the periods before and after the introduction of the LAS. Time-dependent Cox regression and Fine-Gray analyses were performed to compare the chance for transplantation before and after introduction of the LAS. Results. The cohort comprised 1276 patients. After introduction of the LAS, the annual number of transplantations and waiting list mortality did not change. The proportion of patients on the waiting list and transplanted patients with pulmonary fibrosis increased (25%–37%, P < 0.001; 22%–39%, P < 0.001). The chance of transplantation increased significantly for patients with pulmonary fibrosis after introduction of the LAS (hazard ratio 1.9 [95% confidence interval 1.4-2.9]). Patients who died on the waiting list had an increased LAS compared to the time of placement on the waiting list, reflecting clinical deterioration. This was not the case in patients with chronic obstructive pulmonary disease (P < 0.001). Overall survival was similar after introduction of the LAS (5-y survival 68%, compared to 74% [P = 0.171]). Conclusions. After the introduction of the LAS in The Netherlands, an increased proportion of transplantations was performed for patients with pulmonary fibrosis. Overall survival after transplantation did not change.

Background and Objectives: Children born with congenital diaphragmatic hernia (CDH) and treated with extracorporeal membrane oxygenation (ECMO), are at risk for motor function impairment during childhood. We hypothesized that all children born with CDH are at risk for persistent motor function impairment, irrespective of ECMO-treatment. We longitudinally assessed these children's motor function.Methods: Children with CDH with and without ECMO-treatment, born 1999–2007, who joined our structural prospective follow-up program were assessed with the Movement Assessment Battery for Children (M-ABC) at 5, 8, 12 years. Z-scores were used in a general linear model for longitudinal analysis.Results: We included 55 children, of whom 25 had been treated with ECMO. Forty-three (78%) were evaluated at three ages. Estimated mean (95% CI) z-scores from the general linear model were −0.67 (−0.96 to −0.39) at 5 years of age, −0.35 (−0.65 to −0.05) at 8 years, and −0.46 (−0.76 to −0.17) at 12 years. The 5- and 8-years scores differed significantly (p = 0.02). Motor development was significantly below the norm in non-ECMO treated patients at five years; −0.44 (−0.83 to −0.05), and at all ages in the ECMO-treated-patients: −0.90 (−1.32 to −0.49), −0.45 (−0.90 to −0.02) and −0.75 (−1.2 to −0.34) at 5, 8, and 12 years, respectively. Length of hospital stay was negatively associated with estimated total z-score M-ABC (p = 0.004 multivariate analysis).Conclusion: School-age children born with CDH are at risk for motor function impairment, which persists in those who received ECMO-treatment. Especially for them long-term follow up is recommended.

Background: Pets are increasingly becoming part of the family and interactions between pets and their owners is changing. This results in extended and more intimate contact between owners and their pets, which give rise to zoonotic risks. Objective: To establish the presence of potential zoonotic pathogens in pets that sleep with their owner. Methods: As a pilot study, a group of 28 healthy dogs and 22 healthy cats were monitored for the presence of the zoonotic parasites Cheyletiella, Ctenocephalides spp. and Toxocara spp., the dermatophyte Microsporum canis, and the bacteria Clostridium difficile, Salmonella spp., Campylobacter jejuni and Enterobacteriaceae. This was investigated by taking samples from the fur, the footpads and the animal bed. The owners filled in a questionnaire. Results: In total, 29 of the 50 pets (58%) slept on the bed, of which 15 pets (30%) slept in the bed (under the blankets). A total of 19/22 dogs (86%) and 7/22 cats (32%) tested positive for Enterobacteriaceae on the fur or footpads. Fleas were found in 5/22 of the cats’ (23%) and 2/28 of the dogs’ (7%) favourite sleeping spots. High levels of aerobic colonies were found, up to 216 colony forming units/cm2. Other pathogens were not found in this study. Conclusions: The results of this preliminary study confirm literature reports that pets may constitute a potential risk in the transmission of zoonotic pathogens to their owner, especially during direct contact when sleeping in the same bed. Owners should therefore be informed about these risks and educated to interact with their pets in a more responsible way.

RationalePulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering.ObjectivesTo complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States.MethodsWe determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than -950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity.Measurements and main resultsAmong 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10(-8)) and PPT2 (rs10947233; P = 3.2 × 10(-8)), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase-related gene MAN2B1 (rs10411619; P = 1.1 × 10(-9); minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10(-10); MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10(-8); MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 × 10(-6); MAF, 13.3%) was associated with percent emphysema.ConclusionsOur results suggest that some genes previously identified as influencing lung function are independently associated with emphysema rather than lung function, and that genes related to α-mannosidase may influence risk of emphysema.

Background Vitamin D supplementation lowers exacerbation frequency in severe vitamin D-deficient patients with COPD. Data regarding the effect of vitamin D on elastin degradation are lacking. Based on the vitamin's anti-inflammatory properties, we hypothesised that vitamin D supplementation reduces elastin degradation, particularly in vitamin D-deficient COPD patients. We assessed the effect of vitamin D status and supplementation on elastin degradation by measuring plasma desmosine, a biomarker of elastin degradation. Methods Desmosine was measured every 4 months in plasma of 142 vitamin D-naïve COPD patients from the Leuven vitamin D intervention trial (100 000 IU vitamin D3 supplementation every 4 weeks for 1 year). Results No significant association was found between baseline 25-hydroxyvitamin D (25(OH)D) and desmosine levels. No significant difference in desmosine change over time was found between the placebo and intervention group during the course of the trial. In the intervention arm, an unexpected inverse association was found between desmosine change and baseline 25(OH)D levels (p=0.005). Conclusions Vitamin D supplementation did not have a significant overall effect on elastin degradation compared to placebo. Contrary to our hypothesis, the intervention decelerated elastin degradation in vitamin D-sufficient COPD patients and not in vitamin D-deficient subjects.

The article focuses on the incorporation of critical language awareness (CLA) into Writing Studies, with attention given to pedagogies and platforms. Topics include importance of moving between systemic and local assessment, supporting students' capacity to construct knowledge using language; and educators to create a space for students to participate meaningfully in the construction of CLA and reminds of the politically charged nature of language.

Norfloxacin (NORF) is one of the most widely used antibiotics in hospital and animal farming. The large amounts of NORF were discharged into the water environment which caused severe pollution problems. Photocatalysis technology can decompose, mineralize most organic compounds, including NORF. In this study, CdS, g-C3N4 and their composites were prepared as photocatalysts. The composites were characterized by SEM, EDS and XRD. It was showed that NORF in water can be effectively removed by CdS/g-C3N4 composites in visible light. The experimental results proved that the composites have better photocatalytic degradation performance and stability than pure CdS. The best photocatalysis reaction condition of pH was neutral. There was different performance on the degradation of NORF when the interfere ions, NO3-, Cl- and HCO3- were mixed in the reactive system. HCO3- ion was the inhibitory substance on the photocatalysis reaction, and NO3 -, Cl- slightly prompted the reaction. In addition, the main active substances produced in the reaction were confirmed by adding different free radical quenchants in NORF photodegradation reaction system. [ABSTRACT FROM AUTHOR]

PurposeWe aimed to study the association between lung function decline and quantitative computed tomography (CT) air trapping.Materials and methodsCurrent and former heavy smokers in a lung cancer screening trial underwent volumetric low-dose CT in inspiration and expiration. Spirometry was obtained at baseline and after 3 years. The expiratory to inspiratory ratio of mean lung density (E/I-ratioMLD) was used to quantify air trapping. CT emphysema was defined as voxels in inspiratory CT below -950 Hounsfield Unit. Linear mixed modeling was used to determine the association between CT air trapping and lung function.ResultsWe included 985 subjects with a mean age of 61.3 years. Independent of CT emphysema, CT air trapping was significantly associated with a reduction in forced expiratory volume in one second (FEV1) and the ratio of FEV1 over the forced vital capacity (FEV1/FVC); FEV1 declines with 33 mL per percent increase in CT air trapping, while FEV1/FVC declines 0.58% per percent increase (both pConclusionIn a lung cancer screening cohort, quantitatively assessed air trapping on low-dose CT is independently associated with reduced lung function and accelerated decline of FEV1/FVC.

Genetic variation in nicotinic acetylcholine receptor subunit genes (nAChRs) is associated with lung function level and chronic obstructive pulmonary disease (COPD). It is unknown whether these variants also predispose to an accelerated lung function decline. We investigated the association of nAChR susceptibility variants with lung function decline and COPD severity. The rs1051730 and rs8034191 variants were genotyped in a population-based cohort of 1,226 heavy smokers (COPACETIC) and in an independent cohort of 883 heavy smokers, of which 653 with COPD of varying severity (LEUVEN). Participants underwent pulmonary function tests at baseline. Lung function decline was assessed over a median follow-up of 3 years in COPACETIC. Current smokers homozygous for the rs1051730 A-allele or rs8034191 G-allele had significantly greater FEV(1)/FVC decline than homozygous carriers of wild-type alleles (3.3% and 4.3%, p = 0.026 and p = 0.009, respectively). In the LEUVEN cohort, rs1051730 AA-carriers and rs8034191 GG-carriers had a two-fold increased risk to suffer from COPD GOLD IV (OR 2.29, 95% confidence interval [CI] = 1.11-4.75; p = 0.025 and OR = 2.42, 95% [CI] = 1.18-4.95; p = 0.016, respectively). The same risk alleles conferred, respectively, a five- and four-fold increased risk to be referred for lung transplantation because of end-stage COPD (OR = 5.0, 95% [CI] = 1.68-14.89; p = 0.004 and OR = 4.06, 95% [CI] = 1.39-11.88; p = 0.010). In Europeans, variants in nAChRs associate with an accelerated lung function decline in current smokers and with clinically relevant COPD.

BackgroundThere is increasing evidence that structural lung changes may be present before the occurrence of airflow limitation as assessed by spirometry. This study investigated the prevalence of computed tomography (CT) quantified emphysema, airway wall thickening and gas trapping according to classification of airflow limitation (FEV1/FVC MethodsA total number of 1,140 male former and current smokers participating in a lung cancer screenings trial (NELSON) were included and underwent chest CT scanning and spirometry. Emphysema was quantified by the 15(th) percentile, air way wall thickening by the square root of wall area for a theoretical airway with 10mm lumen perimeter (Pi10) and gas trapping by the mean lung density expiratory/inspiratory (E/I)-ratio. Participants were classified by entry FEV1/FVC: group 1>70%; group 2LLN; and group 370% but FEV1 ResultsMean (standard deviation) age was 62.5 (5.2) years and packyears smoked was 41.0 (18.0). Group 2 subjects when compared to group 1 had a significantly lower 15(th) percentile, -920.6 HU versus -912.2 HU; a higher Pi10, 2.87 mm versus 2.57 mm; and a higher E/I-ratio, 88.6% versus 85.6% (all pConclusionSubjects with an FEV1/FVC