Sensing and guiding cell-state transitions by using genetically encoded endoribonuclease-mediated microRNA sensors.

Precisely sensing and guiding cell-state transitions via the conditional genetic activation of appropriate differentiation factors is challenging. Here we show that desired cell-state transitions can be guided via genetically encoded sensors, whereby endogenous cell-state-specific miRNAs regulate the translation of a constitutively transcribed endoribonuclease, which, in turn, controls the translation of a gene of interest. We used this approach to monitor several cell-state transitions, to enrich specific cell types and to automatically guide the multistep differentiation of human induced pluripotent stem cells towards a haematopoietic lineage via endothelial cells as an intermediate state. Such conditional activation of gene expression is durable and resistant to epigenetic silencing and could facilitate the monitoring of cell-state transitions in physiological and pathological conditions and eventually the 'rewiring' of cell-state transitions for applications in organoid-based disease modelling, cellular therapies and regenerative medicine.

High Prevalence of Highly Pathogenic Avian Influenza: A Virus in Vietnam's Live Bird Markets.

Background: In recent years, Vietnam has suffered multiple epizootics of influenza in poultry. Methods: From 10 January 2019 to 26 April 2021, we employed a One Health influenza surveillance approach at live bird markets (LBMs) and swine farms in Northern Vietnam. When the COVID-19 pandemic permitted, each month, field teams collected oral secretion samples from poultry and pigs, animal facility bioaerosol and fecal samples, and animal worker nasal washes at 4 LBMs and 5 swine farms across 5 sites. Initially samples were screened with molecular assays followed by culture in embryonated eggs (poultry swabs) or Madin-Darby canine kidney cells (human or swine swabs). Results: Many of the 3493 samples collected had either molecular or culture evidence for influenza A virus, including 314 (37.5%) of the 837 poultry oropharyngeal swabs, 144 (25.1%) of the 574 bioaerosol samples, 438 (34.9%) of the 1257 poultry fecal swab samples, and 16 (1.9%) of the 828 human nasal washes. Culturing poultry samples yielded 454 influenza A isolates, 83 of which were H5, and 70 (84.3%) of these were highly pathogenic. Additionally, a positive human sample had a H9N2 avian-like PB1 gene. In contrast, the prevalence of influenza A in the swine farms was much lower with only 6 (0.4%) of the 1700 total swine farm samples studied, having molecular evidence for influenza A virus. Conclusions: This study suggests that Vietnam's LBMs continue to harbor high prevalences of avian influenza A viruses, including many highly pathogenic H5N6 strains, which will continue to threaten poultry and humans.

Colorectal endometriosis - a challenging, often overlooked cause of colorectal pathology: a clinicopathological review of 114 cases.

The colon is the most common site for endometriosis outside the genital tract. It has a varied presentation and can mimic numerous other conditions, both clinically and pathologically. We investigated the clinicopathological features of a series of colorectal endometriosis with a particular emphasis on the features seen in cases with colonic mucosal involvement. A total of 114 consecutive cases of colorectal endometriosis were reviewed. Forty-eight percent did not have a prior diagnosis of endometriosis and in 34 patients (30%) the endometriosis was determined as the cause for the presentation. Mucosal involvement was present in 31 specimens. Features of chronic colitis were seen in the adjacent mucosa in 90% of cases whilst there were glandular changes mimicking adenocarcinoma in two cases (1.8%). Fifty percent of cases with mucosal involvement also showed glands with a hybrid intestinal-endometrial phenotype by morphology and/or by immunohistochemistry. Endometriosis is an important mimic of other conditions.

Cholesterol Nanofiber Patches with Sustainable Oil Delivery Eliminate Inflammation in Atopic Skin.

Atopic skin is dry and itchy and lacks integrity. Impaired skin barrier results from altered lipid composition of the skin. A crucial skin lipid, cholesterol, provides flexibility and homeostasis of the cell membranes' lipid bilayer. Cholesterol-based creams and natural oils, especially blackcurrant seed oil, are beneficial for skin care as they hydrate the skin and improve its integrity. The major atopic symptom, skin dryness, can be overcome by the application of porous patches enhanced with cholesterol and natural oil. The base of the patches is constructed of polyimide (PI) nanofibers with cholesterol coatings and externally added blackcurrant seed oil. The presence of cholesterol in PI mats hinders the passage of oil through the patches to the skin, resulting in sustained and prolonged skin hydration. The theoretical and numerical investigations of oil dynamics in porous mats confirmed the experimental results, showing a prolonged skin hydration effect up to 6 h. Additionally, as demonstrated by in vivo tests on atopic mice, cholesterol patches lower serum immunoglobulin E levels and expression of proinflammatory cytokines in the skin, thereby accelerating skin healing. Our results hold great promise for the long-term application of the patches in atopic dermatitis treatment.

ABCA1 and apoA-I dependent 12-hydroxyeicosatetraenoic acid efflux regulates macrophage inflammatory signaling.

Aberrant high-density lipoprotein (HDL) function is implicated in inflammation-associated pathologies. While HDL ABCA1-mediated reverse cholesterol and phospholipid transport are well described, the movement of pro-/anti-inflammatory lipids has not been explored. HDL phospholipids are the largest reservoir of circulating arachidonic acid-derived oxylipins. Endotoxin-stimulation activates inflammatory cells leading to hydroxyeicosatetraenoic acid (HETE) production, oxylipins which are involved in inflammatory response coordination. Active signaling in the non-esterified (NE) pool is terminated by sequestration of HETEs as esterified (Es) forms and degradation. We speculate that an ABCA1-apoA-I-dependent efflux of HETEs from stimulated cells could regulate intracellular HETE availability. Here we test this hypothesis both in vitro and in vivo. In endotoxin-stimulated RAW-264.7 macrophages preloaded with d8-arachidonic acid we use compartmental tracer modeling to characterize the formation of HETEs, and their efflux into HDL. We found that in response to endotoxin: I) Cellular NE 12-HETE is positively associated with MCP-1 secretion (p<0.001); II) HETE transfer from NE to Es pools is ABCA1-depedent (p<0.001); III) Cellular Es HETEs are transported into media when both apoA-I and ABCA1 are present (p<0.001); IV) The stimulated efflux of HETEs >> arachidonate (p<0.001). Finally, in endotoxin challenged humans (n=17), we demonstrate that intravenous lipopolysaccharide (0.6 ng/kg body weight) resulted in accumulation of 12-HETE in HDL over a 168-hour follow-up. Therefore, HDL can suppress inflammatory responses in macrophages by regulating intracellular HETE content in an apoA-I/ABCA1 dependent manner. The described mechanism may apply to other oxylipins and explain anti-inflammatory properties of HDL. This newly defined HDL property opens new doors for the study of lipoprotein interactions in metabolic diseases.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

An operator-independent quality assurance system for automatically generated structure sets.

OBJECTIVE: This study describes geometry-based and intensity-based tools for quality assurance (QA) of automatically generated structures for online adaptive radiotherapy, and designs an operator-independent traffic light system that identifies erroneous structure sets. Approach: A cohort of eight head and neck (HN) patients with daily CBCTs was selected for test development. Radiotherapy contours were propagated from planning CT to daily cone beam CT (CBCT) using deformable image registration (DIR). These propagated structures were visually verified for acceptability. For each CBCT, several error scenarios were used to generate what were judged unacceptable structures. Ten additional HN patients with daily CBCTs and different error scenarios were selected for validation. A suite of tests based on image intensity, intensity gradient, and structure geometry was developed using acceptable and unacceptable HN planning structures. Combinations of one test applied to one structure, referred to as structure-test combinations, were selected for inclusion in the QA system based on their discriminatory power. A traffic light system was used to aggregate the structure-test combinations, and the system was evaluated on all fractions of the ten validation HN patients. Results: The QA system distinguished between acceptable and unacceptable fractions with high accuracy, labeling 294/324 acceptable fractions as green or yellow and 19/20 unacceptable fractions as yellow or red. Significance: This study demonstrates a system to supplement manual review of radiotherapy planning structures. Automated QA is performed by aggregating results from multiple intensity- and geometry-based tests. .

Effect of Different Reduced Training Frequencies after 12 Weeks of Concurrent Resistance and Aerobic Training on Muscle Strength and Morphology.

The aim of the study was to investigate the effect of two long-term reduced concurrent training modalities, in which participants performed one training session every either 7 or 14 days, after 12 weeks of systematic concurrent resistance and aerobic training, on lower extremities' muscle strength, power, and morphology in young females. After the 12-week training period, participants were assigned into three groups and performed either one training session every 7 days (G7) or once every 14 days (G14), or detraining (GD), for 12 weeks, followed by 12 additional weeks of detraining. The following were measured before, after the systematic training period, after the end of the reduced training frequency period, and after the end of complete detraining: body composition, leg press 1-RM, countermovement jump, quadriceps cross-sectional area (CSA), vastus lateralis muscle architecture, and maximum aerobic power. Performance and muscle mass increased after the initial 12-week training period. Thereafter, leg press 1-RM, quadriceps CSA, and aerobic power remained unchanged in the G7 group, but decreased in G14 (-4.4 ± 3.5%; -5.9 ± 1.8%; -9.0 ± 7.8%, respectively, p < 0.05), maintaining 95.6 ± 3.5%, 94.1 ± 1.8%, and 91.0 ± 7.8% of the initial training adaptations, respectively. In conclusion, performing one training session every 2 weeks for 3 months may preserve 90 to 95% of the muscle mass/strength and aerobic power adaptations achieved with systematic concurrent training.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Correction: Hale et al. Differential Expression Profiling Reveals Stress-Induced Cell Fate Divergence in Soybean Microspores. Plants 2020, 9, 1510.

In the original publication [...].

Diffusion tensor transformation for personalizing target volumes in radiation therapy.

Diffusion tensor imaging (DTI) is used in tumor growth models to provide information on the infiltration pathways of tumor cells into the surrounding brain tissue. When a patient-specific DTI is not available, a template image such as a DTI atlas can be transformed to the patient anatomy using image registration. This study investigates a model, the invariance under coordinate transform (ICT), that transforms diffusion tensors from a template image to the patient image, based on the principle that the tumor growth process can be mapped, at any point in time, between the images using the same transformation function that we use to map the anatomy. The ICT model allows the mapping of tumor cell densities and tumor fronts (as iso-levels of tumor cell density) from the template image to the patient image for inclusion in radiotherapy treatment planning. The proposed approach transforms the diffusion tensors to simulate tumor growth in locally deformed anatomy and outputs the tumor cell density distribution over time. The ICT model is validated in a cohort of ten brain tumor patients. Comparative analysis with the tumor cell density in the original template image shows that the ICT model accurately simulates tumor cell densities in the deformed image space. By creating radiotherapy target volumes as tumor fronts, this study provides a framework for more personalized radiotherapy treatment planning, without the use of additional imaging.

Nutrition and the gut-brain axis in neonatal brain injury and development.

Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing gut microbiome, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment.

Impact of Percutaneous Cryoablation on Renal Function in Patients with Stage I Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the effect of cryoablation on renal function (measured by eGFR or serum creatinine) for treating Stage I renal cancer. MATERIALS AND METHODS: MEDLINE, EMBASE, and the CENTRAL databases were systematically searched from inception to May 1, 2023. Cohort studies that included data on change of estimated glomerular filtration rate (eGFR) and serum creatinine increase were included. Meta-analysis was performed by measuring the weighted mean difference and by fitting random-effect models. RESULTS: Overall, 38 studies were included, comprising of 3,202 participants. Percutaneous cryoablation was associated with an absolute eGFFR reduction of -3.06 ml/min/1.73 m2 (95% CI: -4.12 to -2.01; p-value < 0.001) and serum creatinine increase of 0.05 mg/dl (95% CI: -0.02 to 0.11; p-value> 0.05). The weighted absolute mean difference of percutaneous cryoablation for treating stage T1b renal cell carcinoma was estimated at -5.19 ml/min/1.73 m2 (95% CI: -11.1 to 0.72; p-value > 0.05). Lastly, when analyzing studies that included cohorts with solitary kidneys, the pooled weighted mean difference was estimated as -3.27 ml/min/1.73 m2 (95% CI: -6.79 to 0.25; pvalue >0.05). CONCLUSIONS: Percutaneous cryoablation for Stage 1 renal cell carcinoma has minimal significant impact on renal function (measured by eGFR or serum creatinine). The same outcome was observed in patients with larger tumors (T1b) and those with solitary kidneys.

H9N2 influenza A viruses found to be enzootic in Punjab Pakistan's bird markets with evidence of human H9N2 nasal colonization.

OBJECTIVES: This study sought to detect and characterize influenza A (IAV) and influenza D (IDV) viruses circulating among commercial birds and shop owners in Pakistan's live bird markets. METHODS: Oropharyngeal swabs (n = 600; n = 300 pools) collected from poultry and nasopharyngeal swabs (n = 240) collected from poultry workers were studied for molecular evidence of IAV and IDV using real-time and conventional real-time reverse transcription polymerase chain reaction protocols. RESULTS: Nineteen (6.3%) poultry pools were positive for IAV and 73.9% of these were positive for H9N2 subtypes. Two (0.83%) poultry workers had evidence of IAV, and both were also H9N2 subtypes. The poultry and human IAV-positive specimens all clustered phylogenetically by Sanger and next-generation sequencing with previously detected H9N2 poultry isolates. No field specimens were positive for IDV. CONCLUSION: H9N2 IAV is likely enzootic in Punjab Province Pakistan's live bird markets and may be colonizing the noses of workers and market visitors. Regular monitoring for avian influenza-associated human illness in Punjab seems to be a needed public measure.

Bilateral insular cortical lesions reduce sensitivity to the adverse consequences of acute ethanol intoxication in Pavlovian conditioning procedures.

BACKGROUND: Sensitivity to the adverse post-ingestive effects of ethanol likely serves as a deterrent to initiate alcohol consumption early in drinking and later may contribute to efforts to remain abstinent. Administering ethanol to naïve rats prior to Pavlovian conditioning procedures elicits robust ethanol-conditioned taste and place avoidance (CTA; CPA) mediated by its subjective interoceptive properties. The insular cortex (IC) has been implicated as a region involved in mediating sensitivity to the interoceptive properties of ethanol. Here, we examined whether bilateral lesions of the IC affect the acquisition and expression of taste and place avoidance in ethanol-induced CTA and CPA paradigms. METHODS: Adult male and female Wistar rats received bilateral excitotoxic lesions (ibotenic acid; 20 mg/mL; 0.3 µL) of the IC prior to conditioning procedures. Subsequently, rats were conditioned to associate a novel taste stimulus (0.1% saccharin) and context with the effects of ethanol (1.0 g/kg) in a combined CTA/CPP procedure. Conditioning occurred over 8 alternating CS+/CS- days, followed by tests for expression of taste and place preferences. Data from IC-lesioned rats were compared with neurologically intact rats. RESULTS: Our findings revealed that neurologically intact rats showed a significantly stronger ethanol-induced CTA than IC-lesioned rats. There were no significant differences in total fluid intake when rats consumed water (CS-). As with CTA effects, intact rats showed a strong CPA, marked by a greater reduction in time spent on the drug-paired context, while IC-lesioned rats failed to display CPA to ethanol. CONCLUSION: These results indicate that proper IC functioning is necessary for responding to the adverse interoceptive properties of ethanol regardless of which Pavlovian paradigm is used to assess interoceptive responsivity to ethanol. Blunted IC functioning from chronic ethanol use may reduce interoceptive signaling specifically of ethanol's adverse effects thus contributing to increased alcohol use.

Practical Application of a Relationship-Based Model to Engagement for Gene-Drive Vector Control Programs.

Engagement is an important component in the advancement of gene-drive vector control research programs as developers look to transition the technology from the laboratory to the field. As research advances and engagement surrounding this novel technology is put into practice, knowledge can be gained from practical experiences and applications in the field. A relationship-based model (RBM) provides a framework for end-user development of engagement programs and strategies. The model places end users at the center of the engagement decision-making processes rather than as recipients of predetermined strategies, methods, and definitions. Successful RBM application for healthcare delivery has previously been demonstrated, and the University of California Malaria Initiative (UCMI) has applied this model to its gene-drive program in the Democratic Republic of São Tomé and Príncipe. The model emphasizes the importance of local leadership in the planning, development, and implementation of all phases of project engagement. The primary aim of this paper is to translate the model from paper to practice and provide a transparent description, using practical examples, of the UCMI program implementation of RBM at its field site. End-user development of the UCMI engagement program provides a unique approach to the development of ethical, transparent, and effective engagement strategies for malaria control programs. This paper may also serve as a reference and example for projects looking to establish an engagement program model that integrates end-user groups in the decision-making processes surrounding engagement.

Rheumatoid arthritis and changes on spirometry by smoking status in two prospective longitudinal cohorts.

OBJECTIVE: To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators. METHODS: We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5-7 years. RA was identified based on self-report and disease-modifying antirheumatic drug use; non-RA comparators reported neither. The primary outcomes were annual changes in the per cent-predicted forced expiratory volume in 1 s (FEV1%) and per cent predicted forced vital capacity (FVC%). Statistical comparisons were performed using multivariable linear regression. The analysis was stratified based on baseline smoking status and the presence of obstructive pattern (FEV1/FVC <0.7). RESULTS: Among participants who underwent baseline and follow-up spirometry, we identified 233 patients with RA and 37 735 non-RA comparators. Among never-smoking participants without an obstructive pattern, RA was significantly associated with more FEV1% decline (ß=-0.49, p=0.04). However, in ever smokers with ≥10 pack-years, those with RA exhibited significantly less FEV1% decline than non-RA comparators (ß=0.50, p=0.02). This difference was more pronounced among those with an obstructive pattern at baseline (ß=1.12, p=0.01). Results were similar for FEV1/FVC decline. No difference was observed in the annual FVC% change in RA versus non-RA. CONCLUSIONS: Smokers with RA, especially those with baseline obstructive spirometric patterns, experienced lower FEV1% and FEV1/FVC decline than non-RA comparators. Conversely, never smokers with RA had more FEV1% decline than non-RA comparators. Future studies should investigate potential treatments and the pathogenesis of obstructive lung diseases in smokers with RA.