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Background: Whereas differences in inducible laryngeal obstruction (ILO) presentation on the basis of age have been observed within pediatric populations, age-based differences in adult populations are lacking., Objective: To describe differences in ILO on the basis of age in adults., Methods: Patients aged older than 16 years with confirmed ILO (vocal cord adduction > 50% during inspiration) by means of provocation-challenge rhinolaryngoscopy by their treating allergist were included. An investigator-designed questionnaire was administered using Research Electronic Data Capture with corresponding medical data collection. χ 2 tests, Student's t tests, analysis of variance, Cochran-Armitage test for trend, and Fisher's exact test were used., Results: The median age of the 67 patients was 50 years. P values less than .05 were considered significant. Those aged younger than 50 years (n = 31; mean age 35.6 years) reported more symptoms vs age 50 years and older (n = 36; mean age 61.8 years), including shortness of breath at rest and exertion (84% vs 39%, 94% vs 72%), throat tightness (81% vs 50%), chest tightness (81% vs 47%), and difficulty getting air in (81% vs 56%). Those aged younger than 50 years had an increased history of anxiety (68% vs 33%), asthma (55% vs 31%), positive methacholine challenge (52% vs 22%), increasing triggers with time (87% vs 43%), higher Pittsburgh Vocal Cord Dysfunction Index Scores (6.9 vs 5.5), and inspiratory curve flattening (48% vs 24%). Additional age-based subdivisions confirmed significant trends with the lowest reported ILO characteristics and symptoms in those aged 65 years and older., Conclusion: A high index of suspicion for ILO should be maintained in older adults since they may report less typical ILO symptoms and anxiety associations that prompt ILO evaluation., Competing Interests: Disclosures Dr Poole has received research regents (no monies) from AstraZeneca. Dr Poole, Dr Van De Graaff, Dr May, Dr Rorie, and Ms Walenz are site recruiters for clinical studies for asthma, sinus disease, and urticaria for GlaxoSmithKline, AstraZeneca, Regeneron Pharmaceuticals, and CellDex Therapeutics. The remaining authors have no conflicts of interest to report., (Published by Elsevier Inc.)

Objectives: Though interstitial lung disease (ILD) contributes to excess morbidity and mortality in rheumatoid arthritis (RA), RA-ILD pathogenesis remains incompletely defined. As intermediate, non-classical and suppressed CD14+ monocytes are expanded in RA-ILD, this study sought to characterize gene expression profiles of circulating monocytes in RA-ILD., Methods: Peripheral blood mononuclear cells were collected from patients with RA without lung disease (N = 5), RA-ILD (N = 5), idiopathic pulmonary fibrosis (IPF; N = 5), and controls without lung and autoimmune disease (N = 4). RNA was extracted from CD14+ isolated monocytes and subjected to transcriptional analysis of 1365 genes. Gene enrichment and pathway analyses were performed., Results: Unsupervised clustering grouped patients with RA-ILD together with IPF for myeloid innate genes. For fibrosis genes, patients with RA-ILD clustered independent of comparator groups. There were 103, 66, and 64 upregulated and 66, 14, and 25 downregulated genes for RA-ILD, RA, and IPF, vs controls, respectively. For RA-ILD, there was increased expression of genes involved in regulating inflammation and fibrosis (SOCS3, CECAM1, LTB4R2, CLEC7A, IRF7, PHYKPL, GBP5, RAPGEF), epigenetic modification (KDM5D, KMT2D, OGT), and macrophage activation. Top canonical pathways included macrophage differentiation-activation, IL-12, neuroinflammatory, glucocorticoid receptor, and IL-27 signalling., Conclusions: Circulating monocytes in RA-ILD patients demonstrate unique gene expression profiles with innate immune gene features more aligned with IPF as opposed to RA in the absence of clinical lung disease with fibrosis gene expression that was distinct from RA and IPF. These studies are important for understanding disease pathogenesis and may provide information for future therapeutic targets in RA-ILD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Interstitial lung disease (ILD) is associated with significant mortality in rheumatoid arthritis (RA) patients with key cellular players remaining largely unknown. This study aimed to characterize inflammatory and myeloid derived suppressor cell (MDSC) subpopulations in RA-ILD as compared to RA, idiopathic pulmonary fibrosis (IPF) without autoimmunity, and controls., Methods: Peripheral blood was collected from patients with RA, RA-ILD, IPF, and controls (N = 60, 15/cohort). Myeloid cell subpopulations were identified phenotypically by flow cytometry using the following markers:CD45,CD3,CD19,CD56,CD11b,HLA-DR,CD14,CD16,CD15,CD125,CD33. Functionality of subsets were identified with intracellular arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS) expression., Results: There was increased intermediate (CD14 ++ CD16 + ) and nonclassical (CD14 +/- CD16 ++ ) and decreased classical (CD14 ++ CD16 - ) monocytes in RA, RA-ILD, and IPF vs. control. Intermediate monocytes were higher and classical monocytes were lower in RA-ILD vs. RA but not IPF. Monocytic (m)MDSCs were higher in RA-ILD vs. control and RA but not IPF. Granulocytic (g)MDSCs did not significantly differ. In contrast, neutrophils were increased in IPF and RA-ILD patients with elevated expression of Arg-1 sharing similar dimensional clustering pattern. Eosinophils were increased in RA-ILD vs. controls, RA and IPF. Across cohorts, iNOS was decreased in intermediate/nonclassical monocytes but increased in mMDSCs vs. classical monocytes. In RA-ILD, iNOS positive mMDSCs were increased versus classic monocytes., Conclusions: Myeloid cell subpopulations are significantly modulated in RA-ILD patients with expansion of CD16 + monocytes, mMDSCs, and neutrophils, a phenotypic profile more aligned with IPF than other RA patients. Eosinophil expansion was unique to RA-ILD, potentially facilitating disease pathogenesis and providing a future therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)