Storylines of family medicine IV: perspectives on practice-lenses of appreciation.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'IV: perspectives on practice-lenses of appreciation', authors address the following themes: 'Relational connections in the doctor-patient partnership', 'Feminism and family medicine', 'Positive family medicine', 'Mindful practice', 'The new, old ethics of family medicine', 'Public health, prevention and populations', 'Information mastery in family medicine' and 'Clinical courage.' May readers nurture their curiosity through these essays.

Do dimensions of childhood adversity differ in their direct associations with youth psychopathology? A meta-analysis.

Growing evidence supports the unique pathways by which threat and deprivation, two core dimensions of adversity, confer risk for youth psychopathology. However, the extent to which these dimensions differ in their direct associations with youth psychopathology remains unclear. The primary aim of this preregistered meta-analysis was to synthesize the associations between threat, deprivation, internalizing, externalizing, and trauma-specific psychopathology. Because threat is proposed to be directly linked with socioemotional development, we hypothesized that the magnitude of associations between threat and psychopathology would be larger than those with deprivation. We conducted a search for peer-reviewed articles in English using PubMed and PsycINFO databases through August 2022. Studies that assessed both threat and deprivation and used previously validated measures of youth psychopathology were included. One hundred and twenty-seven articles were included in the synthesis (N = 163,767). Results of our three-level meta-analyses indicated that adversity dimension significantly moderated the associations between adversity and psychopathology, such that the magnitude of effects for threat (r's = .21-26) were consistently larger than those for deprivation (r's = .16-.19). These differences were more pronounced when accounting for the threat-deprivation correlation. Additional significant moderators included emotional abuse and youth self-report of adversity. Findings are consistent with the Dimensional Model of Adversity and Psychopathology, with clinical, research, and policy implications.

Adherence to adjuvant endocrine therapy for breast cancer: a qualitative exploration of attribution of symptoms among post-menopausal women.

PURPOSE: Oral adjuvant endocrine therapy (AET) is an effective treatment for hormone receptor positive breast cancer to decrease recurrence and mortality, but adherence is poor. This study explored post-menopausal women's experiences with AET, with a particular focus on adherence to AET as well as distress and symptoms experienced prior to and during AET treatment. METHODS: Participants were recruited from a hospital registry, stratified by adherence to/discontinuation of AET. Telephone interviews followed a semi-structured interview guide and were recorded and transcribed verbatim. Transcripts were systematically coded using team-based coding, with analysis of themes using a grounded theory approach. RESULTS: Thirty-three participants were interviewed; ages ranged from 57 to 86 years. Participants included 10 discontinued patients and 23 patients who completed their AET course or were adherent to AET at the time of interviewing. Both adherent and discontinued patients reported symptoms throughout their AET treatment course, and both attributed symptoms to factors other than AET (e.g., older age and pre-existing comorbidities). However, discontinued patients were more likely to attribute symptoms to AET and to describe difficulty managing their symptoms, with some directly citing symptoms as the reason for discontinuing AET therapy. Conversely, adherent patients were more likely to describe the necessity of taking AET, despite symptoms. CONCLUSIONS: AET adherence was associated with beliefs about AET, symptom attribution, and symptom management. Routine symptom monitoring during AET and addressing both symptoms and patients' understanding of their symptoms may promote adherence to AET.

Projections of the incidence of COVID-19 in Japan and the potential impact of a Fall 2023 COVID-19 vaccine.

BACKGROUND: The study objective was to estimate the incidence of COVID-19 infection, hospitalization, and deaths in Japan from September 2023 to August 2024 and potential impact of a monovalent XBB.1.5 variant-adapted Fall 2023 COVID-19 vaccine (modified version: XBB monovalent) for adults aged ≥18 years on these outcomes. METHODS: A previously developed Susceptible-Exposed-Infected-Recovered model for the United States (US) was adapted to Japan. The numbers of symptomatic infections, COVID-19-related hospitalizations, and deaths were calculated. Given differences in vaccination coverage, masking practices and social mixing patterns between the US and Japan, all inputs were updated to reflect the Japanese context. Vaccine effectiveness (VE) values are hypothetical, but predicted based on existing VE values of bivalent BA.4/BA.5 boosters against BA.4/BA.5 in Japan, from the VERSUS test-negative case-control study. Sensitivity analyses were performed. RESULTS: The base case model predicts overall that there will be approximately 35.2 million symptomatic COVID-19 infections, 690,000 hospitalizations, and 62,000 deaths in Japan between September 2023 and August 2024. If an updated COVID-19 vaccine is offered to all adults aged 18 years and older in Fall 2023, the model predicts that 7.3 million infections, 275,000 hospitalizations and 26,000 deaths will be prevented. If vaccines are only given to those aged 65 years and older, only 2.9 million infections, 180,000 hospitalizations and 19,000 deaths will be prevented. Sensitivity analysis results suggest that hospitalizations and deaths prevented are most sensitive to initial VE against infection and hospitalizations, and the waning rate associated with VE against infection. Symptomatic infections prevented was most sensitive to initial VE against infection and VE waning. CONCLUSIONS: Results suggest that a Fall 2023 COVID-19 vaccine would reduce total numbers of COVID-19-related infections, hospitalizations, and deaths.

Pediatric Orbital and Skull Base Pathology.

Pediatric orbital and skull base pathologies encompass a spectrum of inflammatory, sporadic, syndromic, and neoplastic processes that require a broad and complex clinical approach for both medical and surgical treatment. Given their complexity and often multicompartment involvement, a multidisciplinary approach for diagnosis, patient and family counseling, and ultimately treatment provides the best patient satisfaction and clinical outcomes. Advances in minimally invasive surgical approaches, including endoscopic endonasal and transorbital approaches allows for more targeted surgical approaches through smaller corridors beyond more classic transcranial or transracial approaches.

Looking beyond year 1 in the molecular era of pediatric brain tumor diagnosis: confirmatory testing of germline variants found on tumor sequencing.

Purpose: Somatic molecular profiling of pediatric brain tumors aids with the diagnosis and treatment of patients with a variety of high- and low-grade central nervous system neoplasms. Here, we report follow-up targeted germline evaluation for patients with possible germline variants following tumor only testing in the initial year in which somatic molecular testing was implemented at a single institution. Patients and Methods: Somatic testing was completed for all tumors of the central nervous system (CNS) undergoing diagnostic workup at Seattle Children's Hospital during the study period of November 2015 to November 2016. Sequencing was performed in a College of American Pathologists-accredited, Clinical Laboratory Improvements Amendments-certified laboratory using UW-OncoPlex™ assay (version 5), a DNA-based targeted next generation sequencing panel validated to detect genetic alterations in 262 cancer-related genes. We tracked subsequent clinical evaluation and testing on a subgroup of this cohort found to have potential germline variants of interest. Results: Molecular sequencing of 88 patients' tumors identified 31 patients with variants that warranted consideration of germline testing. To date, 19 (61%) patients have been tested. Testing confirmed germline variants for ten patients (31% of those identified for testing), one with two germline variants (NF1 and mosaic TP53). Eight (26%) patients died before germline testing was sent. One patient (13%) has not yet had testing. Conclusion: Clinically validated molecular profiling of pediatric brain tumors identifies patients who warrant further germline evaluation. Despite this, only a subset of these patients underwent the indicated confirmatory sequencing. Further work is needed to identify barriers and facilitators to this testing, including the role of genetic counseling and consideration of upfront paired somatic-germline testing.

Osteochondral Allograft or Autograft Transplantation of the Femoral Head Leads to Improvement in Outcomes but Variable Survivorship: A Systematic Review.

PURPOSE: To review patient-reported outcomes (PROs) and survivorship in patients undergoing osteochondral autograft or allograft transplantation (OAT) of the femoral head. METHODS: PubMed, Cochrane Center for Register of Controlled Trials, and Scopus databases were searched in November 2022 with an updated search extending to December 2023 using criteria from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the following keywords: (hip OR femoral head) AND (mosaicplasty OR osteochondral allograft OR osteochondral autograft OR osteochondral lesion). Articles were included if they evaluated postoperative PROs in patients who underwent OAT of the femoral head and had a study size of 5 or more hips (n ≥ 5). Survivorship was defined as freedom from conversion to total hip arthroplasty. For PROs evaluated in 3 studies or more, forest plots were created and I2 was calculated. RESULTS: Twelve studies were included in this review, with a total of 156 hips and a mean follow-up time ranging between 16.8 and 222 months. In total, 104 (66.7%) hips were male while 52 (33.3%) were female. Age of patients ranged from 17.0 to 35.4 years, while body mass index ranged from 23.3 to 28.1. Eight studies reported on osteochondral autograft transplantation and 4 studies on osteochondral allograft transplantation. Three studies reported significant improvement in at least 1 PRO. Survivorship ranged from 61.5% to 96% at minimum 2-year follow-up and from 57.1% to 91% at minimum 5-year follow-up. At a follow-up of less than 5 years, osteochondral allograft transplantation studies showed 70% to 87.5% survivorship, while autograft varied from 61.54% to 96%. CONCLUSIONS: Patients with osteochondral lesions of the femoral head who underwent osteochondral autograft or allograft transplantation demonstrated improved PROs but variable survivorship rates. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

Intraoperative neuromonitoring potentials and evidence of preserved neuronal circuitry below the anatomical and functional level in patients with complex spinal dysraphism undergoing detethering reoperations.

OBJECTIVE: Spina bifida represents one of the most common birth defects, occurring in approximately 1-2 children per 1000 live births worldwide. The functional level of patients with spina bifida is highly variable and believed to be correlated with the anatomical level of the lesion. The variable clinical picture is well established, but the correlation with anatomical level and intraoperative neuromonitoring (IONM) data has not been investigated. Furthermore, the potential for preserving function beyond the apparent clinical level has also not been investigated. The objective of this research was to determine the presence and level of intraoperative transcranial motor evoked potential (tcMEP) and triggered electromyography (tEMG) responses, and the association of these responses with preoperative clinical function and radiographic data in pediatric cases of complex tethered cord release reoperations. METHODS: A single-center retrospective review of pediatric patients with complex spinal dysraphism undergoing detethering reoperations was conducted. Preoperative demographic and clinical data, including the radiographic and clinical level of dysraphism, were collected. IONM, including tcMEPs and tEMG responses, were obtained and compared with preoperative clinical data. Descriptive analysis was performed, by patient for demographics and by case for surgeries performed. RESULTS: In 100% of 21 cases of complex detethering reoperations, representing 20 patients, intraoperative tcMEPs could be generated at (4.8%) or below (95.2%) the level of clinical function. Compared with the preoperative clinical examination, 5 cases (23.8%) demonstrated tcMEP responses that were 1 level below the clinical function level, 11 cases (52.4%) were 2 levels below, and 4 cases (19.0%) were 3 levels below. Overall, 18 of 21 cases showed tEMG responses at or below the level of clinical function; of these, 7 cases (33%) were 1 level below and 3 (14%) were ≥ 2 levels below the clinical function level. CONCLUSIONS: The presence of positive stimulation potentials below the level of clinical function in patients with complex spinal dysraphism undergoing detethering reoperations indicates a degree of preserved neuronal connectivity. These findings suggest novel future treatment approaches for these patients, including using devices targeted to stimulation of these neurological pathways.

Gene Expression Profiling in Pediatric Appendicitis.

Importance: Appendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery. Objective: To provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population. Design, Setting, and Participants: The Gene Expression Profiling of Pediatric Appendicitis (GEPPA) study was a single-center prospective exploratory diagnostic study with transcriptomic profiling of peripheral blood collected from a cohort of children aged 5 to 17 years with abdominal pain and suspected appendicitis between November 2016 and April 2017 at the Alberta Children's Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study. Exposure: SA, PA, or nonappendicitis abdominal pain. Main Outcomes and Measures: Blood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics. Results: Seventy-one children (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) presenting to the emergency department with abdominal pain and suspected appendicitis were investigated using whole-blood transcriptomics. A central role for immune system pathways was revealed in PA, including a dampening of major innate interferon responses. Gene expression changes in patients with PA were consistent with downregulation of immune response and inflammation pathways and shared similarities with gene expression signatures derived from patients with sepsis, including the most severe sepsis endotypes. Despite the challenges in identifying early biomarkers of severe appendicitis, a 4-gene signature that was predictive of PA compared to SA, with an accuracy of 85.7% (95% CI, 72.8-94.1) was identified. Conclusions: This study found that PA was complicated by a dysregulated immune response. This finding should inform improved diagnostics of severity, early management strategies, and prevention of further postsurgical complications.

Inhibition of Receptor-Interacting Protein Kinase 1 in Chronic Plaque Psoriasis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: Receptor-interacting protein kinase 1 (RIPK1), a key mediator of inflammation through necroptosis and proinflammatory cytokine production, may play a role in the pathogenesis of immune-mediated inflammatory diseases such as chronic plaque psoriasis. An experimental medicine study of RIPK1 inhibition with GSK2982772 immediate-release formulation at doses up to 60 mg three times daily in mild to moderate plaque psoriasis indicated that efficacy may be improved with higher trough concentrations of GSK2982772. METHODS: This multicenter, randomized, double-blind, placebo-controlled, repeat-dose study (NCT04316585) assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of 960 mg GSK2982772 (once-daily modified-release formulation) in patients with moderate to severe plaque psoriasis. Twenty-nine patients were randomized 2:1 to GSK2982772 (N = 19) or placebo (N = 10) for 12 weeks. RESULTS: GSK2982772 was well tolerated with trough concentrations greater than tenfold higher than the previous phase 1 study with immediate release. Despite near complete RIPK1 target engagement in blood and modest reduction in circulating inflammatory cytokines, the proportion of patients achieving 75% improvement from baseline in Psoriasis Area Severity Index score at week 12 was similar between GSK2982772 and placebo (posterior median 1.8% vs 4.9%, respectively), with an estimated median treatment difference of - 2.3%. This analysis incorporated historical placebo data through the use of an informative prior distribution on the placebo arm. Week 4 changes in skin biopsy gene expression suggested sufficient local drug exposure to elicit a pharmacodynamic response. CONCLUSION: Administration of the RIPK1 inhibitor GSK2982772 to patients with moderate to severe plaque psoriasis did not translate into meaningful clinical improvements.

Psoriasis is thought to be caused by problems with the immune system, including possibly receptor-interacting protein kinase 1 (RIPK1), which plays an important role in the development of inflammation. A previous study suggested that the drug, GSK2982772, which interferes with RIPK1, might improve symptoms in patients with psoriasis. This study examined whether higher doses of GSK2982772 than previously studied would be beneficial for patients with psoriasis. The study found that the severity of psoriasis was similar in patients treated with GSK2982772 for 12 weeks as in those who did not receive the drug, indicating that GSK298772 did not improve psoriasis.

Caldendrin Is a Repressor of PIEZO2 Channels and Touch Sensation in Mice.

The sense of touch is crucial for cognitive, emotional, and social development and relies on mechanically activated (MA) ion channels that transduce force into an electrical signal. Despite advances in the molecular characterization of these channels, the physiological factors that control their activity are poorly understood. Here, we used behavioral assays, electrophysiological recordings, and various mouse strains (males and females analyzed separately) to investigate the role of the calmodulin-like Ca2+ sensor, caldendrin, as a key regulator of MA channels and their roles in touch sensation. In mice lacking caldendrin (Cabp1 KO), heightened responses to tactile stimuli correlate with enlarged MA currents with lower mechanical thresholds in dorsal root ganglion neurons (DRGNs). The expression pattern of caldendrin in the DRG parallels that of the major MA channel required for touch sensation, PIEZO2. In transfected cells, caldendrin interacts with and inhibits the activity of PIEZO2 in a manner that requires an alternatively spliced sequence in the N-terminal domain of caldendrin. Moreover, targeted genetic deletion of caldendrin in Piezo2-expressing DRGNs phenocopies the tactile hypersensitivity of complete Cabp1 KO mice. We conclude that caldendrin is an endogenous repressor of PIEZO2 channels and their contributions to touch sensation in DRGNs.

Factors associated with SARS-CoV-2 infection in unvaccinated children and young adults.

BACKGROUND AND OBJECTIVES: Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC). METHODS: We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults < 25 years between November 2020-May 2021 and phase 2 enrolled children < 10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity. RESULTS: A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups). CONCLUSIONS: SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.

Real-Time Online Demonstration for Skills Education for First-Year Nursing Students.

BACKGROUND: Few studies have investigated first-year nursing students' perspectives after they received real-time online demonstration (RTOD) for fundamental nursing skills education. METHOD: A mixed-methods study was conducted with prospective second-year nursing students after they completed a one-semester RTOD class in their first year. With permission from the original authors, an online questionnaire, the Self-Structured Questionnaire (SSQ), was administered to 277 students in undergraduate and higher-diploma programs, followed by two focus group interviews with 13 students. Survey and focus group data were analyzed using descriptive statistics and thematic analysis, respectively. RESULTS: Regarding students' barriers in administrative, individual, and technological areas, three themes emerged from the focus groups: (1) learning quality; (2) connection; and (3) impediments. CONCLUSION: RTOD contributed to fundamental nursing skills education. However, there was room for improvement. [J Nurs Educ. 2024;63(1):43-47.].

Somatic Versus Germline: A Case Series of Three Children With ATM-Mutated Medulloblastoma.

Somatic versus Germline-A Case Series of Three Children with ATM- mutated Medulloblastoma.

Perceptions to Overcoming Barriers to Prenatal Care in African American Women.

Pregnancy-related deaths affect African American women at a rate four to five times higher than White women. These deaths occur during pregnancy or up to 1 year after childbirth. Inadequate or delayed prenatal care is a factor associated with poor maternal health outcomes in African American women. Identifying factors that pose as facilitators and barriers to prenatal care is essential in developing interventions aimed at improving maternal health outcomes.

Structure-Activity Relationships and Discovery of (S)-6-Isopropyl-2-methoxy-3-(3-methoxypropoxy)-10-oxo-5,10-dihydro-6H-pyrido[1,2-h][1,7]naphthyridine-9-carboxylic Acid (AB-452), a Novel Orally Available HBV RNA Destabilizer.

Approved therapies for hepatitis B virus (HBV) treatment include nucleos(t)ides and interferon alpha (IFN-α) which effectively suppress viral replication, but they rarely lead to cure. Expression of viral proteins, especially surface antigen of the hepatitis B virus (HBsAg) from covalently closed circular DNA (cccDNA) and the integrated genome, is believed to contribute to the persistence of HBV. This work focuses on therapies that target the expression of HBV proteins, in particular HBsAg, which differs from current treatments. Here we describe the identification of AB-452, a dihydroquinolizinone (DHQ) analogue. AB-452 is a potent HBV RNA destabilizer by inhibiting PAPD5/7 proteins in vitro with good in vivo efficacy in a chronic HBV mouse model. AB-452 showed acceptable tolerability in 28-day rat and dog toxicity studies, and a high degree of oral exposure in multiple species. Based on its in vitro and in vivo profiles, AB-452 was identified as a clinical development candidate.

A practical method to simulate realistic reduced-exposure CT images by the addition of computationally generated noise.

Computed tomography (CT) scanning protocols should be optimized to minimize the radiation dose necessary for imaging. The addition of computationally generated noise to the CT images facilitates dose reduction. The objective of this study was to develop a noise addition method that reproduces the complexity of the noise texture present in clinical images with directionality that varies over images according to the underlying anatomy, requiring only Digital Imaging and Communications in Medicine (DICOM) images as input data and commonly available phantoms for calibration. The developed method is based on the estimation of projection data by forward projection from images, the addition of Poisson noise, and the reconstruction of new images. The method was validated by applying it to images acquired from cylindrical and thoracic phantoms using source images with exposures up to 49 mAs and target images between 39 and 5 mAs. 2D noise spectra were derived for regions of interest in the generated low-dose images and compared with those from the scanner-acquired low-dose images. The root mean square difference between the standard deviations of noise was 4%, except for very low exposures in peripheral regions of the cylindrical phantom. The noise spectra from the corresponding regions of interest exhibited remarkable agreement, indicating that the complex nature of the noise was reproduced. A practical method for adding noise to CT images was presented, and the magnitudes of noise and spectral content were validated. This method may be used to optimize CT imaging.

Society for Maternal-Fetal Medicine Special Statement: Emergency checklist, planning worksheet, and system preparedness bundle for placenta accreta spectrum.

Placenta accreta spectrum is a life-threatening complication of pregnancy that is underdiagnosed and can result in massive hemorrhage, disseminated intravascular coagulation, massive transfusion, surgical injury, multisystem organ failure, and even death. Given the rarity and complexity, most obstetrical hospitals and providers do not have comprehensive expertise in the diagnosis and management of placenta accreta spectrum. Emergency management, antenatal interdisciplinary planning, and system preparedness are key pillars of care for this life-threatening disorder. We present an updated sample checklist for emergent and unplanned cases, an antenatal planning worksheet for known or suspected cases, and a bundle of activities to improve system and team preparedness for placenta accreta spectrum.

Concentration-dependent alterations in the human plasma proteome following controlled exposure to diesel exhaust.

Traffic-related air pollution (TRAP) exposure is associated with systemic health effects, which can be studied using blood-based markers. Although we have previously shown that high TRAP concentrations alter the plasma proteome, the concentration-response relationship between blood proteins and TRAP is unexplored in controlled human exposure studies. We aimed to identify concentration-dependent plasma markers of diesel exhaust (DE), a model of TRAP. Fifteen healthy non-smokers were enrolled into a double-blinded, crossover study where they were exposed to filtered air (FA) and DE at 20, 50 and 150 µg/m3 PM2.5 for 4h, separated by ≥ 4-week washouts. We collected blood at 24h post-exposure and used label-free mass spectrometry to quantify proteins in plasma. Proteins exhibiting a concentration-response, as determined by linear mixed effects models (LMEMs), were assessed for pathway enrichment using WebGestalt. Top candidates, identified by sparse partial least squares discriminant analysis and LMEMs, were confirmed using enzyme-linked immunoassays. Thereafter, we assessed correlations between proteins that showed a DE concentration-response and acute inflammatory endpoints, forced expiratory volume in 1 s (FEV1) and methacholine provocation concentration causing a 20% drop in FEV1 (PC20). DE exposure was associated with concentration-dependent alterations in 45 proteins, which were enriched in complement pathways. Of the 9 proteins selected for confirmatory immunoassays, based on complementary bioinformatic approaches to narrow targets and availability of high-quality assays, complement factor I (CFI) exhibited a significant concentration-dependent decrease (-0.02 µg/mL per µg/m3 of PM2.5, p = 0.04). Comparing to FA at discrete concentrations, CFI trended downward at 50 (-2.14 ± 1.18, p = 0.08) and significantly decreased at 150 µg/m3 PM2.5 (-2.93 ± 1.18, p = 0.02). CFI levels were correlated with FEV1, PC20 and nasal interleukin (IL)-6 and IL-1ß. This study details concentration-dependent alterations in the plasma proteome following DE exposure at concentrations relevant to occupational and community settings. CFI shows a robust concentration-response and association with established measures of airway function and inflammation.