Transcriptional coactivation of NRF2 signaling in cardiac fibroblasts promotes resistance to oxidative stress.

We recently discovered that steroid receptor coactivators (SRCs) SRCs-1, 2 and 3, are abundantly expressed in cardiac fibroblasts (CFs) and their activation with the SRC small molecule stimulator MCB-613 improves cardiac function and dramatically lowers pro-fibrotic signaling in CFs post-myocardial infarction. These findings suggest that CF-derived SRC activation could be beneficial in the mitigation of chronic heart failure after ischemic insult. However, the cardioprotective mechanisms by which CFs contribute to cardiac pathological remodeling are unclear. Here we present studies designed to identify the molecular and cellular circuitry that governs the anti-fibrotic effects of an MCB-613 derivative, MCB-613-10-1, in CFs. We performed cytokine profiling and whole transcriptome and proteome analyses of CF-derived signals in response to MCB-613-10-1. We identified the NRF2 pathway as a direct MCB-613-10-1 therapeutic target for promoting resistance to oxidative stress in CFs. We show that MCB-613-10-1 promotes cell survival of anti-fibrotic CFs exposed to oxidative stress by suppressing apoptosis. We demonstrate that an increase in HMOX1 expression contributes to CF resistance to oxidative stress-mediated apoptosis via a mechanism involving SRC co-activation of NRF2, hence reducing inflammation and fibrosis. We provide evidence that MCB-613-10-1 acts as a protectant against oxidative stress-induced mitochondrial damage. Our data reveal that SRC stimulation of the NRF2 transcriptional network promotes resistance to oxidative stress and highlights a mechanistic approach toward addressing pathologic cardiac remodeling.

Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.

Neutrophil-derived proteases are critical to the pathology of many inflammatory lung diseases, both chronic and acute. These abundant enzymes play roles in key neutrophil functions, such as neutrophil extracellular trap formation and reactive oxygen species release. They may also be released, inducing tissue damage and loss of tissue function. Historically, the neutrophil serine proteases (NSPs) have been the main subject of neutrophil protease research. Despite highly promising cell-based and animal model work, clinical trials involving the inhibition of NSPs have shown mixed results in lung disease patients. As such, the cutting edge of neutrophil-derived protease research has shifted to proteases that have had little-to-no research in neutrophils to date. These include the cysteine and serine cathepsins, the metzincins and the calpains, among others. This review aims to outline the previous work carried out on NSPs, including the shortcomings of some of the inhibitor-orientated clinical trials. Our growing understanding of other proteases involved in neutrophil function and neutrophilic lung inflammation will then be discussed. Additionally, the potential of targeting these more obscure neutrophil proteases will be highlighted, as they may represent new targets for inhibitor-based treatments of neutrophil-mediated lung inflammation.

Travel Distance and Spanish-Speaking are Associated with Delays in the Treatment of Cleft Palate.

OBJECTIVE: Delayed repair of cleft palate is associated with worse speech outcomes. Social determinants of health may influence the timing of surgery; however, there are no population health investigations to evaluate factors such as travel distance, language barriers, and payer. This study sought to identify factors that may interfere with timely cleft palate repair. DESIGN: Retrospective cohort. SETTING: National/multi-center. PATIENTS/PARTICIPANTS: All cleft palate repairs within California were extracted from 2000-2021. MAIN OUTCOMES MEASURES: The primary outcome was age at surgical repair, which was modeled with linear regression. Covariates included race, primary language, distance from patient home to hospital, socioeconomic status, primary payer, and managed care enrollment status. RESULTS: 11 260 patients underwent surgical repair of a cleft palate. Black race was associated with delayed repair (22 additional days, P = .004, 95% CI 67.00-37.7) along with Asian/Pacific-Islander race (11 additional days, P = .006, 95% CI 3.26-18.9) compared to white race. Spanish-speaking patients had significantly later cleft palate repairs by 19 days, (P < .001, 95% CI 10.8-27.7) compared with English-speaking. Further distances from the hospital were significantly associated with later cleft surgeries with out-of-state patients undergoing surgery 52 days later (P < .001, 95% CI 11.3-24.3). Managed care plans and Medi-Cal were significantly associated with earlier surgical repair compared with private insurance. CONCLUSION: Black, Asian Pacific Islander, and Spanish-speaking patients and greater distance traveled to hospital were associated with delayed cleft palate repairs. These results underscore the importance of addressing structural and social barriers to care to improve outcomes and reduce health disparities for patients with cleft palate.

Burns Resulting from Electric Vehicle Manufacturing in Silicon Valley.

The development of electric vehicles (EVs) has introduced novel technologies and manufacturing processes that expose workers to new risks of burn injury. We identified six patients who were admitted to our burn center for injuries that occurred while working in EV manufacturing facilities. The burns fell into three categories: flash flame burns due to lithium-ion battery explosions, high-voltage electrical injuries, and burns caused by contact with molten metal. Recognizing these recurrent patterns of injury should inform future prevention efforts and prepare health systems to evaluate and treat patients burned in EV manufacturing.

A national analysis of burn injuries among homeless persons presenting to emergency departments.

INTRODUCTION: Burn injuries among the homeless are increasing as record numbers of people are unsheltered and resort to unsafe heating practices. This study characterizes burns in homeless encounters presenting to US emergency departments (EDs). METHODS: Burn encounters in the 2019 Nationwide Emergency Department Sample (NEDS) were queried. ICD-10 and CPT codes identified homelessness, injury regions, depths, total body surface area (TBSA %), and treatment plans. Demographics, comorbidities, and charges were analyzed. Discharge weights generated national estimates. Statistical analysis included univariate testing and multivariate modeling. RESULTS: Of 316,344 weighted ED visits meeting criteria, 1919 (0.6%) were homeless. Homeless encounters were older (mean age 44.83 vs. 32.39 years), male-predominant (71% vs. 52%), and had more comorbidities, and were more often White or Black race (p < 0.001). They more commonly presented to EDs in the West and were covered by Medicaid (51% vs. 33%) (p < 0.001). 12% and 5% of homeless burn injuries were related to self-harm and assault, respectively (p < 0.001). Homeless encounters experienced more third-degree burns (13% vs. 4%; p < 0.001), though TBSA % deciles were not significantly different (34% vs. 33% had TBSA % of ten or lower; p = 0.516). Homeless encounters were more often admitted (49% vs. 7%; p < 0.001), and homelessness increased odds of admission (OR 4.779; p < 0.001). Odds of transfer were significantly lower (OR 0.405; p = 0.021). CONCLUSION: Homeless burn ED encounters were more likely due to assault and self-inflicted injuries, and more severe. ED practitioners should be aware of these patients' unique presentation and triage to burn centers accordingly.

Updated Trends and Outcomes in Autologous Breast Reconstruction in the United States, 2016-2019.

INTRODUCTION: Autologous breast reconstruction (ABR) has increased in recent decades, although concerns for access remain. As such, our goal is to trend national demographics and operative characteristics of ABR in the United States. METHODS: Using the National Inpatient Sample, 2016-2019, the International Classification of Disease , Tenth Edition codes identified adult female encounters undergoing ABR. Demographics and procedure-related characteristics were recorded. Discharge weights generated national estimates. Statistical analysis included univariate testing and multivariate regression modeling. RESULTS: A total of 52,910 weighted encounters met the criteria (mean age, 51.5 ± 10.0 years). Autologous breast reconstruction utilization increased (Δ = +5%), 2016-2019, primarily driven by a rise in deep inferior epigastric perforator (DIEP) reconstructions (Δ = +28%; incidence rate ratio [IRR], 1.070; P < 0.001), which were predominant throughout the study period (69%). More recent surgery year, bilateral reconstruction, higher income levels, commercial insurance, and care in the South US region increased the odds of DIEP-based ABR ( P ≤ 0.036). Transverse rectus abdominis myocutaneous flaps, bilateral reconstructions, higher comorbidity levels, and experiencing complications increased the length of stay ( P ≤ 0.038). Most ABRs (75%) were privately insured. The rates of immediate reconstructions increased over the study period (from 26% to 46%; IRR, 1.223; P < 0.001), as did the rates of bilateral reconstructions (from 54% to 57%; IRR, 1.026; P = 0.030). The rates of ABRs performed at teaching hospitals remained high (90% to 93%; P = 0.242). CONCLUSIONS: As of 2019, ABR has become more prevalent, with the DIEP flap constituting the most common modality. With the increasing ABR popularity, efforts should be made to ensure geographic and financial accessibility.

Access to Burn Care in the US.

This cross-sectional study examines burn incidence rates and accessibility of American Burn Association­verified or self-designated burn centers from 2013 to 2019.

Inpatient Complications and Outcomes for Burn Patients Admitted with Methamphetamine Intoxication.

Methamphetamine intoxication frequently complicates inpatient burn admissions. While single-institution studies describe adverse outcomes during resuscitation, little is known about the risks of amphetamine intoxication on inpatient complications and perioperative management. The US National Trauma Data Bank was queried for burn encounters between 2017-2021. Amphetamine intoxication was identified on admission. Primary outcomes included death, stroke, and myocardial infarction (MI). Secondary outcomes included organ failure and surgical management. Multivariable regressions modeled outcomes adjusting for available covariates including demographics, total body surface area (TBSA) burned, and inhalation injury. Bonferroni adjustments were applied. Our study identified a total of 73,968 primary burn encounters with toxicology screens. Among these, 800 cases (1.1%) were found to have positive methamphetamine drug screens upon admission. Methamphetamine users were significantly older (41.7 versus 34.9 years, p<.001), had a greater percentage of males (69.6 vs. 65.4, p=.045), were more likely to have inhalation injury (p<.001) and had larger %TBSA burns (16% vs. 13%, (p<.001). Methamphetamine users were no more likely to die, experience MI, or experience stroke during admission. In contrast, methamphetamine users were significantly more likely to have alcohol withdrawal (p=.019), AKI (p<.001), deep vein thrombosis (DVT) (p=.001) , pulmonary embolism (PE) (p=.039), sepsis (p=.026), and longer ICU stays (p<.001). Methamphetamine use was associated with a longer number of days to first procedure (p=.005). Of all patients who required surgery (15.0%), methamphetamine users required significantly more total debridements and reconstructive procedures (p<.001). While not associated with mortality, methamphetamine intoxication was associated with an increased risk of many complications including PE, DVT, AKI, sepsis, and longer ICU stays. Methamphetamine intoxication was associated with delays in surgical care.

Negotiated Rates for Surgical Cancer Care in the Era of Price Transparency-Prices Reflect Market Competition.

OBJECTIVE: To measure commercial price variation for cancer surgery within and across hospitals. BACKGROUND: Surgical care for solid-organ tumors is costly, and negotiated commercial rates have been hidden from public view. The Hospital Price Transparency Rule, enacted in 2021, requires all hospitals to list their negotiated rates on their website, thus opening the door for an examination of pricing for cancer surgery. METHODS: This was a cross-sectional study using 2021 negotiated price data disclosed by US hospitals for the 10 most common cancers treated with surgery. Price variation was measured using within-hospital and across-hospital ratios. Commercial rates relative to cancer center designation and the Herfindahl-Hirschman Index at the facility level were evaluated with mixed effects linear regression with random intercepts per procedural code. RESULTS: In all, 495,200 unique commercial rates from 2232 hospitals resulted for the 10 most common solid-organ tumor cancers. Gynecologic cancer operations had the highest median rates at $6035.8/operation compared with bladder cancer surgery at $3431.0/operation. Compared with competitive markets, moderately and highly concentrated markets were associated with significantly higher rates (HHI 1501, 2500, coefficient $513.6, 95% CI, $295.5, $731.7; HHI >2500, coefficient $1115.5, 95% CI, $913.7, $1317.2). National Cancer Institute designation was associated with higher rates, coefficient $3,451.9 (95% CI, $2853.2, $4050.7). CONCLUSIONS: Commercial payer-negotiated prices for the surgical management of 10 common, solid tumor malignancies varied widely both within and across hospitals. Higher rates were observed in less competitive markets. Future efforts should facilitate price competition and limit health market concentration.

Commercial Insurance Rates and Coding for Lymphedema Procedures: The Current State of Confusion and Need for Consensus.

BACKGROUND: Surgical treatment of lymphedema has outpaced coding paradigms. In the setting of ambiguity regarding coding for physiologic procedures [lymphovenous bypass (LVB) and vascularized lymph node transplant (VLNT)], we hypothesized that there would be variation in commercial reimbursement based on coding pattern. METHODS: The authors performed a cross-sectional analysis of 2021 nationwide hospital pricing data for 21 CPT codes encompassing excisional (direct excision, liposuction), physiologic (LVB, VLNT), and ancillary (lymphangiography) procedures. Within-hospital ratios (WHRs) and across-hospital ratios (AHRs) for adjusted commercial rates per CPT code quantified price variation. Mixed effects linear regression modeled associations of commercial rate with public payer (Medicare and Medicaid), self-pay, and chargemaster rates. RESULTS: A total of 270,254 commercial rates, including 95,774 rates for physiologic procedures, were extracted from 2863 hospitals. Lymphangiography codes varied most in commercial price (WHR, 1.76 to 3.89; AHR, 8.12 to 44.38). For physiologic codes, WHRs ranged from 1.01 (VLNT; free omental flap) to 3.03 (LVB; unlisted lymphatic procedure), and AHRs ranged from 5.23 (LVB; lymphatic channel incision) to 10.36 (LVB; unlisted lymphatic procedure). Median adjusted commercial rates for excisional procedures ($3635.84) were higher than for physiologic procedures ($2560.40; P < 0.001). Commercial rate positively correlated with Medicare rate for all physiologic codes combined, although regression coefficients varied by code. CONCLUSIONS: Commercial payer-negotiated rates for physiologic procedures were highly variable both within and across hospitals, reflective of variation in CPT codes. Physiologic procedures may be undervalued relative to excisional procedures. Consistent coding nomenclature should be developed for physiologic and ancillary procedures.

US air pollution is associated with increased incidence of non-syndromic cleft lip/palate.

Maternal cigarette use is associated with the fetal development of orofacial clefts. Air pollution should be investigated for similar causation. We hypothesize that the incidence of non-syndromic cleft lip with or without palate (NSCLP) and non-syndromic cleft palate (NSCP) would be positively correlated with air pollution concentration. METHODS: The incidence of NSCLP and NSCP per 1000 live births from 2016 to 2020 was extracted from the Centers for Disease Control and Prevention Vital Statistics Database and merged with national reports on air pollution using the Environmental Protection Agency Air Quality Systems annual data. The most commonly reported pollutants were analyzed including benzene, sulfur dioxide (SO2), particulate matter (PM) 2.5, PM 10, ozone (O3), and carbon monoxide (CO). Multivariable negative binomial and Poisson log-linear regression models evaluated the incidence of NSCLP and NSCP as a function of the pollutants, adjusting for race. All p-values are reported with Bonferroni correction. RESULTS: The median NSCLP incidence was 0.22/1000 births, and isolated NSCP incidence was 0.18/1000 births. For NSCLP, SO2 had a coefficient estimate (CE) of 0.60 (95% CI [0.23, 0.98], p < 0.007) and PM 2.5 had a CE of 0.20 (95% CI [0.10, 0.31], p < 0.005). Among isolated NSCP, no pollutants were found to be significantly associated. CONCLUSION: SO2 and PM 2.5 were significantly correlated with increased incidence of NSCLP. The American people and perinatal practitioners should be aware of the connection to allow for risk reduction and in utero screening.

Health Equity Ratings of U.S. Burn Centers-Does For-Profit Status Matter?

Achieving health equity is forefront in national discussions on healthcare structuring. Burn injuries transcend racial and socioeconomic boundaries. Burn center funding ranges from safety-net to for-profit without an understanding of how funding mechanisms translate into equity outcomes. We hypothesized that health equity would be highest at safety-net facilities and lowest at for-profit centers. All verified and non-verified American Burn Association burn centers were collated in 2022. Safety-net status, for-profit status, and health equity rating were extracted from national datasets. Equity ratings were compared across national burn centers and significance was determined with comparative statistics and ordinal logistic regression. On an equity grade of A-D (A is the best), 27.6% of centers were rated A, 27.6% rated B, 41.5% rated C, and 3.3% rated D. About 17.1% of all burn centers were designated as for-profit compared to 21.1% of centers that were safety-net. About 73.1% of safety-net centers scored an A rating, and 14.3% of for-profit centers scored an A rating. Safety-net centers were 21.8 times more likely (P < .001) to have the highest equity score compared to nonsafety-net centers. There was an 80% decrease in the odds of having a rating of A for for-profit centers compared to nonprofit centers (P = .04). Safety-net centers had the highest equity ratings while for-profit burn centers scored the lowest. For-profit funding mechanisms may lead to the delivery of less equitable burn care. Burn centers should focus on health equity in the triage and management of their patients.

Amphetamine Positivity Prior to Burn Surgery Does not Adversely Affect Intraoperative Outcomes.

The treatment of burn patients using amphetamines is challenging due hemodynamic liabilty and altered physiology. Wide variation exists in the operative timing for this patient population. We hypothesize that burn excision in patients admitted with amphetamine positivity is safe regardless of timing. Data from two verified burn centers between 2017 and 2022 with differing practice patterns in operative timing for amphetamine-positive patients. Center A obtains toxicology only on admission and proceeds with surgery based on hemodynamic status and operative urgency, whereas Center B sends daily toxicology until a negative test results. The primary outcome was the use of vasoactive agents during the index operation, modeled using logistic regression adjusting for burn severity and hospital days to index operation. Secondary outcomes included death and inpatient complications. A total of 270 patients were included, and there were no significant differences in demographics or burn characteristics between centers. Center A screened once and Center B obtained a median of four screens prior to the surgery. The adjusted OR of requiring vasoactive support intraoperatively was not associated with negative toxicology result (P = .821). Having a body surface area burned >20% conferred a significantly higher risk of vasoactive support (adj. OR 13.42 [3.90-46.23], P < .001). Mortality, number of operations, stroke, and hospital length of stay were similar between cohorts. Comparison between two verified burn centers indicates that waiting until a negative amphetamine toxicology result does not impact intraoperative management or subsequent burn outcomes. Serial toxicology tests are unnecessary to guide operative timing of burn patients with amphetamine use.

Diminished airway host innate response in people with cystic fibrosis who experience frequent pulmonary exacerbations.

RATIONALE: Pulmonary exacerbations are clinically impactful events that accelerate cystic fibrosis (CF) lung disease progression. The pathophysiological mechanisms underlying an increased frequency of pulmonary exacerbations have not been explored. OBJECTIVES: To compare host immune response during intravenous antibiotic treatment of pulmonary exacerbations in people with CF who have a history of frequent versus infrequent exacerbations. METHODS: Adults with CF were recruited at onset of antibiotic treatment of a pulmonary exacerbation and were categorised as infrequent or frequent exacerbators based on their pulmonary exacerbation frequency in the previous 12 months. Clinical parameters, sputum bacterial load and sputum inflammatory markers were measured on day 0, day 5 and at the end of treatment. Shotgun proteomic analysis was performed on sputum using liquid chromatography-mass spectrometry. MEASUREMENTS AND MAIN RESULTS: Many sputum proteins were differentially enriched between infrequent and frequent exacerbators (day 0 n=23 and day 5 n=31). The majority of these proteins had a higher abundance in infrequent exacerbators and were secreted innate host defence proteins with antimicrobial, antiprotease and immunomodulatory functions. Several differentially enriched proteins were validated using ELISA and Western blot including secretory leukocyte protease inhibitor (SLPI), lipocalin-1 and cystatin SA. Sputum from frequent exacerbators demonstrated potent ability to cleave exogenous recombinant SLPI in a neutrophil elastase dependent manner. Frequent exacerbators had increased sputum inflammatory markers (interleukin (IL)-1ß and IL-8) and total bacterial load compared to infrequent exacerbators. CONCLUSIONS: A diminished innate host protein defence may play a role in the pathophysiological mechanisms of frequent CF pulmonary exacerbations. Frequent exacerbators may benefit from therapies targeting this dysregulated host immune response.

Association of High-Deductible Health Plans and Time to Surgery for Breast and Colon Cancer.

BACKGROUND: High-deductible health plans (HDHPs) have been shown to delay timing of breast and colon cancer screening, although the relationship to the timing of cancer surgery is unknown. The objective of this study was to characterize timing of surgery for breast and colon cancer patients undergoing cancer operations following routine screening. STUDY DESIGN: Data from the IBM MarketScan Commercial Claims Database from 2007 to 2016 were queried to identify patients who underwent screening mammogram and/or colonoscopy. The calendar quarters of screening and surgery were analyzed with ordinal logistic regression. The time from screening to surgery (time to surgery, TTS) was evaluated using a Cox proportional hazard function. RESULTS: Among 32,562,751 patients who had screening mammograms, 0.7% underwent breast cancer surgery within the following year. Among 9,325,238 patients who had screening colonoscopies, 0.9% were followed by colon cancer surgery within a year. The odds of screening (OR 1.146 for mammogram, 1.272 for colonoscopy; p < 0.001) and surgery (OR 1.120 for breast surgery, 1.219 for colon surgery; p < 0.001) increased each quarter for HDHPs compared to low-deductible health plans. Enrollment in an HDHP was not associated with a difference in TTS. Screening in Q3 or Q4 was associated with shorter TTS compared to screening in Q1 (hazard ratio 1.061 and 1.046, respectively; p < 0.001). CONCLUSIONS: HDHPs were associated with delays in screening and surgery. However, HDHPs were not associated with delays in TTS. Interventions to improve cancer care outcomes in the HDHP population should concentrate on reducing barriers to timely screening.

Radiolytically reworked Archean organic matter in a habitable deep ancient high-temperature brine.

Investigations of abiotic and biotic contributions to dissolved organic carbon (DOC) are required to constrain microbial habitability in continental subsurface fluids. Here we investigate a large (101-283 mg C/L) DOC pool in an ancient (>1Ga), high temperature (45-55 °C), low biomass (102-104 cells/mL), and deep (3.2 km) brine from an uranium-enriched South African gold mine. Excitation-emission matrices (EEMs), negative electrospray ionization (-ESI) 21 tesla Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), and amino acid analyses suggest the brine DOC is primarily radiolytically oxidized kerogen-rich shales or reefs, methane and ethane, with trace amounts of C3-C6 hydrocarbons and organic sulfides. δ2H and δ13C of C1-C3 hydrocarbons are consistent with abiotic origins. These findings suggest water-rock processes control redox and C cycling, helping support a meagre, slow biosphere over geologic time. A radiolytic-driven, habitable brine may signal similar settings are good targets in the search for life beyond Earth.

Holistic Approach to Burn Reconstruction and Scar Rehabilitation.

More than 11 million burn injuries occur each year across the world. Many people with burn injuries, regardless of injury size, develop hypertrophic scar, contracture, unstable scar, heterotopic ossification, and disability resulting from these sequelae. Advances in trauma systems, critical care, safe surgery, and multidisciplinary burn care have markedly improved the survival of people who have experienced extensive burn injuries. Burn scar reconstruction aims to improve or restore physical function, confidence, and body image. Like acute burn care, burn scar reconstruction requires thoughtful, coordinated approaches along the continuum of burn injury, recovery, and rehabilitation.

Free Flap Reconstruction in the Era of Commercial Price Transparency - What are We Paying For?

BACKGROUND: Commercial rates for free flap reconstruction were not known publicly prior to the 2021 Hospital Price Transparency Final Rule. The purpose of this study was to examine commercial facility payments to characterize nationwide variation for microsurgical operations and identify opportunities to improve market effectiveness. METHODS: A cross-sectional study was performed using 2022 commercial insurance pricing merged with hospital performance data. Facility payment rates were extracted for nine CPT codes for free flap operations. Price variation was quantified via across-hospital ratios (AHRs) and within-hospital ratios (WHRs). Mixed effects linear models evaluated commercial rates relative to value, outcomes, and equity performance metrics, in addition to facility-level factors that included healthcare market concentration. RESULTS: 20,528 commercial rates across 675 hospitals were compiled. AHRs ranged from 5.85-7.95, while WHRs ranged from 1.00-1.71. Compared to the lowest scoring hospitals (grade D), hospitals with an outcome grade of A and equity grades of B or C were associated with higher commercial rates (p<0.04); there were no significant differences in rate based on value. Higher commercial rates were also associated with nonprofit status and more concentrated markets (p<0.006). Lower commercial rates were correlated with safety-net and teaching hospitals (p<0.001). CONCLUSION: Commercial rates for free flaps varied substantially both across and within hospitals. Associations of higher commercial rates with less competitive markets, and the lack of consistent association with value and equity, identify pricing failures. Additional work is needed to improve market efficiency for free flap operations.

Airway Epithelium Senescence as a Driving Mechanism in COPD Pathogenesis.

Cellular senescence is a state of permanent cell cycle arrest triggered by various intrinsic and extrinsic stressors. Cellular senescence results in impaired tissue repair and remodeling, loss of physiological integrity, organ dysfunction, and changes in the secretome. The systemic accumulation of senescence cells has been observed in many age-related diseases. Likewise, cellular senescence has been implicated as a risk factor and driving mechanism in chronic obstructive pulmonary disease (COPD) pathogenesis. Airway epithelium exhibits hallmark features of senescence in COPD including activation of the p53/p21WAF1/CIP1 and p16INK4A/RB pathways, leading to cell cycle arrest. Airway epithelial senescent cells secrete an array of inflammatory mediators, the so-called senescence-associated secretory phenotype (SASP), leading to a persistent low-grade chronic inflammation in COPD. SASP further promotes senescence in an autocrine and paracrine manner, potentially contributing to the onset and progression of COPD. In addition, cellular senescence in COPD airway epithelium is associated with telomere dysfunction, DNA damage, and oxidative stress. This review discusses the potential mechanisms of airway epithelial cell senescence in COPD, the impact of cellular senescence on the development and severity of the disease, and highlights potential targets for modulating cellular senescence in airway epithelium as a potential therapeutic approach in COPD.