Front Rehabil Sci. 2021 Oct 18;2:751798. doi: 10.3389/fresc.2021.751798. eCollection 2021.

ABSTRACT

Chronic cough is experienced by most patients with idiopathic pulmonary fibrosis (IPF). It is often the first symptom and is associated with reduced quality of life, increased rates of depression and anxiety, more severe physiological impairment, and disease progression. Although not fully understood, recent gains in understanding the pathophysiology of chronic cough in IPF have been made. The pathophysiology is likely multifactorial and includes alterations in mucous production and clearance, architectural distortion, and increased cough reflex sensitivity, suggesting a role for targeted therapies and multidisciplinary treatment. Modifiable comorbidities can also induce cough in patients with IPF. There is a renewed emphasis on measuring cough in IPF, with clinical trials of novel and repurposed therapies for chronic cough emerging in this population. This review provides an update on the clinical characteristics, pathophysiology, and measurement of chronic cough in patients with IPF and summarizes recent developments in non-pharmacological and pharmacological therapies.

PMID:36188759 | PMC:PMC9397801 | DOI:10.3389/fresc.2021.751798

Front Pharmacol. 2022 Sep 16;13:978151. doi: 10.3389/fphar.2022.978151. eCollection 2022.

ABSTRACT

Non-coding RNA is still one of the most popular fields in biology research. In recent years, people paid more attention to the roles of H19 in lung diseases, which expressed abnormally in various pathological process. Therefore, this review focus on the regulatory role of H19 in asthma, pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), lung injury, pneumonia, lung cancer, etc. And the potential therapeutic agents and molecular treatments of H19 are collected. The aim is to demonstrate its underlying mechanism in pulmonary diseases and to guide the basic research targeting H19 into clinical drug translation.

PMID:36188624 | PMC:PMC9523668 | DOI:10.3389/fphar.2022.978151

Front Mol Biosci. 2022 Sep 14;9:977122. doi: 10.3389/fmolb.2022.977122. eCollection 2022.

ABSTRACT

Ubiquitin specific protease (USP)-13 is a deubiquitinase that removes ubiquitin from substrates to prevent protein degradation by the proteasome. Currently, the roles of USP13 in physiology and pathology have been reported. In physiology, USP13 is highly associated with cell cycle regulation, DNA damage repair, myoblast differentiation, quality control of the endoplasmic reticulum, and autophagy. In pathology, it has been reported that USP13 is important in the pathogenesis of infection, inflammation, idiopathic pulmonary fibrosis (IPF), neurodegenerative diseases, and cancers. This mini-review summarizes the most recent advances in USP13 studies involving its pathophysiological roles in different conditions and provides new insights into the prevention and treatment of relevant diseases, as well as further research on USP13.

PMID:36188217 | PMC:PMC9515447 | DOI:10.3389/fmolb.2022.977122

Front Oncol. 2022 Sep 15;12:1002385. doi: 10.3389/fonc.2022.1002385. eCollection 2022.

ABSTRACT

INTRODUCTION: Small cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet.

METHODS: A retrospective cohort analysis was conducted of referred ES SCLC between 2015 and 2017 in British Columbia, Canada. Patient demographics, staging, treatment, and survival data were collected through the Cancer Registry. Retrospective chart review was completed to extract past medical history and missing variables. CASPIAN/IMPower133 excluded patients with autoimmune diseases, active infection, and performance status (PS) ≥2.

RESULTS: Between 2015 and 2017, 349 patients were diagnosed with ES SCLC. In patients who received platinum-doublet chemotherapy (n=227), 15 had medical contraindication to ICI: inflammatory bowel disease (n=4), rheumatoid arthritis (n=4), idiopathic pulmonary fibrosis (n=3), lupus (n=1), Sjogren's (n=1), Takayasu arteritis (n=1), and active tuberculosis (n=1). ECOG PS was 0-1 in 96 (45%), PS was 2 in 61 (29%), and ≥3 in 51 (10%). Prior to cycle 1, 82 (36%) patients were eligible for ICI in addition to platinum doublet, 23% of the entire ES population. After cycles 1 and 2, additional 15 (7%) and 8 (4%) patients became PS 0-1, respectively. mOS for ES SCLC who received first-line platinum doublet, non-platinum chemotherapy, and best supportive care was 8.4 1.9 and 1.5 months (p<0.001).

DISCUSSION: By CASPIAN/IMpower133 trial eligibility, only 36% of our real-world platinum-treated patients would have been eligible for the addition of ICI, which is 23% of the entire ES population in one Canadian province. After one or two cycles of chemotherapy, an additional 11% of patients showed PS improvement to 0-1. While the results of CASPIAN/IMpower133 are practice-changing, the majority of the patients will not meet clinical trial eligibility and clinical trials including patients with poor PS are necessary.

PMID:36185266 | PMC:PMC9520052 | DOI:10.3389/fonc.2022.1002385

Chest. 2022 Sep 29:S0012-3692(22)03901-0. doi: 10.1016/j.chest.2022.09.031. Online ahead of print.

ABSTRACT

Bronchoalveolar cell count at diagnosis is not linked to lung function decline and exacerbations in a large prospective cohort of idiopathic pulmonary fibrosis patients.

PMID:36183786 | DOI:10.1016/j.chest.2022.09.031

Res Vet Sci. 2022 Sep 24;152:557-563. doi: 10.1016/j.rvsc.2022.09.022. Online ahead of print.

ABSTRACT

Brachycephalic obstructive airway syndrome (BOAS) and canine idiopathic pulmonary fibrosis (CIPF) of West Highland White Terriers (WHWTs) often cause intermittent or chronic hypoxemia. Our objective was to evaluate serum and bronchoalveolar lavage fluid (BALF) concentrations of hypoxemia-related proinflammatory mediators vascular endothelial growth factor A (VEGF-A) and chemokine (CC motif) ligand 2 (CCL2) in brachycephalic dogs (BDs) and WHWTs with and without CIPF. Additionally, effects of BOAS severity and ageing on these mediators were assessed. 114 BDs (28 English Bulldogs (EBs), 37 French Bulldogs, 49 Pugs), 16 WHWTs with CIPF, 26 healthy WHWTs, and 39 normocephalic control dogs were included. Fifty-four BDs were re-examined after two to three years. Bead-based immunoassay was used for proinflammatory mediator measurements. Compared with controls, significantly higher serum concentrations of VEGF-A were seen in EBs (P = 0.009) and of CCL2 in CIPF and healthy WHWTs (P < 0.001; P = 0.002). BALF samples were available from controls, EBs, and WHWTs. VEGF-A was significantly lower in EBs (P < 0.001) and in CIPF and healthy WHWTs (P = 0.006; P = 0.007) and CCL2 was higher in CIPF WHWTs (P = 0.01) compared with controls. Between visits, only serum VEGF-A significantly decreased in BDs (P < 0.001), but breed, BOAS severity, or its change had no significant effect. In conclusion, in EBs with BOAS proinflammatory changes in VEGF-A were detected in both serum and BALF. Ageing reduced serum VEGF-A in BDs. In WHWTs, our results confirmed earlier findings of CCL2 as an important biomarker for CIPF.

PMID:36183612 | DOI:10.1016/j.rvsc.2022.09.022

Pulmonology. 2022 Sep 27:S2531-0437(22)00204-5. doi: 10.1016/j.pulmoe.2022.08.004. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking.

METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed.

RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively).

CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.

PMID:36180352 | DOI:10.1016/j.pulmoe.2022.08.004

Clin Radiol. 2022 Sep 27:S0009-9260(22)00514-1. doi: 10.1016/j.crad.2022.08.135. Online ahead of print.

ABSTRACT

Artificial intelligence (AI) is becoming more widespread within radiology. Capabilities that AI algorithms currently provide include detection, segmentation, classification, and quantification of pathological findings. Artificial intelligence software have created challenges for the traditional United States Food and Drug Administration (FDA) approval process for medical devices given their abilities to evolve over time with incremental data input. Currently, there are 190 FDA-approved radiology AI-based software devices, 42 of which pertain specifically to thoracic radiology. The majority of these algorithms are approved for the detection and/or analysis of pulmonary nodules, for monitoring placement of endotracheal tubes and indwelling catheters, for detection of emergent findings, and for assessment of pulmonary parenchyma; however, as technology evolves, there are many other potential applications that can be explored. For example, evaluation of non-idiopathic pulmonary fibrosis interstitial lung diseases, synthesis of imaging, clinical and/or laboratory data to yield comprehensive diagnoses, and survival or prognosis prediction of certain pathologies. With increasing physician and developer engagement, transparency and frequent communication between developers and regulatory agencies, such as the FDA, AI medical devices will be able to provide a critical supplement to patient management and ultimately enhance physicians' ability to improve patient care.

PMID:36180271 | DOI:10.1016/j.crad.2022.08.135

Am J Respir Cell Mol Biol. 2022 Oct;67(4):503-506. doi: 10.1165/rcmb.2021-0482LE.

NO ABSTRACT

PMID:36178855 | DOI:10.1165/rcmb.2021-0482LE

Arkh Patol. 2022;84(5):35-39. doi: 10.17116/patol20228405135.

ABSTRACT

Lung adenocarcinoma against the background of idiopathic pulmonary fibrosis according to the world literature ranges from 2.7% to 48%, the incidence increases every year after the diagnosis of idiopathic pulmonary fibrosis. We present a clinical and morphological analysis of an autopsy observation of lung adenocarcinoma that developed against the background of corticosteroid-treated usual interstitial pneumonia in a 78-year-old woman. According to the results of histological and immunohistochemical studies, the diagnosis was formulated as: multicentric non-mucinous invasive adenocarcinoma of the right and left lungs with a lepidic growth pattern with background of usual interstitial pneumonia.

PMID:36178220 | DOI:10.17116/patol20228405135

Clin Transl Med. 2022 Oct;12(10):e1036. doi: 10.1002/ctm2.1036.

ABSTRACT

BACKGROUND: Emerging evidence provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), and rare anti-PF therapeutic method has promising effect in its treatment. Rho-associated coiled-coil kinases (ROCK) inhibition significantly ameliorates bleomycin-induced PF and decreases macrophage infiltration, but the mechanism remains unclear. We established bleomycin and radiation-induced PF to identify the activity of WXWH0265, a newly designed unselective ROCK inhibitor in regulating macrophages.

METHODS: Bleomycin-induced PF was induced by intratracheal instillation and radiation-induced PF was induced by bilateral thoracic irradiation. Histopathological techniques (haematoxylin and eosin, Masson's trichrome and immunohistochemistry) and hydroxyproline were used to evaluate PF severity. Western blot, quantitative real-time reverse transcription-polymerase chain reaction and flow cytometry were performed to explore the underlying mechanisms. Bone marrow-derived macrophages (BMDMs) were used to verify their therapeutic effect. Clodronate liposomes were applied to deplete macrophages and to identify the therapeutic effect of WXWH0265.

RESULTS: Therapeutic administration of ROCK inhibitor ameliorates bleomycin-induced PF by inhibiting M2 macrophages polarisation. ROCK inhibitor showed no significant anti-fibrotic effect in macrophages-depleted mice. Treatment with WXWH0265 demonstrated superior protection effect in bleomycin-induced PF compared with positive drugs. In radiation-induced PF, ROCK inhibitor effectively ameliorated PF. Fibroblasts co-cultured with supernatant from various M2 macrophages phenotypes revealed that M2 macrophages stimulated by interleukin-4 promoted extracellular matrix production. Polarisation of M2 macrophages was inhibited by ROCK inhibitor treatment in vitro. The p-signal transducer and activator of transcription 3 (STAT3) in lung tissue and BMDMs was significantly decreased in PF in vivo and vitro after treated with ROCK inhibitors.

CONCLUSION: Inhibiting ROCK could significantly attenuate bleomycin- and radiation-induced PF by regulating the macrophages polarisation via phosphorylation of STAT3. WXWH0265 is a kind of efficient unselective ROCK inhibitor in ameliorating PF. Furthermore, the results provide empirical evidence that ROCK inhibitor, WXWH0265 is a potential drug to prevent the development of PF.

PMID:36178087 | DOI:10.1002/ctm2.1036

Acta Pharm Sin B. 2022 Sep;12(9):3602-3617. doi: 10.1016/j.apsb.2022.04.006. Epub 2022 Apr 16.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

PMID:36176913 | PMC:PMC9513499 | DOI:10.1016/j.apsb.2022.04.006

Eur Respir J. 2022 Sep 29;60(3):2201536. doi: 10.1183/13993003.01536-2022. Print 2022 Sep.

NO ABSTRACT

PMID:36175026 | DOI:10.1183/13993003.01536-2022

Nat Med. 2022 Sep 29. doi: 10.1038/s41591-022-02010-y. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a lethal fibrosing interstitial lung disease with a mean survival time of less than 5 years. Nonspecific presentation, a lack of effective early screening tools, unclear pathobiology of early-stage IPF and the need for invasive and expensive procedures for diagnostic confirmation hinder early diagnosis. In this study, we introduce a new screening tool for IPF in primary care settings that requires no new laboratory tests and does not require recognition of early symptoms. Using subtle comorbidity signatures identified from the history of medical encounters of individuals, we developed an algorithm, called the zero-burden comorbidity risk score for IPF (ZCoR-IPF), to predict the future risk of an IPF diagnosis. ZCoR-IPF was trained on a national insurance claims database and validated on three independent databases, comprising a total of 2,983,215 participants, with 54,247 positive cases. The algorithm achieved positive likelihood ratios greater than 30 at a specificity of 0.99 across different cohorts, for both sexes, and for participants with different risk states and history of confounding diseases. The area under the receiver-operating characteristic curve for ZCoR-IPF in predicting IPF exceeded 0.88 and was approximately 0.84 at 1 and 4 years before a conventional diagnosis, respectively. Thus, if adopted, ZCoR-IPF can potentially enable earlier diagnosis of IPF and improve outcomes of disease-modifying therapies and other interventions.

PMID:36175678 | DOI:10.1038/s41591-022-02010-y

Am J Respir Crit Care Med. 2022 Sep 29. doi: 10.1164/rccm.202209-1772LE. Online ahead of print.

NO ABSTRACT

PMID:36174219 | DOI:10.1164/rccm.202209-1772LE

Am J Respir Crit Care Med. 2022 Sep 29. doi: 10.1164/rccm.202209-1807LE. Online ahead of print.

NO ABSTRACT

PMID:36174209 | DOI:10.1164/rccm.202209-1807LE

Eur J Cardiothorac Surg. 2022 Sep 29:ezac479. doi: 10.1093/ejcts/ezac479. Online ahead of print.

ABSTRACT

OBJECTIVES: Weight assessment is an easy-to-understand method of health checkup. The present study investigated the association between weight loss (WL) after lung cancer surgery and short-mid-term prognosis.

METHODS: The data of patients who underwent radical lobectomy for primary lung cancer were assessed between December 2017 and June 2021. Percentage weight gain or loss was determined at 3, 6 and 12 months postoperatively based on preoperative weight. The timing of decreased weight was divided into 0-3, 3-6 and 6-12 months. We also evaluated the relationship between severe WL (SWL) and prognosis.

RESULTS: We reviewed 269 patients, of whom 187 (69.5%) showed WL within 1 year after surgery. The interquartile range for maximal WL was 2.0-8.2% (median 4.0%). Further, we defined SWL as WL ≥ 8%. Twenty-five patients (9.3%) died: 9 from primary lung cancer (LC) and 16 from non-LC causes. Cancer recurrences occurred in 45 patients (16.7%). WL occurred from 6 to 12 months postoperatively was associated with poor overall survival (OS) and recurrence-free survival (RFS) (p < 0.05, both). Body mass index <18.5 kg/m2 and idiopathic pulmonary fibrosis were predictive factors (p < 0.05, all). In the SWL group, OS, RFS and non-cancer-specific were worse (p = 0.001, 0.005 and 0.019, respectively). Age ≥70 years and severe postoperative complications were predictive factors for SWL (p < 0.05, all).

CONCLUSIONS: WL from 6 to 12 months postoperatively and SWL were associated with poor prognosis. Ongoing nutritional management is important to prevent life-threatening WL in patients with predictive factors.

PMID:36173323 | DOI:10.1093/ejcts/ezac479

Respirology. 2022 Sep 29. doi: 10.1111/resp.14378. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Pulmonary hypertension is a life-limiting complication of interstitial lung disease (ILD-PH). We investigated whether treatment with phosphodiesterase 5 inhibitors (PDE5i) in patients with ILD-PH was associated with improved survival.

METHODS: Consecutive incident patients with ILD-PH and right heart catheterisation, echocardiography and spirometry data were followed from diagnosis to death, transplantation or censoring with all follow-up and survival data modelled by Bayesian methods.

RESULTS: The diagnoses in 128 patients were idiopathic pulmonary fibrosis (n = 74, 58%), hypersensitivity pneumonitis (n = 17, 13%), non-specific interstitial pneumonia (n = 12, 9%), undifferentiated ILD (n = 8, 6%) and other lung diseases (n = 17, 13%). Final outcomes were death (n = 106, 83%), transplantation (n = 9, 7%) and censoring (n = 13, 10%). Patients treated with PDE5i (n = 50, 39%) had higher mean pulmonary artery pressure (median 38 mm Hg [interquartile range, IQR: 34, 43] vs. 35 mm Hg [IQR: 31, 38], p = 0.07) and percentage predicted forced vital capacity (FVC; median 57% [IQR: 51, 73] vs. 52% [IQR: 45, 66], p=0.08) though differences did not reach significance. Patients treated with PDE5i survived longer than untreated patients (median 2.18 years [95% CI: 1.43, 3.04] vs. 0.94 years [0.69, 1.51], p = 0.003) independent of all other prognostic markers by Bayesian joint-modelling (HR 0.39, 95% CI: 0.23, 0.59, p < 0.001) and propensity-matched analyses (HR 0.38, 95% CI: 0.22, 0.58, p < 0.001). Survival difference with treatment was significantly larger if right ventricular function was normal, rather than abnormal, at presentation (+2.55 years, 95% CI: -0.03, +3.97 vs. +0.98 years, 95% CI: +0.47, +2.00, p = 0.04).

CONCLUSION: PDE5i treatment in ILD-PH should be investigated by a prospective randomized trial.

PMID:36172951 | DOI:10.1111/resp.14378

Zhongguo Fei Ai Za Zhi. 2022 Sep 28. doi: 10.3779/j.issn.1009-3419.2022.101.45. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrous interstitial lung disease of unknown etiology. IPF is also considered to be among the independent risk factors for lung cancer, increasing the risk of lung cancer by 7% and 20%. The incidence of IPF complicated with lung cancer, especially non-small cell lung cancer (NSCLC), is increasing gradually, but there is no consensus on unified management and treatment. IPF and NSCLC have similar pathological features. Both appear in the surrounding area of the lung. In pathients with IPF complicated with NSCLC, NSCLC often develops from the honeycomb region of IPF, but the mechanism of NSCLC induced by IPF remains unclear. In addition, IPF and NSCLC have similar genetic, molecular and cellular processes and common signal transduction pathways. The universal signal pathways targeting IPF and NSCLC will become potential therapeutic drugs for IPF complicated with NSCLC. This article examines the main molecular mechanisms involved in IPF and NSCLC and the research progress of drugs under development targeting these signal pathways. .

PMID:36167462 | DOI:10.3779/j.issn.1009-3419.2022.101.45

Am J Physiol Lung Cell Mol Physiol. 2022 Sep 27. doi: 10.1152/ajplung.00146.2022. Online ahead of print.

ABSTRACT

Senescent cells can drive age-related tissue dysfunction partially via a senescence-associated secretory phenotype (SASP) involving pro-inflammatory and pro-fibrotic factors. Cellular senescence has been associated with a structural and functional decline during normal lung aging and age-related diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Asthma in the elderly (AIE) represents a major healthcare burden. AIE is associated with bronchial airway hyperresponsiveness and remodeling, which involves increased cell proliferation and higher rates of fibrosis, and resistant to standard therapy. Airway smooth muscle (ASM) cells play a major role in asthma such as remodeling via modulation of inflammation and the extracellular matrix (ECM) environment. Whether senescent ASM accumulate in AIE and contribute to airway structural or functional changes is unknown. Lung tissues from elderly asthmatics showed greater airway fibrosis compared to age-matched non-asthmatics and young age controls. Isolated ASM from elderly asthmatics showed increased expression of multiple senescent markers including phospho-p53, p21, telomere-associated foci (TAF), as well as multiple SASP components. Senescence and SASP components were also increased with aging per se. These data highlight the presence of cellular senescence in AIE that may contribute to airway remodeling.

PMID:36166734 | DOI:10.1152/ajplung.00146.2022