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

Shock. 2022 Aug 1;58(2):137-146. doi: 10.1097/SHK.0000000000001960. Epub 2022 Jul 24.

ABSTRACT

Idiopathic pulmonary fibrosis is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. Interleukin (IL)-11 plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. In this study, we explore whether a potential antifibrotic agent fluorofenidone (FD) exerts its anti-inflammatory and antifibrotic effects through suppressing activation of the IL-11/MEK/ERK signaling pathway in vivo and in vitro. Male C57BL/6 J mice were intratracheally injected with bleomycin or saline. Fluorofenidone was administered throughout the course of the experiment. Lung tissue sections were stained with hemotoxylin and eosin, and Masson trichrome. Cytokines were measured using the enzyme-linked immunosorbent assay. The α-smooth muscle actin (α-SMA), fibronectin, and collagen I were measured using immunohistochemistry, and the phosphorylated extracellular signal-regulated kinase, phosphorylated mitogen-activated protein kinase, IL-11RA, and gp130 were measured using Western blot. The RAW264.7 cells and the normal human lung fibroblasts were treated with IL-11 and/or FD, IL-11RA-siRNA, or MEK inhibitor. The expressions of phosphorylated extracellular signal-regulated kinase, phosphorylated mitogen-activated protein kinase, IL-11RA, gp130, α-SMA, fibronectin, and collagen I were measured using Western blot and/or real-time polymerase chain reaction, and the cytokines were measured using enzyme-linked immunosorbent assay. Results showed that FD markedly reduced the expressions of IL-8, IL-18, IL-11, monocyte chemotactic protein-1, α-SMA, fibronectin, and collagen I in mice lung tissues. In addition, FD attenuated IL-11-induced expressions of α-SMA, fibronectin, and collagen I and inhibited IL-11RA, gp130, and phosphorylation of the ERK and MEK protein expression, as well as reduced the expressions of IL-8, IL-18, and monocyte chemotactic protein-1 in vitro. This study demonstrated that FD attenuated bleomycin-induced pulmonary inflammation and fibrosis in mice by inhibiting the IL-11/MEK/ERK signaling pathway.

PMID:36166195 | DOI:10.1097/SHK.0000000000001960

Sci Rep. 2022 Sep 26;12(1):16040. doi: 10.1038/s41598-022-20040-x.

ABSTRACT

Coronavirus disease 2019 (COVID-19) poses a serious threat to human health and life. The effective prevention and treatment of COVID-19 complications have become crucial to saving patients' lives. During the phase of mass spread of the epidemic, a large number of patients with pulmonary fibrosis and lung cancers were inevitably infected with the SARS-CoV-2 virus. Lung cancers have the highest tumor morbidity and mortality rates worldwide, and pulmonary fibrosis itself is one of the complications of COVID-19. Idiopathic lung fibrosis (IPF) and various lung cancers (primary and metastatic) become risk factors for complications of COVID-19 and significantly increase mortality in patients. Therefore, we applied bioinformatics and systems biology approaches to identify molecular biomarkers and common pathways in COVID-19, IPF, colorectal cancer (CRC) lung metastasis, SCLC and NSCLC. We identified 79 DEGs between COVID-19, IPF, CRC lung metastasis, SCLC and NSCLC. Meanwhile, based on the transcriptome features of DSigDB and common DEGs, we identified 10 drug candidates. In this study, 79 DEGs are the common core genes of the 5 diseases. The 10 drugs were found to have positive effects in treating COVID-19 and lung cancer, potentially reducing the risk of pulmonary fibrosis.

PMID:36163484 | DOI:10.1038/s41598-022-20040-x

BMJ Open Respir Res. 2022 Sep;9(1):e001337. doi: 10.1136/bmjresp-2022-001337.

ABSTRACT

BACKGROUND: Diffuse pulmonary ossification is a specific lung condition that is accompanied by underlying diseases. However, idiopathic dendriform pulmonary ossification (IDPO) is extremely rare, and the clinical features remain unclear. In this study, we aimed to report the clinical characteristics of IDPO.

METHODS: We conducted a nationwide survey of patients with IDPO from 2017 to 2019 in Japan and evaluated the clinical, radiological, and histopathological findings of patients diagnosed with IDPO.

RESULTS: Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.

CONCLUSIONS: IDPO develops at a young age with gradually progressive phenotype. Further research and long-term (>20 years) follow-up are required to clarify the pathogenesis and clinical findings in IDPO.

PMID:36162917 | DOI:10.1136/bmjresp-2022-001337

Turk J Med Sci. 2022 Feb;52(1):83-88. doi: 10.3906/sag-2107-13. Epub 2022 Feb 22.

ABSTRACT

BACKGROUND: To explore the frequency and clinical associations of radiologic pleuroparenchymal fibroelastosis (PPFE) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

METHODS: In this single-center retrospective study, high resolution computed tomography (HRCT) images of 105 patients with SSc-ILD were examined for the presence of PPFE. Demographic, clinical, laboratory, and pulmonary function test (PFT) data of patients with and without PPFE were compared.

RESULTS: PPFE was detected in 19 (18.1%) patients ('definite PPFE' in 13 and 'consistent with PPFE' in 6 patients). Patients with PPFE had higher age and longer disease duration than PPFE (-) patients (p < 0.05 for both). Radiologic usual interstitial pneumoniae (UIP) pattern was more frequent (26.3% vs. 4.7%, p = 0.01) and median force vital capacity (FVC) was lower in patients with PPFE (64% vs. 82%, p = 0.005). Spontaneous pneumothorax developed in one patient with PPFE. More deaths occured in PPFE (+) group during follow-up (31% vs. 11%, p = 0.04).

PMID:36161593 | DOI:10.3906/sag-2107-13

Nat Commun. 2022 Sep 26;13(1):5637. doi: 10.1038/s41467-022-33193-0.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study, we focus on the properties of airway basal cells (ABC) obtained from patients with IPF (IPF-ABC). Single cell RNA sequencing (scRNAseq) of bronchial brushes revealed extensive reprogramming of IPF-ABC towards a KRT17high PTENlow dedifferentiated cell type. In the 3D organoid model, compared to ABC obtained from healthy volunteers, IPF-ABC give rise to more bronchospheres, de novo bronchial structures resembling lung developmental processes, induce fibroblast proliferation and extracellular matrix deposition in co-culture. Intratracheal application of IPF-ABC into minimally injured lungs of Rag2-/- or NRG mice causes severe fibrosis, remodeling of the alveolar compartment, and formation of honeycomb cyst-like structures. Connectivity MAP analysis of scRNAseq of bronchial brushings suggested that gene expression changes in IPF-ABC can be reversed by SRC inhibition. After demonstrating enhanced SRC expression and activity in these cells, and in IPF lungs, we tested the effects of saracatinib, a potent SRC inhibitor previously studied in humans. We demonstrate that saracatinib modified in-vitro and in-vivo the profibrotic changes observed in our 3D culture system and novel mouse xenograft model.

PMID:36163190 | DOI:10.1038/s41467-022-33193-0

Turk J Med Sci. 2021 Dec;51(6):3082-3088. Epub 2021 Dec 13.

ABSTRACT

BACKGROUND: Phase III trials have demonstrated a significant efficacy and an acceptable safety for pirfenidone in patients having mild to moderate idiopathic pulmonary fibrosis (IPF). Real-life data on the use of pirfenidone 200 mg tablets are limited. This study aimed to investigate the efficacy and safety of pirfenidone 200 mg tablets for the treatment of IPF in a real-life setting.

METHODS: A retrospective, multicenter study conducted in four university hospitals in Turkey between January 2017 and January 2019. Clinical records of patients diagnosed with mild to moderate IPF and receiving pirfenidone (200 mg tablets, total 2400 mg/day) were reviewed retrospectively and consecutively. Pulmonary function measurements including forced vital capacity (FVC%) and diffusing capacity of the lungs for carbon monoxide (DLCO%) were analyzed at baseline and after 6-month of pirfenidone treatment. Descriptive statistics were expressed as mean, standard error or median (minimum-maximum), number and percentage, where appropriate.

RESULTS: The study included 82 patients, of whom 87.8% were males (mean age, 66 years). After 6-month of treatment, 7 patients discontinued the treatment. Of the remaining 75 patients, 71 (94.6%) remained stable, 4 (5.4%) had progressive disease as evident by a decline in the FVC% of at least 10% while on treatment, and 45 (61.3%) had improved cough. At least one adverse event (AE) associated with the treatment was observed in 28 (37.3%) patients.

DISCUSSION: Pirfenidone 200 mg was effective and well tolerated and associated with relatively mild and manageable AEs in IPF patients.

PMID:36161644