Respir Med. 2022 Jul 16;201:106933. doi: 10.1016/j.rmed.2022.106933. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is diagnosed incidentally in some patients with minimal or no respiratory symptoms. The clinical features of such patients are unknown. Herein we aimed to clarify the prevalence, clinical course, and prognostic factors of patients who were incidentally diagnosed with IPF.

METHODS: The files of consecutive patients with newly diagnosed IPF were retrospectively reviewed to determine the methods involved in their diagnosis, and their outcomes.

RESULTS: Among a total of 107 patients with newly diagnosed IPF, 35 (32.7%) were diagnosed incidentally, including 18 undergoing annual health check-ups and 17 undergoing assessment for other medical problems. The median survival from the time of diagnosis was 4.9 years for the 35 patients diagnosed incidentally, which was comparable to the median survival of 3.9 years for the 72 who were not diagnosed incidentally. The body mass index (BMI) was the sole independent predictor of survival (hazard ratio 0.78, 95% confidence interval 0.65-0.93, p = 0.006) in patients diagnosed incidentally.

CONCLUSIONS: Nearly one third of patients with IPF were diagnosed incidentally, and their survival was still poor. Identifying patients during the earliest stage of IPF, particularly those with a low BMI, is warranted.

PMID:35930918 | DOI:10.1016/j.rmed.2022.106933

Chron Respir Dis. 2022 Jan-Dec;19:14799731221117298. doi: 10.1177/14799731221117298.

ABSTRACT

OBJECTIVES: Sarcopenia is a syndrome characterized by reduced muscle mass and function. It is well-recognized as a complication in chronic diseases such as chronic obstructive pulmonary disease. However, little is known about sarcopenia in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the clinical characteristics of sarcopenia and the association between quality of life and sarcopenia in patients with IPF.

METHODS: In this pilot cross-sectional study, 56 Japanese outpatients with IPF (49 men) were enrolled prospectively. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2019. Its associations with clinical parameters including age, pulmonary functions, physical performance, and patient-reported outcomes (PROs) were examined.

RESULTS: The frequency of sarcopenia was 39.3% (n = 22) in this cohort. There were significant differences in St George's Respiratory Questionnaire (p = .005), modified Medical Research Council score (p = .004), and Hospital and Anxiety Depression Scale depression score (p = .030) between the sarcopenic and non-sarcopenic groups. On multivariate regression analysis, 6-min walk distance (6MWD) was an independent factor associated with sarcopenia (odds ratio 1.241, 95% confidence interval 1.016-1.515, p = .034).

CONCLUSION: Sarcopenia was associated with PROs and physical performance in patients with IPF.

PMID:35930440 | DOI:10.1177/14799731221117298

J Thorac Dis. 2022 Jul;14(7):2481-2492. doi: 10.21037/jtd-22-40.

ABSTRACT

BACKGROUND: Non-idiopathic pulmonary fibrosis fibrosing interstitial lung diseases (F-ILDs) may demonstrate a progressive disease trajectory similar to idiopathic pulmonary fibrosis (IPF). We aimed to identify novel F-ILD phenotypes in a multi-ethnic South-East Asian population.

METHODS: F-ILD subjects (n=201) were analysed using unsupervised hierarchical cluster analysis and their outcomes compared against IPF (n=86).

RESULTS: Four clusters were identified. Cluster 1 (n=53, 26.4%) comprised older Chinese males with high body mass index (BMI) and comorbidity burden, higher baseline forced vital capacity (FVC) percentage predicted and lower diffusing capacity of the lung for carbon monoxide (DLCO) percentage predicted. They had similar mortality to IPF. Cluster 2 (n=67, 33.3%) had younger female non-smokers with low comorbidity burden, groundglass changes on high-resolution chest computed tomography (HRCT) and a positive anti-nuclear antibody (ANA) titre ≥1:160. They had lower baseline FVC and higher DLCO, low mortality and slower lung function decline. Cluster 3 (n=42, 20.9%) consisted male smokers with low comorbidity burden, emphysema on HRCT and high baseline lung function. They had low mortality and slow lung function decline. Cluster 4 (n=39, 19.4%) was the highest risk and comprised of mainly Indians with high BMI. They had the highest proportion of ischemic heart disease (IHD) and previous pulmonary tuberculosis. Subjects had the lowest baseline lung function, highest mortality, and fastest lung function decline. Survival differences across clusters remained significant following adjustment for treatment.

CONCLUSIONS: We identified four distinct F-ILD clinical phenotypes with varying disease trajectories. This demonstrates heterogeneity in F-ILD and the need for complementary approaches for classification and prognostication beyond ATS/ERS guideline diagnosis.

PMID:35928611 | PMC:PMC9344411 | DOI:10.21037/jtd-22-40

Respir Res. 2022 Aug 4;23(1):201. doi: 10.1186/s12931-022-02116-4.

ABSTRACT

BACKGROUND: Aberrant extracellular matrix (ECM) deposition and remodelling is important in the disease pathogenesis of pulmonary fibrosis (PF). We characterised neoepitope biomarkers released by ECM turnover in lung tissue from bleomycin-treated rats and patients with PF and analysed the effects of two antifibrotic drugs: nintedanib and pirfenidone.

METHODS: Precision-cut lung slices (PCLS) were prepared from bleomycin-treated rats or patients with PF. PCLS were incubated with nintedanib or pirfenidone for 48 h, and levels of neoepitope biomarkers of type I, III and VI collagen formation or degradation (PRO-C1, PRO-C3, PRO-C6 and C3M) as well as fibronectin (FBN-C) were assessed in the culture supernatants.

RESULTS: In rat PCLS, incubation with nintedanib led to a reduction in C3M, reflecting type III collagen degradation. In patient PCLS, incubation with nintedanib reduced the levels of PRO-C3 and C3M, thus showing effects on both formation and degradation of type III collagen. Incubation with pirfenidone had a marginal effect on PRO-C3. There were no other notable effects of either nintedanib or pirfenidone on the other neoepitope biomarkers studied.

CONCLUSIONS: This study demonstrated that nintedanib modulates neoepitope biomarkers of type III collagen turnover and indicated that C3M is a promising translational neoepitope biomarker of PF in terms of therapy assessment.

PMID:35927669 | PMC:PMC9351157 | DOI:10.1186/s12931-022-02116-4

Qual Life Res. 2022 Aug 4. doi: 10.1007/s11136-022-03205-z. Online ahead of print.

ABSTRACT

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating chronic lung disease with a high symptom burden, which has a substantial impact on health-related quality of life (HRQoL). Our study aimed to assess the suitability of the EuroQol five-dimension (EQ-5D-5L) and the Assessment of Quality of Life- eight-dimension (AQoL-8D) questionnaires in measuring HRQoL as health state utility values (HSUVs) in an Australian IPF cohort.

METHODS: Data for estimation of health state utility values (HSUVs) were collected from participants of the Australian IPF Registry (AIPFR) using self-administered surveys which included the EQ-5D-5L and the AQoL-8D. Data on lung function and disease specific HRQoL instruments were collected from the AIPFR. Performance of the two instruments was evaluated based on questionnaire practicality, agreement between the two instruments and test performance (internal and construct validity).

RESULTS: Overall completion rates for the EQ-5D-5L and AQoL-8D were 96% and 85%, respectively. Mean (median) HSUVs were 0.65 (0.70) and 0.69 (0.72) for the EQ-5D-5L and AQoL-8D, respectively. There was reasonable agreement between the two instruments based on the Bland-Altman plot mean difference (-0.04) and intraclass correlation coefficient (0.84), however there were some fundamental differences. A larger range of values was observed with the EQ-5D-5L (-0.57-1.00 vs 0.16-1.00). The EQ-5D-5L had a greater divergent sensitivity and efficacy in relation to assessing HSUVs between clinical groupings. The AQoL-8D ,however, had a higher sensitivity to measure psychosocial aspects of HRQoL in IPF.

CONCLUSION: The EQ-5D-5L demonstrated superior performance when compared to AQoL-8D in persons with IPF. This may be attributable to the high symptom burden which is physically debilitating to which the EQ-5D-5L may be more sensitive.

PMID:35927542 | DOI:10.1007/s11136-022-03205-z

Pulm Ther. 2022 Aug 4. doi: 10.1007/s41030-022-00198-5. Online ahead of print.

ABSTRACT

INTRODUCTION: The disease origins of idiopathic pulmonary fibrosis (IPF), which occurs at higher rates in certain races/ethnicities, are not understood. The highest rates occur in white persons of European descent, particularly those with light skin, who are also susceptible to lysosomal organelle dysfunction of the skin leading to fibroproliferative disease . We had observed clinically that the vast majority of patients with IPF had light-colored eyes, suggesting a phenotypic characteristic.

METHODS: We pursued this observation through a research database from the USA Veterans Administration, a population that has a high occurrence of IPF due to predominance of elderly male smokers. Using this medical records database, which included facial photos, we compared the frequency of light (blue, green, hazel) and dark (light brown, brown) eyes among white patients diagnosed with IPF compared with a control group of lung granuloma only (no other radiologic evidence of interstitial lung disease).

RESULTS: Light eye color was significantly more prevalent in patients with IPF than in the control group with lung granuloma [114/147 (77.6%) versus 129/263 (49.0%], p < 0.001), indicating that light-colored eyes are a phenotype associated with IPF .

CONCLUSION: We provide evidence that light eye color is predominant among white persons with IPF.

PMID:35927537 | DOI:10.1007/s41030-022-00198-5

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Aug 12;45(8):775-782. doi: 10.3760/cma.j.cn112147-20220417-00327.

ABSTRACT

Objectives: To describe the clinical characteristics of patients with autoimmune diseases associated interstitial lung diseases (AID-ILD) initially presented with idiopathic pulmonary fibrosis (IPF) in a tertiary Chinese hospital. Methods: We conducted a retrospective analysis of 14 patients diagnosed with AID-ILD during the IPF follow-up between January 2016 and December 2021. Among the 14 enrolled AID-ILD cases, there were 13 males and 1 female, (69.71±9.07) years old (range from 55 y to 87 y). Results: Detailed clinical consultation and further laboratory analysis were performed during the follow-up when the IPF patients showed exaggerated dyspnea (7 cases), fever of unknown causes (6 cases), microscopic hematuria (5 cases), arthralgia and swelling (4 cases), arthralgia (2 cases), morning stiffness (2 cases) and renal failure (2 cases). Finally, 6 patients showed positive MPO-ANCA, one patient showed positive PR3-ANCA and 7 patients showed positive anti-CCP. During the IPF periods, 7 patients had received antifibrotic agents and 5 patients had been prescribed with N-acetylcysteine, and 1 patient had received antifibrotic agents after N-acetylcysteine. Among them, no medication was prescribed for one IPF patient. After they were diagnosed with AID-ILD, glucocorticoids and/or immunosuppressants were added for 13 of them. Thirteen of cases improved or stable after these treatments, but one didn't show significant changes. Conclusions: AID-UIP, especially ANCA-UIP, AAV-UIP or RA-UIP should be considered when the IPF patients showed fever of unknown origin, microscopic hematuria and/or arthritis related symptoms. They might benefit from the add-on glucocorticoids and/or immunosuppressants.

PMID:35927048 | DOI:10.3760/cma.j.cn112147-20220417-00327

Anal Chem. 2022 Aug 4. doi: 10.1021/acs.analchem.2c01866. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) has been characterized as a chronic inflammatory disease that leads to irreversible damage to pulmonary function. However, there is no specific IPF biomarker that can be used to distinguish IPF and not pneumonia. Endoplasmic reticulum (ER) stress is prominent in IPF. To search for a specific biomarker of IPF, we developed two ER-targeting two-photon (TP) fluorescent probes, TPER-ONOO and TPER-Cys, for peroxynitrite (ONOO-) and cysteine (Cys) imaging, respectively. A significant increase in Cys levels in the lungs was discovered only in mice with IPF, which implied that Cys might be an IPF biomarker candidate. Furthermore, we uncovered the mechanism of glutathione (GSH) deficiency in IPF, which was not due to Cys shortage but instead was attributable to impaired glutamate cysteine ligase and glutathione synthetase activities via ONOO--induced post-transcriptional modification. This work has potential to provide a new method for IPF early diagnosis and drug efficacy evaluation.

PMID:35924865 | DOI:10.1021/acs.analchem.2c01866

J Chest Surg. 2022 Aug 5;55(4):255-264. doi: 10.5090/jcs.22.057.

ABSTRACT

Globally, thousands of patients undergo lung transplantation owing to end-stage lung disease each year. As lung transplantation evolves, recommendations and indications are constantly being updated. In 2021, the International Society for Heart and Lung Transplantation published a new consensus document for selecting candidates for lung transplantation. However, it is still difficult to determine appropriate candidates for lung transplantation among patients with complex medical conditions and various diseases. Therefore, it is necessary to analyze each patient's overall situation and medical condition from various perspectives, and ongoing efforts to optimize the analysis will be necessary. The purpose of this study is to review the extant literature and discuss recent updates.

PMID:35924530 | DOI:10.5090/jcs.22.057

ERJ Open Res. 2022 Aug 1;8(3):00030-2022. doi: 10.1183/23120541.00030-2022. eCollection 2022 Jul.

ABSTRACT

Medication adherence studies in idiopathic pulmonary fibrosis (IPF) are limited, use cross-sectional designs and report discontinuation rates. We prospectively investigated adherence to pirfenidone in IPF patients using electronic monitoring, which provides insights on whether and when the medication was taken on a day-by-day basis. We investigated the impact of nonadherence on lung function and selected predictors for nonadherence based on the COM-B behavioural model. The longitudinal statistical analyses included generalised estimation equations and linear mixed effects models. 55 patients initiating pirfenidone were followed-up for 2 years after diagnosis (76.4% men, mean age 71.1 years (range 50-87 years), mean forced vital capacity (FVC) 88% predicted (sd 18.3), mean diffusing capacity of the lung for carbon monoxide (D LCO) 58.1% predicted (sd 14.7)). Our data showed an association (p=0.03) between the proportion of days with three pirfenidone intakes (i.e. dosing adherence) and FVC % predicted, whereby a high dosing adherence seemed necessary to maintain stable or improving FVC % predicted values. 58.2% of the participants were able to implement at least 90% correct dosing days, yet adherence significantly decreased over time. Too short dosing intervals had negative effects on lung function outcomes. Knowledge on IPF and self-reported adherence were significantly associated with electronically measured adherence. In conclusion, nonadherence is prevalent and might negatively affect lung function. Further research is needed on the impact of nonadherence on outcomes and its predictors, so that tailored interventions can be developed. Meanwhile, a self-report questionnaire could be used to identify adherence issues and teams should equip patients with knowledge about their treatment and how to take it.

PMID:35923422 | PMC:PMC9339768 | DOI:10.1183/23120541.00030-2022

Ann Thorac Cardiovasc Surg. 2022 Aug 2. doi: 10.5761/atcs.oa.22-00087. Online ahead of print.

ABSTRACT

PURPOSE: A pneumothorax occurs in 3%-8% of patients with idiopathic pulmonary fibrosis. A pneumothorax may predict a poor outcome in patients with interstitial lung disease (ILD), and it is difficult to treat patients with ILD and a pneumothorax.

PATIENTS AND METHODS: We retrospectively studied data from all 12 patients with ILD and a pneumothorax who underwent surgical treatment at Toho University Omori Medical Center Hospital between 2009 and 2021.

RESULTS: Of the 12 patients, 2 had home oxygen therapy preoperatively and were classified with grade IV interstitial pneumonia (IP). Six patients had preoperative pleurodesis and two had postoperative one using auto-blood. Three patients (25%) had multi-step surgery ≥2, and 5 patients had surgical resection of bullae. No patients had postoperative acute exacerbations and all were discharged from the hospital in a stable condition. The 5-year overall survival rate for all patients was 70.0%. The median survival time was not reached. One patient with unclassified IP was doing well 116 months after surgery.

CONCLUSION: Patients with ILD and a pneumothorax were shown to require multi-step surgical treatment and can anticipate long-term survival.

PMID:35922909 | DOI:10.5761/atcs.oa.22-00087

Sleep Breath. 2022 Aug 4. doi: 10.1007/s11325-022-02686-z. Online ahead of print.

ABSTRACT

PURPOSE: Sleep-related breathing disorders (SRBD) may be associated with a worse prognosis in idiopathic pulmonary fibrosis (IPF). However, the prevalence of sleep disorders in IPF and the pathophysiological link between SRBD and IPF is unclear.

PATIENTS AND METHODS: In this prospective trial, consecutive patients with stable IPF underwent polysomnography and cardiopulmonary exercise testing. Epworth sleepiness scale, Regensburg insomnia scale, and Pittsburgh sleep quality index were evaluated. Exclusion criteria were oxygen supplementation therapy, lung emphysema, and heart failure. For pairwise comparison of categorical data, the two-proportion z-test was applied. Correlation between continuous variables was assessed via the Pearson correlation coefficient. Patients without and with SRBD were compared. To find predictors for SRBD in IPF, multivariable logistic regression was applied.

RESULTS: A total of 74 IPF patients were evaluated and 45 patients (11 female, median age 74 years, forced vital capacity 71.3%, DLCO 53.9%) were analyzed. Any kind of sleep disorder was found in 89% of patients. SRBD was present in 49% (81% obstructive sleep apnea, 19% central sleep apnea), insomnia in 40%, and periodic leg movements in 47% of subjects. The SRBD subgroup presented with a significantly lower performance (workload(peak)%pred 86.5 vs. 101.0 (p = 0.036); V'O2(AT) 618.5 ml/min vs. 774.0 ml/min (p = 0.043)) and exhibited a significantly higher V'E/V'CO2(peak) of 43.0 l/l vs. 38.5 l/l (p = 0.037). In search of predictors for SRBD by logistic regression, workload(peak)%pred was identified as a significant variable (p = 0.033).

CONCLUSIONS: SRBD is frequent in IPF. Pulmonary vascular limitations may represent the pathophysiological link between IPF and SRBD. Workload(peak)%pred may be an independent risk factor for the occurrence of SRBD.

PMID:35922615 | DOI:10.1007/s11325-022-02686-z

Am J Respir Crit Care Med. 2022 Aug 3. doi: 10.1164/rccm.202207-1420LE. Online ahead of print.

NO ABSTRACT

PMID:35921176 | DOI:10.1164/rccm.202207-1420LE

Quant Imaging Med Surg. 2022 Aug;12(8):4176-4189. doi: 10.21037/qims-21-1133.

ABSTRACT

BACKGROUND: We aimed to evaluate the image quality, feasibility, and diagnostic performance of three-dimensional ultrashort echo time magnetic resonance imaging (3D UTE-MRI) to assess idiopathic pulmonary fibrosis (IPF) compared with high-resolution computed tomography (HRCT) and half-Fourier single-shot turbo spin-echo (HASTE) MRI.

METHODS: A total of 36 patients with IPF (34 men; mean age: 62±8 years, age range: 43 to 78 years) were prospectively included and underwent HRCT and chest MRI on the same day. Chest MRI was performed with a free-breathing 3D spiral UTE pulse sequence and HASTE sequence on a 1.5 T MRI. Two radiologists independently evaluated the image quality of the HRCT, HASTE, and 3D UTE-MRI. They assessed the representative imaging features of IPF, including honeycombing, reticulation, traction bronchiectasis, and ground-glass opacities. Image quality of the 3D UTE-MRI, HASTE, and HRCT were assessed using a 5-point visual scoring method. Kappa and weighted kappa analysis were used to measure intra- and inter-observer and inter-method agreements. Sensitivity (SE), specificity (SP), and accuracy (AC) were used to assess the performance of 3D UTE-MRI for detecting image features of IPF and monitoring the extent of pulmonary fibrosis. Linear regressions and Bland-Altman plots were generated to assess the correlation and agreement between the assessment of the extent of pulmonary fibrosis made by the 2 observers.

RESULTS: The image quality of HRCT was higher than that of HASTE and UTE-MRI (HRCT vs. UTE-MRI vs. HASTE: 4.9±0.3 vs. 4.1±0.7 vs. 3.0±0.3; P<0.001). Interobserver agreement of HRCT, HASTE, and 3D UTE-MRI when assessing pulmonary fibrosis was substantial and excellent (HRCT: 0.727≤ κ ≤1, P<0.001; HASTE: 0.654≤ κ ≤1, P<0.001; 3D UTE-MRI: 0.719≤ κ ≤0.824, P<0.001). In addition, reticulation (SE: 97.1%; SP: 100%; AC: 97.2%; κ =0.654), honeycombing (SE: 83.3%; SP: 100%; AC: 86.1%; κ =0.625) patterns, and traction bronchiectasis (SE: 94.1%; SP: 100%; AC: 94.4%, κ =0.640) were also well-visualized on 3D UTE-MRI, which was significantly superior to HASTE. Compared with HRCT, the sensitivity of 3D UTE-MRI to detect signs of pulmonary fibrosis (n=35) was 97.2%. The interobserver agreement in elevation of the extent of pulmonary fibrosis with HRCT and 3D UTE-MRI was R2=0.84 (P<0.001) and R2=0.84 (P<0.001), respectively. The extent of pulmonary fibrosis assessed with 3D UTE-MRI [median =9, interquartile range (IQR): 6.25 to 10.00] was lower than that from HRCT (median =12, IQR: 9.25 to 13.00; U=320.00, P<0.001); however, they had a positive correlation (R=0.72, P<0.001).

CONCLUSIONS: As a radiation-free non-contrast enhanced imaging method, although the image quality of 3D UTE-MRI is inferior to that of HRCT, it has high reproducibility to identify the imaging features of IPF and evaluate the extent of pulmonary fibrosis.

PMID:35919053 | PMC:PMC9338383 | DOI:10.21037/qims-21-1133

Genet Res (Camb). 2022 Jul 16;2022:7448481. doi: 10.1155/2022/7448481. eCollection 2022.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung fibrosis with a high mortality rate. This study aimed to uncover the underlying molecular features for different types of IPF. IPF microarray datasets were retrieved from GEO databases. Weighted gene co-expression analysis (WGCNA) was used and identified subgroup-specific WGCNA modules. Infiltration-level immune cells in different subgroups of microenvironments were analyzed with CIBERSORT algorithms. The result is we classified 173 IPF cases into two subgroups based on gene expression profiles, which were retrieved from the GEO databases. The SGRQ score and age were significantly higher in C2 than in C1. Using WGCNA, five subgroup-specific modules were identified. M4 was mainly enriched by MAPK signaling, which was mainly expressed in C2; M1, M2, and M3 were mainly enriched by metabolic pathways and Chemokine signaling, and the pathway of M5 was phagosome inflammation; M1, M2, M3, and M5 were mainly expressed in C1. Utilizing the CIBERSORT, we showed that the number of M1 macrophage cells, CD8 T cells, regulatory T cells (Tregs), and Plasma cells was significantly different between C1 and C2. We found the molecular subgroups of IPF revealed that cases from different subgroups may have their unique patterns and provide novel information to understand the mechanisms of IPF itself.

PMID:35919036 | PMC:PMC9308534 | DOI:10.1155/2022/7448481

BMC Pulm Med. 2022 Aug 2;22(1):297. doi: 10.1186/s12890-022-02089-6.

ABSTRACT

BACKGROUND: Recent years, idiopathic pulmonary fibrosis (IPF) is thought to be a disease of alveoli as well as small airways. This study aimed to demonstrate the clinical feature, predictor, and prognosis of small airway dysfunction (SAD) in Chinese patients with IPF.

METHODS: We enrolled 416 patients with IPF who hospitalized in Beijing Chao-Yang Hospital from 2000 to 2014 in this study, and the follow-up ended at December 2016. We collected demographic information, clinical examination results, spirometry results, HRCT results, and blood gas results during the study. Logistic regression analysis was used to identify the predictor for SAD. The COX proportional hazard model was used to analysis the prognosis effect of SAD.

RESULTS: Among all the participants, 165 (39.66%) patients had SAD. FEV1 (% predicted) and FEV3/FVC were significantly associated with SAD in patients with IPF. IPF patients with lower FEV1 (% predicted, OR 30.04, 95% CI 9.61-93.90) and FEV3/FVC (OR 77.76, 95% CI 15.44-391.63) had increased risk for SAD. Patients with SAD were associated with significantly increased risk of mortality in patients with IPF (HR 1.73, 95% CI 1.02-2.92), as well as in IPF patients without other pulmonary comorbidities (COPD, emphysema, and asthma).

CONCLUSIONS: Spirometry-defined SAD was like 40% in patients with IPF. Lower FEV1 (% predicted) and FEV3/FVC were main predictors for SAD. IPF patients with SAD showed poorer prognosis.

PMID:35918677 | DOI:10.1186/s12890-022-02089-6

Pulm Pharmacol Ther. 2022 Jul 30:102149. doi: 10.1016/j.pupt.2022.102149. Online ahead of print.

ABSTRACT

INTRODUCTION: While pirfenidone and nintedanib have greatly influenced the treatment of idiopathic pulmonary fibrosis (IPF), both drugs have significant early adverse drug reactions (ADRs) and almost nothing is known of their rare and delayed ADRs. We collected and analyzed pirfenidone- or nintedanib-related ADRs identified in a French rare lung disease center, recorded their profiles and identified potential safety signals.

METHODS: We analyzed the medical records of IPF patients treated with pirfenidone or nintedanib between January, 2011 and January, 2020 at the Rennes University Hospital to estimate the incidence of serious and non-serious ADRs cases due to each drug and the incidence of ADRs involving the cardiovascular, hepatobiliary, gastro-intestinal, dermatological, and metabolic/nutritional systems.

RESULTS: The 176 patients included 115 (65%) initially treated with pirfenidone and 61 (35%) given nintedanib. ADRs occurred in 78.3% of those given pirfenidone and in 70.5% of those given nintedanib. The incidence of first serious ADRs cases was about 33 per 100 person-years (100 PY) for both drugs; first non-serious pirfenidone ADRs cases were 102 per 100 PY and 130 per 100 PY for nintedanib. The incidence involving each organ system were quite similar, except for the gastro-intestinal and skin disorders. Cardiovascular disorders occurred in about 10 cases per 100 PY in both pirfenidone and nintedanib patients.

DISCUSSION: Most ADRs were consistent with the expected antifibrotic drug safety profiles. As arterial and venous thromboembolic events are rare, it is important to assess the risk associated with using antifibrotics by a dedicated pharmacoepidemiological study.

PMID:35918026 | DOI:10.1016/j.pupt.2022.102149

Tuberc Respir Dis (Seoul). 2022 Aug 2. doi: 10.4046/trd.2022.0031. Online ahead of print.

ABSTRACT

BACKGROUND: An accurate diagnosis in patients with interstitial lung diseases (ILDs) by multidisciplinary discussion (MDD) based on histopathologic information is essential for optimal treatment. Transbronchial lung cryobiopsy (TBLC) has increasingly been used as a diagnostic alternative to surgical lung biopsy. This study aimed to evaluate the appropriate methods of TBLC in patients with ILD in Korea.

METHODS: A total of 27 patients who underwent TBLC were included. TBLC procedure details and clinical MDD diagnosis using TBLC histopathologic information were retrospectively analyzed.

RESULTS: All procedures were performed under general anesthesia with the fluoroscopic guidance in the operation room using flexible bronchoscopy and endobronchial balloon blocker. The median procedure duration was less than 30 minutes, and the median number of biopsies per participant was 2. Most of the bleeding after TBLC was not severe, and the rate of pneumothorax was 25.9%. The most common histopathologic pattern was alternative (48.2%), followed by indeterminate (33.3%) and usual interstitial pneumonia (UIP)/probable UIP (18.5%). In the MDD after TBLC, the most common diagnosis was idiopathic pulmonary fibrosis (33.3%), followed by smoking-related ILD (25.9%), nonspecific interstitial pneumonia (18.6%), unclassifiable-ILD (14.8%), and others (7.4%).

CONCLUSIONS: This first single-center experience showed that TBLC using a flexible bronchoscopy and endobronchial balloon blocker with the fluoroscopic guidance under general anesthesia may be a safe and adequate diagnostic method for ILD patients in Korea. The diagnostic yield of MDD was 85.2%. Further studies are needed to evaluate the diagnostic yield and confidence of TBLC.

PMID:35916002 | DOI:10.4046/trd.2022.0031

PeerJ. 2022 Jul 27;10:e13775. doi: 10.7717/peerj.13775. eCollection 2022.

ABSTRACT

Fibroblasts, in particular myofibroblasts, are the critical effector cells in idiopathic pulmonary fibrosis (IPF), a deadly lung disease characterized by abnormal lung remodeling and the formation of "fibroblastic foci". Aberrant activation of TGF-β1 is frequently encountered and promotes fibroblast proliferation, activation, and differentiation in pulmonary fibrosis. Hence, the inhibition of TGF-β1-induced lung fibroblast activation holds promise as a therapeutic strategy for IPF. The present study aimed to investigate the potential effect and underlying mechanisms of bone morphogenetic protein 4 (BMP4) on TGF-β1-induced proliferation, apoptosis, activation and myofibroblast differentiation of adult lung fibroblasts. Here, we demonstrated that BMP4 expression was significantly decreased in TGF-β1-stimulated mouse primary lung fibroblasts (PLFs). BMP4 inhibited proliferation and apoptosis resistance of TGF-β1-stimulated mouse PLFs. BMP4 suppressed TGF-β1-induced fibroblast activation and differentiation in mouse PLFs. We also found that BMP4 inhibited TGF-β1-induced ERK and p38 MAPK phosphorylation. Our findings indicate that BMP4 exerts its anti-fibrotic effects by regulating fibroblast proliferation, apoptosis, activation and differentiation via the inhibition of the ERK/p38 MAPK signaling pathway, and thus has a potential for the treatment of pulmonary fibrosis.

PMID:35915750 | PMC:PMC9338752 | DOI:10.7717/peerj.13775

Mol Biol Rep. 2022 Aug 1. doi: 10.1007/s11033-022-07777-4. Online ahead of print.

ABSTRACT

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is the process by which epithelial cells transform into mesenchymal cells, which plays a significant role in lung fibrotic disease. Transforming growth factor-β1(TGF-β1) is considered to be the most effective EMT inducer. The purpose of this study was to investigate the effect of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) on TGF-β1-induced EMT and the underlying mechanisms in the human bronchial epithelial cell line BEAS-2B.

METHODS: Human bronchial epithelial BEAS-2B cells were treated with TGF-β1 and TNF-α separately or in combination for 24 h, and qRT-PCR, western blotting, immunofluorescence staining, and migration assays were used to investigate the EMT process. Moreover, to further explore the effect of the NF-κB pathway on the EMT process, inhibitor assays (BAY-117082, NF-κB inhibitor), wound healing assays, and western blotting were performed.

RESULTS: The results showed that both cytokines enhanced the transformation of BEAS-2B cells from epithelial to mesenchymal cells. In addition, combined treatment with TNF-α and TGF-β1 further reduced E-cadherin expression, which conversely elevated α-SMA and vimentin mRNA and protein levels. Correspondingly, the migration rate of BEAS-2B cells was also increased. Furthermore, inhibiting the NF-κB signaling pathway blocked the expression of EMT-related markers and NOX4 induced by TGF-β1 and TNF-α, as well as cell migration.

CONCLUSION: Taken together, TNF-α and TGF-β1 cooperatively promoted EMT and cell migration in BEAS-2B cells through the NF-κB/NOX4 signaling pathway.

PMID:35913579 | DOI:10.1007/s11033-022-07777-4