Am J Respir Crit Care Med. 2022 Sep 12. doi: 10.1164/rccm.202206-1075OC. Online ahead of print.

ABSTRACT

RATIONALE: Relatives of patients with familial interstitial pneumonia are at increased risk for pulmonary fibrosis, and develop preclinical pulmonary fibrosis (PrePF).

OBJECTIVES: We defined the incidence and progression of new onset PrePF; its relationship to survival among first degree relatives of families with familial interstitial pneumonia.

METHODS: This is a cohort study of family members with familial interstitial pneumonia who were initially screened with a questionnaire and chest HRCT scan, and approximately 4 years later, the evaluation was repeated. 493 asymptomatic first-degree relatives of patients with familial interstitial pneumonia were evaluated at baseline, and 296 (60%) of the original subjects participated in subsequent evaluation.

RESULTS: The median interval between HRCTs was 3.9 years (IQ range 3.5-4.4). 252 subjects who agreed to repeat evaluation were originally determined not to have PrePF at baseline; 16 developed PrePF. A conservative estimate of the annual incidence of PrePF is 1,023 per 100, 000 person years (95% CI 511-1831). Of 44 subjects with PrePF at baseline, 38.4% subjects had worsening dyspnea compared to 15.4% of those without PrePF (P=0.002). Usual interstitial pneumonia (UIP) by HRCT (P< 0.0002) and baseline quantitative fibrosis score (P<0.001) are also associated with worsening dyspnea. PrePF at the initial screen is associated with decreased survival (P< 0.001).

CONCLUSIONS: The incidence of PrePF in this at-risk population is at least 100-fold higher than that reported for sporadic idiopathic pulmonary fibrosis (IPF). While PrePF and IPF represent distinct entities, our study demonstrates that PrePF, like IPF, is progressive and associated with decreased survival.

PMID:36094461 | DOI:10.1164/rccm.202206-1075OC

Chest. 2022 Sep 8:S0012-3692(22)03709-6. doi: 10.1016/j.chest.2022.08.2233. Online ahead of print.

ABSTRACT

BACKGROUND: Functional capacity, as measured by the 6-minute walk test (6MWT), is often reduced in fibrotic interstitial lung disease (ILD). This study evaluated longitudinal changes and prognostic significance of 6MWT parameters and explored change in oxygenation status as a physiological criterion to define disease progression in patients with fibrotic ILD.

RESEARCH QUESTIONS: What are the trajectories and prognostic value of 6MWT parameters in patients with fibrotic ILD?

STUDY DESIGN AND METHODS: Using prospective registries in Australia and Canada, patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD were stratified by the presence of criteria for progressive pulmonary fibrosis (PPF). Cumulative incidence of exertional and resting hypoxemia and changes in 6-minute walk distance (6MWD) and composite indices (distance-saturation product and distance-saturation-oxygen product) were determined, with prognostic significance evaluated at the time of meeting criteria for PPF. New-onset exertional or resting hypoxemia was evaluated as another potential criterion for PPF.

RESULTS: IPF/PPF (n=126) and non-IPF/PPF (n=227) had similar cumulative incidence of exertional hypoxemia and annualized decline in 6MWD and composite indices, which varied across each PPF criterion. IPF/non-PPF (n=231) and non-IPF/non-PPF (n=531) had significantly lower incidence of hypoxemia than IPF/PPF, with annualized increase in 6MWD and composite indices in non-IPF/non-PPF. Exertional or resting hypoxemia at the time of meeting criteria for PPF was independently associated with reduced transplant-free survival in IPF and non-IPF, adjusting for patient demographics and lung function. Adding new-onset exertional or resting hypoxemia as a physiological criterion reduced the median time to development of PPF from 11.2 to 6.7 months in IPF and 11.7 to 5.6 months in non-IPF in patients who eventually met both definitions (p<0.001 for both).

INTERPRETATION: Patients with IPF/PPF and non-IPF/PPF have comparable deterioration in functional capacity. Oxygenation status provides prognostic information in PPF and may assist in defining disease progression in fibrotic ILD.

PMID:36089070 | DOI:10.1016/j.chest.2022.08.2233

Toxicol Appl Pharmacol. 2022 Sep 7:116228. doi: 10.1016/j.taap.2022.116228. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis, a condition with likely genetic and environmental etiology, is relatively more prevalent with poor prognosis in human males. However, the underlying mechanisms for these gender-associated differences in the severity of fibrosis remain unknown. Here, we tested the hypothesis that the transcriptomic repertoire of myeloid cells determines the higher susceptibility of male mice to bleomycin (BLM)-induced lung fibrosis. Adult mice were oropharyngeally challenged with saline or BLM. Lung injury, inflammation, and fibrosis was assessed, and airspace myeloid-cells were subjected to RNA-sequencing. As compared with the female mice, the male mice manifested significantly increased lung injury, inflammation, proinflammatory cytokines (IL-6, IL-1β, IL-7, and IP-10), and fibrosis in response to BLM challenge. Interestingly, several pro-inflammatory and extracellular matrix-associated genes were significantly up-regulated in male myeloid-cells compared to female myeloid-cells in the saline-control group. Similarly, BLM-challenge resulted in greater pro-inflammatory and pro-fibrotic transcriptomic changes in male compared to female myeloid cells. On the other hand, anti-inflammatory and regulatory cytokine, Il10 and Ifng respectively, were uniquely upregulated in female but not in male myeloid cells when compared to their respective saline-control groups. Further, cross-sex bone marrow transplantation experiments revealed that male hematopoietic progenitor cells (HPCs) increased the granulocytic infiltration in female mice while female HPCs decreased the granulocytic infiltration in male mice post-BLM challenge. These findings suggest that there are inherent transcriptomic differences between the male and female lung myeloid cells and that the pro-inflammatory nature of male myeloid cells is sufficient to increase the susceptibility of female mice to BLM-induced inflammation.

PMID:36087614 | DOI:10.1016/j.taap.2022.116228

Int Immunopharmacol. 2022 Sep 7;112:109208. doi: 10.1016/j.intimp.2022.109208. Online ahead of print.

ABSTRACT

Pulmonary fibrosis is common in the development of inflammatory lung diseases with no effective clinical drug treatment currently. As an essential redox enzyme, thioredoxin (Trx) has been reported to be involved in pulmonary fibrosis, but the mechanism is to be revealed. Therefore, in bleomycin-indued pulmonary fibrosis model in C57 mice, Trx activity and nitrated Trx were examined.,p38-MAPK apoptosis pathway was determined in lung tissues. Additionally, before BLM administration, C57/BL6 mice were treated with aminoguanidine (AG, a peroxynitrite scavenger), recombinant human Trx-1 (rhTrx-1), or SIN-1 (a peroxynitrite donor) nitrated Trx-1 (N-Trx-1). In bleomycin (BLM)-induced pulmonary fibrosis model in C57/BL6 mice, we observed that nitrated Trx increased, while its activity decreased, with the increase of alveolar epithelial cells (AECs)apoptosis by p38-MAPK pathway. We demonstrated that AG or rhTrx-1, but not N-Trx-1 significantly reduced pulmonary fibrosis. Taken together, the results above revealed that blockade of Trx-1 nitration, or supplementation of exogenous rhTrx-1, might represent novel therapies to attenuate pulmonary fibrosis in idiopathic pulmonary fibrosis patients.

PMID:36087509 | DOI:10.1016/j.intimp.2022.109208

BMC Pulm Med. 2022 Sep 9;22(1):340. doi: 10.1186/s12890-022-02134-4.

ABSTRACT

BACKGROUND: Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival.

METHODS: PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established.

RESULTS: Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9-78.8); p = 0.009].

CONCLUSION: Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis.

PMID:36085057 | DOI:10.1186/s12890-022-02134-4

Clin Respir J. 2022 Sep 9. doi: 10.1111/crj.13541. Online ahead of print.

ABSTRACT

OBJECTIVES: Interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) are the important drivers for excessive type-2 immunity. It has been well elucidated that IL-25/IL-33/TSLP plays an important role in allergic airway inflammation and remodeling, whereas their roles in idiopathic pulmonary fibrosis (IPF) still remained largely unclear. Herein, the aim of the review is to discuss the potential role and mechanism of IL-25/IL-33/TSLP on IPF by literature analysis and summary.

DATA SOURCE: We have done a literature search using the following terms: ("idiopathic pulmonary fibrosis" OR "IPF" OR "lung fibrosis") and (TSLP or "thymic stromal lymphopoietin" or IL-25 OR IL-17E OR IL-33) from the database of PubMed published in English up to July 2018.

STUDY SELECTION: We have totally found 58 articles by using the retrieval terms mentioned above. By careful title and abstract reading, 10 original research articles of high quality were enrolled for the full text reading and analysis. Two additional relevant studies were also included during the course of literature readings.

RESULTS: IL-25/IL-33/TSLP and their corresponding receptors, that is, IL-17BR/ST2L/TSLPR, are shown to be up-regulated both in IPF patients and bleomycin (BLM)-induced lung fibrosis mice model. IL-25 may promote lung fibrosis by activating IL-17BR+fibroblast and IL-17BR+ILC2 (type 2 innate lymphoid cell). Full length (fl)-IL-33, as a transcription factor mainly in the cell nucleus, mediated non-atopic lung inflammation and fibrosis by modulating expressions of several pro-fibrotic mediators, including transforming growth factor (TGF)-b1. By contrast, mature (m)-IL-33 potentiates lung fibrosis by recruiting ST2L+M2 macrophages and ST2L+ILC2 to enlarge type 2 immunity. TSLP was shown to directly promote CCL2 expression in primary human lung fibroblasts (pHLFs).

CONCLUSION: IL-25/IL-33/TSLP contributes to non-allergic lung fibrosis by mediating persistent abnormal epithelial-mesenchymal crosstalk. IL-25/IL-33/TSLP may serve the promising novel target for the treatment of IPF.

PMID:36082495 | DOI:10.1111/crj.13541

Molecules. 2022 Aug 26;27(17):5487. doi: 10.3390/molecules27175487.

ABSTRACT

The ATX-LPA-LPAR1 signaling pathway plays a universal role in stimulating diverse cellular responses, including cell proliferation, migration, survival, and invasion in almost every cell type. The ATX-LPAR1 axis is linked to several metabolic and inflammatory diseases including cancer, fibrosis, and rheumatoid arthritis. Numerous selective ATX or LPAR1 inhibitors have been developed and so far, their clinical efficacy has only been evaluated in idiopathic pulmonary fibrosis. None of the ATX and LPAR1 inhibitors have advanced to clinical trials for cancer and rheumatoid arthritis. Nonetheless, several research groups, including ours, have shown considerable benefit of simultaneous ATX and LPAR1 inhibition through combination therapy. Recent research suggests that dual-targeting therapies are superior to combination therapies that use two selective inhibitors. However, limited reports are available on ATX-LPAR1 dual inhibitors, potentially due to co-expression of multiple different LPARs with close structural similarities at the same target. In this review, we discuss rational design and future directions of dual ATX-LPAR1 inhibitors.

PMID:36080255 | DOI:10.3390/molecules27175487

J Clin Med. 2022 Aug 30;11(17):5081. doi: 10.3390/jcm11175081.

ABSTRACT

A method of rapidly pointing out the risk of developing persistent pulmonary fibrosis from a sample of blood is extraordinarily needed for diagnosis, prediction of death, and post-infection prognosis assessment. Collagen scar formation has been found to play an important role in the lung remodeling following SARS-CoV-2 infection. For this reason, the concentration of collagen degradation products in plasma may reflect the process of lung remodeling and determine the extent of fibrosis. According to our previously published results of an in vitro study, an increase in the concentration of type III collagen degradation products in plasma resulted in a decrease in the fluorescence lifetime of plasma at a wavelength of 450 nm. The aim of this study was to use time-resolved fluorescence spectroscopy to assess pulmonary fibrosis, and to find out if the lifetime of plasma fluorescence is shortened in patients with COVID-19. The presented study is thus far the only one to explore the fluorescence lifetime of plasma in patients with COVID-19 and pulmonary fibrosis. The time-resolved spectrometer Life Spec II with the sub-nanosecond pulsed 360 nm EPLED® diode was used in order to measure the fluorescence lifetime of plasma. The survival analysis showed that COVID-19 mortality was associated with a decreased mean fluorescence lifetime of plasma. The AUC of mean fluorescence lifetime in predicting death was 0.853 (95% CI 0.735-0.972, p &lt; 0.001) with a cut-off value of 7 ns, and with 62% sensitivity and 100% specificity. We observed a significant decrease in the mean fluorescence lifetime in COVID-19 non-survivors (p &lt; 0.001), in bacterial pneumonia patients without COVID-19 (p &lt; 0.001), and in patients diagnosed with idiopathic pulmonary fibrosis (p &lt; 0.001), relative to healthy subjects. Furthermore, these results suggest that the development of pulmonary fibrosis may be a real and serious problem in former COVID-19 patients in the future. A reduction in the mean fluorescence lifetime of plasma was observed in many patients 6 months after discharge. On the basis of these data, it can be concluded that a decrease in the mean fluorescence lifetime of plasma at 450 nm may be a risk factor for mortality, and probably also for pulmonary fibrosis in hospitalized COVID-19 patients.

PMID:36079011 | DOI:10.3390/jcm11175081

J Clin Med. 2022 Aug 26;11(17):5008. doi: 10.3390/jcm11175008.

ABSTRACT

The prevalence of obstructive sleep apnea (OSA) has greatly increased in recent years. Recent data suggest that severe and moderate forms of OSA affect between 6 and 17% of adults in the general population. Many papers are reporting the significantly increased prevalence of OSA in patients suffering from fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Therefore, we performed a systematic review and meta-analysis regarding the dependency between IPF and OSA. Due to the lack of papers focusing on IPF among OSA patients, we focused on the prevalence of OSA among IPF patients. In the search strategy, a total of 684 abstracts were identified, 496 after the removal of duplicates. After the screening of titles and abstracts, 31 studies were qualified for further full-text analysis for eligibility criteria. The final analysis was performed on 614 IPF patients from 18 studies, which met inclusion criteria. There were 469 (76.38%) IPF patients with OSA and 145 (23.62%) without. The mean age varied from 60.9 ± 8.1 up to 70.3 ± 7.9. The obtained prevalence was 76.4 (95% CI: 72.9-79.7) and 75.7 (95% CI: 70.1-80.9) for fixed and random effects, respectively. The median prevalence of OSA among non-IPF patients for all the ethnics groups included in this study was 16,4% (IQR: 3.4%-26.8%). The study provides strong evidence for the increased prevalence of OSA in IPF patients when comparing with the general OSA prevalence.

PMID:36078938 | DOI:10.3390/jcm11175008

Biomed Pharmacother. 2022 Sep;153:113487. doi: 10.1016/j.biopha.2022.113487. Epub 2022 Jul 31.

ABSTRACT

Idiopathic pulmonary fibrosis is a fatal lung disorder in which the etiology and pathogenesis are still unobvious. Effective treatments are urgently needed considering that lung transplantation is the only treatment that could improve outcomes. This study aimed to investigate the therapeutic significance of the dual administration of pimitespib, an HSP90 inhibitor, and nifuroxazide, a STAT3 inhibitor, against bleomycin-induced pulmonary fibrosis in rats. Our results revealed that pimitespib/nifuroxazide inhibited bleomycin-induced alterations in the structure and the function of the lungs. They demonstrated significant decreases in the BALF total and differential cell counts, LDH activity, and total protein. Concurrently, there was a reduction in the accumulation of collagen as proved by decreased hydroxyproline and the gene expression of COL1A1 accompanied by lower levels of PDGF-BB, TIMP-1, and TGF-β. The levels of IL-6 were also downregulated. Pimitespib-induced inhibition of HSP90 led to subsequent inhibition of HIF-1α and STAT3 client proteins since the closed HSP90 would not enclose its client proteins. Therefore, pimitespib resulted in the repression of HIF-1α/CREB-p300 HAT as well as the STAT3/CREB-p300 HAT nuclear interactions. On the other hand, nifuroxazide resulted in a notable decline in pSTAT3 and HIF-1α levels. Subsequently, the combined effects of both drugs led to a substantial reduction in ECM deposition. Herein, pimitespib augmented nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop. Our findings also disclose that this novel loop is a promising therapeutic attack site for possible pulmonary fibrosis repression studies. Therefore, the use of pimitespib/nifuroxazide embodies an evolutionary perspective in managing pulmonary fibrosis.

PMID:36076505 | DOI:10.1016/j.biopha.2022.113487

Korean J Intern Med. 2022 Sep;37(5):945-946. doi: 10.3904/kjim.2022.267. Epub 2022 Sep 1.

NO ABSTRACT

PMID:36068714 | DOI:10.3904/kjim.2022.267

Respir Res. 2022 Sep 7;23(1):235. doi: 10.1186/s12931-022-02154-y.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with decline in lung function and poor prognosis entailing significant impairment in quality of life and high socioeconomic burden. The aim of this study was to characterize clinical management and resources utilization of patients with IPF in Spain, according to predicted forced vital capacity (FVC) % at baseline.

METHODS: Prospective, non-interventional, multicentric real-world data study in patients with IPF in Spain with 12-months follow-up. Clinical management and resources utilization during study period were recorded and compared between groups. FVC decline and acute exacerbations occurrence and associated healthcare resource use were also analysed. FVC decline after 12 months was estimated as relative change.

RESULTS: 204 consecutive patients with IPF were included and divided according to baseline FVC % predicted value. At baseline, patients with FVC < 50% received significantly more pharmacological and non-pharmacological treatments, and more help from caregiver. During the 12-months follow-up, patients with FVC < 50% required more specialized care visits, emergency visits, hospitalizations, pulmonary functions tests, non-health resource use (special transportation), and pharmacological treatments (p < 0.05 for all comparisons). Moreover, patients with FVC < 50% at baseline experienced more AE-IPF (p < 0.05), requiring more health-related resources use (primary care visits, p < 0.05). FVC decline was observed in all groups over the 12 months. FVC decreased on average by 2.50% (95% CI: - 5.98 to 0.98) along the year. More patients experienced an FVC decline > 10% in the more preserved lung function groups than in the FVC < 50% group, because of their already deteriorated condition.

CONCLUSIONS: We observed a significantly higher annual IPF-related resource use in patients with more impaired lung function at baseline. Since FVC decreases irrespective of FVC% predicted at baseline, slowing IPF progression to maintain patients at early disease stages is relevant to improve IPF management and to optimize resource use.

TRIAL REGISTRATION: EU PAS register number EUPAS19387 [June 01, 2017].

PMID:36071483 | DOI:10.1186/s12931-022-02154-y

Monaldi Arch Chest Dis. 2022 Sep 7. doi: 10.4081/monaldi.2022.2356. Online ahead of print.

ABSTRACT

It is unknown what role chest ultrasound plays in distinguishing the various usual interstitial pneumonia (UIP) patterns of high-resolution chest tomography (HRCT). The purpose of this study was to see if there was a link between the results of chest ultrasound (u/s) and HRCT in patients with idiopathic pulmonary fibrosis (IPF). We performed chest u/s in 16 patients with UIP and probable UIP patterns to indeterminate UIP and alternative diagnosis patterns in this single center prospective study to determine any possible relationship with the HRCT findings. A chest radiologist reviewed each HRCT to determine the pattern in accordance with the American Thoracic Society (ATS) / European Respiratory Society (ERS) Guidelines. The local multidisciplinary committee validated the patients' diagnoses before they were included. When compared to the indeterminate for UIP or alternative diagnosis pattern group, there was a trend (p=0.07) toward the presence of more B lines in UIP or probable UIP patterns. There was no statistically significant difference in the presence of small, large, white lung, or pleural line thickening >5mm. Subgroup analysis revealed that patients with honeycombing were more likely to have a fragmented pleural line (p=0.04). To summarize, in our pilot study, chest u/s appears unable to differentiate UIP and probable UIP patterns from indeterminate UIP and alternative diagnosis patterns. However, it appears that this technique can be used to recognize the honeycombing pattern.

PMID:36069640 | DOI:10.4081/monaldi.2022.2356

Expert Rev Respir Med. 2022 Sep 7. doi: 10.1080/17476348.2022.2122444. Online ahead of print.

ABSTRACT

INTRODUCTION: :Cryobiopsy is a novel diagnostic technique for thoracic diseases which has been extensively investigated over the past 20 years. It was originally proposed for the diagnosis of endobronchial lesions and diffuse parenchymal lung disease due to limitations of conventional sampling techniques including small size and presence of artifacts.

AREAS COVERED: :We will review recent evidence related to the expanding use of cryobiopsy in thoracic diseases. To identify references, the MEDLINE database was searched from database inception until May 2022 for case series, cohort studies, randomized controlled trials, systematic reviews and meta-analyses related to cryobiopsy.

EXPERT OPINION: Cryobiopsy has expanding applications in the field of thoracic diseases. Evidence to support transbronchial cryobiopsy as an alternative to surgical lung biopsy is increasing and was recently endorsed as a conditional recommendation by the latest American Thoracic Society guideline update for Idiopathic Pulmonary Fibrosis. Developments in technology and technique, in particular the availability of a 1.1 mm flexible cryoprobe, have extended applications to pulmonary diseases, including diagnosis of interstitial lung diseases, peripheral pulmonary lesions, and lung transplant rejection.

PMID:36069255 | DOI:10.1080/17476348.2022.2122444

Respir Investig. 2022 Sep 3:S2212-5345(22)00111-3. doi: 10.1016/j.resinv.2022.07.004. Online ahead of print.

ABSTRACT

BACKGROUND: Acute exacerbation is an essential prognostic factor in idiopathic pulmonary fibrosis (IPF) and is the leading cause of death in Japanese patients with IPF. Its epidemiology, treatment status, and effect on IPF progression have been insufficiently investigated. We examined the incidence of acute exacerbation and treatment status before and after the onset of acute exacerbation in Japanese patients with IPF to provide basic information for treatment strategies.

METHODS: A Japanese claims database (April 2008-March 2019) from acute-care hospitals was analyzed. Incidence of acute exacerbation, time to the next event, and percentages of patients who received each treatment by the year before and after the onset of acute exacerbation were examined in patients diagnosed with IPF at least once. Acute exacerbation was defined according to the use of steroid pulse therapy.

RESULTS: We identified 9961 patients with IPF and 2629 acute exacerbations (average age at the time of acute exacerbation: 74.8 years, percentage of men: 79%). The annual incidence of acute exacerbation was approximately 10% between 2010 and 2018. The time to the next acute exacerbation shortened with increasing number of these events. The percentage of patients receiving antifibrotic drugs remained constant (30%-40%) throughout the period. The percentages of patients receiving steroid therapy, immunosuppressive drugs, and oxygen therapy increased after the onset of acute exacerbation compared with before the onset.

CONCLUSIONS: The annual incidence of acute exacerbation was approximately 10% in recent years. It is suggested that acute exacerbation worsens respiratory function in patients with IPF.

PMID:36068159 | DOI:10.1016/j.resinv.2022.07.004

Am J Respir Crit Care Med. 2022 Sep 6. doi: 10.1164/rccm.202208-1639ED. Online ahead of print.

NO ABSTRACT

PMID:36066856 | DOI:10.1164/rccm.202208-1639ED

Eur Radiol. 2022 Sep 6. doi: 10.1007/s00330-022-09101-x. Online ahead of print.

ABSTRACT

OBJECTIVES: To identify and evaluate predictive lung imaging markers and their pathways of change during progression of idiopathic pulmonary fibrosis (IPF) from sequential data of an IPF cohort. To test if these imaging markers predict outcome.

METHODS: We studied radiological disease progression in 76 patients with IPF, including overall 190 computed tomography (CT) examinations of the chest. An algorithm identified candidates for imaging patterns marking progression by computationally clustering visual CT features. A classification algorithm selected clusters associated with radiological disease progression by testing their value for recognizing the temporal sequence of examinations. This resulted in radiological disease progression signatures, and pathways of lung tissue change accompanying progression observed across the cohort. Finally, we tested if the dynamics of marker patterns predict outcome, and performed an external validation study on a cohort from a different center.

RESULTS: Progression marker patterns were identified and exhibited high stability in a repeatability experiment with 20 random sub-cohorts of the overall cohort. The 4 top-ranked progression markers were consistently selected as most informative for progression across all random sub-cohorts. After spatial image registration, local tracking of lung pattern transitions revealed a network of tissue transition pathways from healthy to a sequence of disease tissues. The progression markers were predictive for outcome, and the model achieved comparable results on a replication cohort.

CONCLUSIONS: Unsupervised learning can identify radiological disease progression markers that predict outcome. Local tracking of pattern transitions reveals pathways of radiological disease progression from healthy lung tissue through a sequence of diseased tissue types.

KEY POINTS: • Unsupervised learning can identify radiological disease progression markers that predict outcome in patients with idiopathic pulmonary fibrosis. • Local tracking of pattern transitions reveals pathways of radiological disease progression from healthy lung tissue through a sequence of diseased tissue types. • The progression markers achieved comparable results on a replication cohort.

PMID:36066734 | DOI:10.1007/s00330-022-09101-x

J Ethnopharmacol. 2022 Sep 2:115674. doi: 10.1016/j.jep.2022.115674. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects.

AIM OF THE STUDY: Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM.

MATERIALS AND METHODS: The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway.

RESULTS: The results of network composite module analysis showed that ZKMG contained 174 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection.

CONCLUSIONS: The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research.

PMID:36064149 | DOI:10.1016/j.jep.2022.115674

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Sep;38(3):269-272. doi: 10.12047/j.cjap.6247.2022.051.

NO ABSTRACT

PMID:36062798 | DOI:10.12047/j.cjap.6247.2022.051

Heliyon. 2022 Jun 30;8(8):e09773. doi: 10.1016/j.heliyon.2022.e09773. eCollection 2022 Aug.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF), a disorder observed mostly in older human beings, is characterised by chronic and progressive lung scarring leading to an irreversible decline in lung function. This health condition has a dismal prognosis and the currently available drugs only delay but fail to reverse the progression of lung damage. Consequently, it becomes imperative to discover improved therapeutic compounds and their cellular targets to cure IPF. In this regard, a number of recent studies have targeted the epigenetic regulation by histone deacetylases (HDACs) to develop and categorise antifibrotic drugs for lungs. Therefore, this review focuses on how aberrant expression or activity of Classes I, II and III HDACs alter TGF-β signalling to promote events such as epithelial-mesenchymal transition, differentiation of activated fibroblasts into myofibroblasts, and excess deposition of the extracellular matrix to propel lung fibrosis. Further, this study describes how certain chemical compounds or dietary changes modulate dysregulated HDACs to attenuate five faulty TGF-β-dependent profibrotic processes, both in animal models and cell lines replicating IPF, thereby identifying promising means to treat this lung disorder.

PMID:36061031 | PMC:PMC9434059 | DOI:10.1016/j.heliyon.2022.e09773