Respir Med. 2024 Feb 24:107577. doi: 10.1016/j.rmed.2024.107577. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with idiopathic interstitial pneumonia (IIP) have a favourable prognosis when they have interstitial pneumonia with autoimmune features (IPAF). However, precise IPAF-related findings from high-resolution computed tomography (HRCT) and lung histopathological specimens and the treatment response have not been fully determined. Therefore, this study was conducted to evaluate the relationship between findings on HRCT or lung histopathological specimens and the progression of interstitial pneumonia in patients with IPAF.

METHODS: This multicentre cohort study prospectively enrolled consecutive patients with IIP. At the diagnosis of IIP, we systematically evaluated 74 features suggestive of connective tissue diseases and followed them up. HRCT, lung specimens, serum antibodies, and the clinical course were also evaluated.

RESULTS: Among 222 patients with IIP, 26 (11.7%) fulfilled the IPAF criteria. During a median observation period of 36 months, patients with IPAF showed better survival than those without IPAF (p = 0.034). While histopathological findings were not related to IPAF, nonspecific interstitial pneumonia (NSIP) with organizing pneumonia (OP) overlap was the most prevalent HRCT pattern (p < 0.001) and the consolidation opacity was the most common radiological finding in IPAF (p = 0.017). Furthermore, in patients with IPAF, the diagnosis of COP or NSIP with OP overlap was associated with a higher increase in %FVC in 1 year than in those with idiopathic pulmonary fibrosis, NSIP, or unclassifiable IIP (p = 0.002).

CONCLUSIONS: This study shows the presence of consolidation opacity on HRCT and the diagnosis of COP or NSIP with OP overlap are associated with IPAF and its favourable treatment response in patients with IPAF.

PMID:38408707 | DOI:10.1016/j.rmed.2024.107577

MedComm (2020). 2024 Feb 23;5(2):e494. doi: 10.1002/mco2.494. eCollection 2024 Feb.

ABSTRACT

Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials.

PMID:38405059 | PMC:PMC10885188 | DOI:10.1002/mco2.494

Respir Res. 2024 Feb 26;25(1):101. doi: 10.1186/s12931-024-02721-5.

ABSTRACT

BACKGROUND: Although some studies have indicated that Psoriasis could contribute to the risk of idiopathic pulmonary fibrosis (IPF), no study has reported a clear causal association between them. Our aim was to explore the potential relationship between Psoriasis and IPF using Mendelian randomization (MR) design.

METHODS: To explore a causal association between Psoriasis and IPF, we used genetic instruments from the largest available genome-wide association study (GWAS) of European ancestry, including psoriasis (5314 cases, 457,619 controls) and IPF (1028 cases, 196,986 controls). Our main analyses were conducted by inverse-variance weighted (IVW) method with random-effects model, with the other complementary four analyses: weighted median method, weighted mode, multivariable MR and MR-Egger approach.

RESULTS: The results of IVW methods demonstrated that genetically predicted psoriasis was significantly associated with higher odds of IPF, with an odds ratio (OR) of 1.09 (95%CI, 1.01-1.18; P = 0.02). Weighted median method, weighted mode and multivariable MR also demonstrated directionally similar results (P < 0.05), while the MR-Egger regression did not reveal the impact of psoriasis on IPF (OR = 1.09, 95%CI, 0.98-1.21; P = 0.11). In addition, both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between psoriasis and IPF.

CONCLUSIONS: Our study provided potential evidence between genetically predicted psoriasis and IPF, which suggests that understanding the mutual risk factors between psoriasis and IPF can facilitate the clinical management of both diseases.

PMID:38403646 | DOI:10.1186/s12931-024-02721-5

Biomed Pharmacother. 2024 Feb 22;173:116282. doi: 10.1016/j.biopha.2024.116282. Online ahead of print.

ABSTRACT

Pulmonary fibrosis is a chronic and progressive lung disease characterized by the accumulation of scar tissue in the lungs, which leads to impaired lung function and reduced quality of life. The prognosis for idiopathic pulmonary fibrosis (IPF), which is the most common form of pulmonary fibrosis, is generally poor. The median survival for patients with IPF is estimated to be around 3-5 years from the time of diagnosis. Currently, there are two approved drugs (Pirfenidone and Nintedanib) for the treatment of IPF. However, Pirfenidone and Nintedanib are not able to reverse or cure pulmonary fibrosis. There is a need for new pharmacological interventions that can slow or halt disease progression and cure pulmonary fibrosis. This review aims to provide an updated overview of current and future drug interventions for idiopathic pulmonary fibrosis, and to summarize possible targets of potential anti-pulmonary fibrosis drugs, providing theoretical support for further clinical combination therapy or the development of new drugs.

PMID:38401514 | DOI:10.1016/j.biopha.2024.116282

Microorganisms. 2024 Jan 29;12(2):287. doi: 10.3390/microorganisms12020287.

ABSTRACT

The importance of lung microbiome changes in developing chronic lung allograft dysfunction (CLAD) after lung transplantation is poorly understood. The lung microbiome-immune interaction may be critical in developing CLAD. In this context, examining alterations in the microbiome and immune cells of the lungs following CLAD, in comparison to the lung condition immediately after transplantation, can offer valuable insights. Four adult patients who underwent lung retransplantation between January 2019 and June 2020 were included in this study. Lung tissues were collected from the same four individuals at two different time points: at the time of the first transplant and at the time of the explantation of CLAD lungs at retransplantation due to CLAD. We analyzed whole-genome sequencing using the Kraken2 algorithm and quantified the cell fractionation from the bulk tissue gene expression profile for each lung tissue. Finally, we compared the differences in lung microbiome and immune cells between the lung tissues of these two time points. The median age of the recipients was 57 years, and most (75%) had undergone lung transplants for idiopathic pulmonary fibrosis. All patients were administered basiliximab for induction therapy and were maintained on three immunosuppressants. The median CLAD-free survival term was 693.5 days, and the median time to redo the lung transplant was 843.5 days. Bacterial diversity was significantly lower in the CLAD lungs than at transplantation. Bacterial diversity tended to decrease according to the severity of the CLAD. Aerococcus, Caldiericum, Croceibacter, Leptolyngbya, and Pulveribacter genera were uniquely identified in CLAD, whereas no taxa were identified in lungs at transplantation. In particular, six taxa, including Croceibacter atlanticus, Caldiserium exile, Dolichospermum compactum, Stappia sp. ES.058, Kinetoplastibacterium sorsogonicusi, and Pulveribacter suum were uniquely detected in CLAD. Among immune cells, CD8+ T cells were significantly increased, while neutrophils were decreased in the CLAD lung. In conclusion, unique changes in lung microbiome and immune cell composition were confirmed in lung tissue after CLAD compared to at transplantation.

PMID:38399691 | DOI:10.3390/microorganisms12020287

Life (Basel). 2024 Feb 6;14(2):229. doi: 10.3390/life14020229.

ABSTRACT

Interstitial lung diseases comprise a heterogenous range of diffuse lung disorders, potentially resulting in pulmonary fibrosis. While idiopathic pulmonary fibrosis has been recognized as the paradigm of a progressive fibrosing interstitial lung disease, other conditions with a progressive fibrosing phenotype characterized by a significant deterioration of the lung function may lead to a burden of significant symptoms, a reduced quality of life, and increased mortality, despite treatment. There is now evidence indicating that some common underlying biological mechanisms can be shared among different chronic fibrosing disorders; therefore, different biomarkers for disease-activity monitoring and prognostic assessment are under evaluation. Thus, understanding the common pathways that induce the progression of pulmonary fibrosis, comprehending the diversity of these diseases, and identifying new molecular markers and potential therapeutic targets remain highly crucial assignments. The purpose of this review is to examine the main pathological mechanisms regulating the progression of fibrosis in interstitial lung diseases and to provide an overview of potential biomarker and therapeutic options for patients with progressive pulmonary fibrosis.

PMID:38398739 | DOI:10.3390/life14020229

J Clin Med. 2024 Feb 19;13(4):1160. doi: 10.3390/jcm13041160.

ABSTRACT

Background: We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim to quantify drivers of EndMT in IPF patients compared to normal controls (NCs). Methods: Lung resections from thirteen IPF patients and eleven NCs were immunohistochemically stained for EndMT drivers, including TGF-β1, pSmad-2/3, Smad-7, and β-catenin. Intima, media, and adventitia were analysed for expression of each EndMT driver in pulmonary arteries. Computer- and microscope-assisted Image ProPlus7.0 image analysis software was used for quantifications. Results: Significant TGF-β1, pSmad-2/3, Smad-7, and β-catenin expression was apparent across all arterial sizes in IPF (p < 0.05). Intimal TGF-β1, pSmad-2/3, Smad-7, and β-catenin were augmented in the arterial range of 100-1000 μm (p < 0.001) compared to NC. Intimal TGF-β1 and β-catenin percentage expression showed a strong correlation with the percentage expression of intimal vimentin (r' = 0.54, p = 0.05 and r' = 0.61, p = 0.02, respectively) and intimal N-cadherin (r' = 0.62, p = 0.03 and r' = 0.70, p = 0.001, respectively). Intimal TGF-β1 and β-catenin expression were significantly correlated with increased intimal thickness as well (r' = 0.52, p = 0.04; r' = 0.052, p = 0.04, respectively). Moreover, intimal TGF-β1 expression was also significantly associated with increased intimal elastin deposition (r' = 0.79, p = 0.002). Furthermore, total TGF-β1 expression significantly impacted the percentage of DLCO (r' = -0.61, p = 0.03). Conclusions: This is the first study to illustrate the involvement of active TGF-β/Smad-2/3-dependent and β-catenin-dependent Wnt signalling pathways in driving EndMT and resultant pulmonary arterial remodelling in patients with IPF. EndMT is a potential therapeutic target for vascular remodelling and fibrosis in general in patients with IPF.

PMID:38398472 | DOI:10.3390/jcm13041160

Biomedicines. 2024 Feb 8;12(2):402. doi: 10.3390/biomedicines12020402.

ABSTRACT

Mucin-1 is a multi-functional glycoprotein expressed by type II alveolocytes and may be detectable in the circulation following pulmonary fibrosis. The prognostic utility of baseline pre-treatment blood levels of mucin-1 in patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotics has not yet been fully established. We retrospectively studied a cohort of patients (from two hospitals) with IPF who were receiving pirfenidone for >12 weeks. Baseline blood mucin-1 levels were measured via sandwich enzyme-linked immunosorbent assays. We investigated the performance of mucin-1 levels in longitudinally predicting the risks of acute exacerbation of IPF (AE-IPF) and severe adverse outcomes (SAO), including lung transplantation and death. Seventy patients were included; 20 developed AE-IPF; and 31 had SAO during the follow-up period. Patients with baseline mucin-1 levels ≥2.5 ng/mL had enhanced risks of AE-IPF (adjusted hazard ratio [aHR], 14.07; 95% confidence interval [CI], 4.26-46.49) and SAO within 2 years (aHR, 7.87; 95% CI, 2.86-21.70) and anytime during the follow-up (aHR, 4.68; 95% CI, 2.11-10.39). The risks increased across subgroups with increasing mucin-1 levels. Patients in the "mucin-1 ≥ 2.5" group also exhibited an accelerated decline in DLCO. This study supports baseline blood mucin-1 levels as a biomarker for IPF that predicts adverse outcomes during pirfenidone treatment.

PMID:38398004 | DOI:10.3390/biomedicines12020402

Biomed Pharmacother. 2024 Feb 22;173:116298. doi: 10.1016/j.biopha.2024.116298. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease; its cause is unknown, and it leads to notable health problems. Currently, only two drugs are recommended for IPF treatment. Although these drugs can mitigate lung function decline, neither can improve nor stabilize IPF or the symptoms perceived by patients. Therefore, the development of novel treatment options for pulmonary fibrosis is required. The present study investigated the effects of a novel compound, caffeic acid ethanolamide (CAEA), on human pulmonary fibroblasts and evaluated its potential to mitigate bleomycin-induced pulmonary fibrosis in mice. CAEA inhibited TGF-β-induced α-SMA and collagen expression in human pulmonary fibroblasts, indicating that CAEA prevents fibroblasts from differentiating into myofibroblasts following TGF-β exposure. In animal studies, CAEA treatment efficiently suppressed immune cell infiltration and the elevation of TNF-α and IL-6 in bronchoalveolar lavage fluid in mice with bleomycin-induced pulmonary fibrosis. Additionally, CAEA exerted antioxidant effects by recovering the enzymatic activities of oxidant scavengers. CAEA directly inhibited activation of TGF-β receptors and protected against bleomycin-induced pulmonary fibrosis through inhibition of the TGF-β/SMAD/CTGF signaling pathway. The protective effect of CAEA was comparable to that of pirfenidone, a clinically available drug. Our findings support the potential of CAEA as a viable method for preventing the progression of pulmonary fibrosis.

PMID:38394850 | DOI:10.1016/j.biopha.2024.116298

Stem Cells Int. 2024 Feb 15;2024:3429565. doi: 10.1155/2024/3429565. eCollection 2024.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is an age-related lung interstitial disease that occurs predominantly in people over 65 years of age and for which there is a lack of effective therapeutic agents. It has demonstrated that mesenchymal stem cells (MSCs) including alveolar epithelial cells (AECs) can perform repair functions. However, MSCs lose their repair functions due to their distinctive aging characteristics, eventually leading to the progression of IPF. Recent breakthroughs have revealed that the degree of autophagic activity influences the renewal and aging of MSCs and determines the prognosis of IPF. Autophagy is a lysosome-dependent pathway that mediates the degradation and recycling of intracellular material and is an efficient way to renew the nonnuclear (cytoplasmic) part of eukaryotic cells, which is essential for maintaining cellular homeostasis and is a potential target for regulating MSCs function. Therefore, this review focuses on the changes in autophagic activity of MSCs, clarifies the relationship between autophagy and health status of MSCs and the effect of autophagic activity on MSCs senescence and IPF, providing a theoretical basis for promoting the clinical application of MSCs.

PMID:38390035 | PMC:PMC10883747 | DOI:10.1155/2024/3429565

Cureus. 2024 Jan 23;16(1):e52793. doi: 10.7759/cureus.52793. eCollection 2024 Jan.

ABSTRACT

This comprehensive review examines the diagnostic potential of bronchoalveolar lavage (BAL) in interstitial lung disease (ILD), emphasizing its accuracy and significance in various ILDs, including idiopathic pulmonary fibrosis (IPF), sarcoidosis, hypersensitivity pneumonitis, and connective tissue disease-associated ILD. The analysis underscores the importance of abnormalities in both cellular and non-cellular components of BAL fluid for precise ILD diagnosis. Recommendations advocate for the integration of BAL into clinical guidelines, a multidisciplinary diagnostic approach, and further standardization of procedures. Looking toward the future, ongoing research highlights technological advancements, biomarker discovery, and the integration of artificial intelligence in BAL interpretation. These developments not only promise to enhance ILD diagnosis but also offer prospects for a more personalized approach to patient management based on insightful patient stratification guided by BAL findings. This abstract encapsulates the key findings, recommendations, and future prospects identified in the review, providing a concise overview of the diagnostic potential of BAL in ILD.

PMID:38389607 | PMC:PMC10882258 | DOI:10.7759/cureus.52793

Respirol Case Rep. 2024 Feb 21;12(2):e01301. doi: 10.1002/rcr2.1301. eCollection 2024 Feb.

ABSTRACT

Forced vital capacity has been utilized as a parameter of disease progression in idiopathic pulmonary fibrosis (IPF); however, its measurement is difficult when patients do not understand or cooperate. Dynamic digital radiography (DDR) enables sequential chest X-ray imaging during breathing, with lower radiation doses compared to conventional fluoroscopy or computed tomography. There is accumulating evidence showing that parameters obtained from DDR, particularly those related to diaphragmatic dynamics, are correlated with pulmonary function parameters, and are useful for pathophysiological evaluation. We herein present two cases that suggest parameters obtained from DDR during supine normal tidal breathing may predict disease progression of IPF.

PMID:38384743 | PMC:PMC10880408 | DOI:10.1002/rcr2.1301

Front Med (Lausanne). 2024 Feb 7;11:1335758. doi: 10.3389/fmed.2024.1335758. eCollection 2024.

ABSTRACT

OBJECTIVE: This study aimed to identify clinical characteristics associated with the prevalence of progressive pulmonary fibrosis (PPF) in interstitial lung disease (ILD) and to develop a prognostic nomogram model for clinical use.

METHODS: In this single-centered, retrospective study, we enrolled ILD patients with relatively comprehensive clinical data and assessed the incidence of PPF within a year using collected demographics, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results. We used a training cohort of ILD patients to identify early predictors of PPF and then validated them in an internal validation cohort and subsets of ILD patients using a multivariable logistic regression analysis. A prognostic nomogram was formulated based on these predictors, and the accuracy and efficiency were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA).

RESULTS: Among the enrolled patients, 120 (39.09%) cases had connective tissue disease-associated interstitial lung disease (CTD-ILD), 115 (37.46%) had non-idiopathic pulmonary fibrosis idiopathic interstitial pneumonia (non-IPF IIP), and 35 (11.4%) had hypersensitivity pneumonitis (HP). Overall, 118 (38.4%) cases experienced pulmonary fibrosis progression. We found that baseline DLco% pred (OR 0.92; 95% CI, 8.93-0.95) was a protective factor for ILD progression, whereas combined pneumonia (OR 4.57; 95% CI, 1.24-18.43), modified Medical Research Council dyspnea score (mMRC) (OR 4.9; 95% CI, 2.8-9.5), and high-resolution computed tomography (HRCT) score (OR 1.22; 95% CI, 1.07-1.42) were independent risk factors for PPF. The AUC of the proposed nomogram in the development cohort was 0.96 (95% CI, 0.94, 0.98), and the calibration plot showed good agreement between the predicted and observed incidence of PPF (Hosmer-Lemeshow test: P = 0.86).

CONCLUSION: ILD patients with combined pneumonia, low baseline DLco% pred, high mMRC marks, and high HRCT scores were at higher risk of progression. This nomogram demonstrated good discrimination and calibration, indicating its potential utility for clinical practice.

PMID:38384414 | PMC:PMC10879408 | DOI:10.3389/fmed.2024.1335758

Front Pharmacol. 2024 Feb 7;15:1309712. doi: 10.3389/fphar.2024.1309712. eCollection 2024.

ABSTRACT

Background: A growing population of individuals diagnosed with idiopathic pulmonary fibrosis (IPF) are receiving treatment with nintedanib and pirfenidone. The aim of our study was to assess the incidence of drug-induced liver injury (DILI) associated with the use of pirfenidone and nintedanib in patients with IPF in Taiwan. Methods: We collected a cohort of adult patients diagnosed with IPF between 2017 and 2020. The research outcomes involved assessing the incidence of DILI in patients treated with nintedanib or pirfenidone. Poisson regression analysis was employed to estimate incidence rates, with and without adjustments for covariates, to calculate and present both unadjusted and adjusted incidence rate ratios (IRRs). Results: The risk of DILI was greater in patients who received nintedanib than in those who received pirfenidone during the 1-year follow-up. Patients treated with nintedanib exhibited a heightened risk of DILI based on inpatient diagnoses using specific codes after adjusting for variables such as gender, age group, comorbidities and concomitant medications, with an adjusted incidence rate ratio (aIRR) of 3.62 (95% confidence interval (CI) 1.11-11.78). Similarly, the risk of DILI was elevated in patients treated with nintedanib according to a per-protocol Poisson regression analysis of outcomes identified from inpatient diagnoses using specific codes. This was observed after adjusting for variables including gender, age group, comorbidities, and concomitant medications, with an aIRR of 3.60 (95% CI 1.11-11.72). Conclusion: Data from postmarketing surveillance in Taiwan indicate that patients who received nintedanib have a greater risk of DILI than do those who received pirfenidone.

PMID:38384288 | PMC:PMC10879927 | DOI:10.3389/fphar.2024.1309712

Front Pharmacol. 2024 Feb 6;15:1358626. doi: 10.3389/fphar.2024.1358626. eCollection 2024.

ABSTRACT

Introduction: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease characterized by excessive deposition of extracellular matrix. Cannabidiol, a natural component extracted from plant cannabis, has been shown to have therapeutic effects on lung diseases, but its exact mechanism of action is unknown, hindering its therapeutic effectiveness. Methods: To establish a pulmonary fibrosis model, combined with UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing, to explore cannabidiol's mechanism in treating pulmonary fibrosis. The rats were randomly divided into the control group, pulmonary fibrosis model group, prednisone treatment group, and cannabidiol low, medium, and high dose groups. The expression levels of HYP, SOD, and MDA in lung tissue and the expression levels of TNF-α, IL-1β, and IL-6 in serum were detected. Intestinal microbiota was detected using UPLC-QTOF/MS analysis of metabolomic properties and 16S rDNA sequencing. Results: Pathological studies and biochemical indexes showed that cannabidiol treatment could significantly alleviate IPF symptoms, significantly reduce the levels of TNF-α, IL-1β, IL-6, MDA, and HYP, and increase the expression level of SOD (p < 0.05). CBD-H can regulate Lachnospiraceae_NK4A136_group, Pseudomonas, Clostridia_UCG-014, Collinsella, Prevotella, [Eubacterium]_coprostanoligenes_group, Fusobacterium, Ruminococcus, and Streptococcus, it can restore intestinal microbiota function and reverse fecal metabolism trend. It also plays the role of fibrosis through the metabolism of linoleic acid, glycerol, linolenic acid, and sphingolipid. Discussion: Cannabidiol reverses intestinal microbiota imbalance and attenuates pulmonary fibrosis in rats through anti-inflammatory, antioxidant, and anti-fibrotic effects. This study lays the foundation for future research on the pathological mechanisms of IPF and the development of new drug candidates.

PMID:38379898 | PMC:PMC10877013 | DOI:10.3389/fphar.2024.1358626

Zhonghua Er Ke Za Zhi. 2024 Mar 2;62(3):268-272. doi: 10.3760/cma.j.cn112140-20231102-00341.

ABSTRACT

Objective: To analyze the clinical features of children with cryptogenic organizing pneumonia (COP) confirmed by pathology. Methods: The clinical manifestations, imaging, pathology, treatment and outcome data of 4 children with COP confirmed by thoracoscopic lung biopsy were retrospectively analyzed, who were hospitalized at Respiratory Department of Shenzhen Children's Hospital from January 2004 to December 2022. Results: All of the 4 patients were male, the age ranged from 1 year 3 months to 14 years. The time from onset to diagnosis was 3 months to 3 years. The follow-up duration was 6 months to 6 years. All the 4 cases had cough, 2 cases had tachypnea and wheezing, 1 case had expectoration, 1 case had chest pain, 1 case had decreased activity tolerance and weight loss. Rales in 2 cases and hypoxemia in 1 case. Pulmonary high resolution CT showed diffuse distribution, involvement of both lungs in 3 cases, and single lung combined migration in 1 case.Three cases showed ground-glass opacity, consolidation, patchy or fibrous strips, and 1 case presented air bronchogram and "reversed halo sign". All the 4 cases were performed thoracoscopic lung biopsy, and the pathological findings showed cellulose exudate or small nodules filled with granulation tissue or fibroblasts in the alveolar cavity and small airways, and 1 case was Masson corpuscle positive. Three patients achieved remission after glucocorticoid therapy. Spontaneous remission without treatment was seen in 1 patient.Two cases were followed up for 17 months and 6 years, respectively, who had excellent outcome. Conclusions: The manifestations of COP in children include cough, expectoration and chest pain. Infants and young children may have tachypnea and wheezing. The most common chest CT findings are diffuse distribution of ground-glass opacity, patchy and consolidation in both lungs. Diagnosis should depend on pathological examination. The effect of glucocorticoid therapy is good.

PMID:38378290 | DOI:10.3760/cma.j.cn112140-20231102-00341

BMJ Open Respir Res. 2024 Feb 20;11(1):e001803. doi: 10.1136/bmjresp-2023-001803.

ABSTRACT

BACKGROUND: S100A9 is a damage-associated molecular pattern protein that may play an important role in the inflammatory response and fibrotic processes. Paquinimod is an immunomodulatory compound that prevents S100A9 activity. Its safety and pharmacokinetics have been confirmed in human clinical trials. In this study, we investigated the effects of paquinimod in preventing the development of lung fibrosis in vivo and examined the prognostic values of circulatory and lung S100A9 levels in patients with idiopathic pulmonary fibrosis (IPF).

METHODS: The expression and localisation of S100A9 and the preventive effect of S100A9 inhibition on fibrosis development were investigated in a mouse model of bleomycin-induced pulmonary fibrosis. In this retrospective cohort study, the S100A9 levels in the serum and bronchoalveolar lavage fluid (BALF) samples from 76 and 55 patients with IPF, respectively, were examined for associations with patient survival.

RESULTS: S100A9 expression was increased in the mouse lungs, especially in the inflammatory cells and fibrotic interstitium, after bleomycin administration. Treatment with paquinimod ameliorated fibrotic pathological changes and significantly reduced hydroxyproline content in the lung tissues of mice with bleomycin-induced pulmonary fibrosis. Additionally, we found that paquinimod reduced the number of lymphocytes and neutrophils in BALF and suppressed endothelial-mesenchymal transition in vivo. Kaplan-Meier curve analysis and univariate and multivariate Cox hazard proportion analyses revealed that high levels of S100A9 in the serum and BALF were significantly associated with poor prognoses in patients with IPF (Kaplan-Meier curve analysis: p=0.037 (serum) and 0.019 (BALF); multivariate Cox hazard proportion analysis: HR=3.88, 95% CI=1.06 to 14.21, p=0.041 (serum); HR=2.73, 95% CI=1.05 to 7.10, p=0.039 (BALF)).

CONCLUSIONS: The present results indicate that increased S100A9 expression is associated with IPF progression and that the S100A9 inhibitor paquinimod is a potential treatment for IPF.

PMID:38378778 | DOI:10.1136/bmjresp-2023-001803

Lung. 2024 Feb 20. doi: 10.1007/s00408-024-00673-7. Online ahead of print.

ABSTRACT

BACKGROUND: Diagnosis of idiopathic pulmonary fibrosis (IPF) typically relies on high-resolution computed tomography imaging (HRCT) or histopathology, while monitoring disease severity is done via frequent pulmonary function testing (PFT). More reliable and convenient methods of diagnosing fibrotic interstitial lung disease (ILD) type and monitoring severity would allow for early identification and enhance current therapeutic interventions. This study tested the hypothesis that a machine learning (ML) ensemble analysis of comprehensive metabolic panel (CMP) and complete blood count (CBC) data can accurately distinguish IPF from connective tissue disease ILD (CTD-ILD) and predict disease severity as seen with PFT.

METHODS: Outpatient data with diagnosis of IPF or CTD-ILD (n = 103 visits by 53 patients) were analyzed via ML methodology to evaluate (1) IPF vs CTD-ILD diagnosis; (2) %predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) moderate or mild vs severe; (3) %predicted Forced Vital Capacity (FVC) moderate or mild vs severe; and (4) %predicted FVC mild vs moderate or severe.

RESULTS: ML methodology identified IPF from CTD-ILD with AUCTEST = 0.893, while PFT was classified as DLCO moderate or mild vs severe with AUCTEST = 0.749, FVC moderate or mild vs severe with AUCTEST = 0.741, and FVC mild vs moderate or severe with AUCTEST = 0.739. Key features included albumin, alanine transaminase, %lymphocytes, hemoglobin, %eosinophils, white blood cell count, %monocytes, and %neutrophils.

CONCLUSION: Analysis of CMP and CBC data via proposed ML methodology offers the potential to distinguish IPF from CTD-ILD and predict severity on associated PFT with accuracy that meets or exceeds current clinical practice.

PMID:38376581 | DOI:10.1007/s00408-024-00673-7

Clin Infect Dis. 2024 Feb 20:ciad780. doi: 10.1093/cid/ciad780. Online ahead of print.

ABSTRACT

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials.

METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models.

RESULTS: Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time.

CONCLUSIONS: Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

PMID:38376212 | DOI:10.1093/cid/ciad780

Eur Rev Med Pharmacol Sci. 2024 Feb;28(3):1183-1193. doi: 10.26355/eurrev_202402_35357.

ABSTRACT

OBJECTIVE: The aim is to showcase the effectiveness and safety of bosentan or ambrisentan in individuals diagnosed with idiopathic pulmonary fibrosis (IPF) and offer fresh evidence for the management of this condition.

MATERIALS AND METHODS: For this research, we conducted a meta-analysis of randomized controlled trials by searching various databases, including the Cochrane Library, Excerpta Medica Database, PubMed, and Web of Science. The retrieval was conducted until November 2021. We analyzed the variances in 6-minute walk distance (6MWD), death, diffusion capacity for carbon monoxide (DLCO), forced vital capacity (FVC), hospitalization, IPF worsening, mean pulmonary arterial pressure, serious adverse events (SAEs), Short Form-36 improved, and St. George's Respiratory Questionnaire between the treatment and control groups.

RESULTS: A sum of six studies involving 1,928 participants were found to meet the inclusion criteria. The quality of evidence was high. The control group had significantly higher values for 6MWD, DLCO, and FVC compared to the ambrisentan treatment group. The rates of hospitalization and IPF worsening were considerably greater in comparison with the control group. The bosentan group exhibited significantly reduced rates of hospitalization and IPF worsening in comparison with the control group. Both drugs did not cause any raising in death or SAEs when in comparison with the control group.

CONCLUSIONS: The findings of this research validate the effectiveness and safety of bosentan for treating IPF patients. This medication can enhance the quality of life for individuals with IPF without causing any significant increase in SAEs. However, it does not have a notable influence on the long-term prognosis. The findings of this research do not endorse the utilization of ambrisentan in individuals diagnosed with IPF.

PMID:38375723 | DOI:10.26355/eurrev_202402_35357