J Clin Med. 2022 Sep 11;11(18):5336. doi: 10.3390/jcm11185336.

ABSTRACT

BACKGROUND: Although patients with idiopathic pulmonary fibrosis (IPF) often receive treatment with antifibrotic drugs (AFDs) and pulmonary rehabilitation (PR) concurrently, there are no reports on the effect of PR on patients with IPF receiving AFDs. Therefore, we investigated the effect of PR on patients with IPF receiving AFDs.

METHODS: Eighty-seven eligible patients with IPF (61 male; 72.0 ± 8.1 years; GAP severity stage I/II/III: 26/32/12) were recruited for the study. Patients who completed a 3-month outpatient PR program and those who did not participate were classified into four groups according to use of AFDs: PR group (n = 29), PR+AFD group (n = 11), treatment-free observational group (control group; n = 26), and AFD group (n = 21). There was no significant difference in age, sex, or severity among the groups. Patients were evaluated for physical functions such as 6-min walk distance (6MWD) and muscle strength, dyspnea, and health-related quality of life (HRQOL) at baseline and at 3 months.

RESULTS: In the PR group, dyspnea and 6MWD showed significant improvement after the 3-month PR program (p < 0.05 and p < 0.01, respectively). HRQOL was significantly worse at 3 months (p < 0.05) in the AFD group, but not in the other groups. The change in 6MWD from baseline to the 3-month time point was significantly higher in the PR+AFD group than in the AFD groups (p < 0.01).

CONCLUSIONS: It was suggested that AFD treatment reduced exercise tolerance and HRQOL at 3 months; however, the concurrent use of PR may prevent or mitigate these effects.

PMID:36142983 | DOI:10.3390/jcm11185336

Biomedicines. 2022 Sep 16;10(9):2298. doi: 10.3390/biomedicines10092298.

ABSTRACT

Mesenchyme Stem Cells (MSCs) are the most used types of stem cells in regenerative medicine. Regenerative medicine is a rapidly emerging medicine section that creates new methods to regrow, restore, and replace diseased and damaged tissues, organs, and cells. Scholars have shown a positive correlation between MSCs-based therapies and successful treatment of diseases like cardiac ischemia, cartilage problems, bone diseases, diabetes, and even neurological disorders. Although MSCs have several varying features that make them unique, their immuno-regulatory effects in tissue repair emerge from their secretion of paracrine growth factors, exosomes, and cytokines. These cells secrete a secretome, which has regenerative and reparative properties that lead to injury amelioration, immune modulation, or fibrosis reduction. Recent studies have shown that the administration MCSs derived conditioned medium (MSCs-CM) in acute doses in humans is safe and well-tolerated. Studies from animal models and human clinical trials have also shown that they are efficacious tools in regenerative medicine. In this review, we will explore the therapeutic potential of MSCs-CM in pulmonary fibrosis, with further insight into the treatment of Idiopathic Pulmonary Fibrosis (IPF).

PMID:36140399 | DOI:10.3390/biomedicines10092298

Biomedicines. 2022 Aug 31;10(9):2129. doi: 10.3390/biomedicines10092129.

ABSTRACT

Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients and compare disease behavior to that in idiopathic pulmonary fibrosis (IPF) patients. Patients with normal forced vital capacity (FVC > 80% predicted; SSc-ILD: n = 31; IPF: n = 53) were followed for at least 1 year. Predictors of functional decline including clinical symptoms, comorbidities, lung-function values, high-resolution CT pattern, and treatment data were analyzed. SSc-ILD patents were significantly younger (59.8 ± 13.1) and more often women (93 %) than IPF patients. The median yearly FVC decline was similar in both groups (SSc-ILD = -67.5 and IPF = -65.3 mL/year). A total of 11 SSc-ILD patients met the PPF criteria for functional deterioration, presenting an FVC decline of -153.9 mL/year. Cough and pulmonary hypertension were significant prognostic factors for SSc-ILD functional progression. SSc-ILD patients with normal initial spirometry presenting with cough and PH are at higher risk for showing progressive functional decline.

PMID:36140231 | DOI:10.3390/biomedicines10092129

Antioxidants (Basel). 2022 Sep 10;11(9):1789. doi: 10.3390/antiox11091789.

ABSTRACT

Glutathione (GSH), a major antioxidant in mammalian cells, regulates several vital cellular processes, such as nutrient metabolism, protein synthesis, and immune responses. In addition to its role in antioxidant defense, GSH controls biological processes through its conjugation to reactive protein cysteines in a post-translational modification known as protein S-glutathionylation (PSSG). PSSG has recently been implicated in the pathogenesis of multiple diseases including idiopathic pulmonary fibrosis (IPF). Hallmarks of IPF include repeated injury to the alveolar epithelium with aberrant tissue repair, epithelial cell apoptosis and fibroblast resistance to apoptosis, and the accumulation of extracellular matrix and distortion of normal lung architecture. Several studies have linked oxidative stress and PSSG to the development and progression of IPF. Additionally, it has been suggested that the loss of epithelial cell homeostasis and increased apoptosis, accompanied by the release of various metabolites, creates a vicious cycle that aggravates disease progression. In this short review, we highlight some recent studies that link PSSG to epithelial cell apoptosis and highlight the potential implication of metabolites secreted by apoptotic cells.

PMID:36139863 | DOI:10.3390/antiox11091789

Cells. 2022 Sep 13;11(18):2848. doi: 10.3390/cells11182848.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant activation of the alveolar epithelium, the expansion of the fibroblast population, and the accumulation of extracellular matrix. Global gene expression of human lung fibroblasts stimulated with TGFβ-1, a strong fibrotic mediator revealed the overexpression of ZNF365, a zinc finger protein implicated in cell cycle control and telomere stabilization. We evaluated the expression and localization of ZNF365 in IPF lungs and in the fibrotic response induced by bleomycin in WT and deficient mice of the orthologous gene Zfp365. In IPF, ZNF365 was overexpressed and localized in fibroblasts/myofibroblasts and alveolar epithelium. Bleomycin-induced lung fibrosis showed an upregulation of Zfp365 localized in lung epithelium and stromal cell populations. Zfp365 KO mice developed a significantly higher fibrotic response compared with WT mice by morphology and hydroxyproline content. Silencing ZNF365 in human lung fibroblasts and alveolar epithelial cells induced a significant reduction of growth rate and increased senescence markers, including Senescence Associated β Galactosidase activity, p53, p21, and the histone variant γH2AX. Our findings demonstrate that ZNF365 is upregulated in IPF and experimental lung fibrosis and suggest a protective role since its absence increases experimental lung fibrosis mechanistically associated with the induction of cell senescence.

PMID:36139424 | DOI:10.3390/cells11182848

Cells. 2022 Sep 9;11(18):2816. doi: 10.3390/cells11182816.

ABSTRACT

Idiopathic pulmonary fibrosis is a chronic intractable lung disease, leading to respiratory failure and death. Although anti-fibrotic agents delay disease progression, they are not considered curative treatments, and alternative modalities have attracted attention. We examined the effect of human γδ T cells on collagen type I in lung fibroblasts. Collagen type I was markedly reduced in a γδ T cell number-dependent manner following treatment with γδ T cells expanded with tetrakis-pivaloxymethyl 2-(thiazole-2-ylamino) ethylidene-1,1-bisphosphonate (PTA) and interleukin-2. Collagen type I levels remained unchanged on addition of γδ T cells to the culture system through a trans-well culture membrane, suggesting that cell-cell contact is essential for reducing its levels in lung fibroblasts. Re-stimulating γδ T cells with (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP) reduced collagen type I levels without cell-cell contact, indicating the existence of HMBPP-induced soluble anti-fibrotic factors in γδ T cells. Adding anti-interferon-γ (IFN-γ)-neutralizing mAb restored collagen type I levels, demonstrating that human γδ T cell-derived IFN-γ reduces collagen type I levels. Conversely, interleukin-18 augmented γδ T cell-induced suppression of collagen type I. Therefore, human γδ T cells reduce collagen levels in lung fibroblasts via two distinct mechanisms; adoptive γδ T cell transfer is potentially a new therapeutic candidate.

PMID:36139391 | DOI:10.3390/cells11182816

Biomolecules. 2022 Aug 29;12(9):1196. doi: 10.3390/biom12091196.

ABSTRACT

Reducing the health hazards caused by air pollution is a global challenge and is included in the Sustainable Development Goals. Air pollutants, such as PM2.5, induce respiratory and cardiovascular disorders by causing various inflammatory responses via oxidative stress. Catechins and polyphenols, which are components of green tea, have various protective effects, owing to their antioxidant ability. The main catechin in green tea, epigallocatechin gallate (EGCG), is potentially effective against respiratory diseases, such as idiopathic pulmonary fibrosis and asthma, but its effectiveness against air-pollution-dependent lung injury has not yet been investigated. In this study, we examined the effect of EGCG on urban aerosol-induced acute lung injury in mice. Urban aerosol treatment caused increases in inflammatory cell counts, protein levels, and inflammatory cytokine expression in the lungs of ICR mice, but pretreatment with EGCG markedly suppressed these responses. Analyses of oxidative stress revealed that urban aerosol exposure enhanced reactive oxygen species (ROS) production and the formation of ROS-activated neutrophil extracellular traps (NETs) in the lungs of mice. However, ROS production and NETs formation were markedly suppressed by pretreating the mice with EGCG. Gallocatechin gallate (GCG), a heat-epimerized form of EGCG, also markedly suppressed urban aerosol-dependent inflammatory responses and ROS production in vivo and in vitro. These findings suggest that EGCG and GCG prevent acute lung injury caused by urban aerosols through their inhibitory effects on ROS production. Thus, we believe that foods and medications containing EGCG or GCG may be candidates to prevent the onset and progression of acute lung injury caused by air pollutants.

PMID:36139034 | DOI:10.3390/biom12091196

Eur Respir J. 2022 Sep 22:2200777. doi: 10.1183/13993003.00777-2022. Online ahead of print.

ABSTRACT

BACKGROUND: Air pollutants are considered as non-negligible risk factors of idiopathic pulmonary fibrosis (IPF). However, the relationship between long-term air pollution and the incidence of IPF is unknown.

OBJECTIVE: To explore the associations of air pollutants with IPF risk and further assess modification effect of genetic susceptibility.

METHODS: Land-use regression model estimated concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), and particulate matter (PM2.5 and PM10). The polygenic risk score (PRS) was constructed using 13 independent SNPs. The Cox proportional hazard models were used to evaluate the associations of air pollutants with IPF risk and further investigate the modification effect of genetic susceptibility. Additionally, absolute risk was calculated.

RESULTS: Among 433 738 participants from the UK Biobank, the incidence of IPF was 27.45/1 00 000 person-years during a median follow-up of 11.78 years. The adjusted hazard ratios (HRs) [95% confidence interval (CIs)] of IPF for each interquartile range increase in NO2, NOx, and PM2.5 were 1.11 (1.03, 1.19), 1.07 (1.01, 1.13), and 1.09 (1.02, 1.17), respectively. PM2.5 had the highest population attribution risk, followed by NOx and NO2. There were additive interactions between NO2, NOx and PM2.5 and genetic susceptibility. Participants with high PRS and high air pollution had the highest risk of incident IPF compared to those with low PRS and low air pollution [NO2: 3.94 (2.77, 5.60); NOx: 3.08 (2.21, 4.27); PM2.5: 3.65 (2.60, 5.13); PM10: 3.23 (2.32, 4.50)].

CONCLUSION: Long-term air pollutants exposures may elevate the risk of incident IPF. There are additive effects of air pollutants and genetic susceptibility on IPF risk.

PMID:36137588 | DOI:10.1183/13993003.00777-2022

Lung. 2022 Sep 22. doi: 10.1007/s00408-022-00571-w. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible pulmonary interstitial disease that seriously affects the patient's quality of life and lifespan. The pathogenesis of IPF has not been clarified, and its treatment is limited to pirfenidone and nintedanib, which only delays the decline of lung function. Alveolar epithelial type 2 (AT2) cells are indispensable in the regeneration and lung surfactant secretion of alveolar epithelial cells. Studies have shown that AT2 cell dysfunction initiates the occurrence and progression of IPF. This review expounds on the AT2 cell dysfunction in IPF, involving senescence, apoptosis, endoplasmic reticulum stress, mitochondrial damage, metabolic reprogramming, and the transitional state of AT2 cells. This article also briefly summarizes potential treatments targeting AT2 cell dysfunction.

PMID:36136136 | DOI:10.1007/s00408-022-00571-w

Hum Mutat. 2022 Sep 22. doi: 10.1002/humu.24476. Online ahead of print.

ABSTRACT

The role of constitutional genetic defects in idiopathic pulmonary fibrosis (IPF) is increasingly appreciated. Monogenic disorders associated with IPF affect two pathways: telomere maintenance, accounting for approximately 10% of all patients with IPF, and surfactant biology, responsible for 1-3% of cases and often co-occurring with lung cancer. We examined the prevalence of rare variants in five surfactant-related genes, SFTPA1, SFPTA2, SFTPC, ABCA3, and NKX2-1, that were previously linked to lung disease in whole genome sequencing data from 431 patients with IPF. We identified functionally deleterious rare variants in SFTPA2 with a prevalence of 1.3% in individuals with and without a family history of IPF. All individuals had no personal history of lung cancer, but substantial bronchiolar metaplasia was noted on lung explants and biopsies. Five patients had novel missense variants in NKX2-1, but the contribution to disease is unclear. In general, patients were younger and had longer telomeres compared to the majority of patients with IPF suggesting that these features may be useful for identifying this subset of patients in the clinic. These data suggest that SFTPA2 variants may be more common in unselected IPF cohorts and may manifest in the absence of personal/family history of lung cancer or IPF. This article is protected by copyright. All rights reserved.

PMID:36135709 | DOI:10.1002/humu.24476

Respir Med Case Rep. 2022 Sep 13;39:101737. doi: 10.1016/j.rmcr.2022.101737. eCollection 2022.

ABSTRACT

A 77-year-old man was initially diagnosed with idiopathic pulmonary fibrosis (IPF) and treated with anti-fibrotic nintedanib. Despite undergoing anti-fibrotic treatment for one year, his condition remained unstable. The patient was admitted to our hospital for exertional dyspnea. We performed an exposure assessment, including 2-week antigen avoidance and an environmental inhalation challenge, and successfully re-diagnosed him with fibrotic hypersensitivity pneumonitis (HP), known as chronic farmer's lung. Adding oral glucocorticoids to the nintedanib treatment improved his condition. Although antigen avoidance and environmental inhalation challenge tests are not standardized, they may be useful for diagnosing fibrotic HP when properly applied.

PMID:36133420 | PMC:PMC9483807 | DOI:10.1016/j.rmcr.2022.101737

Sci Adv. 2022 Sep 23;8(38):eabo0987. doi: 10.1126/sciadv.abo0987. Epub 2022 Sep 21.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease, and the molecular mechanisms remain poorly understood. Our findings demonstrated that pyruvate kinase M2 (PKM2) promoted fibrosis progression by directly interacting with Smad7 and reinforcing transforming growth factor-β1 (TGF-β1) signaling. Total PKM2 expression and the portion of the tetrameric form elevated in lungs and fibroblasts were derived from mice with bleomycin (BLM)-induced pulmonary fibrosis. Pkm2 deletion markedly alleviated BLM-induced fibrosis progression, myofibroblast differentiation, and TGF-β1 signaling activation. Further study showed that PKM2 tetramer enhanced TGF-β1 signaling by directly binding with Smad7 on its MH2 domain, and thus interfered with the interaction between Smad7 and TGF-β type I receptor (TβR1), decreased TβR1 ubiquitination, and stabilized TβR1. Pharmacologically enhanced PKM2 tetramer by TEPP-46 promoted BLM-induced pulmonary fibrosis, while tetramer disruption by compound 3k alleviated fibrosis progression. Our results demonstrate how PKM2 regulates TGF-β1 signaling and is a key factor in fibrosis progression.

PMID:36129984 | DOI:10.1126/sciadv.abo0987

Clin Transl Sci. 2022 Sep 20. doi: 10.1111/cts.13419. Online ahead of print.

ABSTRACT

Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev®) and pirfenidone (Pirespa®) are the first-line drugs. In this study, we investigated the incidence of ILD possibly caused by antifibrotic agents using data from the Japanese Adverse Drug Event Report (JADER) database, a database of spontaneous adverse event reports published by the Pharmaceuticals and Medical Devices Agency (PMDA), and the FDA Adverse Event Reporting System (FAERS) published by the U.S. Food and Drug Administration. We used the FAERS and JADER to detect the signals of adverse events on the basis of reporting odds ratios. The relationship between indications and adverse events was clarified by separating indications and adverse events using the spontaneous adverse event reporting database with novel drug involvement. Regarding the involvement of nintedanib and pirfenidone in the development of ILD, JADER and FAERS showed signals for both nintedanib and pirfenidone as suspect drugs, and no signals for nintedanib or pirfenidone as concomitant drug interactions were detected. We highlight this because there are only a few effective drugs for IPF, and effective and safe drug therapies should be implemented by taking into consideration drug-induced ILD.

PMID:36128688 | DOI:10.1111/cts.13419

Gastroenterology Res. 2022 Aug;15(4):173-179. doi: 10.14740/gr1537. Epub 2022 Jul 12.

ABSTRACT

BACKGROUND: Lung cancer is a leading cause of mortality in the USA. Non-small cell lung cancer (NSCLC) contributes to 85% of all lung cancers. It is the most prevalent subtype amongst non-smokers, and its incidence has risen in the last 20 years. In addition, gastroesophageal reflux disease (GERD) has been associated with several lung pathologies, namely idiopathic pulmonary fibrosis and asthma. We aimed to investigate the association between GERD and NSCLC by performing a retrospective, multicenter, case-control study. This is the first study of this nature to be carried out in the USA.

METHODS: Data were retrieved from 17 Northwell health care facilities in the New York area between the years 2010 and 2018. Inclusion criteria were patients > 18 years of age with NSCLC (large cell, adenocarcinoma, and squamous cell). They were appropriately matched with controls based on age, gender, weight, comorbidities, and medication use. Our exposure group had a diagnosis of GERD based on the International Classification of Diseases, Ninth/10th Revision (ICD 9/10) codes and endoscopic, in addition to histological evidence if present. We excluded patients with secondary lung cancers, esophageal adenocarcinoma, other primary malignancies, Barrett's esophagus, and smokers. Logistic regression was conducted to determine the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between NSCLC and GERD.

RESULTS: A total of 1,083 subjects were included in our study: 543 (50%) patients were diagnosed with NSCLC. In this population, GERD was twice as prevalent compared to controls (20.4% vs. 11.6%, P < 0.001). Multivariate analysis demonstrated that GERD was associated with a higher risk of NSCLC compared to matched controls (OR = 1.86, 95% CI = 1.26 - 2.73). In addition, GERD patients treated with either antihistamines or proton pump inhibitors did not demonstrate an overall reduced risk of NSCLC (OR = 1.01, 95% CI = 0.48 - 2.12).

CONCLUSIONS: Our study demonstrates that GERD is associated with a higher risk of NSCLC, irrespective of GERD treatment. We postulate that GERD patients suffer from chronic micro-aspirations leading to a prolonged inflammatory state within the lung parenchyma, triggering specific proliferative signaling pathways that may lead to malignant transformation.

PMID:36128185 | PMC:PMC9451582 | DOI:10.14740/gr1537

Chron Respir Dis. 2022 Jan-Dec;19:14799731221125559. doi: 10.1177/14799731221125559.

ABSTRACT

OBJECTIVE: To investigate incidence and prevalence of Systemic Sclerosis (SSc) and association with interstitial lung disease (SSc-ILD) in a nationwide population-based study.

METHODS: Patients with an incident diagnosis of SSc in 2000-2016 were identified in the Danish National Patient Registry and categorised based on diagnosis of ILD. Incidence- and prevalence proportions were calculated based on the annual population estimates. A cox proportional hazards model was used to evaluate the association between age, sex, region and marital status and presence of ILD.

RESULTS: In total, 1869 patients with SSc were identified; 275 patients (14.7%) had SSc-ILD. The majority of patients were females (75.5%). The percentage of males was higher in SSc-ILD than in SSc alone (30.9% and 23.4%, p = 0.008). Median time from SSc to ILD diagnosis was 1.4 years (range 0-14.2). ILD was diagnosed from ≤4 years before to ≥7 years after SSc. Development of ILD was associated with male gender (HR 1.75, 95% CI 1.15-2.66), age 41-50 (HR 1.81, 95% CI 1.07-3.05) and residency in the North Denmark Region (HR 1.95, 9 5% CI 1.12-3.40). Mean annual incidence proportion of SSc was 2.9/100,000 and mean annual prevalence proportion was 16.8/100,000. The incidence remained stable, but prevalence proportion increased from 14.1 - 16.5/100,000 in 2000-2008 to 17.9-19.2/100,000 in 2009-2016.

CONCLUSION: The prevalence of SSc increased during the study period, while the incidence remained stable. The prevalence of SSc-ILD was 14.7% and thus less frequent than expected. Male sex and age between 41 and 50 years were associated with ILD.

PMID:36123773 | PMC:PMC9500307 | DOI:10.1177/14799731221125559

Sci Rep. 2022 Sep 20;12(1):15682. doi: 10.1038/s41598-022-20030-z.

ABSTRACT

This study aimed to assess the diagnostic accuracy and safety of CT-guided percutaneous core needle biopsy (PCNB) with a coaxial needle for the diagnosis of lung cancer in patients with an usual interstitial pneumonia (UIP) pattern of interstitial lung disease. This study included 70 patients with UIP and suspected to have lung cancer. CT-guided PCNB was performed using a 20-gauge coaxial cutting needle. The diagnostic accuracy, sensitivity, specificity, and percentage of nondiagnostic results for PCNB were determined in comparison with the final diagnosis. PCNB-related complications were evaluated. Additionally, the risk factors for nondiagnostic results and pneumothorax were analyzed. The overall diagnostic accuracy, sensitivity, and specificity were 85.7%, 85.5%, and 87.5%, respectively. The percentage of nondiagnostic results was 18.6% (13/70). Two or less biopsy sampling was a risk factor for nondiagnostic results (p = 0.003). The overall complication rate was 35.7% (25/70), and pneumothorax developed in 22 patients (31.4%). A long transpulmonary needle path was a risk factor for the development of pneumothorax (p = 0.007). CT-guided PCNB using a coaxial needle is an effective method with reasonable accuracy and an acceptable complication rate for the diagnosis of lung cancer, even in patients with UIP.

PMID:36127437 | PMC:PMC9489867 | DOI:10.1038/s41598-022-20030-z

JMIR Res Protoc. 2022 Sep 1. doi: 10.2196/37426. Online ahead of print.

ABSTRACT

BACKGROUND: Polymyxin B-immobilized fiber column (PMX, Toraymyxin column) was approved for the relief of SIRS (systemic inflammatory response syndrome) caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal, in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. SARS-CoV-2 virus causes COVID-19 pneumonia that emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity and prolonged prothrombin time were significant factors in non-surviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted but, with the exception of remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is most necessary to prevent further exacerbation by providing treatment that will suppress the above symptoms as soon as possible.

OBJECTIVE: To acquire treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leucocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia.

METHODS: We will conduct a multicenter prospective intervention single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for COVID-19 patients. Efficacy will be evaluated by the primary endpoint, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4.5.6 on Day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia.

RESULTS: This study will help determine PMX-DHP treatment options in the medical setting by quickly collecting and publishing information on patient background and on the efficacy and safety of treatment by PMX-DHP.

CONCLUSIONS: From a clinical perspective, PMX-DHP is expected to become a first-line therapy to address unmet medical needs and prevent the exacerbation from moderate to severe ARDS (acute respiratory distress syndrome) in COVID-19 cases.

INTERNATIONAL REGISTERED REPORT: DERR1-10.2196/37426.

PMID:36126219 | DOI:10.2196/37426

Indian J Med Res. 2022 Mar&Apr;155(3&4):356-363. doi: 10.4103/ijmr.IJMR_3271_20.

ABSTRACT

BACKGROUND & OBJECTIVES: Haemoptysis in children is potentially life-threatening. In most cases, the bleeding arises from the systemic circulation, and in 5-10 per cent of cases, it arises from the pulmonary circulation. The role of computed tomography angiography (CTA) in this setting is important. This study was undertaken (i) to study the role of single-phase split-bolus dual energy contrast-enhanced multidetector row CTA (DECTA) in the evaluation of haemoptysis in children; (ii) to analyze the patterns of abnormal vascular supply in the various aetiologies encountered.

METHODS: A retrospective study of 86 patients who underwent split bolus DECTA for the evaluation of haemoptysis was performed. Final diagnoses were categorized as normal computed tomography, active tuberculosis (TB), post-infectious sequelae, non-TB active infection, cystic fibrosis (CF), non-CF bronchiectasis, congenital heart disease (CHD), interstitial lung disease, vasculitis, pulmonary thromboembolism and idiopathic pulmonary haemosiderosis. Abnormal bronchial arteries (BAs) and non-bronchial systemic collateral arteries (NBSCs) were assessed for number and site and their correlation with underlying aetiologies.

RESULTS: A total of 86 patients (45 males, age from 0.3 to 18 yr, mean 13.88 yr) were included in the study; among these only two patients were less than five years of age. The most common cause of haemoptysis was active infection (n=30), followed by bronchiectasis (n=18), post-infectious sequelae (n=17) and CHD (n=7). One hundred and sixty five abnormal arteries were identified (108 BA and 57 NBSC), and were more marked in bronchiectasis group.

INTERPRETATION & CONCLUSIONS: Active infections and bronchiectasis are the most common causes of haemoptysis in children. While post-infectious sequelae are less common, in patients with haemoptysis, the presence of any abnormal arteries correlates with a more frequent diagnosis of bronchiectasis. NBSCs are more common in post-infectious sequelae and CHD.

PMID:36124510 | DOI:10.4103/ijmr.IJMR_3271_20

Respirology. 2022 Sep 19. doi: 10.1111/resp.14373. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Air pollution affects clinical course and prognosis of idiopathic pulmonary fibrosis (IPF). However, the effect of individual exposure to air pollutants on disease progression is unclear. We aimed to identify the effect of individual exposure to nitrogen dioxide (NO2 ) and particulate matter (aerodynamic diameter ≤ 10 μm [PM10 ]) on disease progression in patients with IPF.

METHODS: The serial lung function data of 946 IPF patients (mean age: 65.4 years, male: 80.9%) were analysed. Individual-level long-term exposures to NO2 and PM10 at the residential addresses of patients were estimated using a national-scale exposure prediction model, constructed based on air quality regulatory monitoring data. Progression was defined as a relative decline (≥10%) in forced vital capacity. Individual- and area-level covariates were adjusted in the primary analysis model.

RESULTS: Overall, 547 patients (57.8%) experienced progression during a median follow-up of 1.0 year (interquartile range: 0.4-2.6 years). In the primary model, a 10-ppb increase in NO2 concentration was associated with a 10.5% increase in the risk of progression (hazard ratio [HR] = 1.105; 95% CI = 1.000-1.219) in patients with IPF. There was also an increasing trend of progression in patients with IPF according to the second to fourth quartiles of NO2 (Q2 [HR = 1.299; 95% CI = 0.972-1.735], Q3 [1.409; 1.001-1.984], Q4 [1.598; 1.106-2.310]) compared to the first quartile. We found no association between PM10 and progression in IPF patients.

CONCLUSION: Our data suggest that increased individual exposure to NO2 can increase the risk of progression in patients with IPF.

PMID:36123769 | DOI:10.1111/resp.14373

Respir Investig. 2022 Sep 16:S2212-5345(22)00116-2. doi: 10.1016/j.resinv.2022.08.004. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment for idiopathic pulmonary fibrosis (IPF) has changed over the past decades. Understanding the actual status of IPF treatment and evaluating the consistency of the guidelines are important for improving the treatment strategy. However, the relevant information is insufficient in Japan. Therefore, this study investigated the treatment status and changes in the treatment of patients with IPF in Japan.

METHODS: This retrospective claims-based study used a Japanese claims database that included data from acute care hospitals (April 2008-March 2019). Patients with at least one record of definitive IPF diagnosis were classified as patients with IPF. We determined the percentage of patients who received each treatment type by the year.

RESULTS: We analyzed 9961 patients with IPF. The mean (standard deviation) age at first diagnosis was 74.4 (9.3) years, and 74.9% of the patients were men. The number of patients who did not take any drug treatment tended to decrease over the years. Nevertheless, approximately 30% of the patients did not take any drug treatment in recent years. The number of patients who received antifibrotic drugs increased over time, and it became the most popular treatment for ≥40% of the patients in and after 2017. Although steroid prescriptions tended to decrease over time, they were still administered to one-third of the patients with IPF who received drug treatment in and after 2017.

CONCLUSIONS: Our findings suggest that changes in the IPF treatment reflect changes in guideline recommendations as well as the availability of treatment in clinical settings in Japan.

PMID:36123241 | DOI:10.1016/j.resinv.2022.08.004