Front Pharmacol. 2022 Nov 7;13:1034464. doi: 10.3389/fphar.2022.1034464. eCollection 2022.

ABSTRACT

Exposure to high concentrations of hydrochloric acid (HCl) can lead to severe acute and chronic lung injury. In the aftermath of accidental spills, victims may be treated for the acute symptoms, but the chronic injury is often overlooked. We have developed a mouse model of acute and chronic lung injury, in which the peak of acute lung injury occurs on the day 4 after HCl exposure. We have also demonstrated that HSP90 inhibitors are effective antidotes when administered starting 24 h after HCl. In this study we examined the hypothesis that the novel oral HSP90 inhibitor TAS-116 can effectively ameliorate HCl-induced lung injury even when treatment starts at the peak of the acute injury, as late as 96 h after HCl. C57BI/6J mice were intratracheally instilled with 0.1N HCl. After 24 or 96 h, TAS-116 treatment began (3.5, 7 or 14 mg/kg, 5 times per week, p. o.) for either 2,3 or 4 or weeks. TAS-116 moderated the HCl-induced alveolar inflammation, as reflected in the reduction of white blood cells and total protein content in bronchoalveolar lavage fluid (BALF), overexpression of NLRP3 inflammasome, and inhibited the activation of pro-fibrotic pathways. Furthermore, TAS-116 normalized lung mechanics and decreased the deposition of extracellular matrix proteins in the lungs of mice exposed to HCl. Delayed and shortened treatment with TAS-116, successfully blocked the adverse chronic effects associated with acute exposure to HCl.

PMID:36419627 | PMC:PMC9676235 | DOI:10.3389/fphar.2022.1034464

Zhongguo Fei Ai Za Zhi. 2022 Nov 20;25(11):811-818. doi: 10.3779/j.issn.1009-3419.2022.101.51.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease (ILD) of unknown causes, which is characterized by pulmonary fibrosis. The median survival period after diagnosis is about 2-4 years. In recent years, the incidence rate of lung cancer associated with IPF (IPF-LC) is increasing, and the prognosis is worse than that of IPF alone. Pulmonary fibrosis may be closely associated with the occurrence and development of lung cancer. Although the pathogenesis of IPF-LC is still unclear, the current research shows that there are similarities between the pathogenesis of these two diseases at molecular and cellular levels. At present, the research on the cellular and molecular mechanism of lung cancer related to pulmonary fibrosis has become the focus of researchers' attention. This article reviews the related literature, focusing on the latest status of the cellular and molecular mechanisms and treatment of IPF-LC, hoping to help clinicians understand IPF-LC. .

PMID:36419395 | DOI:10.3779/j.issn.1009-3419.2022.101.51

Drug Deliv. 2022 Dec;29(1):3384-3396. doi: 10.1080/10717544.2022.2149899.

ABSTRACT

Pirfenidone (PRF) is the first FDA-approved API in the treatment of idiopathic pulmonary fibrosis (IPF). However, PRF induces serious side effects, such as photophobia and gastrointestinal disorder. PRF inhalation can be expected with a lower effective dose and reduced side effects. In this study, PRF was prepared as inhalable co-spray-dried particles for dry powder inhalation. Mannitol, L-leucine (Leu), and NaCl were used as a stabilizer. The kinds and ratios of stabilizers affecting the physicochemical properties of particles were analyzed, including particle size and surface composition, because of the surface enrichment properties of Leu, the most effective stabilizer. The co-spray-dried PRF and Leu microparticle (SD-PL1:1) have the smallest size and highest aerosol performance. The bioavailability was confirmed by in vivo pharmacokinetics (PK) studies. In addition, in vivo pharmacodynamics (PD) experiments were conducted using a bleomycin-induced IPF rat model. In vivo PK experiments demonstrated that pulmonary administration of SD-PL1:1 was 4 times more effective than the oral route. Similar to the PK results, the therapeutic effect was improved when SD-PL1:1 was administered via the pulmonary route compared to the oral route.

PMID:36415157 | DOI:10.1080/10717544.2022.2149899

EBioMedicine. 2022 Nov 19;86:104356. doi: 10.1016/j.ebiom.2022.104356. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a serious disease of the lung parenchyma. It has a known polygenetic risk, with at least seventeen regions of the genome implicated to date. Growing evidence suggests linked multimorbidity of IPF with neurodegenerative or affective disorders. However, no study so far has explicitly explored links between IPF, associated genetic risk profiles, and specific brain features.

METHODS: We exploited imaging and genetic data from more than 32,000 participants available through the UK Biobank population-level resource to explore links between IPF genetic risk and imaging-derived brain endophenotypes. We performed a brain-wide imaging-genetics association study between the presence of 17 known IPF risk variants and 1248 multi-modal imaging-derived features, which characterise brain structure and function.

FINDINGS: We identified strong associations between cortical morphological features, white matter microstructure and IPF risk loci in chromosomes 17 (17q21.31) and 8 (DEPTOR). Through co-localisation analysis, we confirmed that cortical thickness in the anterior cingulate and more widespread white matter microstructure changes share a single causal variant with IPF at the chromosome 8 locus. Post-hoc preliminary analysis suggested that forced vital capacity may partially mediate the association between the DEPTOR variant and white matter microstructure, but not between the DEPTOR risk variant and cortical thickness.

INTERPRETATION: Our results reveal the associations between IPF genetic risk and differences in brain structure, for both cortex and white matter. Differences in tissue-specific imaging signatures suggest distinct underlying mechanisms with focal cortical thinning in regions with known high DEPTOR expression, unrelated to lung function, and more widespread microstructural white matter changes consistent with hypoxia or neuroinflammation with potential mediation by lung function.

FUNDING: This study was supported by the NIHR Nottingham Biomedical Research Centre and the UK Medical Research Council.

PMID:36413936 | DOI:10.1016/j.ebiom.2022.104356

Front Physiol. 2022 Nov 4;13:1072903. doi: 10.3389/fphys.2022.1072903. eCollection 2022.

NO ABSTRACT

PMID:36406978 | PMC:PMC9674031 | DOI:10.3389/fphys.2022.1072903

Front Immunol. 2022 Nov 4;13:1028613. doi: 10.3389/fimmu.2022.1028613. eCollection 2022.

ABSTRACT

SARS-CoV-2 infection causes a variety of physiological responses in the lung, and understanding how the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), and its proteolytic activator, transmembrane serine protease 2 (TMPRSS2), are affected in patients with underlying disease such as interstitial pneumonia will be important in considering COVID-19 progression. We examined the expression of ACE2 and TMPRSS2 in an induced usual interstitial pneumonia (iUIP) mouse model and patients with IPF as well as the changes in whole-lung ACE2 and TMPRSS2 expression under physiological conditions caused by viral infection. Histopathological and biochemical characteristics were analyzed using human specimens from patients with IPF and precision-cut lung slices (PCLS) from iUIP mouse model showing UIP with honeycombing and severe fibrosis after non-specific interstitial pneumonia. ACE2 expression decreased with acute lung inflammation and increased in the abnormal lung epithelium of the iUIP mouse model. ACE2 is also expressed in metaplastic epithelial cells. Poly(I:C), interferons, and cytokines associated with fibrosis decreased ACE2 expression in PCLS in the iUIP model. Hypoxia also decreases ACE2 via HIF1α in PCLS. Antifibrotic agent, nintedanib attenuates ACE2 expression in invasive epithelial cells. Patients with IPF are at a higher risk of SARS-CoV-2 infection due to the high expression of ACE2. However, ACE2 and TMPRSS2 expression is decreased by immune intermediaries, including interferons and cytokines that are associated with viral infection and upon administration of antifibrotic agents, suggesting that most of the viral infection-induced pathophysiological responses aid the development of resistance against SARS-CoV-2 infection.

PMID:36405683 | PMC:PMC9673245 | DOI:10.3389/fimmu.2022.1028613

Front Med (Lausanne). 2022 Nov 3;9:976759. doi: 10.3389/fmed.2022.976759. eCollection 2022.

ABSTRACT

The development of lung fibrosis is a major concern in patients recovered from severe COVID-19 pneumonia. This study aimed to document the evolution of diffuse alveolar damage (DAD) to the fibrosing pattern and define the transcriptional programs involved. Morphological, immunohistochemical and transcriptional analysis were performed in lung samples obtained from autopsy of 33 severe COVID-19 patients (median illness duration: 36 days). Normal lung and idiopathic pulmonary fibrosis (IPF) were used for comparison. Twenty-seven patients with DAD and disease evolution of more than 2 weeks had fibrosis. Pathways and genes related with collagen biosynthesis and extracellular matrix (ECM) biosynthesis and degradation, myofibroblastic differentiation and epithelial to mesenchymal transition (EMT) were overexpressed in COVID-19. This pattern had similarities with that observed in IPF. By immunohistochemistry, pathological fibroblasts (pFBs), with CTHRC1 and SPARC expression, increased in areas of proliferative DAD and decreased in areas of mature fibrosis. Immunohistochemical analysis demonstrated constitutive expression of cadherin-11 in normal epithelial cells and a similar pattern of cadherin and catenin expression in epithelial cells from both normal and COVID-19 samples. Transcriptomic analysis revealed downregulation of the Hippo pathway, concordant with the observation of YAP overexpression in hyperplastic alveolar epithelial cells. Progression to fibrosis in severe COVID-19 is associated with overexpression of fibrogenic pathways and increased in CTHRC1- and SPARC-positive pFBs. Whereas the Hippo pathway seemed to be implicated in the response to epithelial cell damage, EMT was not a major process implicated in COVID-19 mediated lung fibrosis.

PMID:36405615 | PMC:PMC9669577 | DOI:10.3389/fmed.2022.976759

Genome Med. 2022 Nov 21;14(1):126. doi: 10.1186/s13073-022-01127-6.

ABSTRACT

BACKGROUND: Squamous cell carcinoma (SqCC) is a subtype of non-small cell lung cancer for which patient prognosis remains poor. The extracellular matrix (ECM) is critical in regulating cell behavior; however, its importance in tumor aggressiveness remains to be comprehensively characterized.

METHODS: Multi-omics data of SqCC human tumor specimens was combined to characterize ECM features associated with initiation and recurrence. Penalized logistic regression was used to define a matrix risk signature for SqCC tumors and its performance across a panel of tumor types and in SqCC premalignant lesions was evaluated. Consensus clustering was used to define prognostic matreotypes for SqCC tumors. Matreotype-specific tumor biology was defined by integration of bulk RNAseq with scRNAseq data, cell type deconvolution, analysis of ligand-receptor interactions and enriched biological pathways, and through cross comparison of matreotype expression profiles with aging and idiopathic pulmonary fibrosis lung profiles.

RESULTS: This analysis revealed subtype-specific ECM signatures associated with tumor initiation that were predictive of premalignant progression. We identified an ECM-enriched tumor subtype associated with the poorest prognosis. In silico analysis indicates that matrix remodeling programs differentially activate intracellular signaling in tumor and stromal cells to reinforce matrix remodeling associated with resistance and progression. The matrix subtype with the poorest prognosis resembles ECM remodeling in idiopathic pulmonary fibrosis and may represent a field of cancerization associated with elevated cancer risk.

CONCLUSIONS: Collectively, this analysis defines matrix-driven features of poor prognosis to inform precision medicine prevention and treatment strategies towards improving SqCC patient outcome.

PMID:36404344 | DOI:10.1186/s13073-022-01127-6

Respir Med Res. 2022 Oct 30;82:100971. doi: 10.1016/j.resmer.2022.100971. Online ahead of print.

NO ABSTRACT

PMID:36403359 | DOI:10.1016/j.resmer.2022.100971

Clin Exp Med. 2022 Nov 20. doi: 10.1007/s10238-022-00945-7. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is characterized by permanent scarring of lung tissue and declining lung function, and is an incurable disease with increase in prevalence over the past decade. The current consensus is that aberrant wound healing following repeated injuries to the pulmonary epithelium is the most probable cause of IPF, with various immune inflammatory pathways having been reported to impact disease pathogenesis. While the role of immune cells, specifically T lymphocytes and regulatory T cells (Treg), in IPF pathogenesis has been reported and discussed recently, the pathogenic or beneficial roles of these cells in inducing or preventing lung fibrosis is still debated. This lack of understanding could be due in part to the difficulty in obtaining diseased human lung tissue for research purposes. For this reason, many animal models have been developed over the years to attempt to mimic the main clinical hallmarks of IPF: among these, inducing lung injury in rodents with the anti-cancer agent bleomycin has now become the most commonly studied animal model of IPF. Pulmonary fibrosis is the major side effect when bleomycin is administered for cancer treatment in human patients, and a similar effect can be observed after intra-tracheal administration of bleomycin to rodents. Despite many pathophysiological pathways of lung fibrosis having been investigated in bleomycin-injured animal models, one central facet still remains controversial, namely the involvement of specific T lymphocyte subsets, and in particular Treg, in disease pathogenesis. This review aims to summarize the major findings and conclusions regarding the involvement of immune cells and their receptors in the pathogenesis of IPF, and to elaborate on important parallels between animal models and the human disease. A more detailed understanding of the role of Treg and other immune cell subsets in lung injury and fibrosis derived from animal models is a critical basis for translating this knowledge to the development of new immune-based therapies for the treatment of human IPF.

PMID:36403186 | DOI:10.1007/s10238-022-00945-7

Eur J Med Chem. 2022 Nov 11;245(Pt 2):114918. doi: 10.1016/j.ejmech.2022.114918. Online ahead of print.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized with high mortality, unknown etiology, and lack of effective treatment. Many evidences validate that inhibiting the activation of STAT3 is an attractive therapeutic strategy for IPF. Herein, based on our previous findings that nifuroxazide (NIF) could effectively attenuate pulmonary fibrosis by inhibiting STAT3 activation, a series of diarylacylhydrazones derivatives have been designed and synthesized. Among them, compounds 44 and 52 could inhibit TGF-β1-induced abnormal activation of NIH-3T3 and A549 cells, as well as migration and EMT of A549 cells. In a bleomycin-induced mouse pulmonary fibrosis model, the oral administration of 44 and 52 (bioavailability F = 31.75% and 42.08%) improved mouse lung function and slowed the progression of IPF. Moreover, 52 could reverse the pulmonary fibrosis in treatment model. Collectively, this work shows 44 and 52 could be a potential lead compound for the treatment of IPF, and it is worthy of further study.

PMID:36401884 | DOI:10.1016/j.ejmech.2022.114918

Clin Respir J. 2022 Nov 17. doi: 10.1111/crj.13561. Online ahead of print.

ABSTRACT

BACKGROUND: Hypersensitivity pneumonitis (HP) is a common type among all the interstitial lung diseases, and transbronchial lung cryobiopsy is an alternative diagnostic technique for interstitial lung diseases. In this study, we describe the clinical and pathological features of fibrotic hypersensitivity pneumonitis diagnosed with transbronchial lung cryobiopsy (TBLC).

METHODS: A total of 46 diffused parenchyma lung disease (DPLD) patients received TBLC were included in this study. Medical records including medical history spirometry examinations, 6-min walk test (6MWT) results, high resolution computed tomographic (HRCT) scans, BAL, and histopathology were collected. Results of HRCT and histopathology were compared and classified, especially.

RESULTS: Sixteen patients were diagnosed with fibrotic HP, the mean age of whom was 56.3 ± 12.1 years, and 62.5% of them were male. Three of the 16 patients had been misdiagnosed as tuberculosis and received antituberculosis medications, five patients had been diagnosed as unclassifiable pulmonary fibrosis, and five patients had been diagnosed as idiopathic pulmonary fibrosis (IPF). Thirteen (81.3%) patients had a normal lymphocyte count in BAL. The pathological features of usual interstitial pneumonia (UIP) were detected in 11 (68.8%) of the cases, poor defined granulomatous was detected in nine (56.3%) of the cases, and bronchiolocentric fibrosis was detected in two (12.5%) of the 16 cases.

CONCLUSIONS: Fibrotic hypersensitivity pneumonitis should be included in differential diagnosis of pulmonary fibrosis. Pathological characteristics of fibrotic hypersensitivity pneumonitis could be demonstrated from cryobiopsy lung tissue. TBLC is recommended as an alternative diagnostic technique, which may improve the specificity of hypersensitivity pneumonia detection, and UIP is the most frequent pathological finding.

PMID:36397265 | DOI:10.1111/crj.13561

Sci Rep. 2022 Nov 17;12(1):19819. doi: 10.1038/s41598-022-24406-z.

ABSTRACT

Drug-induced interstitial lung disease (DILD) occurs when drug exposure causes inflammation of the lung interstitium. DILD can be caused by different types of drugs, and some DILD patterns results in a high mortality rate; hence, DILD poses a serious problem in clinical practice as well as drug development, and strategies to diagnose and distinguish DILD from other lung diseases are necessary. We aimed to identify novel biomarkers for DILD by performing lipidomics analysis on plasma samples from patients with acute and recovery phase DILD. Having identified lysophosphatidylcholines (LPCs) as candidate biomarkers for DILD, we determined their concentrations using validated liquid chromatography/mass spectrometry biomarker assays. In addition, we evaluated the ability of LPCs to discriminate patients with acute phase DILD from those with recovery phase DILD, DILD-tolerant, or other lung diseases, and characterized their association with clinical characteristics. Lipidomics analysis revealed a clear decrease in LPC concentrations in the plasma of patients with acute phase DILD. In particular, LPC(14:0) had the highest discriminative index against recovery phase and DILD-tolerant patients. LPC(14:0) displayed no clear association with causal drugs, or subjects' backgrounds, but was associated with disease severity. Furthermore, LPC(14:0) was able to discriminate between patients with DILD and other lung diseases, including idiopathic interstitial pneumonia and lung disease associated with connective tissue disease. LPC(14:0) is a promising biomarker for DILD that could improve the diagnosis of DILD and help to differentiate DILD from other lung diseases, such as idiopathic interstitial pneumonia and connective tissue disease.

PMID:36396675 | PMC:PMC9671920 | DOI:10.1038/s41598-022-24406-z

Med Clin (Barc). 2022 Nov 14:S0025-7753(22)00542-5. doi: 10.1016/j.medcli.2022.09.018. Online ahead of print.

NO ABSTRACT

PMID:36396475 | DOI:10.1016/j.medcli.2022.09.018

Biomed Pharmacother. 2022 Nov 14;157:114015. doi: 10.1016/j.biopha.2022.114015. Online ahead of print.

ABSTRACT

The effectiveness of cancer nanotherapeutics is greatly restricted by the dense collagen network in solid tumors. Pirfenidone (PFD) is a clinically approved oral antifibrotic agent widely used to treat idiopathic pulmonary fibrosis. To investigate whether PFD can enhance the penetration and tumor delivery efficiency of Pegylated liposomal doxorubicin (PLD), colorectal cancer xenograft mice were administered PFD, PLD, or combined regimens. As expected, high-dose PFD (H-PFD, 270 mg/kg/day) combined with PLD (H-PFD + PLD) exhibited a significantly higher tumor inhibition rate than PLD monotherapy (75.09% vs. 60.87%). Similarly, the intra-tumoral doxorubicin level was markedly elevated using H-PFD pretreatment, which induced over 34% elevation compared to PLD treatment alone (3.37 ± 0.41 vs. 2.51 ± 0.19 µg/mL). Additionally, Masson's trichrome staining and immunohistochemistry results of the H-PFD + PLD group revealed an attenuation of collagen deposition in vivo, and the in vitro TGF-β1, α-SMA, and collagen protein expression were inhibited using PFD treatment. In contrast, although low-dose PFD (60 mg/kg/day) did not present superior benefits in promoting PLD penetration into tumors, it did downregulate collagen expression in vivo. This study provides a new strategy for PFD combined with chemotherapeutic drugs to improve the antitumor efficacy of nanomedicines.

PMID:36395611 | DOI:10.1016/j.biopha.2022.114015

Int J Gen Med. 2022 Nov 8;15:8081-8092. doi: 10.2147/IJGM.S386984. eCollection 2022.

ABSTRACT

OBJECTIVE: Biomarkers for the acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) are urgently needed to provide better patient management. We aimed to investigate whether serum 1,25(OH)2D3 (1,25-dihydroxy vitamin D3) levels predict AE-IPF and whether they could be a potential prognostic biomarker for IPF.

PARTICIPANTS AND METHODS: This prospective study included 72 patients with IPF (31 with stable IPF and 41 with AE-IPF). All participants were recruited during hospitalisation at Tianjin Chest Hospital and were followed up for at least 12 months. Demographics, comorbidities, arterial blood gas, and serum biochemical profile, radiological features, and anti-fibrotic therapy were evaluated. Serum concentrations of 1,25(OH)2D3 and transforming growth factor beta1 (TGFβ1) were detected using enzyme-linked immunosorbent assay (ELISA). Risk factors for AE-IPF were identified using multivariate analysis. Prognostic factors were assessed using Kaplan-Meier and Cox regression analyses.

RESULTS: Baseline values of alveolar-arterial oxygen difference (A-aDO2) (40.85 mmHg vs 29.2 mmHg, p =0.035), white blood cell counts (10.09 ± 4.2×109/L vs 7.46 ± 7.84×109/L, p <0.001), percentage of monocytes (7.36 ± 1.36% vs 6.6 ± 1.2%, p =0.017), C-reactive protein (CRP) (2.1 mg/dL vs 1.12 mg/dL, p =0.015) and procalcitonin (PCT) (36.59% vs 3.23%, p <0.001) were significantly higher in AE-IPF patients than in stable IPF patients. Instead, the mean concentration of serum calcium and 1,25(OH)2D3 at baseline were higher in IPF patients with stable disease than in those with acute exacerbation (2.17 ± 0.13 nmol/L vs 2.09 ± 0.13 nmol/L, p =0.023 and 16.62 pg/mL vs 11.58 pg/mL, p <0.001, respectively). In multivariate analysis, a higher proportion of patients with lower serum 1,25(OH)2D3 levels experienced AE-IPF (OR 0.884, 95% CI 0.791-0.987, p =0.029), and rising serum PCT level (PCT > 0.05 ng/mL) was associated with an increased risk of mortality (HR 3.664, 95% CI 1.010-12.900, p =0.043).

CONCLUSION: Decreased serum 1,25(OH)2D3 is associated with an increased risk of acute exacerbation for patients with IPF. A high serum PCT level is predictive of worse prognosis in IPF patients. 1,25(OH)2D3 may be a potential biomarker for AE-IPF, while PCT could be a prognostic biomarker for IPF.

PMID:36389018 | PMC:PMC9653052 | DOI:10.2147/IJGM.S386984

Front Pharmacol. 2022 Oct 28;13:1053356. doi: 10.3389/fphar.2022.1053356. eCollection 2022.

ABSTRACT

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a critical disease, with limited treatments available. Clinical practices show that traditional Chinese medicine (TCM) has certain efficacy. This study was preliminarily to evaluate the efficacy and safety of TCM treatment based on syndrome differentiation in IPF. Methods: A study design of exploratory, multi-centers, randomized, double-blinded, placebo controlled trial has been adopted. A total of 80 IPF patients from four sub-centers were enrolled. All the patients were randomly assigned into TCM group (TCMG) or control group (CG) in 1:1. Patients in TCMG were given CM granules, as patients in CG given with the placebo of CM granule. All the patients received a 26-week treatment. The efficacy was assessed by acute exacerbations (AEs) of IPF, pulmonary function, clinical symptoms, dyspnea scores (mMRC), health-related quality of life (HRQoL), 6-min walk test (6MWT) and all-cause mortality. Safety has also been assessed. Results: A total of 67 patients completed the trial with 35 in TCM group and 32 in control group. Meaningful differences have been observed in mean changes in AEs (-1.56 times; 95% CI, -2.69 to -0.43, p = 0.01), DLco% (5.29; 95% CI, 0.76 to 9.81, p = 0.02), cough scores (-0.38 points; 95% CI, -0.73 to -0.04, p = 0.03), and 6MWT (30.43 m; 95% CI, 2.85 to 58.00, p = 0.03), with no statistical differences in FEV1, FVC, expectoration, chest tightness, Shortness of breath, Fatigue, Cyanosis, mMRC, CAT, SF-36, and SGRQ total scores in 26 weeks after treatment than before treatment. At of the end of follow-up, a total of 10 patients died, including three and seven in the TCM and control group respectively. And the HR (Hazard ratio) for CM granules in all-cause mortality was 0.39 (95% CI, 0.10-1.52). The drug-related adverse events were not observed. Conclusion: CM granules, as compared with placebo, could reduce frequencies of AEs, improve pulmonary function, HRQoL, exercise capacity and symptoms and signs for IPF to some extent with acceptable side-effect.

PMID:36386223 | PMC:PMC9649819 | DOI:10.3389/fphar.2022.1053356

BMC Pulm Med. 2022 Nov 17;22(1):422. doi: 10.1186/s12890-022-02232-3.

ABSTRACT

INTRODUCTION: Dysphagia occurs in multiple respiratory pathophysiologies, increasing the risk of pulmonary complications secondary to aspiration. Reflux associated aspiration and a dysregulated lung microbiome is implicated in Idiopathic Pulmonary Fibrosis (IPF), but swallowing dysfunction has not been described. We aimed to explore oropharyngeal swallowing in IPF patients, without known swallowing dysfunction.

METHODS: Fourteen consecutive outpatients with a secure diagnosis of IPF were recruited and the 10-item Eating Assessment Tool (Eat 10) used to assess patient perception of swallowing difficulty. Oropharyngeal swallowing was assessed in ten patients using Videofluoroscopy Swallow Studies (VFSS). The studies were rated using validated scales: Penetration-Aspiration Scale (PAS); standardised Modified Barium Swallow Impairment Profile (MBSImP).

RESULTS: EAT-10 scores indicated frank swallowing difficulty in 4/14 patients. Videofluoroscopy Studies showed that 3/10 patients had airway penetration, and one aspirated liquid without a cough response. Median MBSImp for oral impairment was 5, range [3-7] and pharyngeal impairment 4, range [1-14] indicating, overall mild alteration to swallowing physiology.

CONCLUSION: We conclude that people with IPF can show a range of swallowing dysfunction, including aspiration into an unprotected airway. To our knowledge, this is the first report on swallowing physiology and safety in IPF. We believe a proportion of this group may be at risk of aspiration. Further work is indicated to fully explore swallowing in this vulnerable group.

PMID:36384569 | DOI:10.1186/s12890-022-02232-3

Rev Med Suisse. 2022 Nov 16;18(804):2162-2168. doi: 10.53738/REVMED.2022.18.804.2162.

ABSTRACT

Lung cancer is the leading cause of cancer mortality in the developed world. Diffuse fibrosing interstitial lung disease (ILD) consist of a heterogeneous group that includes idiopathic pulmonary fibrosis (IPF). Diffuse ILD is a risk factor for the development of lung cancer which on its own is associated with an increased risk of morbidity and mortality. Despite common mechanisms between fibrogenesis and carcinogenesis, the underlying pathogenesis of lung cancer and fibrosis overlap is poorly understood. The clinical management of these patients remains a medical challenge requiring a multidisciplinary approach, particularly in view of the risk of acute exacerbation of fibrosing ILD following most lung cancer treatments, leading to a considerable negative outcome on overall prognosis.

PMID:36382977 | DOI:10.53738/REVMED.2022.18.804.2162

Sci Rep. 2022 Nov 15;12(1):19577. doi: 10.1038/s41598-022-24011-0.

ABSTRACT

Progressive fibrosing interstitial lung diseases (PF-ILDs) have a poor prognosis and may be resistant to corticosteroids and/or immunosuppressants, but antifibrotic therapies such as nintedanib and pirfenidone have been shown to slow the deterioration of lung function. The aim of this study was to identify the characteristic cellular profile of bronchoalveolar lavage fluid at diagnostic bronchoscopy for predicting PF-ILDs, defined as fibrotic diseases on chest high-resolution computed tomography with more than a 5% relative decline in the percent predicted value of forced vital capacity (FVC) over 6 months. The proportions of inflammatory cells, CCR6-CXCR3- T helper type 2 (Th2) cells among conventional CD4+ T cells in bronchoalveolar lavage fluid (BALF) and peripheral blood, were measured by flowcytometry. The proportion of lymphocytes in BALF was significantly higher in non-PF-ILD patients than in PF-ILD patients. The proportion of Th2 cells in BALF, but not in peripheral blood, was significantly higher in PF-ILD patients than in non-PF-ILD patients. Multivariate analysis showed that a greater population of Th2 cells in BALF was the only indicator for PF-ILDs. An increased proportion of Th2 cells in BALF is associated with greater deterioration of lung function in fibrotic interstitial lung diseases.

PMID:36380088 | DOI:10.1038/s41598-022-24011-0