A qualitative study to understand the barriers and facilitators in smoking cessation practices among oncology health care practitioners in one health system.

INTRODUCTION: Despite the benefits of quitting smoking for those who have cancer, including improved health outcomes and reduced therapeutic toxicities, it is unclear how many people are supported in quit attempts during this time. Variations in the availability and provision of smoking cessation (SC) services are reported, with little understanding of the challenges and solutions. This co-designed study aimed to understand the perspectives of health care professionals (HCPs) working in oncology settings to engage in SC practices and identify recommendations for developing an SC pathway. METHODS: This was a qualitative study. Eighteen HCPs participated in semi-structured interviews from July 2021 to May 2022. We used thematic analysis approaches to code data and present four emergent themes and SC strategies at micro, meso and organizational levels. RESULTS: Four themes emerged specifically: 1) timing and knowledge, 2) building a relationship, 3) frequent asking with infrequent action, and 4) removing the barriers and tailoring the system. While HCPs discuss SC, there are variations in documentation and when conversations occur. Primarily, HCPs value the time to build therapeutic relationships with patients and thus may limit SC discussions in preference to treatment in clinical interactions. The role of structural barriers, including prescriptive authority for nurses, hinders active SC processes, as it is the lack of continuity and embedding of services supported by a clinical champion for SC. CONCLUSIONS: The study suggests re-evaluating the status quo in SC service, highlighting service gaps and suggesting opportunities at organizational levels to reduce structural barriers. IMPLICATIONS: Variations in smoking cessation services exist in designated cancer centres. The data from this study can be used to inform a real time health systems approach for SC services in oncology settings. Developing tailored smoking cessation services and interventions that are patient-centred and informed by their experiences are required. The data in this study suggests developing specialist education and training to upskill HCPs for equitable engagement if we are to meet EU and Moonshot goals for cancer reduction.

Effects of Active Chronic Cigarette-Smoke Exposure on Circulating Fibrocytes.

PURPOSE: This study aimed to evaluate the hypothesis that active smoking impacts upon mediators and abundance of circulating fibrocyte cells in smoking-related disease characterised by fibrosis. METHODS: Flow cytometry and enzyme-linked immunosorbent assays were used to investigate blood from five patient groups: healthy never-smokers, healthy current smokers, stable chronic obstructive pulmonary disease (COPD) active smokers, idiopathic pulmonary fibrosis (IPF) never-smokers, and IPF active smokers. RESULTS: A significant inverse dose-response relationship was observed in healthy smokers among cumulative smoking burden (pack-years) and fibrocyte abundance (p = 0.006, r = -0.86). Among serum profibrotic fibrocyte chemokines measured, CCL18 rose significantly alongside fibrocyte numbers in all five subject groups, while having an inverse dose-response relationship with pack-year burden in healthy smokers (p = 0.003, r = -0.89). In IPF, CCL2 rose in direct proportion to fibrocyte abundance irrespective of smoking status but had lower serum levels in those currently smoking (p = < 0.001). For the study population, CXCL12 was decreased in pooled current smokers versus never-smokers (p = 0.03). CONCLUSION: The suppressive effect of current, as distinct from former, chronic smoking on circulating fibrocyte abundance in healthy smokers, and modulation of regulatory chemokine levels by active smoking may have implications for future studies of fibrocytes in smoking-related lung diseases as a potential confounding variable.

Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common SNPs. The MUC5B promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF. We address the utility of genetic variation in enhancing understanding of disease pathogenesis and clinical phenotypes, improving disease definitions, and informing prognosis and treatment response. Critical research gaps are highlighted, particularly the underrepresentation of non-European ancestries in PF genetic studies and the exploration of PF phenotypes beyond usual interstitial pneumonia/IPF. We discuss the role of telomere length, often critically short in PF, and its link to progression and mortality, underscoring the genetic complexity involving telomere biology genes (TERT, TERC) and others like SFTPC and MUC5B. In addition, we address the potential of gene-by-environment interactions to modulate disease manifestation, advocating for precision medicine in PF. Insights from gene expression profiling studies and multiomic analyses highlight the promise for understanding disease pathogenesis and offer new approaches to clinical care, therapeutic drug development, and biomarker discovery. Finally, we discuss the ethical, legal, and social implications of genomic research and therapies in PF, stressing the need for sound practices and informed clinical genetic discussions. Looking forward, we advocate for comprehensive genetic testing panels and polygenic risk scores to improve the management of PF and related ILDs across diverse populations.

Smoking Cessation Support: A Marathon, Not a Sprint; The Perspectives of Cancer Patients Who Smoke.

OBJECTIVES: Despite the unfavorable outcomes associated with continued smoking, a substantial proportion of patients with cancer continue to smoke after diagnosis. However, limited use of smoking cessation (SC) interventions has been reported. This study explored the perceptions of patients with cancer who continue to smoke/recently quit regarding SC. DATA SOURCES: Semistructured phone/Zoom/Webex interviews were conducted with 25 participants attending four Irish cancer hospitals who were current smokers or had quit at/after their cancer diagnosis. Thematic analysis was used to analyze the data. CONCLUSION: A total of four key themes emerged: (1) Diagnosis was a shock and a cue to action. (2) Brief and variable SC support: most participants did not feel stigmatized and reported receiving verbal or written information from oncology healthcare providers (HCPs) on SC supports. However, use of SC services was limited and largely ineffective. Some participants reported that SC discussions occurred earlier in their treatment with limited/no discussion later. (3) Facilitators vs barriers: the presence or absence of willpower and motivation was perceived as important. Family and HCP support helped while stress hindered SC. (4) SC support is a "marathon," not a "sprint." Patients with cancer who continue to smoke or recently quit want a sustained, tailored, nonjudgmental approach to SC incorporating pharmacological and behavioral interventions that span hospital-/community-based settings. IMPLICATIONS FOR NURSING PRACTICE: While consultants have been identified as the key HCP to initiate the SC discussion, oncology nurses can support patients with cancer who smoke/recently quit by advocating for comprehensive SC services and by using positive messaging and encouragement.

Analysis of tissue lipidomics and computed tomography pulmonary fat attenuation volume (CTPFAV ) in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers. STUDY DESIGN AND METHODS: IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CTPFAV ) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CTPFAV calculated using a Hounsfield-unit (-40 to -200HU) threshold range expressed as a percentage of total lung volume. CTPFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores. RESULTS: There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CTPFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CTPFAV correlated significantly with DLCO% predicted (R2 = 0.356, p < 0.0001) and FVC% predicted (R2 = 0.407, p < 0.0001) in patients with IPF. CTPFAV correlated with CT features of fibrosis; higher CTPFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CTPFAV showed no correlation with serum lipids. CONCLUSION: CTPFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CTPFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Combined autologous blood patch-immediate patient rollover does not reduce the pneumothorax or chest drain rate following CT-guided lung biopsy compared to immediate patient rollover alone.

PUPROSE: The purpose of this study was to evaluate a combined autologous blood-patch (ABP)-immediate patient rollover (IPR) technique compared with the IPR technique alone on the incidence of pneumothorax and chest drainage following CT-guided lung biopsy. METHODS: In this interventional cohort study of both prospectively and retrospectively acquired data, 652 patients underwent CT-guided lung biopsy. Patient demographics, lesion characteristics and technical biopsy variables including the combined ABP-IPR versus IPR alone were evaluated as predictors of pneumothorax and chest drain rates using regression analysis. RESULTS: The combined ABP-IPR technique was performed in 259 (39.7 %) patients whilst 393 (60.3 %) underwent IPR alone. There was no significant difference in pneumothorax rate or chest drains required between the combined ABP-IPR vs IPR groups (p =.08, p =.60 respectively). Predictors of pneumothorax adjusted for the combined ABP-IPR and IPR alone groups included age (p =.02), lesion size (p =.01), location (p =.005), patient position (p =.008), emphysema along the needle track (p =.005) and lesion distance from the pleura (p =.02). Adjusted predictors of chest drain insertion included lesion location (p =.09), patient position (p =.002), bullae crossed (p =.02) and lesion distance from the pleura (p =.02). CONCLUSION: The combined ABP-IPR technique does not reduce the pneumothorax or chest drain rate compared to the IPR technique alone. Utilising IPR without an ABP following CT-guided lung biopsy results in similar pneumothorax and chest drain rates while minimising the potential risk of systemic air embolism.

Exosomes from EGFR-Mutated Adenocarcinoma Induce a Hybrid EMT and MMP9-Dependant Tumor Invasion.

Exosomes, a class of extra cellular nano-sized vesicles (EVs), and their contents have gained attention as potential sources of information on tumor detection and regulatory drivers of tumor progression and metastasis. The effect of exosomes isolated from patients with an Epidermal Growth Factor Receptor (EGFR)-mutated adenocarcinoma on the promotion of epithelial-mesenchymal transition (EMT) and invasion were examined. Exosomes derived from serum of patients with EGFR-mutated non-small cell lung cancer (NSCLC) mediate the activation of the Phosphoinositide 3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) pathway and induce an invasion through the up-regulation of matrix metalloproteinase-9 (MMP-9) in A549 cells. We observed a significant increase in the expression of vimentin, a mesenchymal marker, while retaining the epithelial characteristics, as evidenced by the unaltered levels of E-cadherin and Epithelial cell adhesion molecule (EPCAM). We also observed an increase of nuclear factor erythroid 2-related factor 2 (NFR2) and P-cadherin expression, markers of hybrid EMT. Exosomes derived from EGFR-mutated adenocarcinoma serum could be a potential mediator of hybrid EMT and tumor invasion. Understanding how cancerous cells communicate and interact with their environment via exosomes will improve our understanding of lung cancer progression and metastasis formation.

Contemporary Concise Review 2021: Interstitial lung disease.

The last 2 years have presented previously unforeseen challenges in pulmonary medicine. Despite the significant impact of the SARS-CoV-2 pandemic on patients, clinicians and communities, advances in the care and understanding of interstitial lung disease (ILD) continued unabated. Recent studies have led to improved guidelines, better understanding of the role for antifibrotics in fibrosing ILDs, prognostic indicators and novel biomarkers. In this concise contemporary review, we summarize many of the important studies published in 2021, highlighting their relevance and impact to the management and knowledge of ILD.

Nanoparticle Biomolecular Corona-Based Enrichment of Plasma Glycoproteins for N-Glycan Profiling and Application in Biomarker Discovery.

Biomolecular corona formation has emerged as a recurring and important phenomenon in nanomedicine that has been investigated for potential applications in disease diagnosis. In this study, we have combined the "personalized protein corona" with the N-glycosylation profiling that has recently gained considerable interest in human plasma biomarker discovery as a powerful early warning diagnostic and patient stratification tool. We envisioned that the protein corona formation could be exploited as an enrichment step that is critically important in both proteomic and proteoglycomic workflows. By using silica nanoparticles, plasma fibrinogen was enriched to a level in which its proteomic and glycomic "fingerprints" could be traced with confidence. Despite being a more simplified glycan profile compared to full plasma, the corona glycan profile revealed a fibrinogen-derived glycan peak that was found to potentially distinguish lung cancer patients from controls in a pilot study.

Vaping-Associated Lung Injury: A Review.

Since commercial development in 2003, the usage of modern electronic cigarette (e-cigarette) continues to increase amongst people who have never smoked, ex-smokers who have switched to e-cigarettes, and dual-users of both conventional cigarettes and e-cigarettes. With such an increase in use, knowledge of the irritative, toxic and potential carcinogenic effects on the lungs is increasing. This review article will discuss the background of e-cigarettes, vaping devices and explore their popularity. We will further summarise the available literature describing the mechanism of lung injury caused by e-cigarette or vaping use.

The utility of gallium-68 DOTATOC PET/CT in lymphangioleiomyomatosis.

Somatostatin receptor functional imaging is of limited utility as an imaging biomarker in LAM, but other PET/CT modalities may be of use https://bit.ly/3l6BVZp.

Exosomes: a new perspective in EGFR-mutated lung cancer.

Exosomes are major contributors in cell to cell communication due to their ability to transfer biological material such as protein, RNA, DNA, and miRNA. Additionally, they play a role in tumor initiation, promotion, and progression, and recently, they have emerged as a potential source of information on tumor detection and may be useful as diagnostic, prognostic, and predictive tools. This review focuses on exosomes from lung cancer with a focus on EGFR mutations. Here, we outline the role of exosomes and their functional effect in carcinogenesis, tumor progression, and metastasis. Finally, we discuss the possibility of exosomes as novel biomarkers in early detection, diagnosis, assessment of prognosis, and prediction of therapeutic response in EGFR-mutated lung cancer.

Clarifying the relationship between pulmonary langerhans cell histiocytosis and Alpha 1 antitrypsin deficiency.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare, smoking related, progressive diffuse cystic lung disease that occurs primarily in smokers. The aim of this study was to determine if there was an increase in alpha-1 antitrypsin deficient alleles or phenotypes in a large series of PLCH patients and whether serum alpha-1 antitrypsin levels correlated with markers of disease severity. Fifty PLCH patients, 24 with a diffuse cystic lung pattern and 26 with a typical nodulo-cystic pattern on imaging were included. The mean alpha-1 antitrypsin levels were in normal range for both the population with diffuse cystic lung pattern population (1.39 g/L ± 0.37) and the nodulo-cystic pattern group (1.41 g/L ± 0.21). Deficiency alleles PiZ and PiS were 1% and 2% respectively in the entire study population of 50 patients, demonstrating no increased incidence of alpha-1 antitrypsin deficiency in PLCH. Alpha-1 antitrypsin levels showed no correlation with lung function parameters or extent of cystic lesions on lung computed tomography.

Differentiating combined pulmonary fibrosis and emphysema from pure emphysema: utility of late gadolinium-enhanced MRI.

BACKGROUND: Differentiating combined pulmonary fibrosis with emphysema (CPFE) from pure emphysema can be challenging on high-resolution computed tomography (HRCT). This has antifibrotic therapy implications. METHODS: Twenty patients with suspected CPFE underwent late gadolinium-enhanced (LGE) thoracic magnetic resonance imaging (LGE-MRI) and HRCT. Data from twelve healthy control subjects from a previous study who underwent thoracic LGE-MRI were included for comparison. Quantitative LGE signal intensity (SI) was retrospectively compared in regions of fibrosis and emphysema in CPFE patients to similar lung regions in controls. Qualitative comparisons for the presence/extent of reticulation, honeycombing, and traction bronchiectasis between LGE-MRI and HRCT were assessed by two readers in consensus. RESULTS: There were significant quantitative differences in fibrosis SI compared to emphysema SI in CPFE patients (25.8, IQR 18.4-31.0 versus 5.3, IQR 5.0-8.1, p < 0.001). Significant differences were found between LGE-MRI and HRCT in the extent of reticulation (12.5, IQR 5.0-20.0 versus 25.0, IQR 15.0-26.3, p = 0.038) and honeycombing (5.0, IQR 0.0-10.0 versus 20.0, IQR 10.6-20.0, p = 0.001) but not traction bronchiectasis (10.0, IQR 5-15 versus 15.0, IQR 5-15, p = 0.878). Receiver operator curve analysis of fibrosis SI compared to similarly located regions in control subjects showed an area under the curve of 0.82 (p = 0.002). A SI cutoff of 19 yielded a sensitivity of 75% and specificity of 86% in differentiating fibrosis from similarly located regions in control subjects. CONCLUSION: LGE-MRI can differentiate CPFE from pure emphysema and may be a useful adjunct test to HRCT in patients with suspected CPFE.

CXCR3A promotes the secretion of the antifibrotic decoy receptor sIL-13Rα2 by pulmonary fibroblasts.

CXC chemokine receptor 3 (CXCR3) A and its IFN-inducible ligands CXCL9 and CXCL10 regulate vascular remodeling and fibroblast motility. IL-13 is a profibrotic cytokine implicated in the pathogenesis of inflammatory and fibroproliferative conditions. Previous work from our laboratory has shown that CXCR3A is negatively regulated by IL-13 and is necessary for the basal regulation of the IL-13 receptor subunit IL-13Rα2. This study investigates the regulation of fibroblast phenotype, function, and downstream IL-13 signaling by CXCR3A in vitro. CXCR3A was overexpressed via transient transfection. CXCR3A-/- lung fibroblasts were isolated for functional analysis. Additionally, the contribution of CXCR3A to tissue remodeling following acute lung injury was assessed in vivo with wild-type (WT) and CXCR3-/- mice challenged with IL-13. CXCR3 and IL-13Rα2 displayed a reciprocal relationship after stimulation with either IL-13 or CXCR3 ligands. CXCR3A reduced expression of fibroblast activation makers, soluble collagen production, and proliferation. CXCR3A enhanced the basal expression of pERK1/2 while inducing IL-13-mediated downregulation of NF-κB-p65. CXCR3A-/- pulmonary fibroblasts were increasingly proliferative and displayed reduced contractility and α-smooth muscle actin expression. IL-13 challenge regulated expression of the CXCR3 ligands and soluble IL-13Rα2 levels in lungs and bronchoalveolar lavage fluid (BALF) of WT mice; this response was absent in CXCR3-/- mice. Alveolar macrophage accumulation and expression of genes involved in lung remodeling was increased in CXCR3-/- mice. We conclude that CXCR3A is a central antifibrotic factor in pulmonary fibroblasts, limiting fibroblast activation and reducing extracellular matrix (ECM) production. Therefore, targeting of CXCR3A may be a novel approach to regulating fibroblast activity in lung fibrosis and remodeling.