Development and Application of Procedures for the Management of Skin Toxicity Related to Immune Checkpoint Inhibitors in Patients with Lung Cancer

Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the Oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in Ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.

What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years

BACKGROUND Lung cancer bone metastasis(LCBM)is a disease with a poor prognosis,high risk and large patient population.Although considerable scientific output has accumulated on LCBM,problems have emerged,such as confusing research structures.AIM To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation,clinical treatment,and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research.METHODS We used tools,including R,VOSviewer and CiteSpace software,to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection.We also performed enrichment and proteinprotein interaction analyses of gene expression datasets from LCBM cases worldwide.RESULTS Research on LCBM has received extensive attention from scholars worldwide over the last 20 years.Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions.The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis.The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence.CONCLUSION Novel therapies for LCBM face animal testing and drug resistance issues.Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.

New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Association of Insulin-like Growth Factors with Lung Development in Neonatal Rats

To explore the relationship between Insulin-like growth factor (IGF)- Ⅰ, -Ⅱ and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley ( SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. Lung tissues were used for histopathological study, the polypeptides analysis of IGF-Ⅰ, -Ⅱ (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF-Ⅰ in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-Ⅰ during gestation age of 18 days to age of 3 days in group B were significantly higher (P<0.01), but significantly lower at other time points (P<0.01). The expression of IGF-Ⅰ was lower in group C all the time and always higher in group D than those in group A (P<0.01). The peak expression of IGF-Ⅱ took place at the gestation age of 18 days, then gradually dropped to trace. During 18 days of gestation to age of 3 days, the expression of IGF-Ⅱ in group B was significantly higher than that in group A (P<0.01). No difference was found among all other groups. The change in the expression of IGF-Ⅰ, -Ⅱ mRNA in all 4 groups was similar to that of their polypeptides. The results suggested that there is a close linking between IGF-Ⅰ, -Ⅱ and lung development in newborns. The IGF-Ⅱ works at early stage and the that of IGF-Ⅰ works at the stage of new septa formation and alveoli maturation. The stronger their expressions, the more mature the lung development.

Effects of Hyperoxia on the Dynamic Expression of Aquaporin5 in Premature Rats Lung Development

To explore the dynamic expression and role of Aquaporin5 ( AQP5) in lung development and hyperoxia lung injury, gestation 21-day Sprague-Dawley (SD) rats (term=22 days) were ran- domly assigned to air group and hyperoxia group within 12-24 h after birth. The rats in hypreoxia group were continuously exposed to about 85% oxygen and those in air group to room air. After 1 to 14 days of exposure, total lung RNA was extracted and the expression of AQP5 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry and west- ern-blot were used to detect the expression of AQP5 protein. The results showed that the expression of AQP5 in premature rats lung could be detected at various time points after birth, and the positive staining was restricted to the type Ⅰ alveolar epithelial cells. In air group, the AQP5 expression was detected in a very low level at day 1, but exhibited a persistent increase after birth. Compared with the air group, the expression of AQP5 in hyperoxia group was increased at day 1, and had significant difference in mRNA level (P<0.05), but decreased significantly in mRNA and protein levels after 4 to 14 days (P<0.01 or P<0.05 respectively). It was concluded that AQP5 might play a key role in the alveolar period of premature rats by regulating the lung water balance. Hyperoxia exposure leads to a down-regulation of the AQP5 expression, which may be an important factor for the development of hyperoxia lung injury.

Growth factors and fetal lung development mediated by mechanical forces

Incomplete development of the lung secondary to extreme prematurity or pulmonary hypoplasia causes significant morbidity and mortality during the neonatal period. Currently, the management is primarily supportive with no specific treatment to stimulate the growth and development of the lung. Mechanical forces generated inside the fetal lung by constant distention pressure and "breathing-like movements" are a major determinant of fetal lung development. However, the mechanisms by which lung cells sense these mechanical signals to promote lung development are not well-defined. Tracheal ligation has been used not only experimentally but also in human fetuses affected by severe congenital diaphragmatic hernia to stimulate lung growth and decrease the degree of pulmonary hypoplasia. Past investigations suggested that the increase of intratracheal pressure after tracheal ligation releases soluble factors that are critical for lung development. Studies from our laboratory have shown that mechanical strain of fetal type Ⅱ epithelial cells, simulating mechanical forces in utero, promotes differentiation via release of epidermal growth factor receptor ligands heparin binding epidermal growth factor-like growth factor and transforming growth factor alpha. The identification of growth factors released by mechanical forces that are importantfor normal lung development could lead to novel treatments to accelerate lung development.

Mechanisms of the alternative activation of macrophages and non-coding RNAs in the development of radiation-induced lung fibrosis

Radiation-induced lung fibrosis(RILF) is a common side effect of thoracic irradiation therapy and leads to high mortality rates after cancer treatment. Radiation injury induces inflammatory M1 macrophage polarization leading to radiation pneumonitis, the first stage of RILF progression. Fibrosis occurs due to the transition of M1 macrophages to the anti-inflammatory pro-fibrotic M2 phenotype, and the resulting imbalance of macrophage regulated inflammatory signaling. Non-coding RNA signaling has been shown to play a large role in the regulation of the M2 mediated signaling pathways that are associated with the development and progression of fibrosis. While many studies show the link between M2 macrophages and fibrosis, there are only a few that explore their distinct role and the regulation of their signaling by non-coding RNA in RILF. In this review we summarize the current body of knowledge describing the roles of M2 macrophages in RILF, with an emphasis on the expression and functions of non-coding RNAs.

Factors affecting complications development and mortality after single lung transplant

Lung transplantation(LT)is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease.Furthermore,as a therapeutic option for high-risk candidates,single LT(SLT)can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single(double)LT(SSLTx).Still,the long-term overall survival is,in general,better for SSLTx.Despite the great success over the years,the early post-SLT period remains a perilous time for these patients.Patients who undergo SLT are predisposed to evolving early or late postoperative complications.This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction,native lung complications,anastomosis complications,infections,cardiovascular,gastrointestinal,renal,and metabolite complications,and their association with morbidity and mortality in these patients.Furthermore,we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.

Effect of Retinoic acid on Platelet-derived Growth Factorand Lung Development in Newborn Rats

Summary: The influence of platelet-derived growth factor (PDGF) on lung development in newborn rats and the effect of retinoic acid (RA) on PDGF in lung development were investigated. Newborn Sprague-Dawley (SD) rats were randomly assigned to two groups: control group and RA group. The rats in RA group was intraperitoneally injected with all trans-retinoic acid (500 μg/kg every day) for consecutive 3 days after birth, while those in the control group were not subjected to intervention. Immunohistochemical assay was performed to locate the expression of PDGF. mRNA levels of PDGF were measured by reverse transcription polymerase chain reaction (RT-PCR) at age of 1, 3, 5, 7, 10, 14, 21 days. The method of radial alveolar counts (RAC) was used to measure the amount of the alveoli of the lungs. It was found that with increasing days, levels of PDGF-A and PDGF-B changed to verying degrees. RA could elevate significantly the expression levels of PDGF-A mRNA and protein (P<0.01), but not affect the expression levels of PDGF-B mRNA and protein markedly (P>0.05). It is suggested that PDGF might play an important role in lung development. RA can stimulate lung development through increasing the expression levels of PDGF-A mRNA and protein.

Lung development:AT1 and AT2 property

The human respiratory system consists of the upper and the lower respiratory tracts.Anatomically,the lower respiratory tract consists of the trachea,bronchi,bronchioles(terminal bronchioles and respiratory bronchioles),alveolar duct,alveolar duct sacs,and alveoli.Alveoli are composed of two epithelial cell types,cuboidal alveolar type 2(AT2)cells that secrete surfactant to prevent alveolar collapse and function as stem cells to regenerate alveolar type 1(AT1)cells during damage repair,and squamous AT1 cells that cover most of the surface area of the alveoli and mediate gas exchange.Previous studies mainly focused on AT2 cells;this review summarizes the current studies on lung development and property of AT1 cells.

LungPoint导航联合吲哚菁绿荧光成像在Ⅰa期非小细胞肺癌淋巴结采样中的应用价值

目的:寻找一种准确定位Ⅰa期非小细胞肺癌患者(NSCLC)前哨淋巴结(SLN)的方法,验证SLN作为淋巴结取样样本的合理性。方法:采用前瞻性研究方法,参照入组标准纳入2021年1月至2023年12月在山东省公共卫生临床中心胸外科临床分期为Ⅰa期NSCLC住院患者50例,术前借助LungPoint导航气管镜下肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像完成SLN定位,并对包括SLN在内的区域淋巴结行病理学检查,使用该方法对SLN的识别率、准确率与假阴性率等验证其作为淋巴结取样样本的合理性。结果:50例患者中,41例检测到SLN,识别率为82.0%(41/50),经病理检测发现3例共计9枚SLN有淋巴结转移(阳性),其中1例亦检出非前哨淋巴结(N-SLN)阳性2枚。9例患者未检测到SLN,清扫淋巴结54枚,未发现转移淋巴结,故SLN准确率为100.0%(41/41),假阴性率为0(0/3)。结论:借助LungPoint气管镜在肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像探寻SLN技术具有较高的区域淋巴结转移预测性,有望成为指导Ⅰa期NSCLC系统性淋巴结采样的依据。

Development of a new choroidal metastasis in resistance to crizotinib therapy in anaplastic lymphoma kinaserearranged non-small cell lung cancer

INTRODUCTION Non-small cell lung cancer（NSCLC）is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,and in 6%to 7%of patients based on postmortem histopathologic studies.

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

Pre-malignant processes of smoking-induced lung adenocarcinoma development: A conceptual biological model

Chronic exposure to cigarette smoke is the leading cause of human lung cancer and its most prevalent form, adenocarcinoma. However, the mechanisms by which smoking induces adenocarcinoma are largely inferred from the analysis of fully developed tumors. The current work focuses on the early events that precede the existence of clinically detectable tumors and where the progressive mechanisms are believed to be different from the ones driving established tumor growth. Biological information was drawn from the literature and generalized into a conceptual model, or framework, which describes and integrates the main processes involved in the early stages of smoking-induced lung adenocarcinoma development. No such integrative representation currently exists. The biological framework presented here is based on the “field of injury” of the lung. It covers the smoking-induced stepwise transition of unexposed (naive) lung tissue to the first appearance of neoplastic cells through defined tissue states referred to as pre-field and field. Each tissue state exhibits its own formalized characteristics (or phenotype properties), which evolve as a result of the combined effects of smoking, the interactions between the different tissue properties, and the local environment represented in the framework as lung inflammation and immune surveillance. The resulting network of influences between the lung tissue states and properties provides a good understanding of the early events involved in lung adenocarcinoma triggered by smoking. The resulting conceptual model—an integrative mechanistic hypothesis—can explain a broad range of cigarette smoking and smoking cessation scenarios.

Development of Aseptic Renal Abscess in a Patient with Non-Small-Cell Lung Cancer with ALK Translocation during Crizotinib Treatment

Background: Crizotinib is a tyrosine kinase inhibitor of ALK, MET and ROS1. In a safety database trial, it was suggested an association of Crizotinib with the development of renal cyst in patients with non-small-cell lung cancer (NSCLC). Aim: To report an uncommon side effect of Crizotinib in a patient with NSLC. Case Presentation: We report the case of a 68-year-old woman with NSCLC who developed bilateral progressive aseptic renal abscesses during Crizotinib treatment. Conclusion: Further studies may be necessary to determinate the risk of renal cyst development and the management of these complications.

Animal Model of Lung Metastasis of Hepatocellular Carcinoma: A Tool for the Development of Anti-Metastatic Therapeutics

We observed that N-nitrosomorpholine (NMOR) given after a multi-carcinogenic treatment induces liver carcinomas with 56% lung metastasis. An additional treatment with diethylnitrosamine (DEN) with NMOR further enhanced the incidence of hepatocellular carcinoma (HCC) with lung metastasis. We have further revised the duration of NMOR treatment to establish an animal model with a simple experimental protocol and an appropriate experimental duration to facilitate investigation exploring the mechanisms of HCC metastasis and development of anti-metastatic therapeutics. We observed that DEN exposure followed by a 16-week treatment with NMOR to be a most efficient protocol for the induction of HCC metastasizing to the lung. In this review, we will discuss about the usefulness of animal models for induction of highly metastatic HCC and the assessment of the efficacy of anti-metastatic therapeutics. Additionally, we will also discuss use of these models in analysis of individual steps in the metastatic process by using non-steroidal anti-inflammatory drugs, aspirin and indomethacin, two nuclear factor kappa B (NF-κB) inhibitors, pentoxifylline and N-acetyl-L-cysteine.

Multilevel Attention Unet Segmentation Algorithmfor Lung Cancer Based on CT Images

Lung cancer is a malady of the lungs that gravely jeopardizes human health.Therefore,early detection and treatment are paramount for the preservation of human life.Lung computed tomography(CT)image sequences can explicitly delineate the pathological condition of the lungs.To meet the imperative for accurate diagnosis by physicians,expeditious segmentation of the region harboring lung cancer is of utmost significance.We utilize computer-aided methods to emulate the diagnostic process in which physicians concentrate on lung cancer in a sequential manner,erect an interpretable model,and attain segmentation of lung cancer.The specific advancements can be encapsulated as follows:1)Concentration on the lung parenchyma region:Based on 16-bit CT image capturing and the luminance characteristics of lung cancer,we proffer an intercept histogram algorithm.2)Focus on the specific locus of lung malignancy:Utilizing the spatial interrelation of lung cancer,we propose a memory-based Unet architecture and incorporate skip connections.3)Data Imbalance:In accordance with the prevalent situation of an overabundance of negative samples and a paucity of positive samples,we scrutinize the existing loss function and suggest a mixed loss function.Experimental results with pre-existing publicly available datasets and assembled datasets demonstrate that the segmentation efficacy,measured as Area Overlap Measure(AOM)is superior to 0.81,which markedly ameliorates in comparison with conventional algorithms,thereby facilitating physicians in diagnosis.

Effect of Impaired Lung Function on the Development and Progression of Endobronchial Premalignant Lesions

Background: Chronic obstructive pulmonary disease (COPD) and presence of endobronchial premalignant lesions (EPL) are individual risk factors for lung cancer (LC). However, effect of impaired lung function (ILF) on the natural history of EPL has not been explored. Patients and Methods: This study included 217 high-risk participants from a hospital-based LC surveillance cohort who underwent pulmonary function testing followed by bronchoscopy with endobronchial biopsies. Baseline histopathology diagnoses included 91 cases (41.9%) with squamous metaplasia (SM), 25 (11.5%) with squamous dysplasia (SD), 1 (0.5%) with in-situ carcinoma and 5 (2.3%) with invasive LC. Follow-up biopsies were obtained for 69 patients, and 16 (23.2%) patients demonstrated progression to a higher grade lesion. Regression models were used to evaluate the relationship between ILF and EPL. All the models were adjusted for age, gender and tobacco smoking. Results: Patients with FEV1% of <50% had 4.5 times greater risk of being diagnosed with an EPL [95% confidence interval: 1.93-10.80] and 8-fold greater risk of SD, compared to patients with FEV1% ≥80. COPD was associated with 2.7 and 4.8 times greater risk of SM and SD, respectively. The mean time to progression to a higher-grade lesion was shorter in COPD patients compared to patients without COPD (27 versus 50 months, p = 0.02). Conclusion: Our results indicate that ILF may be a predictor of prevalence and progression of EPLs among patients at high risk of LC. Therefore, spirometry can be a complementary pre-screening tool for identifying patients with EPL who need more intense LC surveillance.