The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Assessment of toxicological validity using tobacco emission condensates: A comparative analysis of emissions and condensates from 3R4F reference cigarettes and heated tobacco products.

The tobacco emission condensate, henceforth referred to as "tobacco condensate," plays a critical role in assessing the toxicity of tobacco products. This condensate, derived from tobacco emissions, provides an optimized liquid concentrate for storage and concentration control. Thus, the validation of its constituents is vital for toxicity assessments. This study used tobacco condensates from 3R4F cigarettes and three heated tobacco product (HTP) variants to quantify and contrast organic compounds (OCs) therein. The hazard index (HI) for tobacco emissions and condensates was determined to ascertain the assessment validity. The total particulate matter (TPM) for 3R4F registered at 17,667 µg cig-1, with its total OC (TOC) at 3777 µg cig-1. HTPs' TPM and TOC were 9342 ± 1918 µg cig-1 and 5258 ± 593 µg stick-1, respectively. 3R4F's heightened TPM likely arises from tar, while HTPs' OC concentrations are influenced by vegetable glycerin (2236-2688 µg stick-1) and propylene glycol (589-610 µg stick-1). During the condensation process, a substantial proportion of OCs in 3R4F smoke underwent significant concentration decreases, in contrast to HTPs, where fewer than half of the examined OCs exhibited notable concentration declines. The HI for tobacco emissions exhibited a marginally higher value compared to tobacco condensate, with variations ranging from 7.92% (HTPs) to 18.6% (3R4F), denoting a minimal differential. These observations emphasize the importance of accurate OC recovery techniques to maintain the validity and reliability of toxicity assessments based on tobacco condensates. This study not only deepens the comprehension of chemical behaviors in tobacco products but also establishes a novel benchmark for their toxicity evaluation, with profound implications for public health strategies and consumer protection.

NIR-responsive carboxymethyl-cellulose hydrogels containing thioketal-linkages for on-demand drug delivery system.

Near-infrared (NIR) light-responsive hydrogels have emerged as a highly promising strategy for effective anticancer therapy owing to the remotely controlled release of chemotherapeutic molecules with minimal invasive manner. In this study, novel NIR-responsive hydrogels were developed from reactive oxygen species (ROS)-cleavable thioketal cross-linkers which possessed terminal tetrazine groups to undergo a bio-orthogonal inverse electron demand Diels Alder click reaction with norbornene modified carboxymethyl cellulose. The hydrogels were rapidly formed under physiological conditions and generated N2 gas as a by-product, which led to the formation of porous structures within the hydrogel networks. A NIR dye, indocyanine green (ICG) and chemotherapeutic doxorubicin (DOX) were co-encapsulated in the porous network of the hydrogels. Upon NIR-irradiation, the hydrogels showed spatiotemporal release of encapsulated DOX (>96 %) owing to the cleavage of thioketal bonds by interacting with ROS generated from ICG, whereas minimal release of encapsulated DOX (<25 %) was observed in the absence of NIR-light. The in vitro cytotoxicity results revealed that the hydrogels were highly cytocompatible and did not induce any toxic effect on the HEK-293 cells. In contrast, the DOX + ICG-encapsulated hydrogels enhanced the chemotherapeutic effect and effectively inhibited the proliferation of Hela cancer cells when irradiated with NIR-light.

A facile approach for oil-water separation using superhydrophobic polystyrene-silica coated stainless steel mesh bucket.

Inspired by traditional shaduf technology in the irrigation field, we fabricated a superhydrophobic stainless steel mesh bucket by layering polystyrene and SiO2 nanoparticles through a facile dip coating technique for effective oil-water separation. The superhydrophobic steel mesh bucket could effectively lift oil as well as microplastic pollutants from the water surface. The water contact angle of a two-layered polystyrene-silica coating was 158.5° ± 2°, while the oil contact angle was nearly 0°. The oil-water separation performance of superhydrophobic mesh was tested using several kinds of oil. The separation efficiency achieved for low viscous oil was 99.33 %, while 86.66 % efficiency was recorded for high viscous oil. The superhydrophobic mesh showed high durability against mechanical tests including bending, folding, twisting, adhesive tape tearing (25 cycles), and sandpaper abrasion (20 cycles). The mesh presented admirable thermal and chemical durability. The present superhydrophobic steel mesh bucket is a suitable candidate for large-scale application.

Repeated intratracheal instillation of whole-cigarette smoke condensate to assess lung damage in a rat model.

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.

Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal-Photodynamic Anti-Tumor Therapy.

Novel chemically cross-linked hydrogels derived from carboxymethyl cellulose (CMC) and alginate (Alg) were prepared through the utilization of the norbornene (Nb)-methyl tetrazine (mTz) click reaction. The hydrogels were designed to generate reactive oxygen species (ROS) from an NIR dye, indocyanine green (ICG), for combined photothermal and photodynamic therapy (PTT/PDT). The cross-linking reaction between Nb and mTz moieties occurred via an inverse electron-demand Diels-Alder chemistry under physiological conditions avoiding the need for a catalyst. The resulting hydrogels exhibited viscoelastic properties (G' ~ 492-270 Pa) and high porosity. The hydrogels were found to be injectable with tunable mechanical characteristics. The ROS production from the ICG-encapsulated hydrogels was confirmed by DPBF assays, indicating a photodynamic effect (with NIR irradiation at 1-2 W for 5-15 min). The temperature of the ICG-loaded hydrogels also increased upon the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility assessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Furthermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells after NIR exposure.

Effects of comorbid chronic kidney disease on mortality in idiopathic pulmonary fibrosis patients and influence of pirfenidone.

Chronic kidney disease (CKD) is a comorbidity in idiopathic pulmonary fibrosis (IPF), and managing IPF with CKD is challenging due to limited options for antifibrotic therapy. The aim of this study was to examine the prevalence of CKD and prescription status of pirfenidone in IPF patients and to analyze its impact on mortality. Data from the Korean National Health Insurance Service (NHIS) database between October 2015 and September 2021 were used. IPF and CKD were defined based on both International Classification of Diseases 10th Revision (ICD-10) codes and Rare Intractable Disease (RID) codes. The risk of mortality was assessed based on accompanying CKD with or without antifibrotic therapy. Among 5038 patients with IPF, 8.4% had comorbid CKD and 83.3% with CKD did not receive renal replacement therapy (RRT). Patients with IPF and CKD were older, predominantly male, and had more frequent comorbidities such as cardiovascular disease and diabetes mellitus than subjects without CKD. Pirfenidone was prescribed to 105 (24.6%) of 426 CKD patients, and 89.5% of them did not receive RRT. Pirfenidone was also prescribed to 775 (16.8%) of 4612 IPF patients without CKD. Significant difference was not found in all-cause mortality between the IPF patients with or without CKD regardless of pirfenidone treatment. The use of antifibrotics in IPF patients with CKD is limited due to CKD severity; however, evidence is lacking. Mortality did not increase with accompanying CKD regardless of antifibrotic use. Further research on IPF and CKD is needed.

Development and validation of a method for preparing heated tobacco product aerosol condensate (HTPAC) for large-scale toxicity data acquisition.

A method of preparing heated tobacco product aerosol condensate (HTPAC) was developed to expedite HTP toxicity evaluation, and the effectiveness was assessed. To prepare HTPAC, HTP aerosol was generated and collected using a Cambridge filter (particulate phase) and Dulbecco's phosphate buffered saline (DPBS; gaseous phase). The aerosol collected on the Cambridge filter was extracted using methanol, which was thereafter removed by nitrogen purging. The HTP aerosol residue was mixed with DPBS loaded with the collected HTP vapor, ultimately yielding HTPAC. Nicotine and formaldehyde, key harmful compounds in HTP aerosol, were detected in HTPAC (901 ± 224 and 22.2 ± 3.90 µg stick-1, respectively, comparable to those in HTP aerosol (990-1350 (nicotine) and 2.33-21.9 µg stick-1 (formaldehyde)). Propylene glycol and vegetable glycerin, which influence the amount of HTP aerosol, were detected at similar levels in HTPAC and HTP aerosol (propylene glycol = 616 ± 57.1 (HTPAC) and 320-630 µg stick-1 (aerosol) and vegetable glycerin = 2418 ± 224 (HTPAC) and 1667-4000 µg stick-1 (aerosol)). Known components of HTP aerosol (hydroxyacetone, acetic acid, triacetin, and 2-furanmethanol) were also detected in HTPAC. Consequently, HTPAC offers an effective method for concentrating harmful compounds found in HTP aerosols. This, in turn, facilitates comprehensive toxicity assessments, paving the way for guidelines ensuring the safe utilization of HTP.

Identification of predictive factors for early relapse in patients with unresectable stage III non-small cell lung cancer receiving consolidation durvalumab after concurrent chemoradiation therapy.

BACKGROUND: Patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) receiving definitive concurrent chemoradiation therapy (CCRT) benefit from durvalumab consolidation therapy. However, predictive factors for early relapse during durvalumab maintenance have not yet been identified. METHODS: The present study included the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from January 2018 to December 2021. A total of 51 NSCLC patients treated with durvalumab consolidation therapy after definitive CCRT were included in the analysis. Early relapse was defined as patients experiencing relapse within 6 months of starting initial durvalumab therapy. RESULTS: Among the 51 patients, 15 (29.4%) relapsed during the study period. Median time from initial therapy of durvalumab to progression was 451.00 ± 220.87 days (95% confidence interval [CI]: 18.10-883.90) in overall patients. In multivariate analysis, younger age (adjusted odds ratio [aOR], 0.792; 95% CI: 0.642-0.977; p = 0.030), higher pack-years (aOR, 1.315; 95% CI: 1.058-1.635; p = 0.014), non-COPD (aOR, 0.004; 95% CI: 0.000-0.828; p = 0.004) and anemia (aOR, 234.30; 95% CI: 1.212-45280.24; p = 0.042), were independent predictive factors for early relapse during durvalumab consolidation therapy. CONCLUSION: Younger age, higher number of pack-years, non-COPD, and anemia were independent predictive factors for early relapse during durvalumab consolidation therapy in patients with unresectable stage III NSCLC after definitive CCRT. Careful patient selection and clinical attention are needed for high-risk individuals.

Nationwide epidemiologic study for fibrosing interstitial lung disease (F-ILD) in South Korea: a population-based study.

BACKGROUND: Fibrosing interstitial lung disease (F-ILD) is a major public health concern due to its poor prognosis. Recent clinical evidence shows that antifibrotic approaches such as pirfenidone and nintedanib provide better clinical outcome prediction in idiopathic pulmonary fibrosis (IPF) as well as selected progressive fibrosing ILD (PF-ILD) patients. Having epidemiologic insight into these diseases will be essential for the efficient utilization of these therapeutic resources. This study aimed to estimate the current prevalence, incidence, and mortality of F-ILD classified as idiopathic pulmonary fibrosis (IPF), PF-ILD other than IPF, and non-progressive F-ILD and their temporal trend in Korea. METHODS: Population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment (HIRA) database (2011-2018). Patients with IPF were identified using ICD-10 code, RID code, and differential diagnosis approach. By leveraging medical records available from claim data and referencing those used in clinical trials, rigorous diagnostic criteria for PF-ILD detection were implemented. RESULTS: For the past eight years, the prevalence of IPF and PF-ILD has progressively increased, while non-progressive F-ILD has remained stable. IPF, PF-ILD, and non-progressive F-ILD prevalence per 100,000 in 2018 were 16.9, 10.4, and 11.7, respectively. The incidence of IPF in 2018 was more than twice that of 2012. The incidence of PF-ILD in 2018 was 1.5 times higher than that in 2012. In 2018, the mortalites were 10.3% and 12.2% for IPF and PF-ILD, respectively. The mortality rate of PF-ILD was greater than that of IPF in all years. Unclassifiable PF-ILD and rheumatoid arthritis-PF-ILD had the highest proportion and mortality among the PF-ILD subtypes. CONCLUSION: The prevalence and incidence of IPF and PF-ILD have been steadily increasing in recent years. The mortality rate of PF-ILD remained consistently high and exceeded those of IPF in all years.

Comparison of the effects of triglyceride variability and exposure estimate on clinical prognosis in diabetic patients.

BACKGROUND: Hypertriglyceridemia is an important feature of dyslipidemia in type 1 and type 2 diabetic patients and associated with the development of atherosclerotic cardiovascular disease. Recently, variability of lipid profile has been suggested as a residual risk factor for cardiovascular disease. This study compared the clinical impact of serum triglyceride variability, and their cumulative exposure estimates on cardiovascular prognosis in diabetic patients. METHODS: A total of 25,933 diabetic patients who had serum triglyceride levels measured at least 3 times and did not have underlying malignancy, myocardial infarction (MI), and stroke during the initial 3 years (modeling phase) were selected from three tertiary hospitals. They were divided into a high/low group depending on their coefficient of variation (CV) and cumulative exposure estimate (CEE). Incidence of major adverse event (MAE), a composite of all-cause death, MI, and stroke during the following 5 years were compared between groups by multivariable analysis after propensity score matching. RESULTS: Although there was a slight difference, both the high CV group and the high CEE group had a higher cardiovascular risk profile including male-dominance, smoking, alcohol, dyslipidemia, and chronic kidney disease compared to the low groups. After the propensity score matching, the high CV group showed higher MAE incidence compared to the low CV group (9.1% vs 7.7%, p = 0.01). In contrast, there was no significant difference of MAE incidence between the high CEE group and the low CEE group (8.6% vs 9.1%, p = 0.44). After the multivariable analysis with further adjustment for potential residual confounding factors, the high CV was suggested as an independent risk predictor for MAE (HR 1.19 [95% CI 1.03-1.37]). CONCLUSION: Visit-to-visit variability of triglyceride rather than their cumulative exposure is more strongly related to the incidence of MAE in diabetic patients.

Challenge exposure to whole cigarette smoke condensate upregulates locomotor sensitization by stimulating α4ß2 nicotinic acetylcholine receptors in the nucleus accumbens of rats.

Nicotine, the primary addictive substance in tobacco, produces the psychomotor, rewarding, and reinforcing effects of tobacco dependence by stimulating nicotinic acetylcholine receptors (nAChRs) in the brain. The present study determined that α4ß2 nAChRs regulate locomotor sensitization by altering dopamine concentration in the nucleus accumbens (NAc) after systemic challenge exposure to whole cigarette smoke condensate (WCSC). Rats were administered subcutaneous injection of WCSC (0.2 mg/kg nicotine/day) for 7 consecutive days and then re-exposed to WCSC after 3 days of withdrawal. Challenge exposure to WCSC significantly increased locomotor activity. This increase was decreased by the subcutaneous injection of the α4ß2 nAChR antagonist, DHßE (3 mg/kg), but not by the intraperitoneal injection of the α7 nAChR antagonist, MLA (5 mg/kg). In parallel with a decrease in locomotor activity, blockade of α4ß2 nAChRs with DHßE decreased dopamine concentration in the NAc which was elevated by challenge exposure to WCSC. These findings suggest that challenge WCSC leads to the expression of locomotor sensitization by elevating dopamine concentration via stimulation of α4ß2 nAChRs expressed in neurons of the NAc in rats.

Regulation of nuclear DNA damage response by mitochondrial morphofunctional pathway.

Cells are constantly challenged by genotoxic stresses that can lead to genome instability. The integrity of the nuclear genome is preserved by the DNA damage response (DDR) and repair. Additionally, these stresses can induce mitochondria to transiently hyperfuse; however, it remains unclear whether canonical DDR is linked to these mitochondrial morphological changes. Here, we report that the abolition of mitochondrial fusion causes a substantial defect in the ATM-mediated DDR signaling. This deficiency is overcome by the restoration of mitochondria fusion. In cells with fragmented mitochondria, genotoxic stress-induced activation of JNK and its translocation to DNA lesion are lost. Importantly, the mitochondrial fusion machinery of MFN1/MFN2 associates with Sab (SH3BP5) and JNK, and these interactions are indispensable for the Sab-mediated activation of JNK and the ATM-mediated DDR signaling. Accordingly, the formation of BRCA1 and 53BP1 foci, as well as homology and end-joining repair are impaired in cells with fragmented mitochondria. Together, these data show that mitochondrial fusion-dependent JNK signaling is essential for the DDR, providing vital insight into the integration of nuclear and cytoplasmic stress signals.

Comparison of Surgical Outcomes between Trabeculectomy with Mitomycin C and Ahmed Valve Implantation with Mitomycin C in Eyes with Uveitic Glaucoma.

We compared 1-year outcomes of trabeculectomy with mitomycin C (MMC) and Ahmed valve implantation with MMC as a first surgical procedure in patients with uveitic glaucoma. A total 38 eyes of 38 patients undergoing trabeculectomy (n =16) or Ahmed valve implantation (n = 22) were included. Surgical success was defined as intraocular pressure (IOP) ≤21 mmHg, IOP reduction ≥20% from baseline, no secondary glaucoma surgery, and no loss of light perception. The main outcome measurements including success rate, IOP, and the number of antiglaucoma medications and complications were compared. The overall success rates were comparable between the Ahmed and trabeculectomy groups (81.3 vs. 81.8%, p = 0.987). The mean IOPs were similar as well (p = 0.084), though the number of antiglaucoma medications was significantly lower in the trabeculectomy group than in the Ahmed group (1.0 ± 1.2 vs. 2.2 ± 1.1; p = 0.005). A statistically significant reduction in corneal endothelial cell density was noted in the Ahmed group (p = 0.004). Both treatments offered reasonable IOP control and safety for eyes with uveitic glaucoma. However, significantly fewer antiglaucoma medications were used in the trabeculectomy group. Furthermore, our results suggest that cautious postoperative monitoring with regard to corneal endothelial cell density should be additionally performed after Ahmed valve implantation.

Nicotine Rather Than Non-Nicotine Substances in 3R4F WCSC Increases Behavioral Sensitization and Drug-Taking Behavior in Rats.

INTRODUCTION: Nicotine increases reinforcing effects of cigarette smoking by upregulating glutamate and dopamine releases via stimulation of nicotinic acetylcholine receptors (nAChRs) in the dorsal striatum (CPu). The present study was conducted to evaluate whether non-nicotine substances in cigarette smoke potentiate nicotine-induced behaviors by increasing glutamate and dopamine concentrations in the CPu. AIMS AND METHODS: Changes in the levels of glutamate and dopamine in the CPu were analyzed using a glutamate colorimetric assay and dopamine enzyme-linked immunosorbent assay, respectively, after repeated administration of nicotine or whole cigarette smoke condensate (WCSC) in male Sprague-Dawley rats. Changes in locomotion and drug-taking behavior were analyzed using the measurements of locomotor activity and self-administration under a fixed ratio 1 schedule in response to repeated administration of nicotine or WCSC. RESULTS: Repeated subcutaneous (s.c.) injections of nicotine (0.25 mg/kg/day) for 7 consecutive days significantly increased the levels of glutamate and dopamine in the CPu. Similar results were obtained from repeated injections of WCSC (0.25 mg/kg nicotine/day, s.c.) extracted from 3R4F Kentucky reference cigarettes. Parallel with the increases in the neurotransmitter levels in the CPu, both nicotine and WCSC increased locomotor activity and self-administration (0.03 mg/kg nicotine/infusion). However, repeated injections of WCSC did not change the nicotine-induced increases in neurotransmitter levels, locomotor activity, and self-administration. CONCLUSIONS: Nicotine rather than non-nicotine substances in WCSC play a major role in potentiating behavioral sensitization and drug-taking behavior via elevation of glutamate and dopamine concentrations in the CPu of rats. IMPLICATIONS: WCSC does not augment the nicotine-induced increases in behavioral sensitization, drug-taking behavior, and glutamate and dopamine concentrations, suggesting that non-nicotine substances do not potentiate the nicotine-induced behaviors by increasing the concentrations of the neurotransmitters in the CPu. These findings imply that nicotine, but not non-nicotine substances in WCSC, may be a major contributor that induces tobacco dependence in rats.

Volatile organic compounds released in the mainstream smoke of flavor capsule cigarettes.

In this study, the composition of mainstream smoke was investigated with an emphasis on a list of volatile organic compounds (VOCs: e.g., isoprene, acrylonitrile, methyl ethyl ketone, benzene, toluene, m-xylene and styrene) using the two types of flavor capsule cigarettes (FCCs, here coded as F1 and F2) in reference to one commercial, non-flavored (NF) and 3R4F cigarette. The concentrations of all the target compounds from FCCs were quantified under two contrasting conditions (i.e., with and without breaking the capsules). The effect of breaking the capsule was apparent in the FCC products with the enhancement of VOC levels, specifically between after and before breaking the capsules (e.g., 1.10-1.58 folds (benzene) and 1.30-1.53 folds (acetonitrile)). Such increases were apparent in both FCC samples if assessed in terms of the total amount of VOCs (TVOC): (1) F1 (from 2159 to 2530 µg cig-1 (p = 9.42 × 10-6)) and (2) F2 (from 1470 to 2014 µg cig-1 (p = 0.05)). In addition, these TVOC levels determined from the FCCs were 1.62- to 1.83- and 1.29- to 1.46-fold higher than those of the NF cigarette and the 3R4F cigarette, respectively. Thus, these FCC products are suspected to play a role as stronger sources of VOCs than the general cigarette products.

Effects of low-dose pirfenidone on survival and lung function decline in patients with idiopathic pulmonary fibrosis (IPF): Results from a real-world study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia of unknown etiology. In several randomized clinical trials, and in the clinical practice, pirfenidone is used to effectively and safely treat IPF. However, sometimes it is difficult to use the dose of pirfenidone used in clinical trials. This study evaluated the effects of low-dose pirfenidone on IPF disease progression and patient survival in the real-world. METHODS: This retrospective, observational study enrolled IPF patients seen at the time of diagnosis at a single center from 2008 to 2018. Longitudinal clinical and laboratory data were prospectively collected. We compared the clinical characteristics, survival, and pulmonary function decline between patients treated and untreated with various dose of pirfenidone. RESULTS: Of 295 IPF patients, 100 (33.9%) received pirfenidone and 195 (66.1%) received no antifibrotic agent. Of the 100 patients who received pirfenidone, 24 (24%), 50 (50%), and 26 (26%), respectively, were given 600, 1200, and 1800 mg pirfenidone daily. The mean survival time was 57.03 ± 3.90 months in the no-antifibrotic drug group and 73.26 ± 7.87 months in the pirfenidone-treated group (p = 0.027). In the unadjusted analysis, the survival of the patients given pirfenidone was significantly better (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.48-0.99, p = 0.04). After adjusting for age, gender, body mass index, and the GAP score [based on gender (G), age (A), and two physiological lung parameters (P)], survival remained better in the patients given pirfenidone (HR = 0.56, 95% CI: 0.37-0.85, p = 0.006). In terms of pulmonary function, the decreases in forced vital capacity (%), forced expiratory volume in 1 s (%) and the diffusing capacity of lung for carbon monoxide (%) were significantly smaller (p = 0.000, p = 0.001, and p = 0.007, respectively) in patients given pirfenidone. CONCLUSIONS: Low-dose pirfenidone provided beneficial effects on survival and pulmonary function decline in the real-world practice.

Tracheobronchopathia Osteochondroplastica Associated with Fibrotic Interstitial Lung Disease.

Tracheobronchopathia osteochondroplastica (TPO) is a very rare, benign disorder involving the lumen of the trachea-bronchial tree. However, its etiology is unknown. In our first case, observation for several years showed that TPO worsened as interstitial lung disease was aggravated. In the second case, the lung parenchymal lesion on computed tomography (CT) was found to be compatible with interstitial lung abnormality (ILA). We believe that our cases suggest a common pathogenetic relationship between TPO and fibrotic interstitial lung disease. TGF-ß is likely a common factor in the pathogenesis of TPO and fibrotic interstitial lung disease.

Clinical significance of microbial colonization identified by initial bronchoscopy in patients with lung cancer requiring chemotherapy.

BACKGROUND: There are limited data on the association between bronchial colonization and respiratory infections in people with lung cancer requiring cytotoxic chemotherapy. We investigated whether bronchial colonization in initial bronchoscopy specimens can predict the development of pneumonia after chemotherapy in patients with lung cancer. METHODS: Four hundred thirteen patients with lung cancer included in the Catholic Medical Center lung cancer registry were enrolled from March 2015 to August 2018. Demographic data, microbiology results, development of pneumonia after chemotherapy, and clinical information about lung cancer were analyzed retrospectively. RESULTS: A total of 206 lung cancer patients treated with chemotherapy were included in the analysis. Forty patients (19.4%) had positive results for the bronchial washing culture during the initial evaluation of lung cancer. The most common organisms were Klebsiella pneumoniae (n=14) and Streptococcus pneumoniae (n=6) in the surveillance culture, and Pneumocystis jirovecii (n=12) and Staphylococcus aureus (n=8) at the time of pneumonia development. Eighty-nine patients (43.2%) had pneumonia after chemotherapy, but the occurrence of pneumonia did not differ according to the colonization. There were no patients for whom the initial isolated organism was a causative microbe for the development of pneumonia after or during chemotherapy. The pneumonia group had poorer prognosis than the non-pneumonia group (378 vs. 705 days, P=0.0004). CONCLUSIONS: Microbial colonization in bronchoscopy specimens was not associated with pneumonia development or mortality after chemotherapy for lung cancer. This finding suggests that testing surveillance culture may not be helpful for predicting pneumonia or improving survival in lung cancer patients with chemotherapy.