Search

Abstract Background Few data are available on acute exacerbation (AE) in patients with progressive pulmonary fibrosis (PPF) besides idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the AE incidence and outcomes among patients with PPF. Methods Clinical data of patients with PPF (n = 133) were retrospectively collected at a single center. PPF was defined based on the criteria used in the INBUILD trial. AE was defined as a worsening of dyspnea typically within 30 days with new bilateral lung infiltration and no evidence of cardiac failure or fluid overload. Results Among patients with PPF, the mean age was 60.6 years old, 57.1% were females, and the most common etiology was connective tissue disease-related ILDs (63%). During the follow-up (median: 38.0 months) after PPF diagnosis, 42 patients (31.6%) experienced AE. The 1-, 3-, and 5-year AE incidences were 12.5%, 30.3%, and 38.0%, respectively. Older age, rheumatoid arthritis associated ILD, fibrotic hypersensitivity pneumonitis, and lower lung diffusing capacity for carbon monoxide were AE risk factors. Patients with AE demonstrated worse survival (median survival: 30 months vs. not reached; p

Abstract It remains unclear whether pulmonary fibrosis-like changes differ in patients with different SARS-CoV-2 variants. This study aimed to compare pulmonary fibrotic changes between two SARS-CoV-2 variant periods (delta vs. pre-delta) in critically ill patients with SARS-CoV-2 pneumonia. Clinical data and chest CT images of patients with SARS-CoV-2 pneumonia receiving mechanical ventilation were collected from 10 hospitals in South Korea over two periods: delta (July-December, 2021; n = 64) and pre-delta (February, 2020-June, 2021; n = 120). Fibrotic changes on chest CT were evaluated through visual assessment. Of 184 patients, the mean age was 64.6 years, and 60.5% were ale. Fibrosis-like changes on chest CT (median 51 days from enrollment to follow up CT scan, interquartile range 27–76 days) were identified in 75.3%. Delta group showed more fibrosis-like changes (≥ 2) (69.8% vs. 43.1%, P = 0.001) and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Even after propensity score matching with clinical variables, delta group had more severe (≥ 2) fibrosis-like changes (71.4% vs. 38.8%, P = 0.001), and more frequent reticulation and architectural distortion+/-parenchymal band than pre-delta group. Our data suggest that critically ill patients with SARS-CoV-2 in delta period had more severe pulmonary fibrosis-like changes than those in pre-delta period.

Abstract Background Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. Methods This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC)

Abstract Background Dysregulation of lipid metabolism is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the association between the blood lipid profiles and the prognosis of IPF is not well defined. We aimed to identify the impacts of lipid profiles on prognosis in patients with IPF. Methods Clinical data of 371 patients with IPF (145 and 226 in the derivation and validation cohorts, respectively), including serum lipid profiles (total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I [Apo A-I], and apolipoprotein B), were retrospectively collected. The association with mortality was analyzed using the Cox proportional hazard model. Results In the derivation cohort, the mean age was 67.5 years, 86.2% were men, and 30.3% died during the follow-up (median: 18.0 months). Non-survivors showed lower lung function and greater gender-age-physiology scores than survivors. Among the serum lipid profiles, the levels of triglyceride and Apo A-I were significantly lower in non-survivors than in survivors. In the multivariate Cox analysis, low Apo A-I levels (

Backgrounds The management of lung complications, especially fibrosis, after COVID-19 pneumonia, is an important issue in the COVID-19 post-pandemic era. We aimed to investigate risk factors for pulmonary fibrosis development in patients with severe COVID-19 pneumonia.Methods Clinical and radiological data were prospectively collected from 64 patients who required mechanical ventilation due to COVID-19 pneumonia and were enrolled from eight hospitals in South Korea. Fibrotic changes on chest CT were evaluated by visual assessment, and extent of fibrosis (mixed disease score) was measured using automatic quantification system.Results 64 patients were enrolled, and their mean age was 58.2 years (64.1% were males). On chest CT (median interval: 60 days [IQR; 41–78 days] from enrolment), 35 (54.7%) patients showed ≥3 fibrotic lesions. The most frequent fibrotic change was traction bronchiectasis (47 patients, 73.4 %). Median extent of fibrosis measured by automatic quantification was 10.6% (IQR, 3.8–40.7%). In a multivariable Cox proportional hazard model, which included nine variables with a p value of

Abstract This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020–December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2

Abstract Association between body mass index (BMI) and prognosis in patients with idiopathic pulmonary fibrosis (IPF) remains uncertain. We investigated the association between BMI and clinical outcomes in patients with IPF using national health claims data. The study included 11,826 patients with IPF and rare incurable disease exemption codes (mean age: 68.9 years, male: 73.8%) and available BMI data who visited medical institutions between January 2002 and December 2018. Multivariable Cox proportional hazard models were used to evaluate the association of BMI with all-cause mortality and hospitalization. Based on BMI, 3.1%, 32.8%, 27.8%, and 36.4% were classified as underweight, normal, overweight, and obese, respectively. Multivariable analysis showed independent associations of overweight (hazard ratio [HR] 0.856, 95% confidence interval [CI] 0.801–0.916) and underweight (HR 1.538, 95% CI 1.347–1.757) with mortality in patients with IPF. Similarly, overweight (HR 0.887, 95% CI 0.834–0.943) and underweight (HR 1.265, 95% CI 1.104–1.449) were also associated with hospitalization in patients with IPF in the multivariable analysis. Spline HR curve analysis adjusted for all covariates revealed a non-linear relationship between BMI and mortality in patients with IPF. Our data suggest that BMI is associated with clinical outcomes in patients with IPF.

Abstract Background Smoking status has been linked to the development of idiopathic pulmonary fibrosis (IPF). However, the effect of smoking on the prognosis of patients with IPF is unclear. We aimed to investigate the association between smoking status and all-cause mortality or hospitalisation by using national health claims data. Methods IPF cases were defined as people who visited medical institutions between January 2002 and December 2018 with IPF and rare incurable disease exempted calculation codes from the National Health Insurance Database. Total 10,182 patients with available data on smoking status were included in this study. Ever-smoking status was assigned to individuals with a history of smoking ≥ 6 pack-years. The multivariable Cox proportional hazard model was used to evaluate the association between smoking status and prognosis. Results In the entire cohort, the mean age was 69.4 years, 73.9% were males, and 45.2% were ever smokers (current smokers: 14.2%; former smokers: 31.0%). Current smokers (hazard ratio [HR]: 0.709; 95% confidence interval [CI]: 0.643–0.782) and former smokers (HR: 0.926; 95% CI: 0.862–0.996) were independently associated with all-cause mortality compared with non-smokers. Current smokers (HR: 0.884; 95% CI: 0.827–0.945) and former smokers (HR: 0.909; 95% CI: 0.862–0.959) were also associated with a reduced risk of all-cause hospitalisation compared with non-smokers. A non-linear association between smoking amount and prognosis was found in a spline HR curve and showed increasing risk below 6 pack-years. Conclusion Ever-smoking status may be associated with favourable clinical outcomes in patients with IPF.

Interstitial lung diseases (ILDs) are a diverse collection of lung disorders sharing similar features, such as inflammation and fibrosis. The diagnosis and management of ILD require a multidisciplinary approach using clinical, radiological, and pathological evaluation. Progressive pulmonary fibrosis (PPF) is a distinct form of progressive and fibrotic disease, occurring in ILD cases other than in idiopathic pulmonary fibrosis (IPF). It is defined based on clinical symptoms, lung function, and chest imaging, regardless of the underlying condition. The progression to PPF must be monitored through a combination of pulmonary function tests (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide), an assessment of symptoms, and computed tomography scans, with regular follow-up. Although the precise mechanisms of PPF remain unclear, there is evidence of shared pathogenetic mechanisms with IPF, contributing to similar disease behavior and worse prognosis compared to non-PPF ILD. Pharmacological treatment of PPF includes immunomodulatory agents to reduce inflammation and the use of antifibrotics to target progressive fibrosis. Nintedanib, a known antifibrotic agent, was found to be effective in slowing IPF progression and reducing the annual rate of decline in FVC among patients with PPF compared to placebos. Nonpharmacological treatment, including pulmonary rehabilitation, supplemental oxygen therapy, and vaccination, also play important roles in the management of PPF, leading to comprehensive care for patients with ILD. Although there is currently no cure for PPF, there are treatments that can help slow the progression of the disease and improve quality of life.

Background: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder characterized by the proliferation of abnormal smooth muscle-like cells. Although serum vascular endothelial growth factor-D (VEGF-D) is currently used as a diagnostic biomarker for LAM, its diagnostic value in Korean patients is unclear. Objectives: To evaluate the diagnostic value of serum VEGF-D for LAM in Korean patients. Design: A multicenter prospective cohort study Methods: Serum samples were prospectively collected from five medical institutions, from patients with LAM ( n = 40) and controls ( n = 24; healthy participants = 3, other cystic lung diseases = 13, idiopathic pulmonary fibrosis = 4, idiopathic nonspecific interstitial pneumonia = 4). Serum VEGF-D levels were measured using the enzyme-linked immunosorbent assay, and the diagnostic value was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The mean age of patients with LAM was 44.5 years, and all were female (controls: 47.8 years; female: 70.8%, p

BackgroundPirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®.MethodsA nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared.ResultsOf the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were −1.5% and −2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen.ConclusionThe safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence.

Background We used data from the INMARK trial to investigate associations between circulating biomarkers of extracellular matrix (ECM) turnover, inflammation and epithelial dysfunction and disease progression in subjects with idiopathic pulmonary fibrosis (IPF). Methods Subjects with IPF and forced vital capacity (FVC) ≥80% predicted were randomised 1:2 to receive nintedanib 150 mg twice daily or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Associations between baseline biomarker levels and the proportion of subjects with disease progression (decline in FVC ≥10% predicted or death) over 52 weeks were assessed in subjects randomised to placebo using logistic regression. Associations between baseline demographic/clinical characteristics and biomarker levels and disease progression over 52 weeks were analysed using multivariate models. Results Of 230 subjects who received placebo for 12 weeks then open-label nintedanib for 40 weeks, 70 (30.4%) had disease progression over 52 weeks. Baseline levels of CRPM (C-reactive protein (CRP) degraded by matrix metalloproteinase (MMP)-1/8), C3M (collagen 3 degraded by MMP-9), CRP, KL-6 (Krebs von den Lungen-6) and SP-D (surfactant protein D) were not significantly associated with disease progression over 52 weeks in analyses corrected for multiple comparisons. In models including only baseline demographic/clinical characteristics, 61.2–64.2% of subjects were correctly classified as having or not having disease progression over 52 weeks. When both demographic/clinical characteristics and biomarker levels were included in the models, 50.0–64.5% of the test set were correctly classified. Conclusions Among subjects with IPF and preserved FVC, multivariate models based on demographic/clinical characteristics and biomarker levels at baseline did not provide an accurate prediction of which patients would progress.

Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease with a poor prognosis. While there is evidence suggesting that outdoor air pollution affects the clinical course of IPF, the impact of indoor air pollution on patients with IPF has not been extensively studied. Therefore, this prospective multicentre observational study aims to investigate the association between indoor air pollution and clinical outcomes in patients with IPF.Methods and analysis This study enrolled 140 patients with IPF from 12 medical institutes in the Seoul and Metropolitan areas of the Republic of Korea. Over the course of 1 year, participants visited the institutes every 3 months, during which their clinical data and blood samples were collected. Additionally, indoor exposure to particulate matter ≤2.5 µm (PM2.5) was measured using MicroPEM (RTI International, Research Triangle Park, North Carolina, USA) in each participant’s house for 5 days every 3 months. Lung function was assessed using both site spirometry at each institution and portable spirometry at each participant’s house every 3 months. The study will analyse the impact of indoor PM2.5 on clinical outcomes, including mortality, acute exacerbation, changes in lung function and health-related quality of life, in the participants. This study represents the first attempt to evaluate the influence of indoor air pollution on the prognosis of patients with IPF.Ethics and dissemination This study has received approval from the institutional review board of all participating institutions, including Asan Medical Center, Seoul, Republic of Korea (2021-0072).Trial registration number KCT0006217.

Abstract Background Despite the importance of recognizing interstitial lung abnormalities, screening methods using computer-based quantitative analysis are not well developed, and studies on the subject with an Asian population are rare. We aimed to identify the prevalence and progression rate of interstitial lung abnormality evaluated by an automated quantification system in the Korean population. Methods A total of 2,890 healthy participants in a health screening program (mean age: 49 years, men: 79.5%) with serial chest computed tomography images obtained at least 5 years apart were included. Quantitative lung fibrosis scores were measured on the chest images by an automated quantification system. Interstitial lung abnormalities were defined as a score ≥ 3, and progression as any score increased above baseline. Results Interstitial lung abnormalities were identified in 251 participants (8.6%), who were older and had a higher body mass index. The prevalence increased with age. Quantification of the follow-up images (median interval: 6.5 years) showed that 23.5% (59/251) of participants initially diagnosed with interstitial lung abnormality exhibited progression, and 11% had developed abnormalities (290/2639). Older age, higher body mass index, and higher erythrocyte sedimentation rate were independent risk factors for progression or development. The interstitial lung abnormality group had worse survival on follow-up (5-year mortality: 3.4% vs. 1.5%; P = 0.010). Conclusions Interstitial lung abnormality could be identified in one-tenth of the participants, and a quarter of them showed progression. Older age, higher body mass index and higher erythrocyte sedimentation rate increased the risk of development or progression of interstitial lung abnormality.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with a very poor prognosis. Accurate diagnosis of IPF is essential for good outcomes but remains a major medical challenge due to variability in clinical presentation and the shortcomings of existing diagnostic tests. Medical history collection is the first and most important step in the IPF diagnosis process; the clinical probability of IPF is high if the suspected patient is 60 years or older, male, and has a history of cigarette smoking. Systemic assessment for connective tissue disease is essential in the initial evaluation of patients with suspected IPF to identify potential causes of interstitial lung disease (ILD). Radiologic examination using high-resolution computed tomography plays a pivotal role in the evaluation of patients with ILD, and prone and expiratory computed tomography images can be considered. If additional tests such as surgical lung biopsy or transbronchial lung cryobiopsy are needed, transbronchial lung cryobiopsy should be considered as an alternative to surgical lung biopsy in medical centers with experience performing this procedure. Diagnosis through multidisciplinary discussion (MDD) is strongly recommended as MDD has become the cornerstone for diagnosis of IPF, and the scope of MDD has expanded to monitoring of disease progression and suggestion of appropriate treatment options.

Abstract Frailty as a syndrome of physical decline in late life is associated with adverse health outcomes. Knee osteoarthritis (KOA) could contribute to frailty conditions. The objective of this study was to evaluate the impact of KOA on frailty risk in a Korean National Health and Nutrition Examination Survey (KNHANES) cohort. In this study (N, total = 11,910, age; 64.10 years old [63.94–64.27; mean 95% CI], sex (female, %); 6,752 (56.69)), KOA patients were defined as those with knee joint pain and grade 2 Kellgren–Lawrence (K–L) or more on plain radiographic images who were 40 years old or older in Korean population data of KNHANES. The frailty index was calculated using 46 items related to co-morbidities and laboratory parameters. The impact of KOA on frailty risk was evaluated with logistic regression analyses. The prevalence of KOA patients was 35.6% [95% CI 34.7–36.46]. In polytomous logistic regression, the relative risk ratio (RRR) of KOA was significantly increased in the pre-frail group (2.76, 95% CI 2.30–3.31) and the frail group (7.28, 95% CI 5.90–8.98). RRR of frailty was significantly increased in patients with K–L grade 3 (1.36, 95% CI 1.13–1.63) and K-L grade 4 (2.19, 95% CI 1.72–2.79). Older age, higher BMI, smoking status, alcohol intake, low-income status, higher WBC count, higher platelet count, higher serum creatinine level and low estimated GFR were significantly associated with increased frailty risk. High hemoglobin and regular walking habits were associated with decreased frailty risk in KOA patients. In this large observation population- based survey cohort, KOA is linked to an increased risk of frailty syndrome. We found a significant connection between KOA and frailty syndrome. These results show that we need to think about the overall health of people with KOA and give them special care to prevent frailty syndrome.

Background As rhinoplasty techniques have become more complex, surgeons often need more than what septal or conchal cartilage can provide. While costal cartilage became more popular for that reason, some surgeons are still uncomfortable with its invasiveness and donor site morbidity. Here, we used lyophilized allogeneic costal cartilage for septorhinoplasty and investigated its safety and usefulness. Methods The costal cartilage was harvested from a cadaveric donor and treated via multiple steps, including defatting and lyophilization, to remove all viable cells and antigenicity. The cartilage was then stored at room temperature and rehydrated 24 hours before use. Lyophilized cartilage allografts were used in 20 patients. Three types of septal graft were performed — spreader, batten, and extension — to correct septal or columellar deviation and enhance the nasal tip. Results The mean follow-up period was 4.3 years. In all cases, the graft successfully met the rhinoplasty purpose. No significant deformation was detected in any of the patients. Although warping was observed in one patient (5%), there was no case of clinical infection, extrusion, or graft removal and no revisional surgery for an unfavorable aesthetic result. Conclusions Lyophilized allogeneic cartilage was used for septorhinoplasty very safely and effectively. It can be carved into any shape and has all other properties required for perfectly replacing autologous costal cartilage. The main advantage of cartilage allografts is a limitless supply of high-quality cartilage without donor site morbidity. The disadvantages include the need for special facilities and manpower and extra covering cost.

Objectives The effect of air pollution on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains poorly understood. We aimed to evaluate the effect of long-term exposure to particulate matter with an aerodynamic diameter of ≤10 µm (PM10) and nitrogen dioxide (NO2) on mortality in patients with RA-ILD.Methods We included 309 patients (mean age, 61.7 years; male, 44.3%) with RA-ILD. Individual-level long-term exposures to PM10 and NO2 at their residential addresses were estimated using a national-scale exposure prediction model. The effect of the two air pollutants on mortality was estimated using a Cox-proportional hazards model adjusted for individual-level and area-level characteristics.Results The median follow-up period was 4.8 years, and 40.8% of patients died or underwent lung transplantation. The annual average concentrations of PM10 and NO2 were 56.3 μg/m3 and 22.4 ppb, respectively. When air pollutant levels were stratified by quartiles, no association was observed between air pollutant concentration and mortality in patients with RA-ILD. However, when stratified by two groups (high exposure (top 25th percentile) vs low exposure (bottom 75th percentile)), we observed a significant association between high PM10 exposure and mortality (HR 1.68; 95% CI 1.11 to 2.52; p=0.013) but no association between NO2 exposure and mortality. In the subgroup analyses, the effect of high PM10 exposure on mortality was significant in patients aged

Abstract Background Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder characterized by fibrofolliculomas, renal tumors, pulmonary cysts, and recurrent pneumothorax. Pulmonary cysts are the cause of recurrent pneumothorax, which is one of the most important factors influencing patient quality of life. It is unknown whether pulmonary cysts progress with time or influence pulmonary function in patients with BHD syndrome. This study investigated whether pulmonary cysts progress during long-term follow-up (FU) by using thoracic computed tomography (CT) and whether pulmonary function declines during FU. We also evaluated risk factors for pneumothorax in patients with BHD during FU. Methods Our retrospective cohort included 43 patients with BHD (25 women; mean age, 54.2 ± 11.7 years). We evaluated whether cysts progress by visual assessment and quantitative volume analysis using initial and serial thoracic CT. The visual assessment included the size, location, number, shape, distribution, presence of a visible wall, fissural or subpleural cysts, and air-cuff signs. In CT data obtained from a 1-mm section from 17 patients, the quantitative assessment was performed by measuring the volume of the low attenuation area using in-house software. We evaluated whether the pulmonary function declined with time on serial pulmonary function tests (PFT). Risk factors for pneumothorax were analyzed using multiple regression analysis. Results On visual assessment, the largest cyst in the right lung showed a significant interval increase in size (1.0 mm/year, p = 0.0015; 95% confidence interval [CI], 0.42–1.64) between the initial and final CT, and the largest cyst in the left lung also showed significant interval increase in size (0.8 mm/year, p

Background: Recent studies have suggested that combination therapy with pirfenidone and nintedanib is safe and tolerable in patients with idiopathic pulmonary fibrosis (IPF). However, data from real-world practice are limited. Thus, we aimed to investigate the safety and efficacy of this combination therapy in patients with IPF in a real-world setting.Methods: A multicenter retrospective cohort study was conducted to investigate the safety and efficacy of combination therapy with pirfenidone and nintedanib in 45 patients with IPF. Incidences of adverse events and rates of lung function decline were compared before and after the combination therapy. Propensity score matching was performed to compare the outcomes between the combination and monotherapy groups.Results: The mean age of the patients was 68.8 years, and 82.2% of them were male. The median follow-up duration after combination therapy was 12.1 months. The majority of the patients (97.8%) received nintedanib as an add-on to pirfenidone. The most common adverse events after the combination therapy were diarrhea and anorexia. Pirfenidone or nintedanib was stopped in 12 patients owing to gastrointestinal AEs, lung transplantation, or financial problems. In patients with serial lung function data, the rate of decline in the forced vital capacity was significantly reduced after the combination therapy. In the matched analysis, the combination group had a higher incidence of diarrhea than the monotherapy group without an increase in serious adverse events; however, the two groups had similar changes in forced vital capacity (FVC).Conclusion: The combination of pirfenidone and nintedanib in patients with IPF has the potential to reduce the rate of FVC decline. However, in the matched analysis, FVC decline was comparable between the patients on combination therapy and those on monotherapy. The incidence of certain adverse events, particularly diarrhea, was higher with combination therapy, but serious adverse events were similar between the groups.

Abstract Background Antifibrotic therapy can slow disease progression (DP) in patients with idiopathic pulmonary fibrosis (IPF). However, the prognostic biomarkers for DP in patients with IPF receiving antifibrotic therapy have not been identified. Therefore, we aimed to evaluate the prognostic efficacy of serum Krebs von den Lungen-6 (KL-6) for DP in patients with IPF receiving antifibrotic therapy. Methods The clinical data of 188 patients with IPF who initiated antifibrotic therapy at three tertiary hospitals was retrospectively analyzed. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, diffusing capacity for carbon monoxide ≥ 15%, acute exacerbation, or deaths during 6 months after antifibrotic therapy. Results The mean age of patients was 68.9 years, 77.7% were male, and DP occurred in 43 patients (22.9%) during follow-up (median, 7.6 months; interquartile range, 6.2–9.8 months). There was no difference in baseline KL-6 levels between the DP and no-DP groups; however, among patients with high baseline KL-6 levels (≥ 500 U/mL), changes in KL-6 levels over 1 month were higher in the DP group than those in the non-DP group, and higher relative changes in KL-6 over 1 month were independently associated with DP (odds ratio, 1.043; 95% confidence interval 1.005–1.084) in the multivariable logistic analysis adjusted for age and FVC. In the receiver operating characteristic curve analysis, the 1-month change in KL-6 was also useful for predicting DP (area under the curve = 0.707; P

Abstract Polymorphic genes with immune functions, namely those of the human leukocyte antigen (HLA) system, have been implicated in sarcoidosis pathogenesis. As HLA polymorphisms in sarcoidosis have not been yet investigated in the Korean population, we used next-generation sequencing (NGS), allowing detailed characterization of HLA alleles to investigate the role of HLA variation in Korean sarcoidosis patients. We enrolled 103 patients diagnosed by the ATS/ERS/WASOG guidelines at Asan Medical Centre, Seoul, Korea. Among those, genotyping of 7 HLA loci (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -DPB1) was performed using Omixon Holotype™ kit and HLATwin software™. HLA allele frequencies were compared with frequency data on healthy Koreans from the allelic frequency databases, and 4-digit characteristics of HLA genotyping were used. Associations were assessed by two-tailed Fischer’s exact test with correction for multiple comparisons. Variants previously associated with sarcoidosis risk (HLA-C*03:04, HLA-DRB1*12:01, HLA-DRB1*14:54) and a known protective variant HLA-DPB1*04:01, were associated with sarcoidosis in Koreans. Further, we suggest new HLA variants associated with sarcoidosis risk (e.g., HLA-DQA1*05:08) and novel protective variants HLA-DQB1*03:02 and HLA-DQA1*01:02 in Koreans. This first study of HLA variation in Korean patients with sarcoidosis by precise genotyping methodology reports data that could serve future meta-analyses on HLA variation’s role in sarcoidosis.

Abstract Background Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD) featuring dense fibrosis of the visceral pleura and subpleural parenchyma, mostly in the upper lobes. PPFE can present in other ILDs, including rheumatoid arthritis-associated ILD (RA-ILD). The aim of this retrospective study was to investigate the prevalence and clinical implications of coexistent PPFE in RA-ILD. Methods Overall, 477 patients with RA-ILD were recruited from two cohorts; their clinical data and HRCT images were analysed. The criteria for diagnosing PPFE were (1) pleural thickening with bilateral subpleural dense fibrosis in the upper lobes, (2) evidence of disease progression, and (3) absence of other identifiable aetiologies. Results The median follow-up duration was 3.3 years. The mean age of the patients was 63.4 years, and 60.0% were women. PPFE was identified in 31 patients (6.5%). The PPFE group showed significantly lower body mass index and forced vital capacity (FVC) and more frequent usual interstitial pneumonia (UIP)-like pattern on HRCT than no-PPFE group. The risk factors for all-cause mortality were older age, lower FVC, and the presence of UIP-like pattern on HRCT; PPFE was not significantly associated with mortality in both all patients and a subgroup with a UIP-like pattern. The presence of PPFE was associated with a significantly increased risk of pneumothorax and greater decline in diffusing capacity. Conclusions PPFE was not rare in patients with RA-ILD and was significantly associated with an increased risk of pneumothorax and greater lung function decline, though we found no significant association with mortality.

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder with various clinical manifestations. Despite the recognition of several prognostic factors, the long-term clinical course and prognosis of patients with LAM in the era of sirolimus therapy are not established. Methods The clinical data of 104 patients with LAM were retrospectively analyzed. Death or lung transplantation was defined as the primary outcome. Disease progression (DP) was defined as a 10% absolute decline in forced expiratory volume in one second (FEV1). Results The mean age of all patients was 40.3 years. Over a median follow-up period of 7.1 years, of all patients, 6.7% died and 1.9% underwent lung transplantation, while of 92 patients with serial lung function data, 35.9% experienced DP. The 5-year and 10-year overall survival rates were 93.0% and 90.9%, respectively. The multivariable Cox analysis revealed that older age (hazard ratio [HR]: 1.136, P = 0.025), lower FEV1 (HR: 0.956, P = 0.026) or diffusing capacity for carbon monoxide (HR: 0.914, P = 0.003), and shorter distance during the 6-min walk test (HR: 0.993, P = 0.020) were independent prognostic factors for mortality. A propensity score-matched comparative analysis performed between patients who received sirolimus therapy and those who did not, found no differences in survival, DP, complications, and lung function decline rate. Conclusions Over a follow-up period of approximately 7 years, one-tenth of all patients experienced death, while one-third experienced DP. Older age, lower lung function, and reduced exercise capacity were associated with a poor prognosis in patients with LAM.

Abstract The revised definition of acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) was proposed in 2016, but changes in the incidence and impact on prognosis of the re-defined AE compared to those of the previous definition remain unclear. Clinical data of 445 patients with IPF (biopsy proven cases: 165) were retrospectively reviewed. The median follow-up period was 36.8 months and 17.5% (n = 78) experienced AE more than once. The 1- and 3-year incidence rates of AE were 6.7% and 16.6%, respectively, and idiopathic AE accounted for 82.1% of AE. Older age, lower diffusing capacity of the lung for carbon monoxide and 10% relative decline in forced vital capacity for 6 months were independently associated with AE. The in-hospital mortality rate following AE was 29.5%. In the multivariable analysis, AE was independently associated with poor prognosis in patients with IPF. Compared to the old definition, the revised definition relatively increased the incidence of AE by 20.4% and decreased the in-hospital mortality by 10.1%. Our results suggest that the revised definition affects approximately 20% increase in the incidences and 10% reduction in the in-hospital mortality of AE defined by the past definition.

Abstract Background Retinoid-related orphan receptor-α (RORα) and autophagy dysregulation are involved in the pathophysiology of chronic obstructive pulmonary disease (COPD), but little is known regarding their association. We investigated the role of RORα in COPD-related autophagy. Methods The lung tissues and cells from a mouse model were analyzed for autophagy markers by using western blot analysis and transmission electron microscopy. Results Cigarette smoke increased the LC3-II level and decreased the p62 level in whole lung homogenates of a chronic cigarette smoking mouse model. Although cigarette smoke did not affect the levels of p62 in Staggerer mutant mice (RORαsg/sg), the baseline expression levels of p62 were significantly higher than those in wild type (WT) mice. Autophagy was induced by cigarette smoke extract (CSE) in Beas-2B cells and in primary fibroblasts from WT mice. In contrast, fibroblasts from RORαsg/sg mice failed to show CSE-induced autophagy and exhibited fewer autophagosomes, lower LC3-II levels, and higher p62 levels than fibroblasts from WT mice. Damage-regulated autophagy modulator (DRAM), a p53-induced modulator of autophagy, was expressed at significantly lower levels in the fibroblasts from RORαsg/sg mice than in those from WT mice. DRAM knockdown using siRNA in Beas-2B cells inhibited CSE-induced autophagy and cell death. Furthermore, RORα co-immunoprecipitated with p53 and the interaction increased p53 reporter gene activity. Conclusions Our findings suggest that RORα promotes autophagy and contributes to COPD pathogenesis via regulation of the RORα-p53-DRAM pathway.

Background The Korea Interstitial Lung Disease Study Group has made a new nationwide idiopathic pulmonary fibrosis (IPF) registry because the routine clinical practice has changed due to new guidelines and newly developed antifibrotic agents in the recent decade. The aim of this study was to describe recent clinical characteristics of Korean IPF patients. Methods Both newly diagnosed and following IPF patients diagnosed after the previous registry in 2008 were enrolled. Survival analysis was only conducted for patients diagnosed with IPF after 2016 because antifibrotic agents started to be covered by medical insurance of Korea in October 2015. Results A total of 2,139 patients were analyzed. Their mean age at diagnosis was 67.4±9.3 years. Of these patients, 76.1% were males, 71.0% were ever-smokers, 14.4% were asymptomatic at the time of diagnosis, and 56.9% were at gender-age-physiology stage I. Occupational toxic material exposure was reported in 534 patients. The mean forced vital capacity was 74.6% and the diffusing capacity for carbon monoxide was 63.6%. Treatment with pirfenidone was increased over time: 62.4% of IPF patients were treated with pirfenidone initially. And 79.2% of patients were treated with antifiboritics for more than three months during the course of the disease since 2016. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality. Conclusion In the recent Korean IPF registry, the percentage of IPF patients treated with antifibrotics was increased compared to that in the previous IPF registry. Old age, acute exacerbation, treatment without antifibrotics, and exposure to wood and stone dust were associated with higher mortality.

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents and surgical approaches may be beneficial in patients with CPFE, but further studies are needed.

Abstract Interstitial lung disease associated with primary Sjögren’s syndrome (SJS-ILD) has a variable clinical course. We aimed to investigate the role of blood biomarkers in predicting prognosis for SJS-ILD. Clinical data of 46 SJS-ILD patients were retrospectively reviewed. Plasma biomarker levels, including Krebs von den Lungen-6 (KL-6), CC chemokine ligand 18 (CCL18), chitinase-3-like-1 (YKL-40), interleukin-4 receptor alpha (IL-4Ra), and matrix metalloproteinase-7 (MMP-7) were measured using the multiplex Luminex assays (R&D Systems, Minneapolis, USA). The median follow-up period was 69.0 months. The mean age of the patients was 59.4 years; 17.4% were men. The KL-6 level was significantly higher in non-survivors (n = 12; 119.6 vs. 59.5 pg/mL, P = 0.037) than survivors (n = 34), while the levels of the other biomarkers did not differ. Receiver operating characteristic analysis indicated that KL-6 shows the best performance for predicting survival (area under the curve = 0.705, P = 0.037; best cut-off value = 53.5 pg/mL). Multivariable Cox analysis that was adjusted by age and diffusing capacity for carbon monoxide suggested a high KL-6 level (> 53.5 pg/mL) as an independent prognostic factor for survival (hazard ratio = 5.939, 95% confidence interval 1.312–26.881, P = 0.021). Our results suggest that blood KL-6 might be a useful in predicting the prognosis for patients with SJS-ILD.

Abstract Acute exacerbation (AE) significantly affects the prognosis of patients with interstitial lung disease (ILD). This study aimed to investigate the best prognostic biomarker for patients with AE-ILD. Clinical data obtained during hospitalization were retrospectively analyzed for 96 patients with AE-ILD at three tertiary hospitals. The mean age of all subjects was 70.1 years; the percentage of males was 66.7%. Idiopathic pulmonary fibrosis accounted for 60.4% of the cases. During follow-up (median: 88 days), in-hospital mortality was 24%. Non-survivors had higher lactate dehydrogenase and C-reactive protein (CRP) levels, lower ratio of partial pressure of oxygen to the fraction of inspiratory oxygen (P/F ratio), and higher relative change in Krebs von den Lungen-6 (KL-6) levels over 1 week after hospitalization than survivors. In multivariable analysis adjusted by age, the 1-week change in KL-6—along with baseline P/F ratio and CRP levels—was an independent prognostic factor for in-hospital mortality (odds ratio 1.094, P = 0.025). Patients with remarkable increase in KL-6 (≥ 10%) showed significantly worse survival (in-hospital mortality: 63.2 vs. 6.1%) than those without. In addition to baseline CRP and P/F ratio, the relative changes in KL-6 over 1 week after hospitalization might be useful for predicting in-hospital mortality in patients with AE-ILD.

BackgroundVariable clinical courses make it challenging to predict mortality resulting from fibrotic hypersensitivity pneumonitis (HP). This study evaluated the usefulness of radiologic parameters for predicting mortality in patients with fibrotic HP.MethodsClinical data and high-resolution computed tomography (HRCT) images, which were scored for reticulation, honeycombing, ground glass opacity (GGO), consolidation, and mosaic attenuation (MA) by visual assessment, were retrospectively analyzed in a total of 101 patients with fibrotic HP (all biopsy-proven cases). Fibrosis score was defined as the sum of reticulation and honeycombing scores.ResultsThe mean age of the 101 patients was 58.9 years, and 60.4% were females. During the follow-up (median: 55.5 months; interquartile range: 37.7–89.0 months), the 1-, 3-and 5-year mortality rates were 3.9, 16.8, and 32.7%, respectively. The non-survivors were older and had significantly lower lung function and minimum oxygen saturation during the 6-min walk test than the survivors. The non-survivors had higher scores of reticulation, honeycombing, GGO, fibrosis, and MA on HRCT than survivors. In the multivariable Cox analysis, reticulation, GGO, and fibrosis scores were independent prognostic factors for mortality in patients with fibrotic HP, as well as age. Fibrosis score showed great performance for predicting the 5-year mortality (AUC = 0.752, p

Background: Interstitial lung disease (ILD) is a significant complication associated with microscopic polyangiitis (MPA) that has a poor prognosis. However, the long-term clinical course, outcomes, and prognostic factors of MPA-ILD are not well defined. Hence, this study aimed to investigate the long-term clinical course, outcomes, and prognostic factors in patients with MPA-ILD.Methods: Clinical data of 39 patients with MPA-ILD (biopsy proven cases, n = 6) were retrospectively analyzed. High resolution computed tomography (HRCT) patterns were assessed based on the 2018 idiopathic pulmonary fibrosis diagnostic criteria. Acute exacerbation (AE) was defined as the worsening of dyspnea within 30 days, with new bilateral lung infiltration that is not fully explained by heart failure or fluid overload and that does not have identified extra-parenchymal causes (pneumothorax, pleural effusion, or pulmonary embolism).Results: The median follow-up period was 72.0 months (interquartile range: 44–117 months). The mean age of the patients was 62.7 years and 59.0% were male. Usual interstitial pneumonia (UIP) and probable usual interstitial pneumonia patterns on high resolution computed tomography were identified in 61.5 and 17.9% of the patients, respectively. During the follow-up, 51.3% of patients died, and the 5- and 10-year overall survival rates were 73.5% and 42.0%, respectively. Acute exacerbation occurred in 17.9% of the patients. The non-survivors had higher neutrophil counts in bronchoalveolar lavage (BAL) fluid and more frequent acute exacerbation than the survivors. In the multivariable Cox analysis, older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.01–1.14; p = 0.028) and higher BAL counts (HR, 1.09; 95% CI, 1.01–1.17; p = 0.015) were found to be the independent prognostic factors associated with mortality in patients with MPA-ILD.Conclusion: During the 6 years-follow-up, about half of patients with MPA-ILD died and approximately one-fifth experienced acute exacerbation. Our results suggest that older age and higher BAL neutrophil counts mean poor prognosis in patients with MPA-ILD.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD) with variable and heterogeneous clinical course. The GAP (gender, age, and physiology) model had been used to predict mortality in patients with IPF, but does not contain exercise capacity. Therefore, our aim in this study was to develop new prognostic scoring system in the Korea IPF Cohort (KICO) registry.Materials and methodsThis is a retrospective study of Korean patients with IPF in KICO registry from June 2016 to August 2021. We developed new scoring system (the GAP6) based on the GAP model adding nadir saturation of percutaneous oxygen (SpO2) during six-minute walk test (6MWT) in the KICO registry and compared the efficacy of the GAP and the GAP6 model.ResultsAmong 2,412 patients in KICO registry, 966 patients were enrolled. The GAP6 model showed significant prognostic value for mortality between each stage [HR Stage II vs. Stage I = 2.89 (95% CI = 2.38–3.51), HR Stage III vs. Stage II = 2.68 (95% CI = 1.60–4.51)]. In comparison the model performance with area under curve (AUC) using receiver operating characteristic (ROC) curve analysis, the GAP6 model showed a significant improvement for predicting mortality than the GAP model (AUC the GAP vs. the GAP6, 0.646 vs. 0.671, p

Background: Pirfenidone, an antifibrotic medication approved for the treatment of idiopathic pulmonary fibrosis (IPF), often requires dose reduction owing to adverse events. In this study, we evaluated if pirfenidone’s reduced dose has any impact on clinical outcomes in patients with IPF.Methods: We used the data of a prospective post-marketing study of pirfenidone conducted at 10 hospitals in South Korea from 2014 to 2017. Dose reduction was defined when the pirfenidone dose was temporarily or permanently reduced to manage adverse events or when the treatment dose failed to reach the standard dose. Study patients were classified based on the most frequently administered dose during 48-week follow-up—1800 mg, 1,200 mg, and

Dyskeratosis congenita is a rare genetic disorder of telomere insufficiency characterized by a mucocutaneous triad of nail dystrophy, abnormal skin pigmentation, and mucosal leukoplakia. Early diagnosis is important for multidisciplinary approach to its complications including bone marrow failure, malignancy, interstitial lung disease, and liver disease which cause significant morbidity and mortality. We report a genetically confirmed case of dyskeratosis congenita who presented with fibrotic hypersensitivity pneumonitis, highlighting non-mucocutaneous features of dyskeratosis congenita and the need to consider genetic predisposition in a patient with interstitial lung disease and combined unusual manifestations.

Abstract Sarcoidosis is a systemic granulomatous disorder of unknown cause involving multiple organs. Its clinical presentation and prognosis vary among races. We identified the clinical characteristics and outcomes of Korean patients with sarcoidosis. Clinical data of 367 Korean patients with biopsy-proven sarcoidosis diagnosed in 2001–2017 were retrospectively analyzed. Treatment responses included improvement, stability, or progression based on changes in pulmonary sarcoidosis on chest images. The mean age was 47.4 years, and 67.3% of patients were women. The median follow-up period was 80 months. The highest prevalence was observed in individuals aged 50–59 years (30–39 years in men, 50–59 years in women), and the number of diagnoses showed an increasing trend. Lung involvement was the most common (93.5%), followed by the skin, eyes, and extrathoracic lymph nodes. Among patients with lung involvement and a follow-up period of ≥ 3 months, 66.8%, 31.0%, and 2.2% showed improvement, stability, and progression, respectively. Eleven patients (2.9%) died, and the 5-year survival rate was 99%. The number of diagnosed cases showed an increasing trend, and the mean age at diagnosis was increased compared with that in previous reports. Organ involvement was similar to that of Westerners, although the prognosis appeared better.

Abstract Background The progressive fibrosing (PF) phenotype of interstitial lung disease (ILD) is characterised by worsening respiratory symptoms, lung function, and extent of fibrosis on high-resolution computed tomography. We aimed to investigate the prevalence and clinical outcomes of PF-ILD in a real-world cohort and assess the prognostic significance of the PF-ILD diagnostic criteria. Methods Clinical data of patients with fibrosing ILD other than idiopathic pulmonary fibrosis (IPF) consecutively diagnosed at a single centre were retrospectively reviewed. A PF phenotype was defined based on the criteria used in the INBUILD trial. Results The median follow-up duration was 62.7 months. Of the total of 396 patients, the mean age was 58.1 years, 39.9% were men, and rheumatoid arthritis-ILD was the most common (42.4%). A PF phenotype was identified in 135 patients (34.1%). The PF-ILD group showed lower forced vital capacity and total lung capacity (TLC) than the non-PF-ILD group. The PF-ILD group also showed poorer survival (median survival, 91.2 months vs. not reached; P

In this paper, we propose a multi-position cluster-based weighted position estimation method that minimizes the influence of multipath (MP)/non-line-of-sight (NLOS) signals using a global navigation satellite system (GNSS) receiver. The proposed method is suitable for positioning passenger cars, particularly in urban driving environments. Density-based spatial clustering of applications with noise (DBSCAN)-based clustering is performed by generating multi-position data through a subset of observable satellites and analyzing the density characteristics of position data generated by line-of-sight (LOS) satellite signals from the generated multi-position data. To estimate the optimal position through clustered data, we propose a method by constructing a weighted model through Doppler-based velocity measurements, which is robust to MP delay signals compared to code-based pseudorange measurements. In addition, to prevent unnecessary clustering points from having weights, the predicted range is selected based on the nonholonomic constraint of the vehicle. The proposed algorithm was quantitatively validated by selecting a region in an actual urban environment where the MP/NLOS error could occur significantly. It was confirmed that the accuracy of vehicle position was improved by approximately 24% by the proposed method compared to existing positioning solutions.

Abstract Background Acute exacerbation (AE) is the most lethal postoperative complication in idiopathic pulmonary fibrosis (IPF); however, prediction before surgery is difficult. We investigated the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting postoperative AE in IPF. Method Clinical data of 48 IPF patients who underwent 18F-FDG PET/CT before thoracic surgery were retrospectively analyzed. Mean and maximal standardized uptake values (SUVmean and SUVmax, respectively) were measured in the fibrotic area. Additionally, adjusted values-SUV ratio (SUVR, defined as SUVmax-to-liver SUVmean ratio), tissue fraction-corrected SUVmean (SUVmeanTF), and SUVR (SUVRTF)-were calculated. Results The mean age of the subjects was 67.8 years and 91.7% were male. After thoracic surgery, 21 (43.8%) patients experienced postoperative complications including prolonged air leakage (29.2%), death (14.6%), and AE (12.5%) within 30 days. Patients who experienced AE showed higher SUVmax, SUVR, SUVmeanTF, and SUVRTF than those who did not, but other clinical parameters were not different between patients with and without AE. The SUV parameters did not differ for other complications. The SUVR (odds ratio [OR] 29.262; P = 0.030), SUVmeanTF (OR 3.709; P = 0.041) and SUVRTF (OR 20.592; P = 0.017) were significant predicting factors for postoperative AE following a multivariate logistic regression analysis. On receiver operating characteristics curve analysis, SUVRTF had the largest area under the curve (0.806, P = 0.007) for predicting postoperative AE among SUV parameters. Conclusions Our findings suggest that 18F-FDG PET/CT may be useful in predicting postoperative AE in IPF patients and among SUVs, SUVRTF is the best parameter for predicting postoperative AE in IPF patients.

Abstract Sildenafil is a phosphodiesterase-5 inhibitor used to treat idiopathic pulmonary arterial hypertension; however, its benefits are unclear in patients with advanced idiopathic pulmonary fibrosis (IPF). We aimed to evaluate its effect as an add-on to antifibrotic agents on clinical outcomes of real-world IPF patients. Among a total of 607 IPF patients treated with antifibrotic agent, 66 concurrently received sildenafil. Propensity score matching was performed to adjust for differences in age, sex, body mass index, forced vital capacity (FVC), and diffusing capacity (DLCO) between the sildenafil and no-sildenafil groups. The outcomes of these groups in terms of FVC decline rate, all-cause mortality, hospitalization, and acute exacerbation were compared. Propensity score matching identified 51 matched pairs. The mean age of the patients was 69.5 years and 80.4% were male. Mean FVC and DLCO were 51.7% and 29.5% of the predicted values, respectively. The FVC decline rates did not differ significantly (p = 0.714) between the sildenafil (− 101 mL/year) and no-sildenafil (− 117 mL/year) groups. In multivariable analyses adjusted for comorbidities and presence of pulmonary hypertension, sildenafil had no significant impact on all-cause mortality, hospitalization, or acute exacerbation. Sildenafil add-on to antifibrotic treatment had no significant effects on the clinical outcomes of IPF patients.

Abstract The purpose of this study was to evaluate the implications of the 2018 updated guideline for the diagnosis of idiopathic pulmonary fibrosis (IPF) in clinical practice compared to 2011 guideline. This study involved 535 patients including 339 IPF and 196 non-IPF, and we retrospectively evaluated CT classifications of usual interstitial pneumonia (UIP) by two guidelines. Interobserver agreement of 2018 criteria showed moderate reliability (κ = 0.53) comparable to 2011 (κ = 0.56) but interobserver agreement for probable UIP was fair (κ = 0.40). CT pattern of indeterminate for UIP was associated with better prognosis compared with the other groups (adjusted hazard ratio [HR] = 0.36, p

BackgroundThe development of non-caseating epithelioid cell granulomas in cancer patients who do not fulfill the systemic sarcoidosis criteria is termed sarcoid-like reaction (SLR). Little is known about this condition's natural course and impact on the prognosis of malignancy. We aimed to investigate the natural course and prognostic value of cancer-associated SLR.MethodsClinical data were retrospectively analyzed in 32 patients with biopsy-proven cancer-associated SLR. Among patients with non-small cell lung cancer (NSCLC), SLR cases (n = 8) were matched with non-SLR cases (n = 78) for survival analysis.ResultsAmong the included patients, the mean age was 59.7 years, and 68.8% were female. The median follow-up period was 35.6 months [interquartile range (IQR): 14.0–61.4 months]. Of all the included malignancies (n = 32), breast cancer (25.0%) and NSCLC (25.0%) were the most common, with stage I being the most frequent tumor stage (59.4%). During follow-up, SLR progression to overt sarcoidosis was not observed. In the 28 patients with available follow-up computed tomography images (median interval: 24.9 months; IQR: 14.4–41.7), 4 patients received corticosteroids (n = 4), resulting to a decrease of SLR lesions. Meanwhile, among those who did not receive treatment (n = 24), the extent of SLR decreased or did not change in 85.7% of them, whereas 3.6% had increased SLR extent. Furthermore, among patients with NSCLC, SLR was not associated with overall survival [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 0.02–67.71, P = 0.882] and recurrence of malignancy (HR = 1.27, 95% CI 0.21–7.51, P = 0.793) in the Cox proportional hazard regression model.ConclusionsDuring the follow-up of cancer-related SLR, we found no further evidence for systemic sarcoidosis, and most of the lesions decreased or did not change. Development of SLR was also not associated with overall survival or disease-free survival in patients with NSCLC.

Abstract Interstitial lung disease (ILD) is the most common lung manifestation in patients with Sjögren syndrome (SJS) and is associated with poor outcomes. This study aimed to investigate the long-term clinical course and prognostic factors in patients with SJS-ILD. Clinical data and high-resolution computed tomography (HRCT) images of 62 patients with primary SJS-ILD were retrospectively analyzed (biopsy-proven cases, n = 16). The mean patient age was 59.8 years; 83.9% of the patients were females, and 38.7% showed a usual interstitial pneumonia (UIP) pattern on HRCT. The median follow-up period was 61.5 months. During follow-up, 15 patients (24.2%) died, 7 (11.3%) experienced acute exacerbation (AE), and 27 (43.5%) progressed. The 1-, 3- and 5-year survival rates were 93.5%, 85.8%, and 81.1%, respectively. Age (hazard ratio [HR]: 1.158, P = 0.003), C-reactive protein (CRP) level (HR: 1.212, P = 0.045), FVC (HR: 0.902, P = 0.005), and a UIP pattern on HRCT (HR: 4.580, P = 0.029) were significant prognostic factors in multivariable Cox analysis. In conclusion, death, AE, and ILD progression occurred in 25%, 10%, and 50% of the patients with SJS-ILD, respectively. Older age, higher CRP level, lower FVC, and a UIP pattern on HRCT indicated poor prognosis.

Abstract Background Patients with fibrotic hypersensitivity pneumonitis (HP) show variable clinical courses, and some experience rapid deterioration (RD), including acute exacerbation (AE). However, little is known about AE in fibrotic HP. Here, we retrospectively examined the incidence, risk factors, and outcomes of AE in fibrotic HP. Methods The incidence rates of AE were calculated in 101 patients with biopsy-proven HP. AE was defined as the worsening of dyspnoea within 30 days, with new bilateral lung infiltration and no evidence of infection or other causes of dyspnoea. Results During follow-up (median: 30 months), 18 (17.8%) patients experienced AE. The 1, 3, and 5 year incidence rates of AE were 6.0, 13.6, and 22.8%, respectively. Lower diffusing capacity of the lung for carbon monoxide (DLCO) and a radiologic usual interstitial pneumonia (UIP)-like pattern were risk factors for AE. In-hospital mortality after AE was 44.4%. Median survival from diagnosis was significantly shorter in patients with AE (26.0 months) than in those with no-AE RD (55.0 months; p = 0.008) or no RD (not reached; p

Abstract The clinical characteristics of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) differ from those of lung cancer in patients without IPF. Thus, we aimed to evaluate the impact of IPF on the clinical course of patients with lung cancer. Clinical data of IPF patients with lung cancer (n = 122) were compared with those of patients with lung cancer without IPF (n = 488) matched by age, sex, histopathology, stage, and date of diagnosis of lung cancer. The median follow-up period after diagnosis of lung cancer was 16 months. Among patients with IPF, the mean age was 68 years, 95.9% were male, 93.2% were ever-smokers, and squamous cell carcinoma was the most common cancer type (48.4%). The IPF group had poorer lung function and lower lobe predominance of lung cancer than the no-IPF group. The IPF group showed a poorer prognosis than the no-IPF group (5-year survival rate: 14.5% vs. 30.1%, respectively; P

Abstract Background In the INBUILD trial in patients with chronic fibrosing interstitial lung diseases (ILDs) and a progressive phenotype, nintedanib reduced the rate of ILD progression with adverse events that were manageable for most patients. We investigated the potential impact of immunomodulatory therapies on the efficacy and safety of nintedanib. Methods Subjects with fibrosing ILDs other than idiopathic pulmonary fibrosis, who had shown progression of ILD within the prior 24 months despite management in clinical practice, were randomized to receive nintedanib or placebo. Certain immunomodulatory therapies were restricted for the first 6 months. We analyzed post-hoc the rate of decline in forced vital capacity (FVC) over 52 weeks in subgroups by glucocorticoid use at baseline and in analyses excluding subjects or FVC measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies. Results Of 663 subjects, 361 (54.4%) were taking glucocorticoids at baseline (353 at a dose of ≤ 20 mg/day). In the placebo group, the adjusted rate of decline in FVC (mL/year) over 52 weeks was numerically greater in subjects taking than not taking glucocorticoids at baseline (− 206.4 [SE 20.2] vs − 165.8 [21.9]). The difference between the nintedanib and placebo groups was 133.3 (95% CI 76.6, 190.0) mL/year in subjects taking glucocorticoids at baseline and 76.1 (15.0, 137.2) mL/year in subjects who were not (interaction P = 0.18). The effect of nintedanib on reducing the rate of FVC decline in analyses excluding subjects or measurements taken after initiation of restricted immunomodulatory or antifibrotic therapies was similar to the primary analysis. The adverse event profile of nintedanib was similar between subjects who did and did not use prohibited or restricted therapies at baseline or during treatment with trial drug. Conclusions In patients with progressive fibrosing ILDs, the effect of nintedanib on reducing FVC decline was not influenced by the use of immunomodulatory therapies. Nintedanib can be used in combination with immunomodulatory therapies in patients with progressive fibrosing ILDs. Trial registration ClinicalTrials.gov, NCT02999178. Registered 21 December 2016, https://clinicaltrials.gov/ct2/show/NCT02999178

Abstract Background A new clinical guideline for idiopathic pulmonary fibrosis (IPF) uses high-resolution computed tomography (HRCT) patterns for diagnostic purposes. However, it is unknown how they relate to the IPF clinical course. We aimed to investigate whether HRCT patterns could be used to predict lung function changes and survival in patients with IPF. Methods Clinical data were retrospectively reviewed in 337 patients with IPF (all biopsy-proven cases). HRCT patterns were classified according to the 2018 IPF diagnostic criteria. Results The median follow-up was 46.9 months. The mean age was 62.5 years, and 74.2% were men. Among the HRCT patterns, usual interstitial pneumonia (UIP), probable UIP, indeterminate for UIP, and an alternative diagnosis were identified in 163 (48.4%), 110 (32.6%), 33 (9.8%), and 31 (9.2%) patients, respectively. The indeterminate for UIP group showed higher lung function and exercise capacity and better prognosis than the other groups. They also had a lesser decline in lung function than the other groups during follow-up. In the multivariate Cox analysis, which was adjusted by age, smoking status, lung function, exercise capacity, and use of antifibrotic agents, indeterminate for UIP pattern was found to be an independent prognostic factor (hazard ratio 0.559, 95% confidence interval 0.335–0.933, P = 0.026). However, the probable UIP group had similar lung function changes and prognosis when compared the UIP group. Conclusions Our results suggest that indeterminate for UIP pattern on HRCT may predict a more favorable clinical course in patients with IPF, supporting the validity of the new IPF diagnostic guidelines.

Abstract Background Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification. Methods Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes. Results The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial. Conclusions Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.

Abstract Background Pulmonary alveolar proteinosis (PAP) is a very rare lung disease and its prevalence and incidence remain unclear. The prevalence and incidence of PAP were investigated by using nationwide claims data from the Korean Health Insurance Review and Assessment service. Methods Data were extracted for adults who visited any secondary or tertiary medical institute between 2010 and 2016 with the PAP-related Korean Classification of Disease, 7th edition code J84.0 and the Rare Intractable Disease exempted calculation code V222. To robust case definition, a narrow case definition was made when all following factors were met: 1) more than two PAP-coded visits within 1 year of the first claim, and 2) more than one claim for both chest computed tomography and diagnostic procedures (bronchoscopy or surgical lung biopsy) within 90 days before or after the first claim. Results A total of 182 patients (narrow, n = 82) with PAP-related codes were identified from 2010 to 2016 and 89 new patients (narrow, n = 66) visited medical institutes between 2012 and 2015. The prevalence of PAP was 4.44 (narrow: 2.27) per 106 population, with a peak age of 60–69 years. The incidence of PAP was 0.56 (narrow: 0.41) per 106 population at risk, with a peak age of 50–59 years. Among incident cases, the male-to-female ratio was 1.52 and about two-thirds had comorbidities, dyslipidaemia being the most common. Conclusions The prevalence and incidence of PAP in Korea are low, similar to those in other countries; however, Korean patients with PAP are characterized by older diagnostic age and a lower male-to-female ratio.