Impact of Interventional Bronchoscopy on Long-Term Survival in Patients with Primary Tracheal Adenoid Cystic Carcinoma: A Single-Center Experience.

Introduction: Primary tracheal adenoid cystic carcinoma (TACC) is a rare low-grade lung cancer of bronchial gland origin. Surgery is the first choice of treatment; however, in cases of recurrence or inoperability, a combination of radiation and chemotherapy is administered as a multimodality treatment. Interventional bronchoscopy is also used as a multidisciplinary treatment; however, its impact on long-term prognosis has not been thoroughly investigated. Case Presentation: Eight patients diagnosed with TACC and treated at Shinshu University Hospital between December 2000 and August 2023 were analyzed retrospectively. We investigated the duration of intervention and overall survival (OS) in 3 patients with recurrence who underwent interventional bronchoscopy in combination with chemotherapy and evaluated whether interventional bronchoscopy prolonged the survival. The initial treatment for the 3 patients was surgery in 1 patient and chemoradiotherapy in 2. In all patients, raised lesions were observed in the trachea at the time of recurrence. The duration of interventional bronchoscopy, the time from recurrence of the first-line treatment to death, and OS, which was defined time from induction of the first-line treatment to death, were 69.3/70.7/112.5 months, 179.2/196.1/220.4 months, and 15.4/66.3/104.4 months, respectively. Conclusion: Long-term survival benefits may be obtained with concomitant interventional bronchoscopy in combination with chemotherapy in patients with locally recurrent TACC.

The Contribution of Genetic Variants of the Peroxisome Proliferator-Activated Receptor-Alpha Gene to High-Altitude Hypoxia Adaptation in Sherpa Highlanders.

Kinota, Fumiya, Yunden Droma, Nobumitsu Kobayashi, Toshimichi Horiuchi, Yoshiaki Kitaguchi, Masanori Yasuo, Masao Ota, and Masayuki Hanaoka. The contribution of genetic variants of the gene encoding peroxisome proliferator-activated receptor-alpha gene (PPARA) to high-altitude hypoxia adaptation in Sherpa highlanders. High Alt Med Biol. 24:186-192, 2023.-Sherpa highlanders, who play invaluable roles in the exploration of Mount Everest, have exceptional tolerance to hypobaric hypoxia. Sherpa people are well known to possess the traits determined by genetic background for high-altitude adaptation. The metabolic adaptation mechanism is one of the biological ways for Sherpa highlanders in protecting them from hypoxia stress at high altitude. Studies have suggested that the gene encoding PPARA is associated with metabolic adaptation in the Himalayan population of Tibetans. This study attempts to investigate the genetic variants of the PPARA in Sherpa highlanders and the association with high-altitude hypoxia adaptation. Seven single-nucleotide polymorphisms (SNPs; rs135547, rs5769178, rs881740, rs4253712, rs5766741, and rs5767700 in introns and rs1800234 in exon 6) in the PPARA were genotyped in 105 Sherpa highlanders who lived in the Khumbu region (3440 m above sea level) and 111 non-Sherpa lowlanders who resided in Kathmandu (1300 m) in Nepal. By means of analyses of genetic distances, genotype distributions, allele frequencies, linkage disequilibrium, and haplotype constructions of the seven SNPs in the Sherpa highlanders versus the non-Sherpa lowlanders, it was revealed that the frequencies of minor alleles of rs4253712, rs5766741, rs5767700, and rs1800234 SNPs, as well as the frequency of haplotype constructed by the minor alleles of rs5766741-rs5767700-rs1800234, were significantly overrepresented in the Sherpa highlanders in comparison with the non-Sherpa lowlanders. The results strongly suggest that the genetic variants of the PPARA are likely to contribute to the high-altitude adaptation in Sherpa highlanders.

The blunted vascular endothelial growth factor-A (VEGF-A) response to high-altitude hypoxia and genetic variants in the promoter region of the VEGFA gene in Sherpa highlanders.

Background: Sherpa highlanders demonstrate extraordinary tolerance to hypoxia at high altitudes, which may be achieved by mechanisms promoting microcirculatory blood flow and capillary density at high altitudes for restoring oxygen supply to tissues. Vascular endothelial growth factors (VEGFs) are important signaling proteins involved in vasculogenesis and angiogenesis which are stimulated by hypoxia. We hypothesize that the VEGF-A, the major member of the VEGF family, and the gene encoding VEGF-A (VEGFA) play a part in the adaptation to high-altitude hypoxia in Sherpa highlanders. Methods: Fifty-one Sherpa highlanders in Namche Bazaar village at a high altitude of 3,440 meters (m) above sea level and 76 non-Sherpa lowlanders in Kathmandu city at 1,300 m in Nepal were recruited for the study. Venous blood was sampled to obtain plasma and extract DNA from each subject. The plasma VEGF-A concentrations were measured and five single-nucleotide polymorphisms (SNPs, rs699947, rs833061, rs1570360, rs2010963, and rs3025039) in the VEGFA were genotyped. The VEGF-A levels and allelic frequencies of the SNPs were compared between the two populations. Results: A significant difference in oxygen saturation (SpO2) was observed between the two ethnic groups locating at different elevations (93.7 ± 0.2% in Sherpas at 3,440 m vs. 96.7 ± 0.2% in non-Sherpas at 1,300 m, P < 0.05). The plasma VEGF-A concentration in the Sherpas at high altitude was on the same level as that in the non-Sherpas at low altitude (262.8 ± 17.9 pg/ml vs. 266.8 ± 21.8 pg/ml, P = 0.88). This result suggested that the plasma VEGF-A concentration in Sherpa highlanders was stable despite a high-altitude hypoxic stimulus and that therefore the Sherpas exhibited a phenotype of blunted response to hypoxic stress. Moreover, the allele frequencies of the SNPs rs699947, rs833061, and rs2010963 in the promoter region of the VEGFA were different between the Sherpa highlanders and non-Sherpa lowlanders (corrected P values = 3.30 ×10-5, 4.95 ×10-4, and 1.19 ×10-7, respectively). Conclusions: Sherpa highlanders exhibited a blunted VEGF-A response to hypoxia at high altitudes, which was speculated to be associated with the distinctive genetic variations of the SNPs and haplotype in the promoter region of VEGFA in Sherpa highlanders.

Referential equations for pulmonary diffusing capacity using GAMLSS models derived from Japanese individuals with near-normal lung function.

OBJECTIVE: To generate appropriate reference values for the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar volume (VA), and the transfer coefficient of the lungs for carbon monoxide (KCO, often denoted as DLCO/VA) in the Japanese population. We also intended to assess the applicability of these values for the Japanese population by comparing them to those published by the Global Lung Function Initiative in 2017 (GLI-2017) and previous values. METHODS: In this retrospective study, we measured the spirometric indices, DLCO, VA, and KCO of the Japanese population aged 16-85 years. The lambda, mu, and sigma (LMS) method and the generalized additive models for the location, scale, and shape program in R were used to generate the reference values. RESULTS: We conducted a total of 390 tests. The GLI-2017 z-scores of DLCO were approximately zero, whereas those of KCO and VA were far from zero. In the present study, the mean square errors of the DLCO, VA, and KCO reference values were lower than the reference values derived from GLI-2017 and previous linear regression equations. CONCLUSIONS: Reference values obtained in this study were more appropriate for our sample than those reported in GLI-2017. Differences between the two equations were attributed to underestimating KCO (DLCO / VA) and overestimating VA, respectively, by the GLI-2017 for the Japanese population.

Prognostic implication of IgG4 and IgG1-positive cell infiltration in the lung in patients with idiopathic interstitial pneumonia.

Immunoglobulin (Ig) G4-positive cells are rarely observed in the lungs of patients with idiopathic interstitial pneumonias (IIPs). IgG1 may be more pathogenic than IgG4, with IgG4 having both pathogenic and protective roles in IgG4-related disease (IgG4-RD). However, the role of both IgG1 and IgG4 in IIPs remains unclear. We hypothesized that patients with IgG4-positive interstitial pneumonia manifest different clinical characteristics than patients with IgG4-RD. Herein, we identified the correlation of the degree of infiltration of IgG1- and IgG4-positive cells with IIP prognosis, using a Japanese nationwide cloud-based database. We included eighty-eight patients diagnosed with IIPs after multidisciplinary discussion, from April 2009 to March 2014. IgG4-positive cell infiltration was identified in 12/88 patients with IIPs and 8/41 patients with idiopathic pulmonary fibrosis (IPF). Additionally, 31/88 patients with IIPs and 19/41 patients with IPF were diagnosed as having IgG1-positive cell infiltration. IgG4-positive IIPs tended to have a better prognosis. Conversely, overall survival in cases with IgG1-positive IPF was significantly worse. IIPs were prevalent with IgG1- or IgG4-positive cell infiltration. IgG1-positive cell infiltration in IPF significantly correlated with a worse prognosis. Overall, evaluating the degree of IgG1-positive cell infiltration may be prognostically useful in cases of IPF.

Associations Between Morphological Phenotypes of COPD and Clinical Characteristics in Surgically Resected Patients with COPD and Concomitant Lung Cancer.

Purpose: The associations between morphological phenotypes of COPD based on the chest computed tomography (CT) findings and clinical characteristics in surgically resected patients with COPD and concomitant lung cancer are unclear. The purpose of this study was to clarify the differences in clinical characteristics and prognosis among morphological phenotypes based on the chest CT findings in these patients. Patients and Methods: We retrospectively reviewed the medical records of 132 patients with COPD and concomitant lung cancer who had undergone pulmonary resection for primary lung cancer. According to the presence of emphysema and bronchial wall thickness on chest CT, patients were classified into three phenotypes: non-emphysema phenotype, emphysema phenotype, or mixed phenotype. Results: The mixed phenotype was associated with poorer performance status, higher score on the modified British Medical Research Council (mMRC) dyspnea scale, higher residual volume in pulmonary function, and higher proportion of squamous cell carcinoma than the other phenotypes. Univariate and multivariate Cox proportional hazards regression analyses showed that the extent of emphysema on chest CT, presented as a low attenuation area (LAA) score, was an independent determinant that predicted prognosis. In the Kaplan-Meier analysis, the Log rank test showed significant differences in survival between the non-emphysema and mixed phenotypes, and between the emphysema and mixed phenotypes. Conclusion: The cross-sectional pre-operative LAA score can predict the prognosis in surgically resected patients with COPD and concomitant lung cancer. The COPD phenotype with both emphysema and bronchial wall thickness on chest CT was associated with poorer performance status, greater extent of dyspnea, greater impairment of pulmonary function, and worse prognosis.

Obstructive Pneumonia Associated with Endobronchial Aspergilloma: Successful Treatment with Interventional Bronchoscopy and Antifungals.

Endobronchial aspergilloma is a rare disease. A 64-year-old man with severe diabetes mellitus developed a cough and fever and was referred to our hospital. He was diagnosed with obstructive pneumonia associated with endobronchial aspergilloma, underwent interventional bronchoscopy, and was treated with antifungals. While the optimal treatment has not been established, interventional bronchoscopy along with systemic antifungals may improve the outcome in such cases.

Tolerability of nintedanib in the elderly with idiopathic pulmonary fibrosis: A single-center retrospective study.

Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial lung disease, predominantly affects the elderly and is associated with a high mortality risk. Nintedanib, a tyrosine kinase inhibitor, significantly reduces IPF progression. However, data on the tolerability and efficacy of nintedanib in the elderly with IPF are limited. Therefore, this study aimed to examine the tolerability and efficacy of nintedanib in the elderly with IPF in a real-world setting. Medical records of 19 elderly IPF patients (≥ 75 years) and 46 non-elderly IPF patients (< 75 years) newly administered nintedanib were retrospectively analyzed. We compared the forced vital capacity (FVC) level, incidence and severity of adverse events, and continuation rates of nintedanib between the two groups. FVC and percent predicted diffusing capacity of the lung for carbon monoxide (DLco) were lower in the elderly IPF group at baseline. Although the elderly IPF patients had a significantly higher incidence of adverse events, such as diarrhea, nausea, and elevation of hepatic enzymes, the rate of discontinuation of nintedanib owing to adverse events was not different between the groups. The continuation rates of nintedanib treatment at 6 months and 1 year in the elderly IPF group were equivalent. Furthermore, there was a similar trend in the reduction of the annual FVC decline after nintedanib initiation between the groups. Our study demonstrated that nintedanib was tolerable in both the IPF patient groups in a real-world setting. Proper management of adverse events in the elderly with IPF would lead to a better clinical outcome.

Characteristics of airway resistance in obstructive sleep apnea patients with asthma on oscillometry.

BACKGROUND: Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders with a high tendency to coexist. Both diseases involve increased airway resistance in the upright position because of narrow upper or lower airways. Moreover, there is a marked increase in airway resistance in the supine position in patients with OSA. We verified the characteristics of OSA in combination with asthma. METHODS: Airway resistance was measured by oscillometry in the upright and supine position in 11 healthy participants (control), 59 patients with OSA alone, and 33 OSA patients with asthma (coexistence) in the hospital between April 2014 and July 2020. We compared the differences in airway resistance between the upright and supine positions among the three groups. In addition, we performed cephalometry to evaluate the upper airway structure in patients with OSA alone and in patients with both OSA and asthma. RESULTS: A marked increase in airway resistance due to postural change was observed in the "OSA alone" group compared to that in the control group. However, this was not observed in the "coexistence" and control groups. Moreover, the "coexistence" group had fewer structural abnormalities in the upper airway than the "OSA alone" group on cephalometry. CONCLUSIONS: The airway resistance of patients with OSA alone markedly increased with posture change because of upper airway abnormalities. However, there was a smaller increase with postural changes in OSA patients with asthma, suggesting the possibility of a smaller degree of upper airway abnormality compared to patients with OSA alone. CLINICAL TRIAL REGISTRATION NUMBER: This study is approved by the research ethics committee of the Shinshu University School of Medicine (permission number: 4272).

The usefulness of a combination of age, body mass index, and blood urea nitrogen as prognostic factors in predicting oxygen requirements in patients with coronavirus disease 2019.

INTRODUCTION: Risk factors for seriously ill coronavirus disease 19 (COVID-19) patients have been reported in several studies. However, to date, few studies have reported simple risk assessment tools for distinguishing patients becoming severely ill after initial diagnosis. Hence, this study aimed to develop a simple clinical risk nomogram predicting oxygenation risk in patients with COVID-19 at the first triage. METHODS: This retrospective study involved a chart review of the medical records of 84 patients diagnosed with COVID-19 between February 2020 and March 2021 at ten medical facilities. The patients were divided into requiring no oxygen therapy (non-severe group) and requiring oxygen therapy (severe group). Patient characteristics were compared between the two groups. We utilized univariate logistic regression analysis to confirm determinants of high risks of requiring oxygen therapy in patients with moderate COVID-19. RESULTS: Thirty-five patients ware in severe group and forty-nine patients were in non-severe group. In comparison with patients in the non-severe group, patients in the severe group were significantly older with higher body mass index (BMI), and had a history of hypertension and diabetes. Serum blood urea nitrogen (BUN), lactic acid dehydrogenase (LDH), and C-reactive protein (CRP) levels were significantly higher in the severe group. Multivariate analysis showed that older age, higher BMI, and higher BUN levels were significantly associated with oxygen requirements. CONCLUSIONS: This study demonstrated that age, BMI, and BUN were independent risk factors in the moderate-to-severe COVID-19 group. Elderly patients with higher BMI and BUN require close monitoring and early treatment initiation.

IL-6 expression helps distinguish Castleman's disease from IgG4-related disease in the lung.

BACKGROUND: It is difficult to distinguish between multicentric Castleman's disease (MCD) and IgG4-related lung disease (IgG4-LD), an IgG4-related disease (IgG4-RD) in the lung. METHODS: We focused on IL-6, which is elevated in MCD, to distinguish between MCD and IgG4-LD by RNAscope, a highly sensitive RNA in situ method. Six cases of MCD and four cases of IgG4-LD were selected. RESULTS: In all cases of MCD and IgG4-LD, 10 or more IgG4-positive cells were found in one high-power field. All MCD cases were inconsistent with the pathological IgG4-related comprehensive diagnostic criteria, but 2 of 6 cases had an IgG4/IgG ratio greater than 40%. In all IgG4-LD cases, histological features were consistent with the pathological IgG4-RD comprehensive diagnostic criteria. IL-6 expression was observed in all MCD and IgG4-LD cases except for one IgG4-LD biopsy. IL-6-expressing cells were mainly identified in the stroma. Sites of IL-6 expression were not characteristic and were sparse. IL-6 expression tended to be higher in MCD compared with IgG4-LD. A positive correlation was found between the IL-6 H-score and serum IL-6 level. CONCLUSION: Differences in IL-6 expression may help distinguish between MCD and IgG4-LD. In addition, the presence of high IL-6 levels may help elucidate the pathological mechanisms of IgG4-LD.

Automated Diseased Lung Volume Percentage Calculation in Quantitative CT Evaluation of Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis.

OBJECTIVE: Several software-based quantitative computed tomography (CT) analysis methods have been developed for assessing emphysema and interstitial lung disease. Although the texture classification method appeared to be more successful than the other methods, the software programs are not commercially available, to our knowledge. Therefore, this study aimed to investigate the usefulness of a commercially available software program for quantitative CT analyses. METHODS: This prospective cohort study included 80 patients with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). RESULTS: The percentage of low attenuation volume and high attenuation volume had high sensitivity and high specificity for detecting emphysema and pulmonary fibrosis, respectively. The percentage of diseased lung volume (DLV%) was significantly correlated with the lung diffusion capacity for carbon monoxide in all patients with COPD and IPF patients. CONCLUSIONS: The quantitative CT analysis may improve the precision of the assessment of DLV%, which itself could be a useful tool in predicting lung diffusion capacity in patients with the clinical diagnosis of COPD or IPF.

Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice.

BACKGROUND: IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. METHODS: We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33-/- mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. RESULTS: Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33-/- mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33-/- and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33-/- mice than WT mice. IL-33-/- mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. CONCLUSION: These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

The Gly82Ser mutation in AGER contributes to pathogenesis of pulmonary fibrosis in combined pulmonary fibrosis and emphysema (CPFE) in Japanese patients.

The dominant pathogenesis underlying the combined pulmonary fibrosis and emphysema (CPFE) remains unresolved. The receptor for advanced glycation end-products (RAGE) is highly expressed in lung tissues and interacts with distinct multiple ligands, implicating it in certain lung diseases. To elucidate the pathogenesis of CPFE, we genotyped three single nucleotide polymorphisms (SNPs: rs2070600, rs1800625, and rs2853807) of the gene encoding RAGE (AGER) in 111 CPFE patients and 337 chronic obstructive pulmonary disease (COPD) patients of Japanese by using StepOne Real-Time PCR System for SNP genotyping assay. Serum levels of soluble RAGE (sRAGE) were measured by ELISA. We found that the allele frequency of rs2070600 was significantly different between the two groups [corrected P (Pc) = 0.015]. In addition, the minor allele was associated with CPFE patients relative to COPD patients in a dominant effect model (Odds Ratio = 1.93; Pc = 0.018). Moreover, the serum sRAGE level was significantly lower in the CPFE group than the COPD group (P = 0.014). The rs2070600 minor allele was significantly associated with reduced sRAGE level in CPFE patients and independently affected sRAGE level reduction in this group (P = 0.020). We concluded that the AGER rs2070600 minor allele (Gly82Ser mutation) is associated with the pathogenesis of pulmonary fibrosis in CPFE in Japanese patients.

Differences Between Central Airway Obstruction and Chronic Obstructive Pulmonary Disease Detected with the Forced Oscillation Technique.

Background: Obstructive ventilatory disturbances occur in both chronic obstructive pulmonary disease (COPD), a typical disease representative of peripheral airway obstruction, and central airway obstruction (CAO). Pulmonary function tests (PFTs), which depend on patient effort, are traditionally used to evaluate lung function. The forced oscillation technique (FOT) is an effort-independent method for examining lung function during tidal breathing. The FOT is used universally to assess respiratory function in patients with COPD. Several studies have measured FOT to assess ventilatory disturbances in CAO. The results showed that FOT measurements in patients with CAO were similar to those reported in patients with COPD. However, no studies have compared FOT measurements directly between CAO and COPD. The aim of this study was to identify differences in ventilatory disturbances between peripheral and central airway obstructions in COPD and CAO, before patients received pharmacological therapy or bronchoscopic interventions, respectively. Patients and Methods: We retrospectively included 16 patients with CAO (10 cases of tracheal obstruction and 6 cases of bronchial obstruction) and 75 treatment-naïve patients with COPD (60 cases in Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II and 15 cases in GOLD stage III) that were admitted from December 2013 to May 2017. Prior to treatment, patients were examined with the FOT and PFTs. Results: All parameters measured with the FOT in the inspiratory phase were significantly worse in patients with CAO than in patients with COPD. The PFTs showed that the CAO group had a significantly lower peak expiratory flow rate. In the airway wall thickening phenotype of COPD, a difference between the inspiratory and expiratory phases of the resonance frequency (ΔFres) was the best indicator for distinguishing between peripheral and central airway obstructions. Conclusion: This study compared differences between CAO and COPD (mainly GOLD stage II). We found that the FOT measurement, ΔFres, was the optimal indicator of the difference between the airway wall thickening COPD phenotype and CAO. Thus, the difference might be due to mechanical changes that occur in COPD with airway wall thickening.

Successful recovery from critical COVID-19 pneumonia with extracorporeal membrane oxygenation: A case report.

A public health emergency of current international concern is the outbreak of a severe respiratory illness, that is, coronavirus disease (COVID-19). The disease initially started in Wuhan, China, and it rapidly spread to most regions of the world. Herein, we report a case of critical COVID-19 pneumonia treated with extracorporeal membrane oxygenation from symptom onset day 19 (SOD#19) to SOD#30. We describe the patient's clinical course, from mild symptoms at the time of illness onset to symptoms of severe pneumonia as the illness progressed. We provide important information regarding our clinical experience for further understanding of management discrepancies, as treatment with extracorporeal membrane oxygenation or pharmacotherapy (e.g., antivirals, immunomodulators, and glucocorticoids) is often dependent on the severity of symptoms.

Prognosis of patients with acute exacerbation of combined pulmonary fibrosis and emphysema: a retrospective single-centre study.

BACKGROUND: Previous analyses of combined pulmonary fibrosis and emphysema (CPFE) cohorts have provided conflicting data on the survival of patients with CPFE. Therefore, the aim of this study was to investigate the clinical prognosis of acute exacerbations (AE) of CPFE. METHODS: We retrospectively reviewed the medical records of patients who had been treated at the Shinshu University Hospital (Matsumoto, Japan) between 2003 and 2017. We identified 21 patients with AE of CPFE and 41 patients with AE of idiopathic pulmonary fibrosis (IPF) and estimated their prognoses using the Kaplan-Meier method. RESULTS: Treatment content and respiratory management were not significantly different between the two groups before and after exacerbation. At the time of AE, the median serum Krebs von den Lungen-6 level was significantly lower in the CPFE group (Krebs von den Lungen-6: 966 U/µL; white blood cell count: 8810 /µL) than that in the IPF group (Krebs von den Lungen-6: 2130 U/µL, p < 0.001; white blood cells: 10809/µL, p = 0.0096). The baseline Gender-Age-Physiology scores were not significantly different between the two groups (CPFE, 4.5 points; IPF, 4.7 points; p = 0.58). Kaplan-Meier curves revealed that the survival time after AE for patients with CPFE was longer than that for patients with IPF (p < 0.001, log-rank test). CONCLUSIONS: Survival prognoses after AE were significantly better for patients with CPFE than that for those with IPF. Our findings may improve the medical treatment and respiratory management of patients with AE-CPFE.

The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease.

We previously reported higher levels of C-C chemokine ligand (CCL) 1 in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with sarcoidosis than in BALF of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD), indicating that CCL1 might act as a marker of disease activity in sarcoidosis. Notably, less invasive sampling sources are desirable, as BAL cannot always be performed due to its inherent risk. In this study, we sought to decipher the correlation between serum levels of CCL1 and clinical characteristics of sarcoidosis. Serum samples were obtained from 44 patients with clinically confirmed sarcoidosis, 14 patients with IgG4-RD, and 14 healthy controls. The clinical and radiological findings were retrospectively evaluated. Serum levels of CCL1 were measured using a sandwich enzyme-linked immunosorbent assay. Serum levels of other 17 cytokines and chemokines were measured using a MILLIPLEX® MAP KIT and Luminex® magnetic beads. Serum levels of CCL1 were significantly higher in patients with sarcoidosis than in patients with IgG4-RD and healthy controls. Serum CCL1 was positively correlated with the degree of hilar lymph node swelling on chest computed tomography and serum levels of soluble interleukin 2 receptor. Positive correlations were also observed between serum CCL1 and total cell counts, lymphocyte counts in BALF, and serum T helper 1 mediators such as IP-10 and TNF-α in patients with sarcoidosis. Serum CCL1 levels were significantly elevated in sarcoidosis and correlated with clinical parameters of the disease. In addition, serum and BALF levels of CCL1 were positively correlated in a statistically significant manner. Although further research in this field is necessary, CCL1 might have the potential to be a reliable serological marker of disease activity in sarcoidosis.