Effects of Anti-Fibrotic Drugs on Transcriptome of Peripheral Blood Mononuclear Cells in Idiopathic Pulmonary Fibrosis.

Two anti-fibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells (PBMCs) are immunocompetent cells that could orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in the bulk PBMCs of patients with IPF and the effects of anti-fibrotic drugs on these signatures. Differentially expressed genes (DEGs) between "patients with IPF and healthy controls" and "before and after anti-fibrotic treatment" were analyzed. Enrichment analysis suggested that fatty acid elongation interferes with TGF-ß/Smad signaling and the production of oxidative stress since treatment with NTD upregulates the fatty acid elongation enzymes ELOVL6. Treatment with PFD downregulates COL1A1, which produces wound-healing collagens because activated monocyte-derived macrophages participate in the production of collagen, type I, and alpha 1 during tissue damage. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinase activation, and the inhibition of PAI-1 activity attenuates lung fibrosis. DEG analysis suggested that both the PFD and NTD upregulate SERPINE1, which regulates PAI-1 activity. This study embraces a novel approach by using RNA sequencing to examine PBMCs in IPF, potentially revealing systemic biomarkers or pathways that could be targeted for therapy.

TRPV4-dependent Ca2+ influx determines cholesterol dynamics at the plasma membrane.

The activities of the transient receptor potential vanilloid 4 (TRPV4), a Ca2+-permeable nonselective cation channel, are controlled by its surrounding membrane lipids (e.g., cholesterol, phosphoinositides). The transmembrane region of TRPV4 contains a cholesterol recognition amino acid consensus (CRAC) motif and its inverted (CARC) motif located in the plasmalemmal cytosolic leaflet. TRPV4 localizes in caveolae, a bulb-shaped cholesterol-rich domain at the plasma membrane. Here, we visualized the spatiotemporal interactions between TRPV4 and cholesterol at the plasma membrane in living cells by dual-color single-molecule imaging using total internal reflection fluorescence microscopy. To this aim, we labeled cholesterol at the cytosolic leaflets of the plasma membrane using a cholesterol biosensor, D4H. Our single-molecule tracking analysis showed that the TRPV4 molecules colocalize with D4H-accessible cholesterol molecules mainly in the low fluidity membrane domains in which both molecules are highly clustered. Colocalization of TRPV4 and D4H-accessible cholesterol was observed both inside and outside of caveolae. Agonist-evoked TRPV4 activation remarkably decreased colocalization probability and association rate between TRPV4 and D4H-accessible cholesterol molecules. Interestingly, upon TRPV4 activation, the particle density of D4H-accessible cholesterol molecules was decreased and the D4H-accessible cholesterol molecules in the fast-diffusing state were increased at the plasma membrane. The introduction of skeletal dysplasia-associated R616Q mutation into the CRAC/CARC motif of TRPV4, which reduced the interaction with cholesterol clusters, could not alter the D4H-accessible cholesterol dynamics. Mechanistically, TRPV4-mediated Ca2+ influx and the C-terminal calmodulin-binding site of TRPV4 are essential for modulating the plasmalemmal D4H-accessible cholesterol dynamics. We propose that TRPV4 remodels its surrounding plasmalemmal environment by manipulating cholesterol dynamics through Ca2+ influx.

A 65-Year-Old Man with Refractory Hemoptysis Associated with Chronic Progressive Pulmonary Aspergillosis Who Failed to Respond to Combined Endobronchial Occlusion and Bronchial Artery Embolization: A Case Report and Literature Review.

BACKGROUND Hemoptysis due to airway hemorrhage is treated with hemostatic agents, bronchial artery embolization (BAE), or surgical resection. We present the case of a 65-year-old man with refractory hemoptysis associated with chronic progressive pulmonary aspergillosis (CPPA) who failed to respond to combined endobronchial occlusion (EBO) with endobronchial Watanabe spigot (EWS) and BAE. CASE REPORT A 63-year-old man was diagnosed with CPPA in the right upper lung and presented to our hospital 2 years later for hemoptysis at age 65. He developed severe hemoptysis during an outpatient visit, and was urgently admitted, intubated, and ventilated to prevent choking on blood clots. Chest computed tomography showed a large mass in the apical portion of the right lung, constituting apical pleural thickening and an encapsulated pleural effusion, and dilatation in the bronchial artery supplying the right upper lung lobe. Bronchoscopy revealed the right upper lobe B1-B3 as the bleeding source. The patient had recurrent hemoptysis that was not controlled by BAE or 6 EBO+EWS procedures, and he ultimately died of hypoxemia.In the literature review, EBO+EWS can effectively control hemoptysis in appropriate cases, without the need for BAE or surgical lung resection. It is less invasive, is associated with fewer adverse events than BAE or surgery, and can achieve temporary hemostasis for severe hemoptysis. CONCLUSIONS BAE and EBO+EWS were ineffective in controlling recurrent hemoptysis caused by CPPA in this case. However, a multidisciplinary approach such as attempting hemostasis with combined EBO+EWS and BAE may be a viable treatment option in severe cases of hemoptysis.

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases.

BACKGROUND: Drug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need. METHODS: Biomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls. RESULTS: Serum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients. CONCLUSIONS: The serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.

Radiation-induced organizing pneumonia caused by carbon-ion radiotherapy for lung cancer.

Radiation-induced organizing pneumonia is a rare complication of radiation therapy for thoracic cancer. Carbon-ion radiotherapy, an emerging treatment modality for early-stage lung cancer treatment, can also cause lung injuries. However, as cases of radiation-induced organizing pneumonia caused by carbon-ion radiotherapy for lung cancer have not been reported, its clinical features remain unclear. A 69-year-old woman was referred to our hospital 11 months after being diagnosed with early lung cancer due to refractory pneumonitis induced by carbon-ion radiotherapy. She had developed fever and dyspnea 4 months after undergoing carbon-ion radiotherapy and was subsequently diagnosed with radiation pneumonitis. The administration of oral prednisolone resulted in improvement. However, she relapsed each time the dose of prednisolone was tapered. She was diagnosed with radiation-induced organizing pneumonia caused by carbon-ion radiotherapy for lung cancer based on the clinical course and the results of the examination performed at our hospital. An improvement was observed after administering methylprednisolone (1000 mg/d) for 3 days. The dose of oral prednisolone was slowly tapered over a period of ≥6 months with no relapse. Organizing pneumonia caused by carbon-ion radiotherapy for lung cancer is treatable with corticosteroids; however, tapering the dose of corticosteroids may lead to relapse.

Prognostic impact of the cross-sectional area of the erector spinae muscle in patients with pleuroparenchymal fibroelastosis.

Pleuroparenchymal fibroelastosis (PPFE) progresses slowly but sometimes relatively quickly, leading to decreased activities of daily living (ADL) and muscle weakness. Skeletal muscle atrophy and muscle weakness in chronic obstructive pulmonary disease (COPD) patients may be caused by cachexia and are associated with reduced ADLs and increased risk of death. However, the association between skeletal muscle mass and the prognosis of PPFE patients remains unknown. We retrospectively analysed the clinical significance of the cross-sectional area of the erector spinae muscle (ESMCSA), a skeletal muscle index, and predictors of mortality within 3 years in PPFE 51 patients, idiopathic pulmonary fibrosis (IPF) 52 patients and COPD 62 patients. PPFE patients had significantly lower ESMCSA than IPF or COPD patients, and lower ESMCSA (< 22.57 cm2) was associated with prognosis within 3 years (log-rank test; p = 0.006), whereas lower body mass index (BMI) showed no association. Multivariate analysis showed that ESMCSA was an independent predictor of mortality within 3 years in PPFE patients (hazard ratio, 0.854; 95% confidence interval: 0.737-0.990, p = 0.036). These results suggest the importance of monitoring ESMCSA in PPFE patients and that assessing ESMCSA in PPFE patients could be a more useful prognostic indicator than BMI.

Sequential administration of PD­1 inhibitor and cetuximab causes pneumonia.

Severe drug-induced lung injury (DLI) has been reported to be associated with sequential administration of osimertinib, a third-generation tyrosine kinase inhibitor, following a programmed cell death ligand 1 (PD-L1) inhibitor. However, the relationship of sequential treatment with an anti-epidermal growth factor receptor (EGFR) antibody and PD-1 inhibitor with the risk of DLI remains to be elucidated. The present study conducted a retrospective review of the medical records of a total of 179 patients with head and neck cancer who had received treatment with cetuximab and/or a PD-1 inhibitor (nivolumab or pembrolizumab) at Chiba University Hospital (Chiba, Japan) between September 2014 and December 2020. The incidence of pneumonia and the clinical background characteristics of the patients were analyzed. The patients were classified into subgroups for analysis of the outcomes in this study: Patients who had received sequential, but not concurrent, cetuximab and PD-1 inhibitor treatment (Group C+P; n=43); patients who had received cetuximab-containing chemotherapy, but not a PD-1 inhibitor (Group C; n=101); and patients who had received PD-1 inhibitor-containing chemotherapy, but not cetuximab (Group P; n=35). The rates of DLI in the three groups were: Group C+P, 18.6%; Group C, 7.9%; and Group P, 11.4%. Prior use of ICI was not associated with any increase in the risk of DLI. DLI is seen frequently in patients receiving sequential PD-1 inhibitor and anti-EGFR antibody therapy.

A retrospective comparison between digital to conventional drainage systems for secondary spontaneous pneumothorax related to diffuse interstitial lung disease.

INTRODUCTION: Secondary spontaneous pneumothorax (SSP) occurs as one of the complications associated with interstitial pneumonia (IP). Chest drainage is performed when there is a large volume of air in the pleural space. Notably, SSP with IP (SSP-IP) is frequently not curable by chest drainage only. A digital drainage system (DDS) provides an objective evaluation of air leakage and maintains a pre-determined negative pressure, compared to an analog drainage system (ADS). Few studies have reported the effectiveness of DDS in the treatment of SSP-IP. This study aimed to assess the usefulness of DDS for SSP-IP. METHODS: This retrospective study included patients with SSP-IP who had undergone chest drainage. We reviewed the included patients' medical records, laboratory data, computed tomography findings, and pulmonary function data. RESULTS: DDS was used in 24 patients and ADS in 49 patients. The mean duration of chest drainage was 11.4 ± 1.9 days in the DDS group and 14.2 ± 1.3 days in the ADS group, which was not significantly different (p = 0.218). Surgery, pleurodesis, and/or factor XIII administration were performed in 40 patients. Additionally, five (20.8%) patients in the DDS group and nine (18.4%) in the ADS group had a recurrence of pneumothorax within 4 weeks (p = 1.000). One patient (14%) in the DDS group and six (12.2%) in the ADS group (p = 0.414) were cured of pneumothorax but later died. CONCLUSION: DDS did not demonstrate a significant difference in the shortening of chest drainage duration. Further study is needed to validate the results of this study.

Pulmonary Veno-occlusive Disease that Developed Following Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.

We herein report a case of pulmonary veno-occlusive disease (PVOD) induced by allo-hematopoietic stem cell transplantation (HSCT) in a 48-year-old man who was diagnosed with acute myeloid leukemia. Five months after transplantation, he developed dyspnea and was diagnosed with pulmonary hypertension based on right heart catheterization. Although he received treatment with pulmonary vasodilators, diuretics, and corticosteroids, his pulmonary artery pressure did not decrease, and his pulmonary edema worsened. Based on the clinical course, hypoxemia, diffusion impairment, and computed tomography findings, the patient was diagnosed with HSCT-related PVOD. Critical attention should be paid to dyspnea after HSCT for the early diagnosis of PVOD.

Quantitative Evaluation of Changes in Three-Dimensional CT Density Distributions in Pulmonary Alveolar Proteinosis after GM-CSF Inhalation.

BACKGROUND: A previous clinical trial for autoimmune pulmonary alveolar proteinosis (APAP) demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation reduced the mean density of the lung field on computed tomography (CT) across 18 axial slice planes at a two-dimensional level. In contrast, in this study, we challenged three-dimensional analysis for changes in CT density distribution using the same datasets. METHODS: As a sub-study of the trial, CT data of 31 and 27 patients who received GM-CSF and placebo, respectively, were analyzed. To overcome the difference between various shooting conditions, a newly developed automatic lung field segmentation algorithm was applied to CT data to extract the whole lung volume, and the accuracy of the segmentation was evaluated by five pulmonary physicians independently. For normalization, the percent pixel (PP) in a certain density range was calculated as a percentage of the total number of pixels from -1,000 to 0 HU. RESULTS: The automatically segmented images revealed that the lung field was accurately extracted except for 7 patients with minor deletion or addition. Using the change in PP from baseline to week 25 (ΔPP) as the vertical axis, we created a histogram with 143 HU bins set for each patient. The most significant difference in ΔPP between GM-CSF and placebo groups was observed in two ranges: from -1,000 to -857 and -143 to 0 HU. CONCLUSION: Whole lung extraction followed by density histogram analysis of ΔPP may be an appropriate evaluation method for assessing CT improvement in APAP.

A case of primary racemose hemangioma with endobronchial lesions demonstrating recurrent hemoptysis initially treated with bronchial arterial embolization.

Primary racemose hemangioma of the bronchial artery (RHBA) is one of the causes of massive hemoptysis. A 72-year-old woman was admitted to our hospital with recurrent hemoptysis. Bronchoscopy showed an endobronchial lesion, and the angiography of the right bronchial arteries indicated RHBA. Bronchial arterial embolization (BAE) was performed to prevent hemoptysis. Although the endobronchial lesion shrank after the first BAE, the lesion re-increased and caused massive hemoptysis. A thoracoscopic right upper lobectomy was performed, and hemoptysis did not recur. Therefore, in cases of RHBA where there is recurrent hemoptysis and the endobronchial lesions that remain after BAE, additional treatments should be considered.

Stratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage.

Among the various histopathological patterns of drug-induced interstitial lung disease (DILD), diffuse alveolar damage (DAD) is associated with poor prognosis. However, there is no reliable biomarker for its accurate diagnosis. Here, we show stratifin/14-3-3σ (SFN) as a biomarker candidate found in a proteomic analysis. The study includes two independent cohorts (including totally 26 patients with DAD) and controls (total 432 samples). SFN is specifically elevated in DILD patients with DAD, and is superior to the known biomarkers, KL-6 and SP-D, in discrimination of DILD patients with DAD from patients with other DILD patterns or other lung diseases. SFN is also increased in serum from patients with idiopathic DAD, and in lung tissues and bronchoalveolar lavage fluid of patients with DAD. In vitro analysis using cultured lung epithelial cells suggests that extracellular release of SFN occurs via p53-dependent apoptosis. We conclude that serum SFN is a promising biomarker for DAD diagnosis.

Clinical Outcomes of Sotrovimab Treatment in 10 High-Risk Patients with Mild COVID-19: A Case Series.

BACKGROUND Although sotrovimab reduces the risk of hospitalization or death due to COVID-19, there have been few reports of its use in clinical practice. Particularly, information on the effectiveness of sotrovimab against the omicron variant of the virus is limited. We present 10 cases of COVID-19 treated with sotrovimab at our unit between December 2021 and February 2022. CASE REPORT The age of the patients ranged from 32 to 81 years (median: 40 years). The comorbidities included lung cancer, cardiovascular disease, chronic kidney disease requiring hemodialysis, and AIDS. Two of the patients were also organ recipients. Oxygen saturation (SpO2) was above 97% in all patients. None of the patients presented with pneumonia on admission. However, blood test results showed that all patients had risk factors for severe COVID-19 outcomes. The interval from symptom onset to sotrovimab administration and resolution ranged from 2 to 5 days (median: 2 days) and 2 to 15 days (median: 5 days), respectively. Only 1 patient developed pneumonia and was treated with remdesivir after sotrovimab administration. However, this patient did not require oxygen therapy. Although no moderate to severe adverse events were observed, a mild adverse event was observed in 1 patient. CONCLUSIONS Sotrovimab could be safe and effective in preventing progression of COVID-19 in patients with a variety of underlying diseases and who are at high risk of severe disease outcomes.

Pneumocystis pneumonia in an immunocompetent patient developing a subacute disease course with central consolidation.

Pneumocystis pneumonia (PCP) typically occurs in immunocompromised individuals and rarely presents in immunocompetent individuals. A 55-year-old man was referred to our hospital with cough and anorexia that persisted for 2 months. Chest computed tomography revealed bilateral central consolidation. He was diagnosed with PCP via bronchoscopy. His symptoms and imaging findings improved with the administration of only trimethoprim and sulfamethoxazole. Although he had non-alcoholic fatty liver disease, there were no other complications that could potentially cause immunodeficiency. It should be noted that PCP in immunocompetent individuals can have a subacute disease course presenting with bilateral central consolidation.

Clinical Characteristics and Risk Factors of Lung Injury Induced by Nab-Paclitaxel.

Background/Aim: Nab-paclitaxel (Nab-PTX) has been widely used to treat several advanced cancers. Nab-PTX can cause drug-induced lung injury (DILI); however, its clinical and radiographic features have not been clarified. We aimed to assess the clinical characteristics of Nab-PTX-induced lung injury and identify its associated risk factors. Patients and Methods: We retrospectively investigated 304 patients who received Nab-PTX at Chiba University Hospital between November 2010 and November 2017. We obtained information regarding the clinical course, laboratory findings, and chest computed tomography findings from their medical records. Results: Forty-one patients (13%) developed DILI. Grade 1 lung injury occurred in 27 patients (8.8%), grade 2, 8 patients (2.6%); grade 3, 3 patients (0.9%); grade 4, 1 (0.3%); and grade 5, 2 (0.6%). Multivariate analysis revealed that age >56 years (odds ratio [OR]: 3.0), pre-existing interstitial lung changes (OR: 3.2), and combined drugs with gemcitabine (OR: 2.7) were independent risk factors for DILI owing to Nab-PTX administration. Conclusion: Nab-PTX-induced lung injury is not rare; however, most cases are asymptomatic (grade 1). Older age, pre-existing interstitial lung changes, and combined drugs with gemcitabine could increase the incidence of Nab-PTX-induced lung injury; such patients should be treated with greater care.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells in Pulmonary Sarcoidosis.

BACKGROUND: Sarcoidosis is a granulomatous systemic disease of unknown etiology. Mononuclear cells such as macrophages or lymphocytes in lung tissue and hilar or mediastinal lymph nodes have been recognized to play an essential role in granuloma formation in pulmonary sarcoidosis. Peripheral blood mononuclear cells (PBMCs) consist of several immunocompetent cells and have been shown to play a mechanistic role in the pathogenesis of sarcoidosis. However, the genetic modifications that occur in bulk PBMCs of sarcoidosis remain to be elucidated. PURPOSE: This study aimed to explore the pathobiological markers of sarcoidosis in PBMCs by comparing the transcriptional signature of PBMCs from patients with pulmonary sarcoidosis with those of healthy controls by RNA sequencing. METHODS: PBMC samples were collected from subjects with pulmonary sarcoidosis with no steroid/immunosuppressant drugs (n = 8) and healthy controls (n = 11) from August 2020 to April 2021, and RNA sequencing was performed with the PBMC samples. RESULTS: Principal component analysis using RNA sequencing datasets comparing pulmonary sarcoidosis with healthy controls revealed that the two groups appeared to be differentiated, in which 270 differentially expressed genes were found in PBMCs between sarcoidosis and healthy controls. Enrichment analysis for gene ontology suggested that some biological processes related to the pathobiology of sarcoidosis, such as cellular response to interleukin (IL)-1 and IFN-γ, regulation of IL-6 production, IL-8 secretion, regulation of mononuclear cell migration, and response to lipopolysaccharide, were involved. Enrichment analysis of the KEGG pathway indicated the involvement of tumor necrosis factor (TNF), toll-like receptor signaling, IL-17 signaling pathways, phagosomes, and ribosomes. Most of the genes involved in TNF and IL-17 signaling pathways and phagosomes were upregulated, while most of the ribosome-related genes were downregulated. CONCLUSION: The present study demonstrated that bulk gene expression patterns in PBMCs were different between patients with pulmonary sarcoidosis and healthy controls. The changes in the gene expression pattern of PBMCs could reflect the existence of sarcoidosis lesions and influence granuloma formation in sarcoidosis. These new findings are important to strengthen our understanding of the etiology and pathobiology of sarcoidosis and indicate a potential therapeutic target for sarcoidosis.

What are the factors affecting the recovery rate of bronchoalveolar lavage fluid?

BACKGROUND: Bronchoalveolar lavage (BAL) is a useful examination for the evaluation of interstitial lung disease. A high BAL fluid (BALF) recovery rate is desirable because low recovery rates lead to inaccurate diagnoses and increased adverse events. Few studies have explored whether BALF recovery rates are influenced by clinical factors. OBJECTIVES: This study aimed to identify the clinical parameters affecting the recovery rates of BALF and the extent of their effects. METHOD: Data from patients who underwent BAL at the Chiba University Hospital between 2013 and 2019 were retrospectively reviewed. BAL was performed with three aliquots of 50-ml physiological saline. The potential association of the BALF recovery rate with clinical parameters such as age, sex, smoking status, underlying disease, bronchus used for the procedure and pulmonary function, was analysed. RESULTS: Eight hundred twenty-six patients had undergone BAL. The average recovery rate was 52.4%. Factors affecting BALF recovery rates included male sex (odds ratio [OR]: 0.32, 95% confidence interval [CI]: 0.20-0.53, p < 0.001); age ≥ 65 years (OR: 0.50, 95% CI: 0.33-0.76, p < 0.001); use of the left bronchus (OR: 0.46, 95% CI: 0.30-0.71, p = 0.001) and bronchi other than the middle lobe bronchus or lingula (OR: 0.41, 95% CI: 0.25-0.65, p < 0.001); and forced expiratory volume in 1 s divided by forced vital capacity <80% (OR: 0.42, 95% CI: 0.40-1.00, p < 0.001). CONCLUSION: Sex, age, bronchus used for the procedure and pulmonary function may be useful as pre-procedural predictors of BALF recovery rates.

Exacerbation of autoimmune pulmonary alveolar proteinosis that improved with lone treatment of complicating nontuberculous mycobacterial infection: A case report.

Herein, we present the case of a 63-year-old man with autoimmune pulmonary alveolar proteinosis (APAP) complicated by Mycobacterium avium complex (MAC) infection. APAP was diagnosed based on serum anti-granulocyte-macrophage colony-stimulating factor antibody, bronchoalveolar lavage fluid (BALF) findings, and transbronchial lung biopsy. Nodular shadows with cavities were visible on chest CT images, and Mycobacterium intracellulare was identified by BALF culture. Rifampicin, ethambutol, and clarithromycin were administered, and 4 months later, the nodular shadows of MAC had disappeared, and APAP was remarkably improved. Thus, in cases of APAP exacerbation complicated with infections, such as MAC, control of the infections may improve APAP.

DNA-Based Synthetic Growth Factor Surrogates with Fine-Tuned Agonism*.

Designing synthetic surrogates of functional proteins is an important, albeit challenging, task in the field of chemistry. A strategy toward the design of synthetic agonists for growth factor or cytokine receptors that elicit a desired signal activity has been in high demand, as such ligands hold great promise as safer and more effective therapeutics. In the present study, we used a DNA aptamer as a building block and described the strategy-guided design of a synthetic receptor agonist with fine-tuned agonism. The developed synthetic partial agonist can regulate therapeutically relevant cellular activities by eliciting fine-tuned receptor signaling.

Risk factors for acute exacerbation following bronchoalveolar lavage in patients with suspected idiopathic pulmonary fibrosis: A retrospective cohort study.

INTRODUCTION: Bronchoalveolar lavage (BAL) is useful for diagnosing diffuse lung disease and excluding other conditions. However, acute exacerbations (AEs) are recognized as important complications of BAL in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to identify risk factors for BAL-induced AEs in patients with IPF. MATERIAL AND METHODS: We retrospectively analyzed the data of 155 patients with suspected IPF who had undergone BAL between January 2013 and December 2018. BAL-related AE was defined as the development of AE within 30 days after the procedure. We compared clinical features and parameters between patients with AE (AE group) and without AE (non-AE group). We also reviewed the relevant reported literature. RESULTS: Among the 155 patients, 5 (3.2%) developed AE within 30 days after BAL. The average duration from BAL to AE onset was 7.8 days (2-16 days). Results from the univariate analysis revealed PaO2 < 75 mm Hg (p = 0.036), neutrophil content in BAL ≥ 7% (p = 0.0061), %DLCO < 50% (p = 0.019), Gender-Age-Physiology (GAP) stage III (p = 0.034), and BAL recovery rates < 30% (p < 0.001) as significant risk factors for post-BAL AE. All five patients who developed AE recovered and were discharged. CONCLUSIONS: Disease severity, high neutrophil levels in BAL, and poor BAL recovery rates may be risk factors for BAL-induced AEs.