ABSTRACT
Endobronchial tuberculosis often causes bronchial stenosis. Balloon dilation is a minimally invasive and effective bronchoscopic intervention for bronchial stenosis; however, reports on balloon dilation in older individuals are limited. We present a case of a 77-year-old woman with endobronchial tuberculosis and clarify the efficacy and safety of balloon dilation. She presented with dyspnea, right lung atelectasis, and respiratory failure 55 days after initiation of antituberculosis therapy. We performed bronchoscopic balloon dilatation for the right main bronchial stenosis. Consequently, respiratory failure rapidly improved. Chest computed tomography (CT) showed improved lung atelectasis; however, severe bronchial stenosis and rhonchi persisted. Therefore, we performed a second balloon dilatation. CT 3 months after the first balloon dilation showed right upper bronchial stenosis and right lung middle lobe atelectasis. Restenosis was absent 21 months after third balloon dilatation. Bronchoscopic balloon dilation is effective for restenosis with repeated treatment and can be safely performed in older individuals.
ABSTRACT
BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).
Subject(s)
Asthma , Humans , Cohort Studies , Japan/epidemiology , Asthma/diagnosis , Asthma/epidemiology , Asthma/drug therapy , Phenotype , Biomarkers , Cluster AnalysisABSTRACT
BACKGROUND: The clinical course of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is highly variable. The Krebs von den Lungen-6 (KL-6) glycoprotein is a promising biomarker for reflecting epithelial injury. However, serum KL-6 and its association with the progression of SSc-ILD have been understudied. METHODS: We reviewed 77 consecutive patients with SSc-ILD seen from 2004 to 2016. A longitudinal study of forced vital capacity (FVC), serum KL-6 levels, and changes in KL-6 levels from baseline (ΔKL-6) was conducted. The progression of ILD was defined as ≥10% relative decline in FVC predicted or 5%-10% decline in FVC predicted along with radiological progression on chest computed tomography. The risk factors for ILD progression were assessed by univariate and multivariate regression. RESULTS: During a 5-year follow-up period, 10 (13%) patients showed rapid progression of ILD within 2 years, 39 (51%) showed overall progression during the 5 years, and 28 (36%) had stable disease. Most patients with progressive ILD showed elevations in serum KL-6 levels over the initial 1-year follow-up period. The best cut-off value for ΔKL-6 that predicted progression of ILD was 193 U/mL (sensitivity 81.6%, specificity 92.9%). Multivariate analysis adjusted by age, sex, smoking status, and immunosuppressant use found that diffuse cutaneous SSc (hazard ratio [HR] 4.51; 95% confidence interval [CI] 1.56-13.04) and ΔKL-6 > 193 U/mL from baseline (HR 7.19; 95% CI 3.30-15.69) were independent predictors for progression of SSc-ILD. CONCLUSION: Changes in the KL-6 level can be useful for predicting disease progression in patients with SSc-ILD.
Subject(s)
Lung Diseases, Interstitial , Mucin-1/blood , Scleroderma, Systemic , Disease Progression , Humans , Longitudinal Studies , Lung , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/etiology , Scleroderma, Systemic/complications , Vital CapacityABSTRACT
OBJECTIVES: Interstitial lung disease (ILD) associated with the antimelanoma differentiation-associated protein 5 (anti-MDA5) antibody is a rapidly progressive disease that requires timely, aggressive treatment. However, prompt diagnosis is difficult due to the longer time required for antibody detection. This study described the computed tomography (CT) findings of anti-MDA5 antibody-positive ILD (anti-MDA5-ILD). METHODS: CT findings of 20 patients (7 men, 13 women; mean age, 53.6 ± 13.5 years) with anti-MDA5-ILD were retrospectively reviewed. All patients had clinical diagnoses of dermatomyositis, and 14 patients presented with amyopathic findings. RESULTS: Bilateral ground-glass attenuation, air-space consolidation, and reticular shadows were observed in 20 (100%), 15 (75%), and 3 (15%) patients, respectively. The spread of air-space consolidation was 6.0 ± 5.6% (mean ± standard deviation). Univariate analysis revealed that high Krebs von den Lungen-6, high spread of consolidation, low partial pressure of oxygen, and low forced vital capacity were significant predictors for poor survival. The final radiological diagnoses were nonspecific interstitial pneumonia and organising pneumonia (OP) in 2 (10%) and 16 (80%) patients, respectively. Further, 30% of OP patients showed fibrosis. CONCLUSION: The characteristic CT findings of patients with anti-MDA5-ILD were ground-glass attenuation, air-space consolidation, and less reticulation. These CT findings were compatible with those of OP.
Subject(s)
Dermatomyositis , Lung Diseases, Interstitial , Adult , Aged , Autoantibodies , Dermatomyositis/complications , Female , Humans , Interferon-Induced Helicase, IFIH1 , Lung Diseases, Interstitial/complications , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: The utility of bronchoalveolar lavage (BAL) in the evaluation of systemic sclerosis-associated interstitial lung disease (SSc-ILD) remains controversial. Fractional analysis of BAL (FBAL) is a technique that can analyze small airways and alveolar compartments separately and has proven informative in other ILDs. The aim of this study was to explore FBAL characteristics across the spectrum of SSc-ILD severity. METHODS: We retrospectively reviewed patients with SSc-ILD who underwent bronchoscopy with FBAL using three 50 mL aliquots of saline solution. These aliquots were analyzed separately for differential cell composition (FBAL-1, -2, and -3). We compared the FBAL cell composition to the progression of ILD and end-stages of ILD using Cox proportional hazards models. RESULTS: Sixty-eight patients with SSc-ILD were enrolled in this study. The percentage of neutrophils and eosinophils was lower in FBAL-3 compared to FBAL-1. In contrast, the percentage of macrophages and lymphocytes was higher in FBAL-3. Neutrophils in FBAL-2, -3, and the estimated total FBAL cell fraction (FBAL-total) were negatively correlated with the forced vital capacity % predicted (r=-0.420, -0.362, -0.409, respectively). Although FBAL-total was not linked to the progression and end-stage of ILD, a high percentage of neutrophils in FBAL-3 was significantly associated with the development of end-stage ILD (HR 1.093, 95% CI: 1.003-1.190). CONCLUSIONS: A higher percentage of neutrophils in FBAL-3 is correlated with development of end-stage ILD in SSc-ILD as well as mortality.
ABSTRACT
BACKGROUND: Drug-induced pneumonia (d-pneumonia) and bacterial pneumonia (b-pneumonia) are often difficult to differentiate; therefore, this study examined the possibility of differentiating them using serum biomarkers. METHODS: The study included 22 and 16 patients diagnosed with b- and d-pneumonia, respectively, at our institution or affiliated institutions. For d-pneumonia, the causative drug was minocycline hydrochloride in four patients, gefitinib in two patients, nivolumab in two patients, pembrolizumab in two patients, sulfasalazine in two patients, loxoprofen in one patient, Bouiougitou in one patient, edoxaban tosilate hydrate in one patient, and abemaciclib in one patient. White blood cell (WBC), C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, and SP-A levels were measured in each patient and compared between the groups. RESULTS: Significant differences were noted in the WBC and SP-D levels between the two groups (P < 0.05, P < 0.001), but not in the CRP, KL-6, or SP-A levels. CONCLUSION: The study results suggest that SP-D is a useful marker for differentiating b-pneumonia and d-pneumonia.
ABSTRACT
BACKGROUNDS: Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. METHODS: We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. RESULTS: Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). CONCLUSIONS: LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.
ABSTRACT
OBJECTIVE: To identify and characterize a novel connective tissue disease (CTD)-related autoantibody (autoAb) directed against scaffold attachment factor B (SAFB). METHODS: AutoAb specificity was analyzed using RNA and protein-immunoprecipitation assays. Autoimmune targets were affinity purified using patients' sera and subjected to liquid chromatography mass spectrometry. RESULTS: By immunoprecipitation assay, 10 sera reacted with a protein with a molecular weight of approximately 160 kDa. Liquid chromatography mass spectrometry of the partially purified autoantigen and additional immunoblot-based analyses revealed that the Ab specifically recognized SAFB. Anti-SAFB Abs were detected in 2 of 646 patients with systemic sclerosis (SSc) (0.3%), 1 of 1570 patients with polymyositis/dermatomyositis (0.06%), 4 of 270 patients with interstitial lung disease (ILD) (1.5%), 1 of 43 patients with overlap syndrome (2.3%) and 2 patients with other diseases including primary Raynaud's disease and eosinophilic pneumonia. Five patients with anti-SAFB Abs had Raynaud's phenomenon and 3 had nail fold punctate hemorrhage. Of note, 8 of the 10 patients (80%) suffered from ILD. None of the patients with anti-SAFB Abs had pulmonary arterial hypertension, heart disease, or renal involvement. CONCLUSIONS: Anti-SAFB Ab is a novel CTD-related autoAb possibly associated with ILD.
Subject(s)
Autoantibodies/immunology , Autoantigens/immunology , Lung Diseases, Interstitial/immunology , Matrix Attachment Region Binding Proteins/immunology , Nuclear Matrix-Associated Proteins/immunology , Receptors, Estrogen/immunology , Aged , Biomarkers , Case-Control Studies , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lung Diseases, Interstitial/diagnosis , Male , Middle Aged , PhenotypeABSTRACT
OBJECTIVES: To describe the pulmonary CT findings in patients with anti-ARS-antibody-positive interstitial lung disease (anti-ARS-ILD) METHODS: The CT findings of 64 patients with anti-ARS-ILD were retrospectively reviewed. The images were retrospectively reviewed independently by 2 chest radiologists, and the final decision on the CT findings was made by a third chest radiologist. RESULTS: There were 16 male and 48 female patients, aged 54.2±13.4 years. Sixteen patients had anti Jo-1, 24 had anti-EJ, 9 had anti-PL-7, 7 had anti-PL-12, 5 had anti-KS, and 3 had anti-OJ antibodies. Overall, 63 patients (98.4%) had CT findings predominantly in the lower lobe; 61 patients (95.3%) showed peripheral opacities, and 47 patients (73.4%) showed peribronchovascular opacities. Ground-glass attenuation, consolidation, and reticulation showed similar distribution patterns. Regarding detailed CT findings, 89.1% of patients had lower volume loss, 76.6% had interlobular septal thickening, and 67.2% had thickening of bronchovascular bundles. The final radiologic diagnoses were as follows: inconsistent with usual interstitial pneumonia (UIP) in 63 patients (98.4%), which included nonspecific interstitial pneumonia (NSIP) in 35 patients (55.6%), organizing pneumonia (OP) in 4 patients (6.3%), and OP with fibrosis in 22 patients (34.9%). CONCLUSIONS: The characteristic CT findings of patients with anti-ARS-ILD were areas of ground-glass attenuation and reticulation, predominantly distributed as lower and peribronchovascular lesions, which is compatible with NSIP. One-third of patients showed OP with fibrosis.
Subject(s)
Amino Acyl-tRNA Synthetases/immunology , Autoantibodies/immunology , Myositis/diagnostic imaging , Myositis/immunology , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Amino Acyl-tRNA Synthetases/blood , Autoantibodies/blood , Female , Humans , Lung/diagnostic imaging , Lung/immunology , Male , Middle Aged , Myositis/blood , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia defined by pleural and subpleural parenchymal fibrosis predominantly in the upper lobes. Although the radiological and pathological characteristics of PPFE have become increasingly recognized, its pulmonary physiological features are not well understood. METHODS: We reviewed nine patients with radiologically and histologically proven PPFE, and evaluated pulmonary physiological data. RESULTS: Of the nine patients, six were male and three were female. The median age at presentation was 61 years. Common symptoms were dyspnea on exertion, weight loss, and nonproductive cough. Recurrent pneumothorax was found in eight patients and pneumonia in four. Median pulmonary function test results were as follows: forced vital capacity, 55.4% predicted; total lung capacity (TLC), 67.1% predicted; residual volume (RV), 102.3% predicted; and RV/TLC, 143.6% predicted. RV/TLC was increased without evidence of small airway disease according to clinico-radiologic-pathologic evaluation. The median partial pressure of oxygen in arterial blood and the alveolar-arterial gradient of oxygen were within normal limits, although there was a slightly elevated partial pressure of carbon dioxide in arterial blood (PaCO2). PPFE progressed in all patients despite treatment with pirfenidone, corticosteroids, and immunosuppressive agents. Seven patients died during the follow-up, five because of hypercapnic respiratory failure. CONCLUSIONS: PPFE is characterized by severe mechanical restriction with high RV/TLC, causing increased PaCO2 and eventual hypercapnic respiratory failure. These physiological findings may be useful as an adjunct in the diagnosis of PPFE.
Subject(s)
Idiopathic Interstitial Pneumonias/diagnostic imaging , Idiopathic Interstitial Pneumonias/pathology , Lung/diagnostic imaging , Lung/pathology , Adult , Aged , Dyspnea/etiology , Female , Humans , Hypercapnia/etiology , Idiopathic Interstitial Pneumonias/complications , Idiopathic Interstitial Pneumonias/physiopathology , Lung/physiopathology , Male , Middle Aged , Pneumothorax/etiology , Recurrence , Respiratory Function Tests , Respiratory Insufficiency/etiology , Respiratory Physiological Phenomena , Tomography, X-Ray Computed , Young AdultABSTRACT
BACKGROUND: Autoantibodies against aminoacyl-tRNA synthetases (ARS) have been found to be highly specific for polymyositis and dermatomyositis (PM/DM) and to correlate strongly with complicating interstitial pneumonia (IP). The aim of the present study was to compare the clinical presentations of anti-ARS antibody-positive IP patients with or without manifestations of PM/DM. METHODS: We retrospectively examined 36 IP patients with anti-ARS antibodies. Sixteen patients presented with and 20 without the features of PM/DM. They were divided into PM/DM-IP and idiopathic-IP (IIP) groups. Clinical symptoms, findings on physical examination, laboratory data, pulmonary function, computed tomography (CT), and bronchoalveolar lavage fluid (BALF) cell counts were compared. RESULTS: Skin findings, myalgia, and elevation of serum creatinine kinase were found in the PM/DM-IP group. Features common to both groups included: volume loss in lower bilateral lobes; ground-glass opacities, reticular shadows and traction bronchiectasis on chest CT; high percentage of lymphocytes (IIP: 44.0% ± 21.0% (mean ± SD), PM/DM-IP: 50.5% ± 23.5%) and low CD4/8 ratios (IIP: 0.36 ± 0.34, PM/DM-IP: 0.44 ± 0.42) in BALF; decreased pulmonary function, including percentage of predicted vital capacity (VC) (IIP: 80.1% ± 15.4%, PM/DM-IP: 73.6% ± 16.4%), residual volume (RV) (IIP: 70.7% ± 21.7%, PM/DM-IP: 71.5% ± 17.1%), total lung capacity (TLC) (IIP: 73.4% ± 13.6%, PM/DM-IP: 71.6% ± 13.0%), and diffusing capacity DLco (IIP: 57.5% ± 26.7%, PM/DM-IP: 46.4% ± 10.3%). Both groups achieved good responses to initial corticosteroid or immunosuppressant therapy. CONCLUSION: Patients with anti-ARS antibody-positive IP have common pulmonary manifestations regardless of the presence of PM/DM.
Subject(s)
Amino Acyl-tRNA Synthetases/immunology , Autoantibodies/analysis , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/immunology , Polymyositis/complications , Adolescent , Adult , Aged , Bronchoalveolar Lavage Fluid/cytology , Dermatomyositis/complications , Dermatomyositis/immunology , Female , Humans , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Physical Examination/methods , Polymyositis/immunology , Retrospective Studies , Tomography, X-Ray Computed , Total Lung Capacity , Young AdultABSTRACT
DF Thermo, a modified form of double-filtration plasmapheresis (DFPP), has been used for the treatment of various indications such as arteriosclerosis obliterans (ASO). In case of ASO, fibrinogen is a substance to be removed by DFPP. On the other hand, plasmapheresis for chronic viral hepatitis C became an insurance covered treatment in Japan in April 2008. Since then DFPP has also become a treatment of chronic viral hepatitis C as an adjunctive therapy for the purpose of improving the effect of medication. Therefore, there has been a growing concern in recent years about patients' low fibrinogen levels due to DFPP treatment. With the aim of improving fibrinogen retention by DF Thermo, we examined by in vitro trial, the effects when recirculating the filtrate and elevating its temperature. The trial was conducted using bovine plasma, run through experimental circuits with the same configuration as the clinical setting of the One-Way method and DF Thermo method. The DF Thermo circuit contained a thermostat, on which the temperature was set to 40°C. Two One-Way method circuits were prepared with different temperature settings, i.e., 20°C and 40°C. With these three different conditions, variance of the fibrinogen retention under different temperatures and the implementation of recirculation were compared. Results show that the DF Thermo circuit tends to have enhanced the fibrinogen retention compared to the One-Way method 20°C and 40°C. The explanation is likely as follows: viscosity of plasma reduces when warmed, which in turn helps maintain the permeability of membrane, and the recirculation of the plasma helps prevent membrane fouling, thus more fibrinogen is retained in the DF Thermo method.
Subject(s)
Fibrinogen/metabolism , Plasmapheresis/methods , Temperature , Animals , Cattle , Equipment Design , Filtration , Hepatitis C, Chronic/therapy , In Vitro Techniques , Membranes, Artificial , ViscosityABSTRACT
PURPOSE: Decreased ventilation is observed on chest radiographs as small changes in X-ray translucency, and ventilatory impairments can therefore be detected by analyzing the distribution of respiratory-induced changes in pixel value. This study was performed to develop a ventilatory impairment detection method based on the distribution of respiratory-induced changes in pixel values. METHODS: Sequential chest radiographs during respiration were obtained using a dynamic flat panel detector system. Respiratory-induced changes in pixel value were measured in each local area and then compared for symmetrical positions in both lungs, which were located at the same distance from the axis of the thorax at the same level. The right-left symmetry was assessed in 20 clinical cases (Abnormal, 14; Normal, 6). RESULTS: In normal controls, the distribution was symmetrical, and there were good correlations of the pixel value changes in both lungs at symmetrical positions (r = 0.66 ± 0.05). In contrast, abnormal cases did not show a symmetrical distribution of pixel value changes (r = 0.40 ± 0.23) due to ventilation abnormalities observed as reductions in pixel value changes. CONCLUSIONS: Ventilatory impairment could be detected as deviation from the right-left symmetry of respiratory-induced changes in pixel value. In particular, the present method could be useful for detecting unilateral abnormalities. However, to detect bilateral abnormalities, further studies are required to develop multilevel detection methods combined with several methods of pattern analysis.
Subject(s)
Lung Diseases/diagnostic imaging , Radiographic Image Enhancement/methods , Radiography, Thoracic/methods , Respiratory Mechanics/physiology , Adult , Aged , Aged, 80 and over , Feasibility Studies , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Microscopic polyangiitis is a vasculitic disease that may result in a pulmonary renal syndrome. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis is strongly associated with infection. CASE SUMMARY: We describe a case of microscopic polyangiitis that developed in a patient with MPO-ANCA positive pulmonary fibrosis following infection with mycoplasma. A renal biopsy was undertaken following the detection of microscopic hematuria during follow-up but no abnormal findings were evident. The MPO-ANCA titer increased following infection with mycoplasma pneumonia and a second renal biopsy demonstrated crescentic glomerulonephritis. The degree of pulmonary fibrosis was unaffected. DISCUSSION: The present case suggests that the mycoplasma infection triggered the elevation of MPO-ANCA titer and provoked glomerulonephritis in a patient with MPO-ANCA positive IPF. This case indicates the importance of testing for MPO-ANCA at the time of initial diagnosis, performing urinalysis and examining the urine sediment during follow-up and being alert to the potential onset of vasculitis in cases of pulmonary fibrosis.
Subject(s)
Antibodies, Antineutrophil Cytoplasmic/immunology , Microscopic Polyangiitis/etiology , Mycoplasma Infections/complications , Pulmonary Fibrosis/complications , Anti-Infective Agents/therapeutic use , Female , Glomerulonephritis/complications , Glomerulonephritis/diagnosis , Glomerulonephritis/drug therapy , Glomerulonephritis/immunology , Glomerulonephritis/pathology , Humans , Immunosuppressive Agents/therapeutic use , Microscopic Polyangiitis/diagnosis , Microscopic Polyangiitis/drug therapy , Microscopic Polyangiitis/immunology , Middle Aged , Mycoplasma Infections/diagnosis , Mycoplasma Infections/drug therapy , Mycoplasma Infections/immunology , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/immunology , Radiography , Treatment OutcomeABSTRACT
Chymase is a chymotrypsin-like serine protease that is present in mast cells. Its activities include various effects associated with inflammatory responses. But little is known about the effects of chymase in pulmonary fibrosis. The mouse silicosis model was induced by intratracheal injection of 10 mg silica. The Ashcroft pathological score and the hydroxyproline content of lungs were measured to evaluate the effect of a chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl] thiazole-4-carboxylic acid (TY-51469). The cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF) were also examined. Following TY-51469 treatment, the lung fibrosis score and hydroxyproline level were significantly reduced, and the number of neutrophils and the levels of macrophage inflammatory protein-2, monocyte chemoattractant protein-1, and transforming growth factor-ß1 in BALF were reduced on day 21. The administration of TY-51469 at an early stage showed a greater reduction of fibrosis compared to administration at a later stage. The neutrophil number in BALF in mice treated with TY-51469 both at an early stage and late stage was significantly reduced. The level of mouse mast cell proteinase-4 mRNA increased with time in silica-induced fibrosing lung tissue. These results show that the chymase inhibitor TY51469 suppresses the migration of neutrophils, which results in the suppression of lung fibrosis.
Subject(s)
Chymases/antagonists & inhibitors , Neutrophils/drug effects , Neutrophils/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Sulfonamides/pharmacology , Thiophenes/pharmacology , Animals , Bronchoalveolar Lavage Fluid/chemistry , Chemokine CCL2/metabolism , Chemokines, CC/metabolism , Chymases/metabolism , Cytokines/metabolism , Hydroxyproline/metabolism , Macrophage Inflammatory Proteins/metabolism , Male , Mast Cells/drug effects , Mast Cells/metabolism , Mice , Mice, Inbred ICR , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/metabolism , Serine Endopeptidases/biosynthesis , Serine Endopeptidases/genetics , Silicon Dioxide , Transforming Growth Factor beta1/metabolismABSTRACT
Pulmonary blood flow is reflected in dynamic chest radiographs as changes in X-ray translucency, i.e., pixel values. Thus, decreased blood flow should be observed as a reduction of the variation of X-ray translucency. We performed the present study to investigate the feasibility of pulmonary blood flow evaluation with a dynamic flat-panel detector (FPD). Sequential chest radiographs of 14 subjects were obtained with a dynamic FPD system. The changes in pixel value in each local area were measured and mapped on the original image by use of a gray scale in which small and large changes were shown in white and black, respectively. The resulting images were compared to the findings in perfusion scans. The cross-correlation coefficients of the changes in pixel value and radioactivity counts in each local area were also computed. In all patients, pulmonary blood flow disorder was indicated as a reduction of changes in pixel values on the mapping image, and a correlation was observed between the distribution of changes in pixel value and those in radioactivity counts (0.7 Subject(s)
Image Processing, Computer-Assisted/methods
, Lung/blood supply
, Regional Blood Flow
, Adult
, Aged
, Female
, Heart/physiology
, Heart/physiopathology
, Humans
, Image Processing, Computer-Assisted/instrumentation
, Lung/diagnostic imaging
, Lung Diseases/diagnostic imaging
, Lung Diseases/physiopathology
, Male
, Middle Aged
, Radiography
ABSTRACT
A 39-year-old man, who had been working in an aluminum processing industry for 18 years, visited our hospital for right chest pain on March 2, 2007. A relapse of right pneumothorax was found, and he was hospitalized. As the pneumothorax did not improve with conservative treatment, video-assisted thoracoscopic biopsy and suturing of the right upper lobe were successfully performed. The pulmonary parenchyma had collapsed, there was pulmonary fibrosis, and lymphocytes had gathered in follicules. Based on elemental analysis results, we diagnosed aluminum lung. It was thought that overexpansion of the lower lobe with the predominant upper lobe fibrosis was caused by the aluminum deposition. We judged his condition to be serious and we started treatment with 25 mg/day prednisolone (PSL), and 120 mg/day cyclosporine (CyA). At the time of writing, he is an outpatient, and is being monitored on a regimen of 5 mg/day PSL and 160 mg/day CyA without any progression of pulmonary fibrosis or relapse of pneumothorax.
Subject(s)
Aluminum/adverse effects , Occupational Diseases/chemically induced , Occupational Diseases/diagnosis , Pneumothorax/chemically induced , Pneumothorax/diagnosis , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/diagnosis , Adult , Aluminum/analysis , Humans , MaleABSTRACT
BACKGROUND: The clinical features of pneumocystis pneumonia (PCP) differ according to the predisposing factors responsible for immunosuppression. Although PCP in patients with acquired immunodeficiency syndrome (AIDS) has been extensively described, its characteristics in non-AIDS patients, such as those with malignancies, are not thoroughly documented. STUDY OBJECTIVE: To characterize and compare the clinical and imaging features of PCP in patients with malignancies with those in AIDS patients. DESIGN: A multi-center retrospective study. PATIENTS AND MEASUREMENTS: We evaluated the clinical and radiological features of PCP in 21 patients with malignancies and in 17 with AIDS. Clinical presentation, serum markers, oxygenation, CT findings, and outcome were examined. RESULTS: The patients with malignancies showed shorter durations of symptoms before PCP was diagnosed. The levels of serum markers and the oxygenation index did not differ. CT showed diffuse or widespread ground-glass opacity (GGO) in all of the patients evaluated. None of the AIDS patients demonstrated consolidation, whereas half of the patients with malignancy showed consolidation along with GGO. The extent of GGO scored on CT images was significantly greater in the AIDS patients. No correlation was observed between the CT findings and other clinical parameters. All of the AIDS patients recovered from PCP, whereas six patients with malignancies died within a month after the onset of PCP. CONCLUSION: The characteristics of the CT images differed between the patient groups with different underlying disorders, although it remains to be determined whether CT findings are associated with other clinical features or are predictive of the outcome of PCP.
Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , Neoplasms/complications , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/etiology , AIDS-Related Opportunistic Infections/diagnostic imaging , AIDS-Related Opportunistic Infections/drug therapy , Adult , Anti-Infective Agents/therapeutic use , Biomarkers/blood , Female , Humans , Leukocyte Count , Male , Middle Aged , Oxygen/blood , Pneumonia, Pneumocystis/diagnostic imaging , Pneumonia, Pneumocystis/drug therapy , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useABSTRACT
PURPOSE: Pulmonary ventilation and circulation dynamics are reflected on fluoroscopic images as changes in X-ray translucency. The purpose of this study was to investigate the feasibility of non-contrast functional imaging using a dynamic flat-panel detector (FPD). METHODS: Dynamic chest radiographs of 20 subjects (abnormal, n = 12; normal, n = 8) were obtained using the FPD system. Image analysis was performed to get qualitative perfusion mapping image; first, focal pixel value was defined. Second, lung area was determined and pulmonary hilar areas were eliminated. Third, one cardiac cycle was determined in each of the cases. Finally, total changes in pixel values during one cardiac cycle were calculated and their distributions were visualized with mapping on the original image. They were compared with the findings of lung perfusion scintigraphy. RESULTS: In all normal controls, the total changes in pixel value in one cardiac cycle decreased from the hilar region to the peripheral region of the lung with left-right symmetric distribution. In contrast, in many abnormal cases, pulmonary blood flow disorder was indicated as a reduction of changes in pixel values on a mapping image. The findings of mapping image coincided with those of lung perfusion scintigraphy. CONCLUSIONS: Dynamic chest radiography using an FPD system with computer analysis is expected to be a new type of functional imaging, which provides pulmonary blood flow distribution additionally.
Subject(s)
Image Processing, Computer-Assisted/instrumentation , Lung Diseases/diagnostic imaging , Lung Diseases/physiopathology , Pulmonary Circulation/physiology , Radiography, Thoracic/instrumentation , Adult , Aged , Aged, 80 and over , Algorithms , Feasibility Studies , Female , Humans , Male , Middle Aged , Perfusion Imaging , Predictive Value of Tests , Young AdultABSTRACT
Pulmonary ventilation and circulation dynamics are reflected on dynamic chest radiographs as changes in X-ray translucency,i.e., pixel values. The present study was performed to develop a pulmonary functional evaluation method based on the changes in pixel value, and to investigate the clinical usefulness of our method. Sequential chest radiographs of 20 subjects (abnormal,n=12; normal,n=8) during respiration were obtained with a dynamic flat-panel detector (FPD) system. The average pixel value in each local area was measured tracking the same area. To facilitate visual evaluation, the results were mapped on the original image using a grayscale in which small changes were shown in black and large changes were shown in white. In our clinical evaluation in comparison with a pulmonary scintigraphy, pulmonary ventilation disorder was indicated as a reduction of changes in pixel values. In many patients, there was a correlation between our result and a pulmonary scintigraphy (0.7Subject(s)
Radiography, Thoracic/methods
, Respiratory Function Tests/methods
, Adult
, Aged
, Aged, 80 and over
, Algorithms
, Diagnosis, Computer-Assisted/methods
, Female
, Humans
, Lung/diagnostic imaging
, Lung Diseases/diagnostic imaging
, Male
, Middle Aged
, Radiography, Thoracic/instrumentation
, Radionuclide Imaging
, Respiratory Function Tests/instrumentation
, Young Adult