Purpose: Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. Methods: We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. Results: Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. Conclusions The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Purpose: Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease. Methods: We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis. Results: Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81. Conclusions The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.

Adult ; Catheter-Related Infections ; etiology ; Catheterization, Central Venous ; instrumentation ; Central Venous Catheters ; adverse effects ; Female ; Humans ; Pulmonary Embolism ; etiology ; Recurrence ; Sepsis ; etiology ; Tomography, X-Ray Computed

Among various dermatological entities, toxic epidermal necrolysis (TEN) is a rare but potentially fatal delayed hypersensitivity reaction to numerous medications. A 38-year-old male presented with systemic hypersensitivity reaction, such as high fever, pain in the eyes, and diffuse pruritic erythematous maculopapular eruptions with multiple targetoid plaques that became vesicular and bullous. Oral mucosa and conjunctivae were involved. The first sign appeared about 1 week after taking methazolamide (50 mg twice a day) for the management of glaucomatous eyes. Although methazolamide was discontinued, blistering and skin denudation progressed to affect up to 80% of the body surface area and a positive Nikolsky sign was noted. High fever also persisted. Skin lesions started to improve after 2 weeks of management and fever subsided. Cutaneous lesions improved with minimal permanent sequele 2 months later. HLA-B*5901 was found by high-resolution genotyping. The lymphocyte activation test performed 6 months after remission showed a positive response to methazolamide challenge. This is the first case of methazolamide-induced TEN in which methazolamide was confirmed as a culprit drug by the lymphocyte activation test.
Adult ; Blister ; Body Surface Area ; Conjunctiva ; Fever ; Humans ; Hypersensitivity ; Hypersensitivity, Delayed ; Lymphocyte Activation* ; Lymphocytes* ; Male ; Methazolamide ; Mouth Mucosa ; Skin ; Stevens-Johnson Syndrome*

PURPOSE: Recent experimental evidence shows that extracellular vesicles (EVs) in indoor dust induce neurtrophilic pulmonary inflammation, which is a characteristic pathology in patients with severe asthma and chronic obstructive pulmonary disease (COPD). In addition, COPD is known to be an important risk factor for lung cancer, irrespective of cigarette smoking. Here, we evaluated whether sensitization to indoor dust EVs is a risk for the development of asthma, COPD, or lung cancer. METHODS: Serum IgG antibodies against dust EVs were measured in 90 healthy control subjects, 294 asthmatics, 242 COPD patients, and 325 lung cancer patients. Serum anti-dust EV IgG titers were considered high if they exceeded a 95 percentile value of the control subjects. Age-, gender-, and cigarette smoke-adjusted multiple logistic regression analyses were performed to determine odds ratios (ORs) for asthma, COPD, and lung cancer patients vs the control subjects. RESULTS: In total, 4.4%, 13.6%, 29.3%, and 54.9% of the control, asthma, COPD, and lung cancer groups, respectively, had high serum anti-dust EV IgG titers. Adjusted multiple logistic regression revealed that sensitization to dust EVs (high serum anti-dust EV IgG titer) was an independent risk factor for asthma (adjusted OR, 3.3; 95% confidence interval [CI], 1.1-10.0), COPD (adjusted OR, 8.0; 95% CI, 2.0-32.5) and lung cancer (adjusted OR, 38.7; 95% CI, 10.4-144.3). CONCLUSIONS: IgG sensitization to indoor dust EVs appears to be a major risk for the development of asthma, COPD, and lung cancer.
Antibodies ; Asthma* ; Dust* ; Humans ; Immunoglobulin G* ; Logistic Models ; Lung Neoplasms* ; Lung* ; Odds Ratio ; Pathology ; Pneumonia ; Prevalence* ; Pulmonary Disease, Chronic Obstructive* ; Risk Factors ; Smoking ; Tobacco Products

Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his condition worsened. Thus, we recommended photodynamic therapy (PDT) to deal with the dyspnea and MPM. After PDT, the dyspnea improved and the patient then decided to take the combination chemotherapy. Our patient received chemotherapy using pemetrexed/cisplatin. Afterwards, he received a single PDT treatment and then later took chemotherapy using gemcitabine/cisplatin. The patient showed a survival time of 27 months, which is longer than median survival time in advanced MPM patients. Further research and clinical trials are needed to demonstrate any synergistic effect between the combination chemotherapy and PDT.
Aged ; Drug Therapy* ; Drug Therapy, Combination ; Dyspnea ; Humans ; Male ; Mesothelioma* ; Photochemotherapy* ; Pleura

BACKGROUND: Few reports have documented the clinical characteristics and treatment outcomes of adult patients with Elizabethkingia meningoseptica infection. METHODS: Medical records of patients over 18 years of age and suspected of having an E. meningoseptica infection from March 1, 2006 to February 28, 2013 were reviewed retrospectively. Their clinical characteristics, antimicrobial susceptibility results, and treatment outcomes were analyzed. RESULTS: E. meningoseptica was isolated from 30 patients. Median age was 68.5 years, and infections were more frequent in males (17, 56.7%). The most common isolation source was sputum (23, 76.7%), and pneumonia was the most common condition (21, 70%) after excluding two cases of colonization. This bacterium was most susceptible to minocycline (27, 90%) and fluoroquinolones, including levofloxacin (20, 66.7%) and ciprofloxacin (18, 60%). The mortality rate due directly to E. meningoseptica infection was 20% (6/30), and uncontrolled pneumonia was the only cause of death. After isolating E. meningoseptica, the numbers of patients with pneumonia (9/9, 100% vs. 12/21, 57.1%), history of hemodialysis (5/9, 55.6% vs. 3/21, 14.3%), tracheostomy (8/9, 88.9 vs. 10/21, 47.6%), and median Charlson comorbidity index score (6 [range, 3-9] vs. 4 [range, 0-9]) were significantly higher in non-survivors than those in survivors (p < 0.05, for each). However, only 12 (40%) patients received appropriate antibiotics. CONCLUSIONS: E. meningoseptica infection most commonly presented as pneumonia in adults with severe underlying diseases. Despite the high mortality rate, the rate of appropriate antibiotic use was notably low.
Adult* ; Anti-Bacterial Agents ; Cause of Death ; Chryseobacterium ; Ciprofloxacin ; Colon ; Comorbidity ; Cross Infection ; Fluoroquinolones ; Humans ; Levofloxacin ; Male ; Medical Records ; Minocycline ; Mortality ; Pneumonia ; Renal Dialysis ; Retrospective Studies ; Sputum ; Survivors ; Tertiary Care Centers* ; Tracheostomy

BACKGROUND: Few reports have documented the clinical characteristics and treatment outcomes of adult patients with Elizabethkingia meningoseptica infection. METHODS: Medical records of patients over 18 years of age and suspected of having an E. meningoseptica infection from March 1, 2006 to February 28, 2013 were reviewed retrospectively. Their clinical characteristics, antimicrobial susceptibility results, and treatment outcomes were analyzed. RESULTS: E. meningoseptica was isolated from 30 patients. Median age was 68.5 years, and infections were more frequent in males (17, 56.7%). The most common isolation source was sputum (23, 76.7%), and pneumonia was the most common condition (21, 70%) after excluding two cases of colonization. This bacterium was most susceptible to minocycline (27, 90%) and fluoroquinolones, including levofloxacin (20, 66.7%) and ciprofloxacin (18, 60%). The mortality rate due directly to E. meningoseptica infection was 20% (6/30), and uncontrolled pneumonia was the only cause of death. After isolating E. meningoseptica, the numbers of patients with pneumonia (9/9, 100% vs. 12/21, 57.1%), history of hemodialysis (5/9, 55.6% vs. 3/21, 14.3%), tracheostomy (8/9, 88.9 vs. 10/21, 47.6%), and median Charlson comorbidity index score (6 [range, 3-9] vs. 4 [range, 0-9]) were significantly higher in non-survivors than those in survivors (p < 0.05, for each). However, only 12 (40%) patients received appropriate antibiotics. CONCLUSIONS: E. meningoseptica infection most commonly presented as pneumonia in adults with severe underlying diseases. Despite the high mortality rate, the rate of appropriate antibiotic use was notably low.
Adult ; Anti-Bacterial Agents ; Cause of Death ; Chryseobacterium ; Ciprofloxacin ; Colon ; Comorbidity ; Cross Infection ; Fluoroquinolones ; Humans ; Levofloxacin ; Male ; Medical Records ; Minocycline ; Mortality ; Pneumonia ; Renal Dialysis ; Retrospective Studies ; Sputum ; Survivors ; Tertiary Care Centers ; Tracheostomy

PURPOSE: Fibroblast growth factor 2 (FGF2) has been shown to inhibit airway inflammation, mucus production, and airway hyperresponsiveness in mouse model of asthma. The aim of this study was to evaluate the safety and efficacy of inhaled recombinant FGF2 in asthmatic patients. METHODS: Eight asthmatics were eligible for the study. All patients were admitted to a hospital, and recombinant FGF2 was administered using a nebulizer at a concentration of 4.5 ng/mL three times a day for one week. Pulmonary function test, methacholine bronchial provocation test, induced sputum analysis, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ) were performed at the beginning of wash-out period, before and after the treatment, and at the end of study. And all these parameters were compared before and after FGF2 treatment. RESULTS: There were no serious adverse events associated with recombinant FGF2 during five-week study period. Daytime and nocturnal symptoms improved after the treatment (P=0.028 and P=0.012, respectively). AQLQ and ACT also improved after the treatment (P=0.017 and P=0.011, respectively). However, lung function, airway hyperresponsiveness, and airway inflammation showed no significant difference before and after the treatment. CONCLUSION: Inhaled recombinant FGF2 was safely used to eight asthmatics without any serious adverse events, and improved daytime and nocturnal symptoms, and quality of life in adult asthmatics. FGF2 may be a potential drug in the treatment of asthma.
Adult ; Airway Remodeling ; Animals ; Asthma ; Bronchial Provocation Tests ; Fibroblast Growth Factor 2* ; Humans ; Inflammation ; Lung ; Methacholine Chloride ; Mice ; Mucus ; Nebulizers and Vaporizers ; Pilot Projects* ; Quality of Life ; Respiratory Function Tests ; Sputum ; Surveys and Questionnaires

The fourth author's name was misprinted.
Fibroblast Growth Factor 2* ; Humans ; Pilot Projects*