Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.

BACKGROUND: Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made. OBJECTIVE: To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups. METHODS: A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model. RESULTS: Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/µL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/µL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)]. CONCLUSION: Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

Serum IgA augments adhesiveness of cultured lung microvascular endothelial cells and suppresses angiogenesis.

Immunoglobulin A (IgA) is important in local immunity and is also abundant in the blood. This study aimed to evaluate the effects of serum IgA on cultured lung microvascular endothelial cells (HMVEC-Ls), which are involved in the pathogenesis of inflammatory lung diseases. Serum IgA induced adhesion molecules and inflammatory cytokine production from HMVEC-Ls, and enhanced adhesion of peripheral blood mononuclear cells to HMVEC-Ls. In contrast, migration, proliferation, and tube formation of HMVEC-Ls were significantly suppressed by serum IgA. Experiments with siRNAs and western blotting revealed that two known IgA receptors, ß1,4-galactosyltransferase 1 (b4GALT1) and asialoglycoprotein receptor 1 (ASGR1), and mitogen-activated protein kinase and nuclear factor-kappa B pathways were partly involved in serum IgA-induced cytokine production by HMVEC-Ls. Collectively, serum IgA enhanced cytokine production and adhesiveness of HMVEC-L, with b4GALT1 and ASGR1 partially being involved, and suppressed angiogenesis. Thus, serum IgA may be targeted to treat inflammatory lung diseases.

Positive correlation between voriconazole trough concentrations and C-reactive protein levels in patients with chronic pulmonary aspergillosis: A retrospective cohort study.

BACKGROUND: Voriconazole (VRCZ) is the first-line treatment for chronic pulmonary aspergillosis (CPA). VRCZ trough concentration monitoring is recommended for adequate therapy because VRCZ concentrations vary widely. However, factors associated with variations in VRCZ concentrations, especially in the same patient at different time points, have not been identified. The objective of this study was to identify factors influencing VRCZ trough concentrations. PATIENTS AND METHODS: This single-center retrospective study conducted at our institute between April 2014 and August 2016 included patients with CPA who received VRCZ. Patient trough concentrations were measured more than twice while the patients received the same dose using the same administration route (defined as one series). A step-wise method and multiple regression analysis were used to test the effects of patient characteristics on VRCZ trough concentrations. RESULTS: Sixty-nine series in 49 patients were analyzed. VRCZ was administered orally in 59 series, intravenously in 7 series, and by dry syrup in 3 series. The median VRCZ trough concentration and the median variation in VRCZ concentrations were 1.68 and 0.99 µg/ml, respectively. In the simple regression analysis, creatinine, alkaline phosphatase, C-reactive protein (CRP), and creatinine clearance significantly correlated with VRCZ concentrations. Multiple regression analysis demonstrated a significant positive correlation between CRP and VRCZ concentration (P < 0.0001). CONCLUSION: In patients with CPA, VRCZ concentration correlated with CRP levels in the same patients receiving the same dose of VRCZ at different time points.

Non-fumigatus Aspergillus Infection Associated with a Negative Aspergillus Precipitin Test in Patients with Chronic Pulmonary Aspergillosis.

Aspergillus antibody testing is key for the clinical diagnosis of chronic pulmonary aspergillosis (CPA) with high sensitivity. However, false-negative results in patients with CPA might be obtained, depending on the Aspergillus species. The aim of this study was to investigate which factors are associated with false-negative results in Aspergillus precipitin tests and whether the sensitivity of precipitin tests in CPA is influenced by Aspergillus fumigatus and non-fumigatus Aspergillus species. Between February 2012 and December 2020, 116 consecutive antifungal treatment-naive patients with CPA were identified and included in this retrospective chart review. Aspergillus species isolated from the respiratory tract of patients were identified by DNA sequencing. Characteristics of patients with positive and negative results for Aspergillus precipitin tests were compared. The sensitivity of the Aspergillus precipitin tests was compared between patients with A. fumigatus-associated CPA and non-fumigatus Aspergillus-associated CPA. A non-fumigatus Aspergillus species was the only factor significantly associated with negative Aspergillus precipitin test results in patients with CPA in the multivariate analysis (hazard ratio, 8.3; 95% confidence interval, 3.2 to 22.1; P < 0.0001). The positivity of the Aspergillus precipitin test for patients with non-fumigatus Aspergillus-associated CPA was lower than that for patients with A. fumigatus-associated CPA (84.8% versus 37.9%; P < 0.0001). These results revealed that the presence of non-fumigatus Aspergillus-associated CPA should be considered with a negative Aspergillus precipitin test; this finding may prevent diagnostic delay or misdiagnosis for CPA.

Serum total IgE may be a biomarker among chronic pulmonary aspergillosis patients with elevated serum total IgE levels: A cohort study with pathological evaluations.

High serum total immunoglobulin E (IgE) levels have been reported in chronic pulmonary aspergillosis (CPA). However, researchers have not verified if they reflect the disease activity. We aimed to compare the serum total IgE levels in CPA cases with high serum IgE during an exacerbation or when stable and examined the IgE expression patterns in the lesions via immunofluorescence staining. From April 2016 to September 2019, we extracted CPA cases with elevated serum total IgE levels based on the criteria of the Infectious Diseases Society of America. We retrospectively analyzed serum total IgE levels and other parameters and eventually extracted 32 cases. The patients' serum total IgE levels were significantly higher in the exacerbation period than in the stable period (P < .0001). The median rate of change was 1.76 times (quartile 1.41-3.25). In addition, we used surgical specimens of CPA cases with high serum total IgE levels, normal serum total IgE CPA cases, and control surgical specimens and performed immunofluorescence staining with IgE, mast cell tryptase, CD138, and 4,6-diamidino-2-phenylindole. We observed multiple mast cells and plasma cells in the CPA cases regardless of the serum total IgE level. In contrast, multiple IgE-positive cells co-stained with tryptase were observed in CPA cases with high serum total IgE levels. This finding suggested that serum total IgE could serve as a biomarker for evaluating disease severity. Immunofluorescence staining suggested that IgE may play a role in pathogenesis through activation of mast cells by cross-linking in cases of CPA with high serum total IgE levels. LAY SUMMARY: High serum total IgE levels are common in chronic pulmonary aspergillosis. This novel study indicated that serum total IgE is a possible biomarker of the disease activity in the aforementioned condition. Immunofluorescence staining indicated a possible role of IgE in disease pathogenesis.

Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia.

Rationale: Identification of the specific cell types expressing CFTR (cystic fibrosis [CF] transmembrane conductance regulator) is required for precision medicine therapies for CF. However, a full characterization of CFTR expression in normal human airway epithelia is missing. Objectives: To identify the cell types that contribute to CFTR expression and function within the proximal-distal axis of the normal human lung. Methods: Single-cell RNA (scRNA) sequencing (scRNA-seq) was performed on freshly isolated human large and small airway epithelial cells. scRNA in situ hybridization (ISH) and single-cell qRT-PCR were performed for validation. In vitro culture systems correlated CFTR function with cell types. Lentiviruses were used for cell type-specific transduction of wild-type CFTR in CF cells. Measurements and Main Results: scRNA-seq identified secretory cells as dominating CFTR expression in normal human large and, particularly, small airway superficial epithelia, followed by basal cells. Ionocytes expressed the highest CFTR levels but were rare, whereas the expression in ciliated cells was infrequent and low. scRNA ISH and single-cell qRT-PCR confirmed the scRNA-seq findings. CF lungs exhibited distributions of CFTR and ionocytes similar to those of normal control subjects. CFTR mediated Cl- secretion in cultures tracked secretory cell, but not ionocyte, densities. Furthermore, the nucleotide-purinergic regulatory system that controls CFTR-mediated hydration was associated with secretory cells and not with ionocytes. Lentiviral transduction of wild-type CFTR produced CFTR-mediated Cl- secretion in CF airway secretory cells but not in ciliated cells. Conclusions: Secretory cells dominate CFTR expression and function in human airway superficial epithelia. CFTR therapies may need to restore CFTR function to multiple cell types, with a focus on secretory cells.

The accuracy and clinical impact of the morphological identification of Aspergillus species in the age of cryptic species: A single-centre study.

BACKGROUND: Aspergillus spp. is identified morphologically without antifungal susceptibility tests (ASTs) in most clinical laboratories. The aim of this study was to examine the clinical impact of the morphological identification of Aspergillus spp. to ensure the adequate clinical management of Aspergillus infections. PATIENTS/METHODS: Aspergillus isolates (n = 126) from distinct antifungal treatment-naïve patients with aspergillosis were first identified morphologically, followed by species-level identification via DNA sequencing. An AST for itraconazole (ITC) and voriconazole (VRC) was performed on each Aspergillus isolate. RESULTS: Based on the genetic test results, morphology-based identification was accurate for >95% of the isolates at the species sensu lato level although the test concordance of Aspergillus spp. with low detection rates was low. The rates of cryptic species were found to be 1.2% among the isolates of A. fumigatus complex and 96.8% in the A. niger complex. Cryptic species with lower susceptibilities to antifungal drugs than sensu stricto species among the same Aspergillus section were as follows: The A. lentulus (n = 1) isolates had low susceptibilities to azoles among the A. fumigatus complex species (n = 86), and A. tubingensis isolates (n = 18) exhibited lower susceptibility to azoles among the A. niger complex species (n = 31). CONCLUSION: Diagnostic accuracy was high at the A. fumigatus and A. niger complex level. However, in the presence of cryptic species, a solely morphological identification was insufficient. Particularly, ITC and VRC might be inappropriate for aspergillosis treatment when the A. niger complex is identified morphologically because it is possible that the Aspergillus isolate is A. tubingensis.

High detection rate of azole-resistant Aspergillus fumigatus after treatment with azole antifungal drugs among patients with chronic pulmonary aspergillosis in a single hospital setting with low azole resistance.

The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure.

Aspergillus fumigatus can acquire azole resistance during long-term treatment with azole drugs in patients with chronic pulmonary aspergillosis (CPA). The aim of this study was to determine the detection rate of azole-resistant A. fumigatus (ARAF) in isolates from CPA patients who had been treated with azoles. In addition, a potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104). The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF from all isolates was 8.3% (n = 10). Greater than 10% of the 47 isolates obtained from 36 CPA patients who had been treated with azoles exhibited resistance. Furthermore, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients undergoing long-term azole treatment at the time of antifungal therapy failure.

Species identification, antifungal susceptibility, and clinical feature association of Aspergillus section Nigri isolates from the lower respiratory tract.

Species of Aspergillus section Nigri are generally identified by molecular genetics approaches, whereas in clinical practice, they are classified as A. niger by their morphological characteristics. This study aimed to investigate whether the species of Aspergillus section Nigri isolated from the respiratory tract vary depending on clinical diagnosis. Forty-four Aspergillus section Nigri isolates isolated from the lower respiratory tracts of 43 patients were collected from February 2012 to January 2017 at the National Hospital Organization (NHO) Tokyo National Hospital. Species identification was carried out based on ß-tubulin gene analysis. Drug susceptibility tests were performed according to the Clinical and Laboratory Standards Institute (CLSI) M38 3rd edition, and the clinical characteristics were retrospectively reviewed. A. welwitschiae was isolated most frequently, followed by A. tubingensis. More than half of the A. tubingensis isolates exhibited low susceptibility to azoles in contrast to only one A. welwitschiae isolate. Approximately three quarters of the patients from whom A. welwitschiae was isolated were diagnosed with colonization, whereas more than half the patients from whom A. tubingensis was isolated were diagnosed with chronic pulmonary aspergillosis (CPA). More attention needs to be given to the drug choice for patients with CPA with Aspergillus section Nigri infection because A. tubingensis, which was found to be frequently azole-resistant, was the most prevalent in these patients.

Long-Term Outcomes of Bronchial Artery Embolization for Patients with Non-Mycobacterial Non-Fungal Infection Bronchiectasis.

BACKGROUND: There is no study on the predictive factors of recurrent haemoptysis after bronchial artery embolization (BAE) with the long-term outcomes in patients with bronchiectasis (BE). OBJECTIVES: To evaluate the long-term outcomes of BAE in BE patients without accompanying refractory active infection of mycobacteriosis and aspergillosis with analysis for the predictive factors of recurrent haemoptysis. METHODS: Data of 106 patients with BE who underwent BAE using coils between January 2011 and December 2018 were retrospectively reviewed. The cumulative haemoptysis control rate was estimated using Kaplan-Meier methods with log-rank tests to analyze differences in recurrence-free rate between groups based on technical success and failure, bacterial colonization status, number of BE lesions, and vessels embolized to bronchial arteries (BAs) or BAs + non-bronchial systemic arteries (NBSAs). RESULTS: Bacterial colonization was detected in approximately 60% of patients. Computed tomography showed bronchiectatic lesions with 2.9 ± 1.4 lobes. In the first series of BAE, embolization was performed in the BAs alone and BAs + NBSAs in 65.1 and 34.9% of patients, respectively, with 2.4 ± 1.4 embolized vessels in total. The median follow-up period was 1,000 (7-2,790) days. The cumulative haemoptysis control rates were 91.3, 84.2, 81.5, and 78.9% at 1, 2, 3, and 5 years, respectively. The haemoptysis control rates were higher in the technical success group than in the technical failure group (p = 0.029). CONCLUSIONS: High haemoptysis control rates for long-term periods were obtained by embolization for all visualized abnormal arteries, regardless of the colonization status, number of bronchiectatic lobes, and target vessels, irrespective of NBSAs.

Comparison of QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold In-Tube, and T-SPOT.TB among patients with tuberculosis.

OBJECTIVES: This study evaluated the efficacy of the following interferon (IFN)-γ release assays (IGRAs): QuantiFERON-TB Gold Plus (QFT-Plus), QFT-Gold In-Tube (QFT-GIT), and T-SPOT. TB (T-SPOT) with the quantitative values of IFN-γ response. METHODS: Blood samples were collected from patients with active tuberculosis (TB), latent TB infection (LTBI), individuals with previous TB infection, and healthy volunteers enrolled between May 2017 and June 2018. RESULTS: IGRAs results were analyzed in 175 subjects (76 had active TB, 14 had LTBI, 35 had prior TB infection, and 50 were healthy). QFT-Plus and QFT-GIT revealed equal efficacy for IFN-γ values, and the IFN-γ response in QFTs tended to increase with the spot counts in T-SPOT, with similar high sensitivities (approximately 90%) in the active TB group. The test concordance of two of three IGRAs was optimal among all subjects (κ coefficients: 0.82-0.96). Additionally, the median quantitative values of IFN-γ with QFT-Plus and QFT-GIT were higher in the active TB group than in the LTBI and previous TB groups. CONCLUSION: Three IGRAs showed equivalent efficacy with high sensitivities and higher IFN-γ response in active TB group than that in non-active TB group.

Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways.

RATIONALE: MUC5AC and MUC5B are the predominant gel-forming mucins in the mucus layer of human airways. Each mucin has distinct functions and site-specific expression. However, the regional distribution of expression and cell types that secrete each mucin in normal/healthy human airways are not fully understood. OBJECTIVES: To characterize the regional distribution of MUC5B and MUC5AC in normal/healthy human airways and assess which cell types produce these mucins, referenced to the club cell secretory protein (CCSP). METHODS: Multiple airway regions from 16 nonsmoker lungs without a history of lung disease were studied. MUC5AC, MUC5B, and CCSP expression/colocalization were assessed by RNA in situ hybridization and immunohistochemistry in five lungs with histologically healthy airways. Droplet digital PCR and cell cultures were performed for absolute quantification of MUC5AC/5B ratios and protein secretion, respectively. MEASUREMENTS AND MAIN RESULTS: Submucosal glands expressed MUC5B, but not MUC5AC. However, MUC5B was also extensively expressed in superficial epithelia throughout the airways except for the terminal bronchioles. Morphometric calculations revealed that the distal airway superficial epithelium was the predominant site for MUC5B expression, whereas MUC5AC expression was concentrated in proximal, cartilaginous airways. RNA in situ hybridization revealed MUC5AC and MUC5B were colocalized with CCSP-positive secretory cells in proximal superficial epithelia, whereas MUC5B and CCSP-copositive cells dominated distal regions. CONCLUSIONS: In normal/healthy human airways, MUC5B is the dominant secretory mucin in the superficial epithelium and glands, with distal airways being a major site of expression. MUC5B and MUC5AC expression is a property of CCSP-positive secretory cells in superficial airway epithelia.

A case of Mycobacterium tuberculosis laboratory cross-contamination.

SETTING: A laboratory cross-contamination event was suspected because Mycobacterium tuberculosis was unexpectedly detected at a high incidence in the cultures of several clinical specimens at the National Hospital Organization, Tokyo National Hospital, Japan. OBJECTIVE: To describe a case of Mycobacterium tuberculosis laboratory cross-contamination. DESIGN: We reviewed the medical records of 20 patients whose clinical specimens were suspected to have been contaminated by Mycobacterium tuberculosis. Variable number of tandem repeat analysis with 15 loci, the Japan Anti-Tuberculosis Association-12, and three additional hyper-variable loci, was performed to identify the cross-contamination event. RESULTS: The clinical, laboratory, and variable number of tandem repeat data revealed that the cross-contamination had possibly originated from one strongly positive specimen, resulting in false-positive results in 11 other specimens, including a case treated with anti-tuberculosis drugs. CONCLUSION: Clinical and laboratory data must be re-evaluated when cross-contamination is suspected and variable number of tandem repeat analysis should be used to confirm cross-contamination. Furthermore, original isolates should be stored appropriately, without sub-culturing and genotyping should be performed at the earliest possible for better utilization of variable number of tandem repeat for the identification of cross-contamination.

Clinical Features and Prognosis of Nontuberculous Mycobacterial Pleuritis.

BACKGROUND: While nontuberculous mycobacterial (NTM) pleuritis rarely complicates pulmonary NTM infection, high mortality has been reported in case reports and small studies. OBJECTIVES: The purpose of this study was to clarify the clinical features and treatment outcomes of pulmonary NTM infection cases accompanied by NTM pleuritis. METHODS: Medical records of 1,044 patients with pulmonary NTM disease were retrospectively reviewed to select patients complicated by NTM-proven pleuritis. We investigated clinical characteristics, pathogens, pleural effusion examinations, radiographic findings, treatments, and clinical course of the NTM pleuritis patients. RESULTS: Among 1,044 cases with pulmonary NTM, NTM pleuritis occurred in 15 cases (1.4%). The mean age was 69 years with a performance status of mostly 2 or better (80.0%), and 6 cases (40.0%) were complicated by pneumothorax. Subpleural cavities were radiologically detected in 11 cases (73.3%), and extrapulmonary air-fluid level was detected in 14 cases (93.3%). Eleven patients were treated with combinations of 2-4 antimycobacterial drugs, including clarithromycin, and 2 patients were treated with isoniazid, rifampicin, and ethambutol. Chest tube drainage was performed in 11 cases, and surgical approach was added in 6 cases. The pleural effusion of 2 patients treated with only antimycobacterial medications gradually deteriorated. Two patients died from NTM pleuritis, and 1 patient died from pneumonitis during a mean of 1.8 years of follow-up. CONCLUSIONS: Comorbid NTM pleuritis was difficult to treat by medical therapy alone and resulted in a poor prognosis. In addition to antimycobacterial agents, chest tube drainage and surgical procedures in the early stages should be considered to treat NTM pleuritis.

Analysis of drug treatment outcome in clarithromycin-resistant Mycobacterium avium complex lung disease.

BACKGROUND: Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease. METHODS: Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 µg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings. RESULTS: Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found. CONCLUSIONS: Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.

Thoracoscopic examination of empyema in a patient with sparganosis mansoni.

A 27-year-old man was admitted to our hospital with right pleural effusion. He had suffered from right chest and back pain and a high fever for one week prior to the admission. He had been treated with clarithromycin without improvement. Since thoracoscopy under local anesthesia revealed purulent effusion, synechiae and fibrous septa in the thoracic cavity, synechiotomy was performed and we started antibiotic treatment with the diagnosis of acute bacterial empyema. At the same time, we also suspected parasitic infection because of massive eosinophilic infiltration in pleural effusion and his dietary history of eating raw frogs. During the course of the disease, he had an infiltration in the right lower lobe and pneumothorax. Finally, we diagnosed him with sparganosis mansoni because his serum as well as pleural effusion was positive for the binding to sparganosis mansoni plerocercoid antigen, without any positive findings in bacteriology. His pleural effusion and lung infiltration were resolved after the administration of a high-dose praziquantel. We report this rare parasitic empyema with findings by thoracoscopic examination.

[CLINICAL EFFECTS OF INTRAVENOUSLY ADMINISTERED LEVOFLOXACIN IN PATIENTS WITH PULMONARY TUBERCULOSIS: A RETROSPECTIVE STUDY].

OBJECTIVES: Our aim was to investigate the clini- cal effects of levofloxacin (LVFX) administered intravenously to patients with pulmonary tuberculosis. METHODS: We studied 65 patients hospitalized at The National Hospital Organization Tokyo National Hospital between January 2010 and December 2012. The patients did not have human immunodeficiency virus (HIV) infection, and received anti-tuberculous drugs intravenously due to the inability to receive drugs orally. RESULTS: Twenty-seven patients were intravenously treated with isoniazid (INH), streptomycin (SM) and LVFX (HLS), and 38 patients were treated with INH and SM (HS). For both groups, mean age was very high (80.6±15.0 years, HLS group; 81.0± 12.1 years, HS group) and serum albumin levels were low (2.0 ± 0.62 mg/dl and 2.1 ± 0.42 mg/dl, respectively). Most patients were administered oxygen (81.5%, HLS; 78.9 %, HS). In radiological findings, most patients had bilateral (92.6%, HLS; 92.1%, HS) and widely spread (55.6%, HLS; 57.9%, HS) shadows. No significant differences were found between both groups in terms of the above data, except for sex. Almost 70% of all patients died; 51.9% of patients in the HLS group and 50.0% of those in the HS group died of tuberculosis, while 18.5% of patients in the HLS group and 18.4% of those in the HS group died of the other diseases. There were no significant differences in the causes of death and the survival rates of both groups. CONCLUSION: Patients with pulmonary tuberculosis who were administered intravenous drugs were elderly and in poor general health. As such, mortality of these patients was very high. In this study, no clinical effects were found in the patients administered intravenous LVFX with INH and SM compared with patients treated with INH and SM.

[Evaluation of the Efficacy and Safety of Platinum Doublet Re-Challenge Chemotherapy in Patients with Recurrent Advanced Non-Small Cell Lung Cancer].

BACKGROUND: Docetaxel or pemetrexed is the standard treatment for recurrent advanced non-small cell lung cancer (NSCLC). Until now, combination chemotherapy has failed to demonstrate superiority in patients with recurrent advanced NSCLC, compared to single-agent chemotherapy. The aim of the present study was to assess the efficacy and safety of platinum doublet re-challenge chemotherapy in patients with recurrent advanced NSCLC. METHODS: Fifty-eight patients with recurrent advanced NSCLC who underwent platinum doublet re-challenge chemotherapy were retrospectively analyzed. RESULTS: The response rate was 6.9%(95%CI: 1.9-16.7%), the disease control rate was 70.7% (95%CI: 57.3-81.9%), the median progression-free survival (PFS) was 123 days, and the median survival time (MST) after re-challenge chemotherapy was 470 days. The disease control rate and the PFS were significantly better in patients who achieved a partial response to first-line chemotherapy than in patients who had stable or progressive disease. In addition, the PFS and MST were significantly longer in patients whose treatment-free interval was more than 90 days. Toxicities were tolerable in most patients, except for 1 patient who showed drug-induced pneumonia. CONCLUSION: Platinum doublet re-challenge chemotherapy is a treatment option for patients with advanced NSCLC who achieved a partial response to first-line chemotherapy or for patients whose treatment-free interval lasted longer than 90 days.

Evaluation of clinical characteristics and prognosis of chronic pulmonary aspergillosis depending on the underlying lung diseases: Emphysema vs prior tuberculosis.

PURPOSE: There have been scarce data evaluating the differences of clinical characteristics and prognosis of chronic pulmonary aspergillosis (CPA) depending on underlying pulmonary diseases. We tried to clarify them in CPA patients who had pulmonary emphysema or previous pulmonary tuberculosis. METHODS: We reviewed and evaluated CPA patients diagnosed between 2007 and 2013 with pulmonary emphysema (PE group; n = 29), with previous pulmonary tuberculosis (PT group; n = 47) and with combination of these 2 underlying conditions (CTE group; n = 24). RESULTS: In CT findings, fungus balls were rare in PE group (7% in PE group and 36% in PT group; p = 0.006). Compared with PT group, PE group patients exhibited more frequent preceding antibiotics administration (45% vs 11%; p = 0.002) and fever (52% vs 17%; p = 0.002), less frequent hemosputum (24% vs 57%; p = 0.008), and more frequent consolidations in imaging (79% vs 38%; p = 0.001) and respiratory failure (34% vs 13%; p = 0.020), possibly suggesting more acute clinical manifestations of CPA in emphysematous patients. Trend of the differences between PT and PE group was not changed when patients with fungal balls were excluded. Multivariate Cox regression analysis of risks for all-cause mortality revealed age (HR, 1.079; p = 0.002) and emphysema (HR, 2.45; p = 0.040) as risk factors. CONCLUSIONS: Assessment of underlying lung diseases is needed when we estimate prognosis and consider treatment of CPA patients. Particularly, emphysematous patients can be presented as refractory pneumonia and show poor prognosis.