Analysis of the relationship between comorbid obstructive sleep apnea and clinical outcomes in patients with asthma in Japan.

BACKGROUND: Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders, which often coexist and interact with each other. Obesity is an important risk factor shared by them. The rate of obesity is lower in Japan versus Western countries. Hence, the co-existence of asthma and OSA has not been investigated in Japan. METHODS: Ninety-seven outpatients with asthma were recruited. Patients wore a portable monitor for sleep study. Background data, pulmonary function, blood tests, and patient-reported outcomes including gastroesophageal reflux disease, sleepiness, sleep quality, asthma control, cough and respiratory symptoms, and health status, were assessed. RESULTS: Of the patients, 19 (19.6 %), 40 (41.2 %), 24 (24.7 %), and 14 (14.4 %) were classified into non-, mild, moderate, and severe OSA groups. Non-OSA patients were younger than those in other groups (p < 0.05). The BMI of patients with moderate and severe OSA, was higher than that of non-OSA patients (p < 0.05). Pulmonary function, FeNO, serum IgE, and the number of peripheral eosinophils were not significantly different between groups. Nonetheless, compared with the other groups, treatment step was the highest, and the Asthma Control Test, Leicester Cough Questionnaire, COPD Assessment Test, and Asthma Health Questionnaire-33 yielded worst scores in the severe OSA group, and predicted the severe OSA after adjustment by BMI. CONCLUSIONS: Moderate and severe OSA are highly prevalent among patients with asthma in Japan. Pulmonary function did not differ between groups. However, patients with asthma and severe OSA were linked to more asthma treatment, worse asthma control, more symptoms and cough, and worse health status.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2019-2020: General view of the pathogens' antibacterial susceptibility.

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were ß-lactamase-producing ampicillin resistant and ß-lactamase-negative ampicillin resistant, respectively. Extended-spectrum ß-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-ß-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.

Elevated levels of periostin and TGF-ß1 in the bronchoalveolar lavage fluid of patients with idiopathic eosinophilic pneumonia.

BACKGROUND: Periostin is induced in bronchial epithelial cells and fibroblasts by various stimuli including interleukin (IL)13 and transforming growth factor (TGF)-ß1, and is involved in allergic diseases such as asthma and atopic dermatitis, playing an important role in tissue remodeling and fibrosis. The role of periostin in the pathogenesis of eosinophilic lung diseases, however, is unclear. OBJECTIVE: To examine the contribution of periostin to eosinophilic inflammation of the lung in humans, we evaluated periostin, IL-13, and TGF-ß1 levels in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP). METHODS: Periostin, IL-13, and TGF-ß1 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute EP, chronic EP, idiopathic pulmonary fibrosis (IPF), and sarcoidosis. Further, we analyzed the relationship between periostin, IL-13, and TGFß-1, levels and the number of inflammatory cells in the BALF. RESULTS: The absolute number of eosinophils, and the periostin, IL-13, and TGF-ß1 levels in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. Concentrations of periostin significantly correlated with the concentrations of TGF-ß1, but not those of IL-13, in the BALF of patients with EP. Periostin levels also significantly correlated with the absolute number of eosinophils in the BALF of patients with IPF, but not EP. CONCLUSIONS: Our findings suggest that TGF-ß1 might increase the production of periostin in the lungs of patients with EP. Periostin might contribute the pathogenesis of not only EP, but also IPF.

Biomarkers for differentiation of patients with asthma and chronic obstructive pulmonary disease.

OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) are airflow limitation diseases with similar clinical manifestations but different pathophysiologic mechanisms. To implement the appropriate treatment, it is important to distinguish between asthma and COPD which sometimes might result difficult in clinical practice. We evaluated biomarkers to distinguish between asthma and COPD. METHODS: Blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels were analyzed. Serum periostin, interleukin-25 (IL-25), and immunoglobulin E (IgE) concentrations were compared between patients with asthma (n = 60), including atopic-asthma (n = 30) and non-atopic asthma (n = 30), and patients with COPD (n = 30). RESULTS: Significantly higher peripheral blood eosinophil counts (p < 0.001), FeNO levels (p < 0.001), and total serum IgE (P = 0.003) concentrations, but not serum periostin (p = 0.584) or serum IL-25 (p = 0.085) concentrations, were detected in patients with asthma compared to patients with COPD. Serum periostin and IgE concentrations were increased in patients with atopic-asthma compared with those with non-atopic asthma and COPD (p < 0.05). The FeNO levels were significantly correlated with the peripheral blood eosinophil counts (r = 0.430, p = 0.001) and serum IL-25 concentrations (r = 0.338, p = 0.009) in patients with asthma. The serum periostin concentrations were also correlated with the serum IgE concentrations (r = 0.375, p = 0.003)and FeNO levels (r = 0.291, p = 0.024) in patients with asthma. Asthma patients were effectively differentiated from COPD patients based on the FeNO levels (p < 0.001) and peripheral blood eosinophil counts (p < 0.001). CONCLUSIONS: FeNO levels and peripheral blood eosinophil counts were useful biomarkers for distinguishing between patients with asthma and COPD. Serum periostin and IgE concentrations could be biomarkers for atopic asthma.

Possible Role of IL-25 in Eosinophilic Lung Inflammation in Patients with Chronic Eosinophilic Pneumonia.

PURPOSE: Interleukin (IL)-25 and IL-33 induce IL-5 production by various types of cells, such as type 2 helper T (Th2) cells and type 2 innate lymphoid cells. The number of Th2 cells and concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) are increased in patients with eosinophilic pneumonia (EP). To examine the contribution of IL-25 and IL-33 to eosinophilic inflammation of the lung in humans, we evaluated IL-5, IL-25 and IL-33 levels in the BALF of patients with EP. METHODS: IL-5, IL-25, and IL-33 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), idiopathic pulmonary fibrosis (IPF), and sarcoidosis. RESULTS: The absolute number of eosinophils, and IL-5 levels, but not IL-33 levels, in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. IL-25 levels in the BALF were significantly higher in patients with CEP, but not in patients with AEP, than in patients with IPF and sarcoidosis. The absolute number of eosinophils was significantly correlated with the IL-5 concentration in the BALF of patients with EP. IL-5 concentrations were significantly correlated with IL-25 concentrations in the BALF of patients with CEP, but not in patients with AEP. IL-5 levels were not correlated with IL-33 levels in the BALF of patients with EP. CONCLUSIONS: Our findings suggest that IL-25 plays an important role via IL-5 in eosinophilic lung inflammation in patients with CEP.

Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia.

PURPOSE: Galectin-9 (Gal-9) is a ß-galactoside-binding protein that exhibits various biological reactions, such as chemoattraction, cell aggregation, and apoptosis. Recent studies demonstrated that Gal-9 has a role as an immunomodulator in excessive immunological reactions by expanded regulatory T cells (Tregs). We examined the role of Gal-9 in the pathogenesis of one of the major idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) as compared with idiopathic pulmonary fibrosis (IPF). METHODS: Gal-9, transforming growth factor-ß1, and interleukin (IL)-10 levels in the bronchoalveolar lavage fluid (BALF) of patients with COP and IPF were estimated by enzyme-linked immunosorbent assay. Forkhead box protein 3 (Foxp3) expressing Tregs were evaluated by flow cytometry. The effect of Gal-9 on interactions between human lung fibroblast cells and hyarulonan was assessed in vitro. RESULTS: Gal-9 and IL-10 levels in the BALF were significantly higher in patients with COP than in patients with IPF. The number of CD4+Foxp3high+cells was significantly higher in the BALF of patients with COP than in those with IPF. Gal-9 levels significantly correlated with the absolute number of CD4+CD25+Foxp3+cells or CD4+Foxp3high+cells, but not with the absolute number of CD4+CD25+Foxp3-cells, in the BALF of patients with COP. Gal-9 suppressed the CD44-dependent interaction of human lung fibroblast cells with hyarulonan in a dose-dependent manner. CONCLUSIONS: Our findings suggest that increased Gal-9 levels in the lung have a protective role against lung inflammation and fibrosis in patients with COP through the induction of Tregs in the lung and CD44-dependent inhibitory effects on lung fibroblast cells.

Increased levels of plasma galectin-9 in patients with influenza virus infection.

Galectin-9 (Gal-9) is a ß-galactoside-binding protein involved in various biologic processes, including cell aggregation, adhesion, chemoattraction, and apoptosis. Little is known, however, about the regulation mechanisms of Gal-9 production. Recent studies reported high plasma Gal-9 levels in humans infected with human immunodeficiency virus-1 and dengue virus. Viral respiratory infections such as influenza are common human illnesses. A synthetic double-stranded RNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types and induces the expression of Gal-9 in endothelial cells. To examine the potential link between viral infection and Gal-9 expression, we measured plasma Gal-9 concentrations in patients with influenza. Subjects were 43 patients with influenza virus infection, 20 with pneumococcal pneumonia, and 20 healthy adults. Gal-9 concentrations in the plasma and in culture supernatants of human airway epithelial cells were measured using an enzyme-linked immunosorbent assay. Plasma Gal-9 concentrations were higher in patients with influenza infection than in patients with pneumococcal pneumonia and healthy subjects (p < 0.05). Patients with influenza were effectively differentiated from those with pneumococcal pneumonia or healthy subjects, based on the plasma levels of Gal-9 (p < 0.0001). Furthermore, using a human airway epithelial cell line, we showed that the presence of PolyIC but not lipopolysaccharides increased the Gal-9 concentration in the culture medium (p < 0.05), suggesting that PolyIC enhanced Gal-9 production. These findings support our proposal that Gal-9 production is induced by influenza virus infection in humans. In conclusion, plasma Gal-9 could be a new biomarker for patients with influenza infection.

A Case of Pulmonary Mycobacterium heckeshornense Infection in which the Causative Microorganism was Difficult to Identify.

A 44-year-old woman underwent a follow-up examination for Crohn's disease 9 years ago. Chest computed tomography (CT) showed an infiltration shadow with a cavity in the right upper lobe. After a CT-guided lung biopsy, epitheloid granuloma was noted, and an acid-fast bacilli examination was smear-positive, but a culture examination was negative. Because the abnormal chest shadow with cavity gradually increased and right shoulder pain appeared, we performed bronchoscopy again six months later. Mycobacterium heckeshornense was isolated from the bronchoalveolar lavage fluid specimen, so we diagnosed her with pulmonary M. heckeshornense disease. Isoniazid, rifampicin, and ethambutol were administered, and the abnormal chest shadow improved.

Critical role of interleukin-5 in the development of a mite antigen-induced chronic bronchial asthma model.

OBJECTIVE AND DESIGN: Asthma is associated with eosinophilic airway inflammation and characterized by enhanced airway sensitivity. Interleukin (IL)-5 plays an important role in the pathogenesis of asthma. The involvement of IL-5 receptor-mediated cellular signals in the pathogenesis of a mite antigen-induced chronic asthma model was investigated. SUBJECTS: In this study, 48 female C57BL/6J (WT) mice and IL-5 receptor-deficient (IL-5RKO) mice were used. TREATMENT: Mite antigen (50 µl) was intranasally administered 13 times to WT and IL-5RKO mice. METHODS: Airway hypersensitivity (Mch PC200) and specific antigen exposure tests were performed, and lung tissue, bronchoalveolar lavage fluid (BALF), and blood were collected to investigate the asthma pathology and differences in the local pulmonary levels of cytokines and chemokines. RESULTS: Airway sensitivity was enhanced and antigen-specific airway resistance was increased in WT mice. In addition, the number of eosinophils and Th2 cytokine levels in the BALF were increased. In contrast, IL-5RKO mice did not acquire the asthma pathology, such as antigen-specific airway resistance and eosinophilic airway inflammation. Mch PC200 was significantly correlated with cysteinyl leukotriene levels in WT mice. CONCLUSION: These findings suggested that both IL-5 induced eosinophils and cysteinyl leukotrienes are involved in the pathology of this mite antigen-induced chronic asthma model.

Preventive effect of galectin-9 on double-stranded RNA-induced airway hyperresponsiveness in an exacerbation model of mite antigen-induced asthma in mice.

BACKGROUND: Viral respiratory infection is the most common cause of acute asthma exacerbation in patients with stable asthma. The replication of most respiratory viruses requires the generation of double-stranded RNA (dsRNA), resulting in the activation of host immune responses. Synthetic dsRNA, polyinosinic-polycytidylic acid (PolyIC), mimics the effects of viruses in various cell types. To evaluate new therapies for mite antigen-induced chronic asthma, we developed an acute exacerbation model of mouse chronic asthma using mite antigen and PolyIC. We also examined the preventive effects of recombinant galectin-9 (Gal-9) on acute asthma exacerbation in this model. METHODS: Airway hyperresponsiveness (AHR) was examined to evaluate the exacerbation of chronic asthma. To analyze airway inflammation, the numbers of inflammatory cells and concentrations of cytokines in the bronchoalveolar lavage fluid (BALF) were estimated by flow cytometry and enzyme-linked immunosorbent assay, respectively. RESULTS: AHR was accelerated by intranasal administration of PolyIC in addition to mite antigen. Levels of cytokines that contribute to AHR, including interferon-γ, tumor necrosis factor-α, and RANTES (CCR5), and of Gal-9 in the BALF were elevated in this acute asthma exacerbation mouse model. Intranasal administration of recombinant Gal-9 reduced the PolyIC-induced AHR and levels of these cytokines in the BALF. Further, Gal-9 suppressed the production of cytokines induced by PolyIC in the alveolar macrophages. CONCLUSIONS. Our findings demonstrated that exogenous Gal-9 suppressed dsRNA-induced AHR in an acute exacerbation model of chronic asthma in mice, and suggest that recombinant Gal-9 could be therapeutically effective for preventing acute asthma exacerbation.

Serological assay by use of glycopeptidolipid core antigen for Mycobacterium avium complex.

OBJECTIVE: We evaluated the clinical usefulness of glycopeptidolipid (GPL) core antigen for diagnosing Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD), including patients with clinically suspected MAC-PD. METHODS: GPL core antibody levels were measured in 57 patients with MAC-PD satisfying the American Thoracic Society (ATS) criteria for pulmonary disease due to non-tuberculous mycobacteria (NTM), and in 18 patients with clinically suspected MAC-PD, 10 with MAC contamination, 18 with pulmonary tuberculosis (TB), 9 with other NTM disease, 18 with other lung diseases, and 20 healthy subjects. RESULTS: The positive response rate was 77% for MAC-PD, 39% for suspected MAC-PD, 10% for MAC contamination, and 0% for pulmonary TB, other NTM diseases, other lung diseases, and healthy subjects. GPL core antibody levels were significantly higher in patients with MAC-PD than in those of the other groups (p < 0.01). The sensitivity and specificity of the GPL core antibody assay for MAC were 77% and 99%, respectively. Among 13 patients with MAC-PD who showed false-negative results, 5 had immunosuppressive underlying diseases. No significant correlations between the antibody level and species of MAC, clinical disease types, and extent of the disease on chest computed tomography were found in patients with MAC-PD. CONCLUSION: This enzyme immunoassay kit is a useful supportive method for the rapid and convenient diagnosis of MAC-PD using a small dose of serum, and for the differentiation of MAC-PD from other lung diseases. However, underlying diseases need to be considered in the interpretation of negative results.

Step-down of budesonide/formoterol in early stages of asthma treatment leads to insufficient anti-inflammatory effect.

OBJECTIVE: Administration of the combination of an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) is the main treatment strategy for bronchial asthma. The ICS/LABA dosage can be reduced (stepped down) when the patient's symptoms and lung functions are well-controlled. In this study, we obtained fractional exhaled nitric oxide (FeNO) measurements to clarify whether the anti-inflammatory effect of budesonide/formoterol is shortened by step-down. METHODS: Fifty-four patients who visited the Kawasaki Medical School Hospital with newly diagnosed asthma from November 2008 to July 2010 received budesonide/formoterol for 8 weeks or more. In 29 patients, the forced expiratory volume in 1 s% predicted increased to 80% or more, and the Asthma Control Questionnaire (ACQ) score decreased to 0.5 or less within 12 weeks. These 29 patients were randomly divided into two groups: the dosage-continued group (n = 14) and the step-down group (n = 15). Then, the impact of budesonide/formoterol step-down on ACQ score, pulmonary function and FeNO level was compared between the groups. RESULTS: In the step-down group, the dosage was stepped down from 538 mcg/day to 331 mcg/day. In both groups, pulmonary function indicators and symptoms did not change. However, the mean FeNO level decreased significantly in the dosage-continued group (from 50.9 ppb to 45.0 ppb), and increased significantly in the step-down group (from 51.0 ppb to 65.7 ppb). CONCLUSIONS: Clinicians should be more careful when stepping down budesonide/formoterol based solely on patients' symptoms and/or pulmonary function.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2006)].

From October 2006 to September 2007, we collected the specimen from 356 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 414 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 407 strains were examined. The isolated bacteria were: Staphylococcus aureus 64, Streptococcus pneumoniae 96, Haemophilus influenzae 87, Pseudomonas aeruginosa (non-mucoid) 52, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 20, and Moraxella catarrhalis 44. Of 64 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 27 (42.2%) and 37 (57.8%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 microg/ml or less. Against MRSA, vancomycin and linezolid showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.125 and 0.5 microg/ml, respectively. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (45.8%) and clindamycin (20.8%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (50.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 49.2% and 28.1% of all the respiratory infections, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (29.2%), S. aureus (20.8%), and H. influenzae (12.9%). H. influenzae (25.0%) and P. aeruginosa (21.7%) also were frequently isolated from the patients with chronic bronchitis. Before the antibacterial agent administration, the bacteria frequently isolated from the patients were S. pneumoniae (27.5%) and H. influenzae (22.5%). The bacteria frequently isolated from the patients treated with macrolides was P. aeruginosa, and its isolation frequently was 39.4%.

Current status and future landscape of diagnosing tuberculosis infection.

Interferon-γ release assays (IGRAs), such as QuantiFERON-TB Gold (QFT) or T-SPOT.TB, are frequently used as tools for the diagnosis of tuberculosis (TB) infection in the 21st century. QFT-Plus recently emerged as the fourth generation of QFT assays and has replaced QFT In-Tube. However, IGRAs have several problems regarding the identification of active, latent, and cured TB infection, and the time-consuming diagnosis of TB infection because of the overnight incubation of clinical specimens or complexity of measuring the level of interferon (IFN)-γ. To easily diagnose TB infection and quickly compare it with conventional IGRAs, many in vitro tests are developed based on assays other than enzyme-linked immunosorbent assay or enzyme-linked immunospot, such as the fluorescent lateral flow assay that requires less manual operation and a shorter time. Simplified versions of IGRAs are emerging, including QIAreach QuantiFERON-TB. On the other hand, to distinguish active TB from latent or cured TB infection, new immunodiagnostic biomarkers beyond IFN-γ are evaluated using QFT supernatants. While IFN-γ or IFN-γ-related chemokine such as IFN-γ induced protein 10 is a potential biomarker in patients with active TB, interleukin-2 or latency-associated antigen such as heparin-binding hemagglutinin may be useful to distinguish active TB from latent or cured TB infection. There are no potential biomarkers to fully distinguish the time-phase of TB infection at present. It is necessary to discover new immunodiagnostic biomarkers to facilitate decisions on treatment selection for active or latent TB infection.

Clinical and microbiological differences between Mycobacterium abscessus and Mycobacterium massiliense lung diseases.

In recent years, many novel nontuberculous mycobacterial species have been discovered through genetic analysis. Mycobacterium massiliense and M. bolletii have recently been identified as species separate from M. abscessus. However, little is known regarding their clinical and microbiological differences in Japan. We performed a molecular identification of stored M. abscessus clinical isolates for further identification. We compared clinical characteristics, radiological findings, microbiological findings, and treatment outcomes among patients with M. abscessus and M. massiliense lung diseases. An analysis of 102 previous isolates of M. abscessus identified 72 (71%) M. abscessus, 27 (26%) M. massiliense, and 3 (3%) M. bolletii isolates. Clinical and radiological findings were indistinguishable between the M. abscessus and M. massiliense groups. Forty-two (58%) patients with M. abscessus and 20 (74%) patients with M. massiliense infections received antimicrobial treatment. Both the M. abscessus and M. massiliense groups showed a high level of resistance to all antimicrobials, except for clarithromycin, kanamycin, and amikacin. However, resistance to clarithromycin was more frequently observed in the M. abscessus than in the M. massiliense group (16% and 4%, respectively; P = 0.145). Moreover, the level of resistance to imipenem was significantly lower in M. abscessus isolates than in M. massiliense isolates (19% and 48%, respectively; P = 0.007). The proportions of radiological improvement, sputum smear conversion to negativity, and negative culture conversion during the follow-up period were higher in patients with M. massiliense infections than in those with M. abscessus infections. Patients with M. massiliense infections responded more favorably to antimicrobial therapy than those with M. abscessus infections.

Relationship between clinical efficacy for pulmonary MAC and drug-sensitivity test for isolated MAC in a recent 6-year period.

There are a few recent reports about the relationship between the clinical effect and drug-sensitivity test. We investigated the relationship between the clinical efficacy of treatment for pulmonary Mycobacterium avium complex (MAC) and drug-sensitivity test for isolated MAC by comparison between data from 2005 to 2007 and from 2008 to 2010. We studied 60 patients who satisfied diagnostic criteria of nontuberculous mycobacterial infection established by the American Thoracic Society in 2007 and who received combination therapy using rifampicin (RFP), ethambutol (EB), streptomycin (SM), and clarithromycin (CAM). Average CAM dosage was increased from the early (517 mg/day) to the later (800 mg/day) period. Sputum conversion rate increased from 63% in the early period to 83% in the later period. Clinical improvement also increased from 38% in the early period to 53% in the later period. The causative microorganisms isolated were M. avium in 35 patients and M. intracellulare in 25. In both periods, isolated MAC strains showed excellent minimum inhibitory concentration (MIC) for CAM. Regarding the relationship between clinical efficacy and MICs of RFP, EB, CAM, and SM, most patients with good clinical effects showed low MIC for CAM in both periods. Good clinical efficacy, including the sputum conversion rate, was obtained with an increased dose of CAM in the later period. We speculate that the increased dose of CAM influenced the good clinical effect in both periods.

Pneumococcal Pneumonia Co-infection with Mycobacterium avium and Nocardia cyriacigeorgica in an Immunocompetent Patient.

A 61-year-old woman was transferred with a complaint of a fever and productive cough. She had tested positive for Mycobacterium avium and Nocardia cyriacigeorgica at least twice, and Streptococcus pneumonia (PISP) was isolated (3+) from her purulent sputum. As radiological findings, a lower lung field-dominant infiltration shadow and nodular shadow with cavity were recognized in the bilateral lung fields. We diagnosed her with pneumococcal pneumonia co-infection with M. avium and N. cyriacigeorgica. She was treated with MEPM for pneumococcal pneumonia, a standard regimen containing clarithromycin for pulmonary M. avium complex (MAC) disease, and sulfamethoxazole/trimethoprim for pulmonary nocardiosis. She improved with appropriate treatment.

Stability of sealed-bag samples for off-line measurement of fractional exhaled nitric oxide.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) measurement is an index of airway eosinophilic inflammation and is primarily employed to diagnose bronchial asthma and assess airway inflammation. It can be measured with on- and off-line methods. In the latter, sample storage is possible; this is useful in Japan, because the number of facilities in which this instrument has been installed is limited. OBJECTIVE: We investigated the maximum period in which the samples continued to show stable values, as well as the influences of the storage environment. METHODS: Exhaled air samples were collected from 19 bronchial asthma patients (male/female: 8/11; mean age: 54.9 ± 15.6 years), and divided into 2 groups: a group with an FeNO level of less than 30 ppb and that with a level of 30 ppb or more. They were stored at 4 and 25°C to examine serial changes. RESULTS: The off-line-measured FeNO value was 33.7 ± 17.1 ppb, significantly lower than the on-line measured value (71.4 ± 47.7 ppb) (P < .01). In a group with an FeNO level of less than 30 ppb, temperature had no influence. However, in the other group, the period was prolonged to 72 hours when the samples were stored at 4°C. The samples were stable at 4°C for 24 hours, regardless of the initial measurements. CONCLUSION: The duration of sample storage can be prolonged at 4°C. The standard FeNO measurement method is the on-line method, but the alternative use of the off-line method may contribute to the diagnosis and treatment of the patients.

[Usefulness of fractional exhaled nitric oxide measurement for cough treatment].

Cough is a frequent chief complaint of outpatients, and is caused by various diseases. Fractional exhaled nitric oxide (FeNO) measurement is employed to evaluate airway eosinophilic inflammation. We investigated the usefulness of FeNO measurement for the differentiation of diseases in 202 patients who consulted our department. The numbers of consultations required to determine the therapeutic strategy were compared between before and after the introduction of FeNO measurement. The numbers of consultations before treatment were 2.00 +/- 1.31 (n = 140) and 1.60 +/- 0.65 (n = 62) before and after FeNO measurement, respectively (p = 0.046). In patients with cough variant asthma or bronchial asthma, the numbers were 2.15 +/- 1.60 and 1.40 +/- 0.67 before and after FeNO measurement, respectively (p = 0.003). FeNO measurement may be useful for cough treatment.

Rapid diagnosis of tuberculous pericarditis by ELISPOT assay.

We describe a case in which the rapid diagnosis of tuberculous pericarditis was made using the Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay on pericardial effusion mononuclear cells (PEMCs). The analysis of MTB-specific T-cells in PEMCs by ELISPOT may be useful for rapid decision-making in anti-tuberculous treatment.