Tuberculosis and nontuberculous mycobacteriosis in patients with AIDS

Thirty-six patients with AIDS and culture-proven nontuberculous mycobacteriosis were compared to 20 patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis with regard to clinical signs, symptoms, and diagnostic methods. Patients with nontuberculous mycobacteriosis were more often younger and homosexuals, while patients with tuberculosis were usually Haitian-American or users of intravenous drugs. A majority of patients with tuberculosis presented with fever and weight loss. These symptoms were seen in approximately 50 percent of the patients with nontuberculous mycobacteriosis. A distinct syndrome of dyspnea, chills, hemoptysis, and chest pain was seen in a significant minority of patients with nontuberculous mycobacteriosis. Lymphadenopathy was seen almost exclusively in patients with tuberculosis. Pulmonary sources (expectorated sputum or bronchoscopy specimens) were the most common source of diagnosis in both groups. Patients in both groups in whom the diagnosis was obtained from pulmonary sources frequently had negative chest x-ray films on presentation. Cavitary disease was absent from both groups.     

Pulmonary nontuberculous mycobacteriosis in patients with lung cancer

OBJECTIVES: To clarify the clinical features of the coexisting lung cancer and nontuberculous mycobacteriosis of the lung. MATERIALS AND METHODS: We analyzed clinical data on 11 admitted cases of coexisting lung cancer and pulmonary non-tuberculous mycobacteriosis at National Organization Tokyo Hospital during the period from 1997 to 2002. RESULTS: There were 10 men and 1 woman, with a mean age of 66 years. Five of 11 patients had underlying pulmonary disorders, such as healed tuberculosis and lung cyst. Histological types of lung cancer were squamous cell carcinoma in 4, adenocarcinoma and small cell carcinoma in 3 each, and 8 out of 11 cases were in stages III to IV. We classified the 11 cases into 2 groups: (1) lung cancer concurrently detected with mycobacteriosis (8 cases) and (2) lung cancer sequentially detected during the follow-up of mycobacteriosis (3 cases). Lung cancers in the latter group were in relatively early stages and all patients of this group received resection of the cancer, while most of lung cancers in the concurrent group were in far-advanced, and palliative and/or supportive treatment for lung cancer were frequently selected. The strains of mycobacteria were as follows: M. avium complex (6 cases) and M. kansasii (5 cases). The incidence of lung cancer among patients with nontuberculous mycobacteriosis was 2.5 percent (2 percent of M. avium complex diseases patients and 8.2 percent of M. kansasii disease patients), while the incidence of nontuberculous mycobacteriosis in untreated lung cancer patients was 1.4 percent. Analysis of anatomical relationship between lung cancer and non-tuberculous mycobacteriosis revealed that the two diseases located in the same lung in 8 cases, and also in the same lobe in 4 out of the 8 cases. Outcome of treatment for nontuberculous mycobacteriosis was good especially in patients with M. kansasii disease, and it seemed that coexisting nontuberculous mycobacteriosis did not influence on the prognosis of lung cancer patients. CONCLUSION: In the management of lung cancer, physicians should consider the possibility of coexisting pulmonary non-tuberculous mycobacteriosis, as well as coexisting pulmonary tuberculosis.     

Diagnosis and treatment of pulmonary nontuberculous mycobacteriosis

Pulmonary non-tuberculous mycobacteriosis in Japan occurs more than about 5,000 cases annually. Among them, about 70% are occupied by Mycobacterium avium complex (MAC) infection. Considering the frequency and the difficulty of treatment, we discuss mainly on pulmonary MAC infection on this report. At National Tokyo hospital, secondary MAC infection after tuberculosis sequelae were 46.5% out of 170 pulmonary MAC cases since 1969 to 1985, but it decreased to 19.4% out of 268 cases since 1986 to 2000. In this same period, a type of MAC infection like middle lobe syndrome without recognizing preceding pulmonary disease, increased to 69.8% out of all pulmonary MAC cases (Fig. 1). Recently, this type of pulmonary MAC infection, which consists with scattered nodular lesion and local bronchiectasis in middle lobe or lingula, attracts attention. Why is there much frequency in women? Why does it originate from middle lobe or lingula? Although, it shows a characteristic X-ray pattern, ant it is still an interesting problem, the origin of the disease cannot be clarified. First diagnostic standard of nontuberculous mycobacteriosis in Japan was submitted in 1967, and the current diagnostic standard was made in 1985, through several times improvements. These contents are almost similar to that of American diagnostic standard in 1997, but the new revision that reflected chest CT findings and bronchoscopic sampling etc, is pressed now. In the treatment, INH or PZA, which is a key drug in tuberculous chemotherapy, is not a key drug in MAC chemotherapy. MAC chemotherapy is multidrugs combination chemotherapy including EB, CAM, RFP, and aminoglycosides. However, it is difficult to achieve complete regression with current drugs combinations, and an early surgical resection is the most effective in case of localized MAC lesion. We propose a guidance of treatment selection with age and disease severity (Table). Fig. 2 shows survival curves of 104 cases pulmonary MAC infection at National Tokyo Hospital.     

Serological diagnosis of pulmonary tuberculosis and nontuberculous pulmonary mycobacteriosis]

OBJECTIVE: The present study was undertaken to evaluate the utility of the serodiagnosis of pulmonary tuberculosis and nontuberculous pulmonary mycobacteriosis by ELISA using a Pathozyme-Myco kit (Myco kit) and a Pathozyme-TB complex kit (TB kit) (OMEGA Diagnostics Ltd.). STUDY POPULATION: The subjects comprised 256 healthy volunteers (HV, healthy hospital employees), 66 patients with sputum-positive active pulmonary tuberculosis (apTB), 14 patients with healed pulmonary tuberculosis (hpTB), 24 patients with nontuberculous pulmonary mycobacteriosis (NTM) and 32 patients with pulmonary diseases other than mycobacteriosis. RESULTS: 1) The serum IgG antibody titers determined with the Myco kit were significantly higher in the apTB group (p < 0.01), the hpTB group (p < 0.01), and the NTM group (p < 0.01) than those in the HV and the other pulmonary disease group. At a cut-off value of the mean + 2SD of the values obtained in the HV, the positive rate was 47.0% in patients with apTB, 50.0% in those with NTM, 21.4% in those with hpTB, 3.1% in those with other pulmonary diseases, and 1.6% in the HV. Analysis of ROC curves showed that the HV and the pulmonary mycobacteriosis group (apTB and NTM) were best distinguished by a cut-off value of -0.280 OD (log), with the sensitivity and the specificity being 83.3% and 78.5%, respectively. It was impossible to distinguish apTB from NTM. 2) The serum IgG antibody titers determined with the TB kit were significantly higher in the apTB group than those in the HV (p < 0.01), the NTM group (p < 0.05) and the other pulmonary disease group (p < 0.01). No significant difference was observed between the HV and the patients with NTM or those with other pulmonary diseases. Although the positive rate of the test was low in the apTB group (42.4%), there was a significant difference between apTB and NTM (12.5%) (p < 0.05), suggesting that apTB could be distinguished from NTM. 3) Since the serum antibody titers determined by the Myco kit showed no significant difference between apTB and NTM, and there was also no difference in the positivity between the two diseases, we performed serologic examination using the Myco kit to detect both diseases as pulmonary mycobacteriosis. After diagnosing pulmonary mycobacteriosis by the Myco kit, we then used the TB kit to separate apTB from NTM. In this case, the sensitivity and specificity of the test were 55.6% and 85.7%, respectively. Better methods should be developed to distinguish apTB from nontuberculous mycobacteriosis.     

Treatment of relatively rare species nontuberculous pulmonary mycobacteriosis

Today, a treatment guide of relatively rare species nontuberculous mycobacteriosis (NTM) is required ever-increasing. Because, new species are discovered continuously with advanced nucleic identification technique and these results entered routine clinical practice. Secondly, under the influence of newly introduced bioactive drugs for treatment of RA, rare species NTM cases has been really increased. And although there have been over 150 species NTM, the right chemotherapy regimen is not uniform like as TB treatment, it should only rely on accumulated clinical experiences for each species respectively. Case series of relatively rare species NTM are rare enough in itself at a global level, therefor the treatment is also less evidence. However, the following two may be written definitely recommended. M. szulgai pulmonary disease chemotherapy is recommended with RFP, INH, EB chemotherapy includes 12 months of negative sputum cultures. M. fortuitum pulmonary disease should be given at least more than two sensitive drugs including new quinolone for to reach 12 months of negative sputum cultures. For other species, chemotherapy regimen and duration of treatment has not been established. In case of unspecified or unknown species mycobacteriosis, the chemotherapy regimen should be suggested the treatment of in relatively same group on Runyon classification.     

Impaired cough-related quality of life in patients with nontuberculous mycobacteriosis

BackgroundCough and sputum are the significant symptoms of nontuberculous mycobacteriosis (NTM) and impair quality of life (QOL). However, the relationship between these symptoms and clinical features is not fully understood. This study aimed to investigate cough-related QOL in NTM patients.MethodsThe study subjects included 78 patients with NTM at our hospital from October to December 2015. They completed the Leicester Cough Questionnaire (LCQ) and the Cough and Sputum Assessment Questionnaire (CASA-Q) (both questionnaires: the higher, the better); the Frequency Scale for the Symptoms of gastroesophageal reflux disease (GERD) (FSSG), a validated Japanese questionnaire for GERD (the higher, the worse), was also assessed. The FSSG consists of 12 items, including the reflux-related symptoms and dysmotility symptoms domains, each of which is quantified on a scale of 0–4 points, and the cut-off score for GERD is set at 8 points. Associations between these scores and clinical parameters were assessed.ResultsThe total LCQ score was reduced—the physical domain was dominant. The total LCQ and CASA-Q scores were reduced, with dominance in the physical and symptoms domains, respectively. The reflux-related symptoms score was higher than the dysmotility symptoms score. A multivariate linear regression analysis revealed that the mean total LCQ score was independently associated with current smoking, fibrocavitary type, bilateral cavitary lesion, and FSSG total score.ConclusionsCough-related QOL was impaired in NTM patients who currently smoked, had radiological characteristics, and had GERD.     

A case of pulmonary dirofilariasis that required differentiation from nontuberculous mycobacteriosis]

A 48-year-old man was admitted with an abnormal shadow on a chest X ray. Chest X ray and CT revealed a solitary nodule in the right lung field. Mycobacterium gordonae was cultured from sputum. Tumorectomy by video-assisted thoracoscopic surgery was done for histological diagnosis, and Dirofilaria worms accompanied with epithelioid cell granuloma with necrosis were found, while no bacteria were cultured from biopsy specimen, thus we diagnosed dirofilariasis. Because a solitary nodule can be caused by either Dirofilaria species or nontuberculous mycobacteria, this case was of interest with regard to the differential diagnosis of a lung solitary nodule.     

The clinical analysis of chronic obstructive pulmonary disease patients complicated with nontuberculous mycobacterial pulmonary disease

正Objective Long-term use of inhaled corticosteroids(ICS) was reported as a risk factor for patients with chronic obstructive pulmonary disease (COPD) complicated with nontuberculous mycobacterial lung disease (NTMLD).But it was not reported often in China.Methods We conducted a retrospective analysis of patients who     

A case of pulmonary nontuberculous mycobacteriosis induced by tocilizumab treatment for rheumatoid arthritis

A 65-year-old woman whose rheumatoid arthritis was treated with tocilizumab (TCZ) was found in chest radiography to have a new consolidation in the right lower lung field. Positive Mycobacterium intracellulare and Mycobacterium avium cultures in sputum and bronchial secretions yielded a diagnosis of pulmonary nontuberculous mycobacteriosis. The most common adverse TCZ effect is infection. This case highlights the fact that those treated with TCZ should be considered at elevated risk for developing nontuberculous mycobacteriosis.     

Studies on the epidemiology of nontuberculous mycobacteriosis in Japan

The epidemiology of mycobacterial disease in Japan changed considerably over the period 1971 to 1984. During this time, the incidence of pulmonary disease caused by Mycobacterium tuberculosis has steadily declined; disease caused by M. avium complex has remained stable; disease caused by M. kansasii has increased considerably; and, for the first time, substantial numbers of cases caused by M. szulgai, M. fortuitum, M. chelonae, and M. nonchromogenicum have been reported. From 1981 to 1984 the incidence of pulmonary nontuberculous mycobacterioses (NTM) was estimated at 1.73 +/- 0.25 cases per 100,000 population per year; of these, M. avium complex constituted 1.29 +/- 0.24 and M. kansasii 0.34 +/- 0.11 per 100,000 per year. The prevalence of the NTM was relatively high in southwestern Japan (industrialized, warm climate) and low in northern Japan (rural, cold).     

Increased pulmonary gamma interferon production in asbestosis

In order to determine if disordered cellular immune processes are present in the lungs of persons with asbestosis, we performed bronchoalveolar lavage (BAL) on 26 patients with either crocidolite- or chrysotile-induced pulmonary asbestosis and measured the spontaneous release of gamma interferon (IFN gamma), a marker of increased cellular immune activity. For comparison, 18 control subjects and 7 patients with active pulmonary sarcoidosis were also studied. Recovered BAL cells were cultured for 24 h (5 x 10(6)/ml), and the supernatant was assayed for interferon by determining inhibition of cytopathic effect on encephalomyocarditis virus-induced lysis of WISH cells and characterized by monoclonal anti-IFN gamma antibody inhibition. Nine (35%) patients with asbestosis released increased amounts of IFN gamma, up to 320 units/ml, the levels seen in the sarcoidosis patients. All control subjects released less than or equal to 10 units/ml. All interferon released was IFN gamma. In asbestosis patients, IFN gamma production was not related to a history of cigarette smoking, there was no significant difference in the ratio of helper/inducer (Leu-3) to suppressor/cytotoxic (Leu-2) cells in IFN gamma producers compared to non-IFN gamma producers (p greater than 0.05), and IFN gamma production correlated significantly with serum IgG levels (p less than 0.001) but not with the levels of IgM, IgA, antinuclear factor, or rheumatoid factor. These data suggest that active cellular immune processes are present in the lungs of a proportion of patients with asbestosis.     

Analysis of pulmonary nodules caused by nontuberculous mycobacteriosis in 101 resected cases: multi-center retrospective study

BackgroundSolitary pulmonary nodules caused by nontuberculous mycobacteriosis are included as a category of pulmonary nontuberculous mycobacterium disease. Clinical characteristics, treatments and prognosis are not fully known because there are a few related reports.MethodsThis was a multi-center retrospective study of 101 cases diagnosed as solitary nodular type of nontuberculous mycobacteriosis from January 2000 to March 2017 that underwent resection at 9 related facilities belonging to the Thoracic Surgery Study Group of Osaka.ResultsThe most common pathogen was Mycobacterium avium complex (n=77, 87.5%), followed by Mycobacterium kansasii (n=8, 9.1%). Chest computed tomography results showed subpleural locations that were difficult to distinguish from lung cancer. Fluorodeoxyglucose positron emission tomography/computed tomography was performed in 58 cases and positive results were obtained in 35 (60.3%), with an average maximum standardized uptake value of 3.87. The purpose of resection in most cases was for diagnosis. The surgical procedure was wedge resection in 87, segmentectomy in 3, and lobectomy in 11, while 77 underwent thoracoscopic surgery. Postoperative complications occurred in 7 cases, though no infections caused by nontuberculous mycobacteriosis were noted. The median observation period was 27 months. A worsened condition occurred in 10 (9.9%) with Mycobacterium avium complex, though none had local recurrence.ConclusionsSolitary pulmonary nodules due to nontuberculous mycobacteriosis is difficult to diagnose based on preoperative examination results or distinguish from lung cancer. Among the present cases, none had local complications or recurrence, even in those that underwent a wedge resection, thus postoperative chemotherapy was not considered necessary if a complete resection was performed. On the other hand, some cases showed reinfection after a long period following resection, thus patients should be informed of that future possibility.     

Combination therapy with interferon alpha-2b plus low-dose interferon gamma in pretreated patients with Ph-positive chronic myelogenous leukaemia

Between March 1988 and July 1990, 28 adults with chronic myelogenous leukaemia (CML) were treated with a combination of recombinant human interferon (IFN) alpha-2b s.c. (initial dose 4 x 10(6) U/m2) and recombinant human IFN gamma s.c. (50 micrograms totally) daily. All patients were in chronic phase disease and had been treated previously with chemotherapy or bone marrow transplantation. A complete haematologic remission was achieved in three patients (11%), a haematologic remission in 12 patients (43%), and a partial haematologic remission in seven patients (25%). Six patients did not respond to this schedule. Acute side-effects were flu-like symptoms, fever and chills. During long-term treatment six patients developed polyarthralgia. Haematotoxicity WHO grade III occurred in three patients, and WHO grade IV in two patients. One patient developed psychosis, and in another patient an exacerbation of a pre-existing sarcoidosis was observed. We conclude that this combination is tolerable and effective in inducing haematological remissions in pretreated CML patients.     

Pulmonary nontuberculous mycobacteriosis showing wandering shadows in chest roentgenograms.

The case of a 68-year-old woman with pulmonary nontuberculous mycobacteriosis, whose chest roentgenograms showed unusual wandering shadows on separate occasions, is presented. Acid-fast bacilli were detected in her sputa and by bronchial washing, and were identified as Mycobacterium chelonae, subspecies abscessus. The findings of computed tomography and transbronchial lung biopsy were also unique because of multiple peribronchial inflammations. Chemotherapy with anti-tuberculosis agents and a new quinolone drug was successful in this case.     

Sequential treatment of Ph-positive chronic myeloid leukemia with interferon gamma and interferon alpha

Several clinical observations have shown that alpha-IFN is presently the most interesting investigational agent for the treatment of Ph+ chronic myeloid leukemia (CML). Gamma-IFN is also effective, and experimental data as well as preliminary clinical observations suggest that the combination of the two IFNs is worth investigating. No comparative data are available on the effects of the two IFNs, given alone, in the same patients. In this study 11 patients with PH+ CML were first treated with gamma-IFN, up to a maximum period of 35 weeks, and after a short rest period were retreated with alpha-IFN. Both IFNs were ineffective in 3 patients in accelerated or instable chronic phase. Both IFNs were equally effective in 8 patients in stable chronic phase, but none of these patients achieved a karyotypic conversion with either IFN. This study did not show any measurable differences in the therapeutic response to gamma-IFN and alpha-IFN given consecutively to the same patients.     

乙型肝炎患者外周血白细胞膜γ干扰素受体1的变化及其临床意义

目的研究不同临床类型慢性乙型肝炎患者外周血白细胞膜γ干扰素受体1(IFN-γR1)反应的差异性及其临床意义。方法采用流式细胞技术及夹心酶联免疫吸附法检测53例慢性乙型肝炎患者外周血细胞膜IFN-γR1表达及血清IFN-γ水平变化,并与血生物化学指标、肝组织病理变化进行相关性分析。结果慢性重型肝炎淋巴细胞膜IFN-γR1表达水平显著高于正常对照[(28.89％±11.77％)与(9.23％±1.30％)],两者差异有显著性(Z=3.988,P<0.05)。各组间单核细胞膜IFN-γR1表达水平变化差异无显著性。肝硬化、重型肝炎两者血清IFN-γ水平较正常对照,差异有显著性升高,肝硬化、重型肝炎IFN-γ水平组内差异较大,组间无差异。慢性乙型肝炎患者淋巴细胞膜IFN-γR1与总胆红素显著相关(r=0.575,P<0.01),与肝组织炎症活动度显著相关(r=0.621,P<0.01)。结论慢性乙型肝炎淋巴细胞通过上调膜IFN-γR1参与免疫病理。