Efficiency of the Lung Flute for sputum induction in patients with presumed pulmonary tuberculosis.

INTRODUCTION: High quality sputum helps increase the sensitivity of the diagnosis of pulmonary tuberculosis. OBJECTIVES: To evaluate the efficiency of the acoustic device (Lung Flute; LF) in sputum induction compared with the conventional method, hypertonic saline inhalation (HSI). METHODS: In this crossover study, patients with presumed pulmonary tuberculosis submitted 3 consecutive sputa: the first sputum without induction and the second and third ones using LF and HSI. We compared the efficiency of the 2 induction methods. RESULTS: Sixty-four participants were eligible. Thirty-five (54.6%) patients had negative smears on the first sputum without induction. Among those patients, 25.7% and 22.9% patients were smear-positive after using LF and HSI, respectively (P = .001). The positive conversion rate was not significantly different between the methods. The first samples without induction yielded 65.7% positive cultures, whereas 71.4% and 77.1% of the samples from LF and HSI were positive, respectively (P = .284). Similar results were observed in the nucleic acid amplification test [no induction (60.0%), LF (72.0%) and HSI (60.0%); P = .341]. In 29 smear-positive patients on the first sputum without induction, we observed no significant increase in smear grade, culture yield and nucleic acid amplification test positivity with either method. LF tended to induce fewer adverse events; desaturation (3.1% vs 11.1%; P = .082) and throat pain (1.5% vs 9.5%; P = .057). LF showed significantly fewer total adverse events (15.8% vs 34.9%; P = .023). CONCLUSIONS: Our study showed LF had similar sputum induction efficiency to HSI with relatively fewer complications.

Practical study concerning improvements in tuberculosis care practice.

With tuberculosis now relatively well contained in Japan, it is important to reconfigure treatment systems and structures to ensure the most appropriate treatments in the future. A survey of designated tuberculosis treatment facilities in Hiroshima Prefecture revealed declining standards of tuberculosis diagnosis and treatment as well as decreasing knowledge levels in regional areas, suggesting the need for improved collaboration between tuberculosis specialists and regional health care providers. A tuberculosis care pathway designed to promote improved collaboration between referring medical institutions and clinics, and the DOTS (directly observed treatment, short-course) Notebook for patient advice and assistance with compliance, were developed jointly by the Higashihiroshima Medical Center and the Onomichi Medical Association. Following the introduction of tuberculosis care pathway and the DOTS Notebook, we have seen a number of improvements, notably an increase in successful treatment outcomes in regional areas and fewer patients receiving treatment for more than 12 months. These results suggest that better liaison through the regional coordination pathway has led to improved tuberculosis treatment in regional areas. While further refinements and modifications are necessary, it is clear that this represents a step forward in tuberculosis care, and will provide the impetus to bring about meaningful changes to the system.

[Considerations on uses of newly developed anti-tuberculosis drugs for multi-drug resistant tuberculosis].

We, group of tuberculosis experts, made discussions over how to improve the quality of treatment of multidrug resistant tuberculosis using a newly developed anti-tuberculosis drug, and at the same time, how to prevent the disadvantages of the treated patients and also that of persons who would be infected with newly produced drug-resistant bacilli, by preventing the emergence of resistance to the new drug. A series of proposals are made.

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.

[Present and future of tuberculosis care in regions].

As the incidence of active tuberculosis in Japan declines and the healthcare environment changes, restructuring of the medical care system for tuberculosis is required. According to a questionnaire survey in Hiroshima Prefecture, experiences in tuberculosis (TB) care and knowledge, such as standard treatment and DOT, is insufficient in the local medical institutions designated for tuberculosis care. Regional coordination between the tuberculosis hospital and the regional private practitioners will be one of the important issues in proper TB care. In order to strengthen coordination, Higashi-hiroshima Medical Center (HMC) collaborated with Onomichi Medical Association and the health center having jurisdiction over the area (Tobu Health Center) to create liaison clinical paths for doctors, a booklet for patient education and a medication record named "DOTS note". These liaison paths were provided to the regional practitioner from the health center on discharge and referral from HMC. After the start of regional cooperation, treatment outcome of the cohort of sputum smear positive pulmonary tuberculosis in the region were improved: success; 37.0% to 53.3% (cured; 0% to 40.0%, completed; 37.0% to 13.3%), treatment more than 12 months; 17.4% to 6.7%, died 37.0% to 26.7%. It is considered from experience of the regional cooperation in Hiroshima that regional medical cooperation using liaison paths is helpful to provide proper TB care. Treatment of patients with serious complication(s) is another issue in TB care. For example, only a few TB hospitals can treat the patient who needs hemodialysis, on the other hand, most general hospitals do not treat TB patients, because they have no beds and little knowledge. I think the following measures are effective and necessary for the future TB care: 1) one or more of the general hospitals in each region should provide one or more air-controlled bed(s) to treat TB patients, which can be also used for patients with suspected airborne infectious disease, 2) cooperation between tuberculosis experts and general physicians is necessary to provide standard TB care, 3) Rapid communication between TB experts and regional health centers to provide concrete information such as liaison clinical paths, and finally, 4) government commitment is needed to promote the above measures.

Distribution of mycobacterial antigen based on differences of histological characteristics in pulmonary Mycobacterium avium infectious diseases--consideration of the extent of surgical resection from the pathological standpoint.

Quantitative assessment of mycobacterial antigens is very important to determine the surgical indication, as well as the area of resection for pulmonary Mycobacterium avium complex (MAC) infectious disease. However, at present, pathological assessment is only possible as a postoperative examination. We performed quantitative evaluation of mycobacterial antigens using lung tissues with MAC pulmonary infection obtained from surgical resection. The distribution of mycobacterial antigens was evaluated by immunohistochemical staining with monoclonal antibody for mycobacteria. In exudative reactions, many monocyte-lineage cells containing mycobacterial antigens were observed in alveoli, whereas the quantity of mycobacterial antigens was extremely decreased in proliferative reactions. Epithelioid cells or multinucleated giant cells contained mycobacterial antigens in necrotic granulomas. In solitary nodules with central necrosis, mycobacterial antigens were frequently observed, whereas they were rarely observed in solitary nodules without caseous necrosis. Mycobacterial antigens were not observed in the epithelial layer of bronchioles in any cases, although proliferative granulomas were notably observed in the developed lymphoid follicles in subepithelial lesions of bronchiole. Thus, exudative reactions or nodules with caseous necrosis indicate the possibility of numerous mycobacteria remaining in the pulmonary focus. Therefore, intraoperative histological assessment may help in the determination of the area of surgical resection. This is the first study to quantitatively evaluate mycobacterial antigens according to histological characteristics in MAC pulmonary disease.

[Treatment and isolation of non-adherent and/or infectious tuberculosis patients under the infectious diseases control law].

OBJECTIVES: To clarify the present situation regarding isolation of tuberculosis (TB) patients who do not comply with hospital treatment or adhere to treatment. METHODS: A mailed questionnaire survey to 252 hospitals having tuberculosis beds. RESULTS: Answers were returned from 160 hospitals. Answers from 146 hospitals, excluding 14 that had closed their TB wards, were analyzed. Experiences of defaulters were reported from 35 hospitals. Seven of these defaulting patients were homeless, 4 were foreign-born, and 2 had other problems, but for 15 cases no problem was known. Fourteen hospitals reported that the burden of medical fee payment was one of the causes of defaulting. Defaulting occurred in hospitals even having close cooperation with public health centers over DOTS. For chronic excretors under long-term hospitalization, 31 (20.4%) hospitals allow home isolation, whereas 78 (51.3 %) refuse discharge from the TB ward even for a short period. However, 69 (45.4%) answered that home isolation could be allowed under certain conditions. Only 17 (11.2%) think that current TB hospitals are appropriate for long-term hospitalization, and 63 (41.4%) feel that the improvement of the facilities for that purpose is needed. Seventy-two (48.3%) hospitals answered that confinement under detention should be mandatory, while 70 were against it. CONCLUSION: Since 2007 hospital treatment of tuberculosis patients has been mandatory under the Infectious Diseases Control Law in Japan, but this study revealed that there are patients who leave the hospital in violation of the law. There is also a problem of non-infectious but non-compliant patients who are discharged for ambulatory treatment being likely to default and develop relapse. Because these patients are likely to develop M(X)DR-TB and may threaten the community, certain effective legal actions including hospitalization under detention should be imposed on them. At the same time, for chronic excretors with XDR-TB, home isolation should be allowed from the point of view of human rights, under clear conditions for infection prevention, together with the provision of a financial subsidy.

Desensitization therapy for allergic reactions to antituberculous drugs.

OBJECTIVE: We retrospectively evaluated the clinical usefulness of desensitization therapy for many patients showing allergic reactions to anti-mycobacterial drugs (INH and RFP) according to the proposition reported by the Japanese Society for Tuberculosis (JST). METHODS: Desensitization therapy for anti-mycobacterial drugs was performed according to the propositions of JST for forty-six patients with mycobacterial disease in several hospitals participating in the Chugoku-Shikoku Mycobacterial Disease Committee between January 1999 and December 2009. RESULTS: Adverse reactions occurred as drug-induced skin eruptions in 23 patients, drug-induced fever in 16, and drug-induced fever plus eruption in 7. The causative drugs suggested by the clinical course or DLST were RFP in 30 patients and INH in 16. The clinical effects of desensitization therapy for individual drugs was good in 23 of 30 patients (77%) receiving RFP, and in 13 of 16 (81%) receiving INH. Ten patients showing failure of desensitization included 5 elderly patients and 2 patients with a history of drug allergies. The interval until initiation of desensitization therapy ranged from 5 to 30 days after the disappearance of adverse reactions and the interval until the appearance of adverse reactions during desensitization therapy ranged from 3 to 18 days. A comparative study between the patient group with successful desensitization therapy and that with failure of desensitization did not show any significant differences except for the interval until initiation of desensitization therapy. CONCLUSION: We confirmed the clinical effectiveness of desensitization therapy for anti-mycobacterial drugs according to the propositions of JST in this multicenter study.

[The current status of fluoroquinolones and other off-label drug use for tuberculosis in Japan].

OBJECTIVES: To clarify the present state and problems of off-label drug use in tuberculosis treatment in Japan. MATERIALS AND METHODS: Questionnaire survey by mail to 252 hospitals with tuberculosis wards. RESULT: It was found that 146 out of 160 hospitals returning the questionnaire had active tuberculosis ward(s). Fluoroquinolones (FQs) were being used in 119 (81.5%) hospitals, of which 115 used levofloxacin. The reasons for using FQs were: i) adverse reactions to other antituberculosis drug(s) in 97 hospitals, and ii) drug-resistance in 80 hospitals. The perceived problems in using FQs were: i) its use for tuberculosis is not approved (often not reimbursed by medical insurance), cited by 73 hospitals; ii) increased out-of-pocket medical fees for patients (not covered by public service), cited by 48 hospitals; iii) official compensation for severe adverse reactions cannot be guaranteed for off-label use, cited by 19 hospitals. Other off-label drugs such as linezolid are also used in 37 hospitals. DISCUSSION: Fluoroquinolones, especially levofloxacin, are widely used in tuberculosis treatment in Japan for patients with adverse reactions and/or drug-resistance to other antituberculosis drugs. As these drugs have not yet been approved for tuberculosis treatment and therefore are not included in "the Standards of Tuberculosis Treatment" established by the government, the costs for FQs and other off-label drugs are not covered by public subsidies for medical treatment, thus increasing the economic burden for patients, which may in turn cause drop-out, especially in cases of MDR-TB. Further, FQs are not under control of the Tuberculosis Advisory Committee of the Health Center, which has played an important role in ensuring the standard tuberculosis treatment in Japan. CONCLUSION: FQs should be included in the Standards of Tuberculosis Treatment to secure adequate chemotherapy for tuberculosis.

[Future tuberculosis care in Japan].

In Japan, the care of patients with tuberculosis has been mainly dependent on the state of hospital wards. The number of patients that have tuberculosis has steadily declined over the years, and we are now on the way to low prevalence state of tuberculosis. However there is a need for discussion about how future care for patients with tuberculosis should take place. The problems of present tuberculosis care system are as follows: (i) there is inefficiency and difficulty in maintaining the tuberculosis wards because of the declining number of patients and specialists; (ii) there are difficulties in treating complications such as renal insufficiency which requires blood dialysis, delivery, psychiatric diseases in tuberculosis beds; (iii) there is a high proportion of elderly patients that require substantial nursing care and long-term admission in the hospital; (iv) there is not only insufficient patient care but also financial support for patients with socioeconomic problems such as foreign-born worker or homelessness, (v) in addition to the medical care for patients of MDR-TB being insufficient, there are also inappropriate environment and amenities for long-term hospitalization. Moreover the public subsidy system for medical treatment requires patients to pay 5% of expense cost in the outpatient clinic. The following points should be discussed for the future tuberculosis care system: (i) general hospitals should take more part in caring for patients with complications and there should be a close cooperation among general hospitals, tuberculosis specialists and the administration; (ii) there should be a limited number of hospitals maintained for the integrated treatment of MDR-TB including surgical treatment and suitable circumstances for long-term hospital care. Additionally, there should be a system of detention for non-adherent patients or home isolation for adherent patient; (iii) there should be reinforcement of public commitment for patients with socioeconomic problems or MDR patients such as public subsidized full coverage of medical expense, free treatment in regional health centers

[Development of TB treatment system by liaison critical path].

Liaison critical path (LCP) for various diseases is useful to strengthen community medical cooperation and to provide better service for patients. LCP for tuberculosis is not yet spread except for a few trials, while cooperation of health center and hospitals with tuberculosis ward through community DOTS is now going to be established. We started cooperation between Higashihiroshima Medical Center and Onomichi Medical Association to provide better medical care for tuberculosis patients through LCP. The request of health care workers for LCP by questionnaire study were i) schedule of laboratory examination to check adverse reaction of medication, ii) schedule of chemotherapy, iii) report system of tuberculosis, iv) infection control and so on. LCP was made up based on these requests and the guidelines of standard chemotherapy. We made LCP to be concise and 3 parts; i) standard treatment with PZA, ii) standard treatment without PZA and iii) treatment other than standard regimen. In addition to these LCP for TB treatment, we made information sheets for i) when to suspect and how to diagnose, ii) flow chart for deciding regimen, iii) explanation of standard treatment and DOTS, iv) information for patients and their families about treatment, admission and infection control. These sheets were offered to member of medical association with referral letter on discharge from TB ward or by health center nurse just after notification of TB. Though the results of these LCP are not yet fully analyzed, following effects are expected and obtained; i) diffusion of standard chemotherapy and DOTS to medical practitioner, ii) confidence that the treatment is appropriate, iii) reduction of burden on TB hospital through early referral to general practitioner or beginning treatment without referral if admission is not necessary. LCP with community DOTS will help TB patients and healthcare workers around the patients. The most important effect of LCP is establishment of human relationship and network of health care workers molded in the process of development itself. The problems to be faced from now are diffusion of LCP to other TB hospitals and areas, participation of pharmacy and patient care system at home or nursing home. Any part of members may take initiative to develop LCP, but the role of health center nurse is important.

Endobronchial ultrasonography with a guide-sheath and virtual bronchoscopy navigation aids management of peripheral pulmonary nodules.

Occasionally, we have difficulty in diagnosing small peripheral pulmonary nodules. However, efforts have been made to resolve this problem. For instance, computed-tomography (CT), positron emission tomography (PET), flexible bronchoscopy examination (BF), and video-assisted thoracic surgery (VATS) have been performed to investigate such nodules. We have used endobronchial ultrasonography with a guide-sheath (EBUS-GS) for BF examination, and recently applied the virtual reality technique "virtual bronchoscopy (VB)". Here, we present a case in which a combined technique with VB and EBUS-GS was useful. The patient was a 54-year-old man with a persistent cough and chest pain. Small nodules were seen in the bilateral lungs on the chest CT taken at the local hospital. A slight increase in the CEA level (6.1 ng/ml; normal level < 5.0 ng/ml) was shown as well as an uptake in the latter term on PET. As a result, he was referred to our hospital for a detailed work-up. We applied VB to confirm the location of the tumor, which allowed us to approach the lesion easily. Furthermore, we precisely localized the lesion using EBUS-GS. Then a biopsy was performed, which demonstrated bronchiolitis obliterans organizing pneumonia (BOOP). As seen in this case, combining VB and EBUS-GS seems beneficial for diagnosing peripheral pulmonary nodules.

Virtual bronchoscopy aids management of lung cancer.

The development of CT scanning has been beneficial for clinical medicine. In this case, virtual bronchoscopy (VB) was of clinical benefit. A 71-year-old woman with suspected lung cancer in the upper left lobe remained undiagnosed after investigation at another hospital. VB was used to confirm the location of the tumour, which facilitated an appropriate trans-bronchial lung biopsy being performed. The volume-rendering technique yielded information regarding an arterial anomaly, allowing high-quality and safe medical treatment to be provided. VB assists navigation in bronchoscopy, and the volume-rendering technique is effective in finding congenital anomalies of the vessels during preoperative assessment.

[Survey of anti-tuberculosis drug-induced severe liver injury in Japan].

PURPOSE: To clarify the incidence and clinical significance of anti-tuberculosis drug-induced liver injury. SUBJECTS AND METHODS: Questionnaire was sent out by mail to 114 hospitals, to ask whether there were patient(s) from 1994 to 2003 with liver injury induced by anti-tuberculosis drugs with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of more than 1000 IU/l and/or total bilirubin level of more than 2 mg/dl. As for the cases of severe hepatic injury, their backgrounds and clinical courses were investigated. RESULTS: Seventy cases were reported from 24 out of 68 hospitals which treated at least 8095 tuberculosis patients in 2003. Incidence rate of severe liver injury by anti-tuberculosis drugs was 0.50 to 0.59 percent in three hospitals with good surveillance system, and overall incidence was estimated to be between 0.1 to 0.5 percent. We could analyze 33 cases; one was HB antigen positive, one had HCV positive liver cirrhosis, 2 had other hepatic disease, and 17 had other underlying disease including diabetes mellitus. Twenty-three were treated by regimens with isoniazid (INH), rifampicin (RFP) and pyrazinamide (PZA), and 8 by regimens without PZA but with INH and RFP and one was a multidrug-resistant case and was treated by regimen with ethionamide and PZA. The onset of liver injury was within 2 months after starting anti-tuberculosis chemotherapy in 28 (85%) cases. In twenty-eight cases which both ALT and total bilirubin level are known, total bilirubin level at the onset of liver injury was more than 2 mg/dl in 14 cases and most of the cases were hepatocellular type of liver injury. Six out of 10 cases with total bilirubin level more than 5 mg/dl died by liver failure. Total birilubin was less than 2 mg/gl in two of the dead cases; in one case antituberculosis drug were continued despite elevated level of ALT and another case complicated with gastric bleeding. Treatment for liver injury was conservative in most cases, 6 were treated by plasmapheresis and no liver transplantation was carried out. Eight cases died of liver failure, one died of tuberculosis and only 15 were treated successfully for tuberculosis. CONCLUSION: Incidence rate was high comparared with that by other drugs reported previously. The risk factor of liver injury by antituberculosis drugs was not detected, but elevated total bilirubin level more than 5 mg/dl was an alarming sign for poor prognosis.

[Two cases of lung infection due to Mycobacterium shimoidei, with special reference to bacteriological investigation].

Mycobacterium shimoidei (Tsukamura 1982) is an uncommon but widely distributed pathogen usually isolated from respiratory specimens. We report two cases of lung disease due to M. shimoidei and the associated bacteriological results. A 45-year-old man (Case 1) admitted to National Hospital Organization (NHO) Miyagi Hospital, a 75-year-old man (Case 2) admitted to NHO Higashi-Hiroshima Medical Center were found in initial chest X-ray and thoracic computed tomography (CT) to have a tuberculosis-like cavity in the left apex (Case 1) and the right apex (Case 2). In Case 1, the patient was treated with isoniazid and rifampicin for one month and lesions showed a partial response. In Case 2, the patient responded favorably with rifampicin, ethambutol, streptomycin, and clarithromycin therapy. Mycobacteria were repeatedly detected in smear and culture from sputum specimens in both patients. Isolates were nonphotochromogenic and rough. Isolated colonies developed after two to three weeks on 2% Ogawa egg medium. Organisms grew on 2% Ogawa egg medium at 30, 37, 42, and 45 degrees C, but not 25 degrees C. Both organisms were susceptible to 500 microg of p-nitrobenzoate per mL and 5mg of sodium chloride per mL. Isolates were negative for niacin accumulation, nitrate reduction, semiquantitative catalase, 68 degrees C catalase, 3-day aryl-sulfatase, iron uptake, and MPB64 antigen production, but positive for Tween 80 hydrolysis (5 and 10 days), acid phosphatase, and pyrazinamidase. Isolates had typical uv-HPLC chromatograms similar to M. shimoidei, demonstrating triple-peak clusters with peaks in the early cluster. 16S rRNA gene sequencing showed isolates to be consistent with Mycobacterium shimoidei. Based on composite characterization, isolates were identified as M. shimoidei. This is, to our knowledge, the third case of M. shimoidei infection reported in Japan.

Clinical features of eleven cases of Mycobacterium avium-intracellulare complex pulmonary disease associated with pneumoconiosis.

The relationship between silicosis and tuberculosis is well known. Also other mycobacteria such as Mycobacterium kansasii often occur in association with pneumoconiosis. However, there are few reports describing an association of M. avium-intracellulare complex (MAC) lung disease and pneumoconiosis. The purpose of the present study is to describe clinical features of MAC respiratory infection associated with pneumoconiosis. Eleven patients with MAC respiratory infection associated with pneumoconiosis (all men, 6 with silicosis and 5 with welders' pneumoconiosis) were collected. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. Radiologically, cavity formation as well as upper lung field predominance of MAC disease were observed in 8 of 11 cases (72.7%). Two of 11 patients died of respiratory failure. Our present study clearly demonstrates that clinical features of MAC respiratory infection associated with pneumoconiosis were different from MAC without underlying diseases.

Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens.

The tuberculin skin test for immunologic diagnosis of Mycobacterium tuberculosis infection has many limitations, including being confounded by bacillus Calmette-Guérin (BCG) vaccination or exposure to nontuberculous mycobacteria. M. tuberculosis-specific antigens that are absent from BCG and most nontuberculous mycobacteria have been identified. We examined the use of two of these antigens, CFP-10 and ESAT-6, in a whole blood IFN-gamma assay as a diagnostic test for tuberculosis in BCG-vaccinated individuals. Because of the lack of an accurate standard with which to compare new tests for M. tuberculosis infection, specificity of the whole blood IFN-gamma assay was estimated on the basis of data from people with no identified risk for M. tuberculosis exposure (216 BCG-vaccinated Japanese adults) and sensitivity was estimated on the basis of data from 118 patients with culture-confirmed M. tuberculosis infection who had received less than 1 week of treatment. Using a combination of CFP-10 and ESAT-6 responses, the specificity of the test for the low-risk group was 98.1% and the sensitivity for patients with M. tuberculosis infection was 89.0%. The results demonstrate that the whole blood IFN-gamma assay using CFP-10 and ESAT-6 was highly specific and sensitive for M. tuberculosis infection and was unaffected by BCG vaccination status.

Pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex.

It has been argued whether bronchiectasis is truly caused by MAC infection or just a predisposed condition in which MAC colonizes. Our present study was designed to evaluate the pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex (MAC) lung infection and to demonstrate MAC in the lesion of bronchiectases. A retrospective study was performed in nine cases with positive cultures for MAC in whom lung resections were performed. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. In addition, MAC were cultured from all nine lung specimens. Pathological findings of bronchiectases were evaluated in these nine patients. Destruction of bronchial cartilage and smooth muscles layer, obstruction of airway by granulomas, and ulceration of bronchial mucosa were frequently observed. Our present study demonstrates that destruction of fundamental bronchial structure due to extensive granuloma formation throughout the airways was likely the main cause of bronchiectases in MAC infection.