Development of lung cancer in patients with nontuberculous mycobacterial lung disease

Background

As lung cancer development in patients with nontuberculous mycobacterial lung disease (NTM-LD) has never been reported, we investigated its incidence and clinical characteristics.

AIDS合并非结核分枝杆菌肺病的诊治进展

近年来,随着AIDS的流行及实验室检测技术的进步,非结核分枝杆菌(Nontuberculous mycobacteria,NTM)肺病的发病率呈增多趋势。NTM肺病已成为AIDS患者常见的机会性感染及死亡原因之一。AIDS合并NTM肺病临床表现不典型,影像学无特异性,诊断困难,需要结合临床表现、体格检查和辅助检查结果来进行综合分析。提高对该病的认识,尽早诊治,是降低该病病死率的关键。加强对NTM鉴定和分型技术研究以及治疗方案优化是今后发展的方向和重点。     

Long-term case-fatality rate of nontuberculous mycobacterial disease in people living with HIV

Background::Few data are available regarding the long-term case-fatality rate (CFR) among people living with HIV (PLWH) with nontuberculous mycobacteria (NTM) d...     

Influence of chronic sputum symptoms on quality of life in patients with nontuberculous mycobacterial pulmonary disease: A cross-sectional study

BackgroundThe effect of chronic sputum (CS) symptoms on health-related quality of life (HRQOL) in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has not been studied. The aim of this study was to clarify the differences in the clinical characteristics of NTM-PD patients with and without CS and to investigate the effect of CS on HRQOL.MethodsThis cross-sectional study included patients with NTM-PD who were prescribed pulmonary rehabilitation at the Fukujuji Hospital from March 2016 to June 2019. HRQOL was evaluated using the MOS 36-Item Short-Form Health Survey (SF-36).ResultsOf the 99 subjects studied, 71 had CS (CS+) (71.7%), and 28 (28.3%) did not have CS (CS-). Patients in the CS + group had a lower body mass index, forced vital capacity percent predicted, and forced expiratory volume in 1 s percent predicted. Regarding the radiological evaluation, the proportion of patients with the fibrocavitary form and the radiological score were significantly higher in the CS + group. The mental component summary (MCS) score of the SF-36 were significantly lower in the CS + group. Multiple regression analysis showed that the presence of CS was independently associated with a lower MCS score of the SF-36.ConclusionsNTM-PD patients with CS had more severe disease, with reduced pulmonary function and severe radiological findings. CS was shown to independently affect HRQOL, especially mental status.     

Impaired health-related quality of life in pulmonary nontuberculous mycobacterial disease

Introduction

The impact of pulmonary nontuberculous mycobacterial (pNTM) disease on health-related quality of life (HRQL) has not been quantified.

Methods

We performed a prospective observational study of HRQL in 51 patients with pNTM disease. One generic (Short-form 36, version 2 -SF-36), and one pulmonary disease-specific instrument (St. George’s Respiratory Questionnaire – SGRQ) were administered to each subject.

Results

Fifty-one patients with pNTM disease from one ambulatory clinic were enrolled. The mean (sd) age was 67 (10) years and 80% (41/51) were female. The most common causative NTM was MAC in 84% (43/51) followed by Mycobacterium abscessus in 8% (4/51). Radiographic disease type was nodular bronchiectasis in 71% (36/51) and fibrocavitary in 22% (11/51). For SF-36, most raw scores were at least 10 points below Canadian population-based normals, and all normbased scores were below the expected normal value of 50. For SGRQ, all scores were worse by ≥25 points compared with published normals. In multivariable analyses, only FVC and DLCO were significantly associated with SF-36, and only FVC and emphysema were significantly associated with SGRQ.

Conclusion

Patients with pNTM disease have significantly impaired HRQL that is most closely associated with lung function and not readily explained by age, sex or extra-pulmonary comorbidity.     

Pulmonary nontuberculous mycobacterial infections: Antibiotic treatment and associated costs

Recent studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease. In the absence of prevalence and cost data, the public health burden of pulmonary NTM disease is difficult to assess. The goal of this study was to assess costs associated with NTM disease treatment and to identify risk factors associated with increased costs. Records from subjects with pulmonary NTM disease enrolled in a natural history protocol were abstracted for presenting symptoms, comorbidities, microbiology, and treatment histories. Antibiotic frequency, duration, adverse reaction, and costs were noted, the total antibiotic burden and cost were calculated, and risk factors associated with high costs were analyzed. From Jan 2004 to Dec 2005, 33 subjects were enrolled; 27 met disease criteria and had sufficient data to assess antibiotic use. Mycobacterium avium complex was present in 89% and Mycobacterium abscessus was present in 21% of subjects. Subjects received a median of 5 (1–10) antibiotics. Adverse effects were common seen in up to 50% with common antibiotics and up to 100% with uncommonly used antibiotics. Median burden of treatment was 2638 (84–7689) drug-days and the median total cost per patient was $19,876 ($398–70,917). Subjects with high treatment costs had an adjusted 9.5 fold (95% CI 1.5–97.2) likelihood of having M. abscessus and a 4.2 fold (95% CI 0.6–59.3) increased likelihood of having more extensive disease. Pulmonary NTM represent an underappreciated disease burden in the US population, with an associated treatment cost comparable to that for other chronic diseases of infectious origin such as HIV/AIDS.     

Pathophysiology of pulmonary nontuberculous mycobacterial (NTM) disease

In recent years, the incidence and prevalence of pulmonary nontuberculous mycobacterial (NTM) disease have increased worldwide. Although the reasons for this increase are unclear, dealing with this disease is essential. Pulmonary NTM disease is a chronic pulmonary infection caused by NTM bacteria, which are ubiquitous in various environments. In Japan, Mycobacterium avium-intracellulare complex (MAC) accounts for approximately 90% of the causative organisms of pulmonary NTM disease, which is also called pulmonary MAC disease or pulmonary MAI disease.It is important to elucidate the pathophysiology of this disease, which occurs frequently in postmenopausal women despite the absence of obvious immunodeficiency. The pathophysiology of this disease has not been fully elucidated; however, it can largely be divided into bacterial (environmental) and host-side problems. The host factors can be further divided into immune and airway problems. The authors suggest that the triangular relationship between bacteria, immunity, and the airway is important in the pathophysiology of this disease. The latest findings on the pathophysiology of pulmonary NTM disease are reviewed.     

Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan

Abstract

Objective This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA).

Methods We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab.

Results Most cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients.

Conclusion CT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.     

高分辨率CT在非结核分枝杆菌肺病诊治中的价值

搜集广州市胸科医院2015年3月至2017年9月经菌种鉴定为非结核分枝杆菌(NTM)肺病、并行胸部高分辨率CT(HRCT)检查的99例患者,回顾性分析肺内病灶部位、数量、形态、大小、密度、边界、分布及淋巴结的CT征象;评估99例NTM肺病患者治疗前后HRCT的表现。HRCT检查表现为斑点片状渗出、实变93例,支气管扩张78例,空洞60例,纤维条索状影59例,结节状影58例,树芽征55例,磨玻璃样影46例,淋巴结肿大45例,胸膜增厚18例,胸腔积液9例,病变通常以多种形态混杂存在。91例NTM肺病患者经克拉霉素、利福平、乙胺丁醇及阿米卡星治疗6~18个月后CT复查,显示病灶均减少;8例患者经HRCT精准定位后行患侧肺叶切除术,术后肺部病灶明显减少,但均出现术侧胸膜肥厚粘连。胸部HRCT对NTM肺病的诊断及治疗具有重要的应用价值。     

重视非结核分枝杆菌病诊断和治疗的研究

目前,人们对非结核分枝杆菌（NTM）病的了解尚不够深入,许多问题没有定论。本文就NTM病的流行病学、临床诊断和实验室诊断、治疗等方面研究现状进行综述。     

血栓栓塞性疾病与肺癌

目的 提高对肺癌合并血栓栓塞性疾病的认识。方法 从８０￣９０年代由病理学细胞学确诊的１０５０例肺癌中,选择２０例合并血栓栓塞性疾病的肺癌进行回顾性临床分析。结果 肺癌并发下肢深静脉止血栓形成（ＤＶＴ）１２例（１．１４％）;并发肺血栓栓塞（ＰＴＥ０８例（４例同时有ＤＶＴ）（０．７６％）,并发伴动脉栓塞的无菌性血栓性心内膜炎（ＮＢＴＥ）４例（０．３８％）,其中６例ＤＶＴ和（或）ＰＴＥ发生于肺癌确诊前２     

Imaging findings of vertebral osteomyelitis caused by nontuberculous mycobacterial organisms: Three case reports and literature review

Rationale:Prompt diagnosis of nontuberculous Mycobacterial (NTM) vertebral osteomyelitis is challenging, yet necessary to prevent serious morbidity and mortality. Here, we report 3 cases of vertebral osteomyelitis caused by NTM with imaging findings.Patient concerns:Case 1, a 58-year-old male patient, was admitted to our hospital because of the presence of a pulmonary mass for 6 months with cough and chest pain.Case 2, a 50-year-old male patient, had fever and cough for 3 years and was diagnosed with tuberculosis. Antituberculosis treatment was ineffective, accompanied by lymph node enlargement and osteosclerotic changes involving vertebral bodies.Case 3, a 66-year-old female patient, was admitted to our hospital with a mass on the top of her head for 1 month, which ruptured in the last 2 weeks.Diagnoses:Case 1: Sputum culture revealed Mycobacterium (M.) avium.Case 2: The final culture results of the lymph node biopsy samples were M. intracellulare.Case 3: Culture results of the sputum and pus from the abscess were M. gordon.We found sclerosing lesions in the spine in all 3 NTM patients, which were easily misdiagnosed as metastatic tumors. In 2 cases, there was bone destruction in the ilium with limbic sclerosis, and there were abscesses near the ilium and in front of the sacrum in 1 case.Interventions:Case 1 was transferred to other specialist hospital.Case 3 received surgical treatment for cranial lesions and abscess drainage.Case 2 and case 3 received targeted treatment for nontuberculous mycobacteria in our hospital.Outcome:The condition of case 1 was unknown.Recovery of case 2 was uneventful because of prolonged illness; however, inflammation gradually improved overall.Case 3 had no recurrence following surgical treatment.Lessons:In our 3 cases of NTM vertebral osteomyelitis, bone lesions were often misdiagnosed as bony metastases because of the presence of multiple sclerotic lesions. Diagnoses were challenging and delayed. It is important to consider osteomyelitis by NTM when disseminated osteosclerosis with or without osteolytic bone lesions is present in conjunction with continuous inflammatory symptoms and signs. Moreover, an open biopsy of the lesion should be performed for a definitive diagnosis.     

Clinical study on development of nontuberculous mycobacterial lung disease

DEVELOPEMENT OF MAC LUNG DISEASE: An increase of nodular bronchiectatic type of MAC lung disease becomes a problem among respiratory physician today. The reason is still unknown, but it seems to be globally recognized that this type of MAC disease is developing particularly in middle-aged woman. Some papers mentioned the existence of such type of MAC lung disease already early in the 70s, in Japan. Yamamoto described that 17 cases of middle lobe type lung disease out of 154 non-photochoromogen cases, and 76.5% were female, in 1970. Shimoide also pointed such type of 39 cases out of 240 MAC lung disease and 84.6% were female, in 1980. Prince reported MAC lung disease seen in old and middle age female of 21 cases including lethality example of 4 cases without a precedent disease in 1989. After his report, the international consensus of this peculiar type of MAC lung disease seems to be spread. In 1989, we compared 72 cases of nodular bronchiectatic type of MAC lung disease and 56 cases of diffuse panbronchiolitis (DPB) that was a most typical chronic airway disease at that time in Japan. The average age of disease onset of DPB group was 37.0 +/- 16.3 years old and that of MAC group was 54.5 +/- 16.3 years old. The percentage of female was 32% in DPB group and 87.5% in MAC group. It was highly possible that two groups belong different parent population. We could grasp that nodular bronchiectatic type of MAC lung disease patients is a unique group. We observed the serial films of 21 cases of nodular bronchiectatic MAC lung disease, and divide the progression of the disease to sequential 7 steps as Fig. 1. Small nodules progress to cavities in mean about 10 years. However, why is MAC which is opportunistic pathogen with weak virulence, able to form a lesion at unimpaired lung parenchyma? Is there really normal site? Why dose it start from lingula? Why is MAC seen a lot in woman? While it is extremely pathognomonic clinical picture, and, is an extremely interesting problem, most are still unidentified. STUDY OF MAC LUNG DISEASE TREATMENT: It was known that Mycobacterium kansasii lung disease is healed with a chemotherapy like analog of anti-tuberculosis chemotherapy, already in those days. However, the results of MAC lung disease chemotherapy were extremely poor. We tried to express a physicians experience quantitatively as follows, in 1987. The results of 8 weeks sputum culture on Ogawa egg medium were converted semi-quantitatively to CFU numbers based on "Japanese standard guideline of Mycobacterium tuberculosis inspection". We exhibit the ratio of post-treatment consecutive 6 months culture yield to pre-treatment culture yield as response rate, about 110 pulmonary MAC cases. Through this study, we clarify the followings. The results of chemotherapy do not correlate susceptibility test for Mycobacterium tuberculosis. Multidrug regimen is more useful. Small extent of lesion is more responsive. Combination with aminoglycoside chemotherapy is more effective. These conclusions were almost same as the ATS guideline of 1990. New drugs such as, new macrolides and new quinolones appeared for pulmonary MAC treatment through the feedback from systemic MAC complicated AIDS treatments from the latter half of 90's. We measured the sensitive strain ratio at 2 mcg/ml of OFLX, CPFX, LVFX about 990 clinical isolates and could expect availability for M. kansasii or M. fortuitum, but these new quinolones are not enough effective for MAC. Also we examined MIC for various antimycobacterial agent by 50 MAC clinical isolates, and we could expect a certain availability of SPFX, GFLX, CPFX, CAM for MAC. The availability of clarithromycin (CAM) has been established through many randomized clinical trials for disseminated MAC complicated AIDS, but for pulmonary MAC, complete cure is still difficult if we use CAM including regimen. We performed surgical treatment for relatively young patients with localized lesions. We carry out the adaptation reference such as Table, now. The localization of the lesions become a problem at surgical resection. Through the study of our 55 surgical treatment cases, 8 cases (67%) relapsed out of 12 cases which had destructive airway structure in unresected lung field. On the other, only 1 case relapsed (10%) relapsed out of 10 cases without airway destruction in unresected lung. Therefore, even if there is a little dispersal focus without airway destruction in the other pulmonary lobe except purpose focus of resection, it seems that control is possible by post operational chemotherapy. LONG SURVIVAL: As overall consequence, we calculate the survival curves of 201 pulmonary MAC patients visited Tokyo National Hospital from 1953. The survival medium value was 7332 days. The prognosis of nodular bronchiectatic type was better than that of post-tuberculosis type. Extent of disease measured by chest X-ray examination at the time of first visit may be a most affecting factor to the survival rate.     

Neutrophil CD64 for monitoring the activity of nontuberculous mycobacteria infection in patients with rheumatoid arthritis

Abstract

Objective. To evaluate the utility of neutrophil CD64 as a marker for monitoring the activity of nontuberculous mycobacteria (NTM) infection in patients with rheumatoid arthritis (RA).

Methods. We compared neutrophil CD64 expression in nine RA patients with NTM infection in the active and inactive phase of NTM disease chronologically. “Active phase” was here defined as present in patients admitted to hospital to receive intensive treatment for NTM, as well as outpatients with an infectious episode showing positive acid- and alcohol-fast bacillus (AFB) staining of sputa (Grade 2–3) who needed to start treatment for NTM with a multiple antibiotics regimen. The cut-off value for CD64 positivity was 2000 molecules/cell.

Results. Neutrophils from patients with active-phase NTM infection expressed high levels of CD64 with a mean ± SEM of 7335 ± 784 molecules/cell. However, during the inactive phase of disease, this was significantly lower (1481 ± 103 molecules/cell, p < 0.001). The sensitivity and specificity of neutrophil CD64 to detect active-phase NTM infection was 96.3% and 84.6%, respectively. Expression of neutrophil CD64 was not affected by disease activity of the RA itself.

Conclusions. Neutrophil CD64 is useful for monitoring disease activity in NTM infection of patients with RA.     

Biology and clinical use of GM-CSF in lung cancer

Administration of granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to induce an increase in production of neutrophils, monocytes, and eosinophils. This is reflected in an accelerated recovery of myelopoiesis following cytotoxic chemotherapy and radiation. Human trials completed so far have used patients with many tumor types. It was clearly demonstrated that the leukocyte responses are dose and schedule dependent and that the route of factor administration is important. The results of clinical trials suggest that the acute toxicity of cytotoxic chemotherapy may be decreased. This may result in a higher dose of drugs or in a reduction of treatment interval, and it may increase the rate of complete remissions and the number of patients with long-term disease free survival, particularly in small cell lung cancer. However, up to now a definitive statement as to the value of this supportive treatment in solid tumor chemotherapy is not possible.     

Regional differences of nontuberculous mycobacteria species in Ulsan,Korea

Background

In Korea recently, nontuberculous mycobacteria (NTM) have been more frequently isolated in respiratory specimens, while Mycobacterium tuberculosis (MTB) isolations have decreased. The major NTM lung disease species in Korea are M. intracellulare, M. avium, and M. abscessus, whereas M. kansasii is a rare species. This retrospective study was performed to determine if there are region-specific characteristics of lung disease-causing NTM species in Ulsan, a highly industrialized city in Korea.

Methods

Between January 2010 and July 2013, the results of all acid-fast bacilli (AFB) cultures of respiratory specimens performed at Ulsan University Hospital (Ulsan, Korea) were collected. NTM were identified and regional differences of NTM species were compared.

Results

AFB cultures were performed on 33,567 respiratory specimens, obtained from 10,208 patients, during the study period. Further, 10% of the specimens (3,287/33,567) were AFB culture-positive [MTB, 2,288/3,287 (70%); NTM 999/3,287 (30%)]. The proportion of NTM isolations gradually increased between 2010 and 2013, at 25% and 38%, respectively. The most common NTM species was M. intracellulare (356/999, 36%), followed by M. kansasii (295/999, 30%), M. avium (161/999, 16%), M. abscessus (117/999, 12%) and M. fortuitum (39/999, 4%). This trend was maintained throughout the study period.

Conclusions

In Ulsan, NTM isolation from respiratory specimens is increasing, consistent with previous studies performed in Korea. The distribution of respiratory NTM species, however, differed from previous studies that were performed in other regions of Korea: M. kansasii was the second most common NTM species in Ulsan. In Ulsan, there is a regional difference in the NTM species isolated.     

综合治疗晚期肺癌生存期临床研究

目的探讨晚期肺癌综合治疗的生存期。方法2000～2004年将我院住院治疗的99例晚期肺癌病人分为2个治疗组,分别接受化疗54例和化疗诱导治疗后予以手术切除的15例两种治疗模式,另有30例对症支持治疗为对照组。结果两组治疗的患者中位生存期分别为13.3±18.1个月(无手术组)和21.9±19.2个月(有手术组),对照组患者中位生存期为7.1±9.0个月。手术加化疗组1年、2年、3年生存率80%、33%、20%。化疗组为37%、18%、14%。对症组为16%、10%、3%。结论对于晚期肺癌,化疗加手术切除综合治疗其生存率显著高于单纯手术治疗,也高于化疗和对症支持治疗。综合治疗仍是肺癌治疗的主旋律。