Early onset of nontuberculous mycobacterial pulmonary disease contributes to the lethal outcome in lung transplant recipients: report of two cases and review of the literature.

Lung transplant (LuTx) recipients represent a population at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD). Yet the risk factors, the timing of NTM-PD after transplantation, and the association with allograft dysfunction all remain poorly defined. We report 2 cases of early-onset NTM-PD and review the literature, focusing on NTM-PD in LuTx recipients not colonized with NTM prior to transplantation. In addition, we summarize the main characteristics and differences between early- and late-onset disease.

Ki67 index is an independent prognostic factor in epithelioid but not in non-epithelioid malignant pleural mesothelioma: a multicenter study.

BACKGROUND: Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM. METHODS: Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort (n=98). RESULTS: Patients with Ki67 higher than median (>15%) had significantly (P<0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be-beside histology and treatment-an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P<0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid (P<0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort (P=0.048). CONCLUSION: This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.

SUCCESSFUL TREATMENT OF PULMONARY AND LYMPHATIC MANIFESTATIONS OF LYMPHANGIOLEIOMYOMATOSIS WITH SIROLIMUS.

Lymphangioleiomyomatosis (LAM) is a rare, progressive, diffuse cystic lung disease predominantly affecting women of child bearing age. Recently treatment with sirolimus was shown to stabilize lung function decline and improve quality of life in patients with LAM. We treated three premenopausal women suffering from LAM manifesting as diffuse cystic lung disease, chylous effusions, and lymphangioleioyomas with sirolimus (1-3 mg a day; sirolimus trough levels 2.9-8.5 ng/ml). All three patients had a remarkable response to sirolimus, with resolution of effusions, improvement in lung function and shrinking of abdominal lymphangioleiomyomas. Our case series further complements the literature in that sirolimus is a safe and effective treatment for LAM and its lymphatic manifestations.

Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma.

BACKGROUND: To investigate the clinical utility of pretreatment plasma fibrinogen levels in malignant pleural mesothelioma (MPM) patients. METHODS: A retrospective multicenter study was performed in histologically proven MPM patients. All fibrinogen levels were measured at the time of diagnosis and clinical data were retrospectively collected after approval of the corresponding ethics committees. RESULTS: In total, 176 MPM patients (mean age: 63.5 years ± 10.4 years, 38 females and 138 males) were analysed. Most patients (n=154, 87.5%) had elevated (≥ 390 mg dl(-1)) plasma fibrinogen levels. When patients were grouped by median fibrinogen, patients with low level (≤ 627 mg dl(-1)) had significantly longer overall survival (OS) (19.1 months, confidence interval (CI) 14.5-23.7 months) when compared with those with high level (OS 8.5; CI 6.2-10.7 months). In multivariate survival analyses, fibrinogen was found to be an independent prognostic factor (hazard ratio 1.81, CI 1.23-2.65). Most interestingly, fibrinogen (cutoff 75th percentile per 750 mg dl(-1)) proved to be a predictive biomarker indicating treatment benefit achieved by surgery within multimodality therapy (interaction term: P=0.034). Accordingly, only patients below the 75th percentile benefit from surgery within multimodality therapy (31.3 vs 5.3 months OS). CONCLUSIONS: Fibrinogen is a novel independent prognostic biomarker in MPM. Most importantly, fibrinogen predicted treatment benefit achieved by surgery within multimodality therapy.

Lung Abscess: An Early Complication of Lung Transplantation in a Patient with Cystic Fibrosis.

A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare complication caused by multidrug-resistant (MDR) Acinetobacter baumannii infection, after lung transplantation (LT). After 6 months of long-term antibiotic therapy, the abscess was successfully eliminated. In reviewed published literature, no previous report was found describing this kind of complication caused by MDR A. baumannii in post-LT patient with CF. In our experience, lung abscess in LT recipients with CF can be successfully treated with prolonged antibiotic therapy.

Microbiological criteria in non-tuberculous mycobacteria pulmonary disease: a tool for diagnosis and epidemiology.

SETTING: The value of microbiological criteria in diagnosing non-tuberculous mycobacteria pulmonary disease (NTM-PD) and monitoring its epidemiology is unknown. OBJECTIVES: To correlate the rate of NTM-PD based on microbiological criteria (American Thoracic Society/Infectious Diseases Society of America [ATS/IDSA] or stricter microbiological criteria) compared with the full ATS/IDSA criteria, to assess the positive predictive value (PPV) of different microbiological criteria in predicting NTM-PD, and to evaluate the clinical relevance of different NTM species. DESIGN: Retrospective study of all patients with pulmonary NTM isolates in Croatia during an 8-year period. NTM species were divided into low, intermediate and high clinical relevance groups for additional analyses. RESULTS: Good correlation between both microbiological and full ATS/IDSA criteria was observed. The PPV of stricter and ATS/IDSA microbiological criteria was respectively 93.3% and 59.8%. The usefulness of microbiological criteria varied between groups. ATS/IDSA microbiological criteria had a PPV of 89.8% in the high relevance group, while in the intermediate relevance group, the PPV of stricter and ATS/IDSA microbiological criteria was respectively 94.3% and 63.4%. CONCLUSIONS: Microbiological criteria are useful in detecting NTM-PD, allowing laboratory-based monitoring. Stricter criteria should be used for species of low clinical relevance, and less stringent criteria for species of high relevance in the local setting.

Persistent endothelial dysfunction turns the frequent exacerbator COPD from respiratory disorder into a progressive pulmonary and systemic vascular disease.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in developed countries of the world, while the main cause of mortality and morbidity in COPD patients are acute exacerbations and cardiovascular diseases. With regard to the frequency of exacerbations the phenotype "frequent exacerbators" has been defined, which, besides a more severe clinical course and a significantly higher total mortality, is also characterised by an elevated risk of cardiovascular mortality, as some indicators show us. It is notable that during the exacerbation of COPD, next to other changes, a significant aggravation of endothelial function occurs while the ED and COPD relationship seems very complex and is still in greater part unknown. Making the pathophysiological link between the frequency of exacerbations of COPD and ED could change our understanding of the character of this type of pulmonary disease. We hypothesize that frequent exacerbator COPD is a progressive and generalised vascular disease, not only an isolated respiratory disorder with ancillary systemic effects. Our opinion is that differences in COPD phenotype do not only determine the clinical picture but could also be of key importance in defining the progressivity of the disease. ED, which in these patients persists between frequent exacerbations, could be the main cause of the progression of pulmonary disease, and not only of the high cardiovascular risk of these patients. Such a persistent ED in FE COPD, with its pro-inflammatory, vasoconstrictory and prothrombotic mechanisms, could contemporaneously induce new exacerbations of COPD, the progression of pulmonary changes and the development of systemic atherosclerosis as a main extrapulmonary manifestation in these patients. Such a model defines endothelium as a common soil of progressive pulmonary and cardiovascular changes in FE COPD. It can fully explain all the elements of the clinical course and co-morbidity in FE COPD, for which we still do not have adequate explanation.

Geographical distribution and clinical relevance of non-tuberculous mycobacteria in Croatia.

SETTING: The clinical relevance of non-tuberculous mycobacteria (NTM) in Croatia is unknown. OBJECTIVE: To estimate the isolation rate of NTM, record geographical differences and assess the burden of pulmonary NTM disease in Croatia. DESIGN: Nationwide retrospective cohort study of all Croatian residents with NTM isolated by culture in the period from 2006 to 2010. Microbiological criteria of the American Thoracic Society were used to establish a laboratory-based case definition of possible and probable NTM disease. RESULTS: Of 1187 individuals with pulmonary NTM isolates, 8.6% met the possible and 5.5% met the probable disease criteria. We estimated an annual incidence of probable pulmonary NTM disease of 0.23 per 100,000 population. This estimated annual incidence was 0.35/100,000 in the coastal region and 0.17/100,000 in the continental region. Species distribution differed between coastal and continental Croatia. NTM isolation frequency increased over the study period. CONCLUSION: Geography plays an important role in NTM species distribution and possible disease. The overall burden of NTM pulmonary disease in Croatia is still low compared to that of tuberculosis, but it is higher in the coastal region compared to the continental region.