[IgG4-associated lung disease with granulomatous lesions : Coexistence of two entities or the spectrum of one disease?] / IgG4-assoziierte Lungenerkrankung mit granulomatösen Läsionen : Koexistenz zweier Entitäten oder das Spektrum einer Erkrankung?

A 54-year-old patient with a history of pulmonary tuberculosis and occupational exposure to dust in early adulthood presented with symptoms of coughing with sputum, weight loss, occasional night sweats, and thoracic pain. Non-necrotizing granulomatosis in lung and lymph-node biopsies indicated sarcoidosis. Combined immunosuppressive therapy did not lead to an improvement. An atypical lung resectate with fibroinflammatory changes and obliterative endothelialitis may finally lead to the diagnosis of IgG4-associated lung disease with a bronchovascular pattern of involvement. The question discussed here is whether this is a coexistence of IgG4-associated lung disease with sarcoidosis or the spectrum of one disease.

Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study.

RATIONALE: The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears. OBJECTIVES: Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay. METHODS: Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB. CONCLUSIONS: Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.

Antimycobacterial immune responses in patients with pulmonary sarcoidosis.

INTRODUCTION: Sarcoidosis is a multisystem granulomatous disease of unknown origin. Pathogenetic involvement of Mycobacterium tuberculosis has frequently been discussed in the aetiology of sarcoidosis; however, studies still remain contradictory. OBJECTIVE: We addressed the question of mycobacterial involvement in the pathogenesis of sarcoidosis by analysing cellular immune responses to mycobacterial antigens. METHODS: We examined the interferon (IFN)-gamma production by enzyme-linked immunospot in response to purified protein derivate (PPD) mycobacterial-specific antigen early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10 by peripheral blood mononuclear cells (PBMCs) and bronchoalveolar-lavage mononuclear cells (BALMCs) of patients with pulmonary sarcoidosis, smear-negative tuberculosis and controls. RESULTS: Release of IFN-gamma in response to ex vivo contact with PPD, ESAT-6 or CFP-10 by BALMC and PBMC were comparable among patients with sarcoidosis and controls (PBMC P = 0.2326; BALMC P = 0.1767) and were less frequently observed in both groups compared to patients with tuberculosis (BALMC P < 0.05; PBMC P < 0.0001). Within PBMC, the immunophenotype of sarcoidosis patients differed from that of patients with tuberculosis, as well as from that of controls, while within BALMC it resembled that of patients with tuberculosis. CONCLUSION: In contrast to patients with tuberculosis, the frequency of mycobacteria-specific local and systemic immune responses is not elevated in patients with sarcoidosis when compared to controls. The immunophenotype represents the local resemblance of the granulomatous reaction underlying tuberculosis and sarcoidosis while showing systemical difference. These observations do not support a role of an infection with M. tuberculosis in the pathogenesis of sarcoidosis.

Development of pulmonary hypertension in adults after ventriculoatrial shunt implantation.

BACKGROUND: The insertion of ventriculoatrial (VA) shunts for the treatment of hydrocephalus is thought to be associated with the development of pulmonary hypertension in adults. OBJECTIVES: It was the aim of this study to describe the frequency and the clinical spectrum of pulmonary hypertension in adults with VA shunts. METHODS: Patients with pulmonary hypertension were retrospectively evaluated from January 1999 to December 2006. RESULTS: Among the 575 patients with pulmonary hypertension, 6 (mean age 42.5 +/- 8.3 years) were identified as having received a VA shunt. Mean pulmonary artery pressure for these patients was 53.3 +/- 14.9 mm Hg. The interval between shunt placement and the diagnosis of pulmonary hypertension was 9-27 years (median 16.5). While ventilation perfusion scans showed multiple bilateral perfusion defects in all patients, chest CT or pulmonary angiography demonstrated pulmonary thromboembolism in only 2 of the 6 patients. These 2 patients subsequently underwent pulmonary endarterectomy. Another patient required heart-lung transplantation because of severe pulmonary hypertension; lung histology showed prominent eccentric medial hypertrophy and intimal proliferation without evidence of thromboembolism. Contrary to earlier reports, outcomes were generally good, with a 100% survival rate for the first 8 years following diagnosis. CONCLUSIONS: Severe pulmonary hypertension can develop in adult patients with VA shunts. Therefore, clinicians should consider pulmonary hypertension as a potential cause for respiratory symptoms in patients who have received VA shunts.

[Antibiotic drug-resistant tuberculosis]. / Antibiotikaresistente Tuberkulose.

Tuberculosis remains to be one of the most important infectious diseases worldwide. Among the estimated 9 million new cases that are anually recorded, antibiotic drug resistance of Mycobacterium tuberculosis has become an increasing problem. Cases of multidrug resistance (MDR), by definition resistance against at least isoniazid and rifampin, are reported worldwide. Moreover, cases of extensively drug-resistant tuberculosis (XDR-TB) with additional resistance to fluoroquinolones and aminoglycosides are also emerging. Patients who are infected with MDR-TB strains need a carefully selected antibiotic combination therapy consisting of four to six alternative drugs according to the results of in vitro drug susceptibility testing. The duration of treatment against MDR-TB is cost-intensive, and is generally recommended for 18 months beyond the first time of sustained culture negativity. Patient adherence to the therapy is essential. As adverse effects of MDR-TB therapy are common, treatment of these patients should be guided by experienced physicians.

Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot.

RATIONALE: In a large proportion of patients with active pulmonary tuberculosis (pTB), acid-fast bacilli smear results for sputum and bronchial secretions are negative. Detectable growth of Mycobacterium tuberculosis (MTB) in cultures takes several weeks and MTB-specific DNA amplification results on sputum and bronchial secretions are variable in these patients. OBJECTIVE: We investigated whether a rapid diagnosis of pTB can be established by enumeration of MTB-specific mononuclear cells from bronchoalveolar lavage (BAL) fluid in routine clinical practice. METHODS: Patients presenting to a tertiary hospital with medical histories and pulmonary infiltrates compatible with tuberculosis, and negative acid-fast bacilli smear results (three) from sputum, were prospectively enrolled in this study. An MTB-specific enzyme-linked immunospot assay (ELISPOT [T-SPOT.TB; Oxford Immunotec, Abingdon, UK]) with early antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides was performed on peripheral blood mononuclear cells (PBMCs) and mononuclear cells from the BAL fluid (BALMCs). MEASUREMENTS AND MAIN RESULTS: Of 37 patients, 12 were found to have smear-negative pTB and 25 were found to have an alternative diagnosis. Patients with tuberculosis had a median number of 17 ESAT-6-specific cells and 24.5 CFP-10-specific cells per 200,000 PBMCs and 37.5 ESAT-6-specific cells and 49.5 CFP-10-specific cells per 200,000 cells in the BAL fluid. Control patients had a median of 1 ESAT-6-specific cell and 1 CFP-10-specific cell per 200,000 PBMCs and no ESAT-6- and CFP-10-specific cells per 200,000 cells in the BAL fluid (p < 0.0001). All patients with TB but none of the control subjects had more than 5 spot-forming cells per 200,000 BALMCs with either peptide in the BAL fluid ELISPOT. CONCLUSION: Smear-negative pulmonary tuberculosis can be diagnosed rapidly by identification of MTB-specific cells in the BAL fluid.