Inhalation with fucose and galactose for treatment of Pseudomonas aeruginosa in cystic fibrosis patients.

BACKGROUND: Colonisation of cystic fibrosis (CF) lungs with Pseudomonas aeruginosa is facilitated by two lectins, which bind to the sugar coat of the surface lining epithelia and stop the cilia beating. OBJECTIVES: We hypothesized that P. aeruginosa lung infection should be cleared by inhalation of fucose and galactose, which compete for the sugar binding site of the two lectins and thus inhibit the binding of P. aeruginosa. METHODS: 11 adult CF patients with chronic infection with P. aeruginosa were treated twice daily with inhalation of a fucose/galactose solution for 21 days (4 patients only received inhalation, 7 patients received inhalation and intravenous antibiotics). Microbial counts of P. aeruginosa, lung function measurements, and inflammatory markers were determined before and after treatment. RESULTS: The sugar inhalation was well tolerated and no adverse side effects were observed. Inhalation alone as well as combined therapy (inhalation and antibiotics) significantly decreased P. aeruginosa in sputum (P < 0.05). Both therapies also significantly reduced TNFalpha expression in sputum and peripheral blood cells (P < 0.05). No change in lung function measurements was observed. CONCLUSIONS: Inhalation of simple sugars is a safe and effective measure to reduce the P. aeruginosa counts in CF patients. This may provide an alternative therapeutical approach to treat infection with P. aeruginosa.

Mediastinal lymph node involvement in potentially resectable lung cancer: comparison of CT, positron emission tomography, and endoscopic ultrasonography with and without fine-needle aspiration.

PURPOSE: A prospective comparison of three imaging techniques: thoracic CT, positron emission tomography (PET), and endoscopic ultrasonography (EUS) with fine needle aspiration (FNA), each performed under routine conditions, for the detection of metastatic lymph nodes metastases in patients with lung cancer considered for operative resection. PATIENTS AND METHODS: Following bronchoscopic evaluation, CT, PET, and EUS were performed to evaluate potential mediastinal involvement in 33 consecutive patients with bronchoscopic biopsy/cytology proven (n = 25) or radiologically suspected (n = 8) lung cancer prior to surgery. Surgical histology was used as "gold standard" to confirm the diagnosis of the primary tumor and the mediastinal status in all patients. Histology proved non-small cell lung cancer in 30 patients, neuroendocrine tumor in 1 patient, and benign disease in 2 patients. RESULTS: The mean age of the study group was 61.5 years (range, 41 to 80 years; 23 male patients). CT, PET, and EUS detected mediastinal lymph nodes (size, 0.4 to 1.6 cm) in 15, 14, and 27 patients (21 of which were suspected to be malignant on EUS), respectively. With respect to the correct prediction of mediastinal lymph node stage, the sensitivities of CT, PET, and EUS were 57%, 73%, and 94%. Specificities were 74%, 83%, and 71%. Accuracies were 67%, 79%, and 82%. Results of PET could be improved when combined with CT (sensitivity, 81%; specificity, 94%; accuracy, 88%). The specificity of EUS (71%) was improved to 100% by FNA cytology (EUS-guided FNA), which gave a tissue diagnosis including tumor type, without complications. CONCLUSIONS: No single imaging method alone was conclusive in evaluating potential mediastinal involvement in apparently operable lung cancer and routine clinical conditions. A tissue diagnosis is extremely helpful. Because FNA can be performed at the same time as EUS, this combination emerged as the most useful technique in the evaluation of even very small mediastinal metastases of lung cancer. CT seems necessary additionally to evaluate the pretracheal region as well as the rest of the thorax, and PET may be valuable to detect distant metastases.

Decreased interleukin-18 expression in BAL cells and peripheral blood mononuclear cells in adult cystic fibrosis patients.

Lymphocytes from cystic fibrosis (CF) patients secrete less interferon-gamma (IFN-gamma) upon stimulation compared to controls. Expression of interleukin (IL)-18 as an IFN-gamma inducing factor and of IL-10 as an IL-18 inhibiting factor were determined in bronchoalveolar lavage (BAL) cells from CF patients (n=5) and from normal control subjects (n=9) as well as in peripheral blood mononuclear cells (PBMC) from patients (n=12) and from control subjects (n=9) with RT-PCR. IL-18 and IL-10 serum protein levels were measured using ELISA. BAL cells and PBMC of CF patients expressed significantly less IL-18 compared to controls (p<0.05). There was no significant difference for IL-10 in BAL cells. However, PBMC from patients expressed significantly more IL-10 mRNA (p<0.05). IL-18 serum protein levels were decreased in the patient group, whereas IL-10 serum concentrations were elevated. Stimulation with rhIL-10 reduced IL-18 expression in PBMC from CF patients. Decreased IL-18 expression in CF patients may contribute to decreased IFN-gamma production. IL-10 may contribute to inhibit IL-18 expression in PBMC in CF.

Increased expression of Interleukin-13 but not Interleukin-4 in cystic fibrosis patients.

BACKGROUND: Many patients with cystic fibrosis (CF) suffer from allergic disease, which can complicate treatment of CF lung disease. Interleukin (IL)-4 and IL-13 have been shown to be important mediators in allergic disease. OBJECTIVE: To investigate the role of IL-4 and IL-13 in allergic and non-allergic CF patients. METHODS: Expression of IL-4 and IL-13 mRNA was investigated in peripheral blood mononuclear cells (PBM) of seven CF patients with allergy, of six patients without allergy and of nine healthy subjects as well as in BAL cells of four patients and of all controls. PBM from six patients were incubated with recombinant human IL-13 or human antiIL-13 antibody without and with LPS stimulation and TNFalpha levels were measured by ELISA. RESULTS: IL-13 mRNA expression was increased in allergic and non-allergic patients compared to controls. No significant difference in IL-4 expression could be found between patients and controls. Addition of IL-13 decreased TNFalpha in PBM culture supernatants. CONCLUSION: Our data suggest that IL-13 rather than IL-4 might play an important role in both allergic and non-allergic CF patients. IL-13 might also compromise host defence by decreasing TNFalpha production.

Endoscopic ultrasound, positron emission tomography, and computerized tomography for lung cancer.

Staging of patients with lung cancer to determine operability is intended to efficiently limit futile thoracotomies without denying possibly curative surgery. Currently available staging tests are imperfect alone and in combination. Imaged suspected metastases often require tissue confirmation before surgery can be denied. Endoscopic ultrasound (EUS) may help identify inoperable patients by providing tissue proof of inoperability in a single staging test, with similar sensitivity for identifying inoperable patients as other staging tests. Therefore, we compared computed tomography, positron emission tomography (PET), and EUS with fine-needle aspiration under conscious sedation, each test interpreted blinded with respect to the other tests, for identifying inoperable patients in a consecutive cohort of 79 potentially operable patients with suspected or proven lung cancer. An economic analysis was also performed. Thirty-nine patients were found inoperable (a 40th patient's inoperability was missed by all preoperative staging tests). The sensitivity of computerized tomography was 43%. PET and EUS each had similar sensitivities (68 and 63%, respectively) and similar negative predictive values (64 and 68%, respectively), but EUS's superior specificity (100 vs. 72% for PET) and considerably lower expense means it may be preferred to PET early in staging to identify inoperable patients.