A new protocol for multiple inhalation of IFN-gamma successfully treats MDR-TB: a case study.

SETTING: Aerosolized interferon-gamma (IFN-gamma) leads to transient conversion of sputum smears in multidrug-resistant pulmonary tuberculosis (MDR-TB). OBJECTIVE: To test long-term conversion of sputum smears using the new Jena protocol. DESIGN: Four MDR-TB patients were treated with aerosolized recombinant IFN-gamma (rIFN-gamma) twice weekly for 8 weeks and anti-tuberculosis drugs. Patients were monitored clinically and T-cell subpopulations were analyzed. RESULTS: The treatment was well tolerated. All sputum smears cleared within 6-8 weeks, and radiological signs of recovery lasted in all patients for 73-106 months (the entire follow-up period). Before treatment, a patient with a 20+ year history of TB showed no gammadelta T-cells; these cells appeared during treatment. The proportion of natural killer (NK) cells was enhanced during treatment and remained elevated. The proportion of CD4+/CD25+ T-cells in the blood rose after treatment and remained elevated at 2 and 10 months afterwards. No significant change in T-cell levels appeared in patients with a shorter history of TB, except for a tendency toward a slight increase in gammadelta T-cells during treatment. CONCLUSION: We invite further confirmation, but aerosolized rIFN-gamma plus anti-microbial treatment cured MDR-TB in this case study. The optimal dosing schedule needs to be determined.

[Respiratory failure and pulmonary fibrosis as a late side-effect after chemotherapy-induced by oxygen administration]. / Respiratorische Insuffizienz und pulmonale Fibrose als Spätfolge einer Chemotherapie-induziert durch Sauerstoffexposition.

Pulmonary fibrosis (PF) may develop following successful chemotherapy for malignancy, even if such therapy is not combined with radiotherapy. Bleomycin, which is known to induce acute pneumonitis and lung fibrosis, is especially associated with chemotherapy-induced PF, and bleomycin-induced pulmonary fibrosis can occur more than five years after such therapy. Additionally, supplemental oxygen therapy can trigger the onset of pneumonitis and lethal PF in patients who have previously received bleomycin therapy. Careful assessment of lung function via spiroergometry and arterial blood gas analysis during exercise are required if the administration of supplemental oxygen is considered. Two case reports reveal the potential lethal risk of oxygen for patients who have been treated with bleomycin: (1) a patient with successfully resected and treated basal tongue carcinoma and (2) a patient in remission after being treated for non-Hodgkin lymphoma. Single and double lung transplantation is the only therapeutic option for patients with severe, oxygen-induced PF and should be included as an indication for lung transplantation. Early recognition of pulmonary diffusion abnormalities and establishing a risk profile, as well as consequent monitoring of pulmonary function, may help to avoid or at least reduce the risk of PF induced by oxygen therapy when administered to patients who have previously been given bleomycin.

[Self assessment quality of life and lung diseases (SAQOL in patients with pulmonary carcinoma: influence to survival and impact of chronic obstructive pulmonary disease]. / Lebensqualitätsmessung mit "Selbsteinschätzung der Lebensqualität (SAQOL)" bei Patienten mit Bronchialkarzinom und COPD: Lebensqualität hat Einfluss auf Uberlebenszeit.

BACKGROUND: Lung cancer and chronic obstructive pulmonary disease (COPD) often occur concomitantly. Whilst there are several questionnaires relating to COPD that have been translated into German (CCOPDQ, CRQ, SGRQ) there is a need for a short instrument measuring the impact of the concomitant diseases or intervention on a patient's Quality of Life specifically in German language. As there is to date no genuine German questionnaire neither in general, nor in detail for both, lung cancer and the often concomitant COPD, we created and tested an appropriate single instrument. METHODS: The feasibility and validity of a short, self-administered quality of life questionnaire for use with patients diagnosed with COPD and/or pulmonary malignancies was evaluated. The 27 questions of Self Assessment Quality of Life in Lung Diseases (SAQOL) questionnaire were issued to out-patients with lung cancer (18 females, 75 males, mean 62.6 years, 18 to 81), 54 of with concomitant COPD. RESULTS: Correlations to comparable domains of the tumour-related QLQ-C30 of EORTC were good in cancer patients. Quality of life impact scores in the shorter and organ specific SAQOL domains showed even higher values than the QLQ C-30. A higher quote of Quality of life impaction was related to a poorer prognosis despite comparable tumour stages. There was a relevant impact related to the presence of COPD in addition to lung cancer. To investigate the validity in severe COPD an English version of the questionnaire was applied in the Respiratory Unit, Adelaide Australia, together with the Nottingham Health Profile in patients with long-term oxygen therapy (n = 20), which correlated well with the lung specific domains of SAQOL. CONCLUSION: We conclude that SAQOL is an easy to handle questionnaire, which shows on the one hand good correlation to the tumour-related domains of the broadly investigated and reliable QLQ C30, and on the other hand to the long-term used and valid lung specific generic Nottingham Health Profile in COPD. The important influence COPD in quality of life impact highlights the need for an organ specific questionnaire for both, lung cancer and obstructive airway disease. This important factor for quality of life alteration seems to be underestimated in other generic questionnaires or it needs the issue of at least two different and more time consuming instruments for adequate assessment. Additionally a high degree of quality of life impaction was linked to a short survival in our study patients with advanced lung cancer.

[Bronchoscopy and rhythmic disorders. Premedication with atropine-sulfate, as a rule?]. / Bronchoskopie und Herzrhythmusveränderungen. Ist eine Prämedikation mit Atropin stets erforderlich?

Ikeda has introduced flexible bronchoscopy in the seventies of the last century. Since then the over one hundred year old procedure of direct airways inspection has widely spread and enhanced the diagnostic and therapeutic means. Thus the flexible bronchoscopy has become an important part of modern medicine. The close combination of atropine as premedication with bronchoscopy is justified with the terms "cardioprotection" and reduction of mucus secretion. As there is to this date no controlled study to prove this assumption, with the start of bronchoscopy we controlled every patient with a holter-ecg for 24-hours and estimated semiquantitatively the mucus secretion during procedure by a four point scale. Consecutively 55 patients could be randomised, 25 (7 females, 18 males) in the group with and 30 (7 females, 18 males) without atropine. In the records there were no detectable significant differences between the groups with atropine (A) and without atropine (P), as well as for registered bradycardias (A: 0 vs. P: 0, minimum of heart beats A: 63.8 vs. P: 74.1 min -1) as well as for alterations of heart rhythms, e. g. SVES (A: 7.3 % vs. P: 5.5 %), VES (A: 9.0 % vs. P: 9.0 %) or a combination of SVES with VES (A: 12.7 % vs. P: 10.9 %). The same results could be seen for each single of the first twenty minutes, additionally the first and the second recorded hour and the whole registered 24 hours. Moreover the times needed to complete the bronchoscopy showed no significant difference (mean of t A: 16.8 vs. P: 15.6 min, t-minimum 10 vs. 10 min, t-maximum A: 30 vs. P: 35 min). The same absence of differences was seen in estimated endobronchial mucus secretion (mean A: 1.88 vs. P: 2.0). According to these results of our studied group, there are no reasons, why a premedication with atropine in flexible bronchoscopy in local anaesthesia should be used. Even without the administration of atropine, flexible bronchoscopy could be performed as a safe and sophisticated method in direction of not inducing relevant arrhythmia, with low impact on patients.

Bilateral symmetrical upper-lobe opacities: an unusual presentation of bronchiolitis obliterans organizing pneumonia.

A 45-year-old man was admitted with nonresolving fever, cough, and dyspnea 2 months after a common cold. His chest radiograph demonstrated bilateral symmetrical upper-lobe opacities reminiscent of tuberculosis. Transbronchial biopsy revealed inflammatory nonspecific alveolar lesions suggestive of bronchiolitis obliterans organizing pneumonia, which responded well clinically and radiologically to oral corticosteroids. Here, the case of a previously unreported radiographic manifestation of bronchiolitis obliterans organizing pneumonia is presented.

Putting priming into perspective - from cellular heterogeneity to cellular plasticity.

The concept of priming is widely used in cell biology and has come to mean the functional enhancement of a given cell by cytokines. 'Primed' cells have a number of other cellular alterations, although the relationship between functional and phenotypical diversity has not been established. Here, Claus Kroegel and colleagues discuss the dynamic nature of inflammatory-cell priming, which might be part of a broader means of comprehending cell function in disease.

Leukocyte infiltration and secretion of cytokines in pleural drainage fluid after thoracic surgery: impaired cytokine response in malignancy and postoperative complications.

STUDY OBJECTIVE: To assess the postoperative course of pleural leukocyte counts and cytokine concentrations in patients with malignant and nonmalignant lung disease who underwent thoracic surgery. PATIENTS AND INTERVENTIONS: A total of 21 patients undergoing thoracic surgery were included in the study. Twelve patients had a malignant disease, and 9 had a nonmalignant disease. Six patients underwent video-assisted thoracoscopy and 15 underwent thoracotomy. Pleural drainage fluid from the chest tubes was collected postoperatively at Oh, 3h, 6h, 12h, 24h, 48h, 72h, and 96 h. The same schedule, as well as one additional preoperative sample, was applied for blood collections. RESULTS: A trend toward lower concentrations of tumor necrosis factor-alpha (TNF-alpha), granulocytemacrophage colony-stimulating factor, and interleukin-10 was observed in patients with malignant disease compared to those without malignancy. These differences achieved significance for TNF-alpha in the drainage fluid of those patients with nonmalignant disease who had undergone formal thoracotomy. Patients with malignant disease showed significantly lower macrophage fractions in drainage fluid and lymphocyte fractions in serum. All patients with complications had malignant disease and showed the lowest cytokine concentrations, as well as the lowest fractions of both macrophages in drainage fluid and lymphocytes in serum. CONCLUSION: The data suggest that malignancy may lead to impairment of the wound-healing process via modification of the inflammatory cell infiltrate and locally released cytokines.

Evidence for eosinophil activation in bronchiectasis unrelated to cystic fibrosis and bronchopulmonary aspergillosis: discrepancy between blood eosinophil counts and serum eosinophil cationic protein levels.

BACKGROUND: Increased serum levels of eosinophil cationic protein (ECP) have been detected in adolescent patients with cystic fibrosis. However, ECP concentrations in adult patients with bronchiectasis unrelated to cystic fibrosis have not been studied. METHODS: Eosinophil numbers and serum concentrations of ECP were determined in 14 patients with known or newly diagnosed bronchiectasis and compared with age and sex matched patients with allergic bronchial asthma, chronic obstructive pulmonary disease (COPD), and controls in whom bronchiectasis or obstructive pulmonary disease could be excluded. RESULTS: Serum ECP levels were significantly raised both in patients with bronchiectasis (median (range) 22.5 micrograms/l (7-85)) and allergic asthma (35.0 micrograms/l (7-128)) compared with the sex and age matched subjects suffering from COPD (6.7 micrograms/l (1.5-28); p < 0.006) and non-obstructive normal controls (7.5 micrograms/l (3.5-19); p < 0.003). In contrast, significantly increased peripheral eosinophil numbers were observed in patients with bronchial asthma (305 x 10(6)/l; p < 0.01) but not in those with bronchiectasis (10(2) x 10(6)/l), COPD (117 x 10(6)/l), and healthy controls (101 x 10(6)/l). CONCLUSIONS: The discrepancy between eosinophil counts and eosinophil numbers in patients with bronchiectasis suggests that serum ECP levels may be more relevant in assessing local eosinophil involvement than blood eosinophil numbers.

Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype.

In order to gain insight into the role of macrophages in human lung carcinomas, we investigated material from 35 lung carcinomas and 5 healthy lungs with 4 different antibodies (CD68, MRP8, MRP14, 27E10) recognizing different macrophage subtypes. Infiltration with CD68-positive macrophages was highest and comparable in healthy lungs and lung carcinomas. Compared to healthy lungs, the infiltration of MRP8- and MRP14-positive macrophages was reduced in lung carcinomas while the number of 27E10-positive cells was enhanced. No difference in the infiltration of macrophages was observed between the different histological subtypes of carcinomas such as squamous carcinoma, small lung carcinoma, adenocarcinoma and bronchio-alveolar carcinoma. Furthermore, we present a highly suitable technique for the isolation and enrichment of macrophages from human lung carcinomas resulting in a 5-10 fold enrichment and a yield of e.g. 2-3 x 10(6) 27E10-positive macrophages/g tumor biopsy. Together with the recent findings that 27E10-positive macrophages are prevalent in early acute inflammation and release cytotoxic mediators and to inhibit tumor cell proliferation our findings suggest that 27E10-positive macrophages may play a role in antitumor cytotoxicity in human lung carcinomas.

Results after surgery in undifferentiated large cell carcinoma of the lung: the role of neuroendocrine expression.

OBJECTIVE: The objective of this study was to define the incidence of light microscopically undifferentiated large cell carcinomas, to analyze tumor stages, types of resections necessary and postsurgical survival. Additionally we tried to evaluate whether or not neuroendocrine expression influences the biological behavior of these tumors. METHODS: Light microscopic specimens of 105 patients having undergone surgery for undifferentiated large cell carcinoma were reviewed following the 1981 WHO criteria. Fifty eight cases were excluded because elements of adeno- or squamous cell carcinoma, neuroendocrine or combined patterns of histological differentiation were observed. The remaining 47 cases of pure undifferentiated large cell carcinoma were evaluated immunohistochemically for neuroendocrine differentiation using a combination of the markers neuron specific enolase, synaptophysin and chromogranin A. The hospital charts of the patients were analyzed retrospectively recording tumor stage, operative procedure, postoperative complications, postoperative adjuvant treatment procedures, actual tumor state and survival time. RESULTS: Thirteen patients (27.7%) had postsurgical tumor stage I, 5 (10.6%) stage II, 15 (31.9%) stage IIIA, 9 (19.1%) stage IIIB, and 5 (10.6%) stage IV. In 46 of 47 patients resections of lung parenchyma were performed (wedge resection n = 5, segmental resection n = 1, lobectomy n = 27, bilobectomy n = 3, pneumonectomy n = 10), in 6 patients combined with broncho- and/or angioplastic procedures. At the time of chart review 20 (42.5%) patients were still alive. The cause of death in the remaining patients was recurrent lung cancer in the majority of cases (24 or 92.30%). The overall mean survival of the 46 patients undergoing parenchymal resections was 19 months, the 3-year survival rate 31.7%. The immunohistochemical examination demonstrated expression of neuron specific enolase in 15 cases. Synaptophysin and chromogranin A were not detected in any case. For these 15 patients the mean survival was 25.6 months (+/- 4.3) and the 1-year survival rate 67% (confidence interval 43-91%) compared to 13.8 (+/- 2.1) months and 33.5% (confidence interval 15.3-51.7%) in the remainder. The difference was not significant (P = 0.06). CONCLUSIONS: The light microscopic diagnosis of undifferentiated large cell carcinoma revealed to be subject to considerable interobserver variability. Undifferentiated large cell carcinoma takes a more unfavorable clinical course than other non-small cell carcinomas. Despite lack of statistical significance, expression of neuron specific enolase appeared to be associated with less aggressive biological behavior of the respective neoplasms. Immunohistochemical evaluation of undifferentiated large cell carcinomas using a combination of neuron specific enolase, chromogranin A, and synaptophysin did not provide more therapeutically relevant information than that obtained by light microscopic assessment.

Pulmonary arteriovenous malformations. Case reports and literature review.

Pulmonary arteriovenous malformations (PAVM) represent an uncommon disease with only 500 reported cases. To emphasize the resectional surgical standard, 2 patients with PAVM and pulmonary right-to-left shunt are presented and the optional treatments discussed. One patient had suffered from a cerebrovascular accident. The other patient's diagnosis resulted from a coincidental finding in connection with an unrelated illness. Because of the risk of acutely developing complications, especially disabling or fatal cerebral ischemia, therapy is generally recommended even in asymptomatic patients. The 2 patients presented here were treated by resection. Surgical treatment with a very low risk and parenchyma-sparing technique remains the golden standard for large isolated malformations. In addition to the established and reliable operative therapy, since 1978 catheter embolization is becoming the method of choice with an increasing range of indications in those centers experienced with this technique.

Carcinosarcomas of the lung. Three case reports and literature review.

Therapy and course of pulmonary manifestations of carcinosarcomas in three patients are described. For this rare mixed tumor there is a prevalence among men between the ages of forty and seventy. Operative therapy should be employed whenever possible, because of the poor results achieved thus far using radiotherapy or chemotherapy. Carcinosarcomas were thought to have a worse prognosis than other non-small-cell bronchial carcinomas but an increasing number of reports indicate a similar clinical course and prognosis. Pneumonectomy was required for two of our patients and lobectomy was performed in the third. The period of observation extended over two years. One patient, tumor stage T4N0M0 died of his disease after seven months. The two other patients, tumor stages T3N0M0 and T2N1M0, were operated on thirty-three and thirty-five months ago respectively and are clinically disease-free and in good health.