Mw Pletz

Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.

A major feature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is the accumulation of activated neutrophils in the bronchial tree. This phenomenon can be explained by an increased migration and/or by a prolonged survival due to an inhibition of spontaneous apoptosis. The aim of this study was to assess the apoptotic behaviour of peripheral blood neutrophils in COPD patients during an acute exacerbation. Thirty-six hospitalised COPD patients with an acute exacerbation and 10 healthy volunteers were included. Blood samples were obtained at admission, after 3–5 days and at discharge. Spontaneous apoptosis of isolated neutrophils was measured based on Annexin V‐PE binding and nuclear morphology after culturing for 18u2005h. At admission, significantly lower rates of spontaneous apoptosis were noted in COPD patients compared with healthy volunteers (mean±sd 31±13% versus 44±18%). The mean percentages of apoptotic neutrophils were 31±13% at admission, 39±15% after 3–5 days and 47±18% at discharge. There was a statistically significant difference between the rates of spontaneous apoptosis on the first day and at discharge. Neither forced expiratory volume in one second <35% predicted, smoking habit, corticosteroid therapy nor evidence of bacterial infection showed any influence on the spontaneous apopotosis in this study. In conclusion, during acute exacerbations of chronic obstructive pulmonary disease, neutrophil granulocytes show a reduced spontaneous apoptosis that increases progressively after treatment and clinical remission. This raises the question of the importance of neutrophil apoptosis in the development and resolution of exacerbations of chronic obstructive pulmonary disease.

Caspofungin for treatment of invasive aspergillosis in Germany: results of a pre-planned subanalysis of an international registry

BackgroundThis study is a pre-planned country-specific subanalysis of results in Germany from a multinational multicenter registry to prospectively assess real-world experience with caspofungin administered for treatment of proven or probable invasive aspergillosis (IA).MethodsData from patients treated with caspofungin for a single episode of IA were collected. Effectiveness was determined by the local investigator as favorable (complete or partial response) or unfavorable (stable disease, failure or death) at the end of caspofungin therapy. Descriptive statistics with binomial exact confidence intervals were employed.ResultsForty-two consecutive patients were identified in three German centers. Three patients (7%) had proven IA and 39/42 (93%) had probable IA (modified European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria). Forty-one patients had pulmonary IA and one had tracheal IA. Caspofungin monotherapy was received by 36/42 patients (86%); of these, 26/36 (72%) received salvage therapy. A favorable response was observed in 29/42 patients (69%; 95% CI 53 to 82%); of these, 21/29 (72%) had a complete and 8/29 (28%) a partial response. Favorable response rate was 69% in patients with monotherapy (95% CI 52% to 84%; 25/36 patients), and 67% in patients receiving combination therapy (95% CI 22% to 96%; 4/6 patients). Favorable response rate in patients with first line therapy was 64% (95% CI 31% to 89%; 7/11 patients), and 73% in patients with second line therapy (95% CI 54% to 88%; 20/30 patients). No adverse events were reported. In total, 35/42 patients (83%; 95% CI 69 to 93%) survived seven days after completion of caspofungin therapy.ConclusionsThese real-life findings in Germany are consistent with the international findings from this registry and with findings from randomized studies.

Frühe bakterizide Aktivität und Wirksamkeit von Moxifloxacin versus Isoniazid in der Behandlung der akuten Lungentuberkulose – eine prospektive, randomisierte Studie

Hintergrund: In in vitro Untersuchungen konnte gezeigt werden, dass Moxifloxacin derzeitig das aktivste Fluorchinolone gegenuber Mycobacterium tuberculosis (Mtb)ist. Allerdings existieren bisher keine ausreichenden Daten zur Wirksamkeit von Moxifloxacin bei Patienten. Wir untersuchten im Rahmen einer prospektiven, offenen, randomisierten, monozentrischen Studie den Abfall der Kolonie bildenden Einheiten pro Milliliter (cfu) von Mtb im Sputum und die fruhe bakterizide Aktivitat (EBA) von Moxifloxacin im Vergleich zu INH. Methoden: 17 immunkompetente Erwachsene mit einer aktiven und Sputum positiven Lungentuberkulose wurden vor Beginn der Standardtherapie fur 5 Tage mit Moxifloxacin (400mg/Tag; MOX, n=8) oder Isoniazid (5mg/kg KG; INH, n=9) behandelt. Die EBA ist definiert als Abfall des dekadischen Logarithmus der Kolonie bildenden Einheiten pro Milliliter im Sammelsputum innerhalb der ersten 5 Behandlungstage. Ergebnisse: Nach 5 Tagen zeigte sich in beiden Gruppen ein signifikanter Abfall der CFU/ml (INH: Tag 0=11.5×106/ml, Tag 5=1.2×106/ml, p=0.015; MOX: Tag 0=14.2×106/ml, Tag 5=0.70×106/ml, p=0.028). Es bestand kein signifikanter Unterschied zwischen den Gruppen bezuglich der fruhen bakteriziden Aktivitat. Die Studienmedikation wurde in beiden Gruppen gut vertragen. Zusammenfassung: Die in vivo Wirksamkeit von Moxifloxacin ist der von INH vergleichbar. Unter Berucksichtigung der noch kleinen Fallzahl mussen weitere Untersuchungen folgen.