Prophylaxe der invasiven pulmonalen Aspergillose durch dezentrale Luftreiniger mit HEPA-Filter

Abstract

Background: Invasive pulmonary aspergillosis (IPA) is a severe complication in the treatment of haemato-oncological patients. The major risk factor is the depth and duration of neutropenia. The airborne Aspergillus conidia are ubiquitous prevalent. They are continuously inhaled by humans and can reach the alveoli in the lung. High Efficiency Particulate Air (HEPA) filters can eliminate Aspergillus conidia from the ambient air and thus reduce the exposure to them. There has been reported a positive correlation of the exposure to Aspergillus conidia and the incidence of IPA. The results of some studies suggest that the IPA incidence can be reduced by HEPA filtration of the ambient air. It is the first time that the efficacy of mobile air cleaners with HEPA filters was evaluated in a prospective randomised controlled blind trial.Objectives: (1) Evaluation of the suitability of an air cleaner(2) Analysis of historical patient data(3) Evaluation of the efficacy of mobile air cleaners with HEPA-filters to reduce the incidence of IPA in high risk patients.Study designs: (1) Analysis of documents, series of tests with an air cleaner(2) Retrospective analysis of patient records(3) Prospective randomised controlled triple-blind trial.Methods: (1) Evaluation of technical data of the air cleaner, particle measurement, sampling of airborne germs in natural or extremely high spore load, sedimentation test, tests with air cleaners with and without HEPA filters. (2) Inclusion criteria: patients with acute leukaemia, at least 18 years of age, receiving intense chemo therapy. Exclusion criteria: aspergillosis in medical history. (3) Inclusion criteria: patients who were expecting a prolonged neutropenia, at least 18 years of age. Exclusion criteria: aspergillosis in medical history. To achieve a relative risk reduction of 60% at a significance level of 0.05 and a power of 0.80 a sample size of 34 patients per group was necessary.Interventions: (1) Contamination of a room with Aspergillus spores, operating an air cleaner under different conditions.(2) -(3) The intervention group had air cleaners with HEPA filters in their rooms, while the air cleaners of the control group contained 'sham filters'. Patients in both groups were told to keep doors and windows preferably shut and to use high-efficiency masks, when leaving or airing the room.Analysis:(1) Construction of time-effect-curves. (2) and (3) Primary endpoint: IPA incidence. Secondary endpoints: length of IPA-free interval, mortality, duration of antimycotic therapy, overall length of stay.Outcomes:(1) The air cleaner was suitable. (2) 35 patients were included in the retrospective analysis. 80% of the patients suffered from acute myeloid leukemia (AML), 20% from acute lymphoblastic leukemia (ALL), 60% were male. The mean age was 58 years, the average length of neutropenia was 26.4 days. The IPA incidence was 54.29%. On average the IPA-free intervall lasted 76.6 days. 75% of all IPA cases occurred in the first 56 days after initiation of therapy. Mortality rate was 14.3%. The average length of stay in hospital was 118.8 days. IPA patients received systemic antimycotica for treatment for 31.9 days on average. (3) The prospective randomised controlled trial included 76 patients. 70 patients received the allocated treatment. 77.63% of the patients had AML, 19.74% ALL and 2.63% had a non-Hodgkin lymphoma (NHL). 59.21% of the patients were male. The mean age was 53.61 years, the average length of neutropenia was 26.4 days. The IPA incidence was 46.15% (18 of 39) in the intervention group (IG) and 54.05% (20 of 37) in the control group (CG), p = 0.49, relative risk = 0.85. The mean IPA-free interval was 81 days in the IG and 74.38 days in the CG, p = 0.65. The log rank test of the Kaplan-Meier statistics resulted in a p value of 0.39. Mortality rate was 7.69% in the IG and 18.92% in the CG, p = 0.13. Length of stay in hospital and duration of antimycotic therapy did not differ between groups (p = 0.63 and p = 0.8 resp.).Discussion: The expected efficacy of mobile air cleaners could not be verified. The outcome is consistent with outcomes of recent systematic reviews with meta-analyses, in which only non-randomised trials achieved a statistically significant reduction of the infection rate. The problem of air quality control remains unresolved in patients with acute leukemia. Due to the severity of the problem further clinical trials or adequate observational studies are needed.