| Research background and objectives:In recent years, as a result of rapid development of medical technology and self-adaptation of pathogens to host environment, reported number of invasive fungal infection cases in clinical practice has gradually increased. In particular, patients with malignant hematological diseases appear to be more susceptible to fugal infection, especially to invasive pulmonary fungal infection, due to combining effect attributed by various factors, such as deficits on organisms’ immune function, chemotherapy, dosage of broad-spectrum antibiotics and hormones, combined dosage of immunosuppressive drugs and so on. Fungal infection does not only exert a significant effect on the treatment of malignant hematological diseases, it may even independently cause mortality in severe cases. As the clinical features of pulmonary fungal infection are unspecific and undifferentiated, there is difficulty in confirming the etiological cause, disrupting the early diagnosis. In addition, as the primary diseases of the patients are complicated, they are often misdiagnosed, or even miss-diagnosed. Hence, any delay in the diagnosis and treatment would lead to increase of mortality rate. Therefore, study on the host factors, clinical features, medical imaging, characters, diagnosis and treatment of invasive pulmonary fungal infection in hematological diseases, in combination with a follow-up assessment on the efficacy of Itraconazole and a rise in the awareness of such complicated disease, has a significant clinical value. Method:The study mainly presented a systematic review on116cases of pulmonary fungal infection in patients with hematological diseases who had received Itraconazole treatment by our department in Qilu Hospital, Shangdong University, from March2010to January2012, including61males and55females. The subjects aged from16to78, with an average age of49.7. The study summarized the host factors, the clinical features, the medical imaging characteristics, the diagnosis, the anti-fungal treatment for pulmonary fungal infection and the efficacy of Itraconazole.Result:1. Among the116cases of invasive pulmonary fungal infection,37of them were patients with Multiple myeloma (MM),5of them were patients with severe aplastic anemia,4of them were patients with idiopathic thrombocytopenic purpura (ITP),31of them were patients with acute myeloid leukemia (AML),16of them were patients with acute lymphoblastic leukemia (ALL),15of them were patients with non-Hodgkin lymphomas (NHL) and the rest8of them were patients with myelodysplastic syndrome (MDS).2. The clinical features of these116invasive pulmonary fungal infection cases were mainly presentation of fever (94.5%), chest tightness with shortness of breath (35.6%), cough and sputum(65.8%), hypoxemia (57.5%), while the main sign was rales and rhonchi in the lung.3. Among the116patients with invasive pulmonary fungal infection,23of them were infected by sputum-cultured Aspergillus,28were infected by Candida and11were infected by unclassified fungi.4. The medical imaging manifestations showed high degree of diversity, as subpleural nodules was showed in35cases (30.2%), non-specific interstitial pneumonia in30cases (26.0%), pulmonary nodules (diameter>1cm) in23cases (20.1%), halo sign in 14cases (12.1%), the crescent sign in13cases (11.1%), exudative pleural effusion in8cases (6.9%), hollow cavity in10cases (11.6%), pulmonary consolidation in7cases (6%).5. Among the116cases,62of them were definitely diagnosed, while the other54were preliminarily diagnosed.6. All the116patients had been treated with mainlined Itraconazole for2weeks and longer. The efficacy was examined as follow:number of efficacious case was78, clinically efficacious rate was67%; while number of inefficacious case was38(33%); number of death case was16, mortality rate was14%.Conclusion:1. Combined hematological malignancies were observed in a majority of the patients, neutrophile granulocyte reduction was detected for most of the cases after treating with chemotherapy, neutrophile granulocyte deficiency was detected for some of the cases. Generally, the immune function was in poor status, while the probability of IFI was relatively higher.2. Clinical manifestations of invasive fungal infection were unspecific. Except for fever, cough and sputum, chest tightness and respiratory difficulties, patients occasionally depicted some gastrointestinal symptoms, such as nausea and vomiting, or symptoms of exhaustion, such as fatigue and night sweat. When other unspecific symptoms, other than respiratory system symptoms, were observed, fungal infection could not be excluded from the diagnosis.3. The medical imaging manifestations showed high degree of diversity. Among all the116cases in this model, typical "crescent sign" only presented in a very small proportion. Thus, clinical manifestation, host factors and history, etiological study should be taken into a comprehensive consideration for assaying the presence of fungal infection, and thus ensuring an accurate and on-time diagnosis. 4. Most of the cases were complicated with malignant diseases and risk factors. When patients were subjected to post-chemotherapeutic bone marrow suppression or latter stage of malignancies, their physical conditions were generally so poor that could not bear certain medical measure, such as bronchoscopy, surgery and so on, for determining pathological causes. Therefore, the most common and convenient medical approach should be sputum cultivation; however, the positive rate was lower.5. An early diagnosis of invasive fungal infection (IFI) and an early initiation of empirical anti-fungal treatment were both crucial to a successful treatment. As we know, clinical manifestations of IFI were unspecific. If the patients possessed host risk factors, and broad-spectrum antibiotics were inefficacious, then anti-fungal treatment should be initiated with reference to imaging evidences and laboratory assay results.6. At present, the pathological hallmark, which helped assessing the efficacy of IFI treatment as well as quantitatively evaluating the number of pathogens, was not found yet. Occurrence of fever should not be the judging criterion for the efficacy of the anti-fungal treatment. The examination of therapeutic effect was largely depended on clinical manifestation, imaging forensics and laboratory test.7. For treatment of hematological diseases complicated with invasive fungal infection, anti-fungal treatment of Itraconazole in the early stage appeared to have higher efficacy and safety. However, during the application of Itraconazole, liver function should be monitored consistently. |
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