الفهرس 
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Abstract
This prospective cross-sectional analytic study had been designed to study the prevalence of different fungal species in patients presenting with different respiratory diseases in Chest Department and RICU at Assiut University Hospital which is a teaching and tertiary referral Centre in the Upper Egypt during the period from January 2013 to March 2015.
The study included 389 patients with respiratory diseases at risk for pulmonary fungal infection.They were 234(60.2%) males and 155(39.8%) females .The mean age of these participants was 54±11.3 years.
All patients were subjected to the following: History, clinical examination, radiology (Plain chest x-ray and computed tomography of chest).Routine laboratory investigationshad been done.
Mycological analysis: included direct microscopic examination and culture examination of the collectedrespiratory samples.Also, included in vitro antifungal sensitivity test, enzymatic activity (lipases, ureases…) of some fungi and mycotoxins production tests.Serologic diagnosis of fungal infection (by Human 1,3BD Glucosidase and Human Galactomannan ELISA tests) of blood and BAL samples had been done.
The following results were observed:
• 246 patients (63.2%) out of 389 patients with respiratory diseases had culture-positive for fungus and 143 patients (36. 8%) had culture- negative.
• COPD was the commonest disease among patients at risk of pulmonary fungal infection,177(45.5%) of a total 389 patients, 114 (46% out of the positive cases) patients of them had positive culture for fungal infection.
• Among the different co-morbid diseases, the common associations included diabetes mellitus (DM), liver disease, cardiovascular diseases, malignancy and renal disease.
• Diabetes mellitus was found to be the commonest co-morbid disease associated with high fungal recovery rates.
• Antibiotic therapy, mechanical ventilation, immunosuppressive therapy, corticosteroid therapy, cardiovascular diseases, ICU admission, prolonged hospital stay (> week) were risk factors for pulmonary fungal infection (ODR=285.83, P <0.001; ODR=9.88, P <0.001; ODR=4.75, P <0.001; ODR=2.96, P <0.001; ODR=2.82, P <0.05; ODR=2.69, P <0.001; ODR= 1.61, P <0.001respectively).
• Moreover, normal radiology was found in 8.2% patients by chest x-ray while CT was normal in 6.2% patients. There was a significant statistical difference between chest x-ray and CT findings (P<0.001).
• The major fungal species encountered in this study were candida species in 46.3 % followed by Aspergillus species in 33.3%.
• Candida albicans was the most predominant versus candida non albicans being isolated from 74 versus 44 patients respectively.
• Aspergillus non fumigatus percentage exceeded that of Aspergillus fumigatus. Aspergillus spp. included (A. fumigatus in 24 patients versusA. non fumigatusin 58 patients).
• BAL GM yielded a better sensitivity, specificity, positive and negative predictive values of 81%, 87.5%, 98.5% and 31.8%, respectivelythan serum GM assays and 1, 3 BD Glucan.
• Of the 177 COPD patients, there were 81(46%) COPD patients with comorbidities and 96(54%) COPD patients without comorbidities.
• The prevalence of pulmonary fungal infection was significantly higher in COPD patients with comorbidities (77.8%) compared to COPD patients without comorbidities (53%).
• COPD patients with comorbidities at risk of pulmonary fungal infection had statistically significant higher mortality rate (12.3%) than COPD patients without comorbidities (3.1%).
• 48.2% of positive culture in the sputum of patients with COPD wasfilamentous fungi.Predominantly,Aspergillus species which was present in 30.7% of patients. 28.6% of those caseswereAspergillus fumigatus. While, Aspergillus non fumigatus was isolated in 71.4%.
• There were reemergence of non fumigatus aspergillus spp. in COPD patients. Unlike in past, A.fumigatus was the predominant Aspergillus spp.
• The FEV1 % predicted was the best predictor of sensitization and hypersensitivity to A. fumigatusand was associated with reduced lung function independent of A. fumigatus sputum culture(FEV1 =22.5±13.1% predicted versus 30.8±14% predicted; mean difference 11%, 95% CI 3–20%; P =0.01)..
• According to the consensus group EORTC/MSG crieteria, there were four patients of 389 were classified as proven invasive fungal infection (IFI) whom diagnosed mainly by tissue biopsy, 55 patients of 389 patients were classified as probable IFI.While 100 patients of 389 were classified as possible IFI .The remaining 230 patients were classified as non-invasive fungal infection.
• There was statistical significant difference (P<0.001) with predominance of IFI in COPD patients, as COPD patients were 38.4 %( 61 out of 159) of the patients at risk of IFI.
• DM and antibiotics intake more than one week were major risk factors in proven IFI (P <0.01).
• There was predominance of culture isolation of aspergillus species in proven and probable IFI groups, and Aspergillus non fumigatus exceeded aspergillus fumigatus species (P <0.01). While candida species was more predominant in probable group of patients.
• The prevalence of pulmonary fungal infection was significantly higher in RICU patients (77.5%) compared to non ICU patients (56.1%) (P<0.001).
• There was a statistical significant difference as regard fungal species (P<0.001) with a high frequency of candida spp. in ICU group which was isolated from 41.9% versus 23% in non ICU patients, candida albicans exceeded non albicans.
• Aspergillus spp. was more prominent in ICU group and Aspergillus non fumigatus exceeded Aspergillus fumigatus in both groups but was higher in ICU group (P<0.05).
• Antibiotic intake was the independent risk factor of pulmonary fungal infection in ICU versus non ICU patients (P˂ 0.001).
• The overall mortality in ICU patients with super-imposed pulmonary fungal infection was higher (22.5%) than non ICU patients (3.5%) (P<0.01).
• Candida species strains were sensitive to all antifungal agents (except Itraconazole) but with varying degrees. The most active drugs were Nystatin, Amphotericin-B, and Fluconazole (degree of sensitivity was 97.8 %, 84.4% and 62.2% respectively).On the other hand,Aspergillus SP. exhibited higher susceptibility to Voriconazole and Micamine (Degree of sensitivity was 100% and 66.7%).
Recommendation and conclusion
We can conclude thatpulmonary fungal infection appears to be an important problem in patients with respiratory diseases especially patients who are admitted to the medical respiratory ICU. COPD was the commonest respiratory disease among patients at risk of pulmonary fungal infection.Also sensitization to Aspergillus fumigatus in COPD subjects was associated with lowers lung function.DM, antibiotics intake more than one week, steroid therapy and liver disease were major risk factors for pulmonary fungal infection.The BALF-GM assaymay enhance bronchoscopic identification of Aspergillus species as the cause of pulmonary disease. Moreover; IA may be considered an emerging problem in critically ill patients.
We recommend that:
• The validity of the pulmonary fungal infection data needs to be confirmed in other ICUs.
• Also,high index of suspicion for IA must be maintained in patients with COPD. Especially, COPD patients with liver cirrhosis, malnutrition, diabetes,steroid therapyand ICU patients.Those patients need early diagnosisandsuccessful treatment, and bronchoscopy must be done to demonstrate mucosal modifications and allow biopsies, as well as BAL.
• We also, recommend that use of GM ELIZA assay in BAL fluid as a promising mean of establishing early diagnosis of IA in critically ill patients.It should be available as routine investigation in hospitals.
• EORTC/MSG criteria should be followed in the background of host factors, clinical manifestation and mycological and/or serological tests to distinguish simple colonization from invasive or disseminated infection and to start antifungal therapy.
• Finally, the current value of empirical antifungal therapy; its benefit should be reduced due to the availability of effective and safer antifungal therapies and improved diagnostic and risk stratification methods.