FET remains as a rare but fatal disease and leads to a puzzling condition for clinicians. In our study, the proportion of FET case was 15.5% (30/194), which is significantly higher than prior reports of 7.0% conducted in Australia . The growth in the rate of FET is likely related to the increasing application of broad-spectrum antibiotics, transthoracic surgery and the number of critical or immunocompromised patients, as well as better fungal detection techniques recently . In addition, the one-year mortality was up to 33.3% (10/30) in our study, the rate was similar to the study in American, which showed the 6-week all-cause mortality of patients with FET due to Candida or Aspergillus spp. was 34%. However, Ko et al and Lin et al respectively conducted a study about FET in Taiwan, they reported that the mortality was 73.0% (49/67) from January 1990 to December 1997 and 61.9% (39/63) from October 2002 to September 2011[8, 10]. There were several possible explanations to the decrease in mortality: (1) Early administration of antifungal agents for patients with high risk for fungal infection; (2) Thoracic drainage measures were implemented in time for all of patients. Nevertheless, it is worth noting that FET still represents a very important cause of mortality.
Similar to previous studies, Candida was the most common fungal pathogens in our cohort (30/34, 91.2% vs. 47/73, 63.5%) . Candida albicans remains the major causative agent while non-Candida albicans species such as Candida glabrata, Candida tropicalis and Candida parapsilosis were not rare as FET pathogens (11/33, 33.3%). Candida tropicalis was one of most commonly-detected fungi in human gut mycobiome and was detected in 67.0% of samples based on 17 gut mycobiome studies . Notably, 4 of 5(80.0%) Candida tropicalis empyema thoracis in our study had gastrointestinal tract surgery or injury and it is believable that Candida tropicalis is commonly associated with digestive diseases. Apart from Candida, one cryptococcosis empyema thoracis case in our study was comorbid with malignancy B cell lymphoma. Cryptococcosis infection has been reported in immunocompromised patients such as HIV infection, liver cirrhosis or Bruton’s agammaglobulinemia and most cryptococcosis empyema thoracis has similarly been described in immunodeficiency patients .
A number of factors had been proved to predispose patients to fungal infection. Impaired T-cell function followed by high-dose glucocorticoid therapy, chemotherapy, or AIDS, as well as depressed neutrophil number or function were considered to increase the risk of fungal infection . But researches about factors of predispose patients to FET were limited. Masayuki N et al. studied 97 FET patients complicated with malignant tumors and indicated that previous surgical operation was a risk factor for candida infection and the presence of uncommon mold species suggested as the contamination of pleural effusion specimens . FET had been reported as a complication of operation or esophageal pleural fistula [16, 17]. Takashi I et al. found that all of candida empyema (5/5) were secondary to esophageal or gastric fistula and proposed a hypothesis that Candida spices in the pleural effusion can be an important clue for suspecting gastrointestinal tract perforation . From 194 cases of culture-positive empyema thoracis, our study identified 10 cases due to upper gastrointestinal tract perforations, rupture or fistulas including spontaneous esophagus ruptures (6 cases) and gastroduodenal perforations (4 cases), 6 of whom were diagnosed as FET and had confirmed statistical difference compared to non-FET. Those patients with gastroduodenal perforation had variable causes (portal hypertension with cirrhosis, gastric ulcer, iatrogenic perforation or duodenal trauma) and it was hard to assess the risk difference in gastroduodenal perforations with different causes duo to limited simples in this study. Candida species is a kind of normal commensals of humans throughout the entire gastrointestinal tract and can be the pathogen causing empyema when they break out the gastrointestinal tract barrier and enter the pleural cavity through esophagus rupture directly or gastroduodenal perforation . Thus, the damage of gastrointestinal tract barrier had potential risk for development of fungal infections.
Diabetes mellitus has become one of the leading chronic disease burden worldwide and the overall morbidity was estimated to be 11.6% in the China . Patients with diabetes mellitus were proven to have increased respiratory infectious risk due to inadequate clearance or the disturbance of normal pulmonary immune function . It has been reported that diabetic patients conferred a 1.71-fold increased risk of empyema thoracis without any comorbidity . A series of retrospective studies showed that the hazard of developing empyema was higher for patient with diabetes mellitus than those with chronic obstructive lung disease or chronic liver disease and cirrhosis [20, 22]. Gosiewski T et al found the quantity of candida in the feces of patients with diabetes was significantly higher compared to non-diabetic controls. However, the association between diabetes and FET has not yet been fully evaluated. Our study showed that patients with diabetes have an increased risk of FET, suggesting that diabetes mellitus could be an important risk factor for FET.