The Prognosis Of Patients With Chronic Pulmonary Aspergillosis

Objective In recent years,chronic pulmonary aspergillosis(CPA)has attracted increasing clinical attention due to its increased incidence,delayed diagnosis,high disability rate,and heavy medical burden.Even with aggressive antifungal therapy,many patients still experience lung function decline,repeated exacerbation and even death.However,there is limited data on the long-term prognosis of patients with CPA,and the published studies failed to describe the survival of patients with different subtypes of CPA in detail.Moreover,all studies were conducted in highincome countries.In China,the largest developing country,there is a huge population of patients with tuberculosis and chronic obstructive pulmonary disease(COPD),and many CPA patients may secondary to these diseases.We searched the database of MEDLINE and the China National Knowledge Infrastructure(CNKI)to find all published studies to evaluate the long-term survival of CPA in China.Few studies were found,including one study from Hong Kong with a small sample sizes.It is important to further investigate the prognosis of CPA patients in China.Therefore,we conducted an observational study that collecting clinical and prognostic data to investigate the long-term survival of CPA patients,which may help clinicians reasonably diagnose and treat CPA patients.Methods This study is a single-center retrospective clinical review.We reviewed patients who were admitted to Nanjing Jinling Hospital,China,for medical management of CPA between January 1,2002 and January 1,2017.The diagnosis of CPA was based on the latest European guideline by Denning et al.and the case definition of the international expert panel convened by the Global Action Fund for Fungal Infections for resource-constrained settings.The subtype definition of CPA was consistent with the latest European guideline.The clinical and prognostic data of CPA patients were collected,including general information,clinical and radiological appearances on admission,antifungal therapy(including medical therapy and surgical treatment)and survival data.Survival was estimated using a Kaplan-Meier analysis,and the log rank test was used to compare survival between groups.Cox proportional hazards regression analyses were used to identify independent risk factors for mortality.Results A total of 118 patients fulfilled the diagnostic criteria of CPA.Five patients did not fulfill the required follow-up(all of these patients were diagnosed with chronic cavitary pulmonary aspergillosis(CCPA)).The final analysis was based on the data of 113 patients.The mean age was 56 years,and 67(59.3%)patients were males.Previous or current tuberculosis(n=48,42.5%)and COPD or/and emphysema(n=36,31.9%)were the most common underlying pulmonary conditions.Hypertension(n=16,14.2%)and diabetes(n=15,13.3%)were the most common systemic basic diseases.Forty-eight(42.5%)patients had bilateral lesions among the thoracic CT.One or several cavities with or without paracavitary infiltrates were seen in 74(65.5%)patients.According to the definition of different forms of CPA,11(9.7%),44(38.9%),6(5.3%),15(13.3%),and 37(32.7%)patients were diagnosed as having simple aspergilloma(SA),CCPA,chronic fibrosing pulmonary aspergillosis(CFPA),aspergillus nodule and subacute invasive asperillosis(SAIA),respectively.All patients in this study were treated after the diagnosis of CPA with internal medicine or surgical resection.Of these,68(60.2%)patients were given medicine therapy only;45(39.8%)patients underwent surgical procedures,and 19 patients were treated with preoperative or/and postoperative antifungal medicine.Patients received triazole therapy,including the administration of itraconazole and voriconazole,and short-term intravenous liposomal amphotericin B and micafungin when the symptoms worsened.The median treatment course of internal medicine for 68 patients was 5 months.In our series,SA(n=10,90.9%),aspergillus nodule(n=10,66.7%)and CCPA(n=22,50.0%)had higher rates of surgical treatment.Lobectomy(n=36,80.0%)was the most common surgical procedure.The last follow-up data was obtained on September 1,2018,and 28(24.8%)patients died over the study period.The median follow-up period of all patients was 49 months.The survival rates at 1-,5-and 10-year after admission for patients with CPA were 87.6%,77.8%and 59.1%,respectively.The 1-,5-and 10-year survival rates for SA patients were all 90.9%,respectively;for CCPA patients,the survival rates were 95.5%,93.2%and 58.4%,respectively;for CFPA patients,the survival rates at 1-and 5-year were 83.3%and 66.7%,respectively;for aspergillus nodule patients,the survival rates at 1-,5-and 10-year were all 93.3%,respectively;and for SAIA patients,the survival rates were 75.7%,54.3%and 45.3%,respectively.The median follow-up period of patients treated with surgery was 51 months,and the survival rates at 5-and 10-year were 95.6%and 86.9%,respectively.The median follow-up period of patients treated with internal medicine only was 44 months,and the survival rates at 5-and 10-year were 67.0%and 48.1%,respectively.Cox proportional hazards regression analyses were used to identify risk factors related to all-cause mortality of patients with CPA.In the univariate Cox regression model,older age,male gender,COPD or/and emphysema,diabetes,bilateral disease,and SAIA subtype were significantly related to increased death.Higher serum albumin and treatment with surgical therapy were associated with an increased probability of survival.These variables were entered into the multivariate analysis.After multivariate adjustment,age(+1 year)(HR 1.078,95%CI 1.043-1.115,p<0.001)and bilateral disease(HR 3.611,95%CI 1.443-9.037,p=0.006)were identified as independent predictors for CPA patients.Conclusions1.There were clear differences in survival rates among different subtypes of CPA,SA and aspergillus nodule patients had relatively favorable prognosis,CCPA patients had medium prognosis,and SAIA and CFPA patients had relatively poor prognosis.2.Surgical treatment for CPA patients,including patients with SA,aspergillus nodules and CCPA,were usually associated with a favorable prognosis.3.Older age and bilateral diseases were found to be undesirable prognostic factors.