Treatment Of Chronic Pulmonary Aspergillosis Research Articles

Anti-infective treatment of fungal infections by Candida and Aspergillus

Invasive fungal infections caused by Candida or Aspergillus are associated with ahigh mortality. Knowledge about the risk factors, diagnosis and treatment management is crucial for improving the survival of those affected. To give a practical overview about risk factors and treatment management of Candida and Aspergillus infections as well as providing an outlook on new antifungal agents. Summary of the relevant literature and recommendations on candidemia and invasive candidiasis as well as invasive and chronic pulmonary aspergillosis. The first line treatment of candidemia and invasive candidiasis are echinocandins including caspofungin, anidulafungin and micafungin. Regular blood cultures have to be taken to determine the duration of treatment. After the first negative control blood culture treatment should be continued for another 14days. The first line treatment of invasive pulmonary aspergillosis is azoles including voriconazole and isavuconazole. The duration of treatment depends on disease severity and is recommended for 6-12weeks. The duration of treatment for chronic pulmonary aspergillosis is 6-12months. Therapeutic drug monitoring is recommended for voriconazole and for posaconazole. New antifungal agents including olorofim, fosmanogepix, opelconazole, rezafungin or ibrexafungerp will broaden the therapeutic spectrum in the foreseeable future. Knowledge about risk factors and the correct treatment management is crucial for the survival of patients with invasive fungal infections.

Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is associated with significant mortality, and suboptimal antifungal treatment response. We describe predictive factors for treatment response and survival. We retrospectively analysed clinical, serological and radiological parameters at baseline and following antifungal treatment in patients with CPA and correlated with clinical and radiological response and survival. Fifty-nine patients were included with a mean age of 61 years. Thirty (51%) had a diagnosis of COPD. On clinical assessment at 6 months, 21 (36%) had clinically improved, 20 (34%) were clinically stable and 15 (25%) had deteriorated. Radiological improvement was observed in 30 (53%), stability in 11 (19%) and deterioration in 16 (28%). Only a lower C-reactive protein (CRP) at baseline was associated with a favourable clinical-radiological response. On univariate analysis, lower CRP, higher albumin, lower Aspergillus IgG and use of inhaled steroids were associated with lower mortality. An overall favourable response at 6 months was associated with lower mortality. Inflammatory markers and Aspergillus IgG were predictors of mortality in CPA. This suggests that mortality in CPA is driven mainly by the chronic fungal infection itself rather than the underlying disease, therefore early optimised treatment of CPA may lead to improved outcomes.

Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?

In regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success. Evaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA. The measurement was performed at least 7-days after initiation of therapy. The standard treatment at our institution was a 200mg capsule every 12h. We defined that an adequate serum trough concentration of itraconazole during treatment was 1-4mg/L. This study recruited 28 patients. The median value was 0.30mg/L (IQR 0.01-0.70). Only 11% (n = 3) had adequate serum concentrations based on guideline recommendation. All patients with clinical deterioration had itraconazole serum levels ≤ 0.8mg/L. The initial serum concentrations of itraconazole after capsule formulation administration were low. Increasing the dose should be considered when the itraconazole concentration is low, especially if it is ≤ 0.8mg/L, and the patient presents with clinical deterioration. Larger studies are needed to evaluate the adequate concentrations recommended for CPA.

Update on the treatment of chronic pulmonary aspergillosis

Chronic pulmonary aspergillosis is a major global infection in individuals with preexisting structural lung diseases and those with immunodeficiencies, in particular cytokine defects. Current treatment options are confined to just three drug classes, the triazoles, the echinocandins and amphotericin B. However, antifungal resistance is rapidly emerging for the triazoles, the only available oral therapy for this chronic condition. Fortunately, there are now a number of novel antifungals in the development pipeline, mostly now in Phase 3 studies, with a potential for the treatment of chronic pulmonary aspergillosis. However, almost all current randomized triazoles of novel antifungals are primarily undertaken in patients with invasive candidiasis or invasive mould infections. Given the poor outcomes from treatment with antifungals in chronic pulmonary aspergillosis, in part associated with triazole resistance, we urgently need clinical trials of novel agents either as monotherapy or in combination for this disease. In addition, there is an emerging understanding of the role of immunotherapies for the treatment of chronic pulmonary aspergillosis, especially in the context of cytokine defects. Therefore, better understanding of the role of adjunctive immunotherapies such as interferon-gamma is also required. In this review, we give an overview of current management of chronic pulmonary aspergillosis, and novel antifungals and immunotherapies for the future.

Positive correlation between voriconazole trough concentrations and C-reactive protein levels in patients with chronic pulmonary aspergillosis: A retrospective cohort study

BackgroundVoriconazole (VRCZ) is the first-line treatment for chronic pulmonary aspergillosis (CPA). VRCZ trough concentration monitoring is recommended for adequate therapy because VRCZ concentrations vary widely. However, factors associated with variations in VRCZ concentrations, especially in the same patient at different time points, have not been identified. The objective of this study was to identify factors influencing VRCZ trough concentrations. Patients and methodsThis single-center retrospective study conducted at our institute between April 2014 and August 2016 included patients with CPA who received VRCZ. Patient trough concentrations were measured more than twice while the patients received the same dose using the same administration route (defined as one series). A step-wise method and multiple regression analysis were used to test the effects of patient characteristics on VRCZ trough concentrations. ResultsSixty-nine series in 49 patients were analyzed. VRCZ was administered orally in 59 series, intravenously in 7 series, and by dry syrup in 3 series. The median VRCZ trough concentration and the median variation in VRCZ concentrations were 1.68 and 0.99 μg/ml, respectively. In the simple regression analysis, creatinine, alkaline phosphatase, C-reactive protein (CRP), and creatinine clearance significantly correlated with VRCZ concentrations. Multiple regression analysis demonstrated a significant positive correlation between CRP and VRCZ concentration (P < 0.0001). ConclusionIn patients with CPA, VRCZ concentration correlated with CRP levels in the same patients receiving the same dose of VRCZ at different time points.

The minimal important difference of six-minute walk test in subjects with chronic pulmonary aspergillosis treated with six-months of oral itraconazole.

The minimal important difference of six-minute walk test in subjects with chronic pulmonary aspergillosis treated with six-months of oral itraconazole.

Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India

Chronic pulmonary aspergillosis has a 5-year mortality of 50-80% globally, and the optimal duration of treatment for chronic pulmonary aspergillosis remains unclear. We aimed to compare the effect of 6-months of oral itraconazole with 12-months of oral itraconazole on chronic pulmonary aspergillosis clinical outcomes. In this single-centre, open-label, randomised controlled trial conducted in one chest clinic in Chandigarh, India, we screened consecutive patients with chronic pulmonary aspergillosis who were naive to antifungal treatment and randomised eligible patients, using block randomisation, to receive a starting dose of 400 mg/day of oral itraconazole for either 6 months or 12 months. There was no masking of participants or investigators. We excluded patients who were unable to provide informed consent; had an intake of any antifungal drugs for more than 3 weeks in the preceding 6 months; had active Mycobacterium tuberculosis or non-tuberculous mycobacterial pulmonary disease; and had allergic, subacute, or invasive forms of aspergillosis. The primary outcome was the proportion of patients having relapse 2 years after treatment initiation. We performed an intention-to-treat analysis for all outcomes. The study is registered with ClinicalTrials.gov, NCT03920527. We recruited participants between July 1, 2019, and Aug 31, 2021. We screened 250 patients, of which 164 were included in the trial. 81 patients were randomised to the 6-month group and 83 patients were randomised to the 12-month group. The study population was 78 (48%) women and 86 (52%) men, and the mean age of participants was 44·3 (SD 13·3) years. The proportion of patients experiencing relapse was significantly lower in the 12-month group, 31 (38%) had a relapse in the 6-month group compared with 8 (10%) in the 12-month group, with an absolute risk reduction of 0.29 [95% CI 0·16-0·40]. The mean time to first relapse was 23 months in the 12-month group, which is significantly longer than the mean of 18 months in the 6-month group (p<0.0001). There were 16 deaths in total, eight in each group. Ten (12%) of 81 patients in the 6-months group and 18 (22%) of 83 patients in the 12-months group had adverse effects, with none requiring treatment modification. Nausea and anorexia were the most common adverse events in both groups. Treatment of chronic pulmonary aspergillosis with 12 months of oral itraconazole was superior to 6 months of oral itraconazole in reducing relapses at 2 years. Itraconazole should be given for at least 12 months for treating chronic pulmonary aspergillosis. None. For the Hindi translation of the abstract see Supplementary Materials section.

Outcomes of surgery for different types of chronic pulmonary aspergillosis: results from a single-center, retrospective cohort study

BackgroundThe reported experience of surgical treatment for chronic pulmonary aspergillosis (CPA) mainly focused on simple aspergilloma (SA), few about other types of CPA. The present study aims to evaluate the outcomes of surgical treatment for different types of CPA.MethodsWe performed a retrospective analysis of 85 patients with CPA who underwent surgery from 2014 to 2020 at Shandong Provincial Chest Hospital. The patients were divided into four types, including SA, chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN). We collected and analyzed the preoperative, perioperative, and postoperative data to evaluate the outcomes of surgical treatment of different types of CPA.ResultsThe four groups had similar age (p = 0.22), symptoms (p = 0.36), lesion location (p = 0.09), VATS rate (p = 0.08), recurrence rate (p = 0.95), and had significant difference in surgical procedures (p < 0.01), time of surgery (p < 0.01), intraoperative blood loss (p < 0.01), postoperative complication (p = 0.01). CFPA (P = 0.01), longer surgical time (P = 0.001), and more intraoperative blood loss (P = 0.004) were risk factors of postoperative complication, more intraoperative blood loss (> 400 ml) was the independent risk factor (OR 13.5, 95% CI 1.6–112.1, P = 0.02). 6 patients relapsed after surgery with a recurrence rate of 7.1%. The mean time to relapse was 14.8 months (2–30 months) after surgery. Relapse occurred in 2 SA patients, 3 CCPA, and 1 CFPA, respectively, while none of the AN patients relapsed. No risk factor for recurrence was found.ConclusionsSurgical resection seems safe and effective in the treatment of SA, AN, CCPA with a low complication and recurrence rate, while surgery for CFPA should be limited to selected patients because of its higher complication rate.

A CASE OF CHRONIC PULMONARY ASPERGILLOSIS AS THE INITIAL PRESENTATION FOR SARCOIDOSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Subacute invasive pulmonary aspergillosis is a locally invasive subacute form of chronic pulmonary aspergillosis (CPA) which typically involves the upper lobes of individuals with pre-existing lung disease or immunodeficiency. Patients with chronic fibrocystic sarcoidosis are prone to CPA. We described a case of sarcoidosis complicated with CPA which was diagnosed concomitantly. CASE PRESENTATION: A 34 year old male with no past medical history presented with hemoptysis for 3 days, associated with chronic productive cough, exertional dyspnea and skin rashes over his arms and face for the past year. Physical examination revealed multiple violaceous plaque over bilateral upper arms and face; reduced breath sounds over bilateral upper zones. CT Chest revealed bilateral upper lobes cavitations, left upper lobe mass-like consolidation, approximately 2.9 cm with air crescent sign. Laboratory tests were notable for lymphopenia, ESR 43 mm/h, CD4+ count 244, Aspergillus Ag 0.6, Aspergillus IgG positive, serum ACE 178 U/L, fungal culture from bronchial alveolar lavage (BAL) isolated Aspergillus species. ANCA, Histoplasma Ag, Cryptococcal Ag, HIV Ag-Ab, Quantiferon TB, Sputum acid fast smear were negative. Endobronchial ultrasound with fine needle aspiration (FNA) of subcarinal lymph nodes showed non-caseating granuloma. Skin biopsies of upper extremities skin lesions showed non-caseating granulomas without microorganisms seen. The patient was started on Voriconazole for 3 months duration and scheduled for outpatient follow up. DISCUSSION: Patients with sarcoidosis are predisposed to CPA due to underlying pulmonary involvement especially with fibrocystic sarcoidosis in addition to the mildly immunocompromised state, as evidenced by low CD4 count. The diagnosis of CPA was made based on symptomatology (chronic productive cough, dyspnea and hemoptysis), bilateral upper lobe cavitations on CT Chest, positive Aspergillus IgG and positive BAL culture for Aspergillus species. It was a challenge in making concomitant diagnosis of Sarcoidosis as it is a diagnosis of exclusion. Diagnosis of sarcoidosis cannot be made based on the non-caseating granulomas resulted from the FNA of the lymph nodes as aspergillosis can present with similar picture. The skin rash which appeared to be plaque sarcoidosis ultimately leads us to the diagnosis of sarcoidosis after confirmation of non-caseating granuloma on skin biopsy. CONCLUSIONS: Patients with CPA typically present with background risk factors of underlying lung disease. It is essential to have a high clinical suspicion for underlying undiagnosed disease processes especially when individuals presented with CPA without any obvious risk factors. CPA is a serious complication of sarcoidosis and is associated with high mortality and morbidity. Unfortunately, there is no consensus currently on how to best treat patients diagnosed with sarcoidosis and CPA. REFERENCE #1: Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016;47(1):45-68. doi:10.1183/13993003.00583-2015 REFERENCE #2: Alastruey-Izquierdo A, Cadranel J, Flick H, et al. Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018;96(2):159-170. doi:10.1159/000489474 REFERENCE #3: Denning DW, Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis complicating sarcoidosis. Eur Respir J. 2013;41(3):621-626. doi:10.1183/09031936.00226911 DISCLOSURES: No relevant relationships by Farahnaz Anwar, source=Web Response No relevant relationships by James Choi, source=Web Response No relevant relationships by Si Yuan Khor, source=Web Response No relevant relationships by Jason Liu Liu, source=Web Response No relevant relationships by Akhil Sharma, source=Web Response No relevant relationships by Enhua Wang, source=Web Response

Anti-fungal agents in the treatment of chronic pulmonary aspergillosis: Systematic review and a network meta-analysis.

Oral itraconazole and voriconazole are currently recommended in the initial management of chronic pulmonary aspergillosis (CPA). However, only a few studies have compared outcomes with different anti-fungal agents (AFAs) in treating CPA. Herein, we perform a network meta-analysis comparing the efficacy of different AFAs in CPA. We searched the PubMed and EmBase databases to identify studies (either randomised-controlled trials [RCTs] or observational) reporting treatment outcomes with AFAs in patients of CPA. The study quality was assessed using the Newcastle-Ottawa scale (NOS). We performed a network meta-analysis to compare the relative efficacy of different AFAs in treating CPA. The primary outcome was a favourable response to treatment with AFAs. We found ten studies (718 patients) investigating different AFAs (oral AFAs [n=5], intravenous AFAs [n=5]) in the treatment of CPA. There were four RCTs and six observational studies. The studies using oral agents reported long-term outcomes (>12weeks), while those with intravenous agents provided only short-term outcomes (<6weeks). We found one study of posaconazole and none with isavuconazole for treating CPA. Amongst the oral agents, itraconazole was significantly better than supportive care and was ranked as the best oral AFA on network rank analysis. We found all intravenous AFAs to be equally effective. Intravenous echinocandins and voriconazole were ranked best for achieving a favourable treatment response. Oral itraconazole may be preferred over other azoles as the initial therapy for CPA. Amongst the intravenous agents, echinocandins and voriconazole may be preferred over amphotericin B. Randomised-controlled trials comparing different AFAs, especially the newer AFAs, are urgently needed.

Remission of hepatotoxicity in chronic pulmonary aspergillosis patients after lowering trough concentration of voriconazole.

BACKGROUNDChronic pulmonary aspergillosis (CPA) is a rare syndrome that is often accompanied by gradual lung tissue destruction. Voriconazole is usually employed as the first-line agent for CPA treatment. However, some patients can develop hepatotoxicity and often were forced to stop voriconazole treatment.AIMTo record the improving trend of liver function and the therapeutic effects in patients after lowering the trough concentration of voriconazole. METHODSThis study retrospectively analyzed 12 adult CPA patients who developed hepatotoxicity during the voriconazole treatment. In these patients, the oral dose was reduced to 3/4 or 1/2 of the standard dose (4 mg/kg, twice daily), and the lower limit of voriconazole trough concentration was maintained more than 0.5 µg/mL. The trend of remission of liver toxicity after drug reduction in 12 patients was recorded. During the same period, 25 patients who received standard doses served as the control group. Data from the two groups were collected and analyzed for different parameters such as demographic characteristics, underlying pulmonary disorders, laboratory tests, and therapeutic effect. The differences between the two groups were statistically compared.RESULTSHepatotoxicity occurred in 12 patients within 28-65 d after oral voriconazole treatment. Hepatotoxicity was mainly manifested by the significantly increased level of gamma-glutamyltransferase and a slight increase of alanine aminotransferase and aspartate aminotransferase. The oral dose of voriconazole was reduced to approximately 3 mg/kg in seven patients and approximately 2 mg/kg in five patients. The average trough concentrations for the 12 patients before and after voriconazole oral dose reduction were 3.17 ± 1.47 µg/mL (1.5-6.0 µg/mL) and 1.70 ± 0.78 µg/mL (0.6-3.3 µg/mL), respectively (P = 0.02). After lowering the trough concentrations, the hepatotoxicity was alleviated in all the patients. However, gamma-glutamyltransferase levels declined slowly. After 4 mo of treatment, 7 of the 12 patients were successfully treated in the low trough concentrations group (41.7%). Similarly, 8 of the 25 patients in the standard treatment dose group (32.0%) were effectively treated. There was no statistical difference between the groups (P = 0.72).CONCLUSIONReducing the lower limit of the voriconazole trough concentration to 0.5 µg/mL can alleviate the hepatotoxicity and maintained certain clinical efficacy in CPA patients; however, patients should be closely monitored.

Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis.

Isavuconazole is the newest triazole antifungal, and it displays a favorable pharmacokinetic and safety profile. Less is known about its long-term use in immunocompetent hosts. We performed a retrospective service evaluation of isavuconazole therapeutic drug monitoring in patients with chronic pulmonary aspergillosis. Adverse events (AEs) and dose adjustments made during routine clinical practice were recorded, and AEs were classified based on Common Terminology Criteria for Adverse Events v5.0. Forty-five patients (mean age, 64 years) had 285 isavuconazole blood drug levels measured (mean level, 4.1 mg/liter). A total of 117 measurements (41%) were performed on patients on a 100-mg daily dose instead of 200 mg, and all had blood levels of >1 mg/liter. Age (P = 0.012) and a daily dose of 200 mg versus 100 mg (P = 0.02) were independent predictors of levels of >6 mg/liter. AEs were recorded for 25 patients (56%). The mean drug level at the first measurement was 5.5 ± 2 mg/liter for patients reporting AEs, compared with 4.2 ± 1.7 mg/liter for those not reporting AEs (P = 0.032). The cutoff threshold best predictive of an AE was 4.6 mg/liter (area under the concentration-time curve, 0.710). Sixteen patients (36%) discontinued isavuconazole therapy due to AEs. Twenty-six patients (58%) continued on isavuconazole beyond 6 months. Asthma (P = 0.022) and a daily dose of 200 mg versus 100 mg (P = 0.048) were associated with AEs of grade 2 or higher. A reduced daily dose (100 mg versus 200 mg) of isavuconazole resulted in satisfactory drug levels in a substantial number of patients; it was better tolerated and enabled continuation of therapy for prolonged periods.

Optimising the cut-off of the Bordier Aspergillus IgG ELISA for the diagnosis of chronic pulmonary aspergillosis

Aspergillus IgG detection is an essential tool in the diagnosis and treatment of chronic pulmonary aspergillosis (CPA), and is often positive in allergic bronchopulmonary aspergillosis and Aspergillus bronchitis. The Bordier ELISA had an 83.3% sensitivity (identical to ImmunoCap at a cut-off of 40mgA/L) and 97.3% specificity using a cut-off of 0.9 and a diagnostic accuracy of 90.9%.

A Collaborative Tale of Diagnosing and Treating Chronic Pulmonary Aspergillosis, from the Perspectives of Clinical Microbiologists, Surgical Pathologists, and Infectious Disease Clinicians.

Chronic pulmonary aspergillosis (CPA) refers to a spectrum of Aspergillus-mediated disease that is associated with high morbidity and mortality, with its true prevalence vastly underestimated. The diagnosis of CPA includes characteristic radiographical findings in conjunction with persistent and systemic symptoms present for at least three months, and evidence of Aspergillus infection. Traditionally, Aspergillus infection has been confirmed through histopathology and microbiological studies, including fungal culture and serology, but these methodologies have limitations that are discussed in this review. The treatment of CPA requires an individualized approach and consideration of both medical and surgical options. Most Aspergillus species are considered susceptible to mold-active triazoles, echinocandins, and amphotericin B; however, antifungal resistance is emerging and well documented, demonstrating the need for novel therapies and antifungal susceptibility testing that correlates with clinical response. Here, we describe the clinical presentation, diagnosis, and treatment of CPA, with an emphasis on the strengths and pitfalls of diagnostic and treatment approaches, as well as future directions, including whole genome sequencing and metagenomic sequencing. The advancement of molecular technology enables rapid and precise species level identification, and the determination of molecular mechanisms of resistance, bridging the clinical infectious disease, anatomical pathology, microbiology, and molecular biology disciplines.

Intravenous therapy for chronic pulmonary aspergillosis: A systematic review and meta-analysis.

Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening debilitating lung disease necessitating long-term oral antifungal treatment. However, development of antifungal-resistant isolates of Aspergillus and major toxicities requiring discontinuation of treatment limits their use. Intravenous (IV) antifungals are an option in this group of patients. We comprehensively evaluate the response rates to IV antifungals in the management of CPA. We searched Medline and Embase databases to select clinical studies providing information about IV amphotericin B or an echinocandin for the treatment of CPA from inception to May 2020. Reviews, single-case reports and case series reporting <10 patients were excluded. We evaluated 12 eligible studies. A total of 380 patients received amphotericin B (n=143) or an echinocandin (n=237) and were included in the meta-analysis. In a pooled analysis, overall response to IV antifungals was 61% ((95% confidence interval (CI): 52%-70%; I2 =73.3%; P<.001), to amphotericin B was 58% (95% CI: 36%-80%; I2 =86.6%; P<.001) and to echinocandins was 62% (95% CI: 53%-72%; I2 =63.6%; P<.001). Amphotericin B courses were usually doses at slightly <1mg/Kg (deoxycholate) or 3mg/Kg (liposomal) for 2-3weeks. Micafungin doses varied from 12.5 to 300mg (frequently, 150mg) daily for at least 3weeks, and sometimes much longer. Liposomal amphotericin B was well tolerated, but led to renal function loss in 25% of patients. Adverse events were observed in 5-35.3% of patients receiving echinocandins, none of which was considered major. Intravenous antifungals have a place in the management of CPA. A head-to-head comparison of amphotericin B and echinocandins is lacking, and future studies should look at evaluating short- and longer-term outcomes of these agents.

CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry.

Chronic pulmonary aspergillosis (CPA) is a chronic fungal infection of the lung associated with high morbidity and mortality. The CPA Research network (CPAnet) registry established in 2018 is an international multicenter collaboration aiming to improve CPA knowledge and patient care. This study’s aim was to describe the data collection process and content of CPAnet registry with preliminary clinical data. In the CPAnet registry, clinical data are collected through a web-based questionnaire. Data include CPA phenotype, comorbidities, treatment, outcome, and follow-up from several international centers. An exemplary descriptive analysis was performed on 74 patients, who were registered online before April 2020. CPA patients were predominantly (72%) male, 39% had chronic obstructive pulmonary disease, and 68% had a history of smoking. Chronic cavitary pulmonary aspergillosis was the most common CPA subtype (62%). In 32 patients (52%), voriconazole was the preferred first-line therapy. The multicenter multinational CPAnet registry is a valuable approach to gather comprehensive data on a large study population and reflects real-world clinical practice rather than focusing on specific patient populations in more specialized centers. Additional CPA reference centers are being encouraged to join this promising clinical research collaboration.

Intrathoracic Muscle Flap Transposition for the Management of Chronic Pulmonary Aspergillosis

The management of chronic pulmonary aspergillosis remains a challenge for thoracic and reconstructive surgeons. Different management options have been proposed with no consensus regarding the best treatment modality. The goal of this study is to report our experience with the use of intrathoracic muscle flaps for the management of pulmonary aspergillosis. We retrospectively reviewed all patients who underwent intrathoracic muscle flap transposition for the management of pulmonary aspergillosis between 1990 and 2010. Demographics, surgical characteristics, and treatment outcomes were collected and analyzed. A total of 39 patients who underwent 48 muscle flaps were identified. The majority were classified as ASA 3 (n=30, 77%) or ASA 4 (n=8, 21%). Serratus anterior was the most common flap used (n=34), followed by latissimus dorsi (n=6) and pectoralis major (n=5). Flap loss was encountered in three (8%) patients (2 partial, 1 total). Bronchopleural fistula and empyema comprised the two most common intrathoracic complications (26%, 29% respectively). Median follow-up was 33 months (range, 0-216). Successful treatment was achieved in 77% of patients, while operative mortality was 23%. The use of intrathoracic muscle flaps can be a helpful adjunct to surgical resection in the treatment of chronic pulmonary aspergillosis with low rates of flap loss.

Clinical outcomes of patients with chronic pulmonary aspergillosis managed surgically.

Surgical resection is one treatment modality for chronic pulmonary aspergillosis (CPA), and sometimes a preoperative presumption of lung cancer turns out to be CPA. We have audited our surgical experience with regard to risk factors for relapse, and the value of postoperative monitoring of Aspergillus-immunogolubulin G (IgG) titres. All patients with CPA surgically treated at National Aspergillosis Centre (NAC), Manchester, UK (2007-2018), were retrospectively evaluated. Surgical procedures, underlying disorders, Aspergillus-IgG titres (ImmunoCap) and antifungal therapy were evaluated for symptom control, operative complications, CPA relapse and mortality. A total of 61 patients with CPA (28 males, 33 females) were operated on primarily for antifungal therapy failure (51%, n = 31) and presumed lung malignancies (38%, n = 23). Procedures included lobectomy (64%, n = 39), wedge resection (28%, n = 17), segmentectomy (n = 3), pneumonectomy (n = 3) and decortication (n = 2). Overall, 25 (41%) patients relapsed, 26 months (standard deviation: 24.8 months) after surgery. Antifungal therapy before surgery (P = 0.002) or both before and after surgery (P = 0.005) were protective for relapse. The relapse rate within 3 years after surgery (33%, n = 20) was higher than the 3-10 years after surgery (8%, n = 5). At the end of follow-up, the median Aspergillus-IgG titre was lower than at relapse in 12 patients (67 vs 126 mg/l) (P = 0.016). Surgery in these selected patients with CPA resulted in favourable outcomes. Relapse is common after surgical treatment of CPA but can be minimized with antifungal therapy, emphasizing the importance of an accurate diagnosis prior to surgery.

Successful Treatment of Chronic Pulmonary Aspergillosis With Isavuconazole

Successful Treatment of Chronic Pulmonary Aspergillosis With Isavuconazole

Chronic pulmonary aspergillosis in a tertiary care centre in Spain: A retrospective, observational study.

The aim of this study was to describe the characteristics of patients with chronic pulmonary aspergillosis (CPA) in a tertiary care centre in Spain. Retrospective cohort study of all patients diagnosed with CPA between January 2010 and December 2015. The patients were identified through the Microbiology Registry. Demographic, clinical, laboratory, radiological, microbiological and clinical data were recorded. Patients were followed up for 12months. Fifty-three patients were included; median age was 61.5years. Forty-seven had a lung condition, 25 suffered from COPD, 19 an active malignancy, 10 had previous pulmonary tuberculosis and 9 lung interstitial disease. Twenty-eight patients presented with chronic cavitary pulmonary form (CCPA) and 20 with subacute invasive aspergillosis (SAIA). Species identified were Afumigatus (34), Aniger (5), Aterreus (4) and Aflavus (3). All-cause 1-year mortality was 56%. Predictors of mortality were cancer history (OR, 9.5; 95% CI, 2.54-35.51; P<0.01) and SAIA (OR, 5.49; 95% CI, 1.49-19.82; P<0.01). Previous pulmonary tuberculosis, surgery for the treatment of CPA and CCPA were found to be associated with lower mortality (OR, 0.05; 95% CI, <0.01-0.47; P<0.01; OR, 0.16; 95% CI, 0.03-0.88; P=0.035 and OR 0.2, 95% CI, 0.01-0.67; P=0.01, respectively). This is the first study providing an overview of the features of CPA in patients from Spain. CCPA was the most frequent form of CPA and Afumigatus the most frequently isolated species. Patients with cancer history and SAIA had a worse prognosis.