Left Versus Right Destroyed Lung Pneumonectomy: Long Term Prognosis and Key Factors Associated With Poor Treatment Outcomes.

INTRODUCTION: To compare and analyze postoperative short-term and long-term prognosis of destroyed lung (DL) disease patients undergoing left versus right pneumonectomy and to identify potential key factors associated with poor treatment outcomes. METHODS: Retrospective analysis was conducted on clinical data of 128 DL patients who underwent pneumonectomy in the thoracic surgery department of the Beijing Chest Hospital from November 2001 to May 2022. Cases were assigned to two groups according to lesion site: a left pneumonectomy group (104 cases) and right pneumonectomy group (24 cases). Postoperative short-term and long-term DL disease clinical features and prognostic factors were analyzed and compared between groups. RESULTS: As compared with the left pneumonectomy group, the right pneumonectomy group experienced greater rates of preoperative diabetes, chronic pulmonary aspergillosis, intraoperative blood loss, postoperative respiratory failure, rehospitalization, tuberculosis (TB) recurrence, bronchopleural fistula (BPF) and empyema. Binary logistic regression analysis revealed a potential correlation between chronic pulmonary aspergillosis and increased odds of developing secondary respiratory failure (adjusted odds ratio: 5.234, 95% confidence interval [CI]: 1.768-15.498). Results of Cox Proportional Hazards Model regression analysis suggested that right pneumonectomy was correlated with increased odds of TB recurrence (adjusted hazard ratio: 4.017, 95% CI: 1.282-12.933) and BPF/empyema (adjusted hazard ratio: 5.655, 95% CI: 1.254-25.505). CONCLUSIONS: Compared to the group undergoing left pneumonectomy, patients with DL who undergo right-sided pneumonectomy may be at a heightened risk of experiencing secondary postoperative TB recurrence and BPF or edema. It is advised to exercise utmost caution and deliberate consideration of these potential risks when contemplating pneumonectomy, with the intention of proactively preventing adverse events.

Pulmonary cryptococcosis complicated with pulmonary aspergillosis: a series of studies and a literature review.

BACKGROUND/OBJECTIVE: With the development of society, pulmonary fungal diseases, represented by pulmonary aspergillosis and pulmonary cryptococcosis, have become increasingly common. However, there is a lack of clear understanding regarding coinfection by these two types of fungi in immunocompetent individuals. METHODS: A retrospective study from 2014 to 2022 and a systematic literature review of original articles published in English were performed. Patients with pulmonary cryptococcosis complicated with pulmonary aspergillosis including 5 in the retrospective study and 6 in the systematic literature review. RESULT: The diagnosis of concurrent pulmonary cryptococcosis and pulmonary aspergillosis in patients was confirmed through repeated biopsies or surgical resection. Pulmonary cryptococcosis is often diagnosed initially (6/11, 55%), while the diagnosis of pulmonary aspergillosis is established when the lesions become fixed or enlarged during treatment. Transbronchial lung biopsy (3/11, 27%), thoracoscopic lung biopsy (2/11, 18%), and percutaneous aspiration biopsy of the lung (1/11, 9%) were the main methods to confirm concurrent infection. Most patients were treated with voriconazole, resulting in a cure for the coinfection (6/11, 55%). CONCLUSION: Pulmonary cryptococcosis complicated with pulmonary Aspergillus is an easily neglected mixed fungal infection. During the treatment of lesion enlargement in clinical cryptococcus, we need to watch out for Aspergillus infection.

Pathological Diagnosis of Pulmonary Aspergillosis.

Pulmonary aspergillosis constitutes an increasingly prevalent and potentially fatal complex of mycotic diseases, caused by different species of Aspergillus. The broad spectrum of pathological manifestations associated with pulmonary aspergillosis necessitates a differentiation of commensalism from saprophytic colonization, hypersensitivity reactions, and true invasive infections, which highlights the importance of histopathology as a gold standard in a diagnostic setting. For the past decades, changes in terminology and contradicting contributions from different diagnostic disciplines have made the classification of pulmonary aspergillosis rather confusing. This review offers a categorization of aspergillosis lesions based on what can be histopathologically identified and distinguished, differentiating between acute invasive infection and forms of subacute, chronic, and allergic diseases and coinfections, and summarizes important manifestations of lesions associated with the different forms of pulmonary aspergillosis.

Aspergillus and the Lung.

The filamentous fungus Aspergillus causes a wide spectrum of diseases in the human lung, with Aspergillus fumigatus being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of Aspergillus in the respiratory tract is determined by the interaction between host and pathogen. In this review, an oversight of the different clinical entities of pulmonary aspergillosis is given, categorized by their main pathophysiological mechanisms. The underlying immune processes are discussed, and the main clinical, radiological, biochemical, microbiological, and histopathological findings are summarized.

Chronic Pulmonary Aspergillosis: Clinical Presentation and Management.

Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of Aspergillus organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on Aspergillus immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of Aspergillus adaptation in the lung environment, the contribution of non-fumigatus Aspergillus species, and the role of new antifungal agents, immunotherapy, and combination therapy.

Pulmonary Aspergillosis in People with Cystic Fibrosis.

In the last decade, fungal respiratory diseases have been increasingly investigated for their impact on the clinical course of people with cystic fibrosis (CF), with a particular focus on infections caused by Aspergillus spp. The most common organisms from this genus detected from respiratory cultures are Aspergillus fumigatus and Aspergillus terreus, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus nidulans. These species have been identified to be both chronic colonizers and sources of active infection and may negatively impact lung function in people with CF. This review article discusses definitions of aspergillosis, challenges in clinical practice, and current literature available for laboratory findings, clinical diagnosis, and treatment options for pulmonary diseases caused by Aspergillus spp. in people with CF.

Chronic Pulmonary Aspergillosis as a Considerable Complication in Post-Tuberculosis Lung Disease.

Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.

Antifungal Resistance in Pulmonary Aspergillosis.

Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and acute invasive pulmonary aspergillosis (IPA). In addition, chronic colonization may occur in cystic fibrosis (CF). Aspergillus fumigatus represents the main pathogen, which may employ different morphotypes, for example, conidia, hyphal growth, and asexual sporulation, in the various Aspergillus diseases. These morphotypes determine the ease by which A. fumigatus can adapt to stress by antifungal drug exposure, usually resulting in one or more resistance mutations. Key factors that enable the emergence of resistance include genetic variation and selection. The ability to create genetic variation depends on the reproduction mode, including, sexual, parasexual, and asexual, and the population size. These reproduction cycles may take place in the host and/or in the environment, usually when specific conditions are present. Environmental resistance is commonly characterized by tandem repeat (TR)-mediated mutations, while in-host resistance selection results in single-resistance mutations. Reported cases from the literature indicate that environmental resistance mutations are almost exclusively present in patients with IA indicating that the risk for in-host resistance selection is very low. In aspergilloma, single-point mutations are the dominant resistance genotype, while in other chronic Aspergillus diseases, for example, ABPA, CPA, and CF, both TR-mediated and single-resistance mutations are reported. Insights into the pathogenesis of resistance selection in various Aspergillus diseases may help to improve diagnostic and therapeutic strategies.

Microbiological Diagnosis of Pulmonary Aspergillus Infections.

As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge of the diagnostic possibilities and especially their limitations is extremely important. In this review, we aim to reflect critically on the available microbiological diagnostic modalities for diagnosis of pulmonary aspergillosis and formulate some future prospects. Timely start of adequate antifungal treatment leads to a better patient outcome, but overuse of antifungals should be avoided. Current diagnostic possibilities are expanding, and are mainly driven by enzyme immunoassays and lateral flow device tests for the detection of Aspergillus antigens. Most of these tests are directed towards similar antigens, but new antibodies towards different targets are under development. For chronic forms of pulmonary aspergillosis, anti-Aspergillus IgG antibodies and precipitins remain the cornerstone. More studies on the possibilities and limitations of molecular testing including targeting resistance markers are ongoing. Also, metagenomic next-generation sequencing is expanding our future possibilities. It remains important to combine different test results and interpret them in the appropriate clinical context to improve performance. Test performances may differ according to the patient population and test results may be influenced by timing, the tested matrix, and prophylactic and empiric antifungal therapy. Despite the increasing armamentarium, a simple blood or urine test for the diagnosis of aspergillosis in all patient populations at-risk is still lacking. Research on diagnostic tools is broadening from a pathogen focus on biomarkers related to the patient and its immune system.

Complication of Intrapulmonary Cavitary Lesions after COVID-19 Finally Proved as Pulmonary Aspergillosis.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus type 2, which is characterized by high infectiousness and diverse clinical manifestations. They are more likely to become critical in people who have underlying diseases or are immunocompromised. In the daunting task of treating patients with COVID-19, those with comorbid fungal infections are susceptible to underdiagnosis or misdiagnosis, which can ultimately lead to increased morbidity and mortality in this group of patients. We report a case of intrapulmonary cavitary lesions after COVID-19, which was eventually diagnosed as pulmonary aspergillosis (PA) by metagenomic Next Generation Sequencing (mNGS) to improve our understanding of the disease. METHODS: Appropriate laboratory tests, chest computed tomography (CT), mNGS, and serologic tests were performed for diagnosis. RESULTS: Laboratory tests showed Glactomannan (GM) of 1.41, multiple cavitary lesions in both lungs on chest CT and the presence of aspergillus infection was confirmed by sputum sent for mNGS. CONCLUSIONS: In the case of cavitary lesions after COVID-19, we should be alert to the possibility of combined fungi and should promptly perform mNGS to clarify whether there is a combination of specific pathogenic fungal infections.

Aspergillus nodules: Natural history and the effect of antifungals.

BACKGROUND: Aspergillus nodules are classified as a subset of chronic pulmonary aspergillosis. The optimal management approach is not known as their natural evolution following biopsy, the rate of progression to chronic cavitary pulmonary aspergillosis (CCPA) and the effect of antifungal treatment have not been described. OBJECTIVES: To describe the clinical course of patients diagnosed with Aspergillus nodules and the effect of antifungal treatment. PATIENTS/METHODS: We present a series of 23 patients with histologically confirmed Aspergillus nodules and describe serial imaging, antifungal treatment and progression to other diagnoses. RESULTS: Thirteen patients were diagnosed after a CT-guided biopsy and 10 after surgical resection. Among those who had CT-guided biopsy, 8 did not receive antifungal treatment; the nodule was stable or smaller in all cases on subsequent CT scan after a mean of 15.5 months. However, one patient developed squamous cell carcinoma after 16 months and another developed CCPA after 7 months. Among the 5 patients who received antifungals for at least 4 weeks, the nodule was smaller in 1 and stable in 4. One patient developed CCPA 3 years after the biopsy. No patient who had a surgical resection subsequently had a CCPA diagnosis. CONCLUSION: Most Aspergillus nodules remained stable or improved following biopsy, irrespective of the effect of antifungals. However, CCPA can develop occasionally in patients with Aspergillus nodules and ongoing radiological follow-up may be warranted when the nodule is not resected.

Effect of volume of instillate on the diagnostic utility of bronchoalveolar lavage galactomannan in patients with suspected chronic pulmonary aspergillosis-A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. OBJECTIVE: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study. PATIENTS & METHODS: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid. RESULTS: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26). INTERPRETATION: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield.

Incidence and prevalence of chronic pulmonary aspergillosis in patients with post-tuberculosis lung abnormality: Results from a community survey in North India.

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for developing chronic pulmonary aspergillosis (CPA). However, the prevalence and incidence of CPA in PTLA patients in India remain unknown. OBJECTIVES: We aimed to ascertain the incidence and prevalence of CPA in subjects with PTLA. METHODS: We identified a cohort of pulmonary tuberculosis who completed anti-tuberculosis therapy (ATT) before November 2019 from the records of the 12 tuberculosis treatment centers attached to the national program. We recorded the clinical and demographic details. We performed computed tomography (CT) of the chest and estimated serum A. fumigatus-specific IgG. We categorised subjects as PTLA with or without CPA using a composite of clinical, radiological, and microbiological features. We resurveyed the subjects at 6 months (or earlier) for the presence of new symptoms. We calculated the prevalence and the incidence rate (per 100-person years) of CPA. RESULTS: We included 117 subjects with PTLA, with a median of 3 years after ATT completion. Eleven subjects had CPA in the initial survey, and one additional case developed CPA during the second survey. The prevalence of CPA in PTLA subjects was 10.3% (12/117). The total observation period was 286.7 person-years. The median (interquartile range) time to develop CPA after ATT completion was 12.5 (5-36.7) months. We found the CPA incidence rate (95% confidence interval) of 4.2 (1.8-6.5) per 100-person years. CONCLUSION: Chronic pulmonary aspergillosis complicates 10% of PTLA subjects after successful outcomes with ATT. Four new CPA cases may develop per 100-persons years of observation after ATT completion. We suggest screening patients with PTLA who develop new symptoms for CPA.

Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

Risk Factors of Chronic Pulmonary Aspergillosis in Patients with Etiology Positive Pulmonary Tuberculosis.

Objective: Pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) have many similarities in clinical symptoms. In patients with etiology-positive pulmonary tuberculosis (EPTB), Aspergillus infection is easily overlooked, and missed diagnosis occurs. We attempted to analyze the clinical characteristics and risk factors of EPTB combined with CPA (EPTB-CPA), and to suggest to clinicians the possibility of CPA in EPTB patients. Methods: 58 patients with EPTB-CPA diagnosed and treated in Wuhan Pulmonary Hospital from April 2021 to March 2022 were retrospectively collected as the case group. According to the age group of the case group, 174 patients with EPTB were randomly selected as the control group at a ratio of 1:3. Multivariate logistic regression analysis was utilized to analyze the risk factors. Results: Multivariate Logistic regression analysis was performed on the pulmonary cavity, chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, lung damage, anemia, and hypoproteinemia. Among them, pulmonary cavity (P = .001), COPD (P = .006), and bronchiectasis (P = .020) were statistically significant. Conclusion: Our findings suggest that when EPTB patients present with pulmonary cavities and comorbidities such as COPD or bronchiectasis, clinicians should consider the possibility of CPA. Identifying these risk factors can help improve the accuracy of diagnosis and facilitate early detection and management of EPTB-CPA.

Two Different Tumors and Lung Aspergilloma: An Uncommon Etiopathogenic Association.

Several cases reported in the literature have confirmed the link between pulmonary aspergillosis and various malignant diseases. Furthermore, it has been observed that the correlation between carcinoid tumor and lung adenocarcinoma is quite uncommon. The etiopathogenic mechanisms underlying these correlations remain poorly defined. We present the case of a patient with three of these diseases: a lung adenocarcinoma with a lepidic pattern, a typical carcinoid, and pulmonary aspergillosis. An additional noteworthy aspect of this case pertains to the timely detection of both lung malignancies. Thus, the necessity for further investigation to ascertain the pathogenic connection among the three diseases is underscored. The ultimate objective is to enhance the prognosis of individuals diagnosed with lung cancer, which is a prevailing malignant disease on a global scale.

[Expert consensus on the diagnosis and treatment of pulmonary aspergillosis in patients with chronic obstructive pulmonary disease].

The prevalence of pulmonary aspergillosis is increasing in patients with chronic obstructive pulmonary disease (COPD) and can manifest in different forms such as invasive pulmonary aspergillosis (IPA), chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). With the variations of individual conditions such as immune status, these forms of the disease may transform into each other or even overlap. Moreover, the atypical clinical manifestations and the limited use of invasive sampling techniques have posed a challenge to the diagnosis and treatment of invasive pulmonary aspergillosis in patients with COPD. To provide recommendations for the management of pulmonary aspergillosis in patients with COPD and to construct a clinical workflow, the consensus panel reviewed the evidence and critically appraised the existing studies. As the majority of the recommendations were supported by low levels of evidence, the evidence levels were not listed in the consensus and the strong and weak recommendations were expressed as "recommend" and "suggest", respectively.Recommendations for COPD with IPA: The Panel recommends that high-resolution chest computed tomography (HRCT) be performed in patients suspected with IPA. If IPA cannot be excluded by CT scanning, mycological examination of sputum and bronchoalveolar lavage fluid (BALF) is recommended. Bronchoscopy and BALF Aspergillus-related examination are recommended in COPD patients with respiratory symptoms such as dyspnea despite the use of broad-spectrum antibiotics and systemic glucocorticoids and pulmonary infiltrates observed on chest CT. If the diagnosis is in doubt in patients with probable IPA, histopathological examination is recommended. In COPD patients with an acute infection of more than 10 days' duration, the Panel recommended the detection of Aspergillus-specific IgG antibodies in peripheral blood to aid in the diagnosis of IPA, especially in those who cannot obtain BALF. It is not recommended to initiate antifungal therapy based on clinical symptoms such as cough, fever, and dyspnea empirically in COPD patients. In critically ill patients (such as those admitted to ICU and those with respiratory failure) who are unresponsive to broad-spectrum antibiotic treatment and have imaging findings consistent with IPA, patients with HRCT or bronchoscopy findings consistent with airway invasive aspergillosis, patients with a history of oral or intravenous glucocorticoid use in the past 3 months, or patients with a history of airway Aspergillus infection or colonization, empirical antifungal therapy may be initiated after a comprehensive evaluation of Aspergillus infection risk, and at the same time, pathogen examination should be started as early as possible. Voriconazole, isavuconazole, and posaconazole are recommended as the first-line treatments for COPD with IPA. Echinocandins and amphotericin B may be used as alternative options. Antifungal treatment for COPD with IPA should be continued for at least 6-12 weeks. The duration of antifungal therapy should be determined based on clinical symptoms, pulmonary imaging, and microbiological test results. Significant lesion absorption and stabilization, as well as the elimination of related risk factors, are important references for discontinuation of treatment.Recommendations on COPD with CPA: Chest CT scan and dynamic observation are recommended for COPD with suspected CPA. Peripheral blood Aspergillus-specific IgG antibody testing is recommended in COPD patients with suspected CPA. For those who are difficult to diagnose by routine methods or need further differential diagnosis, pulmonary tissue histopathological examination is recommended. Oral itraconazole solution or voriconazole tablets are recommended as the first-line treatment options for COPD with CPA. Oral isavuconazole capsules or enteric-coated posaconazole tablets can be used as an alternative. Intravenous administration of echinocandins or amphotericin B (deoxycholate or lipid formulations) are suggested as a second-line treatment options in cases of triazole treatment failure, resistance, or intolerance. Antifungal treatment for COPD with CPA should be continued for at least 6 months, and for patients with CCPA for at least 9 months. In those with cavities communicating with the bronchial lumen, if systemic antifungal therapy is ineffective or cannot be tolerated due to adverse reactions, and surgery is also not feasible, the Panel suggests considering nebulized inhalation of amphotericin B and intracavitary injection of amphotericin B or azoles (voriconazole, itraconazole) to control recurrent hemoptysis.Recommendations on COPD with Aspergillus sensitization: When COPD patients present with refractory wheezing and/or rapid decline in lung function, it is recommended that an assessment for Aspergillus sensitization be performed, including Aspergillus-specific IgE, skin Aspergillus antigen test, Aspergillus-specific IgG, total IgE, blood eosinophil count, and sputum examination. The Panel recommends that antifungal therapy should not be routinely initiated in COPD patients with Aspergillus sensitization. For those who meet the diagnostic criteria for ABPA, antifungal therapy is suggested. The most commonly used medication is oral itraconazole solution, but other azoles such as voriconazole, isavuconazole and posaconazole enteric-coated tablets can also be chosen. The general course of antifungal therapy is 3-6 months.Recommendations on the use of glucocorticoids in COPD with pulmonary aspergillosis: In exacerbating COPD patients with secondary IPA or subacute invasive aspergillosis, the Panel suggests that the use of glucocorticoids should be controlled. For COPD patients with concomitant CPA who experience exacerbations with predominantly wheezing, it is suggested that short-term, low-dose glucocorticoids be considered on the basis of antifungal treatment to control symptoms. Glucocorticoid use for COPD exacerbations is suggested to be guided by peripheral blood eosinophil count. It is recommended to avoid systemic glucocorticoids and long-term or high-dose inhaled glucocorticoids (ICS) in stable COPD patients with concomitant CPA. In patients with concomitant Aspergillus sensitization and persistent wheezing despite standardized COPD treatment or patients with ABPA, the Panel recommends systemic glucocorticoids in combination with antifungal therapy and consideration of the use of ICS to reduce the dose of systemic glucocorticoids. Close monitoring for progression to IPA or subacute invasive aspergillosis is essential during treatment.

[Issues in the diagnosis and evaluation of pulmonary aspergillosis in patients with chronic obstructive pulmonary disease].

Patients with chronic obstructive pulmonary disease (COPD) may present with various forms of pulmonary aspergillosis, including invasive pulmonary aspergillosis (IPA), chronic cavitary pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis. Accurate diagnosis and disease evaluation are essential for tailoring individualized treatment strategies. Key aspects include: (1) Comprehensive assessment of IPA risk factors, with enhanced monitoring for critically ill patients; (2) Understanding the clinical manifestations and radiological features of different forms of pulmonary aspergillosis and emphasizing the importance of bronchoscopic examination; (3) Obtaining microbiological evidence whenever possible; (4) Differentiating colonization from infection to avoid overdiagnosis; (5) Vigilance for co-existing sensitization to Aspergillus. During treatment and long-term disease management, the use of inhaled or systemic corticosteroids and antifungal agents should be dynamically adjusted according to the patient's condition.

Systematic review and meta-analysis of galactomannan antigen testing in serum and bronchoalveolar lavage for the diagnosis of chronic pulmonary aspergillosis: defining a cutoff.

BACKGROUND: A clear cutoff value of galactomannan (GM) has not been established for chronic pulmonary aspergillosis (CPA) and is frequently extrapolated from invasive pulmonary aspergillosis. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of serum and bronchoalveolar lavage (BAL) GM, and to propose a cutoff. METHODS: We extracted from the studies the cutoff of serum or/and BAL GM associated with true positives, false positives, true negatives, and false negatives. We performed a multi-cutoff model and a non-parametric random effect model. We estimated the optimal cutoff and the area under the curve (AUC) for GM in serum and BAL samples. RESULTS: Nine studies from 1999 to 2021 were included. Overall, the optimal cutoff of serum GM was 0.96 with a sensitivity of 0.29 (95%CI: 0.14-0.51); specificity of 0.88 (95%CI: 0.73-0.95); and AUC of 0.529 (with a CI: [0.415-0.682] [0.307-0.713]). The AUC for the non-parametric ROC model was 0.631. For BAL GM the cutoff was 0.67 with a sensitivity of 0.68 (95%CI: 0.51-0.82), specificity of 0.84 (95%CI: 0.70-0.92), and AUC of 0.814 (with a CI: [0.696-0.895] [0.733-0.881]). The AUC for the non-parametric model was 0.789. CONCLUSION: The diagnosis of CPA requires the assessment of a combination of mycological and serological factors, as no single serum and/or BAL GM antigen test is adequate. BAL GM performed better than serum, with better sensitivity and excellent accuracy.

Detection of serum Aspergillus-specific IgM and IgG antibody levels for the diagnosis of chronic pulmonary aspergillosis developed in patients with tuberculosis.

Chronic pulmonary aspergillosis (CPA) is common among individuals with underlying lung diseases. The clinical manifestations of CPA include systemic symptoms (e.g., weight loss, fatigue, fever), chronic productive cough, chest discomfort, and occasional haemoptysis, which are similar to the manifestations of pulmonary tuberculosis (PTB) and are often misdiagnosed as PTB. Considering the striking similarities between CPA and PTB in clinical manifestations and imaging features, more specific microbiological and serological detections are needed for a definitive diagnosis. This study aimed to explore the clinical characteristics of CPA in TB as well as the diagnostic significance of Aspergillus-specific IgG and Aspergillus-specific IgM.A total of 140 patients diagnosed with TB by culture between December 2017 and February 2019 were included. Enrolled patients were categorized into two groups (CPA group and non-CPA group) according to CPA diagnostic criteria. All collected specimens were subjected to Aspergillus-specific IgG and IgM detection testing.The median concentration of Aspergillus-specific IgG in the CPA group (211.04 AU/ml) was significantly higher than that in the non-CPA group (77.88 AU/ml) (Z value - 6.397, P < 0.001). The sensitivity and specificity of Aspergillus-specific IgG for CPA diagnosis were 81.82% and 72.97%, respectively. In the chronic cavitary pulmonary aspergillosis (CCPA) group, the IgG positivity rate (≥ 120 AU/ml) was 96.2%, which was 21.4% in the non-CCPA patients (P < 0.001).The detection of Aspergillus-specific IgG serological changes is feasible and facilitates reliable differentiation between Aspergillus and Mycobacterium tuberculosis infection. However, Aspergillus-specific IgM has limited diagnostic value, with unsatisfactory sensitivity results.