Chronic Necrotizing Pulmonary Aspergillosis Research Articles

Clinicomycological Study of the Spectrum of Pulmonary Aspergillosis at a Tertiary Care Hospital in Central India.

Knowing the spectrum, prevalence, and modes of diagnosis of pulmonary aspergillosis (PA) will be beneficial to clinicians for its early diagnosis and management. This study aims to estimate the prevalence, spectrum, and role of serological tests and radiological findings in the diagnosis of PA. A total of 150 patients were suspected of having PA after obtaining relevant clinical history and radiological imaging. The patients were grouped into each spectrum of PA as invasive PA (IPA), chronic necrotizing PA (CNPA), aspergilloma, allergic bronchopulmonary aspergillosis (ABPA) based on predisposing factors, clinical and radiological findings, and the guidelines of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG). Samples (bronchoalveolar lavage (BAL), sputum, blood) were collected from these patients and processed in a microbiology lab. BAL and sputum were subjected to microscopy by potassium hydroxide mount, calcofluor white mount, and culture. The serum was separated from blood by centrifugation and subjected to specific serological tests based on the spectrum of PA that the patient was suspected to have. For IPA, serum and BAL galactomannan antigen enzyme-linked immunosorbent assay (ELISA) was performed. For CNPA and aspergilloma, the anti-Aspergillus IgG antibody ELISA was performed. For ABPA, the tests performed were total immunoglobulin E (IgE) ELISA, Aspergillus fumigatus-specific IgE ELISA, and anti-Aspergillus immunoglobulin G (IgG) antibody ELISA. After compiling the clinical, radiological, culture, and serological findings, patients were diagnosed to have a particular spectrum of PA. The prevalence of IPA was 1.4%, CNPA was 4%, ABPA was 3.2%, and aspergilloma was 2.9%. CNPA was the predominant spectrum of PA in our study. Culture positivity for Aspergillus species was seen the highest in aspergilloma patients, followed by IPA, ABPA, and CNPA patients. A. fumigatus was the most common causative agent of PA, except for IPA for which Aspergillus flavus was the most common causative. Aspergillus niger and Aspergillus terreus were less the frequent causes of PA. A combination of radiological, microbiological, and serological tests along with clinical correlation is needed to confirm the diagnosis of PA.

Diagnostic Laboratory Features and Performance of an Aspergillus IgG Lateral Flow Assay in a Chronic Pulmonary Aspergillosis Cohort.

Chronic pulmonary aspergillosis (CPA) is a chronic and progressive fungal disease with high morbidity and mortality. Avoiding diagnostic delay and misdiagnosis are concerns for CPA patients. However, diagnostic practice is poorly evaluated, especially in resource-constrained areas where Aspergillus antibody testing tools are lacking. This study aimed to investigate the diagnostic laboratory findings in a retrospective CPA cohort and to evaluate the performance of a novel Aspergillus IgG lateral flow assay (LFA; Era Biology, Tianjin, China). During January 2016 and December 2021, suspected CPA patients were screened at the Center for Infectious Diseases at Huashan Hospital. A total of 126 CPA patients were enrolled. Aspergillus IgG was positive in 72.1% with chronic cavitary pulmonary aspergillosis, 75.0% with chronic necrotizing pulmonary aspergillosis, 41.7% with simple aspergilloma, and 30.3% with Aspergillus nodule(s). The cavitary CPA subtypes had significantly higher levels of Aspergillus IgG. Aspergillus IgG was negative in 52 patients, who were finally diagnosed by histopathology, respiratory culture, and metagenomic next-generation sequencing (mNGS). Sputum culture was positive in 39.3% (42/107) of patients and Aspergillus fumigatus was the most common species (69.0%, 29/42). For CPA cohort versus controls, the sensitivity and specificity of the LFA were 55.6% and 92.7%, respectively. In a subgroup analysis, the LFA was highly sensitive for A. fumigatus-associated chronic cavitary pulmonary aspergillosis (CCPA; 96.2%, 26/27). Given the complexity of the disease, a combination of serological and non-serological tests should be considered to avoid misdiagnosis of CPA. The novel LFA has a satisfactory performance and allows earlier screening and diagnosis of CPA patients. IMPORTANCE There are concerns on avoiding diagnostic delay and misdiagnosis for chronic pulmonary aspergillosis due to its high morbidity and mortality. A proportion of CPA patients test negative for Aspergillus IgG. An optimal diagnostic strategy for CPA requires in-depth investigation based on real-world diagnostic practice, which has been rarely discussed. We summarized the clinical and diagnostic laboratory findings of 126 CPA patients with various CPA subtypes. Aspergillus IgG was the most sensitive test for diagnosing CPA. However, it was negative in 52 patients, who were finally diagnosed by non-serological tests, including biopsy, respiratory culture, and metagenomic next-generation sequencing. We also evaluated a novel Aspergillus IgG lateral flow assay, which showed a satisfactory performance in cavitary CPA patients and was highly specific to Aspergillus fumigatus. This study gives a full picture of the diagnostic practice for CPA patients in Chinese context and calls for early diagnosis of CPA with combined approaches.

Case series of invasive lung infections by Aspergillus species and zygomycosis among post COVID-19 and post-transplant individuals.

Airborne pathogens like Aspergillus bring the lungs in the frontline for defense. Pulmonary diseases caused by Aspergillus species are broadly classified as aspergilloma, chronic necrotizing pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA), and bronchopulmonary aspergillosis. Intensive care unit (ICU) admission is required for a large number of patients associated with IPA. It is not yet known whether patients with coronavirus disease 2019 (COVID-19) are at a similar risk for IPA as for influenza. However, usage of steroids plays a leading role in COVID-19. The family Mucoraceae includes filamentous fungi of the order Mucorales, causing a rare opportunistic fungal infection known as mucormycosis. The most commonly reported clinical presentations of mucormycosis are rhinocerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and others. Here, we report a case series of invasive pulmonary infection by various fungi like Aspergillus niger, Aspergillus fumigatus, Rhizopus oryzae, and Mucor species. Specific diagnosis was made based on microscopy, histology, culture, lactophenol cotton blue (LPCB) mount, and chest radiography and computed tomography (CT). To conclude, opportunistic fungal infections like those due to Aspergillus species and mucormycosis are most commonly associated with hematological malignancies, neutropenia, transplant patients, and diabetes. Therefore, early diagnosis by direct microscopy, surgical interventions, and effective antifungal treatment form the ideal management for invasive fungal infections like aspergillosis and mucormycosis, instead of waiting for the culture reports.

CHRONIC CAVITARY PULMONARY ASPERGILLOSIS IN A PATIENT WITH IDIOPATHIC PULMONARY FIBROSIS

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Chronic cavitary pulmonary aspergillosis (CCPA) is a rare form of aspergillosis involving patients with structural lung diseases. Here we will describe a case of CCPA in a patient with idiopathic pulmonary fibrosis (IPF), which is rarely reported. CASE PRESENTATION: The patient was a 78-year-old male with a medical history significant for IPF diagnosed 13 years prior, on oral pirfenidone and long-term oxygen therapy, who presented to the hospital for worsening shortness of breath, productive cough, and fatigue of two months duration. The patient was initially hospitalized in another facility for the above symptoms where he received two courses of antibiotics without significant improvement. Chest examination showed bilateral fine inspiratory crackles, worse on the right side. The results of routine blood tests were normal. The nasal swab for the respiratory viral panel was negative. Chest X-ray showed fibrotic lung disease with a superimposed alveolar and interstitial process involving the lung bases and right upper lobe. Computed Tomography (CT) scan of the chest was suggestive of a thick-walled cavitary lesion in the right apex measuring 4.8 x 3.3 cm, enlarged mediastinal and right hilar lymph nodes along with other chronic changes. Three sets of sputum acid-fast bacilli (AFB) smears along with serum Quantiferon TB gold plus test were negative. The patient was empirically started on intravenous (IV) ceftriaxone and azithromycin. Later, blood and sputum cultures were reported negative for bacteriological growth. Interestingly, the sputum cultures were positive for Aspergillus species along with positive serum Aspergillus immunoglobulin (Ig)G level. The patient was diagnosed with CCPA based on the serology, culture results, and radiological findings. IV antibiotics were discontinued and the patient was started on oral posaconazole 300 mg daily resulting in clinical improvement. Currently, the patient is on a 6-month posaconazole regimen. DISCUSSION: Pulmonary aspergillosis is a common opportunistic infection that can present as aspergilloma, allergic bronchopulmonary aspergillosis, CCPA, and invasive pulmonary aspergillosis based on lung changes. Mycobacterium infection and obstructive lung diseases are the most frequent underlying pulmonary diseases that are associated with CCPA. However, IPF with CCPA is rare, and its clinical features and radiological findings lack specificity leading to delays in diagnosis and treatment. Once confirmed, the treatment is straightforward with long-term triazole antifungals. CONCLUSIONS: In a patient with IPF, presenting with rapidly progressing radiologic findings suggestive of pulmonary cavitation, CCPA should be considered in the differential diagnosis. REFERENCE #1: Liu C, Yang J, Lu Z. Idiopathic pulmonary fibrosis with chronic necrotizing pulmonary aspergillosis: a case report. Int J Clin Exp Pathol. 2019 Jul 1;12(7):2653-2656. PMID: 31934094; PMCID:PMC6949565 REFERENCE #2: Graham KG, Nasir A. Chronic Cavitary Pulmonary Aspergillosis: A Case Report and Review of the Literature. Am J Case Rep. 2019 Aug 18;20:1220-1224 doi: 10.12659/AJCR.915893. PMID: 31422416; PMCID: PMC6711266. REFERENCE #3: Sehgal IS, Dhooria S, Muthu V, Prasad KT, Agarwal R. An overview of the available treatments for chronic cavitary pulmonary aspergillosis. Expert Rev Respir Med. 2020 Jul;14(7):715-727. doi: 10.1080/17476348.2020.1750956. Epub 2020 Apr 20. PMID: 32249630. DISCLOSURES: No relevant relationships by Rabab Elmezayen, source=Web Response No relevant relationships by Syed yousaf Shah, source=Web Response

A review on antifungal agents against Candida albicans and Aspergillus niger

Candidiasis is the fungal infection caused by Candida albicans. It causes different type of candidiasis infections in the blood, heart, eyes, brain, bones also other parts of our body. Different types of candidiasis are vaginal candidiasis, pulmonary candidiasis, oral candidiasis. It may be acute or chronic. It can be cured by using natural compounds or synthetic compounds or semisynthetic compounds. Apergillosis is the fungal infections in human caused by Aspergillus niger. Aspergillosis infections are classified into allergic pulmonary sinusitis, cutaneous aspergillosis, invasive aspergillosis, chronic necrotising pulmonary aspergillosis can be cured by using synthetic compounds like intravenous injections, oral medicines of capsules, tropical medicines like creams and some other natural products from plants. Natural products like saponins, flavonoids, alkaloids, xanthones, lectins and polypeptides, quinones, terpenoids, coumarins, essential oils and other compounds are the secondary metabolites extracted from the plants. Those plants are effective against fungal infections. Synthetic drugs like Azole group of drugs composed of imidazoles which includes miconazole, clotrimazole, ketoconazole, and triazoles include itraconazole, Posaconazole, isavuconazole are used to inhibit the ergosterol synthesis of cell membrane of fungi. Echinocandins are antifungal agent and it is used to disrupt the cell wall of fungi and inhibiting the synthesis of beta- 1,3 glucan fungal cell wall. Echinocandins are classified into caspofungin, anidulafungin, micafungin which having antifungal activity and amphotericin B used to treat both candidiasis and aspergillosis. Combination of drugs like synthetic drugs and natural compounds used to treat Candidiasis and Aspergillosis. Comparison and effectiveness of drugs depends upon the infections they are getting affected. Amphotericin B and azole group of drugs are commonly more effective than other group of drugs, but ketoconazole is widely used. Adverse effects of antifungal agents include, skin rashes, irritation, itching, nausea and vomiting, fever, abdominal pain, muscle and joint pain, etc.

The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis

BackgroundThe prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and non-CF bronchiectasis. MethodsNext generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls. ResultsITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with non-CF bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20.4%), whereas in non-CF bronchiectasis sputum Candida albicans (21.8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp. ConclusionThis study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases.

A case of chronic cavitory pulmonary aspergillosis, a rare entity

Aspergillus species cause a wide spectrum of pulmonary disease including allergic, saprophytic, semi-invasive and invasive aspergillosis. Host immune system is the major determinant of the pattern of illness in human beings. Several chronic forms of Aspergillus infections have been described which include chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrotic pulmonary aspergillosis (CFPA) and chronic necrotizing pulmonary aspergillosis (CNPA). Chronic cavitary pulmonary aspergillosis usually runs a progressive course, affects apparently immunocompetent individuals with a pre-existing lung disease. Diagnosis depends on presence of constitutional and pulmonary symptoms, suggestive radiological changes and microbiological or serological evidence of Aspergillus infection. We hereby present a case of 28 years immunocompetent male who had prior history of pulmonary tuberculosis and was subsequently diagnosed as chronic cavitary pulmonary aspergillosis.

The Fungal Airway Microbiome in Cystic Fibrosis and Bronchiectasis

Background: The prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and bronchiectasis. Methods: Next generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls. Findings: ITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20·4%), whereas in bronchiectasis sputum Candida albicans (21·8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp. This study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases. Funding Statement: The project was supported by the Asmarley Trust, the Wellcome Trust and the NIHR Respiratory Disease Biomedical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust, Imperial College London. IF was supported by an NIHR PhD studentship. Declaration of Interests: The authors have no conflicts of interests to disclose. Ethics Approval Statement: The study was approved by the Royal Brompton and Harefield Hospital Biomedical Research Unit Ethics Committee (Advanced Lung Disease Biobank Study Number: 10/H0504/9).

A CASE OF CHRONIC PULMONARY ASPERGILLOSIS IN A HEALTHY IMMUNOCOMPETENT PATIENT

SESSION TITLE: Chest Infections: Find the Fungus SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/21/2019 3:15 PM - 4:15 PM INTRODUCTION: Chronic pulmonary aspergillosis (CPA), and specifically its most common form – chronic cavitary pulmonary aspergillosis (CCPA) - is an uncommon pulmonary disease (1). It may be seen in either patients are who are immunocompromised or patients who are immunocompetent with underlying lung disease. We present a case of CCPA complicated by recurrent hemoptysis necessitating surgical resection in a healthy 19-year-old female without known underlying lung disease. CASE PRESENTATION: A 19 year-old female presented with one month of hemoptysis. She was healthy, without any known medical problems until age 17 when she was found to have a mycetoma and cavitary pneumonia. She underwent an extensive workup, including HIV and Quantiferon Gold testing, at that time which was negative and was treated with antibiotics. She was unable to complete a prolonged course of voriconazole due to financial constraints. Interval imaging demonstrated multiple cavitary lesions with air fluid levels and soft tissue density consistent with aspergilloma. She was asymptomatic between age 17 and 19, when she began to experience hemoptysis. The patient presented to our hospital with persistent hemoptysis. She underwent robotic video-assisted thorascopic surgery (VATS) with right lower lobectomy. The parenchyma was noted to contain numerous cystic cavities. Histological examination demonstrated free-floating aspergillus hyphae within a cyst wall. Although not definitive, the aspergilloma may have formed in an area of interlobar pulmonary sequestration or congenital cystic adenoid malformation. Five days following surgery, the patient had no further hemoptysis and was discharged home. DISCUSSION: CCPA is a common form of CPA, which also encompasses aspergillus nodules, simple aspergilloma, and subacute invasive aspergillosis (SAIA) or chronic necrotizing pulmonary aspergillosis. Left untreated, CCPA may progress to chronic fibrosing pulmonary aspergillosis (CFPA), which is characterized by extensive pulmonary fibrosis. It is exceedingly unusual for CCPA to develop in immunocompetent individuals without underlying pulmonary disease. Our patient is a young and healthy female who had no prior respiratory symptoms who presented at the age of 17 with an already formed aspergilloma. Oral antifungal therapy is considered standard of care for treatment of CCPA (1). Response is slow and requires a minimum of four months. Hemoptysis may necessitate surgical resection in those with adequate pulmonary function. CONCLUSIONS: CCPA may occur in imunnocompetent patients with no prior history of lung disease. The possibility of the presence of a previously unknown and asymptomatic congenital malformation may increase the risk for the development of 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;47:45-68. DISCLOSURES: No relevant relationships by Craig Fryman, source=Web Response No relevant relationships by Sameer Khanijo, source=Web Response No relevant relationships by Kelvin Wong, source=Web Response

Investigation of Virulence Factors by "Omics" Approaches

Aspergillus fumigatus is the predominant fungal pathogen responsible for life-threatening systemic infections in humans. Recently developed high-throughput whole genome sequencing (WGS) and RNA-Seq technologies have proven to be powerful tools for systematically investigating pathogenic organisms. In this review, we present new virulence factors obtained through our "omics" researches on A. fumigatus. We first sequenced genomes of A. fumigatus stains isolated from one infected patient at different time points, and made an important finding that although the genome (microsatellites) type of the infected strain remained unchanged, the strain exhibited several genetic changes, including acquiring therapeutic drug resistance, during patient treatment for 1.5 years. Of the various presentations of aspergillosis, pulmonary aspergilloma (PA) is one of the most common forms of A. fumigatus infection, where fungus balls are composed of fungal hyphae, inflammatory cells, fibrin, mucus, and tissue debris. Chronic necrotizing pulmonary aspergillosis (CNPA), also known as semi-invasive or invasive aspergillosis, is locally invasive and predominantly seen in patients with mild immunodeficiency or with a chronic lung disease. We compared genomes of strains individually isolated from eight PA and eight CNPA patients in Japan, and found that the PA and CNPA strains show indiscernible genetic and ancestral backgrounds as far as genomic SNPs of the strains are concerned. The main route of infections caused by A. fumigatus is via inhalation of conidia. Inhaled conidia rapidly adhere to pulmonary epithelial cells. Nevertheless, little is known of the molecular mechanism of adherence in A. fumigatus resting conidia. We assumed corresponding adhesion molecules were highly expressed in high-adhesion conidia during conidia maturation, and exhaustively searched adhesion molecules by comparing gene expression levels in high- and low-adherence strains using the RNA-Seq technique. We found several factors involved in conidial adhesion and suggest that composite actions of these molecules have roles in conidial adhesion to human pulmonary epithelial cells.

Clinical, radiological, and microbiological profile of pulmonary aspergillosis in treated cases of pulmonary tuberculosis

Context: Clinical studies about detailed spectrum of aspergillosis in treated tuberculosis (TB) patients are lacking. Hence, a study was undertaken at the Institute of Respiratory Disease, Jaipur, Rajasthan, India. Treated patients of pulmonary TB having any symptom such as hemoptysis, cough with expectoration, weight loss, and whose chest X-ray showed residual cavitation were enrolled for the study. Aims: This study aimed to determine the prevalence of pulmonary aspergillosis in treated cases of pulmonary TB and to study the social, demographical, and clinical characteristics of these patients. Settings and Design: A descriptive type of observational study was conducted at the Department of Respiratory Medicine in a tertiary care center of Rajasthan. Subjects and Methods: This descriptive type of observational study was conducted on seventy patients, whose sputum or bronchial wash showed isolation of Aspergillus. Demographic details, predisposing factors, and clinical findings were noted. Statistical Analysis Used: Data collected were entered into Excel spreadsheet and quantitative data were expressed as number and percentage. Results: The presentation of pulmonary aspergillosis in treated cases of pulmonary TB varies from aspergilloma (57%) to chronic necrotizing pulmonary aspergillosis (36%) to allergic bronchopulmonary aspergillosis (7%). The most common symptom was recurrent hemoptysis. Most of the patients were farmers by occupation, but no significant comorbid illness was seen. X-ray chest missed about 70% of cases. The most common species were Aspergillus fumigatus; others were Aspergillus terreus (13%), Aspergillus flavus (13%), and Aspergillus niger (7%). Conclusions: All treated cases of pulmonary TB presenting with recurrent hemoptysis and/or cough with expectoration should be evaluated in detail for pulmonary aspergillosis as chest X-ray alone can miss the diagnosis.

Chronic Pulmonary Aspergillosis Progressing to Invasive Disease

SESSION TITLE: Fungal Infections 1 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Pulmonary aspergillosis has a wide clinical spectrum. Distinctions can be made between invasive versus non-invasive disease and chronic versus acute disease; this helps guide treatment and follow-up. Our patient proposes an interesting discussion; she presents with an overlapping chronic clinical picture with features of both invasive (Chronic Necrotizing Pulmonary Aspergillosis (CNPA)) and non-invasive (Chronic Pulmonary Aspergillosis (CPA)) disease. CASE PRESENTATION: A 74-year old lady with a history of breast cancer (status-post lumpectomy and radiation), COPD, and smoking, presented complaining of fatigue and cough. A lesion in the chest was incidentally appreciated on screening mammogram. A chest X-ray demonstrated a nodule in the right upper lobe (RUL) of the lung. Suspecting malignancy, a PET scan was done demonstrating nodules in the RUL, right middle lobe, and left upper lobe, with imaging favoring an inflammatory versus malignant process. She was treated for an upper respiratory tract infection. On six week follow-up, her symptoms persisted and a CT-scan showed new nodules in the RUL and lingula. Needle biopsy showed fungal colonization, necrosis and giant cell reaction with adjacent fibrosis. Subsequent testing revealed elevated Aspergillus fumigatus IgE levels, normal IgG levels and negative Galactomannan antigen. She was treated with Itraconazole and remained stable without progression of disease. DISCUSSION: Pulmonary Aspergillosis often presents with non-specific symptoms overlying chronic respiratory disease. Our patient presented with cough and fatigue in the background of COPD and chest radiation. But for incidental mammogram findings, her symptoms could have been attributed to chronic disease and diagnosis may have been missed. A high index of suspicion is needed for timely intervention to prevent progression of disease. Classically, CPA presents with non-progressive nodules, fungal balls or peri-cavitary infiltration. Whereas CPNA presents with progressive infiltrates cavitating over 3 months or less. Our patient presented with lung nodules suggestive of nodular CPA. Subsequent development of new nodules indicated progression, raising suspicion for CPNA. Ultimately, biopsy findings did not demonstrate the cavitation characteristically seen in CPNA. Given concern for invasive disease, anti-fungals were prescribed. CONCLUSIONS: This unique case places the concept of CPA and CPNA being distinct entities under scrutiny. It suggests that they may represent a spectrum of the same disease. Our patient’s progression from non-invasive to invasive Aspergillosis could be attributed to localized pulmonary immunodeficiency secondary to emphysematous lung disease and radiation. It is important to suspect a necrotizing process with risk of fibrosis or invasion in patients with CPA, especially if localized lung immunosuppression is suspected. Reference #1: Pulmonary aspergillosis: a clinical review. Kousha M1, Tadi R, Soubani AO. Eur Respir Rev. 2011 Sep. DISCLOSURE: The following authors have nothing to disclose: Reema Qureshi, Patricia Russo-Magno No Product/Research Disclosure Information

Diagnosis and treatment of chronic pulmonary aspergillosis: clinical guidelines of European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society

Chronic pulmonary aspergillosis (CPA) is infrequent respiratory disease which is difficult for diagnosis and can complicate other respiratory diseases and conditions. Currently, there are about 240,000 CPA patients in Europe. The most prevalent variant of CPA is chronic cavitary pulmonary aspergillosis (CCPA) which could progress to chronic fibrosing pulmonary aspergillosis (CFPA) when is untreated. Aspergillus nodules and single aspergilloma are less frequent clinical variants of this disease. All clinical variants of aspergillosis could be found in nonimmunocompromised patients with different underlying pulmonary disorders. Subacute invasive pulmonary aspergillosis, which was referred to as chronic necrotising pulmonary aspergillosis, is the most rapidly progressive clinical variant of the infection (< 3 months); it is typically diagnosed in moderately immunocompromised patients and should be treated as invasive aspergillosis. Diagnosis and management of CPA patients were previously described in sporadic guidelines. Due to this, expert group have been convened to develop clinical, radiological and microbiological guidelines. Diagnosis of CPA requires a combination of the following criteria existing for 3 months or more: one or more cavities in the lungs with or without fungal mass inside or nodules found on radiological examination; direct evidence of Aspergillus infection (using microscopic examination or biopsy culturing) or immunological response to Aspergillus spp. and exclusion of alternative diseases. Antibodies against Aspergillus spp. (precipitins) are increased in > 90% of patients. Aspergilloma should be resected if technically possible; videoassisted thoracic surgery is preferable. Chronic cavitary pulmonary aspergillosis requires longterm oral antifungal therapy to improve the patients' health and respiratory symptoms, to arrest haemoptysis and prevent the disease progression. Azole serum concentration and drug interaction should be thoroughly monitored to avoid toxic effects. Haemoptysis could be arrested using therapy with tranexamic acid or bronchial artery embolization; surgical resection of the lung is rarely required. Haemoptysis could indicate therapeutic failure and / or resistance to antifungals. Patients with a single Aspergillus nodule need antifungal therapy only if surgical resection is impossible. Antifungal therapy could be beneficial in patients with multiple Aspergillusis nodules; these patients need careful followup.

Complications of chronic necrotizing pulmonary aspergillosis: review of published case reports.

ABSTRACTChronic necrotizing pulmonary aspergillosis (CNPA), a form of chronic pulmonary aspergillosis (CPA), affects immunocompetent or mildly immunocompromised persons with underlying pulmonary disease. These conditions are associated with high morbidity and mortality and often require long-term antifungal treatment. The long-term prognosis for patients with CNPA and the potential complications of CNPA have not been well documented. The aim of this study was to review published papers that report cases of CNPA complications and to highlight risk factors for development of CNPA. The complications in conjunction associated with CNPA are as follows: pseudomembranous necrotizing tracheobronchial aspergillosis, ankylosing spondylarthritis, pulmonary silicosis, acute respiratory distress syndrome, pulmonary Mycobacterium avium complex (MAC) disease, superinfection with Mycobacterium tuberculosis, and and pneumothorax. The diagnosis of CNPA is still a challenge. Culture and histologic examinations of bronchoscopically identified tracheobronchial mucus plugs and necrotic material should be performed in all immunocompromised individuals, even when the radiographic findings are unchanged. Early detection of intraluminal growth of Aspergillus and prompt antifungal therapy may facilitate the management of these patients and prevent development of complications.

Conversion of aspergilloma to chronic necrotizing pulmonary aspergillosis following treatment with sunitinib: A case report.

Semi-invasive or invasive aspergillosis occurring following chemotherapy with sunitinib is a rare condition with unknown incidence and prognosis. Here, we report a case involving a 59-year-old male who had a history of underlying stable aspergilloma and was newly diagnosed with metastatic renal cell carcinoma. Following surgical resection for renal cell carcinoma and adjuvant chemotherapy with sunitinib for 8 months, the patient presented with hemoptysis. Chest computed tomography revealed an increased soft tissue mass and air crescent sign of the underlying aspergilloma, combined with consolidation and bronchial artery hypertrophy around the lesion. The patient underwent bronchoscopy with a biopsy of the lesion and was eventually diagnosed with chronic necrotizing pulmonary aspergillosis, which had progressed from the underlying stable aspergilloma. This case highlights the fact that clinicians should be aware of the risk of opportunistic conversion from stable aspergilloma to invasive fungal infections in patients undergoing sunitinib treatment.

Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ~240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include: Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months. Aspergillus antibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferably via video-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with single Aspergillus nodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.

Recent advances in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a slowly progressing pulmonary syndrome caused by Aspergillus spp. Specific knowledge regarding the disease entity, diagnosis method, and management is needed. This review focuses on the recent advances in our understanding of CPA. A new clinical disease entity of chronic progressive pulmonary aspergillosis consisting of chronic necrotizing pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis is proposed. Although newer antifungals are not available, evidence describing the treatment of CPA is accumulating. Longer administration of azoles is required for a better prognosis, but there is a risk of inducing azole resistance. Therapeutic drug monitoring and patient education are required. Establishing a drug-susceptibility test that can be performed in the general laboratory and the referral center are also important. Although the number of publications regarding CPA is growing, there are still many unanswered questions. Additional evidence and translational research regarding diagnosis, management, and drug resistance are urgently needed to improve the outcome of CPA.

Hemoptysis due to fungus ball after tuberculosis: A series of 21 cases treated with hemostatic radiotherapy.

BackgroundIn patients who are not amenable to surgical resection (cavernostomy), it is difficult to achieve palliation of hemoptysis from pulmonary aspergilloma. There are only 9 cases with a short follow-up that have reported the use of radiotherapy for hemoptysis in this scenario.MethodsA retrospective series of 21 patients with chronic necrotizing pulmonary aspergillosis were treated with radiotherapy (20 Gray) from 1990 to 2002. The outcome measures were the period from tuberculosis treatment to the onset of hemoptysis, hemoptysis resolution rate, change in Zubrod performance status after 30 days of the completion of radiotherapy, local failure-free survival, and overall survival.ResultsThe median time between tuberculosis treatment and the onset of hemoptysis due to aspergilloma was 9 years. After radiotherapy, general status improved and the hemoptysis resolved in all patients. During the follow-up period, 4 failures occurred, with a 5-year local failure-free survival rate of 82 % and a 5-year overall survival rate of 59 %. Of these failures, 2 patients died due to recurrence of the hemoptysis, and 2 were rescued (using cavernostomy and reirradiation). The presence of chronic obstructive pulmonary disease (COPD) (p = 0.021) and female gender (p = 0.032) were negatively associated with overall survival. None of the variables was related to local control.ConclusionsBased on these long-term data, radiotherapy is a potential option for controlling bleeding due to fungus balls. Female patients and COPD were associated with lower survival.

Chronic necrotizing pulmonary aspergillosis in a patient with diabetes and marijuana use

A29-year-old man with type 1 diabetes presented to the emergency department with shortness of breath and chest pain that had lasted for one week. The patient initially reported no systemic symptoms. However, upon further questioning, he stated that he had felt generally unwell for the past year,

Calcium oxalate in the sputum may aid in the diagnosis of pulmonary aspergillosis: A report of two cases

We present two cases of pulmonary aspergillosis in which calcium oxalate crystals in the sputum proved to be a useful diagnostic clue. In case 1, Aspergillus hyphae was not identified; however, calcium oxalate crystals were present, and chronic necrotizing pulmonary aspergillosis was diagnosed. In case 2, calcium oxalate was detected and Aspergillus fumigatus was identified later. Thus, the presence of calcium oxalate in the sputum may be an important indicator for an A. fumigatus infection.