Treatment Of Pulmonary Aspergillosis Research Articles

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

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

Development and clinical application of an electronic health record quality control system for pulmonary aspergillosis based on guidelines and natural language processing technology.

BackgroundThere are considerable differences in the diagnosis and treatment of pulmonary aspergillosis (PA) between specialized hospitals and primary hospitals or developed areas and underdeveloped areas in China. There is a lack of electronic systems that assist respiratory physicians in standardizing the diagnosis and treatment of PA.MethodsWe extracted 26 quality control points from the latest guidelines related to PA, and developed a PA quality control system of electronic health record (EHR) based on natural language processing (NLP) techniques. We obtained PA patient records in the Department of Respiratory Medicine of the First Affiliated Hospital of Guangzhou Medical University to verify the effectiveness of the system comparing with manually evaluation of respiratory experts.ResultsWe successfully developed quality control system of PA; 699 PA medical records from EHR of the First Affiliated Hospital of Guangzhou Medical University between January 2015 and March 2020 were obtained and assessed by the system; 162 defects were found, which included 19 medical records with diagnostic defects, 76 medical records with examination defects, and 80 medical records with treatment defects; 200 medical records were sampled for validation, and found that the sensitivity and accuracy of quality control system for pulmonary aspergillosis (QCSA) were 0.99 and 0.96, F1 value was 0.85, and the recall rate was 0.77 compared with experts’ evaluation.ConclusionsOur system successfully uses medical guidelines and NLP technology to detect defects in the diagnosis and treatment of PA, which helps to improve the management quality of PA patients.

Clinical neglect of aspergillosis in pulmonary tuberculosis coinfection: a case report of avoidable mortality in a resourceconstrained setting

Background: Pulmonary aspergillosis (PA) is common among patients with tuberculosis (TB). With both infections presenting with similar clinical and radiologic features, diagnosis of PA is often made too late or missed completely due to lack of clinical suspicion and poor diagnostic laboratory capacity for mycotic infections prevalent in our settings. We present a case of preventable mortality caused by delayed diagnosis and treatment of PA in a patient with pulmonary TB (PTB).
 Case presentation: A 13-year-old female was diagnosed and treated for PTB, having received anti-TB regimen for 8 months in a mission hospital from where she was referred due to worsening cough, chest pain and progressive breathlessness. The patient was re-assessed and investigated, with GeneXpert detecting Mycobacterium tuberculosis, susceptible to rifampicin. Diagnosis of pulmonary tuberculosis complicated by right pneumothorax was made indicating an emergency thoracotomy and chest tube insertion and continuation of the first line anti-TB regimen. At about 2 weeks into admission, patients had features of superimposed acute bacterial sepsis with fever becoming high grade, marked neutrophilia with toxic granulation and elevated sepsis biomarker, and this necessitated empiric antibiotic treatment with parenteral meropenem and vancomycin. However, the patient only had mild clinical improvement following which there was progressively worsening respiratory symptoms and massive haemoptysis. Result of sputum fungal study was available on admission day 20 and revealed a growth of Aspergillus flavus. Treatment with intravenous voriconazole was however commenced rather late when the fungal respiratory disease could no longer be remedied. The patient died on admission day 23.
 Conclusion: Diagnosis of PA in patients with background TB is often made too late to guarantee timely and effective antifungal treatment with negative consequences on patients’ outcomes. Improving clinical and laboratory capacities is essential to reducing mortality from PA in healthcare facilities.

A Critical Review on Emerging Trends in Dry Powder Inhaler Formulation for the Treatment of Pulmonary Aspergillosis.

Pulmonary aspergillosis (PA), a pulmonary fungal infection caused by Aspergillus spp., is a concern for immunocompromised populations. Despite substantial research efforts, conventional treatments of PA using antifungal agents are associated with limitations such as excessive systemic exposure, serious side effects and limited availability of the therapeutics in the lungs for an adequate duration. To overcome the limitations associated with the conventional regimens, pulmonary delivery of antifungal agents has become a focal point of research because of the superiority of local and targeted drug delivery. Dry powder inhalers and nebulized formulations of antifungal agents have been developed and evaluated for their capability to effectively deliver antifungal agents to the lungs. Moreover, progress in nanotechnology and the utilization of nanocarriers in the development of pulmonary delivery formulations has allowed further augmentation of treatment capability and efficiency. Thus, the following review provides an insight into the advantages and therapeutic potential of the utilization of nanocarriers in pulmonary delivery of antifungal agents for the treatment of PA. In addition, discussions on formulation aspects and safety concerns together with the clinical and regulatory aspects of the formulations are presented, which suggest the possibility and desirability of utilization of nanocarriers in the treatment of PA.

The spectrum of pulmonary aspergillosis.

Notable progress has been made in the past years in the classification, diagnosis and treatment of pulmonary aspergillosis. New criteria were proposed by the Working Group of the International Society for Human and Animal Mycology (ISHAM) for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). The latest classification of chronic pulmonary aspergillosis (CPA) suggested by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) has become widely accepted among clinicians. Subacute invasive pulmonary aspergillosis is now considered a type of CPA, yet it is still diagnosed and treated similarly to invasive pulmonary aspergillosis (IPA). Isavuconazole, an extended-spectrum triazole, has recently been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of IPA. The most recent Infectious Diseases Society of America (IDSA) guidelines strongly recommend reducing mold exposure to patients at high risk for pulmonary aspergillosis. The excessive relapse rate following discontinuation of therapy remains a common reality to all forms of this semi-continuous spectrum of diseases. This highlights the need to continuously reassess patients and individualize therapy accordingly. Thus far, the duration of therapy and the frequency of follow-up have to be well characterized.

Можливості хірургічного лікування аспергільозу легень

Мета. Поділитися власним досвідом хірургічного лікування аспергільозу легень.
 Матеріали і методи. За останні 10 років у клініці перебували 14 хворих з аспергільозом легень. У 11 (78,6%) хворих діагностовано аспергілому легені, у 3 (21,4%) - інвазивний аспергільоз після проведення біопсії легені. Резекційні втручання виконані 8 (57,1%) пацієнтам з аспергіломою. Відмовлено в операції внаслідок значних дихальних розладів 3 (21,4%) хворим. Середній вік пацієнтів - (42,6 ± 15,7) року. Всі пацієнти до і після оперативного втручання отримували специфічну протигрибкову терапію.
 Результати. Виконано такі оперативні втручання: 3 (37,5%) плевропульмонектомії, 4 (50,0%) лобектомії, 1 (12,5%) типову резекцію піраміди та S3 справа. У 1 (12,5%) пацієнтки під час оперативного втручання виконано інтраплевральну торакопластику. Середня тривалість операції склала (235,6 ± 77,6) хв, середня інтраопераційна крововтрата - (314 ± 331,9) мл.
 Висновки. Хірургічне лікування аспергільозу легень є досить складним завданням і має багато невирішених питань. Систематизація власного досвіду та досвіду, про який повідомляють інші дослідники, дає змогу покращити результати лікування.

Current Pharmacological Treatment of Pulmonary Aspergillosis

Current Pharmacological Treatment of Pulmonary Aspergillosis

アスペルギルス症における血痰と喀血 その病態と治療

アスペルギルス症における血痰と喀血 その病態と治療

Caspofungin may effective for initial treatment of pulmonary aspergillosis

Introduction: Invasive aspergillosis mostly involves lungs. Patients may present with fever, cough, hemoptysis and many other sign and symptoms. Underlying conditions that compromises pulmonary and immune responses to inhaled Aspergillus species serve as risk factors for pulmonary invasive aspergillosis. We are presenting a case of simple aspergilloma, successfully treated by caspofungin and surgery. Case Report: A 64­ year­old male patient has rheumatoid arthritis for ten years. Since three months he had interstitial pulmonary disease secondary to rheumatoid arthritis and hemoptysis. We performed microbiologic and pathologic investigations of the brochoalveolar lavage after computerized tomography for diagnosis of aspergillosis. Caspofungin was used for initial treatment of simple aspergilloma and also for follow­up treatment after apical wedge resection. The patient was discharged from the hospital at eighth week on itraconazol antifungal therapy. Conclusion: Three classes of drugs are available for the treatment of aspergillosis: polyens, azoles and echinocandins. Echinocandins have activity against Aspergillus spp. But have a limited role because they have not been studied for initial treatment of invasive aspergillosis.

Progress in the Diagnosis and Treatment of Pulmonary Aspergillosis

Aspergillus is the most common fungal pathogen of the respiratory mycosis. The respiratory diseases caused by Aspergillus are mainly classified into four clinical types, namely allergic bronchopulmonary aspergillosis, invasive aspergillosis, aspergilloma, and chronic pulmonary aspergillosis. Among the four clinical types of pulmonary aspergillosis, invasive aspergillosis is the most dangerous and difficult to treat disease. The diagnosis of invasive aspergillosis is established initially on clinical aspects and confirmed by the finding of pathogen in culture and histopathology. A number of methods can be conducted to obtain tissue samples from patients with invasive aspergillosis, chronic pulmonary aspergillosis or aspergilloma. Besides BAL detection and transbronchial biopsy, a fine-needle biopsy can be performed and guided by CT to diagnose these diseases. Antifungal agents including those with activity against Aspergillus have been developed. Several agents such as voriconazole, amphotericin B lipid complex, caspofungin, micafungin and anidulafungin are promising in the treatment of the pulmonary aspergillosis in the future. Moreover, under certain condition, surgical intervention is needed to combine with antifungal therapy to deal with aspergilloma or chronic pulmonary aspergillosis, and the use of glucocorticoids to control the inflammatory response is also very important in therapy of allergic bronchopulmonary aspergillosis besides antifungal agents. Keywords: Allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, invasive aspergillosis.

Successful Treatment of Invasive Pulmonary Aspergillosis in a Neonatal Foal

Successful Treatment of Invasive Pulmonary Aspergillosis in a Neonatal Foal

Comparative Study on the Efficacy of Liposomal Amphotericin B and Voriconazole in a Murine Pulmonary Aspergillosis Model

Background:No clinical studies have compared the efficacy of liposomal formulation AMB (L-AMB) and voriconazole (VRC) in the treatment of pulmonary aspergillosis. The aim of this study was to compare the efficacy of L-AMB and VRC in murine pulmonary aspergillosis.Methods: Leucopenic mice were infected intratracheally with Aspergillus fumigatus and treated intravenously with L-AMB (once a day) or VRC (twice a day). Results: L-AMB and VRC at a dose of ≥5 and ≥20 mg/kg, respectively, significantly prolonged the survival time of infected mice and reduced the pulmonary fungal burden in comparison with the control group. At the maximum recommended dose for clinical use, 5 mg/kg of L-AMB exhibited greater efficacy than 10 mg/kg of VRC, which achieved an area under the concentration-time curve level equivalent to that of 6 mg/kg (loading dose) in humans, in terms of increasing survival and reducing the fungal burden. Conclusion: The in vivo efficacy of L-AMB was superior to that of VRC at the maximum recommended dose in a murine pulmonary aspergillosis model.

SUCCESSFUL COMBINATION OF ANTIFUNGAL AGENTS AND SURGICAL RESECTION FOR PULMONARY ASPERGILLOSIS IN A CHILD WITH HODGKIN DISEASE: Review of the Literature

The authors report on a 14-year-old adolescent boy suffering of Hodgkin disease in remission, who developed autoimmune anemia and thrombopenia. He was treated with high-dose steroids and he developed serious invasive lung aspergillosis, which was treated with antifungal agents and surgical intervention. Children suffering from cancer are prone to develop systemic fungal infections secondary to the severe immunosuppression caused by the disease itself and the antineoplastic therapy. Intravenous antifungal medications and, when feasible, surgery are used for treatment of pulmonary aspergillosis. Factors related to better outcome are early diagnosis, remission of underlying disease, aggressive antifungal therapy, and recovery from neutropenia.

Predictors of Postoperative Complications After Radical Resection for Pulmonary Aspergillosis

Although surgery has proven to be the best treatment for pulmonary aspergillosis, with the highest chance of achieving complete remission, it is difficult to determine the surgical indications for this disease because of the high incidence of postoperative complications. We conducted this study to identify some predictors of postoperative complications, in an attempt to reduce the morbidity rate. We retrospectively analyzed the medical records of 31 patients (18 men, 13 women; median age 53 years) who underwent radical resection for pulmonary aspergillosis between 1976 and 2004. The clinical manifestations, surgical procedures, and postoperative complications were reviewed to clarify the predictors of postoperative complications. The morbidity rate associated with major complications such as intrapleural bleeding, bronchopleural fistula, and empyema, resulting in further surgery, was 19%. Univariate analysis revealed the predictors of major complications to be sex, severe preoperative symptoms, and extensive pulmonary resection. Multivariate analyses also indicated that preoperative symptom severity was an independent predictor of major complications. Pulmonary aspergillosis should be resected before the symptoms become too severe if the patient is a surgical candidate.

In vitroandin vivoantifungal activities of FX0685, a novel triazole antifungal agent with potent activity against fluconazole-resistantCandida albicans

To evaluate the therapeutic potential of FX0685, a new triazole antifungal agent, for the treatment of opportunistic fungal infections, particularly systemic candidiasis and aspergillosis, in vitro and in vivo studies were performed using fluconazole (FLC), itraconazole (ITC) and/or amphotericin B (AMB) as reference drugs. A preliminary in vitro study showed that the antifungal activity of FX0685 against FLC-susceptible Candida albicans, several non-C. albicans Candida species and Cryptococcus neoformans was superior to that of FLC and comparable or superior to those of ITC and AMB, while the anti-Aspergillus fumigatus activity of FX0685 was to varying degrees lower than that of ITC. FX0685 appeared to be comparable to FLC and ITC in the treatment of murine systemic C. albicans and pulmonary A. fumigatus infection, respectively. The biological property of FX0685 was characterized by its potent in vitro and in vivo activity against FLC-resistant C. albicans. Part of this unique property was explained by the finding that it retained potent inhibitory activity against those CYP51 molecules in which amino acid substitutions confer a phenotype of resistance to FLC and some other azole derivatives. All of these results lead to the possibility that FX0685 may be a potential antifungal drug candidate for the treatment of various clinical forms of systemic candidiasis, including those caused by FLC-resistant C. albicans, as well as for the treatment of pulmonary aspergillosis.

Aspergillus spondylodiskitis in a patient with chronic obstructive pulmonary disease

Invasive aspergillosis is a well-known complication in immunocompromised patients. There are only a few reports of invasive aspergillosis in non-immunocompromised patients. We describe a 72-year-old female patient with clinical signs of spondylodiskitis occurring 4 months after what had appeared to be successful treatment of pulmonary aspergillosis. The patient used inhalation corticosteroids on a daily basis because of chronic obstructive pulmonary disease (COPD). Spondylodiskitis of the intervertebral disc Th11 and Th12 with involvement of both adjacent vertebral bodies was confirmed by magnetic resonance imaging. Histopathological examination revealed the presence of septate hyphae, indicative of Aspergillus species. Subsequently, evidence of Aspergillus spondylodiskitis was obtained by amplification of Aspergillus-DNA with a specific polymerase chain reaction method. Aspergillus spondylodiskitis after pulmonary aspergillosis is only very rarely encountered. Patients with COPD, managed with short-term courses of systemic corticosteroids or with high-dose corticosteroid inhalation therapies, are considered non-immunocompromised but might be at risk of developing invasive aspergillosis.

RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR AUGMENTS PULMONARY HOST DEFENCES AGAINST ASPERGILLUS FUMIGATUS

The in vivo and ex vivo effects of macrophage colony-stimulating factor (M-CSF) were studied in a profoundly neutropenic rabbit model in order to determine its potential to augment pulmonary host defence againstAspergillus . M-CSF (100–600μg/kg/d) was administered prophylactically to neutropenic rabbits with pulmonary aspergillosis starting three days pre-inoculation and then throughout neutropenia. Rabbits receiving M-CSF had significantly increased survival (P=0.01) and decreased pulmonary injury, as measured by decreased pulmonary infarction (P=0.004), when compared with untreated controls. Microscopic studies demonstrated greater numbers of activated pulmonary alveolar macrophages (PAMs) in lung tissue of rabbits receiving M-CSF, in comparison to controls (P<0.001). PAMs harvested from rabbits treated with M-CSF had a significantly greater percent phagocytosis ofAspergillus fumigatus conidia than did PAMs from controls (P=0.04). These data indicate that prophylactic administration of M-CSF augments pulmonary host defence against A. fumigatus and suggest a potential role for this cytokine as adjunctive therapy in the treatment of pulmonary aspergillosis in the setting of profound neutropenia.

New antifungal agents and preparations

In neutropenic patients amphotericin B remains the drug of choice for the treatment of systemic fungal infections. On the basis of a superior efficacy in combination with a lower toxicity, the triazoles have superseded the older azoles. Regularly, amphotericin B and a triazole are used simultaneously without any evidence from clinical trials that such a strategy is safe and efficacious. Liposomal preparation, lipid complex or colloidal dispersion of amphotericin B have been produced successfully to reduce toxicity. However, there is only one small randomised study that hints at the superiority of liposomal amphotericin B over amphotericin B deoxycholate. Promising new agents like candins, sordarins, high dose oral terbinafine, the third generation azoles, and liposomal nystatin are under development. The first phase II study on voriconazole in the treatment of pulmonary aspergillosis has produced encouraging results. The major promise of the new candins lies in the activity against Candida species, including those resistant to the azoles and polyenes, and in a mechanism of action totally different from the established antifungals. Cytokines and colony stimulating factors are theoretically very promising but there are no clinical studies that warrant routine use.

Pulmonary Aspergillosis in Mice: Treatment with a New Triazole SCH39304

The triazole SCH39304 was compared with amphotericin B and fluconazole for the treatment of pulmonary aspergillosis in corticoid-immunosuppressed mice intranasally challenged with 5 x 10(6) conidia of Aspergillus fumigatus. In vitro, the minimum inhibitory concentration (MIC) for fluconazole was greater than 80 micrograms/ml, for SCH39304 40 micrograms/ml, and for amphotericin B 0.29 micrograms/ml. Beginning 1 day after challenge, groups of 10 mice were treated orally, twice daily, for 15 days with Noble agar (control), SCH39304, fluconazole, or amphotericin B at various doses. For lung tissue counts of A. fumigatus, mice were similarly challenged and treated only for 5 days with SCH39304, fluconazole, or amphotericin B. Only SCH39304 significantly reduced the number of A. fumigatus in the lung. SCH39304 at doses of 5 mg/kg or higher significantly prolonged the survival of mice, as did amphotericin B at 3 mg/kg. Fluconazole did not significantly prolong survival at doses of 15 or 30 mg/kg. SCH39304 appears to be as effective as amphotericin B in murine pulmonary aspergillosis and warrants further evaluation for aspergillosis in humans.

Treatment of pulmonary aspergillosis with di-iodohydroxyquinoline.

Thirteen patients with a clinical diagnosis of pulmonary aspergillosis were treated with the anti-amoebic drug di-iodohydroxyquinoline, 1500-1800 mg/day orally, for 20 days. All were precipitin positive before treatment and all but one became negative after treatment. Sputum became negative in all of the 10 patients in whom it had been positive before treatment. Clinical improvement was marked in four patients, moderate in three, and slight in three, no change occurring in the remaining three. These results suggest that di-iodohydroxyquinoline may be of value in the treatment of pulmonary aspergillosis.