First guidelines for chronic fungal lung infections

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The world’s first guidelines for chronic fungal lung infections for doctors and laboratories have been published, by the European Respiratory Society (ERS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These new guidelines describe the important features of this disease and provide comprehensive treatment recommendations.

Chronic pulmonary aspergillosis (CPA) is a subtle and insidious problem in patients who already have damaged lungs. It kills about 80% of sufferers over five years unless diagnosed and treated with long-term anti-fungals. Across Europe, an estimated 240,000 people have CPA, and worldwide around 3m. The late stages of CPA (aspergilloma) are familiar to respiratory specialists, but the early features are often missed.

Major improvements in understanding this debilitating and ultimately fatal disorder have resulted from research undertaken in Europe, India and Japan over the past 10 years. However, no therapies are approved by the European Medicines Agency (EMA) for treatment, and very few diagnostic tests and therapies have been compared. In many parts of the world, the basic tests required are not yet available.

Professor David Denning of the University of Manchester, who lead the CPA guidelines group, said: “The UK National Health Service recognised the challenges posed by these patients by setting up the National Aspergillosis Centre and its associated laboratory the Mycology Reference Centre in 2009. The experience gained from seeing hundreds of patients has contributed to the quality of care, although much more research and new oral antifungal drugs are required to reduce the marked disability caused by CPA.”

ESCMID president Professor Murat Akova stated: “I am delighted that this groundbreaking clinical guideline has been published; the management of chronic fungal infection, notably CPA, is difficult, requiring a high level of laboratory and clinical expertise.”

ERS Guidelines director, Dr Marc Miravitlles, commented: “We welcome the publication of this guideline, which provides key insights into the main features of the disease and treatment recommendations. By establishing this expert consensus on the topic, we aim to improve the early diagnosis of CPA and increase recognition of the condition to ultimately improve outcomes for patients.”

The guidelines are a product of a two-year collaboration between ESCMID and ERS. In parallel to these CPA recommendations, ESCMID is currently developing wider guidelines for invasive aspergillosis in general, which will be published in due course. The latter are developed by Professor Andrew Ullmann of the Julius Maximilian University of Würzburg, chair of ESCMID’s fungal infection study group EFISG.

Ullmann commented: “This is the first guideline on chronic pulmonary aspergillosis worldwide. It is the result of another joint effort of ESCMID and ERS experts who, in a truly interdisciplinary collaboration, prepared and published guidance for colleagues on a group of complex diseases that is difficult to manage. Aspergillosis is more than chronic lung infection and a larger document addressing all aspects of aspergillosis infections is under preparation by EFISG.”

Abstract
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.  

European Respiratory Society material
European Respiratory Journal abstract


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