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Pulmonary Fungal Diseases in Non-Immunocompromised Patients

In an article published in The Lancet Infectious Diseases, David W. Denning, MB, BS, FRCP, FRCPath, DCH, FMedSci, from the University of Manchester, United Kingdom, and Arunaloke Chakrabarti, MD, Dip NB, FAMS, FNASc, from the Postgraduate Institute of Medical Education & Research, Chandigarh, India, discuss common fungal respiratory diseases in non-immunocompromised patients, summarizing their prevalence, presentation, diagnosis, and therapy options.

“A very small number of the fungi that cause pulmonary infection are true pathogens,the authors write. Other pathogens, such as Aspergillus spp and Cryptococcus spp, can overwhelm innate defences when inhaled in substantial quantities or when patients have defects in the innate immunity.”

This article highlights some of these diseases described by Dr. Denning and Dr. Chakrabarti.
Primary Pulmonary Fungal Diseases

Although some fungi are primary pulmonary pathogens of otherwise healthy individuals, infections with these organisms resolve in most individuals, causing disease in only a few cases. Fungi that act as primary pulmonary pathogens include Histoplasma capsulatum, Coccidioides spp, Blastomyces dermatitidis, and Paracoccidioides brasiliensis.

Pulmonary histoplasmosis, for example, may manifest as acute disease after heavy exposure to Histoplasma capsulatum (especially in individuals who have visited caves), chronic cavitation of the lung in immunocompetent individuals, or disseminated disease in immunocompromised patients. Although many cases of histoplasmosis are subclinical, diagnosis in symptomatic patients involves chest radiography and serology (to detect Histoplasma antigen or antibody, or both). In patients with chronic disease, fungal culture of respiratory samples is also useful. Itraconazole is typically used to treat patients with symptoms of disease, and long-term therapy (12 to 24 months) may be required in those with chronic disease.

Other Pulmonary Fungal Diseases

Chronic pulmonary aspergillosis most frequently affects men aged 50 years to 75 years. It is a challenging disease that complicates several respiratory conditions, the authors write, and manifests in various ways, including aspergilloma, Aspergillus nodules, chronic cavitary lesions, and subacute invasive pulmonary aspergillosis. The key diagnostic test for this disease is detection of IgG to Aspergillus. Although simple aspergillomas may be resectable, Aspergillus nodules may require azole therapy. Chronic cavitary lesions typically require long-term (>6 months) oral antifungal therapy (posaconazole, liposomal amphotericin B, or micafungin).

Community-acquired aspergillus pneumonia may also occur if substantial exposure to Aspergillus conidia overwhelm a patient’s innate immune system and cause acute lung disease. Even low-level exposure to the fungus in individuals with a history of influenza, lung disease, and corticosteroid therapy, may also predispose patients to this form of aspergillosis.

Mounting evidence also suggests that high indoor fungal exposures can trigger asthma in children, and worsen asthma symptoms, according to the authors. In the latter instance, poor asthma control is linked to sensitivity to several fungi, including Aspergillus spp, and is referred to as fungal asthma. The most well-characterized form of fungal asthma is allergic bronchopulmonary aspergillosis, which presents as poorly controlled asthma; its diagnosis is based on clinical, radiological, and immunological findings—especially elevated serum IgE to A. fumigatus. Management of the fungal component of fungal asthma includes treatment with oral (itraconazole) or inhaled (such as amphotericin B) antifungal therapy, if tolerated.

The authors note that other environmental conditions have been attributed to triggering asthma. For example, high humidity and high winds associated with certain thunderstorms have been associated with fungal dissemination that triggers asthma (thunderstorm asthma). Some workers have also been reported to develop asthma or worsening asthma because of exposure to fungi in their work environment (occupational asthma). These cases have been described, for example, in mushroom workers, orchid growers, and individuals in the plywood industry. Poor quality buildings, water leaks, and inadequate ventilation can also lead to excess fungal growth inside a building. The authors state that these factors can trigger asthma or worsen its symptoms and can also lead to patients developing other symptoms (building sickness syndrome).

The authors emphasize that, although fungi may cause a wide range of pulmonary diseases, underlying respiratory disease or exposure to large numbers of fungal spores or conidia are common contributing factors in the development of fungal pulmonary diseases. 

However, “Most infectious syndromes and some allergic manifestations improve with antifungal therapy,” they conclude.

Feature Picture: Giemsa-stained photomicrograph reveals numerous Histoplasma capsulatum fungal organisms in their yeast-stage of development, which were seen in this liver tissue specimen, in this case of disseminated histoplasmosis. Feature Picture Source: CDC/Dr. Lucille K. Georg.
Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.
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