Seminars in respiratory and critical care medicine
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Semin Respir Crit Care Med · Dec 2011
ReviewAllergic bronchopulmonary aspergillosis and related allergic syndromes.
While allergic bronchopulmonary aspergillosis (ABPA) is well recognized as a fungal complication of asthma, severe asthma with fungal sensitization (SAFS) is not. In ABPA the total immunoglobulin E (IgE) is usually >1,000 IU/mL, whereas in SAFS it is <1,000 IU/mL, and either skin prick tests or fungus-specific IgE tests are positive. ABPA may present with any severity of asthma, and occasionally with no asthma or cystic fibrosis, the other common underlying disease. ⋯ Complications of ABPA include bronchiectasis, typically central in distribution, and chronic pulmonary aspergillosis. Most patients with ABPA and SAFS can be stabilized for long periods with inhaled corticosteroids and itraconazole or another antifungal agent. Novel immunotherapies are on the horizon.
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Aspergillosis remains a significant cause of morbidity and mortality. The spectrum of disease is diverse and ranges from noninvasive disease with an excessive immune response, such as in allergic bronchopulmonary aspergillosis (ABPA), to a lack of an immune response as seen in patients with quantitative or qualitative granulocyte deficits and subsequent invasive pulmonary aspergillosis. ⋯ Voriconazole remains the preferred agent in the treatment of invasive pulmonary aspergillosis, and recent data have increased interest in the potential of combination therapy against this often lethal infection. The role of host genetics in selecting patients that may benefit from more aggressive antifungal prophylaxis or treatment practices remains unclear but is likely to guide therapeutic choices as newer data become available.
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Blastomyces dermatitidis is acquired in almost all cases via inhalation, and pulmonary disease is the most frequent clinical manifestation of blastomycosis. Pulmonary disease can range from asymptomatic infection to rapidly severe and fatal disease. Most cases will present as pneumonia, either acute or chronic, or as a lung mass. ⋯ Detection of urinary Blastomyces antigen is a recent addition to diagnostic options. Itraconazole is the drug of choice for most forms of the disease; amphotericin B is reserved for the more severe forms. Newer azoles such as voriconazole and posaconazole have a limited role in the treatment of pulmonary blastomycosis.
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Pulmonary histoplasmosis is an important cause of morbidity in the United States. Several outbreaks of acute pulmonary histoplasmosis have been linked to potentially preventable environmental exposures. Progressive disseminated histoplasmosis, which is seen frequently in the growing population of immunocompromised hosts, often presents with prominent pulmonary manifestations and is more commonly encountered in hospitalized patients than acute, subacute, or chronic pulmonary histoplasmosis. ⋯ Posaconazole exhibits promise as a salvage agent. Antifungal prophylaxis is not routinely recommended for at-risk populations. Measures to minimize environmental contamination may reduce the risk of epidemic-type acute pulmonary histoplasmosis related to high-risk exposures.
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Cryptococcosis is an invasive fungal infection (IFI), caused predominantly by Cryptococcus neoformans or Cryptococcus gattii, that affects both immunocompromised (IC) and non-IC patients. Although the most serious disease manifestation is meningoencephalitis, cryptococcal pneumonia is underdiagnosed and may disseminate to the central nervous system (CNS) and other sites depending upon host defenses and administration of appropriate antifungal therapy. ⋯ Treatment recommendations include induction therapy with an amphotericin B preparation and flucytosine for IC patients and those with severe disease and fluconazole for mild-to-moderate, localized disease. Knowledge of the pathophysiology, epidemiology, clinical presentation, and treatment of pulmonary cryptococcosis may lead to greater recognition of this underdiagnosed IFI and improved outcomes.