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Diagnosis and Treatment of Pulmonary Aspergillosis Syndromes

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Diagnosis and Treatment of Pulmonary Aspergillosis Syndromes [ Recent Advances in Chest Medicine ] Diagnosis and Treatment of Pulmonary Aspergillosis Syndromes Karen C. Patterson , MD ; and Mary E. Strek , MD, FCCP Both inherited and acquired immunodefi ciency and chronic pulmonary disease predispose to the development of a variety of pulmonary syndromes in response to Aspergillus , a fungus that is ubiquitous in the environment. These syndromes include invasive aspergillosis, which is now recognized to occur in patients with critical illness without neutropenia and in those with mild degrees of immunosuppression, including from corticosteroid use in the setting of COPD. Chronic pulmonary aspergillosis includes simple aspergilloma, which is occasionally complicated by life-threatening hemoptysis, and progressive destructive cavitary disease requiring antifungal therapy. Allergic bronchopulmonary aspergillosis occurs almost exclu- sively in patients with asthma or cystic fi brosis. Recent advances in each of these syndromes include a greater understanding of the underlying pathophysiology and hosts at risk; improved diagnostic algorithms; and the availability of more eff ective and well-tolerated therapies. Improvement in outcomes for Aspergillus pulmonary syndromes requires that physicians recognize the varied and sometimes subtle presentations, be aware of populations at risk of illness, and institute potentially life-saving therapies early in the disease course. CHEST 2014; 146(5):1358 - 1368 ABBREVIATIONS: ABPA 5 allergic bronchopulmonary aspergillosis; IFN- g 5 interferon g ; SAFS 5 severe asthma with fungal sensitization; Th 5 T-helper Pulmonary aspergillosis refers to a spec- Aspergillus is a ubiquitous and hardy trum of diseases that result from Aspergillus organism. It grows best in moist environ- becoming resident in the lung. Th ese ments, although spore aerosolization and include invasive aspergillosis from angioin- dispersion occur most eff ectively in dry vasive disease, simple aspergilloma from climates. Spores survive harsh external con- inert colonization of pulmonary cavities, ditions and adapt to a range of internal envi- and chronic cavitary pulmonary aspergil- ronments. 1-3 Although there are hundreds losis from fungal germination and immune of Aspergillus species, Aspergillus fumigatus activation ( Table 1 ). Allergic bronchopul- is by far the most common pathogenic spe- monary aspergillosis (ABPA), driven by cies in humans, where the small size and allergic responses, has an important place hydrophobicity of its spores confer a dis- along this spectrum as well. persion advantage. 4-6 Although less common, Manuscript received April 17, 2014; revision accepted June 29, 2014. Spruce St, Philadelphia, PA 19104; e-mail: karen.patterson@uphs. AFFILIATIONS: From the Pulmonary, Allergy and Critical Care Divi- upenn.edu sion (Dr Patterson), University of Pennsylvania, Pennsylvania, PA; and © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of the Section of Pulmonary and Critical Care (Dr Strek), University of this article is prohibited without written permission from the American Chicago, Chicago, IL . College of Chest Physicians. See online for more details. CORRESPONDENCE TO : Karen C. Patterson, MD, Pulmonary, Allergy, DOI: 10.1378/chest.14-0917 and Critical Care Division, University of Pennsylvania, 828 Gates, 3600 1358 Recent Advances in Chest Medicine [ 146 # 5 CHEST NOVEMBER 2014 ] Downloaded From: http://journal.publications.chestnet.org/ by a CAPES User on 11/11/2014 TABLE 1 ] Pulmonary Aspergillosis Syndromes Aspergillus Syndrome Syndrome Clinical Features Recent Updates Allergic aspergillosis ABPA Worsening of underlying asthma Cystic fi brosis is a risk factor Markedly elevated total IgE for ABPA Sensitization: (1 ) skin testing and/or Bronchiectasis may be absent elevated Aspergillus -specifi c IgE early in the disease course Bronchiectasis Antifungal agents benefi t some patients Case reports of benefi t from anti-IgE therapy Chronic pulmonary Simple Quiescent mycetoma in a preexisting Small case series suggests aspergillosis aspergilloma lung cavity benefi t of percutaneous Hemoptysis may occur intracavitary amphotericin for refractory hemoptysis Chronic cavitary Systemic symptoms: malaise, fevers, Immune dysfunction may pulmonary weight loss contribute to risk of disease aspergillosis Elevated Aspergillus -specifi c IgG Long-term antifungal therapy New or expanding cavities in setting of generally recommended chronic lung disease Surgical resection is often Intracavitary mycetoma risky but may benefi t those Extensive parenchymal destruction with focal disease and limited Fibrosis pleural involvement Invasive disease Angioinvasive Seen in neutropenia and stem cell Expanded populations at risk disease transplant Positive Aspergillus respiratory Presentation ranges from asymptomatic culture may require further macronodules to overt respiratory evaluation failure Serum and BAL galactomannan CT scan more sensitive than plain testing may aid in diagnosis chest radiograph Voriconazole fi rst-line therapy; dual therapy in some Invasive Neutropenia and lung transplant are Expanded populations at risk: tracheobronchial risk factors COPD, critical illness, HIV disease Ulcerative, pseudomembranous, and infection obstructive variants Requires bronchoscopy for Atelectasis and unilateral wheeze are diagnosis suggestive ABPA 5 allergic bronchopulmonary aspergillosis. Aspergillus fl avus and Aspergillus niger also contribute to advances in the diagnosis and treatment of pulmonary the total burden of pulmonary aspergillosis. When aspergillosis relevant to clinical care. Th ese include inhaled, spores deposit by sedimentation in distal airways the recognition of additional hosts at risk of invasive and alveolar spaces. In healthy hosts, spores are elimi- disease, as well as an expanded array of diagnostic and nated by mucociliary clearance and immune defenses. treatment options; a delineation of the features and out- Germination is the conversion of dormant spores into comes of chronic pulmonary aspergillosis; and, updated growing hyphal elements. diagnostic criteria and an evolving understanding of the role of triazole and anti-IgE treatment options in ABPA. Aspergillus is an inadvertent human pathogen, and pul- monary aspergillosis is largely the result of impaired Invasive Aspergillosis: Epidemiology, airway clearance from a compromised immune function Diagnostic Testing, and Treatment Updates or a chronic lung disease such as COPD and sarcoidosis. Invasive aspergillosis has been described classically in Advances in the domains of stem cell transplant and patients with neutropenia in the setting of hematologic immunosuppressive therapies and an increased prevalence malignancy but is seen increasingly in patients with of chronic pulmonary diseases have inadvertently led to even milder immune compromise from immunosup- a rise in pulmonary aspergillosis syndromes. Now com- pression, chronic pulmonary or liver disease, or critical monly encountered by pulmonologists and intensivists illness. 7 As the portal of entry, the upper and lower worldwide, these syndromes have a high associated respiratory tracts are most commonly infected, although morbidity and can be fatal. In this review, we highlight dissemination to any organ may occur. Aspergillus journal.publications.chestnet.org 1359 Downloaded From: http://journal.publications.chestnet.org/ by a CAPES User on 11/11/2014 tracheobronchitis and CNS infection are associated with site positive for Aspergillus , 12% had evidence for invasive especially poor outcomes. An informative review of the disease. 15 Although patients with hematologic malignancy pathogenesis of invasive aspergillosis has been published.8 or transplant or neutropenia accounted for the majority Th e diagnosis may be delayed from lack of awareness of of cases, malnutrition (27%), corticosteroid use (20%), the expanded patient populations at risk and because of HIV infection (19%), diabetes mellitus (11%), and failure to recognize the signifi cance of positive Aspergillus chronic pulmonary disease (9%) were associated with respiratory cultures or to use available diagnostic tests. invasive infection as well. In a single-center retrospective Early diagnosis of invasive aspergillosis, along with the study of 239 patients hospitalized with COPD who had use of therapeutic agents with greater tolerability and Aspergillus isolated from a lower respiratory tract sample, effi cacy, have the potential to decrease mortality, which 22% had probable invasive aspergillosis. 12 M u l t i v a r i a t e remains high. regression identifi ed the following predictors of invasive aspergillosis: ICU admission, heart failure, 3 months of Criteria for the diagnosis of invasive fungal disease were antibiotics use, and . 700 mg cumulative prednisone formulated in 2002 and updated in 2008. 9 Although from admission to Aspergillus isolation. Inhaled cortico- intended for research purposes, they serve as a useful steroids may increase the risk of invasive aspergillosis in conceptual framework for the physician at the bedside. patients with COPD. 16,17 Importantly, mortality may be Proven invasive aspergillosis requires histopathologic or increased in critically ill patients when Aspergillus is cytologic evidence of fungus, or culturing Aspergillus isolated, irrespective of evidence for invasive disease.11,18 from a sterile site regardless of immune status. Th e cri- teria for probable disease include clinical upper or lower Th e clinical presentation of invasive aspergillosis respiratory
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