- Author: Eloise M Harman, MD; Chief Editor: Ryland P Byrd, Jr, MD more...
Further Outpatient Care
ABPA is usually managed in an outpatient setting. Serial measurement of the serum IgE level is a useful way to monitor response to therapy and to predict relapse after initial management. Levels are measured every 1-2 months during an exacerbation and every 3 months during remission. The rationale for repeat measurements of IgE levels during clinical remission is that 35% of exacerbations are asymptomatic but may result in lung damage. Elevated IgE levels should be evaluated further with a chest radiograph and institution of therapy with prednisone and possibly itraconazole.
Patients with invasive aspergillosis or CNPA who respond to initial inpatient treatment may require several weeks of antifungal therapy. Oral voriconazole or itraconazole (sometimes chosen because of cost) is administered until clinical and radiographic resolution.
Further Inpatient Care
For invasive aspergillosis, monitor the patient for resolution of fever, hypoxemia, and pulmonary infiltrates. Patients who do not respond to therapy with voriconazole or combination therapy with voriconazole and caspofungin should be seen in consultation by an infectious disease specialist. Monitoring of serum voriconazole levels may be considered in nonresponders. Consider reducing immunosuppression if possible based on the underlying disease. Other considerations include surgical resection for localized disease and the addition of other antifungal agents.
Inpatient & Outpatient Medications
ABPA therapy includes oral prednisone and, in selected cases, oral itraconazole, usually for several months. As the patient is tapered off oral steroids, inhaled corticosteroids should be added for control of underlying asthma. The concomitant use of inhaled budesonide and oral itraconazole has been found to cause adrenal suppression in a significant proportion of patients with CF and ABPA.
For aspergilloma, oral itraconazole therapy may be beneficial. A Japanese study found that 60% of patients with aspergilloma had some response to oral itraconazole. In patients with bilateral aspergillomas or severe underlying disease preventing surgical resection, oral itraconazole therapy may be continued for several months.
For invasive aspergillosis and CNPA, specific antifungal therapy with oral or intravenous voriconazole is the usual initial therapy. Response to therapy may be poor. In patients who respond, prolonged therapy may be required.
Transfer to a tertiary care center may be warranted in patients with aspergilloma or invasive aspergillosis with massive hemoptysis if bronchial artery embolization or surgical resection is considered. Patients with invasive aspergillosis who do not respond to initial antifungal therapy may also benefit from transfer to a center where infectious disease expertise in the management of fungal infections is available.
Invasive aspergillosis is frequently fatal, and prevention is the best way to decrease its associated morbidity and mortality. The use of LAF rooms or HEPA filters decreases the concentration of fungi and bacteria in hospital rooms. Use of LAF rooms has been shown to decrease the incidence of invasive Aspergillus infection in patients undergoing bone marrow transplantation.
Prophylactic antifungal therapy is also indicated in high-risk patients, as follows:
Although fluconazole is not effective against Aspergillus, it significantly decreases the incidence of fungal infections after bone marrow transplantation and is the most frequently used oral prophylactic antifungal therapy 
Oral itraconazole has been found to be less effective than fluconazole, probably because of poor bioavailability of the drug in capsule form
Posaconazole has been shown to be more effective than fluconazole for preventing invasive Aspergillus infection in patients with graft-versus-host disease (GVHD), though the overall incidence of fungal infections is similar for the two drugs.  ; posaconazole is approved for prophylaxis of invasive Aspergillus and Candida infections in high-risk patients, including those with GVHD and prolonged neutropenia from chemotherapy; because posaconazole is a broad-spectrum antifungal agent and widespread use would promote resistance, posaconazole prophylaxis should be limited to patients at highest risk or those with known resistance to other antifungals 
Oral itraconazole appears to be a safe and effective prophylactic antifungal for children with chronic granulomatous disease
ABPA may cause atelectasis, asthma exacerbation, and steroid dependence. Recurrent ABPA episodes may result in widespread bronchiectasis and fibrosis.
Hemoptysis is a frequent complication of aspergilloma.
Invasive aspergillosis may result in respiratory failure and death. Massive hemoptysis may occur. Aspergillus may disseminate to other organs, including the central nervous system, kidneys, and heart, and result in multisystem organ failure.
The prognosis for ABPA is fairly good in patients with mildly abnormal pulmonary function. However, patients may remain steroid-dependent. If ABPA is detected late, after the establishment of fibrosis, the response to steroids frequently is poor.
The prognosis for patients with invasive pulmonary aspergillosis is poor. Of these patients, 25-60% may respond to antifungal therapy, but the mortality remains high because of the severity of the underlying disease and the need for continued immunosuppressives and steroids in many patients. If patients respond, at least a 50% chance of relapse exists with subsequent courses of immunosuppression. Disease disseminated to the central nervous system carries a mortality of 100%, as does fungal endocarditis without surgery.
Development of triazole resistance has been blamed for eventual loss of control of the disease in patients receiving long-term triazole therapy. Detection of resistance is made difficult by the high frequency of negative cultures, a problem addressed by a study using hypersensitive real-time PCR assays to assess fungal load in BAL and sputum samples. In culture-negative specimens that were PCR-positive, the CYP51A gene (responsible for most triazole resistance) was amplified to reveal resistance markers in 55% of patients with ABPA or chronic pulmonary aspergillosis. The authors suggest a connection between this "remarkably high" rate and limitations to the effectiveness of azole therapy.
For patient education information, see Bronchoscopy.
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