Common misconceptions and mistakes
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Confusing an aspergilloma or fungus ball with chronic fibrosing pulmonary aspergillosis
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Failing to make the distinction between allergic bronchopulmonary aspergillosis (ABPA) and asthma with fungal sensitization
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Believing that invasive pulmonary aspergillosis only occurs in bone marrow transplant patients
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Not attempting antifungal therapy in a steroid-dependent asthmatic with mucus plugging and bronchiectasis, because of negative aspergillus serology
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Failing to diagnose and treat chronic fibrosing aspergillosis
Aspergillus
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Aspergillus is:
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The most common invasive mold
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Ubiquitous—found in soil and decomposing organic matter (worldwide)
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The most common contaminant seen in specimens exposed to unfiltered air (during processing)
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A common colonizer seen in the sputum of ~ 3% of healthy individuals and ~ 10% of cigarette smokers, HIV-infected individuals, or those with chronic parenchymal lung disease
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Aspergillus fumigatus causes ~ 90% of human diseases
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Together, Aspergillus flavus, Aspergillus terreus, and Aspergillus niger are responsible for the rest
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Serology is not available for these less common human-pathogen Aspergillus species
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Aspergillus disease begins with (the relatively common event of) accidental spore inhalation
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In the normal host, inhaled spores are rapidly cleared by the immune system
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In individuals with underlying lung disease or in those with immunologic sensitization to Aspergillus or immunosuppression, inhalation of spores may result in colonization, hypersensitivity, or invasive disease, respectively
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Small clusters of invasive pulmonary aspergillosis have been reported when an environmental focus (eg, hospital construction) exposes a group of immunosuppressed patients (eg, bone marrow transplant ward)
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Human-to-human transmission does not occur
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Aspergillus causes seven distinct pulmonary syndromes in allergic individuals and those with parenchymal lung disease or immunosuppression:
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Atopic/allergic/asthmatic individuals are vulnerable to:
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Severe asthma with fungal sensitization (immunoglobulin E [IgE]-mediated asthma)
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Allergic bronchopulmonary aspergillosis (ABPA)
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Hypersensitivity pneumonitis (HP)
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Individuals with chronic parenchymal lung disease (especially chronic obstructive pulmonary disease [COPD]) are vulnerable to:
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Aspergilloma
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Chronic pulmonary aspergillosis (CPA)
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Semiinvasive (noncavitary)
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Chronic fibrosing (cavitary)
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Patients with any degree of immune suppression are at risk for:
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Invasive pulmonary aspergillosis (IPA) ranging from:
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Atypical (nodular) bronchopneumonia to
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Vessel-invasive disseminated disease
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Tracheobronchial aspergillosis (seen after lung transplant and in HIV infection)
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Significant overlap may be seen in these syndromes (eg, allergic disease may progress to invasive disease in the setting of high-dose prednisone therapy)
Allergic aspergillus diseases
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Severe asthma with fungal sensitization (IgE-mediated asthma):
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Patients with severe extrinsic IgE-mediated asthma triggered by environmental Aspergillus antigens (and many others) are different from individuals with ABPA
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~ 30% of individuals with asthma demonstrate fungal sensitization (immediate skin test reactivity to Aspergillus)
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Asthma with fungal sensitization can be differentiated from ABPA by the absence of bronchiectasis, mucus plugging, and high IgE levels
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IgE levels < 1000 IU/mL (obtained off of prednisone) makes severe asthma with fungal sensitization more likely than ABPA
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Avoidance of antigen (eg, moldy environments) is crucial for asthma control in these individuals
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HP:
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Inhalation of organic matter contaminated with Aspergillus species has been associated with HP (eg, Malt-worker’s lung)
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Hypersensitivity pneumonitis is a clinical diagnosis such that specific allergen testing is not sensitive, specific, or helpful
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ABPA:
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ABPA is a clinical syndrome involving a hypersensitivity to A. fumigatus, which occurs in predisposed individuals (ie, those with asthma or cystic fibrosis)
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Age of onset is 30–50 years old
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The clinical syndrome of ABPA is characterized by:
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Episodic “or fleeting” chest radiograph infiltrates
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Significant IgE elevations (> 1000 IU/mL)
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Poorly controlled asthma (~ 80% of the time)
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Common symptoms of ABPA, aside from poorly controlled asthma, include:
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Productive cough with mucus plugs
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A history of recurrent pneumonia (diagnoses)
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Often with a clinical radiographic discrepancy between a significant infiltrate on chest x-ray, and muted clinical findings
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Fleeting ABPA infiltrates are often a result of mucus plugging and subsegmental atelectasis (rather than representing true infectious consolidations)
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Intermittent fever (immune system activation)
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Chest pain (often from mucus plugging and atelectasis)
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Hemoptysis
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Occurs on a spectrum from (nonmassive) blood-tinged sputum, secondary to mucosal irritation associated with coughing, to bronchiectatic bleeding (potentially massive)
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Radiographic findings seen in/suggestive of ABPA include:
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The “finger in glove” sign describing branching tubular (vascular-looking) homogeneous opacities (actually representing mucus-impacted airways) ( Fig. 10.1 ])
Fig. 10.1
Posterioranterior (PA) and lateral chest x-ray (with mark-up) showing the “finger in glove” sign of mucus impaction in allergic bronchopulmonary aspergillosis (ABPA). Computed tomography (CT) scan confirms that the tubular branching opacities are completely impacted airways.
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Fleeting upper lobe infiltrates and wedge-shaped infiltrates (subsegmental atelectasis) ( Fig. 10.2 )
Fig. 10.2
Posterioranterior (PA) and lateral chest x-ray (CXR) showing a “fleeting” or rapidly resolving consolidation (time course too fast for resolution of an infectious consolidation). Computed tomography (CT) scan shows central bronchiectasis occurring in the same region, supporting the diagnosis of subsegmental atelectasis from mucus impaction (rather than a pneumonic consolidation).
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Tramline and ring shadows (bronchial wall thickening)
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Bronchiectasis, classically central (medial two-thirds of the chest), but may also be distal; often identified by computed tomography (CT) scan (see Fig. 10.2 )
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High-attenuation mucus (HAM) impaction seen on CT scan is nearly pathognomonic for ABPA and is predictive of relapsing, progressive disease
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The differential diagnosis of ABPA includes:
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Allergic bronchopulmonary mycosis (same syndrome, different fungus, serology not available/helpful)
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IgE-mediated asthma with fungal sensitization (as discussed previously)
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pulmonary infiltration with eosinophilia syndromes, helminthic lung disease, and other types of hypersensitivity pneumonitis
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The diagnosis of ABPA can be confidently made when an individual has a compatible clinical syndrome and the following:
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Asthma or cystic fibrosis (ie, predisposing condition)
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Type I allergic response to Aspergillus (ie, positive serum IgE specific for Aspergillus or a positive skin test)
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Two of the following three:
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Positive IgG specific to A. fumigatus
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Imaging findings suggestive of ABPA (eg, fleeting infiltrates, bronchiectasis, or HAM plugs)
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Total eosinophil count > 500 cells/μL and/or IgE > 1000 IU/mL (during a flare and while off prednisone)
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Patients with ABPA can be divided into five clinical stages:
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Acute ABPA (stage I) describes the initial presentation of classic ABPA
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Remission (stage II) is defined as no recurrence for at least 6 months after prednisone therapy is stopped
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Remission is expected (and achieved in over 90% of all patients)
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Relapse is common and may occur several years later
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Patients in remission should be screened with serial IgE measurements every 3–6 months (for the first year)
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ABPA exacerbation (stage III) occurs in nearly half of all patients and may be clinically silent, consisting only of asymptomatic infiltrates or an increase in IgE levels (2–10 times higher than baseline values)
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Almost half of all patients with ABPA who experience exacerbations progress to steroid-dependent asthma
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ABPA with corticosteroid-dependent asthma (stage IV) lacks the typical features of IgE elevation and fleeting infiltrates (because of prednisone)
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Diagnosing ABPA at stage IV involves paring a clinically compatible history with imaging, demonstrating either:
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Bronchiectasis, HAM impaction on chest CT, or previous fleeting upper lobe infiltrates
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Fibrotic ABPA (stage V) refers to patients with ABPA who develop mixed obstructive–restrictive lung disease with symptomatic bronchiectasis and respiratory failure
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Treatment of ABPA focuses on decreasing organism colonization and burden with antifungals and control of exaggerated inflammation with prednisone
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Both the initial presentation and subsequent exacerbations should be treated with antifungal therapy
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Itraconazole is first line (because of cost) but has poor oral absorption known to cause treatment failures
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Voriconazole is a reasonable alternative
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Antifungal therapy should be given for 3–6 months based on clinical improvement/ability to taper (and remain off of) prednisone
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Prednisone should be initiated, dosed, and tapered based on symptomatic bronchospasm (as in asthma) rather than IgE levels in isolation (which take time to fall)
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Once prednisone is stopped, individuals should be screened for recurrent infiltrates, clinical symptoms, or a rise in total serum IgE
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ABPA should rapidly improve with therapy (resolution of infiltrates, improved asthma, reduced sputum, and decreased peripheral blood eosinophilia by 4 weeks, with decreased total serum IgE by 6 weeks)
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Bronchoscopy can be used to clear proximal airway mucus impaction and segmental lung collapse not relieved by chest physiotherapy
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Persistent proximal mucus impaction (> 3 weeks) increases the risk of bronchiectasis
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Allergic bronchopulmonary mycosis:
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Some individuals have the clinical syndrome of ABPA, involving to either a non-fumigatus species of Aspergillus or another environmental fungus, making serology and skin testing unhelpful
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Because of this, most steroid-dependent asthmatics deserve an empiric trial of antifungal therapy before being condemned to lifelong prednisone
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Aspergilloma
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Aspergilloma (a.k.a. fungus ball) refers to a mobile, intracavitary mass of fungal mycelia, inflammatory cells, and tissue debris occurring in a preexisting, poorly communicating lung cavity, bullae, or cyst
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Aspergilloma commonly occurs in emphysematous bullae or in association with prior cavitary lung disease (eg, tuberculosis [TB], lung cancer treated with XRT, coccidioidomycosis, cysts)
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Most aspergillomas are discovered incidentally on chest imaging
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Commonly appear as an intraluminal irregularity in an upper lobe cavity
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Prone CT imaging and/or fluoroscopy should demonstrate mobility of the irregularity with positional changes ( Fig. 10.3 )
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