INTRODUCTION — Chronic pulmonary aspergillosis includes several disease manifestations, including aspergilloma, Aspergillus nodules, chronic cavitary pulmonary aspergillosis, and chronic fibrosing pulmonary aspergillosis. Subacute invasive pulmonary aspergillosis (formerly known as chronic necrotizing aspergillosis) is on the spectrum between chronic and acute forms of pulmonary aspergillosis (see 'Definitions' below). A duration of disease longer than three months distinguishes chronic pulmonary aspergillosis from acute and subacute pulmonary aspergillosis.
The pathophysiology, clinical manifestations, and diagnosis of chronic pulmonary aspergillosis will be reviewed here. The treatment of chronic pulmonary aspergillosis as well as allergic bronchopulmonary aspergillosis and invasive aspergillosis is discussed separately. (See "Treatment of chronic pulmonary aspergillosis" and "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis" and "Epidemiology and clinical manifestations of invasive aspergillosis".)
DEFINITIONS — Chronic pulmonary aspergillosis describes several patterns of disease. However, the terminology that has been developed can be difficult to apply to a spectrum of disease entities that have considerable overlap and variation in severity. The following terminology will be used to describe the spectrum of disease; each entity is characterized by specific radiographic findings [1,2].
Aspergilloma — An aspergilloma is a fungus ball composed of Aspergillus hyphae, fibrin, mucus, and cellular debris, constituting a huge biofilm structure, found within a pulmonary cavity [3]. Aspergillomas arise in preexisting pulmonary cavities that have become colonized with Aspergillus spp and are the result of growth of fungus on the cavity wall that detaches into the cavity, often forming a rounded shape, sometimes with air within it [1].
If the aspergilloma is single, the cavity stable over months, and the patient has few symptoms (ie, a mild cough only) and little evidence of systemic inflammation, a simple aspergilloma may be diagnosed. We will use the term "simple aspergilloma" to distinguish this entity from the more complex forms of chronic pulmonary aspergillosis. (See 'Diagnosis' below.)
Aspergillus nodule — Aspergillus nodules occur in immunocompetent hosts, may be single or multiple, and may or may not have cavitation within them [4]. The differential diagnosis includes carcinoma of the lung, nontuberculous mycobacterial infection, and coccidioidal or other fungal nodules. Patients are usually asymptomatic, but some have a new minor pulmonary symptom such as cough, an incidental chest infection, or an exacerbation of asthma or chronic obstructive pulmonary disease. Using positron emission tomography (PET) scanning, Aspergillus nodules are fluorodeoxyglucose avid to variable degrees [5] and are usually accompanied by a positive Aspergillus immunoglobulin (Ig)G titer in the blood. On histopathology, necrosis is surrounded by granulomatous inflammation with occasional multinucleate giant cells [6]. The center of the necrotic material contains fungal hyphae.
Chronic cavitary pulmonary aspergillosis — The term "chronic cavitary pulmonary aspergillosis" describes a pattern of disease in immunocompetent patients in whom there is formation and expansion of one or more pulmonary cavities over months (image 1 and image 2 and image 3 and image 4) [1]. This term is preferred over the older term "complex aspergilloma" because more than 50 percent of such patients don't have an aspergilloma visible radiographically. Over 90 percent of patients with chronic cavitary pulmonary aspergillosis have Aspergillus IgG antibodies in the blood. (See 'Radiographic features' below and 'Laboratory findings' below.)
Chronic fibrosing pulmonary aspergillosis — Chronic fibrosing pulmonary aspergillosis is a late-stage manifestation of chronic cavitary pulmonary aspergillosis in which progression to marked and extensive fibrosis has occurred, sometimes called "destroyed lung" [1,7].
Subacute invasive pulmonary aspergillosis (chronic necrotizing pulmonary aspergillosis) — Patients with some degree of immunocompromise who present with progressive features over one to three months have subacute invasive pulmonary aspergillosis [8] (formerly known as chronic necrotizing pulmonary aspergillosis). This manifestation typically occurs in patients with diabetes mellitus, malnutrition, alcoholism, advanced age, prolonged glucocorticoid use or other modestly immunosuppressive agents, chronic obstructive pulmonary disease, connective disease, radiation therapy, nontuberculous mycobacterial infection, or HIV infection [2]. Hyphal invasion of tissue is observed histologically or can be inferred based upon radiographic findings, including cavitation [1]. Such patients usually have a single thin-walled cavity or area of cavitating pneumonia/consolidation and may have detectable Aspergillus antigen (galactomannan) or Aspergillus IgG antibodies in blood.
PATHOPHYSIOLOGY — The pathogenesis of chronic pulmonary aspergillosis remains incompletely understood. Although patients with chronic pulmonary aspergillosis are generally immunocompetent, most patients with chronic pulmonary aspergillosis have either prior pulmonary damage or disease. Some have subtle immune defects, such as interferon-gamma or interleukin-12 deficiency, reduced production of interferon-gamma, or poor immune response to Streptococcus pneumoniae [9,10]. Aspergillomas usually always arise in pre-existing cavities in the lungs, but the cavity may form initially as a component of chronic pulmonary aspergillosis. Increasing evidence supports major and complex genetic factors in patients with chronic cavitary pulmonary aspergillosis, consistent with an inability to control Aspergillus in the lung, and subsequent persistent inflammation. Low numbers of CD19, CD56, and/or CD4 cells are common in patients with chronic pulmonary aspergillosis [11].
Mycology — Almost all cases of chronic pulmonary aspergillosis are caused by Aspergillus fumigatus, although patients have been described with A. niger or A. flavus infection [12,13]. Occasionally, A. fumigatus isolates may be atypical, growing slowly with poor sporulation, delaying identification.
Underlying diseases — The most common underlying diseases that predispose patients to chronic pulmonary aspergillosis include pulmonary tuberculosis, nontuberculous mycobacterial infection, allergic bronchopulmonary aspergillosis, asthma (usually treated by courses of glucocorticoids), lung cancer (following successful treatment), prior pneumothorax with associated bulla formation, chronic obstructive pulmonary disease, and fibrocavitary sarcoidosis (table 1) [14-16]. Rarer causes include rheumatoid arthritis, ankylosing spondylitis, silicosis, pneumoconiosis, pulmonary hydatid disease, and hyperimmunoglobulin E syndrome. Chronic pulmonary aspergillosis can also evolve from invasive pulmonary aspergillosis that has not completely resolved.
Patients with classical pulmonary tuberculosis who are left with cavities of ≥2 cm have an approximately 20 percent chance of subsequently developing aspergillomas and/or chronic pulmonary aspergillosis [17-19]. In a study that used modeling to estimate the global burden of chronic pulmonary aspergillosis as a sequela of pulmonary tuberculosis, the prevalence of chronic pulmonary aspergillosis varied widely, with a lower prevalence in developed countries than in developing countries [20]. Overall, an estimated 1.2 million people have chronic pulmonary aspergillosis following pulmonary tuberculosis, of whom approximately 300,000 live in India [21]. A cross-sectional study from Nigeria indicates that 8.7 percent of patients with tuberculosis had chronic pulmonary aspergillosis, whether HIV infected or not, with the highest rate in smear and GeneXpert negative TB cases (19 percent) [22]. In a study performed in Uganda, the annual rate of chronic pulmonary aspergillosis was 6.5 percent among patients who had a history of pulmonary tuberculosis with persistent residual cavities; this rate was 30-fold higher than those without residual cavities [15]. Patients with a history of pulmonary infection caused by nontuberculous mycobacteria, such as M. xenopi, M. malmoense, or M. avium complex, may have a higher rate of subsequent chronic pulmonary aspergillosis when compared with patients with a history of pulmonary tuberculosis [14].
Unlike the other forms of chronic pulmonary aspergillosis, subacute invasive pulmonary aspergillosis often occurs in immunocompromised patients such as those with diabetes mellitus, alcoholism, and individuals receiving glucocorticoids [1] (see 'Role of glucocorticoids' below). In contrast, invasive aspergillosis occurs most commonly in profoundly immunocompromised patients, such as neutropenic patients with hematologic malignancies, and transplant recipients. (See "Epidemiology and clinical manifestations of invasive aspergillosis".)
Genetic defects — Many patients with chronic pulmonary aspergillosis appear to have genetic defects in one or more innate immune functions, such as toll-like receptor (TLR) 4, interleukin 15, TLR3, TLR10, triggering receptor expressed on myeloid cells (TREM1), vascular endothelial growth factor A (VEGFA), DENND1B (a gene expressed by natural killer cells and dendritic cells), and/or plasminogen activator gene (PLAT) [23-25]. The interrelationship of these defects with disease expression is complex. Cytokine production profiles are most consistent with a Th2 profile in these patients [26]. Macrophages from patients with chronic cavitary pulmonary aspergillosis produce large amounts of the neutrophil chemoattractant pro-platelet basic protein (CXCL7), suggesting low interleukin 10 levels or activity [27]. (See "The adaptive cellular immune response: T cells and cytokines", section on 'Th2'.)
Patients with chronic pulmonary aspergillosis frequently have poor antibody responses to polysaccharide antigens [28]. Many have a diminished interferon-gamma response [10]. (See "Treatment of chronic pulmonary aspergillosis", section on 'Clinical failure'.)
Role of glucocorticoids — Glucocorticoids given without antifungal therapy in patients with chronic pulmonary aspergillosis may accelerate lung destruction, especially in patients with sarcoidosis or rheumatoid arthritis. Presumably, cavities expand because the Aspergillus growing on the interior surface of the cavity secretes proteins (eg, proteases, phospholipases, catalases, and others) or secondary metabolic products (eg, gliotoxin), which lead to ongoing inflammation and progressive localized lung tissue damage. It is not clear why new cavities form without tissue invasion being demonstrable, why fungal balls are present in some cavities and not others, and why abnormal bronchial arterial vasculature forms, resulting in hemoptysis. Glucocorticoids may be helpful in resolving inflammation in those receiving adequate antifungal therapy.
Pathology — Aspergillomas in the lung are rounded conglomerates of hyphae, mucus, and cellular debris that may be loosely attached to the wall of a pulmonary cavity [3]. On histologic section, a pulmonary aspergilloma has a lamellar appearance due to the accumulation of sequential layers of fungal hyphae combined with fungal extracellular matrix that have grown on the interior surface of the cavity and sloughed off. Oxalate crystals may be visible in tissue, especially in patients with A. niger infection [12].
Chronic cavitary pulmonary aspergillosis is characterized pathologically by chronic inflammation with localized fibrosis, usually without granulomas, necrosis, or eosinophilic infiltrates. Cavity walls may be composed of three layers: necrotic, granulation, and fibrotic tissue [29]. Hyphae do not invade tissue unless the patient becomes immunocompromised, when localized invasive disease supervenes. The distinction between chronic cavitary pulmonary aspergillosis and subacute invasive pulmonary aspergillosis is particularly difficult in patients with rheumatoid arthritis receiving modest doses of immunosuppressants.
Chronic fibrosing pulmonary aspergillosis is characterized by extensive fibrosis and some chronic inflammation distant from a cavity and involving large sections of lung [1].
CLINICAL FEATURES — Patients with chronic pulmonary aspergillosis vary in age from 20 to over 80 years old but are typically in their middle years. In a series of 392 patients with chronic pulmonary aspergillosis, the median age was 59.4 years [1,30]; in series of 194 patients in Japan, the mean age was 68.5 years [31]. The cavitary and fibrosing forms of chronic pulmonary aspergillosis usually progress slowly over months or years, but the subacute invasive form usually progresses more rapidly over weeks.
Signs and symptoms — Patients with chronic pulmonary aspergillosis present most commonly with a several month history of weight loss, chronic productive cough, hemoptysis of variable severity, fatigue, and/or shortness of breath [1,32-34]. Some patients are asymptomatic and identified radiologically. Fever and night sweats occur occasionally. The systemic symptoms of chronic cavitary pulmonary aspergillosis are an important point of distinction from a simple aspergilloma, in which these do not occur.
In a series of 18 patients with chronic pulmonary aspergillosis, the various signs and symptoms were present with the following frequencies [1]:
●Weight loss – 17 patients (94 percent)
●Cough, which is usually productive – 14 patients (78 percent)
●Shortness of breath – 9 patients (50 percent)
●Hemoptysis – 10 patients (58 percent)
●Moderate to severe fatigue/malaise – 5 patients (28 percent)
●Chest pain – 3 patients (17 percent)
●Substantial sputum production – 2 patients (11 percent)
●Fever – 2 patients (11 percent)
It is likely that the patients with fever had subacute invasive pulmonary aspergillosis or a coexistent bacterial infection, as patients with the other forms of chronic aspergillosis rarely have fever.
Radiographic features — Radiographic examination usually reveals one or more cavities, typically within the upper lobes, which may or may not contain fungus balls (image 1 and image 2 and image 3 and image 4) [1,35].
A simple aspergilloma is a fungus ball, visualized because of a rim of air (the original "air crescent sign" or "meniscus sign") in a single pulmonary cavity with limited surrounding inflammation, pleural thickening, or fibrosis. The radiographic appearance often remains stable over several months, unlike in chronic cavitary pulmonary aspergillosis, in which cavities may expand or coalesce. It develops from detachment of layers of growth of fungus on the inner cavity wall over weeks or months, with several intermediate appearances before being seen as a typical fungal ball [36].
Chronic cavitary pulmonary aspergillosis usually begins as ill-defined regions of consolidation that progress to form clearly defined cavities [1]. Cavities may contain fungus balls, debris, or fluid. There are often multiple cavities of different sizes. It is most common for the cavities to be thin-walled and to lack associated pleural thickening, although both thick cavity walls and pleural thickening occur in some cases. If pericavitary infiltrates and pleural thickening adjacent to cavities are present, they generally improve very slowly with appropriate therapy, leaving residual thin-walled empty cavities. New cavity formation or expansion of one or more existing cavities over time is highly characteristic and typically occurs over months in the absence of treatment.
Single or multiple nodules are also seen in chronic pulmonary aspergillosis [5]. They are not usually spiculated and are therefore not typical of lung carcinoma; nevertheless, carcinoma should always be considered in the differential diagnosis. These may or may not cavitate, forming a small air crescent, and may develop into larger cavities over time. Such nodules have been noted to be moderately or strongly positive on positron emission tomography (PET) scanning, mimicking carcinoma of the lung [5].
Chronic fibrosing pulmonary aspergillosis is characterized by the same radiographic findings that occur with chronic cavitary pulmonary aspergillosis in combination with significant fibrosis.
In contrast with chronic cavitary pulmonary aspergillosis, thin-walled cavities or consolidation with cavitation associated with subacute invasive pulmonary aspergillosis usually worsen over weeks to a few months [1].
Although the diagnosis of chronic pulmonary aspergillosis can be inferred from a single chest radiograph, detailed and sequentially acquired radiographic data may be required to observe both the typical radiographic features and the very slow progression (over months or years) that is characteristic of the cavitary and fibrotic forms of this disease. Computed tomography (CT) scans are useful to define the precise pattern and extent of involvement. PET scans of chronic cavity pulmonary aspergillosis show marked pleural inflammation, and nodules are usually positive at varying levels of intensity but do not discriminate between different causes [5,37].
Serial imaging is useful not only for following the progression of disease prior to starting therapy but also for evaluating the response to therapy, although it improves very slowly. (See 'Monitoring during therapy' below.)
Laboratory findings — The cardinal test for chronic pulmonary aspergillosis is a positive Aspergillus IgG antibody test from the serum [38-41]. Previously, Aspergillus precipitins were done but appear to be less sensitive [38,42]. Most (85 to 92 percent) patients with chronic cavitary pulmonary aspergillosis, including those with simple aspergillomas and Aspergillus nodules, have positive Aspergillus IgG antibodies in the blood [41,43-46]. Patients with a negative test but highly suspicious findings should have an alternative Aspergillus IgG test performed. Patients with characteristic features of chronic pulmonary aspergillosis and negative Aspergillus IgG have more immune deficits than those with positive antibody titers [9]; some may have positive Aspergillus IgE tests. Very few centers offer Aspergillus IgG testing for non-fumigatus species. These tests may be useful in those with negative A. fumigatus IgG tests but are not standardized or validated.
The differential diagnosis of a positive Aspergillus IgG test if there is radiologic or clinical uncertainty about the diagnosis of chronic pulmonary aspergillosis includes Aspergillus bronchitis, allergic bronchopulmonary aspergillosis, chronic or allergic Aspergillus rhinosinusitis, invasive pulmonary aspergillosis (acute or resolved), and subacute invasive pulmonary aspergillosis.
More than 50 percent of patients with chronic pulmonary aspergillosis have positive Aspergillus IgE tests, and some have slightly elevated total serum IgE levels without having allergic bronchopulmonary aspergillosis (ABPA) [1]. Patients with ABPA as their underlying diagnosis usually have very high total IgE and Aspergillus IgE results. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)
A minority of patients (10 to 40 percent) with chronic pulmonary aspergillosis have positive cultures of A. fumigatus (or rarely other Aspergillus species) in their sputum [32]. Multiple samples increase the recovery rate. A higher proportion has a positive Aspergillus polymerase chain reaction (PCR) from the sputum or bronchoalveolar lavage (BAL) fluid. Among 42 patients with chronic pulmonary aspergillosis, 71 percent had a positive PCR from the sputum but only 17 percent had a positive culture [47]. High volume cultures have a higher yield [48]. However, 4 of 11 normal volunteers had a positive PCR from BAL, so false-positive PCR results can occur and are likely due to transient colonization or contamination of samples. Galactomannan is also detectable in BAL fluid in about 50 to 90 percent of patients [49,50]. Galactomannan in sputum is not a useful test as it is so frequently positive and cut-offs have not been established for chronic pulmonary aspergillosis [51].
Elevated galactomannan and 1,3-beta-D-glucan levels have been reported in serum in some patients with chronic pulmonary aspergillosis [37,50,52,53]. In a retrospective cohort study that included 48 patients with pulmonary aspergilloma, the galactomannan assay had a sensitivity of 38 percent for serum and 92 percent for BAL fluid [49]. Galactomannan detection from serum was higher in patients with hemoptysis compared with those without hemoptysis (52 versus 9 percent). (See "Diagnosis of invasive aspergillosis", section on 'Galactomannan antigen detection'.)
Elevated inflammatory markers, such as C-reactive protein and/or erythrocyte sedimentation rate, are very common in patients with chronic pulmonary aspergillosis but are not specific [1].
Pulmonary function testing — Most patients have significant reduction in pulmonary function, with the character and degree of abnormalities reflecting their underlying pulmonary disease. Chronic fibrosing pulmonary aspergillosis leads to major reductions in vital and diffusing capacity, often with abnormally low oxygen saturations. Hypoxic respiratory failure with either hypocapnia or hypercapnia may occur, typically during an acute bacterial infection.
A flight assessment is useful to determine the need for supplemental oxygen for air travel. (See "Evaluation of patients for supplemental oxygen during air travel".)
DIAGNOSIS — Once chronic pulmonary aspergillosis is considered, usually on the basis of general symptoms of fatigue and weight loss with one or more cavities in one or both lung apices with negative tests for tuberculosis, the diagnosis is established by a positive Aspergillus IgG serology. Some patients have a positive culture of Aspergillus spp from the lungs, but this alone is insufficient to make the diagnosis of chronic pulmonary aspergillosis if Aspergillus IgG antibodies are negative or pending.
In patients with negative fungal cultures, bronchoscopy should be considered to collect samples for fungal and mycobacterial stains and cultures and to exclude malignancy. Nontuberculous mycobacterial disease can precede, occur concurrently with, or follow chronic pulmonary aspergillosis. Concurrent bacterial infection (often an exacerbation of bronchiectasis) is common and occasionally occurs in a cavity, resulting in a fluid level. Ultrasound- or computed tomography (CT)-guided aspiration may be required to document the pathogen, such as methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa.
Aspergilloma — The criteria for the diagnosis of aspergilloma are radiologic evidence of a rounded mass in a pulmonary cavity combined with microbiologic evidence of Aspergillus as the causative agent, usually a positive culture from sputum or detectable Aspergillus IgG. Since aspergillomas may occur in the context of chronic cavitary pulmonary aspergillosis, the distinction between a simple aspergilloma and chronic cavitary pulmonary aspergillosis relies on symptomatology, evidence of inflammation, the radiologic appearance, and change over time. If the aspergilloma is single, the cavity stable over months, and the patient has few symptoms (ie, a mild cough only) and little evidence of systemic inflammation, a simple aspergilloma may be diagnosed.
Aspergillus nodule — The diagnosis of an Aspergillus nodule can be made in an immunocompetent patient in whom lung carcinoma has been excluded by the combination of one or more lung nodules on lung imaging and either a percutaneous or surgical biopsy (eg, by video-assisted thorascopic surgery) showing Aspergillus in tissue or a positive Aspergillus IgG titer in blood [2,4].
Chronic cavitary pulmonary aspergillosis — The specific criteria used for the diagnosis of chronic cavitary pulmonary aspergillosis are [1,2,32]:
●One large cavity or two or more cavities on chest imaging with or without a fungal ball (aspergilloma) in one or more of the cavities
and
●At least one of the following symptoms for at least three months: fever, weight loss, fatigue, cough, sputum production, hemoptysis, or shortness of breath
and
●A positive Aspergillus IgG with or without culture of Aspergillus spp from the lungs
Some patients may have concurrent infection with Mycobacterium tuberculosis, nontuberculous mycobacteria or other bacteria. Coccidioidomycosis, chronic cavitary pulmonary histoplasmosis, and paracoccidioidomycosis should be excluded with serology and culture; chronic pulmonary histoplasmosis with an aspergilloma has been described.
Chronic fibrosing pulmonary aspergillosis — The criteria for the diagnosis of chronic fibrosing pulmonary aspergillosis are similar to those for chronic cavitary pulmonary aspergillosis. In addition, substantial areas of fibrosis (determined by biopsy or inferred from CT scanning of the thorax) in immediate proximity to an area of chronic cavitary pulmonary aspergillosis are seen, and there is major impairment of respiratory function.
Subacute invasive pulmonary aspergillosis (chronic necrotizing pulmonary aspergillosis) — As noted above, most patients with subacute invasive pulmonary aspergillosis (formerly known as chronic necrotizing pulmonary aspergillosis) have some evidence of immunosuppression. The criteria for the diagnosis of subacute invasive pulmonary aspergillosis are similar to those for invasive pulmonary aspergillosis, but the subacute form progresses more slowly than the acute form (over 1 to 3 months versus over 0 to 4 weeks) [2]. Patients may have detectable Aspergillus antigen (galactomannan) or Aspergillus IgG antibody in the blood. Confirmation requires a biopsy of the pulmonary lesion. (See "Diagnosis of invasive aspergillosis", section on 'Diagnostic modalities'.)
MONITORING DURING THERAPY — Aspergillus IgG and inflammatory markers (C-reactive protein, plasma viscosity, and/or erythrocyte sedimentation rate) should be repeated approximately every three months during therapy, and they usually fall slowly with successful therapy [54]. Patients with very high Aspergillus IgG levels (often beyond the dynamic range of the assay) respond more rapidly than those with modest titers [54]. Chest radiographs should be repeated every 6 to 12 months, depending on clinical status (ie, earlier if deterioration occurs). Computed tomography (CT) scans of the thorax are indicated if there is a major change in clinical status not attributable to a concurrent bacterial infection, new chest radiographic findings despite apparent clinical improvement, and for follow-up evaluation every 12 to 24 months, until clinical stability on therapy is achieved. If the patient does not have hemoptysis, contrast is not required. Low-dose CT is a useful means of minimizing the radiation dose. The expected changes in laboratory and radiographic findings following the initiation of therapy are discussed separately. Relapse following surgical resection of chronic pulmonary aspergillosis can be monitored with Aspergillus IgG, a rise in titer signifying relapse, often years after surgery [55]. (See "Treatment of chronic pulmonary aspergillosis", section on 'Assessing treatment response'.)
Apparent exacerbations must be distinguished from concurrent bacterial respiratory infections, exacerbations of asthma and/or allergic bronchopulmonary aspergillosis, recurrence or development of tuberculosis or nontuberculous mycobacterial infection, and tumor development or recurrence in those at risk. (See "Treatment of chronic pulmonary aspergillosis", section on 'Clinical failure'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Aspergillosis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topic (see "Patient education: Chronic pulmonary aspergillosis (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Chronic pulmonary aspergillosis includes several disease manifestations, including aspergilloma, Aspergillus nodules, chronic cavitary pulmonary aspergillosis, and chronic fibrosing pulmonary aspergillosis. Subacute invasive pulmonary aspergillosis (formerly known as chronic necrotizing aspergillosis) is on the spectrum between chronic and acute forms of pulmonary aspergillosis. A duration of disease longer than three months distinguishes chronic pulmonary aspergillosis from acute and subacute pulmonary aspergillosis. (See 'Introduction' above and 'Definitions' above.)
●Almost all cases of chronic pulmonary aspergillosis are caused by Aspergillus fumigatus, although patients have been described with A. niger or A. flavus infection. (See 'Mycology' above.)
●Almost all patients with chronic pulmonary aspergillosis have either prior pulmonary damage or disease. The most common underlying diseases that predispose patients to chronic pulmonary aspergillosis include pulmonary tuberculosis, nontuberculous mycobacterial infection, allergic bronchopulmonary aspergillosis, lung cancer (following successful treatment), prior pneumothorax with associated bulla formation, chronic obstructive pulmonary disease, and fibrocavitary sarcoidosis (table 1). (See 'Underlying diseases' above.)
●Many patients with chronic pulmonary aspergillosis have genetic defects in one or more innate immune functions and have a diminished interferon-gamma response. (See 'Genetic defects' above.)
●Patients with chronic cavitary pulmonary aspergillosis present most commonly with weight loss, chronic productive cough, hemoptysis of variable severity, fatigue, and/or shortness of breath. Fever and night sweats occur occasionally. The systemic symptoms of chronic cavitary pulmonary aspergillosis are an important point of distinction from a simple aspergilloma, in which these do not occur. (See 'Signs and symptoms' above.)
●Radiographic examination usually reveals one or more cavities, typically within the upper lobes, which may or may not contain fungus balls. New cavity formation or expansion of one or more existing cavities over time is highly characteristic of chronic cavitary pulmonary aspergillosis. (See 'Radiographic features' above.)
●The cardinal test for chronic pulmonary aspergillosis is a positive Aspergillus immunoglobulin (Ig)G antibody test from the serum. Serum galactomannan is usually negative, and 1,3-betaD-glucan is often positive. However, standardization of this testing is not well established for this indication. A minority of patients with chronic pulmonary aspergillosis has positive cultures of A. fumigatus (or rarely other Aspergillus species) in their sputum, but Aspergillus polymerase chain reaction from the sputum is usually positive. More than 50 percent of patients have positive Aspergillus IgE tests, and some have slightly elevated total serum IgE levels without having allergic bronchopulmonary aspergillosis. (See 'Laboratory findings' above.)
●Elevated inflammatory markers, such as C-reactive protein and/or erythrocyte sedimentation rate, are very common in patients with chronic pulmonary aspergillosis but are not specific. (See 'Laboratory findings' above.)
●Once chronic pulmonary aspergillosis is considered, usually on the basis of general symptoms of fatigue and weight loss with one or more cavities in one or both lung apices with negative tests for tuberculosis, the diagnosis is established by a positive Aspergillus IgG. Some patients have a positive culture of Aspergillus spp from the lungs, but this alone is insufficient to make the diagnosis of chronic pulmonary aspergillosis if Aspergillus IgG antibodies are negative or pending. (See 'Diagnosis' above.)
●Aspergillus IgG and inflammatory markers (C-reactive protein and erythrocyte sedimentation rate) should be repeated approximately every 3 months during therapy and chest radiographs every 6 to 12 months, depending on clinical status (ie, earlier if deterioration occurs). (See 'Monitoring during therapy' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David Denning, MBBS, FRCP, FRCPath, FMedSci, who contributed to an earlier version of this topic review.
