eMedicine Specialties > Radiology > Chest

Aspergillosis, Thoracic

Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia
Coauthor(s): Sarah Al Ghanem, MBBS, Consulting Staff, Department of Medical Imaging, King Fahad National Guard Hospital, Riyadh, Saudi Arabia; Klaus L Irion, MD, PhD, Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK; Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Carolyn M Allen, MB, BCh, MRCP, FRCR, CCST, Consultant Radiologist, Department of Clinical Radiology, North Manchester General Hospital, UK
Contributor Information and Disclosures

Updated: May 1, 2008

Introduction

Background

Pulmonary aspergillosis is a spectrum of mycotic diseases caused by the Aspergillus species, usually Aspergillus fumigatus.^1,2 This intensely antigenic and ubiquitous soil fungus is commonly found in the sputum of healthy individuals. However, in susceptible hosts, its ability to invade the arteries and veins facilitates its hematogenous spread.

The development of disease and its histologic, clinical, and radiologic manifestations depend on the virulence and number of spores inhaled and, more importantly, on the patient's immune status.

Pulmonary aspergillosis may take any of 4 forms^1,2 :

• Allergic bronchopulmonary aspergillosis (ABPA) is caused by a hypersensitivity reaction to the fungus and most commonly occurs in those with asthma.
• Saprophytic aspergillosis, or aspergilloma, is the most common form, which is noninvasive and involves colonization of preexisting cavities.
• Chronic necrotizing aspergillosis, also called airway-invasive or semi-invasive aspergillosis, is a chronic cavitary pneumonic illness that often affects patients with preexisting chronic lung disease.
• Angioinvasive aspergillosis affects immunocompromised patients and is often fatal.

For excellent patient education resources, visit eMedicine's Lung and Airway Center and Asthma Center. Also, see eMedicine's patient education articles Asthma, Allergy, and Acute Respiratory Distress Syndrome.

Related eMedicine topics:
Asthma
Chronic Granulomatous Disease
Lung, Primary Tuberculosis
Pneumonia, Fungal

Related Medscape topics:
Resource Center Allergy
Resource Center Immune Reconstitution
Resource Center Pneumonia
CME/CE Guidelines for the Diagnosis and Management of Asthma -- Part 1: Introduction -- Diagnosing Asthma
CME/CE Guidelines for the Diagnosis and Management of Asthma -- Part 2 - Managing Asthma Long Term
CME Highlights of the United States and Canadian Academy of Pathology 2007 Annual Meeting: Pulmonary Pathology of Transplantation

Pathophysiology

A fumigatus exists in 2 forms: (1) conidiophores, the reproductive forms that produce and release thousands of spores, and (2) hyphae, which represent mature spores that are characterized by a 45º dichotomous branching pattern (see Images 1 and 2). The fungus grows widely in soil, water, and decaying vegetable or animal material. The spores are readily inhaled, and the fungus is a common commensal organism in the upper respiratory tract.

Most patients with pulmonary aspergillosis have either an underlying preexisting chronic lung disease or impaired immunity. Examples of preexisting chronic lung disease include bronchiectasis, chronic obstructive lung disease (COPD), and tuberculosis. Impaired immunity secondary to alcoholism, advanced age, poorly controlled diabetes mellitus, underlying malignancy, cirrhosis, malnutrition, sepsis, organ transplantation, or acquired immunodeficiency syndrome (AIDS), for example.^3,4,5,6,7,8

ABPA represents a hypersensitivity reaction to A fumigatus in patients with long-standing asthma or cystic fibrosis. Excessive mucus production in association with impaired ciliary function leads to mucoid impaction of the airways. The plugs of inspissated mucus contain A fumigatus and eosinophils, but the organisms remain within the bronchial lumen; this feature differentiates ABPA from invasive aspergillosis.

Precipitating antibodies incite a type I acute hypersensitivity reaction with the subsequent release of immunoglobulin E (IgE) and immunoglobulin G (IgG). Immune complexes and inflammatory cells are then deposited within the bronchial mucosa. This deposition produces tissue necrosis and eosinophilic infiltrate, a type III reaction, and results in damage to the bronchial wall with the subsequent development of bronchiectasis. Patients may cough up mucus plugs, from which hyphal elements can be cultured or observed at microscopy.

The primary diagnostic criteria for ABPA include the following:

• Asthma, 84-96%
• Blood eosinophilia, 8-40%
• Elevated serum IgE levels
• Positive skin test results for A fumigatus
• Elevated serum levels of IgE and IgG specific for A fumigatus
• Presence of precipitating antibodies to A fumigatus

The primary radiologic criteria include fixed or transitory pulmonary infiltrates and central bronchiectasis as a late manifestation.^9,10 A set of secondary criteria can sometimes be applied; these include the presence of A fumigatus mycelia in the sputum, the expectoration of brown sputum plugs, and a delayed cutaneous reaction to A fumigatus antigen.

ABPA can be staged by using the following clinical and radiologic criteria:

• Stage I – Acute presentation with 6 of the 8 primary diagnostic criteria listed above
• Stage II – Resolving pulmonary infiltrates with decreasing IgE levels leading to remission
• Stage III – Recurrence of acute symptoms after a period of remission
• Stage IV – Steroid dependency
• Stage V – Irreversible lung damage leading to fibrosis

In the saprophytic form (ie, aspergilloma), noninvasive colonization of a preexisting cavity, cyst, bulla, or ectatic bronchus occurs. The most common underlying conditions are tuberculosis, sarcoidosis, and bronchiectasis. Others include cystic fibrosis, ankylosing spondylitis, bronchogenic cysts, pneumoconiosis, pulmonary sequestration, cavitating malignancy, and pneumatoceles secondary to Pneumocystis carinii pneumonia.

Histologically, the aspergilloma represents a fungal ball, or mycetoma, which consists of a masslike conglomerate of intertwined hyphae intermingled with fibrin, cellular debris, mucus, and other blood products. This mycetoma may calcify in an amorphous or ringlike fashion. Elevated serum precipitin levels are present in approximately 50% of the patients.

Chronic necrotizing aspergillosis, or semi-invasive aspergillosis, is an indolent disease that affects patients with mild immunosuppression due to chronic debilitating illness, particularly those with COPD. Other recognized predisposing illnesses include alcoholism, advanced age, and prolonged steroid administration. Bronchiolitis and bronchopneumonia develop, with slowly progressive cavitating consolidation predominating in the upper lobes (see Images 7 and 8). This consolidation may be indistinguishable from tuberculosis. Histologically, a proliferation of organisms within the alveolar spaces, intra-alveolar hemorrhage, and bronchial wall invasion that leads to tissue necrosis with microabscess formation are present, but no angioinvasion is observed.

Invasive aspergillosis is the most common fungal pulmonary infection in severely immunocompromised patients, particularly those with reticuloses. Transplant recipients are also at particular risk.^6,7 The spores proliferate in the airways; this proliferation leads to transbronchial angioinvasion that causes hemorrhagic infarction. These areas may become cavitated and contain a devitalized sequestrum of infected lung; moreover, these areas can mimic a mycetoma. Also, the fungus can disseminate systemically in approximately 33% of cases and affect the heart, brain, kidneys, liver, spleen, thyroid, and gastrointestinal tract.

A fumigatus may also infect the pleura, causing an empyema in patients with pulmonary tuberculosis or bronchopleural fistulae. Occasionally, A fumigatus may secondarily infect an existing bacterial empyema.

Frequency

United States

Approximately 1-2% of asthmatic patients and 10% of patients with cystic fibrosis have ABPA. Aspergillomas are reported to account for 0.02% of hospital admissions. The precise incidence of chronic necrotizing aspergillosis is unknown, but it is thought to be increasing.

The number of patients with invasive aspergillosis has substantially increased. One of the reasons for this increasing incidence is the development of new intensive chemotherapy for leukemia, lymphoma, and myeloma, as well as the increasing numbers of solid organ transplantations. Invasive pulmonary aspergillosis (IPA) is reported in 5% of bone marrow transplant recipients, 3-9% of renal transplant recipients, and 1-5% of heart and/or lung or liver transplant recipients.

Related Medscape topics:
Specialty Site Hematology-Oncology
Specialty Site Transplantation

International

Aspergillomas are complications in 15-20% of patients with lung cavities 2 cm or larger. The incidence of invasive aspergillosis in AIDS patients is 1-12% worldwide. In the United Kingdom, the incidence is estimated to be 4-5%.

Mortality/Morbidity

The mortality and morbidity rates with pulmonary aspergillosis depend on the type of disease.^1,2,11

• In most patients, ABPA responds to steroids, but a small proportion of cases are refractory to treatment and progress to stage V disease.
• Approximately 10% of mycetomas resolve spontaneously. Massive hemoptysis, defined as the expectoration of more than 600 mL of blood in 48 hours, is a well-recognized complication.^12,13 Most patients are not candidates for surgery and are treated conservatively. However, the mortality rate in these patients can be as high as 50-55%, compared with a 1-23% surgical mortality rate.
• Chronic necrotizing aspergillosis has a significant morbidity rate, and, if left untreated, this condition has a significant mortality rate. However, the precise incidences are unknown. The slow progression of clinical and radiologic findings may contribute to a delay in diagnosis.
• The prognosis in invasive aspergillosis is uniformly poor, and the mortality rate is high. Early diagnosis and prompt treatment are essential in determining survival.

Sex

The male-to-female incidence is 3:1.

Age

Pulmonary aspergillosis mostly affects adults aged 20-90 years.

Anatomy

Most mycetomas derive their blood supply from the bronchial arteries. The bronchial arteries not only perfuse the bronchi but also contribute blood supply to the mid esophagus, diaphragm, mediastinal visceral pleura, and vasa vasorum of the aorta and pulmonary arteries. In addition, an occasional contribution to the thoracic spinal cord and the myocardium may be present. Knowledge of the bronchial arterial supply is important to prevent potentially catastrophic complications from arterial embolization of mycetomas.

Presentation

Acute clinical symptoms in ABPA include a low-grade fever, wheezing, productive cough, weight loss, malaise, headaches, and chest pain. Patients with ABPA also have a history of recurrent pneumonia. However, patients with aspergillomas are frequently asymptomatic. The most common clinical manifestation is hemoptysis, which may be life threatening.

Symptoms of chronic necrotizing aspergillosis are often insidious at onset and nonspecific. These symptoms include a productive cough, fever, and constitutional upset, and they represent acute tracheobronchitis, bronchiolitis, or bronchopneumonia. Hemoptysis occurs in only 15% of patients.

The angioinvasive form often causes nonspecific constitutional symptoms that make clinical diagnosis difficult. Patients often have an unremitting fever and pleuritic chest pain, which may mimic the findings of pulmonary embolism.

Aspergillus spp cultured in the aspirates/sputum of patients with COPD are generally considered contaminants.³ However, despite poor documentation of the IPA incidence in this population, patients with severe COPD may be at higher risk of developing IPA. There are some data to suggest that COPD is the underlying disease in 1% of patients with IPA. Because the clinical diagnosis of IPA in patients with COPD is often difficult to ascertain, it is based on a combination of clinical findings, high-resolution computed tomography (HRCT) findings, microbiologic results, and, occasionally, serologic tests.^1,2

Bulpa and associates analyzed the literature reports of 56 patients with IPA and COPD and found that 77% were receiving corticosteroids on hospital admission.³ Breathlessness with wheezing was present in 79% of patients, whereas fever occurred in 38.5%, and chest pain and hemoptysis were unusual. In this group, the median delay between symptoms and diagnosis was 8.5 days. The prognosis in the group was extremely poor, with a mortality of 95% despite invasive ventilation and antifungal treatment. The authors suggested that the outcome in these patients could perhaps have been improved by more rapid diagnosis and prompt therapy.

Preferred Examination

Chest radiography is an initial examination of choice in patients with respiratory symptoms or suspected pulmonary disease.^9,10 However, many different causes of bronchiectasis, including ABPA, cannot be accurately diagnosed on chest radiographs. Also, radiographic features of pulmonary aspergillosis are generally nonspecific.

Although the CT scan features of ABPA are not specific, the demonstration of bronchial dilatation, wall thickening, and centrilobular nodules in an asthmatic patient should suggest the diagnosis.¹⁴ The demonstration of a mobile mass within a cavity on supine and prone scans is virtually diagnostic of a mycetoma. The CT scan appearances of chronic necrotizing aspergillosis are also nonspecific, but CT does provide useful information regarding the extent of pulmonary disease and any associated pleural thickening. CT scan findings in angioinvasive aspergillosis are more specific, and the presence of nodules with a halo of ground-glass attenuation in the appropriate clinical setting allows confident diagnosis.

Limitations of Techniques

The appearances of the different types of thoracic aspergillosis are nonspecific, and a wide variety of lesions can mimic an aspergilloma. Examples of these include chronic necrotizing aspergillosis, angioinvasive aspergillosis, a tuberculous cavity with a Rasmussen aneurysm, cavitating bronchogenic carcinoma, lung abscess, hematoma, and P carinii pneumonia. Similarly, bronchial dilatation has a variety of causes.

Differential Diagnoses

Asthma
Bronchiectasis
Bronchogenic Cyst
Pneumonia, Pneumocystis Carinii
Wegener Granulomatosis, Thoracic

Other Problems to Be Considered

Differential diagnosis of cavitating upper lobe consolidation

Amyloidosis
Chronic necrotizing aspergillosis
Mucormycosis
Mycobacterium avium-intracellulare complex (MAIC) infection
Sarcoidosis
Tuberculosis
Viral and mycoplasmal pneumonia

Differential diagnosis of multiple pulmonary nodules

Angioinvasive aspergillosis
Hemorrhagic metastases
Infection with Mucorales fungi, Candida spp, herpes simplex virus, or cytomegalovirus
Wegener granulomatosis
Kaposi sarcoma

Differential diagnosis of tree-in-bud appearance

Okada and associates analyzed the clinical/pathologic findings in 553 patients undergoing HRCT with 2 patterns of centrilobular opacities with a tree-in-bud appearance.¹⁴ Their findings revealed that centrilobular nodules with a tree-in-bud appearance and bronchial wall thickening were observed in patients who were carriers of human T-lymphotropic virus type 1, Mycoplasma pneumoniae, Mycobacterium tuberculosis, MAIC, M kansasii, allergic bronchopulmonary aspergillosis, diffuse panbronchiolitis, and diffuse aspiration bronchiolitis.

The authors also noted that ill-defined centrilobular nodules of ground-glass attenuation were frequently seen in patients with conditions such as subacute hypersensitivity pneumonitis, metastatic calcification, Churg-Strauss syndrome, microscopic polyangiitis, systemic lupus erythematosus, and respiratory bronchiolitis-associated interstitial lung disease.¹⁴ Okada et al concluded that knowledge of the 2 centrilobular patterns is of proven benefit in the differential diagnosis when a tree-in-bud appearance is encountered.

• Search for CME/CE on This Topic »

• Thoracic Outlet Syndrome (Sports Medicine)
• Thoracic Discogenic Pain Syndrome (Sports Medicine)
• Intravascular Stents, Thoracic Aorta (Clinical Procedures)
• Thoracic Disc Injuries (Sports Medicine)

• Surgery First Improves Empyema Outcomes
• Invasive Fungal Infections Still a Significant Problem in Adult Stem Cell Recipients
• Stem Cells Destroy Lung Metastases in Mice

• Multicenter Cross-Sectional Study of Nontuberculous Mycobacterial Infections Among Cystic Fibrosis Patients, Israel
• Thoracoplasty in Thoracic Adolescent Idiopathic Scoliosis
• Outcome-Based Classification for Assessment of Thoracic Pedicular Screw Placement

• Spinal Disorders Resource Center
• Spinal Disorders