Aspergillosis
Aspergillus Fungus: Essential Concepts
Aspergillus is a filamentous saprophytic fungus found in soil, decomposing organic matter, ventilation systems, construction sites, and dusty environments. Its conidia, measuring 2 to 3 micrometers in diameter, are A. fumigatus, are small enough to reach the pulmonary alveoli during inhalation. Under normal conditions, alveolar macrophages and neutrophils quickly destroy inhaled spores, preventing infection. The pathogenicity of'Aspergillus is therefore essentially dependent on the host's immune status, although certain factors specific to the fungus, notably thermotolerance at 37°C, mycotoxin production, and resistance to oxidative stress, contribute to its virulence.
Clinical forms of aspergillosis
Aspergillosis does not present as a single entity but as a spectrum of distinct diseases, each corresponding to a different host profile and pathophysiological relationship with the fungus.
| Clinical form | Typical Host Profile | Mechanism | Gravity |
|---|---|---|---|
| Allergic bronchopulmonary aspergillosis (ABPA) | Asthma, cystic fibrosis | Hypersensitivity reaction (IgE-mediated) to antigens of'Aspergillus colonizing the bronchi; no tissue invasion | Moderate; chronic with risk of progressive bronchiectasis if untreated |
| Aspergilloma (fungal ball) | Pre-existing pulmonary cavity (sequela of tuberculosis, sarcoidosis, bullous emphysema) | Colonization of a preformed air cavity by a compact mass of fungal filaments; no invasion of adjacent parenchyma | Variable; risk of potentially severe hemoptysis |
| Chronic pulmonary aspergillosis (CPA) | Moderate immunodeficiency, structural lung disease, diabetes, malnutrition | Slow and progressive invasion of the lung parenchyma; evolution over months to years | Moderate to severe; progressive deterioration of respiratory function |
| Acute invasive aspergillosis (AI) | Profound and prolonged neutropenia, hematopoietic stem cell transplant, solid organ transplant, prolonged high-dose corticosteroid therapy, HIV stage AIDS | Aggressive vascular and tissue invasion by fungal hyphae; pulmonary thromboses and infarcts; possible hematogenous dissemination | Severe; mortality ranging from 40% to 90% depending on the patient's condition and the timeliness of treatment |
| Allergic fungal sinusitis | Immunocompetent (chronic form) or immunocompromised (invasive form) | Invasion or colonization of the paranasal sinuses; invasive form with possible orbital or intracranial extension | From benign (chronic form) to very severe (fulminant invasive form) |
| Disseminated aspergillosis | Profound immunodeficiency | Hematogenous dissemination from the primary pulmonary focus to the brain, heart, kidneys, liver, and skin | Very severe; high mortality |
Risk factors for invasive aspergillosis
- Severe and prolonged neutropenia (neutrophils below 500/mm³ for more than 10 days): context of intensive chemotherapy for hematologic malignancy, bone marrow aplasia; highest risk
- Allogeneic hematopoietic stem cell transplantation: maximal risk in the aplastic pre-engraftment phase and during graft-versus-host disease episodes treated with immunosuppressants
- Solid organ transplant: lung, heart, and liver present the most significant risks; transplanted lungs are directly exposed to the Aspergillus environment
- Prolonged high-dose systemic corticosteroid therapy (prednisone equivalent greater than 0.3 mg/kg/day for more than 3 weeks): impaired macrophage and neutrophil function
- HIV infection with CD4 counts below 50/mm³: significant risk without antifungal prophylaxis
- Treatment with kinase inhibitors (ibrutinib, idelalisib) or biological agents targeting immune pathways (anti-TNF, JAK inhibitors)
- Severe COVID-19 requiring ICU admission: Invasive pulmonary aspergillosis (IPA) and COVID-19-associated pulmonary aspergillosis (CAPA) recognized as emerging complications.
- Prolonged intensive care stay, invasive mechanical ventilation, severe liver failure
- Increased environmental exposure: construction or renovation work near a hospital, intensive gardening by an immunocompromised patient
Symptoms by clinical form
| Shape | Main symptoms | Warning signs |
|---|---|---|
| ABPA | Poorly controlled or aggravated asthma, expectoration of brownish mucus plugs, recurrent bronchospasm, labile pulmonary infiltrates | Proximal bronchiectasis characteristic; very high total IgE |
| Aspergilloma | Often asymptomatic; chronic cough; hemoptysis of varying volume, sometimes massive and potentially fatal | Massive hemoptysis: surgical or radiological emergency (embolization) |
| Chronic pulmonary aspergillosis | Persistent cough, purulent sputum, recurrent hemoptysis, weight loss, chronic fatigue, prolonged fever | Insidious evolution over months; often delayed diagnosis |
| Invasive aspergillosis | Fever unresponsive to antibiotics, pleuritic chest pain, dry cough, dyspnea, hemoptysis | Pleural effusion; halo sign on CT scan (early); air crescent sign (late); neurological or cutaneous dissemination |
| Invasive aspergillosis of the sinuses | Nasal obstruction, epistaxis, facial pain, fever; orbital extension: ptosis, exophthalmos, visual disturbances; intracranial extension: headaches, neurological deficits | Necrosis of the turbinates or palate: surgical emergency |
Diagnosis
The diagnosis of invasive aspergillosis is difficult because direct mycological samples (biopsy, cultures) are often impossible to obtain from frail patients, and cultures remain poorly sensitive. An approach combining clinical, radiological, and biological criteria is essential, according to the EORTC/MSGERC criteria.
| Review | Diagnostic approach | Details |
|---|---|---|
| High-resolution chest scanner | Referral imaging test; early and suggestive halo sign (ground-glass opacity surrounding a nodule); late air crescent sign | Perform without delay upon suspicion in the immunocompromised; standard chest X-ray is insufficient for early diagnosis |
| Serum galactomannan | Polysaccharide cell wall antigen'Aspergillus detected by ELISA; diagnostic threshold at 0.5 index | Sensitivity of 70–80% for % in neutropenic patients; lower sensitivity when patients are on azole antifungal prophylaxis; false positives are possible (piperacillin-tazobactam, certain foods) |
| Galactomannan in bronchoalveolar lavage (BAL) | Superior serum sensitivity for pulmonary forms; diagnostic threshold at 1.0 index | Perform a fiberoptic bronchoscopy with bronchoalveolar lavage as soon as the clinical condition allows. |
| Serum Beta-D-glucan | Non-specific panfungal marker'Aspergillus; Useful in addition to galactomannan | Frequent false positives (dialysis, albumin, certain antibiotics); contextual interpretation |
| PCR Aspergillus (sang, LBA) | High sensitivity; two consecutive positive PCR tests on whole blood increase diagnostic specificity | Integrated into the EORTC/MSGERC diagnostic criteria since 2019; standardization underway between laboratories |
| Mycology culture (LBA, biopsy) | Species identification and performing an antifungal susceptibility test are essential; formal confirmation. | Sensitivity of 40% to 60% (% only); turnaround time of 3 to 7 days; do not wait for the results to begin treatment if there is strong suspicion |
| Total and specific IgE antibody levelsAspergillus, skin test | Diagnosis of ABPA; modified Rosenberg-Patterson criteria | Total IgE greater than 1,000 IU/mL strongly suggestive of ABPA in an asthmatic context |
| Serology (anti-precipitinsAspergillus) | Diagnosis of Aspergilloma and Chronic Pulmonary Aspergillosis in Immunocompetent Individuals | Of limited use in invasive forms in immunocompromised individuals (insufficient antibody response) |
Antifungal treatment
Voriconazole has been the standard antifungal treatment for invasive aspergillosis since the publication of the Herbrecht et al. clinical trial in 2002, demonstrating its superiority over amphotericin B deoxycholate. Current recommendations from the IDSA (2016) and ESCMID/ECMM (2018) guide therapeutic choices based on clinical form and host status.
| Treatment | Main indication | Precautions and side effects |
|---|---|---|
| Voriconazole (oral or IV) | First-line treatment of invasive aspergillosis | IV loading dose, then oral maintenance; plasma level monitoring (target level: 1 to 5.5 mg/L); adverse effects: visual disturbances (phosphosphenes, photophobia), hepatotoxicity, photosensitivity, hallucinations, significant drug interactions |
| Isavuconazole (oral or IV) | First-line alternative to voriconazole; superior tolerability profile | Not inferior to voriconazole in the SECURE trial; better neurological and hepatic tolerance; active against Aspergillus and Mucor; fewer drug interactions |
| Liposomal Amphotericin B (AmBisome) | Invasive aspergillosis that is refractory or in case of intolerance to azoles; liposomal form preferred over conventional formulation | Lower nephrotoxicity with the liposomal form; hypokalemia; fever and chills during infusion; natural resistance of'A. terreus |
| Micafungin or caspofungin (echinocandins) | Salvage therapy or combination therapy in case of failure or refractory disease | Fungicidal activity on growing hyphae; well-tolerated; not recommended as first-line monotherapy; voriconazole + caspofungin combination possible in severe refractory cases |
| Itraconazole (oral) | Treatment of ABPA; aspergilloma; chronic pulmonary aspergillosis | Absorption variable depending on formulation (oral solution better than capsules); numerous drug interactions; plasma level monitoring recommended |
| Systemic corticosteroids | Treatment of ABPA in association with itraconazole: reduction of the inflammatory component | Prednisone 0.5 mg/kg/day during the acute phase, with gradual tapering over 3 to 6 months; monitor blood glucose and blood pressure |
The duration of antifungal treatment for invasive aspergillosis is usually at least 6 to 12 weeks, and may be extended as long as immunosuppression persists. Reducing or correcting the underlying cause (recovery of neutrophils, decrease in corticosteroids, immune reconstitution) is a therapeutic element as important as antifungal treatment itself.
Surgical and Interventional Treatment
- Surgical resection of aspergilloma: indicated in cases of recurrent or threatening hemoptysis; lobectomy or segmental resection depending on the location; significant operative mortality in debilitated patients
- Arterial bronchial embolization: an alternative to surgery for controlling hemoptysis in aspergilloma patients with high surgical risk; a non-curative palliative treatment
- Decompression surgery for invasive aspergillosis sinusitis with orbital or intracranial extension: emergency surgical drainage and debridement of necrotic tissue, in combination with systemic antifungal treatment
- Limited lung resection for invasive aspergillosis with a single lesion threatening a major vascular structure or refractory to well-managed medical treatment
Antifungal prophylaxis
Primary antifungal prophylaxis is recommended in patients at high risk of invasive aspergillosis, particularly during periods of prolonged neutropenia and in the context of allogeneic hematopoietic stem cell transplantation. Oral posaconazole is the standard prophylaxis for patients receiving induction chemotherapy for acute myeloid leukemia or for high-risk myelodysplastic syndromes.
Differential diagnosis
| Condition | Distinctive elements |
|---|---|
| Mucormycosis | Similar presentation but even more marked angiotropism; typical rhino-cerebral disease in diabetics; natural resistance to voriconazole; treatment with liposomal amphotericin B |
| Invasive candidiasis | Yeast, not mold; bacteremia originating from a catheter or the digestive tract; different morphology in culture; first-line treatment with echinocandin |
| Pneumocystis (PCP) | Pneumocystis jirovecii; Bilateral ground-glass interstitial pneumonia; elevated LDH; HIV or profound immunosuppression; treatment with cotrimoxazole |
| Pulmonary tuberculosis | Pulmonary cavities in the apex; acid-fast bacilli; TST or IGRA positive; specific antitubercular treatment |
| Septic pulmonary embolism | Multiple peripheral nodules; possible right-sided endocarditis or septic thrombophlebitis; positive blood cultures for bacteria |
| Lymphoma or pulmonary metastases | Pulmonary nodules or masses in the immunocompromised; biopsy essential for diagnosis; galactomannan negative |
Consult at Clinique Omicron
Clinique Omicron, at its service points in Quebec, has physicians capable of evaluating patients with chronic or unusual respiratory symptoms, particularly in the context of pre-existing structural lung disease or immunosuppression. In cases of suspected allergic bronchopulmonary aspergillosis, aspergilloma, or atypical pulmonary infections, our practitioners can initiate the appropriate diagnostic workup, coordinate specialized consultations in pulmonology or infectious diseases, and ensure follow-up in conjunction with hospital teams. For any acute situation or severe presentation in an immunocompromised patient, referral to the hospital emergency department remains a priority. Book an appointment at one of our service points on the South Shore or at one of our branches in Quebec. Teleconsultation is available for the follow-up of patients on outpatient antifungal treatment or for the initial evaluation of persistent respiratory symptoms.
The content of this page is provided for informational purposes only and is not intended to replace the advice of a qualified healthcare professional. Consult a physician for any symptoms, questions or decisions you may have regarding your health.
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