pulmonary aspergillosis



OVERVIEW

Definition.

A series of diseases of the lungs caused by the invasion of the respiratory tract by fungi of the genus Aspergillus.

Aspergillus has more than 600 kinds of fungi, there are about 40 kinds of human infections, with Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger are more common. 95% of pulmonary aspergillosis is caused by Aspergillus fumigatus, followed by Aspergillus flavus.

Aspergillus belongs to the conditionally pathogenic bacteria, less common in normal people with normal immune function, preferred in the immunocompromised population.

Classification

Aspergillus pulmonary manifestations are diverse, clinically can be divided into invasive pulmonary aspergillosis, invasive tracheobronchial aspergillosis, chronic necrotizing pulmonary aspergillosis, aspergilloma, allergic bronchopulmonary aspergillosis 5 categories.

Invasive pulmonary aspergillosis (IPA)

It is a common type of pulmonary aspergillosis.

The prognosis is related to the body’s immune function, and in severe cases, the lung tissue is widely destroyed and the prognosis is poor.

Invasive tracheobronchial aspergillosis (ITBA)

The lesions are mainly confined to the large airways.

The disease needs to be diagnosed by bronchoscopy.

Chronic necrotizing pulmonary aspergillosis (CNPA)

High morbidity and mortality, with a 1-year survival rate of only 50% in untreated patients.

It is a localized invasion of lung tissue and less frequently spreads to other organs.

Aspergilloma (Aspergilloma)

Also known as Aspergillus ball.

Usually does not invade tissues, but can progress to invasive pulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA)

An allergic disease caused by Aspergillus.

Clinical presentation is highly variable and treatment outcome is related to a number of factors.

Incidence

The overall incidence of pulmonary aspergillosis is unknown.

The incidence of invasive pulmonary aspergillosis is higher in patients with malignancies, hematologic disorders, AIDS (AIDS), organ transplantation, and other immunosuppressed patients.

The incidence of invasive aspergillosis has been estimated to be about 5% to 25% in patients with acute leukemia and 1% to 12% in patients with AIDS, and has been increasing in recent years.

Causes

Causes

Pulmonary aspergillosis is due to invasion of the respiratory tract by Aspergillus.

Sources of infection

Aspergillus spores are found in dust and soil and are the main source of infection.

Route of transmission

The disease is often contracted through inhalation of air containing Aspergillus spores, contact with moldy rice, or close contact with Aspergillus-carrying poultry or birds.

Human-to-human transmission has not been reported.

Susceptible people

The susceptible groups of pulmonary aspergillosis are those with low immunity and poor resistance.

Elderly people.

Malnourished people.

Underlying diseases such as diabetes mellitus, malignancy, leukemia, uremia, and human immunodeficiency virus (HIV) infection.

Prolonged and heavy use of antibiotics, glucocorticoids or immunosuppressants, undergoing radiotherapy and other treatments.

Burns and organ transplant patients.

Symptoms

Main Symptoms

The clinical manifestations of pulmonary aspergillosis are complex, and the clinical manifestations of different subtypes are not completely consistent.

Invasive pulmonary aspergillosis

Dry cough and chest pain are common symptoms, and hemoptysis may occur in some cases.

When the lesion is extensive, shortness of breath and dyspnea may occur.

About 30% of patients may have extrapulmonary organ involvement, mainly in blood-rich organs (heart, liver, kidney, brain, gastrointestinal, etc.).

Invasive tracheobronchial aspergillosis

Frequent cough, chest pain, fever with hemoptysis are the main manifestations.

The disease needs to be diagnosed by bronchoscopy, which reveals pseudomembranes, ulcers and nodules on the airway wall.

Chronic necrotizing pulmonary aspergillosis

The history of the disease is long.

Symptoms are often insidious, including chronic cough, sputum, fever and non-specific symptoms, about 15% of patients may have hemoptysis, manifested as chronic bronchitis and repeated mild hemoptysis.

Aspergilloma

Often secondary to bronchial cysts, bronchiectasis, lung abscesses and tuberculosis cavities.

There may be irritating cough with little sputum.

Hemoptysis is often present, even hemoptysis.

Allergic bronchopulmonary aspergillosis

Respiratory symptoms such as wheezing, irritating cough and coughing up sputum (brownish yellow purulent sputum, occasionally with blood in the sputum) may be present.

Asthma attacks as its prominent clinical manifestations, the general antispasmodic and asthma drugs are difficult to be effective.

Complications

Pulmonary aspergillosis can lead to the following complications.

Diffuse pulmonary fibrosis

Prolonged pulmonary aspergillus infection can lead to pulmonary fibrosis and even diffuse pulmonary fibrosis.

Symptoms such as chest tightness and dyspnea can occur.

Respiratory failure can be induced endangering the patient’s life.

Respiratory failure

Pulmonary aspergillosis can lead to pulmonary fibrosis, cavitation, obstruction and other pathological changes, affecting the normal ventilation function of the lungs, unable to carry out effective gas exchange, thus causing respiratory failure.

Cyanosis, dyspnea, irritability, coma and other symptoms may occur.

If not corrected in time can endanger the patient’s life.

Other parts of Aspergillosis

Aspergillus invasion of the respiratory tract can be spread to the extrapulmonary airways through the bloodstream, resulting in central nervous system, cardiovascular system, digestive system and other parts of the body of aspergillosis.

Corresponding symptoms may appear, such as dizziness, headache, convulsions, impaired consciousness after invasion of the central nervous system; palpitations, chest tightness, dyspnea after invasion of the cardiovascular system; abdominal pain, diarrhea, etc. after invasion of the digestive system.

Complications such as central respiratory and circulatory failure, heart failure, pericardial tamponade, gastrointestinal perforation and other life-threatening complications may occur.

Consultation

Department of Medicine

Respiratory Medicine

When symptoms such as fever, cough, sputum, hemoptysis, chest pain occur, it is recommended to consult a doctor promptly.

Infectious Diseases

If you are suffering from AIDS or viral hepatitis, you can consult the Department of Infectious Diseases for the above symptoms.

Emergency Medicine

If you experience hemoptysis, severe respiratory distress, or an uncontrollable asthma attack, you need to call 120 or the Emergency Department.

Preparation for medical treatment

Preparing for your visit: registering, preparing your documents, and common problems.

Tips for seeking medical treatment

If you have a fever, monitor and record your temperature before going to the doctor.

If symptoms of chest tightness and shortness of breath occur, bed rest is needed, reduce activities and lifting, and oxygen can be given if possible.

Preparation Checklist

(1) Symptom list

Particular attention should be paid to the time of symptom onset, special manifestations, etc.

Are there any symptoms such as fever, cough, sputum, hemoptysis, chest pain, etc.?

What is the highest temperature? Is the fever regular?

What is the nature of the sputum coughed up?

What is the exact location of chest pain?

What is the degree of pain?

What is the nature of the pain (e.g., cutting, swelling, dullness, etc.)?

How long did the pain last?

Is there pain or discomfort anywhere else?

Are there any symptoms of dyspnea, cyanosis, impaired consciousness, shock, etc.?

How long have these symptoms been present?

(2) Medical history checklist

What is the living environment?

Are there any diseases such as diabetes, malignant tumors, leukemia, uremia, AIDS, etc.?

Are there any long-term use of antibiotics, glucocorticoids, immunosuppressants and other drugs?

Has he/she received radiotherapy treatment?

Is there any history of organ transplantation?

(3) Checklist

Examination results in the past six months, which can be brought to the doctor

Imaging examination: chest radiograph, chest CT, etc.

Laboratory tests: blood test, C-reactive protein, GM test, etc.

(4) Medication list

Medications used in the last 3 months, if there is a medicine box or package, you can bring it to the doctor

Glucocorticoid: e.g. methylprednisolone, dexamethasone, etc.

Immunosuppressants: e.g. cyclophosphamide, etc.

Chemotherapy drugs: e.g. carboplatin, cisplatin, etc.

Diagnosis

Diagnostic basis

In addition to the medical history (including occupational history), it should be combined with the typical clinical symptoms, with the results of chest X-ray and CT examination, and the diagnosis depends on the fungal microscopy and culture, biopsy and histopathological examination, as well as the comprehensive clinical judgment.

Medical history

A medical history is not necessary for diagnosis, but is favorable in the presence of the following conditions.

Elderly, malnourished individuals.

Underlying diseases such as diabetes mellitus, malignant tumors, and HIV infection.

Immunocompromised people with long-term antibiotic use, long-term glucocorticoid use, immunosuppressants, burns, organ transplantation, etc.

Clinical manifestations

The clinical manifestations of different types of pulmonary aspergillosis are not exactly the same, mostly manifested as fever, chest pain, shortness of breath, cough, and/or hemoptysis. Some types of pulmonary aspergillosis have insidious onset and atypical symptoms.

Signs of different types of pulmonary aspergillosis vary greatly, and are related to the location of the lesion, the extent of involvement, the duration of the disease, the underlying disease state and other factors.

Chest imaging

Chest imaging is valuable for the diagnosis of pulmonary aspergillosis as it can help to understand the condition of the lungs.

Chest X-ray and chest CT are commonly used.

Chest X-ray shows multiple wedges, nodules, masses or cavities based on the pleura.

Typical chest CT presentation is a halo sign in the early stage, which is a lung nodule shadow (edema or hemorrhage) surrounded by a hypodense shadow (ischemia), and a crescent sign in the later stage.

Imaging is unremarkable and requires bronchoscopy to confirm the diagnosis.

CT shows unilateral or bilateral rounded solid lesions in lung segments with or without cavitation and adjacent pleural thickening, which may be multiple nodular hyperdense shadows.

Chest radiograph or CT shows a spherical shadow within the existing chronic cavity, and in individual cases the spherical shadow may move within the cavity with changes in body position.

Chest radiograph or CT shows central bronchiectasis (bronchioles in the medial 2/3 of the lung field) and a transient pulmonary infiltrate manifesting as a transient solid or atelectasis in the upper lobes, a ground-glass shadow with mosaic sign, and mucus inclusions, which may occur bilaterally.

Laboratory tests

(1) Pathologic examination

Sputum, nasal secretion, bronchoalveolar lavage fluid, fiberscope brushings are taken for smear and culture.

A single positive does not serve as a diagnostic indicator, may be colonized or contaminated, but if there is immunosuppression based on repeated culture of the same species of Aspergillus can be used as a diagnostic reference.

(2) Aspergillus antigen skin test

Method: Take Aspergillus antigen and inject it intradermally into the patient’s inner forearm, then observe the skin reaction after 15-20 minutes, if there are symptoms such as red rash and itching, it is positive, otherwise it is negative.

It is mainly used to diagnose ABPA and has no significance in the diagnosis of IPA.

Positive Aspergillus skin test helps the diagnosis of ABPA.

(3) Galactomannan antigen test (GM test)

Aids in the diagnosis of Aspergillus infection by detecting the presence of galactomannan in the patient’s blood.

It has high sensitivity and specificity for invasive Aspergillus infections in neutrophil-deficient hosts, and continuous testing can be used to monitor disease changes and assess prognosis.

The diagnostic threshold is still controversial, and 0.5 is used as the threshold for high-risk patients, especially patients with malignant hematological diseases, especially when the concentration is >1.0-1.5mg/ml or when it shows a progressive increase on follow-up, which is of early diagnostic value.

The release of GM is proportional to the amount of bacteria, but there is a certain possibility of error and false positives or false negatives can occur.

(4) Fungal D-glucan (BDG) test (G test)

Rapidly diagnose the presence of fungal infection by taking the patient’s blood and then using a fungal detector or fungal detection reagent.

It has a suggestive role in the diagnosis of pulmonary aspergillosis, but the specificity is not high, and can be combined with other indicators for diagnosis, or as a diagnosis of exclusion.

BDG test can be positive in pulmonary aspergillosis.

(5) Determination of Aspergillus antibody

Detect the level of Aspergillus antibody (IgG, IgM, IgE) in human blood to determine whether there is fungal infection.

It can be used as a dynamic monitoring indicator of pulmonary aspergillosis, but cannot be used for early diagnosis.

ABPA can be diagnosed when the serum total IgE level is elevated above 1000 IU/ml.

It is basically worthless for diagnosing invasive aspergillosis.

(6) Nucleic acid measurement

By using Aspergillus fungal nucleic acid test kit on patient’s sputum, if it is positive, there is fungal infection, otherwise not.

The sensitivity and specificity are high, but the specimen is easily contaminated and the clinical diagnostic significance is yet to be confirmed by further studies as specimen handling techniques are still lacking standardization.

Most researchers recommend testing at least 2 times per week, with 2 consecutive positive results as the diagnostic criterion.

Histopathologic examination

It is important for the diagnosis and staging of pulmonary aspergillosis.

Specimens can be taken by fibrinoscopy or percutaneous lung puncture biopsy and sent for examination, but they cannot differentiate Aspergillus species.

The most diagnostic value is to see typical Aspergillus filaments in the specimen.

Fibrilloscopy

It can understand the patient’s airway condition, and at the same time, it can collect sputum, lavage, brushing, biopsy and other ways to obtain specimens to send for examination, and clarify the diagnosis.

It is the definitive diagnosis of ITBA.

Differential Diagnosis

Pulmonary aspergillosis needs to be differentiated from the following diseases.

Pneumonia due to other pathogenic bacteria

Similarities: both can cause fever, cough, sputum and other symptoms, chest imaging is common in the lungs, such as exudates.

Differences: Pneumonia caused by different pathogenic bacteria have their own characteristics, but it is usually difficult to distinguish them based on history, physical signs and imaging. Pathogenetic examination is of great value in identifying pneumonia caused by different pathogenic bacteria.

Bronchial asthma

ABPA needs to be differentiated from bronchial asthma.

Similarities: both can cause symptoms of cough, sputum, chest tightness and wheezing.

Differences:

Cough variant asthma usually has no fever or only low-grade fever, little or no sputum, good at night, and lung auscultation may have no signs or audible rales. Chest imaging is usually not abnormal, or show increased lung texture, disorders, blood tests are often normal white blood cells, eosinophils increased.

Patients with pulmonary aspergillosis are mostly immunocompromised, with poor general condition, coughing up white sticky sputum or yellow pus sputum, and wet rales can be heard on lung auscultation. Chest imaging shows infiltrating shadows on the lungs, and the GM test and G test can be positive, and aspergillus infection can be seen in the pathogenetic examination.

Tuberculosis

Similarity: Both can cause cough, fever, hemoptysis and other symptoms.

Differences:

Patients with pulmonary tuberculosis usually have a history of tuberculosis-related contact, pulmonary auscultation rales are not obvious, tuberculosis foci can be seen in the lungs on chest imaging, tuberculin test is positive, GM test and G test are mostly negative, and tuberculosis infection can be seen on pathogenetic examination.

Patients with pulmonary aspergillosis often cough white sticky sputum or yellow pus sputum, lung auscultation can be heard wet rales, chest imaging can be seen in the lung infiltration shadow, GM test and G test can be positive, pathogenic examination can be seen in fungal infection.

Pulmonary embolism

Similarity: Both can cause chest pain, dyspnea, hemoptysis and other symptoms.

Differences:

Patients with pulmonary embolism usually do not have fever, dyspnea symptoms are more obvious, lung auscultation can be heard on the affected side of the decreased breath sounds, chest imaging can be seen in the lung embolism foci, D-dimer test is often elevated.

Patients with pulmonary aspergillosis are mostly immunocompromised, with poor general condition, coughing white sticky sputum or yellow pus sputum, wet rales on lung auscultation, pulmonary infiltrates on chest imaging, positive GM test and G test, fungal infections on pathogenetic examination, and low D-dimer.

Treatment

Aim of treatment: control and alleviate the disease as soon as possible, prevent and avoid complications.

Principle of treatment: according to the pathogenic bacteria of infection, select the corresponding antifungal drug treatment, meanwhile, cooperate with rehydration, oxygenation and other symptomatic supportive treatment.

General treatment

Body position

Bed rest.

Those with respiratory distress can be placed in semi-recumbent position.

Those with hemoptysis should lie on the affected side.

Maintenance of water-electrolyte balance

Appropriate intravenous rehydration to maintain stable water and electrolytes.

Nutritional support

Pay attention to nutritional supplementation, ensure that patients consume enough calories every day, and at the same time, ensure balanced nutrition.

Patients who have difficulty in eating can be given parenteral nutritional support.

Oxygen therapy

If the patient has irritability, cyanosis and other hypoxic manifestations, or arterial partial pressure of oxygen is less than 60mmHg, it is necessary to inhale oxygen.

Low-flow oxygen is the main focus, it is appropriate to maintain the patient’s blood oxygen to more than 90%.

Patients with severe respiratory failure can be treated with mechanical ventilation.

Avoid cross-infection

Wear masks and disinfect the living environment regularly to avoid cross-infection.

Medication

Invasive pulmonary aspergillosis, invasive tracheobronchial aspergillosis, and chronic necrotizing pulmonary aspergillosis.

Voriconazole is preferred. It is recommended to start with intravenous infusion, and then switch to oral administration when the condition improves. The course of treatment should be at least 6 to 12 weeks, with the recommended course of treatment for invasive pulmonary aspergillosis being 4 to 6 months.

Alternative drugs such as amphotericin B, caspofungin and micafungin are available.

Aspergillosis

The main concern is to prevent life-threatening hemoptysis, which should be treated surgically if conditions permit.

Endobronchial and intrapulmonary injections and oral antifungals (e.g., voriconazole) may be effective.

Allergic bronchopulmonary aspergillosis (ABPA)

Glucocorticoids are preferred for acute ABPA. The course of therapy is determined by the condition and usually takes 3 months or longer.

Antifungal therapy with itraconazole, voriconazole, and posaconazole can help reduce hormone dosage and shorten the course of hormone therapy.

Beta2 agonists (e.g., salbutamol, terbutaline) or inhaled glucocorticoids (e.g., budesonide) may be used as appropriate.

Non-pharmacologic treatment

Bronchial artery embolization

(1) Indications

Patients with pulmonary aspergillosis invading the bronchial artery, resulting in rupture of the bronchial artery causing hemoptysis.

(2) Contraindications

Coagulation dysfunction.

Patients with severe respiratory failure and cardiac insufficiency.

Combined with other conditions that cannot tolerate surgery and anesthesia.

Surgical treatment

(1) Indications

Surgery can be considered if one of the following indications exists:

Pulmonary aspergillosis should be surgically resected if there is no contraindication, especially when the lesion is confined with recurrent hemoptysis and the possibility of life-threatening hemoptysis exists.

In the case of repeated hospital admissions, the presence of risk factors affecting the prognosis, or an unknown diagnosis, the diseased lung lobe should be resected if the physical condition and pulmonary function do not contraindicate surgery.

If lobectomy is contraindicated, cavernous drainage or transbronchoscopic injection of medication into the cavern can be performed.

In the case of concurrent Aspergillus pyothorax, it is necessary to perform pyothorax drainage, pleural fibroplasty, thoracic reshaping, or bronchopleural fistula repair according to the situation, and postoperative pharmacological treatment is required.

If pulmonary aspergillosis causes limited thin-walled cyst-like lesions, and the surrounding tissues are not invaded, pneumonectomy can be performed with good efficacy.

(2) Surgical methods

Lobectomy, abscess drainage, pleural fibroplasty, thoracic reshaping or bronchopleural fistula repair.

(3) Surgical complications

Postoperative complications such as abscess, hemopneumothorax, celiac chest, broncho-pleural fistula, delayed wound healing, bleeding, etc. may occur, and even induce respiratory failure, cardiac arrhythmia, circulatory failure, etc. leading to death.

(4) Precautions

For immunocompromised people, even if the lesion has been adequately resected by surgery, regular postoperative antifungal therapy is still required.

If the lesion has not been fully resected, postoperative close follow-up is required to dynamically monitor changes in imaging, treponemal antibodies and other indicators to assess whether recurrence or progression is occurring.

(5) Contraindications

Uncorrected coagulation dysfunction.

Patients with severe respiratory failure and cardiac insufficiency.

Combined with other conditions that cannot tolerate surgery and anesthesia.

Prognosis

Cure

Overall prognosis

The prognosis of allergic bronchopulmonary aspergillosis and aspergillosis is favorable after treatment, but aspergillosis may recur.

Invasive pulmonary aspergillosis, invasive tracheobronchial aspergillosis and chronic necrotizing pulmonary aspergillosis can also achieve satisfactory results if diagnosed and treated early, but the prognosis is poorer if treatment is not timely. Especially chronic chronic necrotizing pulmonary aspergillosis, untreated patients 1 year survival rate of only 50%.

Daily

Daily Management

Dietary management

Avoid spicy and stimulating foods such as chili, mustard and pepper, which may irritate the respiratory tract and aggravate the patient’s cough and sputum.

Avoid eating foods with high sugar content, which may cause sputum to be sticky and not easy to cough out, aggravating the condition.

Daily care

Keep the indoor air circulating and maintain the appropriate temperature and humidity in the room.

Ensure adequate rest and avoid exertion and late nights.

Remove sputum and secretions from the oropharynx in time, turn over and pat the back to promote the discharge of sputum to keep the airway open.

Disease monitoring

Pay attention to changes in the patient’s condition, and seek immediate medical follow-up if there is persistent high fever, dyspnea, cyanosis, depression, or shock.

If the patient has diabetes mellitus, regular monitoring and recording of blood glucose changes should be performed. Stabilizing blood glucose control will help recovery from pulmonary aspergillosis.

Follow-up

Follow the doctor’s instructions for regular follow-up.

Follow-up blood tests, chest imaging and other tests to check for changes in the condition.

Liver and kidney function should be monitored regularly during the medication period.

Prevention

Reduce or avoid contact with Aspergillus spores

When cleaning items with mold growth, wear a mask and wipe with a damp cloth first to avoid causing Aspergillus spores to fly and contaminate the air.

Avoid contact with moldy rice, straw or rotting flowers and plants, avoid entering the Aspergillus-contaminated environment and dusty places, and wear protective masks when you must contact them.

Regularly clean and disinfect air conditioning ducts.

Enhance immunity

Pay attention to balanced diet and nutrition, and ensure a reasonable daily routine.

Quit smoking and avoid excessive alcohol consumption.

Take appropriate physical exercise to enhance immunity.

Adopt good hygiene habits

Ensure personal hygiene.

Keep your daily environment clean and tidy.

Actively treat underlying diseases

Those who suffer from diabetes and other underlying diseases should be actively treated to control the stabilization of the disease.