Eosinophilic lung diseases: causes, symptoms, diagnosis, treatment

Pulmonary eosinophilia is a group of conditions in which eosinophils accumulate in the lung parenchyma and bronchoalveolar fluid, often in association with peripheral blood eosinophilia, leading to inflammation, infiltrates, and respiratory symptoms. This group includes acute and chronic eosinophilic pneumonias, allergic bronchopulmonary mycosis, drug-induced and parasitic variants, and pulmonary manifestations of hypereosinophilic syndrome. [1]

The clinical presentation varies from a fulminant onset with respiratory failure in acute eosinophilic pneumonia to a subacute course with relapses in chronic eosinophilic pneumonia. Accurate verification of the cause is important, as therapeutic approaches vary, ranging from drug withdrawal and anthelmintic therapy to systemic glucocorticosteroids and targeted biologics. [2]

An increased proportion of eosinophils in bronchoalveolar lavage fluid is considered a key diagnostic feature. A threshold of 20-25 percent strongly supports the diagnosis of eosinophilic alveolitis and helps differentiate it from other interstitial and infectious processes. However, interpretation must take into account the context, including the timing of the disease, medication use, and concomitant infections. [3]

Classification by etiology and phenotype improves prognosis and treatment selection. Recent reviews emphasize the role of a multidisciplinary approach involving a pulmonologist, radiologist, pathologist, and infectious disease specialist for accurate classification and risk assessment of relapse or fibrosis. [4]

Epidemiology

Pulmonary eosinophilia is relatively rare and accounts for a small proportion of all interstitial lung diseases, but its incidence varies by region due to differences in exposure, parasite load, and drug profile of the population. Allergic bronchopulmonary mycosis accounts for a significant proportion of cases in patients with asthma. [5]

Acute eosinophilic pneumonia is more common in young adults and can be triggered by intense environmental exposure, including changes in inhalation patterns, such as rapidly increasing tobacco smoking or exposure to aerosols. The disease can develop within days and require emergency care. [6]

Chronic eosinophilic pneumonia is more common in middle-aged women, is often associated with asthma, and is characterized by a tendency to relapse when glucocorticosteroids are discontinued or rapidly tapered. This places a strain on the healthcare system due to long-term monitoring and repeated courses of therapy. [7]

The advent of targeted therapies, including anti-interleukin-5 and anti-interleukin-5 receptor drugs, has expanded options for refractory cases, but such treatments still focus on limited subgroups and require selection based on phenotype and drug availability. [8]

Reasons

The etiologic spectrum includes non-infectious immune processes, infections, drugs, and systemic diseases. Non-infectious causes include idiopathic acute and chronic forms, allergic bronchopulmonary mycosis, eosinophilic granulomatosis with polyangiitis, and eosinophilic asthma phenotypes. Infectious causes are predominantly parasitic, less commonly bacterial or fungal. [9]

Drug-induced eosinophilic pneumonia has been described with a wide range of medications, from antibiotics to nonsteroidal anti-inflammatory drugs and antineoplastic agents. If suspected, the drug should be discontinued immediately and the response assessed after treatment. [10]

Allergic bronchopulmonary mycosis, most often caused by aspergilli, develops in patients with asthma or cystic fibrosis. It is characterized by immune hyperreactivity to fungal antigens, resulting in the formation of mucus plugs and bronchiectasis, leading to eosinophilic inflammation, exacerbations, and progressive bronchial remodeling. [11]

Parasitic infestations migrating through the lungs can cause marked blood eosinophilia and pulmonary symptoms. In endemic regions and with a relevant travel history, parasitic causes should be excluded before initiating immunosuppression. [12]

Risk factors

Acute eosinophilic pneumonia has been associated with intense inhalation exposure—for example, sudden initiation or increase in smoking, exposure to smoke, or aerosols. In some cases, changes in inhalation patterns over a short period of time have been the trigger. [13]

For chronic eosinophilic pneumonia, concomitant asthma and atopy are risk factors. Relapses are more likely to occur with rapid dose reduction or premature discontinuation of glucocorticosteroids, as well as with continued exposure to allergens in the home. [14]

In allergic bronchopulmonary mycosis, colonization of the respiratory tract by fungi and sensitization to them play a key role. The presence of bronchiectasis, high immunoglobulin E concentrations, and blood eosinophilia increase the likelihood of diagnosis and an unfavorable course with frequent exacerbations. [15]

Parasitic causes become more common when traveling to endemic areas, working with animals, and consuming undercooked food. Timely collection of an epidemiological history helps avoid erroneous immunosuppression. [16]

Pathogenesis

Eosinophils, activated by cytokine cascades, primarily interleukin-5, migrate into lung tissue, where they release inflammatory mediators, increase vascular permeability, and support alveolar infiltrates. If the trigger persists, chronic inflammation develops, with the risk of remodeling and decreased diffusion capacity. [17]

In allergic bronchopulmonary mycosis, immunoglobulin E-mediated and non-immunoglobulin E-dependent mechanisms are involved with the formation of mucus plugs, bronchiectasis and deposition of fungal elements, which maintains eosinophilic inflammation and bronchial obstruction. [18]

Drug-induced and parasitic variants trigger a similar terminal loop of eosinophil activation, but elimination of the causative factor can quickly interrupt the cascade. This explains the pronounced steroid sensitivity of many forms once the trigger is eliminated. [19]

In a number of cases with severe asthma and chronic eosinophilic pneumonia, targeted suppression of interleukin-5 or its receptor leads to a reduction in eosinophilic inflammation and a steroid-sparing effect, which confirms the key role of this axis. [20]

Symptoms

Acute eosinophilic pneumonia presents with fever, increasing shortness of breath, dry cough, myalgia, and sometimes rapidly developing respiratory failure. Hospitalization and oxygen support are often required. Symptoms progress over several days. [21]

Chronic eosinophilic pneumonia develops subacutely, with a weekly or monthly course, characterized by a nonproductive cough, shortness of breath during exertion, night sweats, and weight loss. Symptoms rapidly improve with glucocorticosteroids but tend to recur when the dose is reduced. [22]

Allergic bronchopulmonary mycosis is accompanied by asthma exacerbations, productive cough with mucus plugs, wheezing, and sometimes hemoptysis. Long-term progression leads to bronchiectasis and a decrease in quality of life. [23]

Drug-induced and parasitic variants can mimic infectious pneumonia. The presence of blood eosinophilia, a corresponding history, and characteristic tomographic features should suggest an eosinophilic nature of the process. [24]

Forms and stages

Idiopathic forms are distinguished: acute and chronic eosinophilic pneumonia, as well as secondary forms: allergic bronchopulmonary mycosis, drug-induced and parasitic variants, eosinophilic granulomatosis with polyangiitis, and pulmonary manifestations of hypereosinophilic syndrome. Classification by etiology guides diagnosis and therapy. [25]

The acute form manifests as a rapidly progressive lesion with pronounced alveolar inflammatory activity, often with normal or moderate blood eosinophilia at onset, but with a high proportion of eosinophils in bronchoalveolar lavage. The chronic form has a slower progression and pronounced blood eosinophilia. [26]

Allergic bronchopulmonary mycosis is characterized by exacerbation and remission phases against a background of underlying asthma, possibly progressing to bronchiectasis and fixed obstruction. Early diagnosis and antifungal therapy combined with an anti-inflammatory strategy reduce the risk of structural changes. [27]

Severity is determined by the severity of respiratory failure, the volume of infiltrates, lung function and the level of eosinophilia, which is used to select the intensity of therapy and the frequency of monitoring. [28]

Complications and consequences

Without timely diagnosis and treatment, respiratory failure may progress, secondary infection may develop, and pulmonary hypertension may develop. In the acute form, these events can develop rapidly and require intensive care. [29]

The chronic form is prone to relapse, which entails steroid overload and associated adverse effects, including metabolic disturbances, osteoporosis, and the risk of infections. This stimulates the search for steroid-sparing strategies, including inhaled agents and biological therapy. [30]

Allergic bronchopulmonary mycosis causes bronchiectasis, mucus plugs, and fixed obstruction, worsening the prognosis and increasing the risk of hospitalization. Recurrent infections require long-term observation and complex therapy. [31]

Delay in excluding a parasitic cause may lead to inappropriate immunosuppression and severe complications. Therefore, appropriate testing should be performed before initiating systemic steroids in at-risk patients. [32]

Diagnostics

The diagnosis is based on a combination of clinical presentation, laboratory data, imaging, and bronchoscopy with bronchoalveolar lavage. An elevated eosinophil count in bronchoalveolar fluid strongly supports the diagnosis of pulmonary eosinophilia. For the acute form, values of at least 25 percent are typical, although thresholds vary by stage. [33]

Criteria for acute eosinophilic pneumonia include acute onset of respiratory illness within 1 month, bilateral infiltrates on imaging, hypoxemia, eosinophilia in bronchoalveolar lavage fluid, and exclusion of alternatives, including infections. These landmarks help distinguish it from other acute interstitial processes.[34]

Chronic eosinophilic pneumonia is characterized by peripheral subpleural infiltrates on high-definition computed tomography (HDCT), marked blood eosinophilia, and a rapid response to glucocorticosteroids with a risk of relapse upon dose reduction. Verification of the causative factor remains key. [35]

If allergic bronchopulmonary mycosis is suspected, criteria are used that take into account sensitization to fungal antigens, elevated levels of immunoglobulin E, blood eosinophilia, and characteristic changes on computed tomography - central bronchiectasis and mucus plugs. [36]

Tests and instrumental diagnostics

A complete blood count with leukocyte count, biochemistry and inflammation markers, sputum analysis, and immunological tests for sensitization to fungal antigens are mandatory if allergic bronchopulmonary mycosis is suspected. If there is a risk of parasitosis, serology and other specific tests are performed. [37]

High-definition computed tomography (HDCT) scans in the acute form show diffuse ground-glass opacities and areas of consolidation, while in the chronic form, peripheral subpleural infiltrates are present, sometimes called the "reverse sign" due to their peripheral distribution. Bronchiectasis and mucus plugs are characteristic of allergic bronchopulmonary mycosis. [38]

Bronchoscopy with bronchoalveolar lavage is a key step in confirming eosinophilic alveolitis, ruling out infection, and guiding further management. Follow-up studies are used in cases of protracted or recurrent disease. [39]

Functional respiratory tests often reveal restrictive changes in pneumonia and an obstructive component in allergic bronchopulmonary mycosis and asthma. Changes in forced vital capacity and diffusion capacity reflect the effectiveness of therapy and the risk of relapse. [40]

Differential diagnosis

The main alternatives include infectious pneumonias, other interstitial lung diseases, pulmonary hemorrhage syndrome, vasculitis, hypersensitivity pneumonitis, and drug-induced injuries. A comparison of clinical presentation, bronchoalveolar lavage data, serology, and imaging can help narrow the field. [41]

In cases of acute onset with hypoxemia, differentiation is made from acute respiratory distress syndrome, viral, and atypical infections. A high proportion of eosinophils in the bronchoalveolar fluid and a rapid response to steroids support the eosinophilic nature. [42]

The chronic variant must be distinguished from sarcoidosis, hypersensitivity pneumonitis, and organizing pneumonia. Peripheral distribution of infiltrates and pronounced blood eosinophilia with a rapid steroid response are typical of chronic eosinophilic pneumonia. [43]

In allergic bronchopulmonary mycosis, isolated asthma and other causes of bronchiectasis must be excluded. The presence of sensitization to fungal antigens and the radiological triad makes the diagnosis more likely and guides therapy. [44]

Treatment

The basic principle is elimination of the causative factor. In the case of a medicinal variant, immediate discontinuation of the drug is required; in the case of a parasitic etiology, specific anthelmintic therapy is recommended. In all cases, the need for and duration of anti-inflammatory therapy is considered. [45]

In acute eosinophilic pneumonia, systemic glucocorticosteroids produce rapid clinical and radiological improvement in most patients. Oxygen support and early escalation in case of deterioration are vital. The duration of treatment is individualized based on symptom regression. [46]

Chronic eosinophilic pneumonia responds well to glucocorticosteroids, but relapses are common with rapid discontinuation. Therefore, slow dose reduction, the use of high-dose inhaled steroids as a steroid-sparing option, and regular monitoring are being discussed. Biologics, particularly anti-interleukin-5 and anti-interleukin-5 receptor, are being studied for refractory cases. [47]

Allergic bronchopulmonary mycosis is treated with systemic glucocorticosteroids and antifungal agents, with current guidelines allowing both monotherapy with each class in specific clinical situations and their combination. In refractory cases, anti-immunoglobulin-E and anti-interleukin-5 strategies are discussed as indicated. [48]

Prevention

Prevention includes rational drug administration based on safety profile, early recognition of adverse reactions, and patient education to report new symptoms after initiation of therapy. In endemic areas, sanitation and hygiene measures and dietary recommendations are important. [49]

For patients with allergic bronchopulmonary mycosis, relapse prevention is based on asthma control, environmental care, regular monitoring, and timely escalation of therapy at signs of exacerbation. Individualized steroid tapering plans help reduce the risk of relapse. [50]

Forecast

In acute eosinophilic pneumonia, the prognosis is favorable with early initiation of steroids and the absence of severe complications. Most patients achieve complete remission, although monitoring for relapse and exclusion of the causative factor is required. [51]

The chronic form is prone to relapse, but with controlled dose reduction, steroid-sparing strategies, and targeted therapy in refractory patients, it is possible to maintain remission and reduce the cumulative steroid load. In allergic bronchopulmonary mycosis, the prognosis depends on controlling inflammation and preventing structural changes in the bronchi. [52]

Tables

Table 1. Classification of pulmonary eosinophilia

Category	Examples	Key Features
Idiopathic	Acute and chronic eosinophilic pneumonia	Acute - rapid onset, chronic - subacute course and relapses
Infectious	Parasitic infestations with a pulmonary phase	Often pronounced blood eosinophilia, epidemiological history
Medicinal	Antibiotics, antitumor, other classes	Improvement after discontinuation of the suspected drug
Immune	Allergic bronchopulmonary mycosis, eosinophilic granulomatosis with polyangiitis	Sensitization to fungal antigens, bronchiectasis, systemic manifestations in vasculitis

Table 2. Diagnostic landmarks for bronchoalveolar lavage

Indicator	Approximate thresholds	Comment
Eosinophil count	≥ 20-25 percent supports the diagnosis	Particularly informative in acute form
Microbiology	Exclusion of infections	Important before starting immunosuppression
Dynamics	Decrease during therapy	Used to monitor response

Table 3. Computed tomography patterns

Nosology	Common signs	Practical tip
Acute eosinophilic pneumonia	Double-sided frosted glass, seals	Correlates with acute alveolar inflammation
Chronic eosinophilic pneumonia	Peripheral subpleural infiltrates	Rapid response to steroids, risk of relapse
Allergic bronchopulmonary mycosis	Central bronchiectasis, mucus plugs	Associated with asthma and mushroom sensitization

Table 4. Treatment by etiology

Situation	First line	Additionally	Notes
Acute eosinophilic pneumonia	Systemic glucocorticosteroids	Oxygen supportive therapy	Rapid clinical response
Chronic eosinophilic pneumonia	Slow-taper glucocorticosteroids	High doses of inhaled steroids, biologics for relapses	Relapse control and steroid sparing
Allergic bronchopulmonary mycosis	Glucocorticosteroids or antifungal drugs	Combination of classes, biopreparations according to indications	Follow current recommendations

Table 5. Red flags in favor of an alternative diagnosis

Sign	Possible alternative	Action
Absence of eosinophilia in bronchoalveolar fluid	Other interstitial diseases, infections	Expand the search, postpone immunosuppression
Local cavitation, pronounced neutrophilia	Bacterial or fungal infection	Targeted microbiology, anti-infective therapy
Hemoptysis with anemia	Pulmonary hemorrhage, vasculitis	Immunological profile, consultation with a rheumatologist

Table 6. Relapses and steroid-sparing approaches in chronic eosinophilic pneumonia

Strategy	Evidence base	Expected effect
Slow tapering of glucocorticosteroids	Historical cohort observations	Reducing the frequency of relapses
High doses of inhaled steroids	Observational data and early studies	Reducing system load
Anti-interleukin-5 and anti-interleukin-5 receptor	Case series and reviews	Reduced recurrence and steroid requirements

FAQ

• How reliable is bronchoalveolar fluid analysis?

A high proportion of eosinophils in bronchoalveolar fluid is a strong supportive sign, especially in acute onset. However, the result must be interpreted taking into account the clinical picture and the exclusion of infections. [53]

• Are systemic steroids always necessary?

In acute cases, they almost always do, as they quickly improve the condition. In chronic cases, yes, but the dose reduction strategy is selected individually, adding inhaled steroids and considering biologics in refractory patients. [54]

• When should you think about allergic bronchopulmonary mycosis?

In asthma, elevated immunoglobulin E, blood eosinophilia, mucus plugs, and central bronchiectasis on CT scan. Current guidelines detail diagnostic and treatment algorithms. [55]

• Is there a role for biological therapy?

Yes, in cases of recurrent chronic eosinophilic pneumonia and severe eosinophilic asthma phenotypes, anti-interleukin-5 and anti-interleukin-5 receptor drugs are possible, which can reduce the systemic steroid load. The decision is made after excluding secondary causes. [56]