Respiratory Pathology

Bassam Mansour, MD, EDICM

Head, Pulmonary Division
The Lebanese University, Faculty of Medicine
Head, Pulmonary & Critical Care Medicine
Zahraa Hospital University Medical Center
Eosinophilic Pneumonias
 Definition

❖ Eosinophilic lung diseases are a heterogeneous group of

clinical entities in which there is an increased number of
eosinophils in the airways and/or lung parenchyma.

❖ These disorders may or may not be accompanied by

peripheral eosinophilia.
 Classification
❖ They are classified in 2 main categories: Airway disorders
& Interstitial disorders.
❖ Airway disorders:
❖ Asthma
❖ Eosinophilic bronchitis
❖ Allergic bronchopulmonary aspergillosis
❖ Bronchocentric granulomatosis
 Classification
❖ The Eosinophylic lung diseases affecting the Interstitium
are also divided in 2: Primary & Secondary.
❖ Secondary to a known underlying disease processes:
❖ Bacterial (brucellosis, mycobacterial), Fungal infections
(Coccidiomycosis, Pneumocystis, &Aspergillus), Parasitic.
❖ ILD: Idiopathic pulmonary fibrosis, Sarcoidosis, Systemic lupus
erythematosus, Eosinophilic granuloma.
❖ Others: Hypereosinophilic syndrome, Pulmonary vasculitis,
Hodgkin disease Drug reactions Lung cancer.
 Classification

❖ The Eosinophylic lung diseases affecting the Interstitium

are also divided in 2: Primary & Secondary.
❖ Primary or idopathic eosinophilic pneumonia:
❖ Simple pulmonary eosinophilia.
❖ Chronic eosinophilic pneumonia.
❖ Acute eosinophilic pulmonary pneumonia.
 The Eosinophil
❖ The eosinophil is a leukocyte that contains an eosin-
specific granule population responsible for the red
staining.
❖ Primarily a tissue cell (~ 300 times > blood), it settle in
submucosal areas of organs exposed to the environment
such as the lungs, the GI tract, & the GU tract.
❖ Its likely function is: host defense against parasites,
modulator of inflammation, and tissue-destructive cell.
 Eosinophilic Lung Disease
Airway Disorders
❖ Asthma: eosinophilia is present in many asthmatics,
intrinsic or extrinsic. Counts can be used to follow the
disease as there is a linear relationship with the
inflammation, & the airflow limitation.

❖ Eosinophilic Bronchitis: a well-recognized cause of

chronic cough, we find a high percentage of eosinophils
in sputum (~ 40%). It is steroid responsive. In contrast
with asthma, they do not have airflow limitation or
bronchial hyperresponsiveness.
 Eosinophilic Lung Disease
Airway Disorders
❖ Fungus-Induced Asthmatic Reactions: Inhalation of
fungal spores by the asthmatic may result in IgE-
mediated allergic rhinitis & asthma, and allergic
bronchopulmonary mycosis.
❖ Fungal IgE-mediated asthma is a noninfectious disease
resulting from the immune response of the atopic host.
❖ The response to the fungal resembles an exposure to
another allergen like dust mites.
 Eosinophilic Lung Disease
Airway Disorders

❖ Allergic bronchopulmonary mycosis is an “infectious

disease” characterized by periods of persistent fungal
growth or colonization of the respiratory tract.

❖ Both types of disorders can cause longstanding

asthmatic manifestations in susceptible individuals.
 Eosinophilic Lung Disease
Airway Disorders
❖ Allergic Bronchopulmonary Aspergillosis: ABPA is the most
common type of allergic bronchopulmonary mycosis (other
fungi include C. albicans)
❖ A complication of allergic asthma (2-28%) where Aspergillus
fumigatus colonizes the airways.
❖ Patients with cystic fibrosis are also quite susceptible.
❖ The hyphae persist in the airways & release Ag that combines
with specific IgG & IgE & cause tissue damage.
❖ This damage may be permanent, like bronchiectasis &
irreversible airways obstruction.
 Eosinophilic Lung Disease
Parenchymal Disorders
❖ Interstitial Lung Diseases: Increased BAL eosinophils is
present in ~ 10 to 20% of interstitial lung diseases.
❖ These ILD include idiopathic pulmonary fibrosis where it
may correlate with clinical deterioration and may predict
a poor response to Rx.
❖ Other ILD with BAL eosinophila include sarcoidosis,
systemic lupus erythematosus, & eosinophilic
granuloma.
 Eosinophilic Lung Disease
Parenchymal Disorders
❖ Pulmonary Vasculitis: Eosinophils may be associated with
lung lesions that accompany pulmonary vasculitis
syndromes like 1ary systemic vasculitis but also in
systemic lupus erythematosus and polymyositis;
lymphoma; sarcoidosis; & extrinsic allergic alveolitis.
❖ 1ary vasculitic processes: include giant cell arteritis,
pulmonary capillaritis, Takayasu arteritis, & those
associated with circulating Ab to neutrophil cytoplasmic
enzymes (eg, Churg-Strauss syndrome, Wegener
granulomatosis, and microscopic polyangiitis).
 Eosinophilic Lung Disease
Churg-Strauss
❖ Also known as allergic granulomatosis and angiitis.

❖ A rare but distinctive disorder: long-standing asthma &

dramatic peripheral eosinophilia.

❖ It’s a granulomatous inflammation leading to vascular

necrosis, affecting primarily the lungs.

❖ Diagnosis is usually on open lung biopsy.

 Eosinophilic Lung Disease
Churg-Strauss
❖ Pathophysiology:
❖ Immune complex deposition in the walls of small- and
medium-sized arteries and veins.
❖ A likely the role for anti-neutrophilic cytoplasmic antibody
(ANCA).
❖ The association with asthma and eosinophilia is unexplained.

❖ Clinical features:
❖ Atopic asthma, fever, malaise, and weight loss.
 Eosinophilic Lung Disease
Churg-Strauss
❖ Systemic manifestations:
❖ Upper airway involvement (sinusitis, rhinitis, nasal polyps)
❖ Skin changes (nodules, purpura, urticaria)
❖ Arthralgias; myalgias, mononeuritis multiplex
❖ Abdominal symptoms (pain, diarrhea, bleeding)
❖ Cardiac findings (heart failure, pericarditis, hypertension)
❖ Microscopic hematuria.
 Eosinophilic Lung Disease
Churg-Strauss

❖ Typical findings on imaging:

❖ CXR: patchy & transient (fleeting) infiltrates.
❖ CT findings: subpleural consolidation, centrilobular ground-
glass opacities & multiple nodules, bronchial wall thickening.
❖ Pleural effusions are noted in ⅓ of cases; they are typically
exudative with a significant number of eosinophils.
 Eosinophilic Lung Disease
Churg-Strauss

❖ Common laboratory findings:

❖ Leukocytosis with marked eosinophilia & an eosinophilic
predominance on BAL, ↑ ESR, & anemia.
❖ IgE level is also markedly increased & correlates with disease
activity.
❖ (+) p-ANCA in 44 - 66% (as opposed to c-ANCA seen in
Wegener granulomatosis).
 Eosinophilic Lung Disease
Churg-Strauss
❖ There are 3 distinct clinical phases:
1. A prodromal phase with asthma, often preceded by allergic
rhinitis, then often many years later
2. Marked peripheral eosinophilia and eosinophilic tissue
infiltration resembling Loeffler syndrome, or chronic
eosinophilic pneumonia, which may recur during a period of
years.
3. Life-threatening vasculitic phase.
 Eosinophilic Lung Disease
Churg-Strauss
❖ Without Rx, 50% died within 3 months; Myocardial involvement is
the most frequent cause of death.
❖ With corticosteroids, a mean survival of 9 years has been
reported. Corticosteroids alone usually are effective.
❖ Cyclophosphamide may reduce the rate of relapse but has not
been shown to improve survival.
❖ In refractory patients, “pulse” methylprednisolone, azathioprine,
or cyclophosphamide may be effective.
❖ Important to separate the Churg-Strauss from other necrotizing
vasculitides, (Wegener’s and polyarteritis nodosa), which may
require treatment with cytotoxic agents.
 Eosinophilic Lung Disease
Parasitic Disease
❖ Pulmonary infiltrates with Eosinophilia may develop in
conjunction with a number of parasitic infections (Strongyloides,
Ascaris, Toxocara...)
❖ Eosinophils may be recruited to kill the parasite as it is present in
the lung at certain stages of its life cycle.
❖ But eosinophils can be present in the lung, when parasites are not
demonstrable, which suggests an immunologic mechanisms.
❖ GI symptoms dominate the clinical picture of parasitic infestation.
❖ Respiratory symptoms include mild cough & wheezing &
commonly resolves with the Rx directed at the specific parasite.
 Eosinophilic Lung Disease
Parasitic Disease
❖ The most serious parasitic eosinophilic lung disease is tropical
pulmonary eosinophilia caused by a filarial worm Wuchereria
bancrofti & Brugia malayi found in India, Africa, South America,
and Southeast Asia).
❖ Microfilariae released from the adult worms cause an intense
inflammatory reaction in the lung with nocturnal cough, dyspnea,
wheezing, fever, weight loss, and malaise.
❖ Residence in am endemic region & an eosinophilia > 3,000/mm3
should initiate a consideration especially in the context of what is
believed to be a acute severe or refractory asthma.
❖ Rx is diethylcarbamazine; untreated or treated late, it may lead to
fibrosis or chronic bronchitis with chronic respiratory failure.
 Eosinophilic Lung Disease
Idiopathic Hypereosinophilic Syndrome
❖ A rare illness of unknown etiology that affects multiple
organ systems, as the result of the infiltration of mature
eosinophils:
1. peripheral eosinophilia > 1,500 / mcL for 6 months.
2. Involvement of various organs with end organ damage.
3. No evidence for parasitic, allergic, vasculitic, or other known
causes of eosinophilia.
❖ The illness be fatal, in the event of cardiac disease with
endocardial fibrosis leading to restrictive
cardiomyopathy, valvular damage, & mural thrombus.
 Eosinophilic Lung Disease
Idiopathic Hypereosinophilic Syndrome
❖ Lung involvement occurs in 40% with dry cough and
dyspnea.
❖ Imaging:
❖ Pulmonary edema and pleural effusions in the event of CHF.
❖ Interstitial infiltrates due to perivascular eosinophilic
infiltration &/or fibrosis.
❖ Oral corticosteroids lead to a ~ 50% response.
❖ Busulfan, interferon alfa, hydroxyurea, & imatinib
(Gleevac, tyrosine kinase inhibitor), may be used in
steroid-unresponsive patients.
 Eosinophilic Lung Disease
Simple Pulmonary Eosinophilia
❖ 1932: Loeffler describes a disorder characterized by
migratory pulmonary infiltrates, peripheral eosinophilia,
& minimal or absent symptoms: Loefler’s pneumonia.
❖ Occasional malaise, fever, and cough may be noted.
❖ Resolves without Rx within 4 weeks with excellent
prognosis.
❖ Imaging: transitory and migratory ill defined periferal
densities.
❖ Etiology: Parasitic infection, drug reaction, or idiopathic
in ⅓ of cases (idiopathic eosinophilic pneumonias).
 Chronic Eosinophylic Pneumonia
❖ Uncommon disease of the idiopathic eosinophilic
pneumonia syndromes, CEP is a serious disease that
requires specific treatment.
❖ Typically affects middle-aged atopic women. but it has
been reported in both sexes and all ages.
❖ Insidious respiratory and constitutional symptoms with
cough, dyspnea, fever, night sweats, malaise, and weight
loss.
❖ Asthma is present in 50 to 60% of patients and is usually
of recent onset.
 Chronic Eosinophylic Pneumonia
❖ Laboratory: ↑ IgE, peripheral eosinophilia in ~ 88%.
❖ Imaging: Diffuse peripherally based infiltrates in 63%,
they can be so characteristic as to be diagnostic. They
may form a pattern described as “the photographic
negative of pulmonary edema.”
❖ Biopsy: interstitial and alveolar eosinophils, eosinophilic
microabscesses (aggregates of necrotic eosinophils
surrounded by histiocytes), low-grade vasculitis, &
interstitial fibrosis.
 Chronic Eosinophylic Pneumonia
❖ BAL specimens usually show eosinophilia that average
44%.
❖ < 10% of patients will have spontaneous resolution;
deaths have been reported.
❖ It responds very well & quickly to corticosteroid therapy.
❖ The patient may become asymptomatic in hours or a
days, but Rx for prolonged periods is usually necessary
(at least 6 months) with a slow steroid taper as the
disease tends to relapse.
 Acute Eosinophylic Pneumonia
❖ Ac. respiratory failure with ↑ BAL or tissue eosinophils
of unknown cause; it could be a hypersensitivity reaction
to an inhaled Ag or a drug toxicity:
1. Acute febrile illness of 5 days in duration.
2. Hypoxemic respiratory failure.
3. Diffuse mixed alveolar and interstitial infiltrates.
4. BAL eosinophilia ( 25%).
5. No apparent infectious etiology.
6. Rapid and complete response to corticosteroid therapy.
7. No relapse after discontinuing steroid therapy.
 Acute Eosinophylic Pneumonia
❖ Patients typically present with fever, myalgias, pleuritic
chest pain, and hypoxemic failure, often requiring
mechanical ventilation, clinically, difficult to distinguish
from an acute infectious process or ARDS.
❖ The BAL that provides the clue since blood eosinophil
percentage is normal.
❖ Pleural effusions are frequent with a ↑ % of eosinophils.
❖ Patients respond rapidly to high doses of corticosteroids,
usually within 24 to 48 h.
 Acute Eosinophylic Pneumonia
❖ Patients respond rapidly to high doses of corticosteroids,
usually within 24 to 48 h. The dose is then tapered, but
treatment is usually continued for 2 to 4 weeks.
❖ Most patients survive to recover normal lung function.
❖ AEP is a diagnosis of exclusion, An infectious etiology
should be pursued even after corticosteroid therapy is
begun, especially looking closely for disseminated fungal
disease & P carinii in the HIV-positive patients.
 Conclusion
❖ The eosinophil may be:
❖ A good guy: host defense against parasitic infections.
❖ A bad guy when activated at sites of inflammation &
responsible for the actual tissue damage.
❖ An innocent bystander: modulator of inflammation.
❖ It is important to remember that the disease processes
lumped together as eosinophilic that are either
appropriately or artificially connected by their
association with the eosinophil.
Respiratory Pathology

Thank you