Lipoid pneumonia overview

# Overview
In 1925, G. F. LAUGHLEN, M.D. was the first physician to describe lipoid pneumonia. He first interacted with the disease by routine autopsy at the Toronto, Ontario hospital for sick children. He described grayish red nodules at the autopsy with three types of exudates, found out mononuclear cells which were unexpected in the exudates. In 1949 McDonald et al described endogenous lipoid pneumonia for the first time. He observed so-called "obstructive pneumonia" in patients with lung neoplasms. In September 2019, there was an outbreak of lipoid pneumonia related to vaping. it was then reported to be because of vitamin E soluble in THC e-cigarette juice. Lipoid pneumonia may be classified according to source of the lipid exposure into 2 subtypes: Exogenus, more common type reported, due to aspiration or inhalation of fatty substance, and endogenus, due to obstructive pneumonia.lipoid pneumonia parthenogenesis is different in its two sub-types: Exegenous form:it is understood that exogenus lipoid pneumonia is the result of chronic body reaction to fatty substance in the alveol. Lipid reaches alveoli by aspiration or inhalation. Some mineral oils can cause lung injuries such as gasoline. Mineral oils can enter the tracheobronchial tree without causing cough reflex which will bother mucociliary transport system chronically. Injected lipids mechanism of further producing lipid pneumonia is more complicated. As the lipid goes inside the alveoli, it is trapped and hard to expectorate, this condition may be worsen by associated neurological and gastrointestinal disorders affecting swallowing or cough. Lipids in alveoli form emulsion and then consumed by macrophages via phagocytosis. Since the alveolar macrophages cannot metabolize consumed fatty substance, oil is repeatedly released into alveoli after death of these macrophages. The oil released, illicits a giant-cell granulomatosis reaction. Endogenous form: The pathogenesis of endogenous lipoid pneumonia is still not well understood however there are plenty of suggested mechanisms, endogenous lipoid pneumonia can be caused by transbronchial dissemination of cancer cell breakdown products. Poorly differentiated adenocarcinoma cells secreting mucin is the most common neoplastic reason. Another mechanism suggested is anoxic tissue injury stimulating various enzymes such as phospholipase and mono-oxygenases.Infection changes to endogenous lipid pneumonia is generally localized in airways because the souronding lung is already consolidated, limiting the spread of bacteria. On gross and microscopic histology well circumscribed, firm with prominent lymphatics on lung surface in exogenous typelipoid material (or empty spaces), inflammatory cells and young fibroblasts. Reactive endarteritis, marked alveolar lining cell hyperplasia. Lipid-laden foamy macrophages are seen.Vaping is a common cause of lipoid pneumonia. occupationally related lipoid pneumonia is seen in fire-eaters(caused by Kedran oil). some trivial habits such as: use of oil-based laxatives, lip balm, lip gloss petroleum jelly play a role in lipoid pneumonia development. siphoning various mineral oils such as diesel is another common risk factor especially in India may be another causetive factor.Lipod pneumonia must be differentiated from other diseases that cause Cough with basilar infiltrates, such as bacterial pneumonia, viral pneumonia, congestive heart failure, pulmonary fibrosis, and aspiration pneumonia. Exogenous lipoid pneumonia is usually misdiagnosed as community-acquired pneumonia. in patients at risk of aspiration early CT scan is very useful for further diagnosis of lipoid pneumonia. Since lipid-laden pneumonia is is very sensitive but may not be very specific, the diagnosis of exogenous lipoid pneumonia is based on the triad of: History of mineral oil ingestion or vaping, compatible radiological findings, and presence of intra-alveolar lipids and/or lipid-laden macrophages.The incidence and prevalence of lipoid pneumonia are underestimated. It is mostly because of similarities between pneumonias from different causes and lack of specific marker to distinguish pneumonias from each other. In 2019 there was an outbreak of vaping based pulmonary complications.Lipoid pneumonia pathogenicity is because of lipid aspiration. Common risk factors in the development of aspiration pneumonia include dysphagia, swallowing dysfunction, altered mental status, COPD, and hospitalization. Less common risk factors in the development of aspiration pneumonia include medications, esophageal motility disorders, vomiting, enteral feeding, oropharyngeal colonization, male sex, and smoking.There is insufficient evidence to recommend routine screening for lipoid pneumonia.Patients might present acutely with inflammation and cough, fever, and dyspnea. However, they might be asymptomatic and present with an incidental mass on radiographs. Owing to its nonspecific symptoms and radiological features, lipoid pneumonia often remains undiagnosed or diagnosis is delayed. The oil released illicits a giant-cell granulomatous reaction (hence also called lipid granulomatosis), chronic inflammation, and alveolar and interstitial fibrosis. Evolution of lesions with time has been described: Fresh lesions show alveolar infiltration by lipid-laden macrophages and almost normal alveolar walls and septa, and advanced lesions show larger vacuoles and inflammatory infiltrates in alveolar walls, bronchial walls and septa. Diagnostic Study of Choice: lipoid pneumonia is mainly diagnosed based on clinical presentation. The CURB-65 and the eCURB scoring systems are used to evaluate and predict mortality in patients with pneumonia. However, they are not helpful in aspiration pneumonia. History and Symptoms; Patients with exogenous lipoid pneumonia have a positive history of oil contaminating prescription, E-cigarette smoking, vaping, using oily laxative, or other oil related history. in some cases high susceptibility to aspiration must be considered. Common symptoms of aspiration pneumonia include: Chest pain, cough, fever, sweating, and shaking chills.Physical examination of lipoid pneumonia does not reveal any different feature and is usually mistaken with community acquired pneumonia (CAP). may reveal low grade fever or sometimes low body temperature, an increased respiratory rate, low blood pressure, a fast heart rate, or a low oxygen saturation, which is the amount of oxygen in the blood as indicated by either pulse oximetry or blood gas analysis. Patients who have difficulty breathing, who are confused, or who have cyanosis (blue-tinged skin) require immediate attention. Auscultation findings include lack of normal breath sounds, the presence of crackling sounds (rales), or increased loudness of whispered speech (whispered pectoriloquy) with areas of the lung that are stiff and full of fluid, called consolidation. Vital signs are useful in determining the severity of illness and have predictive values. However, a high degree of suspicion should be kept in elderly as the presentation could be subtle in them. Different laboratory tests might be used in patients with aspiration pneumonia. Sputum analysis including lipid laden macrophage, gram stain and culture must be done in patients with cough. ABG may show acute hypoxemia and decreased mixed venous oxygen saturation. CBC shows leukocytosis with left shift or leukopenia, anemia, or thrombocytopenia. There are some non-specific findings on ECG of a patient with lipoid pneumonia which include sinus tachycardia, minor nonspecific ST-segment or T-wave changes, right atrial enlargement, QRS abnormalities like right axis deviation, and presence of S1S2S3.Chest x-rays may be helpful in the diagnosis of aspiration pneumonia. Findings on an chest x-ray suggestive of aspiration pneumonia include lobar pneumonia, areas of opacity, unilateral consolidation, air bronchogram, or cavitation. In some cases, ultrasound is used for the diagnosis and follow-up of a patient with pneumonia, for a guided thoracocentesis and to quantify the amount of pleural effusion, however its benefits are not yet indicated for lipoid pneumonia. Chest CT scan might be used in patients with aspiration pneumonia if a chest x-ray is not conclusive. CT findings may include lobar consolidation, ground-glass opacities, bronchiectasis, atelectasis, pleural effusion, and consolidation. A chest CT can also help to assess reasons for therapy failure and complications, such as lung abscess, and pleural effusions. Chest MRI may be helpful in the diagnosis of lipoid pneumonia. Findings on MRI suggestive of lipoid aspiration pneumonia may differentiate disease from other forms of aspiration pneumonia. Other findings are: atelectasis, consolidation and opacities.Bronchoscopy with bronchoalveolar lavage is useful to obtain samples for finding lipid-laden macrophages. In some cases of lipoid pneumonia, transbronchial lung biopsy or even surgical biopsy may be required to determine the exact cause of lipoid pneumonia, specially in endogenous form. videofluoroscopic swallow study (VFSS) might be used to evaluate swallowing difficulties. Treatment of lipoid pneumonia is not well studied and published experience is only with case reports.Bronchoalveolar lavage (BAL) is both diagnostic and therapeutic procedure in lipoid pneumonia, specially in children. Surgery is not a common treatment for lipoid pneumonia, but if there is a high suspicion of cancer, it would be considered as a therapy plan. video-assisted thoracoscopic surgery (VATS) lobectomy, is the favored method for these interventions. Lipoid pneumonia can be prevented by cessation of underlying cause like E-cigarette smoking or lipid based medications.it is also preventable by preventing aspiration pneumonia. effective measures for the primary prevention of aspiration pneumonia include dietary habit changes, maintaining oral hygiene, postural maneuvers, and medications such as H2 antagonists, metoclopramide, mosapride, amantadine, or cilostazol. Lipoid pneumonia can be prevented by cessation of underlying cause like E-cigarette smoking or lipid based medications.it is also preventable by preventing aspiration pneumonia. effective measures for the primary prevention of aspiration pneumonia include dietary habit changes, maintaining oral hygiene, postural maneuvers, and medications such as H2 antagonists, metoclopramide, mosapride, amantadine, or cilostazol.

# Historical Perspective
In 1925, G. F. LAUGHLEN, M.D. was the first physician to describe lipoid pneumonia. He first interacted with the disease by routine autopsy at the Toronto, Ontario hospital for sick children. He described grayish red nodules at the autopsy with three types of exudates, found out mononuclear cells which were unexpected in the exudates. In 1949 McDonald et al described endogenous lipoid pneumonia for the first time. He observed so-called "obstructive pneumonia" in patients with lung neoplasms.

# Classification
Lipoid pneumonia may be classified according to source of the lipid exposure into 2 subtypes: Exogenus, more common type reported, due to aspiration or inhalation of fatty substance, and endogenus, due to obstructive pneumonia.

# Pathophysiology
lipoid pneumonia parthenogenesis is different in its two sub-types: Exegenous form:it is understood that exogenus lipoid pneumonia is the result of chronic body reaction to fatty substance in the alveol. Lipid reaches alveoli by aspiration or inhalation. Some mineral oils can cause lung injuries such as gasoline. Mineral oils can enter the tracheobronchial tree without causing cough reflex which will bother mucociliary transport system chronically. Injected lipids mechanism of further producing lipid pneumonia is more complicated. As the lipid goes inside the alveoli, it is trapped and hard to expectorate, this condition may be worsen by associated neurological and gastrointestinal disorders affecting swallowing or cough. Lipids in alveoli form emulsion and then consumed by macrophages via phagocytosis. Since the alveolar macrophages cannot metabolize consumed fatty substance, oil is repeatedly released into alveoli after death of these macrophages. The oil released, illicits a giant-cell granulomatosis reaction. Endogenous form: The pathogenesis of endogenous lipoid pneumonia is still not well understood however there are plenty of suggested mechanisms, endogenous lipoid pneumonia can be caused by transbronchial dissemination of cancer cell breakdown products. Poorly differentiated adenocarcinoma cells secreting mucin is the most common neoplastic reason. Another mechanism suggested is anoxic tissue injury stimulating various enzymes such as phospholipase and mono-oxygenases.Infection changes to endogenous lipid pneumonia is generally localized in airways because the souronding lung is already consolidated, limiting the spread of bacteria. On gross and microscopic histology well circumscribed, firm with prominent lymphatics on lung surface in exogenous typelipoid material (or empty spaces), inflammatory cells and young fibroblasts. Reactive endarteritis, marked alveolar lining cell hyperplasia. Lipid-laden foamy macrophages are seen.

# Causes
Vaping is a common cause of lipoid pneumonia. occupationally related lipoid pneumonia is seen in fire-eaters(caused by Kedran oil). some trivial habits such as: use of oil-based laxatives, lip balm, lip gloss petroleum jelly play a role in lipoid pneumonia development. siphoning various mineral oils such as diesel is another common risk factor especially in India may be another causetive factor.

# Differentiating Lipoid pneumonia from Other Diseases
Lipod pneumonia must be differentiated from other diseases that cause Cough with basilar infiltrates, such as bacterial pneumonia, viral pneumonia, congestive heart failure, pulmonary fibrosis, and aspiration pneumonia. Exogenous lipoid pneumonia is usually misdiagnosed as community-acquired pneumonia. in patients at risk of aspiration early CT scan is very useful for further diagnosis of lipoid pneumonia. Since lipid-laden pneumonia is is very sensitive but may not be very specific, the diagnosis of exogenous lipoid pneumonia is based on the triad of: History of mineral oil ingestion or vaping, compatible radiological findings, and presence of intra-alveolar lipids and/or lipid-laden macrophages.

# Epidemiology and Demographics
The incidence and prevalence of lipoid pneumonia are underestimated. It is mostly because of similarities between pneumonias from different causes and lack of specific marker to distinguish pneumonias from each other. In 2019 there was an outbreak of vaping based pulmonary complications.

# Risk Factors
Lipoid pneumonia pathogenicity is because of lipid aspiration. Common risk factors in the development of aspiration pneumonia include dysphagia, swallowing dysfunction, altered mental status, COPD, and hospitalization. Less common risk factors in the development of aspiration pneumonia include medications, esophageal motility disorders, vomiting, enteral feeding, oropharyngeal colonization, male sex, and smoking.

# Screening
There is insufficient evidence to recommend routine screening for lipoid pneumonia.

# Natural History, Complications, and Prognosis
Patients might present acutely with inflammation and cough, fever, and dyspnea. However, they might be asymptomatic and present with an incidental mass on radiographs. Owing to its nonspecific symptoms and radiological features, lipoid pneumonia often remains undiagnosed or diagnosis is delayed. The oil released illicits a giant-cell granulomatous reaction (hence also called lipid granulomatosis), chronic inflammation, and alveolar and interstitial fibrosis. Evolution of lesions with time has been described: Fresh lesions show alveolar infiltration by lipid-laden macrophages and almost normal alveolar walls and septa, and advanced lesions show larger vacuoles and inflammatory infiltrates in alveolar walls, bronchial walls and septa

# Diagnosis

## Diagnostic Study of Choice
Lipoid pneumonia is mainly diagnosed based on clinical presentation. The CURB-65 and the eCURB scoring systems are used to evaluate and predict mortality in patients with pneumonia. However, they are not helpful in aspiration pneumonia.

## History and Symptoms
Patients with exogenous lipoid pneumonia have a positive history of oil contaminating prescription, E-cigarette smoking, vaping, using oily laxative, or other oil related history. in some cases high susceptibility to aspiration must be considered. Common symptoms of aspiration pneumonia include: Chest pain, cough, fever, sweating, and shaking chills.

## Physical Examination
Physical examination of lipoid pneumonia does not reveal any different feature and is usually mistaken with community acquired pneumonia (CAP). May reveal low grade fever or sometimes low body temperature, an increased respiratory rate, low blood pressure, a fast heart rate, or a low oxygen saturation, which is the amount of oxygen in the blood as indicated by either pulse oximetry or blood gas analysis. Patients who have difficulty breathing, who are confused, or who have cyanosis (blue-tinged skin) require immediate attention. Auscultation findings include lack of normal breath sounds, the presence of crackling sounds (rales), or increased loudness of whispered speech (whispered pectoriloquy) with areas of the lung that are stiff and full of fluid, called consolidation. Vital signs are useful in determining the severity of illness and have predictive values. However, a high degree of suspicion should be kept in elderly as the presentation could be subtle in them.

## Laboratory Findings
Different laboratory tests might be used in patients with aspiration pneumonia. Sputum analysis including lipid laden macrophage, gram stain and culture must be done in patients with cough. ABG may show acute hypoxemia and decreased mixed venous oxygen saturation. CBC shows leukocytosis with left shift or leukopenia, anemia, or thrombocytopenia.

## Electrocardiogram
There are some non-specific findings on ECG of a patient with lipoid pneumonia which include sinus tachycardia, minor nonspecific ST-segment or T-wave changes, right atrial enlargement, QRS abnormalities like right axis deviation, and presence of S1S2S3.

## X-ray
Chest x-rays may be helpful in the diagnosis of aspiration pneumonia. Findings on an chest x-ray suggestive of aspiration pneumonia include lobar pneumonia, areas of opacity, unilateral consolidation, air bronchogram, or cavitation.

## Echocardiography and Ultrasound
In some cases, ultrasound is used for the diagnosis and follow-up of a patient with pneumonia, for a guided thoracocentesis and to quantify the amount of pleural effusion. However its benefits are not yet indicated for lipoid pneumonia.

## CT scan
A chest CT scan might be used in patients with aspiration pneumonia if a chest x-ray is not conclusive. CT findings may include lobar consolidation, ground-glass opacities, bronchiectasis, atelectasis, pleural effusion, and consolidation. A chest CT can also help to assess reasons for therapy failure and complications, such as lung abscess, and pleural effusions.

## MRI
Chest MRI may be helpful in the diagnosis of lipoid pneumonia. Findings on MRI suggestive of lipoid aspiration pneumonia may differentiate disease from other forms of aspiration pneumonia. Other findings are: atelectasis, consolidation and opacities.

## Other Imaging Findings
Bronchoscopy with bronchoalveolar lavage is useful to obtain samples for finding lipid-laden macrophages.

## Other Diagnostic Studies
In some cases of lipoid pneumonia, transbronchial lung biopsy or even surgical biopsy may be required to determine the exact cause of lipoid pneumonia, specially in endogenous form. videofluoroscopic swallow study (VFSS) might be used to evaluate swallowing difficulties.

# Treatment

## Medical Therapy
Treatment of lipoid pneumonia is not well studied and published experience is only with case reports.

## Interventions
Bronchoalveolar lavage (BAL) is both diagnostic and therapeutic procedure in lipoid pneumonia, specially in children.

## Surgery
Surgery is not a common treatment for lipoid pneumonia, but if there is a high suspicion of cancer, it would be considered as a therapy plan. video-assisted thoracoscopic surgery (VATS) lobectomy, is the favored method for these interventions.

## Primary Prevention
Lipoid pneumonia can be prevented by cessation of underlying cause like E-cigarette smoking or lipid based medications.it is also preventable by preventing aspiration pneumonia. effective measures for the primary prevention of aspiration pneumonia include dietary habit changes, maintaining oral hygiene, postural maneuvers, and medications such as H2 antagonists, metoclopramide, mosapride, amantadine, or cilostazol.

## Secondary Prevention
Lipoid pneumonia can be prevented by cessation of underlying cause like E-cigarette smoking or lipid based medications.it is also preventable by preventing aspiration pneumonia. Effective measures for the primary prevention of aspiration pneumonia include dietary habit changes, maintaining oral hygiene, postural maneuvers, and medications such as H2 antagonists, metoclopramide, mosapride, amantadine, or cilostazol.