Discussion
Exogenous lipoid pneumonia (ELP) is a rare condition that can be difficult to recognize and results from accumulation of oily materials in the alveoli that are aspirated from vegetable, mineral and animal origins, characterized by lipid-ladden macrophages in the sputum or bronchoscopy lavage.5,18,19 In the present study, we demonstrated that acute ELP frequently is symptomatic, with respiratory symptoms reported by almost all of affected children patients who had a median 2 years of age. Bilateral areas of consolidative and ground-glass opacities were the most common radiological findings, but crazy-paving pattern on CT scan images was present in less than one-half of affected individuals. Aspirated mineral oil was the most conmmonly implicated materials. After discontinuation of the causative agent and supportive treatment, such as oxygen therapy, bronchoalveolar lavage and glucocorticoid use, a large percentage of the children patients significantly improved clinically and radiologically. All of the patients had acute ELP in our study, rather than chronic. Pathologically, acute ELP is generally believed to be caused by a foreign body response to fatty substances in the lung lobe,20 therefore, we found that all affected individuals had a markedly higher percentage of neutrophils in BAL fluid and peripheral blood in comparison with the normal range. Acute ELP is more common in the literature report and occurs in association with large-dose inhalation or aspiration in specific clinical settings, such as accidental ingestions in children or fire-eaters, suicide attempts and illegal drug use.1,9,13
The mechanisms by which lipids reach alveoli are aspiration or inhalation, mineral oils enter the respiratory tract without stimulating the cough reflex and impair the mucociliary transport system.1 Risk factors for ELP include infancy and elderly who usually have anatomic or functional gastroesophageal dysmotility disorder, cleft palate or neuromuscular disorder.4 All of children with acute ELP were included in the present study, who had aspirated a large sum of oily materials in an incidental episode and had no other congenital disorders, except the only one malnutrition and two obesity.
In the light of the source of the lipid exposure, lipoid pnuemonia is generally categorized as the follows: endogenous lipoid pneumonia, related to intra-alveolar lipoid accumulation as a result from obstruction, chronic lung infection/disorder, a lipoid storage disease; exogenous lipoid pneumonia, due to recurrent or accidental aspiration of fatty substances; and idiopathic lipoid pneumonia, with no identifiable causative agents or underlying conditions.3,11 To precisely review the effect of bronchoalveolar lavage on acute ELP, we only included patients with a confirmed history of aspiration, clinical symptoms and CT scan images, LP is a rarity and, although it’s difficult to determine the precise clinical prevalence, autopsy series have reported an incidence of only 1.0%~2.5%.13 However, due to lack of specific radiological and clinical features and no awareness of LP, LP is difficult to establish and sometime histopathologic confirmation of the diagnosis may be necessary from respiratory specimens.21 Although many of the reports have used lipoid-laden macrophage in the spatum or BAL specimen as a diagnostic marker for LP, its specificity and accuracy have been questioned by some researchers.21 In the present study, BAL fluid analysis shows the presence of lipoid-laden macrophage in the only one case. Therefore, diagnosis of ELP should be based on the triad of history of mineral oil inhalation, compatible radiological imagings, and presence of intra-alveolar lipids and/lipid-laden macrophages.4,6,18,20
BAL is a successful method recommended in the therapy of pulmonary alveolar proteinosis,22-24 but a great many investigations and case-reports have demonstrated good response of whole/segmental lung lavage in the therapy of individuals with LP. In 2020, a systematic review that included 90 ELP patients from 25 case reports and 8 case series studies indicated that therapeutic lung lavage might be an effective and safe therapy with long-term benefits for EL.12 Whole or segmental BAL is a simple and safe procedure that does not require general anesthesia but cough and hypoxemia may eventually occur during the procedure.24BAL may result in transient hypoxemia in few children individuals, but it was swiftly corrected by nasal oxygen and, children caregivers did not report any complication after the procedure.25 In our research, all affected children were performed by BAL and had full resolution until the last follow-up, even multiple BAL in some patients on the basis of the clinical-radiological patterns of paediatric ELP.23Indeed, it has been reported in the literature that 6 months after ELP diagnosis, untreated children had recurrent respiratory infections that required antibiotic therapy and chest CT pattern still showed areas of ground-glass opacities in the lower lobes and atelectasis.11 BAL is a good strategy recommended in the treatment of paediatric acute ELP in terms of our clinical research.25,26
The development of parenchymal abnormalities in ELP is dependent on the type, amount, frequency, and length of time of inhaled oils. Mineral oil (a mixture of inert, long-chain, saturated hydrocarbons obtained from petroleum) and vegetable-based oils tend to cause minimal to mild inflammatory reactions.1,2 The intra-alveolar oils can coalesce in the alveoli and is encapsulated by fibrous tissue, resulting in a nodule or mass (paraffinoma). Conversely, animal fats are hydrolyzed by lung lipases into free fatty acids that trigger a severe inflammatory reaction that manifests as focal edema and intraalveolar hemorrhage.6 Fatty acids either remain in the alveolar spaces or are phagocytosed by macrophages that then migrate to the interlobular septa. Regardless of location, the inflammatory response can destroy the alveolar walls and the interstitium, and the resultant fibrosis can occasionally progress to end-stage lung disease.18,20,27,28 In this study, we divided all patients into two groups based on the source of aspirated substances, the clinical-radiological features were found no statistical difference in both group.
There are also several limitations in the present study. First, this was a respective study conducted in only one hospital so that many confounding factors and various bias could not be avoided due to the inherent nature of the retrospective study. Second, since the affected children were clinically symptomatic in the present study and there was no any other alternative therapy we did not consider it warranted to include a control group of individuals without treatment, so we did not provide significant statistical power to demonstrate the risks and benefits of treatment, especially in radiological aspects. Nonetheless it was possible to establish a comparison with clinic and radiologic features from few children whose parents did not sign the consent for therapeutic BAL, but all parents did approve of aggressive therapy in our study. Third, the radiological findings of all children varied greatly from CT scan images at initial presentation to X-ray films during the follow-up period, therefore, we did not get quantitative data to compare. Finally, the number of children was insufficient to reach a credible and robust conclusion. In the future, larger multicenter prospective cohorts are needed to elucidate the risks and benefits of bronchoscopic lavage and glucocorticoids on children with ELP.
In conclusion, diagnosis of acute ELP is often difficult. Causative agents of ELP can vary depending on differences in culture and life style of the affected countries and regions. Diagnosis of acute ELP should be based on confirmed exposure to lipid substances and clinical-radiological features. Sufficient exposure data is necessary to reach a diagnosis of acute ELP, and to differentiate it from pneumoconiosis. Therefore, primary preventative measures are essential for protecting these children, and the preventative measures should include increased safety awareness of children’s parents or caregivers, appropriately being away from oil-containing substances, children safe health education, and the establishment of an occupational safe education videos for parents.