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.