Discussion
Although for a long time it was thought that LUS was not feasible due to
the air content, numerous studies in adults and subsequently in
children, showed its efficacy for the diagnosis of pneumonia with
sensitivity and specificity superior to CXR. (17,19-24) Therefore, LUS
is now identified as a valid substitute for CXR in the course of
respiratory tract infections in children with the aim of reducing
exposure to ionizing radiation. Moreover, CXR does not allow
localization of infection in cancer patients in over 44% of cases. (13)
As demonstrated by Gerristen et al., the sensitivity of CT at low doses
of radiation is 73% performed on the first day of febrile neutropenia
versus the sensitivity of 36% of CXR. (13) Heussel et al. showed that
in more than 50% of febrile neutropenic patients with normal CXR, there
were signs of pulmonary inflammation on CT. (25)
Ultrasonography is the ideal tool for its speed, non-invasiveness, easy
repeatability and simple interpretation of the examination after
appropriate training even by non-radiology specialists. This last
feature is of increasing importance in relation to the concept of
personalized medicine. (5) The ”bed side” ultrasonography, performed in
the emergency departments or in critically patients, allows a more
detailed evaluation of the individual patient obtaining an ever more
patient-based rather than disease-based care approach. (5)
If in pediatric clinical practice, LUS is becoming an increasingly
useful examination; howevwer, no study about its accuracy has ever been
performed on the pediatric cancer population, where factors such as type
of neoplasia, chemotherapy and thoracic radiotherapy with its pulmonary
toxic effects and neutropenia may reduce the specificity and sensitivity
of the tests.
Our data indicated that the underlying cancer, the administered
therapies, the number of neutrophils did not influence the result, and
the specificity was 95%, comparable to that described in the pediatric
population for the diagnosis of pneumonia.(26) The sensitivity, even if
calculated in a small series, was 100%.
Our data, with the limit of a small sample, showed that in
non-neutropenic febrile patients, LUS has an important role, comparable
with the literature on pneumonia cases in pediatric age. (26-30) In this
population, LUS showed better diagnostic accuracy than CXR, which had a
specificity of 80%, and a sensitivity of 50%, considerably lower than
literature data on pediatric population but similar to adult cancer
population. (13) LUS showed to have early positivization, even before
the onset of clinical respiratory symptoms. This test could therefore be
used as a screening tool for pulmonary infections in febrile cancer
patients, in order to undertake early specific and targeted treatments
or to direct the diagnostic-therapeutic work-up. Moreover, a LUS
follow-up allowed to modify or to stop the anti-infection treatment
according to the evolution of the process.
In febrile neutropenic patients, despite the absence of respiratory
symptoms, it was possible to find lung lesions on ultrasound in 50% of
cases, indicating that this method can be an aid technique for the
diagnosis of infections during neutropenia, while CXR, with its low
sensitivity is not indicated in the suspicion of lung infection during
neutropenia. Five out of 10 patients presented a positive LUS for
pneumonia. These data show that in 50% of patients with febrile
neutropenia there is an ongoing lung infection; the latter often
resolves thanks to empirical broad-spectrum antibiotic therapy but in a
smaller percentage of cases it can evolve towards acute respiratory
failure or sepsis. (31) Likely the reason why LUS has greater
sensitivity than CXR in this population can be explained by the results
obtained by Shah VP et al. (32) This study demonstrated that while for
pulmonary thickenings of size greater than 1 cm the CXR and the LUS have
a similar diagnostic accuracy, in pulmonary thickenings smaller than 1
cm LUS has a clearly superior sensitivity. Therefore, it can be
hypothesized that in the patient with a low number of neutrophils and
consequent deficient inflammatory response, the infection predisposes to
develop subcentimetric thickening, not detectable on CXR. This
hypothesis is confirmed by the few data we collected: in 4 out of 5
febrile neutropenic patients (80%), pulmonary thickening on LUS were
subcentimetric. This finding could open the door to a new simple
diagnostic tool to be used in all neutropenic febrile cancer patients.
Most patients were compliant to LUS, demonstrating the low invasiveness
of the method even in this population. The less cooperative patients
were younger than 6 year or patients at the onset of cancer, often
frightened by many diagnostic procedures (bone marrow aspirate, lumbar
puncture, placement of central venous catheters or excisional biopsy),
the hospital environment and the disease itself. Moreover, LUS was
efficaciously performed, without the need of sedation, what is not
always feasible for CXR or CT.
The possibility of using a tool, such as LUS, which is minimally
invasive, repeatable, bedside suitable, radiation free and, at the same
time, accurate, as a screening for the early detection of lung infection
and monitoring its evolution, can have a great impact on the management
and outcome of the pediatric cancer patient.
We hypothesize a role for LUS, as a first imaging technique, and propose
a possible diagnostic work-up flow chart that includes LUS for the
management of patients with signs of infection, with the aim of reducing
radiation exposure and inserting a non-invasive and bed side examination
(Fig. 2). Obviously, the proposed flow chart does not exempt from
individual evaluation and specific clinical management.