Treatment
Treatment strategies in SPDS are
varied and not standardized given its heterogeneity and rarity. Two
major clinical practice guidelines exist based on the consensus of
clinicians. The first is the European treatment guideline that was
developed though a Delphi consensus process and provides a consensus
between clinicians from Europe and Australasia for children up to the
age of 16[70, 79]. The second guideline was developed by the
American Thoracic society for children under the age of two
years[71]. Treatment of SPDS
is often through immunosuppression as an attempt to reduce pulmonary
fibrosis[12] and the need for lung transplant in severe
cases[80].
Through the Delphi consensus process, the use of corticosteroids whether
enterally or parenterally with subsequent consideration of other adjunct
add-on therapies for example hydroxychloroquine and azithromycin was
recommended. [79]The rationale of using pulse methylprednisolone
stems from the postulate that glucocorticoids increase the expression of
ABCA3 in vitro . Nevertheless, there is limited evidence of any
benefits in the use of glucocorticoid in clinical practice. The decision
to trial glucocorticoids should then be made on an individual basis and
more importantly these patients should be monitored for the notorious
side effects of steroids. Surveillance with long term steroid use should
include serial ophthalmological review for cataracts, bone mineral
density scanning and growth monitoring. The next option is
hydroxychloroquine which also requires close monitoring in terms of
retinal toxicity, bone marrow suppression and cataract formation[81,
82]. Retinal toxicity is a serious side effect that is relates to the
total accumulated dose. The risk of developing retinal toxicity is
~40% following use for 20 years[83, 84]. At
present, there is an international, prospective, randomized controlled
phase 2a trial ongoing to evaluate the efficacy, risks and benefits of
hydroxychloroquine in children with chILD[85]. Azithromycin has also
been used in to provide immunomodulation in SFTPC and ABCA3
deficiencies[86].
Studies into amino acid sequence of surfactant protein has enabled
studies into the production of recombinant surfactant. Synthetic
surfactants have been modelled from the structures of SP-B and SP-C for
example KL4, an amphipathic peptide which is modelled after SP-B was
approved for the use of respiratory distress syndrome in the USA by Food
and Drug Administration[87]. Similarly, SP-B and SP-C like peptides
has managed to improve lung function in animal models[88]. The
clinical application in surfactant protein deficiency is yet to be
clearly explored.
Supportive therapy is essential towards the management of SPDS. The use
of supplemental oxygen should be evaluated in these children and in more
severe cases of SPDS non-invasive ventilation may also have a role.
Therefore, continuous saturation monitoring or performing overnight
oximetry and capnography is important to elucidate requirement.
Nutrition also likely plays an important role in the prognosis of SPDS
and is taken in the assumption that nutritional rehabilitation helps in
children with cystic fibrosis and bronchiectasis. Increased work of
breathing leading to increased calorie expenditure is fairly common in
these chronic conditions and long-term nutritional support may be
necessary[89].
Vaccination plays an important role in the supportive care of these
children with suggestions of annual flu vaccination. In view of the
severe RSV bronchiolitis that occurs in patients with SPDS, in infants
with severe SPDS it has been recommended for the use of palivizumab.
Additionally, prophylaxis for Pneumocystis jeroveci should
be given to children on immunosuppressants.
Although the psychological aspects of the management of SPDS in both
patients and families is limited and often underappreciated in view of
its rarity[90], evidence from families affected by other chronic
lung diseases e.g. cystic fibrosis and bronchiectasis may benefits from
psychological support both before and after diagnosis is made. In cases
of more severe SPDS, the involvement of the palliative care service
where available and socially accepted is also an important aspect in
managing the psychosocial aspects of this disease.
Timing of lung transplant in SPDS is dependent on the age of the child,
for infants they are most commonly transplanted for SP-B or ABCA3
deficiency while children were more commonly transplanted for SP-C or
ABCA3 deficiency[91]. For infants, they were more likely to be
mechanically ventilated at time of transplant and were less likely to
develop bronchiolitis obliterans post- transplant, which is a feared
complication particularly in children beyond 1 year from
transplant[91]. Regardless of this however, studies have shown that
there is no significant difference in the mortality rate of transplant
either occurring in infancy or during childhood[92]. The 5 year
survival rates are approximately 50% in patients undergoing lung
transplant[93]. Although transplant permits for short term survival
in an otherwise lethal disease, there is significant burden of care of
these children post lung transplant which includes regular clinic
reviews, admission, repeated blood test, bronchoscopies and CT scan in
addition to medications that has significant side effect
profiles[91]. The significant challenges and impact on families in
this aspect must be properly evaluated. Discussion with families and
allowing them to have a say in this decision is imperative and a review
on decisions to transplant these children has shown that up to 50% of
families have actually refused lung transplant[94].
Given the rarity of SPDS and the heterogeneity of this condition, it is
important that the management is approached in a multidisciplinary
perspective. This multidisciplinary team should include paediatric
pulmonologists, cardiologist, geneticist, pathologists, genetics
counsellor and other members of the allied health team[86]. Multiple
such platforms exists worldwide; for example chILD-EU[79], chILD
research network (chILDRN)[95] and chILD Research Australia and New
Zealand (chILDRANZ)[96] and chILD network[97] to facilitate
discussions, provide support for diagnosis and management of these
conditions.