DISCUSSION
The development of TALS has been attributed to the Macklin effect, which
consists in air leak into the pulmonary interstitium with retrograde
dissection along the perivascular sheats9, 11. Air leak
is secondary to alveolar rupture caused by high intra-alveolar pressure,
related to small airways stenosis and chronic
coughing2 associated with alveolar wall weakness
caused by pulmonary fibrosis9, 12. The sharp reduction in FEF 25-75% described in
this series, which has been associated with small distal airways
dysfunction 13,
is consistent with this mechanism.
Risk factors associated with increased incidence of TALS include history
of extra-pulmonary chronic GvHD, previous Bronchiolitis Obliterans (BO),
male sex, age younger than 38 years and history of repeated allogenic
HSCT 3, 5,7.
The occurrence of TALS significantly worsens long-term prognosis of
patients with a history of allogenic HSCT, with a survival rate of 44%
at 1 year and 15% at 3 years 5 and overall mortality
rate among patients between 66.7% and 100% 8, 9despite multiple surgical strategies that include simple chest drain,
pleurodesis, thoracoscopic resection, open thoracic surgery4 – 7 and even lung transplantation in extreme cases6.
In the present case series, all the patients experienced temporary
relief from symptoms related to TALS after surgery, but in all cases
respiratory function deteriorated, eventually leading to exitus (Table
4).
It has been proposed that the development of TALS might be interpreted
as a sign of severe worsening of pulmonary GvHD, which eventually leads
to respiratory failure and death, even in patients in whom air leak has
resolved 4, 5, 7; the present data are consistent with
this hypothesis.
Kunou et al have described the successful use of pleural covering
technique in two adults affected by recurrent TALS after HSCT14. This
technique consists in covering the visceral pleura with sheets of
bioabsorbable material15, 16, which
induces thickening of the visceral pleural with minimal or no pleural
adhesion 17 and
reduces the risk of recurrence of TALS 16. This
technique might be a promising surgical option for air leak resolution;
however, it cannot address the problems related to worsening respiratory
function.
Referral for lung transplantation could be a surgical option for these
patients; however, many of them might be judged as non-eligible because
of history of hematologic malignancy with a disease-free interval
shorter than 5 years, previous thoracic surgery, malnutrition or other
comorbidities 18.
Repeated allogenic HSCT has become a therapeutic option in pediatric
patients with relapsed hematologic malignancies19 – 21; as
the number of children and adolescents who receive second allogenic HSCT
increases, a higher incidence of TALS should be anticipated.
In conclusion, surgery provides temporary relief to symptoms related to
TALS but has no impact on the progression of pulmonary GvHD. When TALS
develops, patients are at high risk of respiratory failure and death.
Multidisciplinary efforts are mandatory to develop novel strategies for
the prevention of TALS, the identification of high-risk patients and the
treatment of TALS.
Conflict of Interest: The authors declare that the research was
conducted in the absence of any commercial or financial relationships
that could be construed as a potential conflict of interest.
Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted
in accordance with the Declaration of Helsinki, and Ethical review and
approval were waived for this study due to its retrospective
observational structure.
Informed Consent Statement: Written informed consent was
obtained from the minor(s)’ legal guardian/next of kid for the
publication of any potentially identifiable images or data included in
this article.
Data Availability Statement: The raw data supporting the
conclusions of this article will be made available by the authors,
without undue reservation.