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Chen et al. Rare Dis Orphan Drugs J 2022;1:15 https://dx.doi.org/10.20517/rdodj.2022.18 Page 9 of 12

Replenishing AAT to restore protection against proteinase-driven damage is a logical and straightforward
strategy but is costly and requires weekly infusions. Although AAT has broad immunomodulatory
functions, it plays a passive role in preventing downstream injury as a side effect of excess neutrophil
trafficking in response to chemoattractants. In comparison to the greater than $100,000 per patient per year
for delivering augmentation therapy, novel oral drug candidates are likely to be cheaper but, importantly,
less invasive and therefore more convenient for the patients.

CONCLUSION
Understanding the steps that lead to neutrophil migration, degranulation and tissue damage offers several
potential strategies to modulate the proteinase/antiproteinase balance, although this has to ensure the
important secondary host defensive functions are retained.

DECLARATIONS
Acknowledgments
Celine H. Chen would like to thank Dr Aaron Scott for his help with manuscript orientation.

Authors’ contributions
Both authors made substantial contributions to the conception and writing of the chapter.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Authors 2022.

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