Response to “Multi-agent pleurodesis: a new horizon in management”

We would like to sincerely thank Nadella and Carr for their thoughtful Editorial Commentary, “Multi-agent pleurodesis: a new horizon in management”, regarding our recently published case report of spontaneous pneumothorax in a patient with tuberculosis-induced destroyed lung successfully treated with autologous blood and minocycline pleurodesis (1,2). We are grateful that the authors highlighted not only the clinical relevance of our case but also the broader implications of multi-agent pleurodesis for high-risk patients with persistent air leak.

We agree with the authors that secondary spontaneous pneumothorax remains a clinically challenging condition, particularly in patients with severely impaired pulmonary reserve or extensive underlying lung disease. In such patients, persistent air leak can result in prolonged drainage, infection, empyema, extended hospitalization, and readmission. While surgical intervention may provide definitive control in selected patients, it is not always feasible. In our case, the presence of contralateral tuberculosis-destroyed lung created a particularly high-risk situation in which operative management and single-lung ventilation were considered unsafe. Therefore, a minimally invasive bedside strategy was selected.

The commentary appropriately emphasizes that guideline-based management of secondary spontaneous pneumothorax provides general principles, including tube thoracostomy and escalation when air leak persists, but does not establish a uniform consensus on the optimal non-surgical pleurodesis regimen in patients who are unfit for surgery. This clinical gap is important. For physicians managing patients with destroyed lung, diffuse fibrosis, or marked frailty, the therapeutic decision is often individualized, balancing efficacy, invasiveness, and risk of complications. Our intent in reporting this case was to provide a practical example of such individualized decision-making.

We also appreciate the authors’ discussion of the potential mechanistic rationale for multi-agent pleurodesis. Autologous blood may act rapidly by promoting fibrin-mediated sealing of the air leak and facilitating pleural adhesion. Minocycline, as a tetracycline-class sclerosing agent, may contribute through chemical pleural irritation and subsequent inflammatory-fibrotic adhesion. The combination of these two mechanisms may be particularly useful when immediate sealing and durable pleurodesis are both desired. In addition, we considered that minocycline’s antimicrobial properties might theoretically reduce the risk of secondary pleural infection, although we agree that this possible preventive role requires further validation and should not be overinterpreted from a single case.

We fully agree with Nadella and Carr that the current evidence for multi-agent pleurodesis remains limited. Our case report should be interpreted as hypothesis-generating rather than definitive evidence. Nevertheless, together with our subsequent reports, including another case report and a case series of high-risk non-surgical patients treated with the same combined autologous blood and minocycline regimen (3,4), we believe that this combination may represent a useful option when conventional conservative management fails and surgery is contraindicated. Future studies should clarify patient selection, optimal dosing, timing of repeated instillation, comparative efficacy versus single-agent pleurodesis, and safety outcomes such as fever, pain, empyema, recurrence, and need for additional intervention.

In conclusion, we are honored that our case report has stimulated discussion on multi-agent pleurodesis. We share the view that this approach may represent a promising direction for selected high-risk patients with persistent air leak. However, further prospective and comparative research is needed before such regimens can be standardized. We hope that our report, together with the insightful commentary by Nadella and Carr, will encourage further investigation into safe, practical, and individualized non-surgical strategies for patients with difficult secondary spontaneous pneumothorax.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, AME Case Reports. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2026-0168/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Nadella N, Carr SR. Multi-agent pleurodesis: a new horizon in management. AME Case Rep 2026;10:82. [Crossref] [PubMed]
2. Koh E, Sekine Y. Spontaneous pneumothorax in a patient with tuberculosis-induced destroyed lung successfully treated with autologous blood and minocycline pleurodesis: a case report. AME Case Rep 2026;10:32. [Crossref] [PubMed]
3. Koh E. Successful Combined Autologous Blood and Minocycline Pleurodesis for Intractable Bilateral Pneumothorax in an Elderly Patient With Combined Pulmonary Fibrosis and Emphysema: A Case Report. Respirol Case Rep 2025;13:e70358. [Crossref] [PubMed]
4. Koh E, Sekine Y. Efficacy and Safety of Combined Autologous Blood and Minocycline Pleurodesis for Intractable Pneumothorax in High-Risk Non-Surgical Patients: A Case Series. Respirol Case Rep 2025;13:e70430. [Crossref] [PubMed]