COPD is a severe lung disease characterized by persistent airflow limitation that progresses over time. In China, it has a prevalence rate of 8.2% in those over 40 years of age. Diffuse emphysema and subpleural bullae are often found on chest x-rays, and these bullae are the main causes of persistent air leakage, which is difficult to treat. Once air leakage occurs, it devastates the patients because their baseline lung function becomes more limited, and it pushes them to undergo a surgical procedure under general anesthesia [2]. The post-operative complications could also jeopardize their general condition, so the management of pneumothorax secondary to COPD is complicated. Furthermore, patients with this condition could suffer from pneumonia and respiratory failure after lung volume reduction surgery, making it difficult for them to be weaned from ventilators.
The main objective of management of patients with COPD complicated by pneumothorax is to stop air leaks using relatively simple and safe methods, and various methods have been used to meet this objective. If a patient is still in good condition and an operation is tolerable, surgical removal of the subpleural bullae is considered the first line treatment. This prevents the enlarging bullae from gradually compressing the normal lung tissues. However, surgical intervention appears to be a radical method for recurrent pneumothorax, and there are patients who cannot undergo such a procedure. The management of COPD-related pneumothorax by bronchial occlusion in combination with talc powder has been reported to be successful in three cases [6]. Though no recurrences were observed for more than 1 year, the long hospitalization and complex procedure associated with it made it less favorable. Tube thoracostomy is effective in providing symptomatic improvement, but when it is repeated, it can be a physical and emotional burden to the patients. Another method is to rub the pleural membranes during surgical intervention, which leads to pleural adhesion and prevents the recurrence of pneumothorax. According to the BTS guidelines, medical pleurodesis remains the first choice for treating persistent air leakage [5], as it is safe and easy to perform. It induces pleural adhesion through aseptic inflammation and is indicated for patients with near-normal pulmonary function and no obvious bullae on CT imaging. However, the use of this method has problems, as there is no consensus yet on the best technique to follow. Additionally, the sclerosing agents used for this procedure have variable efficacy and safety.
A recent meta-analysis confirmed the superiority of talc as a sclerosing agent. Talc use can induce intense intrapleural inflammation by producing numerous pro-fibrotic factors that cause adhesions and fibrosis between the pleural membranes [7]. Common side effects of talc include fever (10-17%), pain, and gastrointestinal symptoms. Less common side effects include arrhythmia, dyspnea, respiratory failure, a systemic inflammatory response, empyema, and the dissemination of talc to other regions [8–10]. However, talc particles and other pro-fibrotic factors hypothetically have the potential to be absorbed and lead to systemic inflammation. This problem has raised questions about the safety of talc as a sclerosing agent [10]. Therefore, scientists are still searching for the most suitable sclerosing agent for pleurodesis – one that could yield a high success rate with a low risk of severe adverse reactions.
Mannose-binding hemagglutinins in extracts of Pseudomonas aeruginosa were first proposed in 1977 and have now gained more consideration because of their anti-tumor effects [11]. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PAMSHA) is a peritrichous P. aeruginosa strain with MSHA fimbriae that can inhibit activation of the epidermal growth factor receptor signaling pathway in tumor cells [12]. Animal studies have shown that PAMSHA affects both the pro-inflammatory and anti-inflammatory processes, which help limit the severe adverse reactions caused by systemic inflammation [13]. In other studies, it has been reported to induce apoptosis in tumor cells and improve immune function, which can prevent metastasis and the recurrence of certain types of cancer [14–19]. It has also been used to treat malignant pleural effusion [20–22].
In this study, we report our experience performing pleurodesis using PAMSHA as the sclerosing agent. We think that this method is more convenient than bronchial occlusion followed by the addition of talc powder. Medical pleurodesis with PAMSHA can produce similar results but without the risk of severe side effects and the trouble of doing a multi-step procedure. After observing the effects of the intrapleural administration of PAMSHA in 78 inoperable cases of pneumothorax secondary to COPD, our follow-up imaging studies showed signs of resolution of the pneumothorax. After a year of follow-up, none of our patients reported readmission due to recurrence of a pneumothorax. For us, this is enough information to report that we had a success rate of 100% for the procedure. Additionally, adverse effects such as chest pain and low-grade fever were only transient and resolved well with supportive care. No gastrointestinal and neurologic dysfunction, bone marrow inhibition, or liver/kidney impairment were reported.
There are limitations to this study. First, this study was retrospective, and there was no standardized evaluation of the inoperability of the patients from the perspective of pulmonary function. Second, the reporting of adverse effects after pleurodesis was relatively subjective and did not employ standardized scoring systems to quantify clinical improvement properly. We believe that a prospective study with precise definitions of the variables and a standardized treatment protocol will be helpful in validating our results.