Clinical Meetings at RH Year 2009

2009 - Bubbles, Bubbles, Bubbles...! - Endobronchial One-way Valves for the Treatment of Persistent Air Leaks Complicating Secondary Spontaneous Pneumothorax

Dr Kwok Hau Cung Jones and Dr Yeung Yiu Cheong. Department of Medicine and Geriatrics, Princess Margaret Hospital

Fig.1 Bronchoscopic view of the right upper lobe bronchus in patient 1 showing EBVs inserted at each of the three upper lobe segments (top) and the lingular segments (bottom).

Introduction
Persistent air leak is common in spontaneous pneumothorax (SP) with proportions at 48 hours, 7 days and 14 days after chest drain insertion reported at 51%, 34.6%, and 15.4% respectively [1, 2]. It signifies that the lesion which allows air to escape from the lung into the pleural spaces has not healed up, and surgery is the treatment of choice for air leaks of 5-10 days’ duration [3].

Patients with underlying lung diseases, secondary spontaneous pneumothorax (SSP), tend to have prolonged air leaks and account for most cases with air leaks longer than 14 days [1, 2]. They are also older and with compromised lung function and hence higher surgical risks. There are few other treatment choices and such patients often have to carry a chest drain (CD) for prolonged periods with wound pain and increased risk of wound infection, subcutaneous emphysema, misplacement of chest tube or dislodgement requiring re-insertion. Prolonged bed confinement with deconditioning is also a very important consideration in such patients and prolonged rehabilitation is often necessary after removal of CD. We describe our early experience of using endobronchial one-way valves (EBV) for the treatment of persistent air leak complicating secondary pneumothorax.

Case 1
A 73 year-old man heavy smoker and ex-intravenous drug user, had history of pulmonary TB. He was admitted for acute shortness of breath. CXR revealed left pneumothorax with near-complete left lung collapse. CD was inserted with satisfactory lung expansion, but the air leak persisted. HRCT showed left pneumothorax with chest drain in-situ. There were fibrocalcific foci in the left upper lobe (LUL), diffuse emphysema, and some small bullae. Thoracic surgeon was consulted but surgical treatment was declined for the high operative risk. Flexible bronchoscopy under local anaesthesia (LA) was done on day 23. Blockage of the LUL bronchus (inclusive of the lingular segments) resulted in immediate cessation of air leak, whereas no such effect was seen when the left lower lobe (LLL) bronchus or the individual LUL segments were blocked. One EBV (Emphasys Medical Inc, California, CA) was placed to block both LB4 and LB5, and air leak continued. The second EBV was placed into LB3, and the third EBV placed into LB1, and airleak still continued. The LB3 valve was taken out and put into LB2, but air leak still continued. Finally, when a fourth EBV was put into LB3 (i.e. with all LUL segments blocked), the air leak stopped. (Fig.1)CXR on the following day showed LLL fully expanded and LUL partially collapsed. As there was no air leak, CD was removed and patient was discharged one day afterwards (day 25). During follow-up assessment, there was no recurrence of pneumothorax. Bronchoscopy was repeated 43 days after the first one and all the EBVs were removed. Subsequent CXR showed no recurrence of pneumothorax and LUL was expanded. There was progressive improvement in his general condition, with no recurrence of pneumothorax 9 months after removal of chest drain. Post bronchodilator FEV1 was 0.84L (44% predicted) and FEV1/FVC was 48%

Case 2
This is a 61 year-old man with history of chronic obstructive pulmonary disease (COPD), bronchiectasis, and right pneumothorax 10 years ago with medical pleurodesis performed. He was admitted for increased shortness of breath. Chest radiograph (CXR) showed an 80% right pneumothorax with apical pleural adhesions as well as emphysematous changes and cystic bronchiectasis. After insertion of an 18-Fr CD, there was some re-expansion of the right lung, yet the air leak continued. HRCT showed right pneumothorax with CD in-situ, fibrocalcified foci in the RUL, severe diffuse emphysema with multiple sub-pleural bullae of up to 2.7cm in diameter, blebs over the RUL and RLL, and extensive cystic bronchiectasis in the RML, lingular segments, and bilateral LLs. Thoracic surgeon was consulted but surgery was considered unsafe for him. Flexible bronchoscopy (LA) was performed on day 34 in bronchoscopy suite. Attempts at identifying the leaking lobe or segment was done by sequential occlusions with balloon catheter to observe for cessation of air leak during bronchoscopy. Immediate cessation of air leak occurred when the RUL bronchus was occluded, whereas occlusion of individual segments of the right upper lobe as well as the right bronchus intermedius did not bring about any change. EBV was placed into RB1, RB2 and RB3. There was prompt and complete cessation of airleak. However, air leak resumed 30 minutes later but at a reduced rate and CXR showed expansion of the lung with minimal collapse of the RUL. Air leak stopped completely at day 37 and the CD was removed on day 39 (9 days after the EBV insertion). Because he required oxygen supplement to maintain satisfactory oxygenation, he stayed until day 53 when he was discharged with home oxygen therapy. No recurrence was noted afterwards although he was readmitted for 2 times for acute exacerbations of COPD. When the condition was stabilized, bronchoscopy was repeated (10 weeks after the first bronchoscopy) and all 3 endobronchial valves were removed. After that the patient experienced subjective improvement in breathing and body weight also progressively increased back to the earlier level. Spirometry showed a post-bronchodilator FEV1 0.92L (32% predicted) and a FEV1/FVC ratio of 46%. Home oxygen therapy was no longer required and there was no recurrence of pneumothorax 9 months after removal of CD.

Case 3
This is a 26 year-old man with good past health, who presented with dyspnoea for one month. CXR showed right pneumothorax and multiple patchy consolidations. CT thorax revealed features of right tension pneumothorax. Right CD was immediately inserted. As he was later found to have positive AFB smear in sputum examination, anti-tuberculous therapy with isoniazid, rifampicin, pyrazinamide and ethambutol was started. He was found to have persistent air leak one month after chest drainage. Thoracic surgeons suggested conservative management in view of his active tuberculous infection. Bronchoscopy was done on day 34 after CD insertion. Balloon test was done sequentially with RUL, RML and then RLL. There was immediate cessation of the air leak when the RML bronchus was occluded. Further testing revealed immediate cessation of the air leak when RB4 (but not RB5) was occluded. One EBV was therefore inserted in the RB4 segment with immediate cessation of the air leak. However, one hour after the procedure, air leak resumed though at a reduced rate. Complete cessation of air leak was observed 4 days after the EBV insertion and the CD was then taken off. He was discharged a few days later with continued anti-tuberculous therapy in chest clinic. The EBV was removed 2 months after insertion with no recurrence of pneumothorax.

Discussion
Patients suffering from pneumothorax with persistent air leaks of longer than 10 days and who are not surgical candidates often present a therapeutic challenge. Prolonged chest drainage is associated with numerous potential complications discussed earlier. While the use of small-bore drainage catheters with Heimlich flutter valves has been reported to be useful as an ambulatory treatment [4, 5], their safety for the management of high-risk patients with secondary spontaneous pneumothorax is questionable. Interventions that stop the air leaks are thus highly desirable and can broadly be divided into two approaches. One is medical pleurodesis using substances like tetracycline [6, 7], autologous blood patch [8-11], or talc [12]. The intrinsic limitation of this approach is that successful pleurodesis requires the visceral and parietal pleurae to be in good apposition, and when air leak is ongoing this can be difficult to achieve [13]. Although the loop method allows continued drainage of pleural air while retaining the pleurodesis agent within the pleural cavity [14], suction is usually required to be switched off and hence apposition of the two pleural membranes will be further compromised.

The other approach would be the endobronchial interventions with the use of agents such as plugs [15], sealants [16, 17], doxycycline and blood. [18] More recently, one-way endobronchial valves such as the Emphasys can be deployed via the flexible bronchoscope into the target airway. After deployment, they self-expand and stay, and allow air and secretions to escape from the lower airways while preventing air from entering. It is originally developed for bronchoscopic lung volume reduction for treatment of diffuse pulmonary emphysema, but its potential in treating persistent air leaks was soon recognized. To date most reports were made from isolated cases of post-operative broncho-pleural fistulae [19-23] and cases of iatrogenic pneumothorax with persistent air leaks [24, 25]. Only one case of successful treatment for spontaneous pneumothorax had been reported which described a 32 year-old lady with severe pneumonia and adult respiratory distress syndrome [23].

There are two possible mechanisms to explain the finding in our patients that all segments of a lobe have to be blocked in order to be successful. Firstly, the air leak may be due to a focal sub-pleural emphysema-like change in the form of bulla or bleb, but with collateral ventilation across segments and lobes. Collateral ventilation is defined as “the ventilation of alveolar structures through channels or structures that bypass the normal airways”. Airflow through these channels is insignificant in healthy lungs but can increase markedly in subjects with diffuse emphysema [26]. In the latter situation it was believed that the collateral ventilation allow lung units which are severely affected by airflow obstruction to continue contributing to gas exchange. Publications on bronchoscopic treatment for pulmonary emphysema reported that only 0-50% of lung lobes did collapse following EBV placement to block it [27]. This poses a problem for endobronchial treatment of both emphysema [28] and persistent air leaks. For the latter one probably have to be prepared to occlude a number of segments to be successful in patients with emphysema. On the other hand, one might need to block just one segment in patients with primary spontaneous pneumothorax (PSP), where collateral ventilation is less of a problem. However, PSP is less associated with prolonged air leaks, and surgery is currently the standard treatment in this situation.

Secondly, the air leak may be due to “enhanced pleural porosity” which may involve the visceral pleura and subpleural lung tissues extensively [29]. The general belief that spontaneous pneumothorax is the result of rupture of emphysema-like changes has been debated since surgically resected subpleural blebs or bullae had not consistently demonstrated defects responsible for the air leak in the resected bullae [30], and pleural porosity has been proposed as an alternative or additional mechanism. The observation in our patients can potentially be explained by air leaks originating from two or more such lesions simultaneously and with the lesions located in different segments or lobes, though how likely this happens even in the presence of pleural porosity is unclear. It would be attractive to attempt segmental bronchi blockade in PSP where collateral ventilation would not be a confounder to determine whether air leaks from multiple sites does in fact exist.

Experiences of EBV in the treatment of diffuse pulmonary emphysema indicate that adverse effects do occur. In a case series of 98 cases, there was one death, three patients with pneumothorax requiring surgical intervention, and 4 patients with pneumothorax with prolonged air leaks [31]. There were no reports of post-obstructive pneumonia. Other non-serious complications include pneumothorax with drainage less than 7 days, pneumonia of non-involved lobes, COPD exacerbation and pleural effusion. In our limited experience with EBV for persistent air leaks, we have not seen any of these complications.

Treatment efficacy in our three reported cases varied and was rather inconsistent. While successes in case 1 and case 3 were rather obvious, that in case 2 was less certain. One significant limitation to the use of EBV in SSP would be the high cost of this device (at US$1,680 per piece), and more valves may have to used that would further increase the cost. Furthermore, it is generally recommended that pleurodesis should be attempted following successful treatment of SSP even if the episode is the first one [32-34]. However, if EBVs are used in the treatment of persistent air leak, there is a significant chance that whatever material used for pleurodesis might reach the central airways via the EBVs. This might reduce the effective dose of the sclerosing agent and also impose a theoretical risk of collateral damage to the airways. As a result, pleurodesis had not been attempted in our patients.

In conclusion, there is a sound theoretical basis for the use of EBV in the treatment of persistent air leaks complicating SP. Our cases suggested that this approach may in fact be useful in SSP, and also appeared to be safe when performed in the bronchoscopy suite under LA. More data should be obtained for its use in SSP, and opportunities should be sought for using EBV in persistent air leaks complicating SSP.

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