Minimally invasive resection of a marijuana-associated giant bulla

The first case report on giant bullous emphysema was published by Burke in 1937.¹ It is a rare manifestation of emphysema.

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), chronic obstructive pulmonary disease (COPD) is defined as a “common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases”.²    The report continues to elaborate that small airway disease and emphysema are the two main constituents of COPD. 

Emphysema is a pathological term, which refers to the destruction of airspace walls distal to the terminal bronchioles, with the creation of permanently enlarged airspaces but without any fibrosis.³  In some patients, this continues to advance to bullous emphysema, which consists of multiple bullae within emphysematous lung parenchyma.  By definition, bullae are air spaces which are at least 1cm in size, encompassed by walls made of visceral pleura and remnants of alveolar and interlobular septae.⁴  When bullae occupy more than a third of the hemithorax they are located in, they are labelled as giant bullae.^5-6  If no complications occur, the usual development of giant emphysematous bullae is gradual enlargement, which would ultimately impair breathing.  However, rare spontaneous regression of giant emphysematous bullae have been reported, with symptomatic and radiological improvement.⁷

Nowadays, the international gold standard treatment for this disease is VATS-bullectomy, replacing open surgery. We describe here the first case of a giant bulla resected in this minimally invasive way in Malta.

Case

A 31-year-old patient, with a past history of right pneumothorax 3 years before, presented with a recurrent ipsilateral pneumothorax. This second pneumothorax was treated with a Seldinger insertion 12Fr intercostal chest drain for a few days. The lung re-inflated successfully, and the patient was referred electively to the cardiothoracic clinic.

His past medical history includes severe eczema requiring steroids and immunosuppressants. He is a cigarette smoker and has smoked approximately 1 packet a day for the past 17 years.  He has also beensmoking marijuana heavily, every day for the past 8 years.    While being followed up 1 week later in the cardiothoracic clinic, he was not short of breath, and was otherwise asymptomatic. On examination, he had decreased air entry bilaterally, but was hyper-resonant over the upper 2/3 of his left lung.  Pulse oximetry showed an oxygen saturation of 100% on air and his breathing rate was 12 breaths per minute.  The rest of his parameters were stable.

A chest X-ray showed decreased lung markings over the upper half of the left lung (Figure 1).  A CT scan of the thorax was performed.  This revealed a large emphysematous bulla in the left upper lobe, about 17 centimetres by 21 centimetres in size.  Another bulla, measuring 7 centimetres by 6 centimetres, was also visualised in the superior lingular segment (Figure 1). 

Figure 1

Left: Chest X-ray done on admission, showing decreased lung markings over the upper half of the left lung.
Right: CT scan showing the giant bulla in the left upper lobe, and the smaller bulla in the superior lingular segment.

Accompanying this, there was also a very small pneumothorax of up to 9mm in depth around the left lung, and some para-septal emphysema in the right upper lobe.

In view of his recent pneumothorax, no pulmonary function tests were done.

An elective VATS bullectomy was done, using single lung ventilation under general anaesthesia. Two port technique was used with adhesions removed between the giant bulla and the chest wall. The upper lobe giant bulla was resected using an Endo GIA™ (Covidien, Metronic, Minneapolis, Minnesota, USA) trilinear stapler. The resection was performed a centimetre beneath the origin of the bulla, to ensure that healthy lung seals well at the staple line. The second smaller bulla was resected in the same manner. A total pleurectomy was also performed to help prevent recurrence of the pneumothorax. One drain was placedbut no suction was applied onto the drain, unlike routine pleurectomy operations for primary spontaneous pneumothorax. This was omitted to avoid sudden re-expansion of a chronically compressed lung with risk of staple line dehiscence. The patient mobilized the day after the procedure, his drain was removed 2 days post-operatively and he was discharged that same day.

The patient was reviewed two weeks after the surgery and all wounds were healing well (Figure 2).  A repeat chest X-ray showed full re-expansion of the lung (Figure 3). The patient also stated that he was feeling quite well and was very happy with the care he had received.

Figure 2

The port through which the VATS bullectomy was carried out, 2 weeks post-surgery

Figure 3

Chest X-ray 2 weeks post-surgery, showing full re-expansion of the lung

Discussion

Giant bullae are classified in many ways, such as; Reid⁸, Wakabayashi⁹, and DeVries & Wolfe’s¹⁰ practical classification into 4 groups. However, we favour the classification by Klingman which categorizes giant bullae according to the quality of the underlying lung.¹¹ Type 1 is where the giant bulla is surrounded by normal lung, type 2 by emphysematous lung and multiple other bullae and type 3 is that of vanishing lung syndrome (VLS).

VLS is the most extreme form of giant bullous disease where the bullae, with their low compliance, continue to be ventilated preferentially and the remaining lung involutes into nothing but a hilar bud. No lobes are discernible and unfortunately the condition is not amenable to surgical cure at this stage.

The indications for surgery in giant bullae include dyspnoeic patients with high residual volume and hyperinflation present, and the emergence of complications. Surgery is also indicated as a prophylacticmeasure in bullae occupying more than 50% of a hemithorax, and also if a longstanding bulla is occupying one third of the hemithorax, since this prolonged compression renders the remaining lung less likely to expand.

The commonest complications of giant bullae include infection, haemorrhage, and pneumothorax.^12-13   A rare complication that has been reported with giant bullous disease is superior vena cava obstruction, which unless treated early could lead to death.¹⁴  Ischaemic stroke caused by air emboli from a ruptured giant bulla has been reported to occur although this is a very rare complication.¹⁵  Interestingly, giant bullae are an emerging risk factor or even aetiological factor for lung cancer.  Multiple cases of lung cancer associated with giant bulla and with differing histology have been reported.^16-17 More research about this association is needed, but this could potentially give another valid reason for preventative surgical treatment of giant bullae, especially in older patients, to improve the prognosis.

The case described here was a Klingman type 2 with the complication of recurrent pneumothorax. He had no other potential causes besides cigarette and cannabis smoking.

Marijuana abuse is highly linked with giant bullous disease of the lung.  It is suggested that marijuana is more likely to cause giant emphysematous bullae when compared to tobacco smoking, which in contrast has a higher chance of causing emphysematous changes with smaller bullae.^18-20  This could potentially be due to the higher inspiratory pressures and prolonged breath-holding that are associated with marijuana smoking, accompanied by direct toxic damage to the lung parenchyma.²¹  Studies indicate that bullous disease secondary to marijuana abuse tends to occur in a younger cohort of patients, and tends to be asymmetrical – as is the case in our patient.^22-23  It also seems to have a specific predilection for the lung apices.^{18, 24} 

Giant bullae affect gaseous exchange in a variety of ways.  First of all, a ventilation-perfusion mismatch is created, since the destruction of alveolar walls creates a bulla which has minimal blood supply.  Apart from that, the giant bulla compresses nearby parenchyma which has a better blood supply, therefore limiting ventilation in these airspaces.⁴  Secondly, the destruction of the air space walls decreases the elastance hence increasing the compliance of the lung in that hemithorax.  This leads to air entering preferentially into the bulla on ventilation, down the pathway of least resistance resulting in a decrease in the ventilatory capacity of the lung, since gaseous exchange is minimal across the fibrous membrane of the giant bulla. 

A study performed in 2005 by Palla et al showed that elective surgery is the treatment of choice for bullectomy.  For the cases studied, the mortality rate in the first post-operative year was 7.3%, while the late mortality rate at 5 years post-op was 4.9%.²⁵  In our case, VATS-bullectomy was utilised, which has been proven to be a safe and effective treatment modality for giant bullae, with long-term symptomatic improvement.^26-27  In fact, VATS bullectomy results in a shorter hospital stay, quicker recovery, less post-operative pain and most importantly better ventilation with reduced chest infection rates, when compared to thoracotomy, and is therefore preferred.⁶ Debate continues in the thoracic surgical community on the use of cellulose mesh and fibrin glue to reinforce the suture line²⁸ or use of BioGlue™(Cryolife, Kennesaw, Georgia, USA) to reduce staple line dehiscence.²⁹  The technique described here relies on the presence of healthy lung to staple through at the margin of the bulla. If doubt exists on the strength of tissue one can lay open the bulla and staple the base from within, with the walls of the bulla acting as their own buttress.

Conclusion

There is a misconception that cannabis is less harmful to the lungs than cigarettes. This is not the case as we can see from numerous young people with very severe bullous lung disease. Cigarette smokers do not present so young and with such large bullae. Perhaps the fact that cigarettes are smoked through a filter for large particles plays a part in this difference.

Patients with giant bullae can undergo a novel minimally invasive operation, which carries less risk and a shorter recovery time than the conventional open operation. However, the long-term prognosis of the patient depends on their ability to stop smoking.

References

1. Burke RM. Vanishing Lungs: A Case Report of Bullous Emphysema. Radiology. 1937;28:367-71.
2. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (2020 Report). 2020.
3. Rennard SI. COPD: overview of definitions, epidemiology, and factors influencing its development. Chest. 1998 Apr;113(4 Suppl):235s-41s.
4. Deslauriers J, Leblanc P. Management of bullous disease. Chest Surg Clin N Am. 1994 Aug;4(3):539-59.
5. Im Y, Farooqi S, Mora A, Jr. Vanishing lung syndrome. Proc (Bayl Univ Med Cent). 2016 Oct;29(4):399-401.
6. Greenberg JA, Singhal S, Kaiser LR. Giant bullous lung disease: evaluation, selection, techniques, and outcomes. Chest Surg Clin N Am. 2003 Nov;13(4):631-49.
7. Bradshaw DA, Murray KM, Amundson DE. Spontaneous regression of a giant pulmonary bulla. Thorax. 1996 May;51(5):549-50.
8. Reid L. The pathology of emphysema: Lloyd-Luke (MedicalBooks) Limited; 1967.
9. Wakabayashi A. Thoracoscopic technique for management of giant bullous lung disease. Ann Thorac Surg. 1993 Sep;56(3):708-12.
10. DeVries WC, Wolfe WG. The management of spontaneous pneumothorax and bullous emphysema. Surg Clin North Am. 1980 Aug;60(4):851-66.
11. Klingman RR, Angelillo VA, DeMeester TR. Cystic and bullous lung disease. Ann Thorac Surg. 1991 Sep;52(3):576-80.
12. Nagashima O, Suzuki Y, Iwase A, Takahashi K. Acute hemorrhage in a giant bulla. Intern Med. 2012;51(18):2673.
13. Córdoba Alonso AI, Arlabán Carpintero M, Olmos Martínez JM. Giant Pulmonary Bulla Superinfection. Arch Bronconeumol. 2017 Jul;53(7):395.
14. Batihan G, Usluer O, Kaya SO. Rare cause of superior vena cava syndrome: a giant bulla. BMJ Case Rep. 2018 Dec 3;11(1).
15. Gudmundsdottir JF, Geirsson A, Hannesson P, Gudbjartsson T. Major ischaemic stroke caused by an air embolism from a ruptured giant pulmonary bulla. BMJ Case Rep. 2015 Mar 5;2015.
16. Arab WA, Echave V, Sirois M, Gomes MM. Incidental carcinoma in bullous emphysema. Can J Surg. 2009 Jun;52(3):E56-7.
17. Hatakeyama S, Tatibana A, Suzuki K, Kobayashi R. [Five cases of lung cancer with emphysematous bullae]. Nihon Kokyuki Gakkai Zasshi. 2001 Jun;39(6):415-8.
18. Johnson MK, Smith RP, Morrison D, Laszlo G, White RJ. Large lung bullae in marijuana smokers. Thorax. 2000 Apr;55(4):340-2.
19. Aldington S, Williams M, Nowitz M, Weatherall M, Pritchard A, McNaughton A, et al. Effects of cannabis on pulmonary structure, function and symptoms. Thorax. 2007 Dec;62(12):1058-63.
20. Golwala H. Marijuana abuse and bullous emphysema. Lung India. 2012 Jan;29(1):56-8.
21. Tashkin DP, Coulson AH, Clark VA, Simmons M, Bourque LB, Duann S, et al. Respiratory symptoms and lung function in habitual heavy smokers of marijuana alone, smokers of marijuana and tobacco, smokers of tobacco alone, and nonsmokers. Am Rev Respir Dis. 1987 Jan;135(1):209-16.
22. Hii SW, Tam JD, Thompson BR, Naughton MT. Bullous lung disease due to marijuana. Respirology. 2008 Jan;13(1):122-7.
23. Beshay M, Kaiser H, Niedhart D, Reymond MA, Schmid RA. Emphysema and secondary pneumothorax in young adults smoking cannabis. Eur J Cardiothorac Surg. 2007 Dec;32(6):834-8.
24. Thompson CS, White RJ. Lung bullae and marijuana. Thorax. 2002 Jun;57(6):563.
25. Palla A, Desideri M, Rossi G, Bardi G, Mazzantini D, Mussi A, et al. Elective surgery for giant bullous emphysema: a 5-year clinical and functional follow-up. Chest. 2005 Oct;128(4):2043-50.
26. Zhu C, Chen Z, Chen B, Zhu H, Rice-Narusch W, Cai X, et al. Thoracoscopic Treatment of Giant Pulmonary Bullae. J Surg Res. 2019 Nov;243:206-12.
27. Oparka J, Yan TD, Ryan E, Dunning J. Does video-assisted thoracic surgery provide a safe alternative to conventional techniques in patients with limited pulmonary function who are otherwise suitable for lung resection? Interact Cardiovasc Thorac Surg. 2013 Jul;17(1):159-62.
28. Sakamoto K, Takei H, Nishii T, Maehara T, Omori T, Tajiri M, et al. Staple line coverage with absorbable mesh after thoracoscopic bullectomy for spontaneous pneumothorax. Surg Endosc. 2004 Mar;18(3):478-81.
29. Potaris K, Mihos P, Gakidis I. Experience with an albumin-glutaraldehyde tissue adhesive in sealing air leaks after bullectomy. Heart Surg Forum. 2003;6(5):429-33.

Figure

Test image