Discussion
To our knowledge, this is the first publication of BAE using only coils in patients with massive haemoptysis and CF. In the literature, coil embolisation is often not recommended as it is believed to show high rates of recanalisation on the one hand and to preclude any more peripheral access in case of recanalisation on the other.23 28–31 We could not find robust evidence for this theory and our recanalisation rate was low with 8.8%. Incomplete embolisation of NBSA was the cause of recurrence in the same lobe in only one case, and recanalisation of NBSA was found in one case. Hypertrophied NBSA were found in 50% of patients, but only 24% of NBSA were embolised. Neovascularisation seems to play an important role in recurrence in the same lobe as this was the cause in 69% of patients.
In a recent study by Ishikawa et al, ssBACE was both safe and long-term effective in patients with haemoptysis.21 However, patients in this study suffered from a variety of underlying diseases and emergency interventions were excluded. Our data show that ssBACE is safe and effective as immediate and long-term treatment in massive haemoptysis in patients with CF including emergency interventions.
Henig et al raised concern about overall benefit as 14% of patients with CF who undergo m-BAE died within 5 months after intervention without conclusive explanation of this excess mortality.32 Martin et al reported a 30-day mortality rate of 14% after m-BAE20; Sweezey and Fellows reported a 3-month mortality rate of 30%.23 Five months after embolisation, only two patients (6%) had died in our study group, one of uncontrollable haemoptysis and the other of respiratory failure with FEV1% pred. of 19% before intervention. In our study group, 24-hour immediate success rate was 97%; intermediate outcome is good with 88.2% of our patients alive after 1 year as opposed to 64.8%–68% after m-BAE.5 23 Of our total number of patients, 72.8% were alive after 5 years as opposed to 24%–50% after m-BAE.5 22 23 This is especially important, considering that 39% of our patients had severely impaired initial FEV1 <40% predicted. After m-BAE, patients showed deterioration of lung function and higher risk of death and lung transplant.22 23 33 Massive haemoptysis itself causes significant deterioration of lung function over the year following massive haemoptysis.5 Interestingly, our study group showed significant improvement of FEV1% pred. after ssBACE, and especially in severely compromised patients with FEV1 pred. <40%. The 9-month non-recurrence rate of 64.7% in our cohort meets the suggested threshold of 65% success rate 9 months after BAE set by the Society of Interventional Radiology Standard of Practice Committee.27 Our reintervention rate of 58.8% is higher than 25%–55% of studies using m-BAE, but our observation interval was longer and mortality was lower, which both influence reintervention rate.13 21 34 Embolisation of hypertrophied bronchial arteries, be it selective or more radical, will immediately produce higher flow in other vessels. This mechanism, together with continuous inflammation in CF and concomitant upregulation of serum vascular endothelial growth factor, may promote hypertrophy of other vessels in the same region.32 Kato et al found control of inflammation caused by the underlying disease as the most significant factor affecting long-term results and recurrence rates after m-BAE.14 Thus, in CF, embolisation of all hypertrophied bronchial arteries at one point may not prevent future hypertrophy of other bronchial arteries and possible bleeding. Extensive occlusion of entire arterial territories might even harm patients suffering from CF, explaining accelerated respiratory failure after m-BAE.5 6 11 18 23 32 Vidal et al described patients who had undergone m-BAE to be more likely to die than to present with recurrent major haemoptysis.22 Considering these data, many patients will not suffer from recurrence but from respiratory failure after m-BAE. m-BAE might cause ischaemia of larger areas of lung tissue in an already compromised lung in CF and might impede antibiotic exposure of infected tissue in advanced CF lung disease. In ssBACE, the embolised territory is smaller and collateral vessels remain open for blood supply as we followed a protocol of restricting intervention to the culprit vessel only and to a maximum of three lobes per intervention. Preservation of more vital lung tissue and herewith possibly better antibiotic access to the affected lung tissue might explain the striking difference in FEV1% pred. development after ssBACE compared with m-BAE.20 22–24 35 In our cohort, ssBACE not only achieved sufficient haemostasis but, as important, also provided excellent long-term outcome. However, PVA being the most commonly used microsphere embolic material, we could not differentiate between different microsphere materials in the literature. We therefore cannot directly compare coils with a specific microsphere material.
In advanced CF lung disease, bronchial artery-to-pulmonary artery shunting is common.6 8 14 36 One hundred per cent of our patients showed shunting, suggesting this to be part of the pathogenesis of haemoptysis in CF. The use of small embolisation particles in the presence of shunting may cause severe complications such as microembolisms to lung tissue, spine and brain with dysphagia, bronchial necrosis, bowel ischaemia, paraplegia, myocardial infarction and cerebral stroke with complication rates up to 6.6% in m-BAE.6 23 36–39 In our study group, no severe complications were reported despite the presence of shunts in all patients. Bronchopulmonary anastomoses are approximately 325 µm in size,28 why several authors advise the use of particles not smaller than 500 µm or even 2 mm in case of visible shunting.6 8 20 Inadvertent embolisation of pulmonary arteries with microspheres might therefore be discussed as explanation for deterioration of FEV1% pred. in m-BAE but not in ssBACE. Perhaps the use of larger microspheres 900–1200 µm in size should be considered. Adverse events with ischaemia of different organ systems seem to be a major risk worth taking into consideration when carrying out BAE. Coils are at least 2 mm in size, ruling out direct inadvertent embolisation and embolisation through shunts. The prevention of severe complications due to the large size of coils and at the same time only flow reduction and not complete flow cessation in the affected lung territory might be valuable arguments for the use of coils.
Chronic hypercapnic respiratory failure is a common finding in advanced CF. Arterial blood is delivered to alveolar capillaries through these bronchopulmonary anastomoses transporting arterial hypercapnic blood. In animal models, 30% of CO2 elimination is through a hypertrophied bronchial circulation.40 Henig et al postulate that in abnormal ventilation/perfusion distribution in CF, increased bronchial flow delivers arterial blood with high PaCO2 providing a second opportunity for gas exchange. This effective recirculation of blood with increased PaCO2 augments the elimination of carbon dioxide.32 At the same time, oxygen exchange might be impaired as arterial blood is shunting into pulmonary vessels. The role of bronchial artery-to-pulmonary artery shunting and its contribution to pathogenesis and gas exchange is not yet well understood.
Microbiology
Chronic infection with Pseudomonas aeruginosa and B. cepacia is associated with more rapid decline in lung function but with reduced association with massive haemoptysis.5 In our cohort, record of P. aeruginosa and B. cepacia was as well associated with reduced lung function as 92% of patients with FEV1 <40% pred. showed positive sputum cultures. However, we cannot confirm a reduced association with haemoptysis as 79% of patients had positive sputum cultures for P. aeruginosa compared with 58% normal prevalence in this age group.41 The prevalence of 44% of Staphylococcus aureus is lower than the normal prevalence of 68% at this age.41 Chronic infection with Aspergillus fumigatus was higher with 47.1% in our cohort compared with 35% normal prevalence at this age. The role of fungi in the CF lung is still not well elucidated, but evidence of a harmful and complex role is getting stronger.42
Nine per cent of patients presented with liver cirrhosis as opposed to 4.2% in the American CF population, and 17.6% of patients had concomitant diabetes mellitus compared with 30.6%.41